Sample records for age-associated diseases including

  1. Shared molecular and cellular mechanisms of premature ageing and ageing-associated diseases.

    PubMed

    Kubben, Nard; Misteli, Tom

    2017-10-01

    Ageing is the predominant risk factor for many common diseases. Human premature ageing diseases are powerful model systems to identify and characterize cellular mechanisms that underpin physiological ageing. Their study also leads to a better understanding of the causes, drivers and potential therapeutic strategies of common diseases associated with ageing, including neurological disorders, diabetes, cardiovascular diseases and cancer. Using the rare premature ageing disorder Hutchinson-Gilford progeria syndrome as a paradigm, we discuss here the shared mechanisms between premature ageing and ageing-associated diseases, including defects in genetic, epigenetic and metabolic pathways; mitochondrial and protein homeostasis; cell cycle; and stem cell-regenerative capacity.

  2. Association of age-related macular degeneration and reticular macular disease with cardiovascular disease.

    PubMed

    Rastogi, Neelesh; Smith, R Theodore

    2016-01-01

    Age-related macular degeneration is the leading cause of adult blindness in the developed world. Thus, major endeavors to understand the risk factors and pathogenesis of this disease have been undertaken. Reticular macular disease is a proposed subtype of age-related macular degeneration correlating histologically with subretinal drusenoid deposits located between the retinal pigment epithelium and the inner segment ellipsoid zone. Reticular lesions are more prevalent in females and in older age groups and are associated with a higher mortality rate. Risk factors for developing age-related macular degeneration include hypertension, smoking, and angina. Several genes related to increased risk for age-related macular degeneration and reticular macular disease are also associated with cardiovascular disease. Better understanding of the clinical and genetic risk factors for age-related macular degeneration and reticular macular disease has led to the hypothesis that these eye diseases are systemic. A systemic origin may help to explain why reticular disease is diagnosed more frequently in females as males suffer cardiovascular mortality at an earlier age, before the age of diagnosis of reticular macular disease and age-related macular degeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Age-associated chronic diseases require age-old medicine: role of chronic inflammation.

    PubMed

    Prasad, Sahdeo; Sung, Bokyung; Aggarwal, Bharat B

    2012-05-01

    Most chronic diseases--such as cancer, cardiovascular disease (CVD), Alzheimer disease, Parkinson disease, arthritis, diabetes and obesity--are becoming leading causes of disability and death all over the world. Some of the most common causes of these age-associated chronic diseases are lack of physical activity, poor nutrition, tobacco use, and excessive alcohol consumption. All the risk factors linked to these chronic diseases have been shown to up-regulate inflammation. Therefore, downregulation of inflammation-associated risk factors could prevent or delay these age-associated diseases. Although modern science has developed several drugs for treating chronic diseases, most of these drugs are enormously expensive and are associated with serious side effects and morbidity. In this review, we present evidence on how chronic inflammation leads to age-associated chronic disease. Furthermore, we discuss diet and lifestyle as solutions for age-associated chronic disease. Published by Elsevier Inc.

  4. Therapeutic Potential and Recent Advances of Curcumin in the Treatment of Aging-Associated Diseases.

    PubMed

    Sundar Dhilip Kumar, Sathish; Houreld, Nicolette Nadene; Abrahamse, Heidi

    2018-04-05

    Curcumin, a low molecular weight, lipophilic, major yellow natural polyphenolic, and the most well-known plant-derived compound, is extracted from the rhizomes of the turmeric ( Curcuma longa ) plant. Curcumin has been demonstrated as an effective therapeutic agent in traditional medicine for the treatment and prevention of different diseases. It has also shown a wide range of biological and pharmacological effects in drug delivery, and has actively been used for the treatment of aging-associated diseases, including cardiovascular diseases, atherosclerosis, neurodegenerative diseases, cancer, rheumatoid arthritis, ocular diseases, osteoporosis, diabetes, hypertension, chronic kidney diseases, chronic inflammation and infection. The functional application and therapeutic potential of curcumin in the treatment of aging-associated diseases is well documented in the literature. This review article focuses mainly on the potential role of plant-derived natural compounds such as curcumin, their mechanism of action and recent advances in the treatment of aging-associated diseases. Moreover, the review briefly recaps on the recent progress made in the preparation of nanocurcumins and their therapeutic potential in clinical research for the treatment of aging-associated diseases.

  5. Potential importance of B cells in aging and aging-associated neurodegenerative diseases.

    PubMed

    Biragyn, Arya; Aliseychik, Maria; Rogaev, Evgeny

    2017-04-01

    Our understanding of B cells as merely antibody producers is slowly changing. Alone or in concert with antibody, they control outcomes of seemingly different diseases such as cancer, rheumatoid arthritis, diabetes, and multiple sclerosis. While their role in activation of effector immune cells is beneficial in cancer but bad in autoimmune diseases, their immunosuppressive and regulatory subsets (Bregs) inhibit autoimmune and anticancer responses. These pathogenic and suppressive functions are not static and appear to be regulated by the nature and strength of inflammation. Although aging increases inflammation and changes the composition and function of B cells, surprisingly, little is known whether the change affects aging-associated neurodegenerative disease, such as Alzheimer's disease (AD). Here, by analyzing B cells in cancer and autoimmune and neuroinflammatory diseases, we elucidate their potential importance in AD and other aging-associated neuroinflammatory diseases.

  6. Aging-associated renal disease in mice is fructokinase dependent.

    PubMed

    Roncal-Jimenez, Carlos A; Ishimoto, Takuji; Lanaspa, Miguel A; Milagres, Tamara; Hernando, Ana Andres; Jensen, Thomas; Miyazaki, Makoto; Doke, Tomohito; Hayasaki, Takahiro; Nakagawa, Takahiko; Marumaya, Shoichi; Long, David A; Garcia, Gabriela E; Kuwabara, Masanari; Sánchez-Lozada, Laura G; Kang, Duk-Hee; Johnson, Richard J

    2016-10-01

    Aging-associated kidney disease is usually considered a degenerative process associated with aging. Recently, it has been shown that animals can produce fructose endogenously, and that this can be a mechanism for causing kidney damage in diabetic nephropathy and in association with recurrent dehydration. We therefore hypothesized that low-level metabolism of endogenous fructose might play a role in aging-associated kidney disease. Wild-type and fructokinase knockout mice were fed a normal diet for 2 yr that had minimal (<5%) fructose content. At the end of 2 yr, wild-type mice showed elevations in systolic blood pressure, mild albuminuria, and glomerular changes with mesangial matrix expansion, variable mesangiolysis, and segmental thrombi. The renal injury was amplified by provision of high-salt diet for 3 wk, as noted by the presence of glomerular hypertrophy, mesangial matrix expansion, and alpha smooth muscle actin expression, and with segmental thrombi. Fructokinase knockout mice were protected from renal injury both at baseline and after high salt intake (3 wk) compared with wild-type mice. This was associated with higher levels of active (phosphorylated serine 1177) endothelial nitric oxide synthase in their kidneys. These studies suggest that aging-associated renal disease might be due to activation of specific metabolic pathways that could theoretically be targeted therapeutically, and raise the hypothesis that aging-associated renal injury may represent a disease process as opposed to normal age-related degeneration.

  7. Influence of age on androgen deprivation therapy-associated Alzheimer’s disease

    NASA Astrophysics Data System (ADS)

    Nead, Kevin T.; Gaskin, Greg; Chester, Cariad; Swisher-McClure, Samuel; Dudley, Joel T.; Leeper, Nicholas J.; Shah, Nigam H.

    2016-10-01

    We recently found an association between androgen deprivation therapy (ADT) and Alzheimer’s disease. As Alzheimer’s disease is a disease of advanced age, we hypothesize that older individuals on ADT may be at greatest risk. We conducted a retrospective multi-institutional analysis among 16,888 individuals with prostate cancer using an informatics approach. We tested the effect of ADT on Alzheimer’s disease using Kaplan-Meier age stratified analyses in a propensity score matched cohort. We found a lower cumulative probability of remaining Alzheimer’s disease-free between non-ADT users age ≥70 versus those age <70 years (p < 0.001) and between ADT versus non-ADT users ≥70 years (p = 0.034). The 5-year probability of developing Alzheimer’s disease was 2.9%, 1.9% and 0.5% among ADT users ≥70, non-ADT users ≥70 and individuals <70 years, respectively. Compared to younger individuals older men on ADT may have the greatest absolute Alzheimer’s disease risk. Future work should investigate the ADT Alzheimer’s disease association in advanced age populations given the greater potential clinical impact.

  8. Association between Age at Diagnosis of Graves' Disease and Variants in Genes Involved in Immune Response

    PubMed Central

    Jurecka-Lubieniecka, Beata; Ploski, Rafal; Kula, Dorota; Krol, Aleksandra; Bednarczuk, Tomasz; Kolosza, Zofia; Tukiendorf, Andrzej; Szpak-Ulczok, Sylwia; Stanjek-Cichoracka, Anita; Polanska, Joanna; Jarzab, Barbara

    2013-01-01

    Background Graves' disease (GD) is a complex disease in which genetic predisposition is modified by environmental factors. The aim of the study was to examine the association between genetic variants in genes encoding proteins involved in immune response and the age at diagnosis of GD. Methods 735 GD patients and 1216 healthy controls from Poland were included into the study. Eight genetic variants in the HLA-DRB1, TNF, CTLA4, CD40, NFKb, PTPN22, IL4 and IL10 genes were genotyped. Patients were stratified by the age at diagnosis of GD and the association with genotype was analysed. Results Polymorphism in the HLA-DRB1, TNF and CTLA4 genes were associated with GD. The carriers of the HLA DRB1*03 allele were more frequent in patients with age at GD diagnosis ≤30 years than in patients with older age at GD diagnosis. Conclusions HLADRB1*03 allele is associated with young age at diagnosis of Graves' disease in polish population. PMID:23544060

  9. Extracellular vesicles and their synthetic analogues in aging and age-associated brain diseases

    PubMed Central

    Smith, J. A.; Leonardi, T.; Huang, B.; Iraci, N.; Vega, B.; Pluchino, S.

    2015-01-01

    Multicellular organisms rely upon diverse and complex intercellular communications networks for a myriad of physiological processes. Disruption of these processes is implicated in the onset and propagation of disease and disorder, including the mechanisms of senescence at both cellular and organismal levels. In recent years, secreted extracellular vesicles (EVs) have been identified as a particularly novel vector by which cell-to-cell communications are enacted. EVs actively and specifically traffic bioactive proteins, nucleic acids, and metabolites between cells at local and systemic levels, modulating cellular responses in a bidirectional manner under both homeostatic and pathological conditions. EVs are being implicated not only in the generic aging process, but also as vehicles of pathology in a number of age-related diseases, including cancer and neurodegenerative and disease. Thus, circulating EVs—or specific EV cargoes—are being utilised as putative biomarkers of disease. On the other hand, EVs, as targeted intercellular shuttles of multipotent bioactive payloads, have demonstrated promising therapeutic properties, which can potentially be modulated and enhanced through cellular engineering. Furthermore, there is considerable interest in employing nanomedicinal approaches to mimic the putative therapeutic properties of EVs by employing synthetic analogues for targeted drug delivery. Herein we describe what is known about the origin and nature of EVs and subsequently review their putative roles in biology and medicine (including the use of synthetic EV analogues), with a particular focus on their role in aging and age-related brain diseases. PMID:24973266

  10. Extracellular vesicles and their synthetic analogues in aging and age-associated brain diseases.

    PubMed

    Smith, J A; Leonardi, T; Huang, B; Iraci, N; Vega, B; Pluchino, S

    2015-04-01

    Multicellular organisms rely upon diverse and complex intercellular communications networks for a myriad of physiological processes. Disruption of these processes is implicated in the onset and propagation of disease and disorder, including the mechanisms of senescence at both cellular and organismal levels. In recent years, secreted extracellular vesicles (EVs) have been identified as a particularly novel vector by which cell-to-cell communications are enacted. EVs actively and specifically traffic bioactive proteins, nucleic acids, and metabolites between cells at local and systemic levels, modulating cellular responses in a bidirectional manner under both homeostatic and pathological conditions. EVs are being implicated not only in the generic aging process, but also as vehicles of pathology in a number of age-related diseases, including cancer and neurodegenerative and disease. Thus, circulating EVs-or specific EV cargoes-are being utilised as putative biomarkers of disease. On the other hand, EVs, as targeted intercellular shuttles of multipotent bioactive payloads, have demonstrated promising therapeutic properties, which can potentially be modulated and enhanced through cellular engineering. Furthermore, there is considerable interest in employing nanomedicinal approaches to mimic the putative therapeutic properties of EVs by employing synthetic analogues for targeted drug delivery. Herein we describe what is known about the origin and nature of EVs and subsequently review their putative roles in biology and medicine (including the use of synthetic EV analogues), with a particular focus on their role in aging and age-related brain diseases.

  11. Hippocampal Sclerosis but Not Normal Aging or Alzheimer Disease Is Associated With TDP-43 Pathology in the Basal Forebrain of Aged Persons.

    PubMed

    Cykowski, Matthew D; Takei, Hidehiro; Van Eldik, Linda J; Schmitt, Frederick A; Jicha, Gregory A; Powell, Suzanne Z; Nelson, Peter T

    2016-05-01

    Transactivating responsive sequence (TAR) DNA-binding protein 43-kDa (TDP-43) pathology has been described in various brain diseases, but the full anatomical distribution and clinical and biological implications of that pathology are incompletely characterized. Here, we describe TDP-43 neuropathology in the basal forebrain, hypothalamus, and adjacent nuclei in 98 individuals (mean age, 86 years; median final mini-mental state examination score, 27). On examination blinded to clinical and pathologic diagnoses, we identified TDP-43 pathology that most frequently involved the ventromedial basal forebrain in 19 individuals (19.4%). As expected, many of these brains had comorbid pathologies including those of Alzheimer disease (AD), Lewy body disease (LBD), and/or hippocampal sclerosis of aging (HS-Aging). The basal forebrain TDP-43 pathology was strongly associated with comorbid HS-Aging (odds ratio = 6.8, p = 0.001), whereas there was no significant association between basal forebrain TDP-43 pathology and either AD or LBD neuropathology. In this sample, there were some cases with apparent preclinical TDP-43 pathology in the basal forebrain that may indicate that this is an early affected area in HS-Aging. We conclude that TDP-43 pathology in the basal forebrain is strongly associated with HS-Aging. These results raise questions about a specific pathogenetic relationship between basal forebrain TDP-43 and non-HS-Aging comorbid diseases (AD and LBD). © 2016 American Association of Neuropathologists, Inc. All rights reserved.

  12. The maternal-age-associated risk of congenital heart disease is modifiable.

    PubMed

    Schulkey, Claire E; Regmi, Suk D; Magnan, Rachel A; Danzo, Megan T; Luther, Herman; Hutchinson, Alayna K; Panzer, Adam A; Grady, Mary M; Wilson, David B; Jay, Patrick Y

    2015-04-09

    Maternal age is a risk factor for congenital heart disease even in the absence of any chromosomal abnormality in the newborn. Whether the basis of this risk resides with the mother or oocyte is unknown. The impact of maternal age on congenital heart disease can be modelled in mouse pups that harbour a mutation of the cardiac transcription factor gene Nkx2-5 (ref. 8). Here, reciprocal ovarian transplants between young and old mothers establish a maternal basis for the age-associated risk in mice. A high-fat diet does not accelerate the effect of maternal ageing, so hyperglycaemia and obesity do not simply explain the mechanism. The age-associated risk varies with the mother's strain background, making it a quantitative genetic trait. Most remarkably, voluntary exercise, whether begun by mothers at a young age or later in life, can mitigate the risk when they are older. Thus, even when the offspring carry a causal mutation, an intervention aimed at the mother can meaningfully reduce their risk of congenital heart disease.

  13. Bone quality changes associated with aging and disease: a review.

    PubMed

    Boskey, Adele L; Imbert, Laurianne

    2017-12-01

    Bone quality encompasses all the characteristics of bone that, in addition to density, contribute to its resistance to fracture. In this review, we consider changes in architecture, porosity, and composition, including collagen structure, mineral composition, and crystal size. These factors all are known to vary with tissue and animal ages, and health status. Bone morphology and presence of microcracks, which also contribute to bone quality, will not be discussed in this review. Correlations with mechanical performance for collagen cross-linking, crystallinity, and carbonate content are contrasted with mineral content. Age-dependent changes in humans and rodents are discussed in relation to rodent models of disease. Examples are osteoporosis, osteomalacia, osteogenesis imperfecta (OI), and osteopetrosis in both humans and animal models. Each of these conditions, along with aging, is associated with increased fracture risk for distinct reasons. © 2017 New York Academy of Sciences.

  14. Hippocampal Sclerosis but Not Normal Aging or Alzheimer Disease Is Associated With TDP-43 Pathology in the Basal Forebrain of Aged Persons

    PubMed Central

    Takei, Hidehiro; Van Eldik, Linda J.; Schmitt, Frederick A.; Jicha, Gregory A.; Powell, Suzanne Z.; Nelson, Peter T.

    2016-01-01

    Transactivating responsive sequence (TAR) DNA-binding protein 43-kDa (TDP-43) pathology has been described in various brain diseases, but the full anatomical distribution and clinical and biological implications of that pathology are incompletely characterized. Here, we describe TDP-43 neuropathology in the basal forebrain, hypothalamus, and adjacent nuclei in 98 individuals (mean age, 86 years; median final mini-mental state examination score, 27). On examination blinded to clinical and pathologic diagnoses, we identified TDP-43 pathology that most frequently involved the ventromedial basal forebrain in 19 individuals (19.4%). As expected, many of these brains had comorbid pathologies including those of Alzheimer disease (AD), Lewy body disease (LBD), and/or hippocampal sclerosis of aging (HS-Aging). The basal forebrain TDP-43 pathology was strongly associated with comorbid HS-Aging (odds ratio = 6.8, p = 0.001), whereas there was no significant association between basal forebrain TDP-43 pathology and either AD or LBD neuropathology. In this sample, there were some cases with apparent preclinical TDP-43 pathology in the basal forebrain that may indicate that this is an early affected area in HS-Aging. We conclude that TDP-43 pathology in the basal forebrain is strongly associated with HS-Aging. These results raise questions about a specific pathogenetic relationship between basal forebrain TDP-43 and non-HS-Aging comorbid diseases (AD and LBD). PMID:26971127

  15. Association of Perivascular Localization of Aquaporin-4 With Cognition and Alzheimer Disease in Aging Brains.

    PubMed

    Zeppenfeld, Douglas M; Simon, Matthew; Haswell, J Douglas; D'Abreo, Daryl; Murchison, Charles; Quinn, Joseph F; Grafe, Marjorie R; Woltjer, Randall L; Kaye, Jeffrey; Iliff, Jeffrey J

    2017-01-01

    Cognitive impairment and dementia, including Alzheimer disease (AD), are common within the aging population, yet the factors that render the aging brain vulnerable to these processes are unknown. Perivascular localization of aquaporin-4 (AQP4) facilitates the clearance of interstitial solutes, including amyloid-β, through the brainwide network of perivascular pathways termed the glymphatic system, which may be compromised in the aging brain. To determine whether alterations in AQP4 expression or loss of perivascular AQP4 localization are features of the aging human brain and to define their association with AD pathology. Expression of AQP4 was analyzed in postmortem frontal cortex of cognitively healthy and histopathologically confirmed individuals with AD by Western blot or immunofluorescence for AQP4, amyloid-β 1-42, and glial fibrillary acidic protein. Postmortem tissue and clinical data were provided by the Oregon Health and Science University Layton Aging and Alzheimer Disease Center and Oregon Brain Bank. Postmortem tissue from 79 individuals was evaluated, including cognitively intact "young" individuals aged younger than 60 years (range, 33-57 years), cognitively intact "aged" individuals aged older than 60 years (range, 61-96 years) with no known neurological disease, and individuals older than 60 years (range, 61-105 years) of age with a clinical history of AD confirmed by histopathological evaluation. Forty-eight patient samples (10 young, 20 aged, and 18 with AD) underwent histological analysis. Sixty patient samples underwent Western blot analysis (15 young, 24 aged, and 21 with AD). Expression of AQP4 protein, AQP4 immunoreactivity, and perivascular AQP4 localization in the frontal cortex were evaluated. Expression of AQP4 was associated with advancing age among all individuals (R2 = 0.17; P = .003). Perivascular AQP4 localization was significantly associated with AD status independent of age (OR, 11.7 per 10% increase in localization; z

  16. Disease-aging network reveals significant roles of aging genes in connecting genetic diseases.

    PubMed

    Wang, Jiguang; Zhang, Shihua; Wang, Yong; Chen, Luonan; Zhang, Xiang-Sun

    2009-09-01

    One of the challenging problems in biology and medicine is exploring the underlying mechanisms of genetic diseases. Recent studies suggest that the relationship between genetic diseases and the aging process is important in understanding the molecular mechanisms of complex diseases. Although some intricate associations have been investigated for a long time, the studies are still in their early stages. In this paper, we construct a human disease-aging network to study the relationship among aging genes and genetic disease genes. Specifically, we integrate human protein-protein interactions (PPIs), disease-gene associations, aging-gene associations, and physiological system-based genetic disease classification information in a single graph-theoretic framework and find that (1) human disease genes are much closer to aging genes than expected by chance; and (2) diseases can be categorized into two types according to their relationships with aging. Type I diseases have their genes significantly close to aging genes, while type II diseases do not. Furthermore, we examine the topological characters of the disease-aging network from a systems perspective. Theoretical results reveal that the genes of type I diseases are in a central position of a PPI network while type II are not; (3) more importantly, we define an asymmetric closeness based on the PPI network to describe relationships between diseases, and find that aging genes make a significant contribution to associations among diseases, especially among type I diseases. In conclusion, the network-based study provides not only evidence for the intricate relationship between the aging process and genetic diseases, but also biological implications for prying into the nature of human diseases.

  17. Animal models of aging research: implications for human aging and age-related diseases.

    PubMed

    Mitchell, Sarah J; Scheibye-Knudsen, Morten; Longo, Dan L; de Cabo, Rafael

    2015-01-01

    Aging is characterized by an increasing morbidity and functional decline that eventually results in the death of an organism. Aging is the largest risk factor for numerous human diseases, and understanding the aging process may thereby facilitate the development of new treatments for age-associated diseases. The use of humans in aging research is complicated by many factors, including ethical issues; environmental and social factors; and perhaps most importantly, their long natural life span. Although cellular models of human disease provide valuable mechanistic information, they are limited in that they may not replicate the in vivo biology. Almost all organisms age, and thus animal models can be useful for studying aging. Herein, we review some of the major models currently used in aging research and discuss their benefits and pitfalls, including interventions known to extend life span and health span. Finally, we conclude by discussing the future of animal models in aging research.

  18. The Association of Statin Use with Age-Related Macular Degeneration Progression The Age-Related Eye Disease Study 2 Report Number 9

    PubMed Central

    Al-Holou, Shaza N.; Tucker, William R.; Agrón, Elvira; Clemons, Traci E.; Cukras, Catherine; Ferris, Frederick L.; Chew, Emily Y.

    2015-01-01

    Objective/purpose To evaluate the association of statin use with progression of age-related macular degeneration (AMD). Design Preplanned, prospective cohort study within a controlled clinical trial of oral supplementation for age-related eye diseases. Subjects Age-Related Eye Disease Study 2 participants, aged 50 to 85 years. Methods Factors, including age, gender, smoking status, aspirin use, and history of diabetes, hypertension, heart disease, angina, and stroke, all known to be associated with statin use, were included in a logistic regression model to estimate propensity scores for each participant. Age-adjusted proportional hazards regression models, with and without propensity score matching, were performed to evaluate the association of statin use with progression to late AMD. Analyses were also performed adjusting for the competing risk of death. Main Outcome Measures Baseline and annual stereoscopic fundus photographs were assessed centrally by masked graders for the development of late AMD, either neovascular AMD or geographic atrophy (GA). Results Of the 3791 participants (2462 with bilateral large drusen and 1329 with unilateral late AMD at baseline), 1659 (43.8%) were statin users. The overall analysis, with no matching of propensity scores and no adjustment for death as a competing risk, showed that statin use was not associated with progression to late AMD (hazard ratios [HR] of 1.08, 95% confidence intervals [CI] of 0.83–1.41, P=0.56). When matched for propensity scores and adjusted for death as a competing risk, the result was not statistically significant with HR: 0.81, 95% CI: 0.55–1.20, P=0.29. Further subgroup analyses of persons with or without late AMD at baseline to the various components of late AMD (neovascular, central geographic atrophy, or any geographic atrophy) also showed no statistically significant association of statin use with progression to AMD. Conclusions Statin use was not statistically significantly associated with the

  19. The Association of Statin Use with Age-Related Macular Degeneration Progression: The Age-Related Eye Disease Study 2 Report Number 9.

    PubMed

    Al-Holou, Shaza N; Tucker, William R; Agrón, Elvira; Clemons, Traci E; Cukras, Catherine; Ferris, Frederick L; Chew, Emily Y

    2015-12-01

    To evaluate the association of statin use with progression of age-related macular degeneration (AMD). Preplanned, prospective cohort study within a controlled clinical trial of oral supplementation for age-related eye diseases. Age-Related Eye Disease Study 2 (AREDS2) participants, aged 50 to 85 years. Factors, including age, gender, smoking status, aspirin use, and history of diabetes, hypertension, heart disease, angina, and stroke-all known to be associated with statin use-were included in a logistic regression model to estimate propensity scores for each participant. Age-adjusted proportional hazards regression models, with and without propensity score matching, were performed to evaluate the association of statin use with progression to late AMD. Analyses adjusting for the competing risk of death were also performed. Baseline and annual stereoscopic fundus photographs were assessed centrally by masked graders for the development of late AMD, either neovascular AMD or geographic atrophy (GA). Of the 3791 participants (2462 with bilateral large drusen and 1329 with unilateral late AMD at baseline), 1659 (43.8%) were statin users. The overall analysis, with no matching of propensity scores and no adjustment for death as a competing risk, showed that statin use was not associated with progression to late AMD (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.83-1.41; P = 0.56). When matched for propensity scores and adjusted for death as a competing risk, the result was not statistically significant (HR, 0.81; 95% CI, 0.55-1.20; P = 0.29). Furthermore, subgroup analyses of persons with or without late AMD at baseline and the various components of late AMD (neovascular AMD, central GA, or any GA) also showed no statistically significant association of statin use with progression to AMD. Statin use was not statistically significantly associated with progression to late AMD in the AREDS2 participants, and these findings are consistent with findings in the

  20. Pleiotropic Meta-Analyses of Longitudinal Studies Discover Novel Genetic Variants Associated with Age-Related Diseases

    PubMed Central

    He, Liang; Kernogitski, Yelena; Kulminskaya, Irina; Loika, Yury; Arbeev, Konstantin G.; Loiko, Elena; Bagley, Olivia; Duan, Matt; Yashkin, Arseniy; Ukraintseva, Svetlana V.; Kovtun, Mikhail; Yashin, Anatoliy I.; Kulminski, Alexander M.

    2016-01-01

    Age-related diseases may result from shared biological mechanisms in intrinsic processes of aging. Genetic effects on age-related diseases are often modulated by environmental factors due to their little contribution to fitness or are mediated through certain endophenotypes. Identification of genetic variants with pleiotropic effects on both common complex diseases and endophenotypes may reveal potential conflicting evolutionary pressures and deliver new insights into shared genetic contribution to healthspan and lifespan. Here, we performed pleiotropic meta-analyses of genetic variants using five NIH-funded datasets by integrating univariate summary statistics for age-related diseases and endophenotypes. We investigated three groups of traits: (1) endophenotypes such as blood glucose, blood pressure, lipids, hematocrit, and body mass index, (2) time-to-event outcomes such as the age-at-onset of diabetes mellitus (DM), cancer, cardiovascular diseases (CVDs) and neurodegenerative diseases (NDs), and (3) both combined. In addition to replicating previous findings, we identify seven novel genome-wide significant loci (< 5e-08), out of which five are low-frequency variants. Specifically, from Group 2, we find rs7632505 on 3q21.1 in SEMA5B, rs460976 on 21q22.3 (1 kb from TMPRSS2) and rs12420422 on 11q24.1 predominantly associated with a variety of CVDs, rs4905014 in ITPK1 associated with stroke and heart failure, rs7081476 on 10p12.1 in ANKRD26 associated with multiple diseases including DM, CVDs, and NDs. From Group 3, we find rs8082812 on 18p11.22 and rs1869717 on 4q31.3 associated with both endophenotypes and CVDs. Our follow-up analyses show that rs7632505, rs4905014, and rs8082812 have age-dependent effects on coronary heart disease or stroke. Functional annotation suggests that most of these SNPs are within regulatory regions or DNase clusters and in linkage disequilibrium with expression quantitative trait loci, implying their potential regulatory influence on

  1. Neurodegenerative disease concomitant proteinopathies are prevalent, age-related and APOE4-associated.

    PubMed

    Robinson, John L; Lee, Edward B; Xie, Sharon X; Rennert, Lior; Suh, EunRan; Bredenberg, Colin; Caswell, Carrie; Van Deerlin, Vivianna M; Yan, Ning; Yousef, Ahmed; Hurtig, Howard I; Siderowf, Andrew; Grossman, Murray; McMillan, Corey T; Miller, Bruce; Duda, John E; Irwin, David J; Wolk, David; Elman, Lauren; McCluskey, Leo; Chen-Plotkin, Alice; Weintraub, Daniel; Arnold, Steven E; Brettschneider, Johannes; Lee, Virginia M-Y; Trojanowski, John Q

    2018-06-05

    Lewy bodies commonly occur in Alzheimer's disease, and Alzheimer's disease pathology is frequent in Lewy body diseases, but the burden of co-pathologies across neurodegenerative diseases is unknown. We assessed the extent of tau, amyloid-β, α-synuclein and TDP-43 proteinopathies in 766 autopsied individuals representing a broad spectrum of clinical neurodegenerative disease. We interrogated pathological Alzheimer's disease (n = 247); other tauopathies (n = 95) including Pick's disease, corticobasal disease and progressive supranuclear palsy; the synucleinopathies (n = 164) including multiple system atrophy and Lewy body disease; the TDP-43 proteinopathies (n = 188) including frontotemporal lobar degeneration with TDP-43 inclusions and amyotrophic lateral sclerosis; and a minimal pathology group (n = 72). Each group was divided into subgroups without or with co-pathologies. Age and sex matched logistic regression models compared co-pathology prevalence between groups. Co-pathology prevalence was similar between the minimal pathology group and most neurodegenerative diseases for each proteinopathy: tau was nearly universal (92-100%), amyloid-β common (20-57%); α-synuclein less common (4-16%); and TDP-43 the rarest (0-16%). In several neurodegenerative diseases, co-pathology increased: in Alzheimer's disease, α-synuclein (41-55%) and TDP-43 (33-40%) increased; in progressive supranuclear palsy, α-synuclein increased (22%); in corticobasal disease, TDP-43 increased (24%); and in neocortical Lewy body disease, amyloid-β (80%) and TDP-43 (22%) increased. Total co-pathology prevalence varied across groups (27-68%), and was increased in high Alzheimer's disease, progressive supranuclear palsy, and neocortical Lewy body disease (70-81%). Increased age at death was observed in the minimal pathology group, amyotrophic lateral sclerosis, and multiple system atrophy cases with co-pathologies. In amyotrophic lateral sclerosis and neocortical Lewy body disease, co

  2. Healthy aging and disease: role for telomere biology?

    PubMed Central

    Zhu, Haidong; Belcher, Matthew; van der Harst, Pim

    2011-01-01

    Aging is a biological process that affects most cells, organisms and species. Human aging is associated with increased susceptibility to a variety of chronic diseases, including cardiovascular disease, Type 2 diabetes, neurological diseases and cancer. Despite the remarkable progress made during the last two decades, our understanding of the biology of aging remains incomplete. Telomere biology has recently emerged as an important player in the aging and disease process. PMID:21271986

  3. Molecular inflammation: underpinnings of aging and age-related diseases.

    PubMed

    Chung, Hae Young; Cesari, Matteo; Anton, Stephen; Marzetti, Emanuele; Giovannini, Silvia; Seo, Arnold Young; Carter, Christy; Yu, Byung Pal; Leeuwenburgh, Christiaan

    2009-01-01

    Recent scientific studies have advanced the notion of chronic inflammation as a major risk factor underlying aging and age-related diseases. In this review, low-grade, unresolved, molecular inflammation is described as an underlying mechanism of aging and age-related diseases, which may serve as a bridge between normal aging and age-related pathological processes. Accumulated data strongly suggest that continuous (chronic) upregulation of pro-inflammatory mediators (e.g., TNF-alpha, IL-1beta, IL-6, COX-2, iNOS) are induced during the aging process due to an age-related redox imbalance that activates many pro-inflammatory signaling pathways, including the NF-kappaB signaling pathway. These pro-inflammatory molecular events are discussed in relation to their role as basic mechanisms underlying aging and age-related diseases. Further, the anti-inflammatory actions of aging-retarding caloric restriction and exercise are reviewed. Thus, the purpose of this review is to describe the molecular roles of age-related physiological functional declines and the accompanying chronic diseases associated with aging. This new view on the role of molecular inflammation as a mechanism of aging and age-related pathogenesis can provide insights into potential interventions that may affect the aging process and reduce age-related diseases, thereby promoting healthy longevity.

  4. Molecular Inflammation: Underpinnings of Aging and Age-related Diseases

    PubMed Central

    Chung, Hae Young; Cesari, Matteo; Anton, Stephen; Marzetti, Emanuele; Giovannini, Silvia; Seo, Arnold Young; Carter, Christy; Yu, Byung Pal; Leeuwenburgh, Christiaan

    2013-01-01

    Recent scientific studies have advanced the notion of chronic inflammation as a major risk factor underlying aging and age-related diseases. In this review, low-grade, unresolved, molecular inflammation is described as an underlying mechanism of aging and age-related diseases, which may serve as a bridge between normal aging and age-related pathological processes. Accumulated data strongly suggest that continuous (chronic) up-regulation of pro-inflammatory mediators (e.g., TNF-α, IL-1β, 6, COX-2, iNOS) are induced during the aging process due to an age-related redox imbalance that activates many pro-inflammatory signaling pathways, including the NF-κB signaling pathway. These pro-inflammatory molecular events are discussed in relation to their role as basic mechanisms underlying aging and age-related diseases. Further, the anti-inflammatory actions of aging-retarding caloric restriction and exercise are reviewed. Thus, the purpose of this review is to describe the molecular roles of age-related physiological functional declines and the accompanying chronic diseases associated with aging. This new view on the role of molecular inflammation as a mechanism of aging and age-related pathogenesis can provide insights into potential interventions that may affect the aging process and reduce age-related diseases, thereby promoting healthy longevity. PMID:18692159

  5. Productivity losses attributable to untreated chlamydial infection and associated pelvic inflammatory disease in reproductive-aged women.

    PubMed

    Blandford, John M; Gift, Thomas L

    2006-10-01

    The productivity losses attributable to disease-related morbidity and mortality impose a burden on society in general and on employers in particular. A reliable assessment of the productivity losses associated with untreated infection with Chlamydia trachomatis (Ct) would complement earlier work on direct medical costs and contribute to an estimate of the full cost of chlamydial disease. The goal of this study was to estimate the discounted lifetime productivity losses attributable to untreated chlamydial infection in reproductive-aged women. We developed a cost model using Monte Carlo methods to estimate the lifetime discounted productivity losses attributable to untreated lower genital tract Ct infection among reproductive-aged women. The model considered the impact of disability resulting from acute pelvic inflammatory disease (PID) associated with untreated Ct infection and from the sequelae of acute PID, including chronic pelvic pain, ectopic pregnancy, and infertility. To accommodate disparate Ct infection rates and labor market characteristics across age groups, we matched age-based risk factors for Ct infection with labor market patterns. Data sources included the 2001 National Chlamydia Surveillance Data, the 2001 Current Population Survey, and published literature. Estimates indicate that the mean weighted productivity losses per untreated Ct infection were approximately US dollars 130 (in year 2001 dollars). Mean weighted productivity losses per case of acute PID were estimated at US dollars 649. Estimated productivity losses were highly correlated with age, reflecting age-dependent differences in labor market characteristics. The productivity losses attributable to untreated infection with Ct and to sequelae of this infection form a substantial portion of the total economic burden of disease. Effective programs to prevent chlamydial infection and effective screening, diagnosis, and treatment of Ct-infected women may reduce productivity losses and

  6. Autophagy and ageing: implications for age-related neurodegenerative diseases.

    PubMed

    Carroll, Bernadette; Hewitt, Graeme; Korolchuk, Viktor I

    2013-01-01

    Autophagy is a process of lysosome-dependent intracellular degradation that participates in the liberation of resources including amino acids and energy to maintain homoeostasis. Autophagy is particularly important in stress conditions such as nutrient starvation and any perturbation in the ability of the cell to activate or regulate autophagy can lead to cellular dysfunction and disease. An area of intense research interest is the role and indeed the fate of autophagy during cellular and organismal ageing. Age-related disorders are associated with increased cellular stress and assault including DNA damage, reduced energy availability, protein aggregation and accumulation of damaged organelles. A reduction in autophagy activity has been observed in a number of ageing models and its up-regulation via pharmacological and genetic methods can alleviate age-related pathologies. In particular, autophagy induction can enhance clearance of toxic intracellular waste associated with neurodegenerative diseases and has been comprehensively demonstrated to improve lifespan in yeast, worms, flies, rodents and primates. The situation, however, has been complicated by the identification that autophagy up-regulation can also occur during ageing. Indeed, in certain situations, reduced autophagosome induction may actually provide benefits to ageing cells. Future studies will undoubtedly improve our understanding of exactly how the multiple signals that are integrated to control appropriate autophagy activity change during ageing, what affect this has on autophagy and to what extent autophagy contributes to age-associated pathologies. Identification of mechanisms that influence a healthy lifespan is of economic, medical and social importance in our 'ageing' world.

  7. Nutritional Considerations for Healthy Aging and Reduction in Age-Related Chronic Disease.

    PubMed

    Shlisky, Julie; Bloom, David E; Beaudreault, Amy R; Tucker, Katherine L; Keller, Heather H; Freund-Levi, Yvonne; Fielding, Roger A; Cheng, Feon W; Jensen, Gordon L; Wu, Dayong; Meydani, Simin N

    2017-01-01

    A projected doubling in the global population of people aged ≥60 y by the year 2050 has major health and economic implications, especially in developing regions. Burdens of unhealthy aging associated with chronic noncommunicable and other age-related diseases may be largely preventable with lifestyle modification, including diet. However, as adults age they become at risk of "nutritional frailty," which can compromise their ability to meet nutritional requirements at a time when specific nutrient needs may be high. This review highlights the role of nutrition science in promoting healthy aging and in improving the prognosis in cases of age-related diseases. It serves to identify key knowledge gaps and implementation challenges to support adequate nutrition for healthy aging, including applicability of metrics used in body-composition and diet adequacy for older adults and mechanisms to reduce nutritional frailty and to promote diet resilience. This review also discusses management recommendations for several leading chronic conditions common in aging populations, including cognitive decline and dementia, sarcopenia, and compromised immunity to infectious disease. The role of health systems in incorporating nutrition care routinely for those aged ≥60 y and living independently and current actions to address nutritional status before hospitalization and the development of disease are discussed. © 2017 American Society for Nutrition.

  8. Quantitative proteomic analysis of age-related subventricular zone proteins associated with neurodegenerative disease.

    PubMed

    Wang, Xianli; Dong, Chuanming; Sun, Lixin; Zhu, Liang; Sun, Chenxi; Ma, Rongjie; Ning, Ke; Lu, Bing; Zhang, Jinfu; Xu, Jun

    2016-11-18

    Aging is characterized by a progressive decline in the function of adult tissues which can lead to neurodegenerative disorders. However, little is known about the correlation between protein changes in the subventricular zone (SVZ) and neurodegenerative diseases with age. In the present study, neural stem cells (NSCs) were derived from the SVZ on postnatal 7 d, 1 m, and 12 m-old mice. With age, NSCs exhibited increased SA-β-gal activity and decreased proliferation and pool size in the SVZ zone, and were associated with elevated inflammatory chemokines and cytokines. Furthermore, quantitative proteomics and ingenuity pathway analysis were used to evaluate the significant age-related alterations in proteins and their functions. Some downregulated proteins such as DPYSL2, TPI1, ALDH, and UCHL1 were found to play critical roles in the neurological disease and PSMA1, PSMA3, PSMC2, PSMD11, and UCHL1 in protein homeostasis. Taken together, we have provided valuable insight into the cellular and molecular processes that underlie aging-associated declines in SVZ neurogenesis for the early detection of differences in gene expression and the potential risk of neurological disease, which is beneficial in the prevention of the diseases.

  9. The Spectrum of Epstein-Barr Virus-Associated Lymphoproliferative Disease in Korea: Incidence of Disease Entities by Age Groups

    PubMed Central

    Cho, Eun-Yoon; Kim, Ki-Hyun; Kim, Won-Seog; Yoo, Keon Hee; Koo, Hong-Hoe

    2008-01-01

    This study is to identify the spectrum of Epstein-Barr virus (EBV)-positive lymphoproliferative diseases (LPD) and relationships between these diseases in Korea. The EBV status and clinicopathology of 764 patients, including acute EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), chronic active EBV (CAEBV) infections, B-LPD arising in chronic latent EBV infection, T & natural killer (NK) cell non-Hodgkin's lymphomas (NHL), B-NHLs, and Hodgkin's lymphomas (HD), were analyzed. T or NK cell NHLs were the most common forms of EBV-positive NHLs (107/167, 64%); among these, nasal-type NK/T cell lymphomas were the most common (89/107, 83%). According to the age, Burkitt's lymphoma was the most common in early childhood; in teenagers, chronic (active) EBV infection-associated LPD was the most common type. The incidence of NK/T cell lymphoma began to increase from the twenties and formed the major type of EBV-associated tumor throughout life. Diffuse large B cell lymphoma formed the major type in the sixties and seventies. In conclusion, primary infections in early childhood are complicated by the development of CAEBV infections that are main predisposing factors for EBV-associated T or NK cell malignancies in young adults. In old patients, decreased immunity associated with old age and environmental cofactors may provoke the development of peripheral T cell lymphoma, unspecified, and diffuse large B cell lymphoma. PMID:18436998

  10. The spectrum of Epstein-Barr virus-associated lymphoproliferative disease in Korea: incidence of disease entities by age groups.

    PubMed

    Cho, Eun-Yoon; Kim, Ki-Hyun; Kim, Won-Seog; Yoo, Keon Hee; Koo, Hong-Hoe; Ko, Young-Hyeh

    2008-04-01

    This study is to identify the spectrum of Epstein-Barr virus (EBV)-positive lymphoproliferative diseases (LPD) and relationships between these diseases in Korea. The EBV status and clinicopathology of 764 patients, including acute EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), chronic active EBV (CAEBV) infections, B-LPD arising in chronic latent EBV infection, T & natural killer (NK) cell non-Hodgkin's lymphomas (NHL), B-NHLs, and Hodgkin's lymphomas (HD), were analyzed. T or NK cell NHLs were the most common forms of EBV-positive NHLs (107/167, 64%); among these, nasal-type NK/T cell lymphomas were the most common (89/107, 83%). According to the age, Burkitt's lymphoma was the most common in early childhood; in teenagers, chronic (active) EBV infection-associated LPD was the most common type. The incidence of NK/T cell lymphoma began to increase from the twenties and formed the major type of EBV-associated tumor throughout life. Diffuse large B cell lymphoma formed the major type in the sixties and seventies. In conclusion, primary infections in early childhood are complicated by the development of CAEBV infections that are main predisposing factors for EBV-associated T or NK cell malignancies in young adults. In old patients, decreased immunity associated with old age and environmental cofactors may provoke the development of peripheral T cell lymphoma, unspecified, and diffuse large B cell lymphoma.

  11. The association of antidepressant drug usage with cognitive impairment or dementia, including Alzheimer disease: A systematic review and meta‐analysis

    PubMed Central

    Moraros, John; Nwankwo, Chijioke; Patten, Scott B.

    2016-01-01

    1 Objective To determine if antidepressant drug usage is associated with cognitive impairment or dementia, including Alzheimer disease (AD). 2 Method We conducted a systematic search of Medline, PubMed, PsycINFO, Web of Science, Embase, CINAHL, and the Cochrane Library. An initial screen by abstracts and titles was performed, and relevant full articles were then reviewed and assessed for their methodologic quality. Crude effect estimates were extracted from the included articles and a pooled estimate was obtained using a random effects model. 3 Results Five articles were selected from an initial pool of 4,123 articles. Use of antidepressant drugs was associated with a significant twofold increase in the odds of some form of cognitive impairment or dementia (OR = 2.17). Age was identified as a likely modifier of the association between antidepressant use and some form of cognitive impairment or AD/dementia. Studies that included participants with an average age equal to or greater than 65 years showed an increased odds of some form of cognitive impairment with antidepressant drug usage (OR = 1.65), whereas those with participants less than age 65 revealed an even stronger association (OR = 3.25). 4 Conclusions Antidepressant drug usage is associated with AD/dementia and this is particularly evident if usage begins before age 65. This association may arise due to confounding by depression or depression severity. However, biological mechanisms potentially linking antidepressant exposure to dementia have been described, so an etiological effect of antidepressants is possible. With this confirmation that an association exists, clarification of underlying etiologic pathways requires urgent attention. PMID:28029715

  12. Tocotrienol is a cardioprotective agent against ageing-associated cardiovascular disease and its associated morbidities.

    PubMed

    Ramanathan, Nardev; Tan, Esther; Loh, Li Jun; Soh, Boon Seng; Yap, Wei Ney

    2018-01-01

    Ageing is a nonmodifiable risk factor that is linked to increased likelihood of cardiovascular morbidities. Whilst many pharmacological interventions currently exist to treat many of these disorders such as statins for hypercholesterolemia or beta-blockers for hypertension, the elderly appear to present a greater likelihood of suffering non-related side effects such as increased risk of developing new onset type 2 diabetes (NODM). In some cases, lower efficacy in the elderly have also been reported. Alternative forms of treatment have been sought to address these issues, and there has been a growing interest in looking at herbal remedies or plant-based natural compounds. Oxidative stress and inflammation are implicated in the manifestation of ageing-related cardiovascular disease. Thus, it is natural that a compound that possesses both antioxidative and anti-inflammatory bioactivities would be considered. This review article examines the potential of tocotrienols, a class of Vitamin E compounds with proven superior antioxidative and anti-inflammatory activity compared to tocopherols (the other class of Vitamin E compounds), in ameliorating ageing-related cardiovascular diseases and its associated morbidities. In particular, the potential of tocotrienols in improving inflammaging, dyslipidemia and mitochondrial dysfunction in ageing-related cardiovascular diseases are discussed.

  13. Nutritional Considerations for Healthy Aging and Reduction in Age-Related Chronic Disease12

    PubMed Central

    Shlisky, Julie; Bloom, David E; Beaudreault, Amy R; Tucker, Katherine L; Keller, Heather H; Freund-Levi, Yvonne; Fielding, Roger A; Cheng, Feon W; Jensen, Gordon L; Wu, Dayong; Meydani, Simin N

    2017-01-01

    A projected doubling in the global population of people aged ≥60 y by the year 2050 has major health and economic implications, especially in developing regions. Burdens of unhealthy aging associated with chronic noncommunicable and other age-related diseases may be largely preventable with lifestyle modification, including diet. However, as adults age they become at risk of “nutritional frailty,” which can compromise their ability to meet nutritional requirements at a time when specific nutrient needs may be high. This review highlights the role of nutrition science in promoting healthy aging and in improving the prognosis in cases of age-related diseases. It serves to identify key knowledge gaps and implementation challenges to support adequate nutrition for healthy aging, including applicability of metrics used in body-composition and diet adequacy for older adults and mechanisms to reduce nutritional frailty and to promote diet resilience. This review also discusses management recommendations for several leading chronic conditions common in aging populations, including cognitive decline and dementia, sarcopenia, and compromised immunity to infectious disease. The role of health systems in incorporating nutrition care routinely for those aged ≥60 y and living independently and current actions to address nutritional status before hospitalization and the development of disease are discussed. PMID:28096124

  14. The aging mouth: differentiating normal aging from disease.

    PubMed

    Lamster, Ira B; Asadourian, Lynda; Del Carmen, Tessa; Friedman, Paula K

    2016-10-01

    Aging is the physiologic change that occurs over time. In humans, this change occurs at different rates and are related to lifestyle, environment and genetics. It can be challenging to differentiate normal aging from disease. In the oral cavity, with increasing age the teeth demonstrate wearing of the enamel, chipping and fracture lines, and a darker color. The pulp chamber and canals are reduced in size as a result of the deposition of secondary dentin. Coronal or root caries, however, represent disease. A limited amount of periodontal attachment loss occurs in association with aging, usually manifesting as recession on the buccal surface of teeth. Severe periodontitis occurs in 10.5-12% of the population, with the peak incidence being observed at 35-40 years of age. Changes to the mucosal tissue that occur with age include reduced wound-healing capacity. However, environmental factors, such as smoking, dramatically increase the risk of mucosal pathology. Reduced salivary gland function is often seen in association with medication usage, as well as with disorders such as diabetes mellitus. Both medication use and chronic disorders are more common in older adults. Masticatory function is of particular importance for older adults. Maintenance of a nutritionally complete diet is important for avoiding sarcopenia and the frailty syndrome. Successful oral aging is associated with adequate function and comfort. A reduced, but functional, dentition of 20 teeth in occlusion has been proposed as a measure of successful oral aging. Healthy oral aging is important to healthy aging from both biological and social perspectives. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. The role of cerebrovascular disease and the association between diabetes mellitus and dementia among aged medicare beneficiaries.

    PubMed

    Lu, Z Kevin; Li, Minghui; Yuan, Jing; Wu, Jun

    2016-01-01

    The aim of this study is to assess whether diabetes mellitus is associated with overall dementia and its subtypes (Alzheimer's disease and vascular dementia) among the elderly and to identify the role of cerebrovascular disease in the association between diabetes and dementia. In a retrospective cross-sectional study, 5160 community-dwelling and institutionalized Medicare beneficiaries aged 65 years or over without health maintenance organization enrollment from the Medicare Current Beneficiary Survey in 2010 were included. The International Classification of Diseases-9 codes were used to identify the outcome and independent variables from the Medicare claims. The key predictor was diabetes mellitus and the outcomes were overall dementia and its subtypes. Logistic regression was employed to assess the association between dementia and diabetes after adjusting for age, gender, race, education, income, smoking status, and Charlson Comorbidity Index. After adjusting for potential confounders, diabetes mellitus was significantly associated with overall dementia (odds ratio [OR] = 1.42; 95% confidence interval [CI], 1.14-1.77), vascular dementia (OR = 1.29; 95% CI, 1.02-1.64), and Alzheimer's disease (OR = 1.51, 95% CI, 1.10-2.09). The OR decreased to 1.26 (95% CI, 1.01-1.58) for overall dementia, controlling for cerebrovascular disease. The associations between diabetes mellitus and vascular dementia (OR = 1.13, 95% CI, 0.89-1.44) and Alzheimer's disease (OR = 1.39, 95% CI, 1.00-1.92) were no longer statistically significant once cerebrovascular disease was controlled. The association between diabetes mellitus and dementia is only partially mediated through cerebrovascular disease, suggesting that diabetes mellitus is associated independently with overall dementia among the elderly, but not with vascular dementia and Alzheimer's disease. Copyright © 2015 John Wiley & Sons, Ltd.

  16. The promise of human embryonic stem cells in aging-associated diseases

    PubMed Central

    Yabut, Odessa; Bernstein, Harold S.

    2011-01-01

    Aging-associated diseases are often caused by progressive loss or dysfunction of cells that ultimately affect the overall function of tissues and organs. Successful treatment of these diseases could benefit from cell-based therapy that would regenerate lost cells or otherwise restore tissue function. Human embryonic stem cells (hESCs) promise to be an important therapeutic candidate in treating aging-associated diseases due to their unique capacity for self-renewal and pluripotency. To date, there are numerous hESC lines that have been developed and characterized. We will discuss how hESC lines are derived, their molecular and cellular properties, and how their ability to differentiate into all three embryonic germ layers is determined. We will also outline the methods currently employed to direct their differentiation into populations of tissue-specific, functional cells. Finally, we will highlight the general challenges that must be overcome and the strategies being developed to generate highly-purified hESC-derived cell populations that can safely be used for clinical applications. PMID:21566262

  17. The association of antidepressant drug usage with cognitive impairment or dementia, including Alzheimer disease: A systematic review and meta-analysis.

    PubMed

    Moraros, John; Nwankwo, Chijioke; Patten, Scott B; Mousseau, Darrell D

    2017-03-01

    To determine if antidepressant drug usage is associated with cognitive impairment or dementia, including Alzheimer disease (AD). We conducted a systematic search of Medline, PubMed, PsycINFO, Web of Science, Embase, CINAHL, and the Cochrane Library. An initial screen by abstracts and titles was performed, and relevant full articles were then reviewed and assessed for their methodologic quality. Crude effect estimates were extracted from the included articles and a pooled estimate was obtained using a random effects model. Five articles were selected from an initial pool of 4,123 articles. Use of antidepressant drugs was associated with a significant twofold increase in the odds of some form of cognitive impairment or dementia (OR = 2.17). Age was identified as a likely modifier of the association between antidepressant use and some form of cognitive impairment or AD/dementia. Studies that included participants with an average age equal to or greater than 65 years showed an increased odds of some form of cognitive impairment with antidepressant drug usage (OR = 1.65), whereas those with participants less than age 65 revealed an even stronger association (OR = 3.25). Antidepressant drug usage is associated with AD/dementia and this is particularly evident if usage begins before age 65. This association may arise due to confounding by depression or depression severity. However, biological mechanisms potentially linking antidepressant exposure to dementia have been described, so an etiological effect of antidepressants is possible. With this confirmation that an association exists, clarification of underlying etiologic pathways requires urgent attention. © 2016 The Authors. Depression and Anxiety published by Wiley Periodicals, Inc.

  18. Association of Alzheimer's disease GWAS loci with MRI markers of brain aging.

    PubMed

    Chauhan, Ganesh; Adams, Hieab H H; Bis, Joshua C; Weinstein, Galit; Yu, Lei; Töglhofer, Anna Maria; Smith, Albert Vernon; van der Lee, Sven J; Gottesman, Rebecca F; Thomson, Russell; Wang, Jing; Yang, Qiong; Niessen, Wiro J; Lopez, Oscar L; Becker, James T; Phan, Thanh G; Beare, Richard J; Arfanakis, Konstantinos; Fleischman, Debra; Vernooij, Meike W; Mazoyer, Bernard; Schmidt, Helena; Srikanth, Velandai; Knopman, David S; Jack, Clifford R; Amouyel, Philippe; Hofman, Albert; DeCarli, Charles; Tzourio, Christophe; van Duijn, Cornelia M; Bennett, David A; Schmidt, Reinhold; Longstreth, William T; Mosley, Thomas H; Fornage, Myriam; Launer, Lenore J; Seshadri, Sudha; Ikram, M Arfan; Debette, Stephanie

    2015-04-01

    Whether novel risk variants of Alzheimer's disease (AD) identified through genome-wide association studies also influence magnetic resonance imaging-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume, total brain volume, hippocampal volume (HV), white matter hyperintensity burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N = 8175-11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (p = 0.0054) and CD33 (rs3865444) with smaller intracranial volume (p = 0.0058). In gene-based tests, there was associations of HLA-DRB1 with total brain volume (p = 0.0006) and BIN1 with HV (p = 0.00089). A weighted AD genetic risk score was associated with smaller HV (beta ± SE = -0.047 ± 0.013, p = 0.00041), even after excluding the APOE locus (p = 0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in nondemented older community persons. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Age-Associated Pathology in Rhesus Macaques (Macaca mulatta)

    PubMed Central

    Simmons, H. A.

    2018-01-01

    The rhesus macaque (Macaca mulatta) is one of the most extensively used nonhuman primate models for human diseases. This article presents a literature review focusing on major organ systems and age-associated conditions in humans and primates, combined with information from the Wisconsin National Primate Research Center Electronic Health Record database to highlight and contrast age-associated lesions in geriatric rhesus macaques with younger cohorts. Rhesus macaques are excellent models for age-associated conditions, including diabetes, osteoarthritis, endometriosis, visual accommodation, hypertension, osteoporosis, and amyloidosis. Adenocarcinoma of the large intestine (ileocecocolic junction, cecum, and colon) is the most common spontaneous neoplasm in the rhesus macaque. A combination of cross-sectional and longitudinal studies is required to truly define mechanisms of maturation, aging, and the pathology of age-associated conditions in macaques and thus humans. The rhesus macaque is and will continue to be an appropriate and valuable model for investigation of the mechanisms and treatment of age-associated diseases. PMID:26864889

  20. Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines

    PubMed Central

    Rea, Irene Maeve; Gibson, David S.; McGilligan, Victoria; McNerlan, Susan E.; Alexander, H. Denis; Ross, Owen A.

    2018-01-01

    Cytokine dysregulation is believed to play a key role in the remodeling of the immune system at older age, with evidence pointing to an inability to fine-control systemic inflammation, which seems to be a marker of unsuccessful aging. This reshaping of cytokine expression pattern, with a progressive tendency toward a pro-inflammatory phenotype has been called “inflamm-aging.” Despite research there is no clear understanding about the causes of “inflamm-aging” that underpin most major age-related diseases, including atherosclerosis, diabetes, Alzheimer’s disease, rheumatoid arthritis, cancer, and aging itself. While inflammation is part of the normal repair response for healing, and essential in keeping us safe from bacterial and viral infections and noxious environmental agents, not all inflammation is good. When inflammation becomes prolonged and persists, it can become damaging and destructive. Several common molecular pathways have been identified that are associated with both aging and low-grade inflammation. The age-related change in redox balance, the increase in age-related senescent cells, the senescence-associated secretory phenotype (SASP) and the decline in effective autophagy that can trigger the inflammasome, suggest that it may be possible to delay age-related diseases and aging itself by suppressing pro-inflammatory molecular mechanisms or improving the timely resolution of inflammation. Conversely there may be learning from molecular or genetic pathways from long-lived cohorts who exemplify good quality aging. Here, we will discuss some of the current ideas and highlight molecular pathways that appear to contribute to the immune imbalance and the cytokine dysregulation, which is associated with “inflammageing” or parainflammation. Evidence of these findings will be drawn from research in cardiovascular disease, cancer, neurological inflammation and rheumatoid arthritis. PMID:29686666

  1. Chronic disease prevalence and associations in a cohort of Australian men: The Florey Adelaide Male Ageing Study (FAMAS)

    PubMed Central

    Martin, Sean A; Haren, Matthew T; Taylor, Anne W; Middleton, Sue M; Wittert, Gary A

    2008-01-01

    Background An increasing proportion of Australia's chronic disease burden is carried by the ageing male. The aim of this study was to determine the prevalence of asthma, cancer, diabetes, angina and musculoskeletal conditions and their relationship to behavioural and socio-demographic factors in a cohort of Australian men. Methods Self-reports of disease status were obtained from baseline clinic visits (August 2002 – July 2003 & July 2004 – May 2005) from 1195 randomly selected men, aged 35–80 years and living in the north-west regions of Adelaide. Initially, relative risks were assessed by regression against selected variables for each outcome. Where age-independent associations were observed with the relevant chronic disease, independent variables were fitted to customized multiadjusted models. Results The prevalence of all conditions was moderately higher in comparison to national data for age-matched men. In particular, there was an unusually high rate of men with cancer. Multiadjusted analyses revealed age as a predictor of chronic conditions (type 2 diabetes mellitus, angina, cancer & osteoarthritis). A number of socio-demographic factors, independent of age, were associated with chronic disease, including: low income status (diabetes), separation/divorce (asthma), unemployment (cancer), high waist circumference (diabetes), elevated cholesterol (angina) and a family history of obesity (angina). Conclusion Socio-demographic factors interact to determine disease status in this broadly representative group of Australian men. In addition to obesity and a positive personal and family history of disease, men who are socially disadvantaged (low income, unemployed, separated) should be specifically targeted by public health initiatives. PMID:18664294

  2. The endoplasmic reticulum stress response in aging and age-related diseases

    PubMed Central

    Brown, Marishka K.; Naidoo, Nirinjini

    2012-01-01

    The endoplasmic reticulum(ER) is a multifunctional organelle within which protein folding, lipid biosynthesis, and calcium storage occurs. Perturbations such as energy or nutrient depletion, disturbances in calcium or redox status that disrupt ER homeostasis lead to the misfolding of proteins, ER stress and up-regulation of several signaling pathways coordinately called the unfolded protein response (UPR). The UPR is characterized by the induction of chaperones, degradation of misfolded proteins and attenuation of protein translation. The UPR plays a fundamental role in the maintenance of cellular homeostasis and thus is central to normal physiology. However, sustained unresolved ER stress leads to apoptosis. Aging linked declines in expression and activity of key ER molecular chaperones and folding enzymes compromise proper protein folding and the adaptive response of the UPR. One mechanism to explain age associated declines in cellular functions and age-related diseases is a progressive failure of chaperoning systems. In many of these diseases, proteins or fragments of proteins convert from their normally soluble forms to insoluble fibrils or plaques that accumulate in a variety of organs including the liver, brain or spleen. This group of diseases, which typically occur late in life includes Alzheimer's, Parkinson's, type II diabetes and a host of less well known but often equally serious conditions such as fatal familial insomnia. The UPR is implicated in many of these neurodegenerative and familial protein folding diseases as well as several cancers and a host of inflammatory diseases including diabetes, atherosclerosis, inflammatory bowel disease and arthritis. This review will discuss age-related changes in the ER stress response and the role of the UPR in age-related diseases. PMID:22934019

  3. Systemic oxidative stress associated with the neurological diseases of aging.

    PubMed

    Serra, Jorge A; Domínguez, Raúl O; Marschoff, Enrique R; Guareschi, Eduardo M; Famulari, Arturo L; Boveris, Alberto

    2009-12-01

    Markers of oxidative stress were measured in blood samples of 338 subjects (965 observations): Alzheimer's, vascular dementia, diabetes (type II) superimposed to dementias, Parkinson's disease and controls. Patients showed increased thiobarbituric acid reactive substances (+21%; P < 0.05), copper-zinc superoxide dismutase (+64%; P < 0.001) and decreased antioxidant capacity (-28%; P < 0.001); pairs of variables resulted linearly related across groups (P < 0.001). Catalase and glutathione peroxidase, involved in discrimination between diseases, resulted non-significant. When diabetes is superimposed with dementias, changes resulted less marked but significant. Also, superoxide dismutase resulted not linearly correlated with any other variable or age-related (pure Alzheimer's peaks at 70 years, P < 0.001). Systemic oxidative stress was significantly associated (P < 0.001) with all diseases indicating a disbalance in peripheral/adaptive responses to oxidative disorders through different free radical metabolic pathways. While other changes - methionine cycle, insulin correlation - are also associated with dementias, the responses presented here show a simple linear relation between prooxidants and antioxidant defenses.

  4. Molecular Diagnostics of Ageing and Tackling Age-related Disease.

    PubMed

    Timmons, James A

    2017-01-01

    As average life expectancy increases there is a greater focus on health-span and, in particular, how to treat or prevent chronic age-associated diseases. Therapies which were able to control 'biological age' with the aim of postponing chronic and costly diseases of old age require an entirely new approach to drug development. Molecular technologies and machine-learning methods have already yielded diagnostics that help guide cancer treatment and cardiovascular procedures. Discovery of valid and clinically informative diagnostics of human biological age (combined with disease-specific biomarkers) has the potential to alter current drug-discovery strategies, aid clinical trial recruitment and maximize healthy ageing. I will review some basic principles that govern the development of 'ageing' diagnostics, how such assays could be used during the drug-discovery or development process. Important logistical and statistical considerations are illustrated by reviewing recent biomarker activity in the field of Alzheimer's disease, as dementia represents the most pressing of priorities for the pharmaceutical industry, as well as the chronic disease in humans most associated with age. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Epidemiology of Clostridium difficile-associated disease at University Hospital Basel including molecular characterisation of the isolates 2006-2007.

    PubMed

    Fenner, L; Frei, R; Gregory, M; Dangel, M; Stranden, A; Widmer, A F

    2008-12-01

    A prospective study was conducted during a one-year period between 2006 and 2007 to describe the epidemiology of Clostridium difficile-associated disease (CDAD) at University Hospital Basel, Switzerland (UHBS) and to determine phenotypic and genotypic features of C. difficile strains isolated at the Microbiology Laboratory UHBS including strains from regional non-university hospitals. We prospectively identified 78 CDAD cases at UHBS with an incidence of 2.65/1,000 hospitalised patients or 2.3/10,000 patient-days. Sixteen patients (20.5%) were infected with clindamycin-resistant strains of PCR-ribotype 027 during an outbreak at the geriatric hospital. Among 124 single-patient isolates, 28 (22.6%) were resistant to moxifloxacin and 34 (27.4%) were resistant to clindamycin, but all remained susceptible to metronidazole and vancomycin. Of 102 toxigenic isolates, 19 (18.7%) had an 18-bp deletion in the tcdC gene, eight (7.8%) a 39-bp deletion, and one (1.0%) a 54-bp deletion. Genes for binary toxin were present in 27 (21.8%). PCR-ribotype 027 was associated with older age (median age 83.5 vs. 65.5 years, p < 0.0001) and longer duration of hospitalisation before onset of disease (median 15.5 vs. 9 days, p = 0.014) with a trend towards higher crude mortality, more severe disease, and previous use of macrolides compared to ribotype non-027. Overall, severe disease correlated with use of a nasogastric tube and surprisingly shorter duration of hospitalisation before onset of disease. Today, laboratory-based and epidemiological surveillance systems are required to monitor CDAD cases and emergence of new epidemic strains.

  6. The role of p66Shc deletion in age-associated arterial dysfunction and disease states.

    PubMed

    Camici, Giovanni G; Cosentino, Francesco; Tanner, Felix C; Lüscher, Thomas F

    2008-11-01

    Accumulation of oxidative stress with age is hypothesized to be the primary causative mediator of age-associated diseases. Among different tissues, aging vessels are known to accumulate oxidative damage and undergo functional impairment. Oxidative stress affects the availability and/or balance of key regulators of vascular homeostasis and favors the development of cardiovascular disease. Reactive oxygen species are generated by different intracellular molecular pathways principally located in the cytoplasm and in the mitochondria. The mitochondrial enzyme p66Shc is an adaptor protein and plays an important role as a redox enzyme implicated in mitochondrial reactive oxygen species generation and translation of oxidative signals into apoptosis. Mice lacking p66Shc-/- gene display reduced production of intracellular oxidants and a 30% prolonged life span. For this reasons, a series of studies conceived to elucidate the function of p66Shc and its possible implication in age-associated cardiovascular diseases have been carried out. Indeed, p66Shc-/- mice have been shown to be protected from age-dependent endothelial dysfunction as well as age-related risk factors such as diabetes and hypercholesterolemia. This review focuses on delineating the role of the p66Shc adaptor protein and its potential implication in the pathophysiology of aging and age-related cardiovascular disease.

  7. Physical activity and telomere biology: exploring the link with aging-related disease prevention.

    PubMed

    Ludlow, Andrew T; Roth, Stephen M

    2011-02-21

    Physical activity is associated with reduced risk of several age-related diseases as well as with increased longevity in both rodents and humans. Though these associations are well established, evidence of the molecular and cellular factors associated with reduced disease risk and increased longevity resulting from physical activity is sparse. A long-standing hypothesis of aging is the telomere hypothesis: as a cell divides, telomeres shorten resulting eventually in replicative senescence and an aged phenotype. Several reports have recently associated telomeres and telomere-related proteins to diseases associated with physical inactivity and aging including cardiovascular disease, insulin resistance, and hypertension. Interestingly several reports have also shown that longer telomeres are associated with higher physical activity levels, indicating a potential mechanistic link between physical activity, reduced age-related disease risk, and longevity. The primary purpose of this review is to discuss the potential importance of physical activity in telomere biology in the context of inactivity- and age-related diseases. A secondary purpose is to explore potential mechanisms and important avenues for future research in the field of telomeres and diseases associated with physical inactivity and aging.

  8. Nonalcoholic fatty liver disease is associated with atherosclerosis in middle-aged and elderly Chinese.

    PubMed

    Huang, Yun; Bi, Yufang; Xu, Min; Ma, Zhimin; Xu, Yu; Wang, Tiange; Li, Mian; Liu, Yu; Lu, Jieli; Chen, Yuhong; Huang, Fei; Xu, Baihui; Zhang, Jie; Wang, Weiqing; Li, Xiaoying; Ning, Guang

    2012-09-01

    To evaluate the associations between nonalcoholic fatty liver disease (NAFLD) and atherosclerosis. A total of 8632 participants aged ≥ 40 years from Jiading district, Shanghai, were included in the present study. The presence of NAFLD was evaluated by ultrasonography. Carotid intima-media thickness (CIMT) and brachial-ankle pulse wave velocity (ba-PWV) were measured in each participant. The prevalence of NAFLD was 30.0% in the total population, with 30.3% in men and 29.9% in women, respectively. Subjects with NAFLD had remarkably higher CIMT and ba-PWV compared with those without NAFLD (0.594 ± 0.105 mm versus 0.578±0.109 mm, P<0.0001; 1665 ± 424 cm/s versus 1558 ± 430 cm/s, P<0.0001). Subjects with both NAFLD and metabolic syndrome had significantly higher CIMT and ba-PWV compared with those with neither or either of these 2 diseases after adjustment for age and sex (all P<0.05). Logistic regressions also revealed that NAFLD conferred 35% and 30% increased odds ratios of elevated CIMT and ba-PWV, independent of conventional risk factors and the presence of metabolic syndrome. NAFLD was associated with elevated CIMT and ba-PWV, independent of conventional cardiovascular disease risk factors and metabolic syndrome. The effects of NAFLD and metabolic syndrome on atherosclerosis might not fully overlap.

  9. Physical frailty in older persons is associated with Alzheimer disease pathology.

    PubMed

    Buchman, Aron S; Schneider, Julie A; Leurgans, Sue; Bennett, David A

    2008-08-12

    We examined the extent to which physical frailty in older persons is associated with common age-related brain pathology, including cerebral infarcts, Lewy body pathology, and Alzheimer disease (AD) pathology. We studied brain autopsies from 165 deceased participants from the Rush Memory and Aging Project, a longitudinal clinical-pathologic study of aging. Physical frailty, based on four components, including grip strength, time to walk 8 feet, body composition, and fatigue, was assessed at annual clinical evaluations. Multiple regression analyses were used to examine the relation of postmortem neuropathologic findings to frailty proximate to death, controlling for age, sex, and education. The mean age at death was 88.1 years (SD = 5.7 years). The level of AD pathology was associated with frailty proximate to death ( = 0.252, SE = 0.077, p = 0.001), accounting for 4% of the variance of physical frailty. Neither cerebral infarcts ( = -0.121, SE = 0.115, p = 0.294) nor Lewy body disease pathology ( = 0.07, SE = 0.156, p = 0.678) was associated with frailty. These associations were unchanged after controlling for the time interval from last clinical evaluation to autopsy. The association of AD pathology with frailty did not differ by the presence of dementia, and this association was unchanged even after considering potential confounders, including physical activity; parkinsonian signs; pulmonary function; or history of chronic diseases, including vascular risk factors, vascular disease burden, falls, joint pain, or use of antipsychotic or antihypertensive medications. Physical frailty in old age is associated with Alzheimer disease pathology in older persons with and without dementia.

  10. Amniotic Epithelial Cells: A New Tool to Combat Aging and Age-Related Diseases?

    PubMed Central

    Di Germanio, Clara; Bernier, Michel; de Cabo, Rafael; Barboni, Barbara

    2016-01-01

    The number of elderly people is growing at an unprecedented rate and this increase of the aging population is expected to have a direct impact on the incidence of age-related diseases and healthcare-associated costs. Thus, it is imperative that new tools are developed to fight and slow age-related diseases. Regenerative medicine is a promising strategy for the maintenance of health and function late in life; however, stem cell-based therapies face several challenges including rejection and tumor transformation. As an alternative, the placenta offers an extraordinary source of fetal stem cells, including the amniotic epithelial cells (AECs), which retain some of the characteristics of embryonic stem cells, but show low immunogenicity, together with immunomodulatory and anti-inflammatory activities. Because of these characteristics, AECs have been widely utilized in regenerative medicine. This perspective highlights different mechanisms triggered by transplanted AECs that could be potentially useful for anti-aging therapies, which include: Graft and differentiation for tissue regeneration in age-related settings, anti-inflammatory behavior to combat “inflammaging,” anti-tumor activity, direct lifespan and healthspan extension properties, and possibly rejuvenation in a manner reminiscent of heterochronic parabiosis. Here, we critically discuss benefits and limitation of AECs-based therapies in age-related diseases. PMID:27921031

  11. Nosocomial (Health Care-Associated) Legionnaire's Disease.

    PubMed

    Agarwal, Shanu; Abell, Virginia; File, Thomas M

    2017-03-01

    Nosocomial Legionnaire's disease is most frequently associated with presence of the organism in hospital water systems. Patients are often susceptible as a result of age, underlying comorbidities, or immunosuppression. Prevention focuses on reducing the reservoir within water systems and includes super heating, ultraviolent light, chlorination, silver-copper ionization, and distal filtration. This article reviews the epidemiology of health care-associated Legionnaire's disease, reviews characteristics of several health care-associated outbreaks, and discusses strategies to prevent health care-associated infection. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Prevention of Mutation, Cancer, and Other Age-Associated Diseases by Optimizing Micronutrient Intake

    PubMed Central

    Ames, Bruce N.

    2010-01-01

    I review three of our research efforts which suggest that optimizing micronutrient intake will in turn optimize metabolism, resulting in decreased DNA damage and less cancer as well as other degenerative diseases of aging. (1) Research on delay of the mitochondrial decay of aging, including release of mutagenic oxidants, by supplementing rats with lipoic acid and acetyl carnitine. (2) The triage theory, which posits that modest micronutrient deficiencies (common in much of the population) accelerate molecular aging, including DNA damage, mitochondrial decay, and supportive evidence for the theory, including an in-depth analysis of vitamin K that suggests the importance of achieving optimal micronutrient intake for longevity. (3) The finding that decreased enzyme binding constants (increased Km) for coenzymes (or substrates) can result from protein deformation and loss of function due to an age-related decline in membrane fluidity, or to polymorphisms or mutation. The loss of enzyme function can be compensated by a high dietary intake of any of the B vitamins, which increases the level of the vitamin-derived coenzyme. This dietary remediation illustrates the importance of understanding the effects of age and polymorphisms on optimal micronutrient requirements. Optimizing micronutrient intake could have a major effect on the prevention of cancer and other degenerative diseases of aging. PMID:20936173

  13. A common copy number variation polymorphism in the CNTNAP2 gene: sexual dimorphism in association with healthy aging and disease.

    PubMed

    Iakoubov, Leonid; Mossakowska, Malgorzata; Szwed, Malgorzata; Puzianowska-Kuznicka, Monika

    2015-01-01

    New therapeutic targets are needed to fight aging-related diseases and increase life span. A new female-specific association with diseases and limited survival past 80 years was recently reported for a copy number variation (CNV) in the CNTNAP4 gene from the neurexin superfamily. We asked whether there are CNVs that are associated with aging phenotypes within other genes from the neurexin superfamily and whether this association is sex specific. Select CNV polymorphisms were genotyped with proprietary TaqMan qPCR assays. A case/control study, in which a group of 81- to 90-year-old community-dwelling Caucasians with no chronic diseases (case) was compared to a similar control group of 65- to 75-year-olds, revealed a negative association with healthy aging for the ins allele of common esv11910 CNV in the CNTNAP2 gene (n = 388; OR = 0.29, 95% CI: 0.14-0.59, p = 0.0004 for males, and OR = 0.82, 95% CI: 0.42-1.57, p = 0.625 for females). This male-specific association was validated in a study of an independent group of 76- to 80-year-olds. To look for a corresponding positive association of the allele with aging-related diseases, two case subgroups of 81- to 90-year-olds, one composed of individuals with cognitive impairment and the other with various diseases not directly related to the nervous system, such as cardiovascular diseases, etc., were compared to a healthy control subgroup of the same age. A positive male-specific association was found for both cases (OR = 2.75, p = 0.008 for association with cognitive impairment, and OR = 3.18, p = 0.002 for other diseases combined). A new male-specific association with aging is reported for a CNV in the CNTNAP2 gene. The polymorphism might be useful for diagnosing individual genetic predispositions to healthy aging versus aging complicated by chronic diseases. © 2014 S. Karger AG, Basel.

  14. Dihydrocapsiate improved age-associated impairments in mice by increasing energy expenditure.

    PubMed

    Ohyama, Kana; Suzuki, Katsuya

    2017-11-01

    Metabolic dysfunction is associated with aging and results in age-associated chronic diseases, including type 2 diabetes mellitus, cardiovascular disease, and stroke. Hence, there has been a focus on increasing energy expenditure in aged populations to protect them from age-associated diseases. Dihydrocapsiate (DCT) is a compound that belongs to the capsinoid family. Capsinoids are capsaicin analogs that are found in nonpungent peppers and increase whole body energy expenditure. However, their effect on energy expenditure has been reported only in young populations, and to date the effectiveness of DCT in increasing energy expenditure in aged populations has not been investigated. In this study, we investigated whether DCT supplementation in aged mice improves age-associated impairments. We obtained 5-wk-old and 1-yr-old male C57BL/6J mice and randomly assigned the aged mice to two groups, resulting in a total of three groups: 1 ) young mice, 2 ) old mice, and 3 ) old mice supplemented with 0.3% DCT. After 12 wk of supplementation, blood and tissue samples were collected and analyzed. DCT significantly suppressed age-associated fat accumulation, adipocyte hypertrophy, and liver steatosis. In addition, the DCT treatment dramatically suppressed age-associated increases in hepatic inflammation, immune cell infiltration, and oxidative stress. DCT exerted these suppression effects by increasing energy expenditure linked to upregulation of both the oxidative phosphorylation gene program and fatty acid oxidation in skeletal muscle. These results indicate that DCT efficiently improves age-associated impairments, including liver steatosis and inflammation, in part by increasing energy expenditure via activation of the fat oxidation pathway in skeletal muscle. Copyright © 2017 the American Physiological Society.

  15. Is Chronic Obstructive Pulmonary Disease an Accelerated Aging Disease?

    PubMed

    MacNee, William

    2016-12-01

    Aging is one of the most important risk factors for most chronic diseases. The worldwide increase in life expectancy has been accompanied by an increase in the prevalence of age-related diseases that result in significant morbidity and mortality and place an enormous burden on healthcare and resources. Aging is a progressive degeneration of the tissues that has a negative impact on the structure and function of vital organs. The lung ages, resulting in decreased function and reduced capacity to respond to environmental stresses and injury. Many of the changes that occur in the lungs with normal aging, such as decline in lung function, increased gas trapping, loss of lung elastic recoil, and enlargement of the distal air spaces, also are present in chronic obstructive pulmonary disease (COPD). The prevalence of COPD is two to three times higher in people over the age of 60 years than in younger age groups. Indeed, COPD has been considered a condition of accelerated lung aging. Several mechanisms associated with aging are present in the lungs of patients with COPD. Cell senescence is present in emphysematous lungs and is associated with shortened telomeres and decreased antiaging molecules, suggesting accelerated aging in the lungs of patients with COPD. Increasing age leads to elevated basal levels of inflammation and oxidative stress (inflammaging) and to increased immunosenescence associated with changes in both the innate and adaptive immune responses. These changes are similar to those that occur in COPD and may enhance the activity of the disease as well as increase susceptibility to exacerbations in patients with COPD. Understanding the mechanism of age-related changes in COPD may identify novel therapies for this condition.

  16. Glutathione S-transferase omega genes in Alzheimer and Parkinson disease risk, age-at-diagnosis and brain gene expression: an association study with mechanistic implications.

    PubMed

    Allen, Mariet; Zou, Fanggeng; Chai, High Seng; Younkin, Curtis S; Miles, Richard; Nair, Asha A; Crook, Julia E; Pankratz, V Shane; Carrasquillo, Minerva M; Rowley, Christopher N; Nguyen, Thuy; Ma, Li; Malphrus, Kimberly G; Bisceglio, Gina; Ortolaza, Alexandra I; Palusak, Ryan; Middha, Sumit; Maharjan, Sooraj; Georgescu, Constantin; Schultz, Debra; Rakhshan, Fariborz; Kolbert, Christopher P; Jen, Jin; Sando, Sigrid B; Aasly, Jan O; Barcikowska, Maria; Uitti, Ryan J; Wszolek, Zbigniew K; Ross, Owen A; Petersen, Ronald C; Graff-Radford, Neill R; Dickson, Dennis W; Younkin, Steven G; Ertekin-Taner, Nilüfer

    2012-04-11

    Glutathione S-transferase omega-1 and 2 genes (GSTO1, GSTO2), residing within an Alzheimer and Parkinson disease (AD and PD) linkage region, have diverse functions including mitigation of oxidative stress and may underlie the pathophysiology of both diseases. GSTO polymorphisms were previously reported to associate with risk and age-at-onset of these diseases, although inconsistent follow-up study designs make interpretation of results difficult. We assessed two previously reported SNPs, GSTO1 rs4925 and GSTO2 rs156697, in AD (3,493 ADs vs. 4,617 controls) and PD (678 PDs vs. 712 controls) for association with disease risk (case-controls), age-at-diagnosis (cases) and brain gene expression levels (autopsied subjects). We found that rs156697 minor allele associates with significantly increased risk (odds ratio = 1.14, p = 0.038) in the older ADs with age-at-diagnosis > 80 years. The minor allele of GSTO1 rs4925 associates with decreased risk in familial PD (odds ratio = 0.78, p = 0.034). There was no other association with disease risk or age-at-diagnosis. The minor alleles of both GSTO SNPs associate with lower brain levels of GSTO2 (p = 4.7 × 10-11-1.9 × 10-27), but not GSTO1. Pathway analysis of significant genes in our brain expression GWAS, identified significant enrichment for glutathione metabolism genes (p = 0.003). These results suggest that GSTO locus variants may lower brain GSTO2 levels and consequently confer AD risk in older age. Other glutathione metabolism genes should be assessed for their effects on AD and other chronic, neurologic diseases.

  17. Visualizing disease associations: graphic analysis of frequency distributions as a function of age using moving average plots (MAP) with application to Alzheimer's and Parkinson's disease.

    PubMed

    Payami, Haydeh; Kay, Denise M; Zabetian, Cyrus P; Schellenberg, Gerard D; Factor, Stewart A; McCulloch, Colin C

    2010-01-01

    Age-related variation in marker frequency can be a confounder in association studies, leading to both false-positive and false-negative findings and subsequently to inconsistent reproducibility. We have developed a simple method, based on a novel extension of moving average plots (MAP), which allows investigators to inspect the frequency data for hidden age-related variations. MAP uses the standard case-control association data and generates a birds-eye view of the frequency distributions across the age spectrum; a picture in which one can see if, how, and when the marker frequencies in cases differ from that in controls. The marker can be specified as an allele, genotype, haplotype, or environmental factor; and age can be age-at-onset, age when subject was last known to be unaffected, or duration of exposure. Signature patterns that emerge can help distinguish true disease associations from spurious associations due to age effects, age-varying associations from associations that are uniform across all ages, and associations with risk from associations with age-at-onset. Utility of MAP is illustrated by application to genetic and epidemiological association data for Alzheimer's and Parkinson's disease. MAP is intended as a descriptive method, to complement standard statistical techniques. Although originally developed for age patterns, MAP is equally useful for visualizing any quantitative trait.

  18. Lipid and Alzheimer's disease genes associated with healthy aging and longevity in healthy oldest-old.

    PubMed

    Tindale, Lauren C; Leach, Stephen; Spinelli, John J; Brooks-Wilson, Angela R

    2017-03-28

    Several studies have found that long-lived individuals do not appear to carry lower numbers of common disease-associated variants than ordinary people; it has been hypothesized that they may instead carry protective variants. An intriguing type of protective variant is buffering variants that protect against variants that have deleterious effects. We genotyped 18 variants in 15 genes related to longevity or healthy aging that had been previously reported as having a gene-gene interaction or buffering effect. We compared a group of 446 healthy oldest-old 'Super-Seniors' (individuals 85 or older who have never been diagnosed with cancer, cardiovascular disease, dementia, diabetes or major pulmonary disease) to 421 random population-based midlife controls. Cases and controls were of European ancestry. Association tests of individual SNPs showed that Super-Seniors were less likely than controls to carry an APOEε4 allele or a haptoglobin HP2 allele. Interactions between APOE/FOXO3, APOE/CRYL1, and LPA/CRYL1 did not remain significant after multiple testing correction. In a network analysis of the candidate genes, lipid and cholesterol metabolism was a common theme. APOE, HP, and CRYL1 have all been associated with Alzheimer's Disease, the pathology of which involves lipid and cholesterol pathways. Age-related changes in lipid and cholesterol maintenance, particularly in the brain, may be central to healthy aging and longevity.

  19. Dietary Approaches that Delay Age-Related Diseases

    PubMed Central

    Everitt, Arthur V; Hilmer, Sarah N; Brand-Miller, Jennie C; Jamieson, Hamish A; Truswell, A Stewart; Sharma, Anita P; Mason, Rebecca S; Morris, Brian J; Le Couteur, David G

    2006-01-01

    Reducing food intake in lower animals such as the rat decreases body weight, retards many aging processes, delays the onset of most diseases of old age, and prolongs life. A number of clinical trials of food restriction in healthy adult human subjects running over 2–15 years show significant reductions in body weight, blood cholesterol, blood glucose, and blood pressure, which are risk factors for the development of cardiovascular disease and diabetes. Lifestyle interventions that lower energy balance by reducing body weight such as physical exercise can also delay the development of diabetes and cardiovascular disease. In general, clinical trials are suggesting that diets high in calories or fat along with overweight are associated with increased risk for cardiovascular disease, type 2 diabetes, some cancers, and dementia. There is a growing literature indicating that specific dietary constituents are able to influence the development of age-related diseases, including certain fats (trans fatty acids, saturated, and polyunsaturated fats) and cholesterol for cardiovascular disease, glycemic index and fiber for diabetes, fruits and vegetables for cardiovascular disease, and calcium and vitamin D for osteoporosis and bone fracture. In addition, there are dietary compounds from different functional foods, herbs, and neutraceuticals such as ginseng, nuts, grains, and polyphenols that may affect the development of age-related diseases. Long-term prospective clinical trials will be needed to confirm these diet—disease relationships. On the basis of current research, the best diet to delay age-related disease onset is one low in calories and saturated fat and high in wholegrain cereals, legumes, fruits and vegetables, and which maintains a lean body weight. Such a diet should become a key component of healthy aging, delaying age-related diseases and perhaps intervening in the aging process itself. Furthermore, there are studies suggesting that nutrition in childhood

  20. Telomeres in aging and disease: lessons from zebrafish.

    PubMed

    Carneiro, Madalena C; de Castro, Inês Pimenta; Ferreira, Miguel Godinho

    2016-07-01

    Age is the highest risk factor for some of the most prevalent human diseases, including cancer. Telomere shortening is thought to play a central role in the aging process in humans. The link between telomeres and aging is highlighted by the fact that genetic diseases causing telomerase deficiency are associated with premature aging and increased risk of cancer. For the last two decades, this link has been mostly investigated using mice that have long telomeres. However, zebrafish has recently emerged as a powerful and complementary model system to study telomere biology. Zebrafish possess human-like short telomeres that progressively decline with age, reaching lengths in old age that are observed when telomerase is mutated. The extensive characterization of its well-conserved molecular and cellular physiology makes this vertebrate an excellent model to unravel the underlying relationship between telomere shortening, tissue regeneration, aging and disease. In this Review, we explore the advantages of using zebrafish in telomere research and discuss the primary discoveries made in this model that have contributed to expanding our knowledge of how telomere attrition contributes to cellular senescence, organ dysfunction and disease. © 2016. Published by The Company of Biologists Ltd.

  1. Oxidative Stress and Epigenetic Regulation in Ageing and Age-Related Diseases

    PubMed Central

    Cencioni, Chiara; Spallotta, Francesco; Martelli, Fabio; Valente, Sergio; Mai, Antonello; Zeiher, Andreas M.; Gaetano, Carlo

    2013-01-01

    Recent statistics indicate that the human population is ageing rapidly. Healthy, but also diseased, elderly people are increasing. This trend is particularly evident in Western countries, where healthier living conditions and better cures are available. To understand the process leading to age-associated alterations is, therefore, of the highest relevance for the development of new treatments for age-associated diseases, such as cancer, diabetes, Alzheimer and cardiovascular accidents. Mechanistically, it is well accepted that the accumulation of intracellular damage determined by reactive oxygen species (ROS) might orchestrate the progressive loss of control over biological homeostasis and the functional impairment typical of aged tissues. Here, we review how epigenetics takes part in the control of stress stimuli and the mechanisms of ageing physiology and physiopathology. Alteration of epigenetic enzyme activity, histone modifications and DNA-methylation is, in fact, typically associated with the ageing process. Specifically, ageing presents peculiar epigenetic markers that, taken altogether, form the still ill-defined “ageing epigenome”. The comprehension of mechanisms and pathways leading to epigenetic modifications associated with ageing may help the development of anti-ageing therapies. PMID:23989608

  2. The nutritional geometry of liver disease including non-alcoholic fatty liver disease.

    PubMed

    Simpson, Stephen J; Raubenheimer, David; Cogger, Victoria C; Macia, Laurence; Solon-Biet, Samantha M; Le Couteur, David G; George, Jacob

    2018-02-01

    Nutrition has a profound effect on chronic liver disease, especially non-alcoholic fatty liver disease (NAFLD). Most observational studies and clinical trials have focussed on the effects of total energy intake, or the intake of individual macronutrients and certain micronutrients, such as vitamin D, on liver disease. Although these studies have shown the importance of nutrition on hepatic outcomes, there is not yet any unifying framework for understanding the relationship between diet and liver disease. The Geometric Framework for Nutrition (GFN) is an innovative model for designing nutritional experiments or interpreting nutritional data that can determine the effects of nutrients and their interactions on animal behaviour and phenotypes. Recently the GFN has provided insights into the relationship between dietary energy and macronutrients on obesity and ageing in mammals including humans. Mouse studies using the GFN have disentangled the effects of macronutrients on fatty liver and the gut microbiome. The GFN is likely to play a significant role in disentangling the effects of nutrients on liver disease, especially NAFLD, in humans. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  3. Genome and Epigenome Editing in Mechanistic Studies of Human Aging and Aging-Related Disease

    PubMed Central

    Lau, Cia-Hin; Suh, Yousin

    2016-01-01

    The recent advent of genome and epigenome editing technologies has provided a new paradigm in which the landscape of the human genome and epigenome can be precisely manipulated in their native context. Genome and epigenome editing technologies can be applied to many aspects of aging research and offer the potential to development novel therapeutics against age-related diseases. Here, we discuss the latest technological advances in the CRISPR-based genome and epigenome editing toolbox, and provide an insight into how these synthetic biology tools could facilitate aging research by establishing in vitro cell- and in vivo animal-models to dissect genetic and epigenetic mechanisms underlying aging and age-related diseases. We discuss recent developments in the field with the aims to precisely modulate gene expression and dynamic epigenetic landscapes in a spatial- and temporal- manner in cellular and animal models, by complementing the CRISPR-based editing capability with conditional genetic manipulation tools, including chemically inducible expression system, optogenetics, logic gate genetic circuits, tissue-specific promoters, and serotype-specific adeno-associated virus. We also discuss how the combined use of genome and epigenome editing tools permits investigators to uncover novel molecular pathways involved in pathophysiology and etiology conferred by risk variants associated with aging and aging-related disease. A better understanding of the genetic and epigenetic regulatory mechanisms underlying human aging and age-related disease will significantly contribute to the developments of new therapeutic interventions for extending healthspan and lifespan, ultimately improving the quality of life in the elderly populations. PMID:27974723

  4. Genome and Epigenome Editing in Mechanistic Studies of Human Aging and Aging-Related Disease.

    PubMed

    Lau, Cia-Hin; Suh, Yousin

    2017-01-01

    The recent advent of genome and epigenome editing technologies has provided a new paradigm in which the landscape of the human genome and epigenome can be precisely manipulated in their native context. Genome and epigenome editing technologies can be applied to many aspects of aging research and offer the potential to develop novel therapeutics against age-related diseases. Here, we discuss the latest technological advances in the CRISPR-based genome and epigenome editing toolbox, and provide insight into how these synthetic biology tools could facilitate aging research by establishing in vitro cell and in vivo animal models to dissect genetic and epigenetic mechanisms underlying aging and age-related diseases. We discuss recent developments in the field with the aims to precisely modulate gene expression and dynamic epigenetic landscapes in a spatial and temporal manner in cellular and animal models, by complementing the CRISPR-based editing capability with conditional genetic manipulation tools including chemically inducible expression systems, optogenetics, logic gate genetic circuits, tissue-specific promoters, and the serotype-specific adeno-associated virus. We also discuss how the combined use of genome and epigenome editing tools permits investigators to uncover novel molecular pathways involved in the pathophysiology and etiology conferred by risk variants associated with aging and aging-related disease. A better understanding of the genetic and epigenetic regulatory mechanisms underlying human aging and age-related disease will significantly contribute to the developments of new therapeutic interventions for extending health span and life span, ultimately improving the quality of life in the elderly populations. © 2016 S. Karger AG, Basel.

  5. Involvement of blood mononuclear cells in the infertility, age-associated diseases and cancer treatment

    PubMed Central

    Bukovsky, Antonin

    2016-01-01

    Blood mononuclear cells consist of T cells and monocyte derived cells. Beside immunity, the blood mononuclear cells belong to the complex tissue control system (TCS), where they exhibit morphostatic function by stimulating proliferation of tissue stem cells followed by cellular differentiation, that is stopped after attaining the proper functional stage, which differs among various tissue types. Therefore, the term immune and morphostatic system (IMS) should be implied. The TCS-mediated morphostasis also consists of vascular pericytes controlled by autonomic innervation, which is regulating the quantity of distinct tissues in vivo. Lack of proper differentiation of tissue cells by TCS causes either tissue underdevelopment, e.g., muscular dystrophy, or degenerative functional failures, e.g., type 1 diabetes and age-associated diseases. With the gradual IMS regression after 35 years of age the gonadal infertility develops, followed by a growing incidence of age-associated diseases and cancers. Without restoring an altered TCS function in a degenerative disease, the implantation of tissue-specific stem cells alone by regenerative medicine can not be successful. Transfused young blood could temporarily restore fertility to enable parenthood. The young blood could also temporarily alleviate aging diseases, and this can be extended by substances inducing IMS regeneration, like the honey bee propolis. The local and/or systemic use of honey bee propolis stopped hair and teeth loss, regressed varicose veins, improved altered hearing, and lowered high blood pressure and sugar levels. Complete regression of stage IV ovarian cancer with liver metastases after a simple elaborated immunotherapy is also reported. PMID:28074124

  6. Molecular Insights into the Pathogenesis of Alzheimer's Disease and Its Relationship to Normal Aging

    PubMed Central

    Podtelezhnikov, Alexei A.; Tanis, Keith Q.; Nebozhyn, Michael; Ray, William J.

    2011-01-01

    Alzheimer's disease (AD) is a complex neurodegenerative disorder that diverges from the process of normal brain aging by unknown mechanisms. We analyzed the global structure of age- and disease-dependent gene expression patterns in three regions from more than 600 brains. Gene expression variation could be almost completely explained by four transcriptional biomarkers that we named BioAge (biological age), Alz (Alzheimer), Inflame (inflammation), and NdStress (neurodegenerative stress). BioAge captures the first principal component of variation and includes genes statistically associated with neuronal loss, glial activation, and lipid metabolism. Normally BioAge increases with chronological age, but in AD it is prematurely expressed as if some of the subjects were 140 years old. A component of BioAge, Lipa, contains the AD risk factor APOE and reflects an apparent early disturbance in lipid metabolism. The rate of biological aging in AD patients, which cannot be explained by BioAge, is associated instead with NdStress, which includes genes related to protein folding and metabolism. Inflame, comprised of inflammatory cytokines and microglial genes, is broadly activated and appears early in the disease process. In contrast, the disease-specific biomarker Alz was selectively present only in the affected areas of the AD brain, appears later in pathogenesis, and is enriched in genes associated with the signaling and cell adhesion changes during the epithelial to mesenchymal (EMT) transition. Together these biomarkers provide detailed description of the aging process and its contribution to Alzheimer's disease progression. PMID:22216330

  7. Life stress, glucocorticoid signaling, and the aging epigenome: Implications for aging-related diseases.

    PubMed

    Gassen, Nils C; Chrousos, George P; Binder, Elisabeth B; Zannas, Anthony S

    2017-03-01

    Life stress has been associated with accelerated cellular aging and increased risk for developing aging-related diseases; however, the underlying molecular mechanisms remain elusive. A highly relevant process that may underlie this association is epigenetic regulation. In this review, we build upon existing evidence to propose a model whereby exposure to life stress, in part via its effects on the hypothalamic-pituitary axis and the glucocorticoid signaling system, may alter the epigenetic landscape across the lifespan and, consequently, influence genomic regulation and function in ways that are conducive to the development of aging-related diseases. This model is supported by recent studies showing that life stressors and stress-related phenotypes can accelerate epigenetic aging, a measure that is based on DNA methylation prediction of chronological age and has been associated with several aging-related disease phenotypes. We discuss the implications of this model for the prevention and treatment of aging-related diseases, as well as the challenges and limitations of this line of research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Disease and age pattern of hospitalisation and associated costs in India: 1995-2014.

    PubMed

    Kastor, Anshul; Mohanty, Sanjay K

    2018-01-24

    The prime objective of this study is to examine the trends of disease and age pattern of hospitalisation and associated costs in India during 1995-2014. Present study used nationally representative data on morbidity and healthcare from the 52nd (1995) and 71st (2014) rounds of the National Sample Survey. A total of 120 942 and 65 932 households were surveyed in 1995 and 2014, respectively. Descriptive statistics, logistic regression analyses and decomposition analyses were used in examining the changes in patterns of hospitalisation and associated costs. Hospitalisation rates and costs per hospitalisation (out-of-pocket expenditure) were estimated for selected diseases and in four broad categories: communicable diseases, non-communicable diseases (NCDs), injuries and others. All the costs are presented at 2014 prices in US$. Hospitalisation rate in India has increased from 1661 in 1995 to 3699 in 2014 (per 100 000 population). It has more than doubled across all age groups. Hospitalisation among children was primarily because of communicable diseases, while NCDs were the leading cause of hospitalisation for the 40+ population. Costs per hospitalisation have increased from US$177 in 1995 to US$316 in 2014 (an increase of 79%). Costs per hospitalisation for NCDs in 2014 were US$471 compared with US$175 for communicable diseases. It was highest for cancer inpatients (US$942) followed by heart diseases (US$674). Age is the significant predictor of hospitalisation for all the selected diseases. Decomposition results showed that about three-fifth of the increase in unconditional costs per hospitalisation was due to increase in mean hospital costs, and the other two-fifth was due to increase in hospitalisation rates. There has been more than twofold increase in hospitalisation rates in India during the last two decades, and significantly higher rates were observed among infants and older adults. Increasing hospitalisation rates and costs per hospitalisation are

  9. A novel diagnostic tool reveals mitochondrial pathology in human diseases and aging.

    PubMed

    Scheibye-Knudsen, Morten; Scheibye-Alsing, Karsten; Canugovi, Chandrika; Croteau, Deborah L; Bohr, Vilhelm A

    2013-03-01

    The inherent complex and pleiotropic phenotype of mitochondrial diseases poses a significant diagnostic challenge for clinicians as well as an analytical barrier for scientists. To overcome these obstacles we compiled a novel database, www.mitodb.com, containing the clinical features of primary mitochondrial diseases. Based on this we developed a number of qualitative and quantitative measures, enabling us to determine whether a disorder can be characterized as mitochondrial. These included a clustering algorithm, a disease network, a mitochondrial barcode and two scoring algorithms. Using these tools we detected mitochondrial involvement in a number of diseases not previously recorded as mitochondrial. As a proof of principle Cockayne syndrome, ataxia with oculomotor apraxia 1 (AOA1), spinocerebellar ataxia with axonal neuropathy 1 (SCAN1) and ataxia-telangiectasia have recently been shown to have mitochondrial dysfunction and those diseases showed strong association with mitochondrial disorders. We next evaluated mitochondrial involvement in aging and detected two distinct categories of accelerated aging disorders, one of them being associated with mitochondrial dysfunction. Normal aging seemed to associate stronger with the mitochondrial diseases than the non-mitochondrial partially supporting a mitochondrial theory of aging.

  10. Infectious disease burden and cognitive function in young to middle-aged adults.

    PubMed

    Gale, Shawn D; Erickson, Lance D; Berrett, Andrew; Brown, Bruce L; Hedges, Dawson W

    2016-02-01

    Prior research has suggested an association between exposure to infectious disease and neurocognitive function in humans. While most of these studies have explored individual viral, bacterial, and even parasitic sources of infection, few have considered the potential neurocognitive burden associated with multiple infections. In this study, we utilized publically available data from a large dataset produced by the Centers for Disease Control and Prevention that included measures of neurocognitive function, sociodemographic variables, and serum antibody data for several infectious diseases. Specifically, immunoglobulin G antibodies for toxocariasis, toxoplasmosis, hepatitis A, hepatitis B, and hepatitis C, cytomegalovirus, and herpes 1 and 2 were available in 5662 subjects. We calculated an overall index of infectious-disease burden to determine if an aggregate measure of exposure to infectious disease would be associated with neurocognitive function in adults aged 20-59 years. The index predicted processing speed and learning and memory but not reaction time after controlling for age, sex, race-ethnicity, immigration status, education, and the poverty-to-income ratio. Interactions between the infectious-disease index and some sociodemographic variables were also associated with neurocognitive function. In summary, an index aggregating exposure to several infectious diseases was associated with neurocognitive function in young- to middle-aged adults. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Association between demyelinating disease and autoimmune rheumatic disease in a pediatric population.

    PubMed

    Amorim, Ana Luiza M; Cabral, Nadia C; Osaku, Fabiane M; Len, Claudio A; Oliveira, Enedina M L; Terreri, Maria Teresa

    Multiple sclerosis (MS) and neuromyelitis optica (NMO) are demyelinating diseases of the central nervous system. Autoimmunity in patients with demyelinating disease and in their families has been broadly investigated and discussed. Recent studies show a higher incidence of rheumatic autoimmune diseases among adult patients with MS or NMO and their families, but there are no studies in the pediatric population. To evaluate an association of MS and NMO with autoimmune rheumatic diseases in pediatric patients. 22 patients younger than 21 years old with MS or NMO diagnosed before the age of 18 years were evaluated regarding epidemiological data, clinical presentation, association with autoimmune diseases, family history of autoimmune diseases, laboratory findings, imaging studies and presence of auto-antibodies. Among the patients studied, there was a prevalence of females (68.1%). The mean age of symptoms onset was 8 years and 9 months and the mean current age was 16 years and 4 months. Two patients (9%) had a history of associated autoimmune rheumatic disease: one case of juvenile dermatomyositis in a patient with NMO and another of systemic lupus erythematosus in a patient with MS. Three patients (13%) had a family history of autoimmunity in first-degree relatives. Antinuclear antibody was found positive in 80% of patients with NMO and 52% of patients with MS. About 15% of antinuclear antibody-positive patients were diagnosed with rheumatologic autoimmune diseases. Among patients with demyelinating diseases diagnosed in childhood included in this study there was a high frequency of antinuclear antibody positivity but a lower association with rheumatologic autoimmune diseases than that observed in studies conducted in adults. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

  12. Genome-wide association analysis of age-at-onset in Alzheimer's disease.

    PubMed

    Kamboh, M I; Barmada, M M; Demirci, F Y; Minster, R L; Carrasquillo, M M; Pankratz, V S; Younkin, S G; Saykin, A J; Sweet, R A; Feingold, E; DeKosky, S T; Lopez, O L

    2012-12-01

    The risk of Alzheimer's disease (AD) is strongly determined by genetic factors and recent genome-wide association studies (GWAS) have identified several genes for the disease risk. In addition to the disease risk, age-at-onset (AAO) of AD has also strong genetic component with an estimated heritability of 42%. Identification of AAO genes may help to understand the biological mechanisms that regulate the onset of the disease. Here we report the first GWAS focused on identifying genes for the AAO of AD. We performed a genome-wide meta-analysis on three samples comprising a total of 2222 AD cases. A total of ~2.5 million directly genotyped or imputed single-nucleotide polymorphisms (SNPs) were analyzed in relation to AAO of AD. As expected, the most significant associations were observed in the apolipoprotein E (APOE) region on chromosome 19 where several SNPs surpassed the conservative genome-wide significant threshold (P<5E-08). The most significant SNP outside the APOE region was located in the DCHS2 gene on chromosome 4q31.3 (rs1466662; P=4.95E-07). There were 19 additional significant SNPs in this region at P<1E-04 and the DCHS2 gene is expressed in the cerebral cortex and thus is a potential candidate for affecting AAO in AD. These findings need to be confirmed in additional well-powered samples.

  13. [Association of age, inflammatory markers and subclinical atherosclerosis in subjects free from cardiovascular disease].

    PubMed

    Páramo, José A; Orbe, Josune; Beloqui, Oscar; Colina, Inmaculada; Benito, Alberto; Rodríguez, José A; Díez, Javier

    2008-09-27

    We assessed whether an independent association between inflammatory markers and age-related subclinical atherosclerosis could be found in subjects free from cardiovascular disease. Metabolic parameters, inflammatory and endothelial markers, such as high-sensitivity C-reactive protein, interleukin-6, fibrinogen and von Willebrand factor, as well as the carotid intima-media thickness were assessed in 890 asymptomatic subjects (mean age: 55 years; range: 20-80 years; 80% men) with cardiovascular risk factors. Subjects in the upper quartile (age 61-80 years) showed a significant increase of traditional risk factors, particularly arterial pressure and glucose levels (p < 0.01) as compared with lower quartiles. We also found a significant increase in the levels on inflammatory and endothelial markers (p < 0.001) and intima-media thickness (p < 0.001) in older adults. In the multivarate analysis, after adjustment for cardiovascular risk factors, intima-media thickness was independently associated with inflammation and endothelial dysfunction in older adults (p < 0.01). Besides age, systemic inflammation and vascular damage are associated with subclinical atherosclerosis in asymptomatic subjects. The age-related inflammatory profile may predispose to cardiovascular complications.

  14. Hippocampal Sclerosis of Aging, a Common Alzheimer's Disease 'Mimic': Risk Genotypes are Associated with Brain Atrophy Outside the Temporal Lobe.

    PubMed

    Nho, Kwangsik; Saykin, Andrew J; Nelson, Peter T

    2016-01-01

    Hippocampal sclerosis of aging (HS-Aging) is a common brain disease in older adults with a clinical course that is similar to Alzheimer's disease. Four single-nucleotide polymorphisms (SNPs) have previously shown association with HS-Aging. The present study investigated structural brain changes associated with these SNPs using surface-based analysis. Participants from the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI; n = 1,239), with both MRI scans and genotype data, were used to assess the association between brain atrophy and previously identified HS-Aging risk SNPs in the following genes: GRN, TMEM106B, ABCC9, and KCNMB2 (minor allele frequency for each is >30%). A fifth SNP (near the ABCC9 gene) was evaluated in post-hoc analysis. The GRN risk SNP (rs5848_T) was associated with a pattern of atrophy in the dorsomedial frontal lobes bilaterally, remarkable since GRN is a risk factor for frontotemporal dementia. The ABCC9 risk SNP (rs704180_A) was associated with multifocal atrophy whereas a SNP (rs7488080_A) nearby (∼50 kb upstream) ABCC9 was associated with atrophy in the right entorhinal cortex. Neither TMEM106B (rs1990622_T), KCNMB2 (rs9637454_A), nor any of the non-risk alleles were associated with brain atrophy. When all four previously identified HS-Aging risk SNPs were summed into a polygenic risk score, there was a pattern of associated multifocal brain atrophy in a predominately frontal pattern. We conclude that common SNPs previously linked to HS-Aging pathology were associated with a distinct pattern of anterior cortical atrophy. Genetic variation associated with HS-Aging pathology may represent a non-Alzheimer's disease contribution to atrophy outside of the hippocampus in older adults.

  15. Molecular insights into the pathogenesis of Alzheimer's disease and its relationship to normal aging.

    PubMed

    Podtelezhnikov, Alexei A; Tanis, Keith Q; Nebozhyn, Michael; Ray, William J; Stone, David J; Loboda, Andrey P

    2011-01-01

    Alzheimer's disease (AD) is a complex neurodegenerative disorder that diverges from the process of normal brain aging by unknown mechanisms. We analyzed the global structure of age- and disease-dependent gene expression patterns in three regions from more than 600 brains. Gene expression variation could be almost completely explained by four transcriptional biomarkers that we named BioAge (biological age), Alz (Alzheimer), Inflame (inflammation), and NdStress (neurodegenerative stress). BioAge captures the first principal component of variation and includes genes statistically associated with neuronal loss, glial activation, and lipid metabolism. Normally BioAge increases with chronological age, but in AD it is prematurely expressed as if some of the subjects were 140 years old. A component of BioAge, Lipa, contains the AD risk factor APOE and reflects an apparent early disturbance in lipid metabolism. The rate of biological aging in AD patients, which cannot be explained by BioAge, is associated instead with NdStress, which includes genes related to protein folding and metabolism. Inflame, comprised of inflammatory cytokines and microglial genes, is broadly activated and appears early in the disease process. In contrast, the disease-specific biomarker Alz was selectively present only in the affected areas of the AD brain, appears later in pathogenesis, and is enriched in genes associated with the signaling and cell adhesion changes during the epithelial to mesenchymal (EMT) transition. Together these biomarkers provide detailed description of the aging process and its contribution to Alzheimer's disease progression. © 2011 Podtelezhnikov et al.

  16. Distinct brain metabolic patterns separately associated with cognition, motor function, and aging in Parkinson's disease dementia.

    PubMed

    Ko, Ji Hyun; Katako, Audrey; Aljuaid, Maram; Goertzen, Andrew L; Borys, Andrew; Hobson, Douglas E; Kim, Seok Min; Lee, Chong Sik

    2017-12-01

    We explored whether patients with Parkinson's disease dementia (PDD) show a distinct spatial metabolic pattern that characterizes cognitive deficits in addition to motor dysfunction. Eighteen patients with PDD underwent 3 separate positron emission tomography sessions with [ 18 F]fluorodeoxyglucose (for glucose metabolism), fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane (for dopamine transporter density) and Pittsburgh compound-B (for beta-amyloid load). We confirmed in PDD versus normal controls, overall hypometabolism in the posterior and prefrontal brain regions accompanied with hypermetabolism in subcortical structures and the cerebellar vermis. A multivariate network analysis then revealed 3 metabolic patterns that are separately associated with cognitive performance (p = 0.042), age (p = 0.042), and motor symptom severity (p = 0.039). The age-related pattern's association with aging was replicated in healthy controls (p = 0.047) and patients with Alzheimer's disease (p = 0.002). The cognition-related pattern's association with cognitive performance was observed, with a trend-level of correlation, in patients with dementia with Lewy bodies (p = 0.084) but not in patients with Alzheimer's disease (p = 0.974). We found no association with fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane and Pittsburgh compound-B positron emission tomography with patients' cognitive performance. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Is childhood immunisation associated with atopic disease from age 7 to 32 years?

    PubMed Central

    Nakajima, Kazunori; Dharmage, Shyamali C; Carlin, John B; Wharton, Cathryn L; Jenkins, Mark A; Giles, Graham G; Abramson, Michael J; Walters, E Haydn; Hopper, John L

    2007-01-01

    Background There is ongoing conjecture over whether childhood immunisation leads to an increased risk of developing atopic diseases. Objective To examine associations between childhood immunisation and the risk of atopic disease. Method Immunisation histories of 8443 Tasmanian children born in 1961 obtained from school medical records were linked to the Tasmanian Asthma Study. Associations between immunisation status and atopic diseases were examined while adjusting for possible confounders using multiple logistic regression. Results Diphtheria immunisation was weakly associated with an increased risk of asthma by age 7 years (odds ratio (OR) 1.3, 95% confidence interval (CI) 1.1 to 1.7), but there was no evidence of any association for four other vaccinations studied. An increased risk of eczema by age 7 years was associated with immunisation against diphtheria (OR 1.5, 95% CI 1.1 to 2.1), tetanus (OR 1.5, 95% CI, 1.1 to 2.0), pertussis (OR 1.5, 95% CI 1.1 to 1.9) and polio (OR 1.4, 95% CI 1.0 to 1.9) but not small pox. Similar but slightly weaker patterns of association were observed between the risk of food allergies and immunisation against diphtheria (OR 1.5, 95% CI 1.0 to 2.1), pertussis (OR 1.4, 95% CI 1.1 to 1.9), polio (OR 1.4, 95% CI 1.00 to 2.1) and tetanus (OR 1.30 95% CI 0.99 to 1.70), but not with small pox. There was no evidence of associations between immunisation history and hay fever, or incidence of later‐onset atopic outcomes. Conclusions The few effects seen in this study are small and age‐dependent, and nearly all our findings support numerous previous studies of no effect of vaccines on asthma. Based on these findings, the fear of their child developing atopic disease should not deter parents from immunising their children, especially when weighed against the benefits. PMID:17090571

  18. Mitotic Dysfunction Associated with Aging Hallmarks.

    PubMed

    Macedo, Joana Catarina; Vaz, Sara; Logarinho, Elsa

    2017-01-01

    Aging is a biological process characterized by the progressive deterioration of physiological functions known to be the main risk factor for chronic diseases and declining health. There has been an emerging connection between aging and aneuploidy, an aberrant number of chromosomes, even though the molecular mechanisms behind age-associated aneuploidy remain largely unknown. In recent years, several genetic pathways and biochemical processes controlling the rate of aging have been identified and proposed as aging hallmarks. Primary hallmarks that cause the accumulation of cellular damage include genomic instability, telomere attrition, epigenetic alterations and loss of proteostasis (López-Otín et al., Cell 153:1194-1217, 2013). Here we review the provocative link between these aging hallmarks and the loss of chromosome segregation fidelity during cell division, which could support the correlation between aging and aneuploidy seen over the past decades. Secondly, we review the systemic impacts of aneuploidy in cell physiology and emphasize how these include some of the primary hallmarks of aging. Based on the evidence, we propose a mutual causality between aging and aneuploidy, and suggest modulation of mitotic fidelity as a potential means to ameliorate healthy lifespan.

  19. Association among oral health, apical periodontitis, CD14 polymorphisms, and coronary heart disease in middle-aged adults.

    PubMed

    Pasqualini, Damiano; Bergandi, Loredana; Palumbo, Luigi; Borraccino, Alberto; Dambra, Valentina; Alovisi, Mario; Migliaretti, Giuseppe; Ferraro, Gaetana; Ghigo, Dario; Bergerone, Serena; Scotti, Nicola; Aimetti, Mario; Berutti, Elio

    2012-12-01

    There is evidence to suggest that an association exists between oral infections and coronary heart disease (CHD). Subjects presenting lesions of endodontic origin (LEOs) or pulpal inflammation had an increased risk of developing CHD. However, findings concerning systemic manifestations of apical periodontitis (AP) remain controversial. An association between CD14 gene polymorphisms and atherosclerosis-associated diseases has been shown, but there are no data regarding an association between CD14 polymorphism and AP. This study evaluated associations between clinical oral health status, CD14 polymorphisms, and CHD. A case-controlled clinical trial was designed to compare middle-aged adults with acute myocardial infarction or unstable angina (n = 51) within 12 months of the acute event defined as first manifestation with healthy controls (n = 49). Participants were matched for age, sex, and socioeconomic status. Indicators of oral disease and compliance were evaluated. CD14 polymorphisms were analyzed by restriction fragment length polymorphism-polymerase chain reaction. CHD subjects had a higher prevalence of oral diseases and lower compliance to oral preventive strategies than healthy controls. Multivariate analysis showed a positive association between missing teeth (odds ratio [OR] = 1.37; 95% confidence interval [CI], 1.02-1.85), the number of LEOs (OR = 4.37; 95% CI, 1.69-11.28), chronic periodontitis (OR = 5.87; 95% CI, 1.17-29.4), and CHD. No statistically significant association emerged between the CD14 C(-260)T and the CD14 C(-159)T polymorphism, endodontic or periodontal disease, and CHD. Chronic oral diseases may increase the risk of CHD and may be an unconventional risk factor for CHD. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  20. The microbiota and microbiome in aging: potential implications in health and age-related diseases.

    PubMed

    Zapata, Heidi J; Quagliarello, Vincent J

    2015-04-01

    Advances in bacterial deoxyribonucleic acid sequencing allow for characterization of the human commensal bacterial community (microbiota) and its corresponding genome (microbiome). Surveys of healthy adults reveal that a signature composite of bacteria characterizes each unique body habitat (e.g., gut, skin, oral cavity, vagina). A myriad of clinical changes, including a basal proinflammatory state (inflamm-aging), that directly interface with the microbiota of older adults and enhance susceptibility to disease accompany aging. Studies in older adults demonstrate that the gut microbiota correlates with diet, location of residence (e.g., community dwelling, long-term care settings), and basal level of inflammation. Links exist between the microbiota and a variety of clinical problems plaguing older adults, including physical frailty, Clostridium difficile colitis, vulvovaginal atrophy, colorectal carcinoma, and atherosclerotic disease. Manipulation of the microbiota and microbiome of older adults holds promise as an innovative strategy to influence the development of comorbidities associated with aging. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

  1. The effects of age on associations between markers of HIV progression and markers of metabolic function including albumin, haemoglobin and lipid concentrations.

    PubMed

    Samuel, M; Jose, S; Winston, A; Nelson, M; Johnson, M; Chadwick, D; Fisher, M; Leen, C; Gompels, M; Gilson, R; Post, F A; Hay, P; Sabin, C A

    2014-05-01

    We investigated whether age modified associations between markers of HIV progression, CD4 T lymphocyte count and HIV RNA viral load (VL), and the following markers of metabolic function: albumin, haemoglobin, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). A retrospective analysis of data from the United Kingdom Collaborative HIV Cohort was carried out. Analyses were limited to antiretroviral-naïve subjects to focus on the impact of HIV disease itself. A total of 16670 subjects were included in the analysis. Multilevel linear regression models assessed associations between CD4 count/VL and each of the outcomes. Statistical tests for interactions assessed whether associations differed among age groups. After adjustment for gender and ethnicity, there was evidence that lower CD4 count and higher VL were associated with lower TC, LDL-C, haemoglobin and albumin concentrations but higher triglyceride concentrations. Age modified associations between CD4 count and albumin (P < 0.001) and haemoglobin (P = 0.001), but not between CD4 count and HDL-C, LDL-C and TC, or VL and any outcome. Among participants aged < 30, 30-50 and > 50 years, a 50 cells/μL lower CD4 count correlated with a 2.4 [95% confidence interval (CI) 1.7-3.0], 3.6 (95% CI 3.2-4.0) and 5.1 (95% CI 4.0-6.1) g/L lower haemoglobin concentration and a 0.09 (95% CI 0.07-0.11), 0.12 (95% CI 0.11-0.13) and 0.16 (95% CI 0.13-0.19) g/L lower albumin concentration, respectively. We present evidence that age modifies associations between CD4 count and plasma albumin and haemoglobin levels. A given reduction in CD4 count was associated with a greater reduction in haemoglobin and albumin concentrations among older people living with HIV. These findings increase our understanding of how the metabolic impact of HIV is influenced by age. © 2013 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.

  2. NO-Synthase Activity in Patients with Coronary Heart Disease Associated with Hypertension of Different Age Groups.

    PubMed

    Besedina, Anna

    2016-01-01

    Coronary heart disease is the leading cause of death and disability worldwide. Hypertension is a major independent risk factor for the development of CHD. Abnormalities in NO generation or activity have been proposed as a major mechanism of CHD. The purpose of this article is to determine the activity of eNOS and iNOS in patients with isolated CHD and CHD associated with HT of different age groups. Fifty patients with isolated CHD and 42 patients with CHD associated with HT were enrolled in this study. NOS activity was determined by nitrite anion formed in the reaction. A statistically significant increase in iNOS activity is observed in elderly donors. In patients with isolated coronary heart disease cNOS activity is statistically significantly reduced with respect to the control group. The reduction of enzymatic activity of cNOS is more expressed in elderly patients than in middle-aged patients with coronary heart disease. Alterations in eNOS activity are more expressed in patients with coronary heart disease associated with hypertension than in patients with isolated coronary heart disease. Against the background of cNOS inhibition in the patients, a sharp increase in iNOS activity is observed. It has been shown that disturbance of endothelial function in patients with coronary heart disease associated with hypertension is characterized by reduced endothelial NO synthesis by cNOS and increased systemic NO synthesis due to increased iNOS activity. It has been found that the lack of endothelial NO and hyperproduction of »harmful« NO by iNOS are more expressed in elderly patients.

  3. Energy metabolism and inflammation in brain aging and Alzheimer's disease.

    PubMed

    Yin, Fei; Sancheti, Harsh; Patil, Ishan; Cadenas, Enrique

    2016-11-01

    The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer's disease. As important cellular sources of H 2 O 2 , mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer's disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer's disease. Interaction of these systems is reviewed based on basic research and clinical studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Pathways of cellular proteostasis in aging and disease.

    PubMed

    Klaips, Courtney L; Jayaraj, Gopal Gunanathan; Hartl, F Ulrich

    2018-01-02

    Ensuring cellular protein homeostasis, or proteostasis, requires precise control of protein synthesis, folding, conformational maintenance, and degradation. A complex and adaptive proteostasis network coordinates these processes with molecular chaperones of different classes and their regulators functioning as major players. This network serves to ensure that cells have the proteins they need while minimizing misfolding or aggregation events that are hallmarks of age-associated proteinopathies, including neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. It is now clear that the capacity of cells to maintain proteostasis undergoes a decline during aging, rendering the organism susceptible to these pathologies. Here we discuss the major proteostasis pathways in light of recent research suggesting that their age-dependent failure can both contribute to and result from disease. We consider different strategies to modulate proteostasis capacity, which may help develop urgently needed therapies for neurodegeneration and other age-dependent pathologies. © 2018 Klaips et al.

  5. Genetic assessment of age-associated Alzheimer disease risk: Development and validation of a polygenic hazard score.

    PubMed

    Desikan, Rahul S; Fan, Chun Chieh; Wang, Yunpeng; Schork, Andrew J; Cabral, Howard J; Cupples, L Adrienne; Thompson, Wesley K; Besser, Lilah; Kukull, Walter A; Holland, Dominic; Chen, Chi-Hua; Brewer, James B; Karow, David S; Kauppi, Karolina; Witoelar, Aree; Karch, Celeste M; Bonham, Luke W; Yokoyama, Jennifer S; Rosen, Howard J; Miller, Bruce L; Dillon, William P; Wilson, David M; Hess, Christopher P; Pericak-Vance, Margaret; Haines, Jonathan L; Farrer, Lindsay A; Mayeux, Richard; Hardy, John; Goate, Alison M; Hyman, Bradley T; Schellenberg, Gerard D; McEvoy, Linda K; Andreassen, Ole A; Dale, Anders M

    2017-03-01

    Identifying individuals at risk for developing Alzheimer disease (AD) is of utmost importance. Although genetic studies have identified AD-associated SNPs in APOE and other genes, genetic information has not been integrated into an epidemiological framework for risk prediction. Using genotype data from 17,008 AD cases and 37,154 controls from the International Genomics of Alzheimer's Project (IGAP Stage 1), we identified AD-associated SNPs (at p < 10-5). We then integrated these AD-associated SNPs into a Cox proportional hazard model using genotype data from a subset of 6,409 AD patients and 9,386 older controls from Phase 1 of the Alzheimer's Disease Genetics Consortium (ADGC), providing a polygenic hazard score (PHS) for each participant. By combining population-based incidence rates and the genotype-derived PHS for each individual, we derived estimates of instantaneous risk for developing AD, based on genotype and age, and tested replication in multiple independent cohorts (ADGC Phase 2, National Institute on Aging Alzheimer's Disease Center [NIA ADC], and Alzheimer's Disease Neuroimaging Initiative [ADNI], total n = 20,680). Within the ADGC Phase 1 cohort, individuals in the highest PHS quartile developed AD at a considerably lower age and had the highest yearly AD incidence rate. Among APOE ε3/3 individuals, the PHS modified expected age of AD onset by more than 10 y between the lowest and highest deciles (hazard ratio 3.34, 95% CI 2.62-4.24, p = 1.0 × 10-22). In independent cohorts, the PHS strongly predicted empirical age of AD onset (ADGC Phase 2, r = 0.90, p = 1.1 × 10-26) and longitudinal progression from normal aging to AD (NIA ADC, Cochran-Armitage trend test, p = 1.5 × 10-10), and was associated with neuropathology (NIA ADC, Braak stage of neurofibrillary tangles, p = 3.9 × 10-6, and Consortium to Establish a Registry for Alzheimer's Disease score for neuritic plaques, p = 6.8 × 10-6) and in vivo markers of AD neurodegeneration (ADNI, volume loss

  6. Periodontal disease severity is associated with micronutrient intake.

    PubMed

    Luo, P-P; Xu, H-S; Chen, Y-W; Wu, S-P

    2018-03-06

    This study aimed to examine if specific micronutrients were associated with periodontal disease using data from the US National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. Participants who were aged 30 years or more and received complete periodontal examinations were included. Regression analyses were performed to determine associations of variables of interest with periodontal disease. Data of 6415 NHANES participants were included in the analysis. Multivariable analysis revealed that less intake of vitamin A (adjusted odds ratio (aOR) = 1.784), vitamin B1 (aOR = 1.334), vitamin C (aOR = 1.401), vitamin E (aOR = 1.576), iron (aOR = 1.234), folate (aOR = 1.254) and phosphorus (aOR = 1.280) was associated with increased severity of periodontal disease. Compared with the highest level of vitamin D intake, the second highest level of vitamin D intake was associated with lower severity of periodontal disease (aOR = 0.727). Insufficient intake of vitamin A, B1, C and E, iron, folate and phosphorus was significantly associated with severity of periodontal disease. Results of the present study suggest that the above micronutrients may be increased in the diet or taken as dietary supplements in order to reduce severity of periodontal disease. © 2018 Australian Dental Association.

  7. Evaluating Alzheimer's disease biomarkers as mediators of age-related cognitive decline.

    PubMed

    Hohman, Timothy J; Tommet, Doug; Marks, Shawn; Contreras, Joey; Jones, Rich; Mungas, Dan

    2017-10-01

    Age-related changes in cognition are partially mediated by the presence of neuropathology and neurodegeneration. This manuscript evaluates the degree to which biomarkers of Alzheimer's disease, (AD) neuropathology and longitudinal changes in brain structure, account for age-related differences in cognition. Data from the AD Neuroimaging Initiative (n = 1012) were analyzed, including individuals with normal cognition and mild cognitive impairment. Parallel process mixed effects regression models characterized longitudinal trajectories of cognitive variables and time-varying changes in brain volumes. Baseline age was associated with both memory and executive function at baseline (p's < 0.001) and change in memory and executive function performances over time (p's < 0.05). After adjusting for clinical diagnosis, baseline, and longitudinal changes in brain volume, and baseline levels of cerebrospinal fluid biomarkers, age effects on change in episodic memory and executive function were fully attenuated, age effects on baseline memory were substantially attenuated, but an association remained between age and baseline executive function. Results support previous studies that show that age effects on cognitive decline are fully mediated by disease and neurodegeneration variables but also show domain-specific age effects on baseline cognition, specifically an age pathway to executive function that is independent of brain and disease pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Genome-wide association analysis of age-at-onset in Alzheimer’s disease

    PubMed Central

    Kamboh, M. Ilyas; Barmada, M. Michael; Demirci, F. Yesim; Minster, Ryan L.; Carrasquillo, Minerva M.; Pankratz, V. Shane; Younkin, Steven G.; Saykin, Andrew J.; Sweet, Robert A.; Feingold, Eleanor; DeKosky, Steven T.; Lopez, Oscar L.

    2011-01-01

    The risk of Alzheimer’s disease (AD) is strongly determined by genetic factors and recent genome-wide association studies (GWAS) have identified several genes for the disease risk. In addition to the disease risk, age-at-onset (AAO) of AD has also strong genetic component with an estimated heritability of 42%. Identification of AAO genes may help to understand the biological mechanisms that regulate the onset of the disease. Here we report the first GWAS focused on identifying genes for the AAO of AD. We performed a genome-wide meta analysis on 3 samples comprising a total of 2,222 AD cases. A total of ~2.5 million directly genotyped or imputed SNPs were analyzed in relation to AAO of AD. As expected, the most significant associations were observed in the APOE region on chromosome 19 where several SNPs surpassed the conservative genome-wide significant threshold (P<5E-08). The most significant SNP outside the APOE region was located in the DCHS2 gene on chromosome 4q31.3 (rs1466662; P=4.95E-07). There were 19 additional significant SNPs in this region at P<1E-04 and the DCHS2 gene is expressed in the cerebral cortex and thus is a potential candidate for affecting AAO in AD. These findings need to be confirmed in additional well-powered samples. PMID:22005931

  9. Splicing regulatory factors, ageing and age-related disease.

    PubMed

    Latorre, Eva; Harries, Lorna W

    2017-07-01

    Alternative splicing is a co-transcriptional process, which allows for the production of multiple transcripts from a single gene and is emerging as an important control point for gene expression. Alternatively expressed isoforms often have antagonistic function and differential temporal or spatial expression patterns, yielding enormous plasticity and adaptability to cells and increasing their ability to respond to environmental challenge. The regulation of alternative splicing is critical for numerous cellular functions in both pathological and physiological conditions, and deregulated alternative splicing is a key feature of common chronic diseases. Isoform choice is controlled by a battery of splicing regulatory proteins, which include the serine arginine rich (SRSF) proteins and the heterogeneous ribonucleoprotein (hnRNP) classes of genes. These important splicing regulators have been implicated in age-related disease, and in the ageing process itself. This review will outline the important contribution of splicing regulator proteins to ageing and age-related disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Obligatory role for GPER in cardiovascular aging and disease.

    PubMed

    Meyer, Matthias R; Fredette, Natalie C; Daniel, Christoph; Sharma, Geetanjali; Amann, Kerstin; Arterburn, Jeffrey B; Barton, Matthias; Prossnitz, Eric R

    2016-11-01

    Pharmacological activation of the heptahelical G protein-coupled estrogen receptor (GPER) by selective ligands counteracts multiple aspects of cardiovascular disease. We thus expected that genetic deletion or pharmacological inhibition of GPER would further aggravate such disease states, particularly with age. To the contrary, we found that genetic ablation of Gper in mice prevented cardiovascular pathologies associated with aging by reducing superoxide (⋅O 2 - ) formation by NADPH oxidase (Nox) specifically through reducing the expression of the Nox isoform Nox1 Blocking GPER activity pharmacologically with G36, a synthetic, small-molecule, GPER-selective blocker (GRB), decreased Nox1 abundance and ⋅O 2 - production to basal amounts in cells exposed to angiotensin II and in mice chronically infused with angiotensin II, reducing arterial hypertension. Thus, this study revealed a role for GPER activity in regulating Nox1 abundance and associated ⋅O 2 - -mediated structural and functional damage that contributes to disease pathology. Our results indicated that GRBs represent a new class of drugs that can reduce Nox abundance and activity and could be used for the treatment of chronic disease processes involving excessive ⋅O 2 - formation, including arterial hypertension and heart failure. Copyright © 2016, American Association for the Advancement of Science.

  11. Genetic assessment of age-associated Alzheimer disease risk: Development and validation of a polygenic hazard score

    PubMed Central

    Cupples, L. Adrienne; Thompson, Wesley K.; Besser, Lilah; Kukull, Walter A.; Holland, Dominic; Chen, Chi-Hua; Brewer, James B.; Karow, David S.; Kauppi, Karolina; Bonham, Luke W.; Rosen, Howard J.; Miller, Bruce L.; Dillon, William P.; Wilson, David M.; Pericak-Vance, Margaret; Haines, Jonathan L.; Farrer, Lindsay A.; Mayeux, Richard; Hardy, John; Goate, Alison M.; Schellenberg, Gerard D.; Andreassen, Ole A.

    2017-01-01

    Background Identifying individuals at risk for developing Alzheimer disease (AD) is of utmost importance. Although genetic studies have identified AD-associated SNPs in APOE and other genes, genetic information has not been integrated into an epidemiological framework for risk prediction. Methods and findings Using genotype data from 17,008 AD cases and 37,154 controls from the International Genomics of Alzheimer’s Project (IGAP Stage 1), we identified AD-associated SNPs (at p < 10−5). We then integrated these AD-associated SNPs into a Cox proportional hazard model using genotype data from a subset of 6,409 AD patients and 9,386 older controls from Phase 1 of the Alzheimer’s Disease Genetics Consortium (ADGC), providing a polygenic hazard score (PHS) for each participant. By combining population-based incidence rates and the genotype-derived PHS for each individual, we derived estimates of instantaneous risk for developing AD, based on genotype and age, and tested replication in multiple independent cohorts (ADGC Phase 2, National Institute on Aging Alzheimer’s Disease Center [NIA ADC], and Alzheimer’s Disease Neuroimaging Initiative [ADNI], total n = 20,680). Within the ADGC Phase 1 cohort, individuals in the highest PHS quartile developed AD at a considerably lower age and had the highest yearly AD incidence rate. Among APOE ε3/3 individuals, the PHS modified expected age of AD onset by more than 10 y between the lowest and highest deciles (hazard ratio 3.34, 95% CI 2.62–4.24, p = 1.0 × 10−22). In independent cohorts, the PHS strongly predicted empirical age of AD onset (ADGC Phase 2, r = 0.90, p = 1.1 × 10−26) and longitudinal progression from normal aging to AD (NIA ADC, Cochran–Armitage trend test, p = 1.5 × 10−10), and was associated with neuropathology (NIA ADC, Braak stage of neurofibrillary tangles, p = 3.9 × 10−6, and Consortium to Establish a Registry for Alzheimer’s Disease score for neuritic plaques, p = 6.8 × 10−6) and

  12. Aging and physiological changes of the kidneys including changes in glomerular filtration rate.

    PubMed

    Musso, Carlos G; Oreopoulos, Dimitrios G

    2011-01-01

    In addition to the structural changes in the kidney associated with aging, physiological changes in renal function are also found in older adults, such as decreased glomerular filtration rate, vascular dysautonomia, altered tubular handling of creatinine, reduction in sodium reabsorption and potassium secretion, and diminished renal reserve. These alterations make aged individuals susceptible to the development of clinical conditions in response to usual stimuli that would otherwise be compensated for in younger individuals, including acute kidney injury, volume depletion and overload, disorders of serum sodium and potassium concentration, and toxic reactions to water-soluble drugs excreted by the kidneys. Additionally, the preservation with aging of a normal urinalysis, normal serum urea and creatinine values, erythropoietin synthesis, and normal phosphorus, calcium and magnesium tubular handling distinguishes decreased GFR due to normal aging from that due to chronic kidney disease. Copyright © 2011 S. Karger AG, Basel.

  13. Hippocampal Sclerosis of Aging, a Common Alzheimer’s Disease ‘Mimic’: Risk Genotypes are Associated with Brain Atrophy Outside the Temporal Lobe

    PubMed Central

    Nho, Kwangsik; Saykin, Andrew J.; Nelson, Peter T.

    2016-01-01

    Hippocampal sclerosis of aging (HS-Aging) is a common brain disease in older adults with a clinical course that is similar to Alzheimer’s disease. Four single-nucleotide polymorphisms (SNPs) have previously shown association with HS-Aging. The present study investigated structural brain changes associated with these SNPs using surface-based analysis. Participants from the Alzheimer’s Disease Neuroimaging Initiative cohort (ADNI; n = 1,239), with both MRI scans and genotype data, were used to assess the association between brain atrophy and previously identified HS-Aging risk SNPs in the following genes: GRN, TMEM106B, ABCC9, and KCNMB2 (minor allele frequency for each is >30%). A fifth SNP (near the ABCC9 gene) was evaluated in post-hoc analysis. The GRN risk SNP (rs5848_T) was associated with a pattern of atrophy in the dorsomedial frontal lobes bilaterally, remarkable since GRN is a risk factor for frontotemporal dementia. The ABCC9 risk SNP (rs704180_A) was associated with multifocal atrophy whereas a SNP (rs7488080_A) nearby (~50 kb upstream) ABCC9 was associated with atrophy in the right entorhinal cortex. Neither TMEM106B (rs1990622_T), KCNMB2 (rs9637454_A), nor any of the non-risk alleles were associated with brain atrophy. When all four previously identified HS-Aging risk SNPs were summed into a polygenic risk score, there was a pattern of associated multifocal brain atrophy in a predominately frontal pattern. We conclude that common SNPs previously linked to HS-Aging pathology were associated with a distinct pattern of anterior cortical atrophy. Genetic variation associated with HS-Aging pathology may represent a non-Alzheimer’s disease contribution to atrophy outside of the hippocampus in older adults. PMID:27003218

  14. Energy Metabolism and Inflammation in Brain Aging and Alzheimer’s Disease

    PubMed Central

    Yin, Fei; Sancheti, Harsh; Patil, Ishan; Cadenas, Enrique

    2016-01-01

    The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer’s disease. As important cellular sources of H2O2, mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer’s disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer’s disease. Interactions of these systems is reviewed based on basic research and clinical studies. PMID:27154981

  15. Enteric disease in postweaned beef calves associated with a Bovine coronavirus clade 2

    USDA-ARS?s Scientific Manuscript database

    Bovine coronavirus (BoCV) infections are associated with varied clinical presentations including neonatal diarrhea, winter dysentery in dairy cattle, and respiratory disease in various ages of cattle. This report presents information on BoCV infections associated with enteric disease of postweaned b...

  16. Glaucoma and Alzheimer Disease: A Single Age-Related Neurodegenerative Disease of the Brain.

    PubMed

    Mancino, Raffaele; Martucci, Alessio; Cesareo, Massimo; Giannini, Clarissa; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Nucci, Carlo

    2017-12-06

    Open Angle Glaucoma is one of the leading causes of irreversible blindness worldwide. Elevated intraocular pressure is considered an important risk factor for glaucoma, however a subset of patients experience disease progression even in presence of normal intraocular pressure values. This implies that risk factors other than intraocular pressure are involved in the pathogenesis of glaucoma. A possible relationship between glaucoma and neurodegenerative diseases such as Alzheimer Disease has been suggested. In this regard, we have recently described a high prevalence of alterations typical of glaucoma, using Heidelberg Retinal Tomograph-3 (HRT-3), in a group of patients with Alzheimer Disease. Interestingly, these alterations were not associated with elevated intraocular pressure or abnormal Central Corneal Thickness values. Alzheimer Disease is the most common form of dementia associated with progressive deterioration of memory and cognition. Complaints related to vision are common among Alzheimer Disease patients. Features common to both diseases, including risk factors and pathophysiological mechanisms, gleaned from the recent literature do suggest that Alzheimer Disease and glaucoma can be considered age-related neurodegenerative diseases that may co-exist in the elderly. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Chronic kidney disease: a clinical model of premature aging.

    PubMed

    Stenvinkel, Peter; Larsson, Tobias E

    2013-08-01

    Premature aging is a process associated with a progressive accumulation of deleterious changes over time, an impairment of physiologic functions, and an increase in the risk of disease and death. Regardless of genetic background, aging can be accelerated by the lifestyle choices and environmental conditions to which our genes are exposed. Chronic kidney disease is a common condition that promotes cellular senescence and premature aging through toxic alterations in the internal milieu. This occurs through several mechanisms, including DNA and mitochondria damage, increased reactive oxygen species generation, persistent inflammation, stem cell exhaustion, phosphate toxicity, decreased klotho expression, and telomere attrition. Because recent evidence suggests that both increased local signaling of growth factors (through the nutrient-sensing mammalian target of rapamycin) and decreased klotho expression are important modulators of aging, interventions that target these should be tested in this prematurely aged population. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  18. Impact of age on markers of HIV-1 disease

    PubMed Central

    Pirrone, Vanessa; Libon, David J; Sell, Christian; Lerner, Chad A; Nonnemacher, Michael R; Wigdahl, Brian

    2013-01-01

    Aging is a complicated process characterized by a progressive loss of homeostasis, which results in an increased vulnerability to multiple diseases. HIV-1-infected patients demonstrate a premature aging phenotype and develop certain age-related diseases earlier in their lifespan than what is seen in the general population. Age-related comorbidities may include the development of bone disease, metabolic disorders, neurologic impairment and immunosenescence. Age also appears to have an effect on traditional markers of HIV-1 disease progression, including CD4+ T-cell count and viral load. These effects are not only a consequence of HIV-1 infection, but in many cases, are also linked to antiretroviral therapy. This review summarizes the complex interplay between HIV-1 infection and aging, and the impact that aging has on markers of HIV-1 disease. PMID:23596462

  19. Obligatory role for GPER in cardiovascular aging and disease^

    PubMed Central

    Daniel, Christoph; Sharma, Geetanjali; Amann, Kerstin; Arterburn, Jeffrey B.; Barton, Matthias; Prossnitz, Eric R.

    2016-01-01

    Pharmacological activation of the heptahelical G protein-coupled receptor GPER by selective ligands counteracts multiple aspects of cardiovascular disease. We thus expected that genetic deletion or pharmacological inhibition of GPER would further aggravate such disease states, particularly with age. To the contrary, we found that genetic ablation of Gper in mice prevented cardiovascular pathologies associated with aging by reducing superoxide (.O2−) formation by NADPH oxidase (Nox) and reduced expression the Nox isoform Nox1. Blocking GPER activity pharmacologically with G36, a synthetic, small molecule, GPER-selective blocker (GRB), decreased Nox1 abundance and .O2− production to basal amounts in cells exposed to angiotensin II and in mice chronically infused with angiotensin II. Thus, this study revealed a role for GPER activity in regulating Nox1 abundance and associated .O2−-mediated structural and functional damage that contributes to disease pathology. Our results indicated that GRBs represent a new class of drugs that can indirectly reduce Nox activity and could be used for the treatment of chronic disease processes involving excessive .O2− formation, including arterial hypertension and diastolic heart failure. PMID:27803283

  20. Can Neglected Tropical Diseases Compromise Human Wellbeing in Sex-, Age-, and Trait-Specific Ways?

    PubMed Central

    Geary, David C.

    2016-01-01

    Traits that facilitate competition for reproductive resources or that influence mate choice have evolved to signal resilience to infectious disease and other stressors. As a result, the dynamics of competition and choice can, in theory, be used to generate predictions about sex-, age-, and trait-specific vulnerabilities for any sexually reproducing species, including humans. These dynamics and associated vulnerabilities are reviewed for nonhuman species, focusing on traits that are compromised by exposure to parasites. Using the same approach, sex-, age-, and trait-specific vulnerabilities to parasitic disease are illustrated for children’s and adolescent’s physical growth and fitness. Suggestions are then provided for widening the assessment of human vulnerabilities to include age-appropriate measures of behavioral (e.g., children’s play) and cognitive (e.g., language fluency) traits. These are traits that are likely to be compromised by infection in age- and sex-specific ways. Inclusion of these types of measures in studies of neglected tropic diseases has the potential to provide a more nuanced understanding of how these diseases undermine human wellbeing and may provide a useful means to study the efficacy of associated treatments. PMID:27077746

  1. Inflammatory bowel disease is associated with an increased risk of inflammatory skin diseases: A population-based cross-sectional study.

    PubMed

    Kim, Miri; Choi, Kwang Hyun; Hwang, Se Won; Lee, Young Bok; Park, Hyun Jeong; Bae, Jung Min

    2017-01-01

    Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract attributed to aberrant activity of the immune system. Increasing evidence suggests that patients with IBD are at an increased risk of inflammatory skin diseases (ISDs). We sought to clarify the association between IBD and ISDs using a nationwide health claims database maintained in Korea. We interrogated Korean health claim database data from 2009 to 2013. We enrolled all patients with IBD, and age- and sex-matched control subjects, and evaluated the risks of ISDs, including psoriasis, rosacea, and atopic dermatitis, and the risks of autoimmune skin diseases, including vitiligo and alopecia areata. We used multivariable logistic regression to this end. ISDs including rosacea, psoriasis, and atopic dermatitis were significantly associated with IBD, whereas the associations between IBD and autoimmune skin diseases including vitiligo and alopecia areata were less marked or nonexistent. Ulcerative colitis and Crohn's disease were both associated with ISDs. We were unable to distinguish phenotypes and severities of skin diseases. IBD was significantly associated with ISDs, but less so or not at all with autoimmune skin diseases. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  2. The natural history of prevalent ischaemic heart disease in middle-aged men.

    PubMed

    Lampe, F C; Whincup, P H; Wannamethee, S G; Shaper, A G; Walker, M; Ebrahim, S

    2000-07-01

    To describe the long-term outcome of different forms of symptomatic and asymptomatic ischaemic heart disease in middle-aged men. 7735 men aged 40-59, randomly selected from 24 general practices in Britain were classified into one of seven ischaemic heart disease groups according to a questionnaire and electrocardiogram (ECG): I=diagnosed myocardial infarction; II=unrecognized myocardial infarction; III= diagnosed angina; IV=angina symptoms; V=possible myocardial infarction symptoms; VI=ECG ischaemia or possible myocardial infarction; VII=no evidence of ischaemic heart disease. The association of disease group with a range of fatal and non-fatal outcomes during 15 years of follow-up was assessed. At baseline 25% of men had evidence of ischaemic heart disease (groups I-VI). Risks of major ischaemic heart disease events, total and cardiovascular mortality, stroke, and major cardiovascular events tended to increase strongly from group VII to I. Diagnosed myocardial infarction was associated with a much poorer prognosis than all other groups (including unrecognized infarction) for all cardiovascular outcomes other than stroke. The relative risk associated with ischaemic heart disease at baseline declined dramatically over time. However, men with myocardial infarction who survived event-free for 10 years continued to experience a high excess risk in the subsequent 5 years, in contrast to event-free survivors of angina and other ischaemic heart disease. Adjusted to an average age of 50, the percentage of men surviving for 15 years free of a new major cardiovascular event was 44 for diagnosed myocardial infarction, 52 for unrecognized myocardial infarction, 66 for diagnosed angina, 68 for angina symptoms, 73 for possible myocardial infarction symptoms, 73 for ECG ischaemia, and 79 for no ischaemic heart disease. Comparison of outcome between prevalent and incident myocardial infarction illustrated the improved prognosis of men surviving the initial years after their event

  3. Nutritional considerations for healthy aging and reduction in age-related chronic disease

    USDA-ARS?s Scientific Manuscript database

    A projected doubling in the global population of people aged >/= 60 y by the year 2050 has major health and economic implications, especially in developing regions. Burdens of unhealthy aging associated with chronic noncommunicable and other age-related diseases may be largely preventable with lifes...

  4. Identification of ageing-associated naturally occurring peptides in human urine

    PubMed Central

    Nkuipou-Kenfack, Esther; Bhat, Akshay; Klein, Julie; Jankowski, Vera; Mullen, William; Vlahou, Antonia; Dakna, Mohammed; Koeck, Thomas; Schanstra, Joost P.; Zürbig, Petra; Rudolph, Karl L.; Schumacher, Björn; Pich, Andreas; Mischak, Harald

    2015-01-01

    To assess normal and pathological peptidomic changes that may lead to an improved understanding of molecular mechanisms underlying ageing, urinary peptidomes of 1227 healthy and 10333 diseased individuals between 20 and 86 years of age were investigated. The diseases thereby comprised diabetes mellitus, renal and cardiovascular diseases. Using age as a continuous variable, 116 peptides were identified that significantly (p < 0.05; |ρ|≥0.2) correlated with age in the healthy cohort. The same approach was applied to the diseased cohort. Upon comparison of the peptide patterns of the two cohorts 112 common age-correlated peptides were identified. These 112 peptides predominantly originated from collagen, uromodulin and fibrinogen. While most fibrillar and basement membrane collagen fragments showed a decreased age-related excretion, uromodulin, beta-2-microglobulin and fibrinogen fragments showed an increase. Peptide-based in silico protease analysis was performed and 32 proteases, including matrix metalloproteinases and cathepsins, were predicted to be involved in ageing. Identified peptides, predicted proteases and patient information were combined in a systems biology pathway analysis to identify molecular pathways associated with normal and/or pathological ageing. While perturbations in collagen homeostasis, trafficking of toll-like receptors and endosomal pathways were commonly identified, degradation of insulin-like growth factor-binding proteins was uniquely identified in pathological ageing. PMID:26431327

  5. The Role of DNA Methylation in Aging, Rejuvenation, and Age-Related Disease

    PubMed Central

    Johnson, Adiv A.; Akman, Kemal; Calimport, Stuart R.G.; Wuttke, Daniel; de Magalhães, João Pedro

    2012-01-01

    Abstract DNA methylation is a major control program that modulates gene expression in a plethora of organisms. Gene silencing through methylation occurs through the activity of DNA methyltransferases, enzymes that transfer a methyl group from S-adenosyl-l-methionine to the carbon 5 position of cytosine. DNA methylation patterns are established by the de novo DNA methyltransferases (DNMTs) DNMT3A and DNMT3B and are subsequently maintained by DNMT1. Aging and age-related diseases include defined changes in 5-methylcytosine content and are generally characterized by genome-wide hypomethylation and promoter-specific hypermethylation. These changes in the epigenetic landscape represent potential disease biomarkers and are thought to contribute to age-related pathologies, such as cancer, osteoarthritis, and neurodegeneration. Some diseases, such as a hereditary form of sensory neuropathy accompanied by dementia, are directly caused by methylomic changes. Epigenetic modifications, however, are reversible and are therefore a prime target for therapeutic intervention. Numerous drugs that specifically target DNMTs are being tested in ongoing clinical trials for a variety of cancers, and data from finished trials demonstrate that some, such as 5-azacytidine, may even be superior to standard care. DNMTs, demethylases, and associated partners are dynamically shaping the methylome and demonstrate great promise with regard to rejuvenation. PMID:23098078

  6. Parental Age of Onset of Cardiovascular Disease as a Predictor for Offspring Age of Onset of Cardiovascular Disease.

    PubMed

    Allport, Shannon Anjelica; Kikah, Ngum; Abu Saif, Nessim; Ekokobe, Fonkem; Atem, Folefac D

    2016-01-01

    The risk for cardiovascular disease (CVD) is higher for individuals with a first-degree relative who developed premature CVD (with a threshold at age 55 years for a male or 65 years for a female). However, little is known about the effect that each unit increase or decrease of maternal or paternal age of onset of CVD has on offspring age of onset of CVD. We hypothesized that there is an association between maternal and paternal age of onset of CVD and offspring age of onset of CVD. We used the Framingham Heart Study database and performed conditional imputation for CVD-censored parental age (i.e. parents that didn't experience onset of CVD) and Cox proportional regression analysis, with offspring's age of onset of CVD as the dependent variable and parental age of onset of CVD as the primary predictor. Modifiable risk factors in offspring, such as cigarette smoking, body mass index (BMI), diabetes mellitus, systolic blood pressure (SBP), high-density lipoprotein (HDL) level, and low-density lipoprotein (LDL) level, were controlled for. Separate analyses were performed for the association between maternal age of onset of CVD and offspring age of onset of CVD and the association between paternal age of onset of CVD and offspring age of onset of CVD. Parental age of onset of CVD was predictive of offspring age of onset of CVD for maternal age of onset of CVD (P < .0001; N = 1401) and for paternal age of onset of CVD (P = 0.0134; N = 1221). A negative estimate of the coefficient of interest signifies that late onset of cardiovascular events in parents is protective of onset of CVD in offspring. Cigarette smoking and HDL level were important associated confounders. Offspring age of onset of cardiovascular disease is significantly associated with both maternal and paternal age of onset CVD. The incorporation of the parameters, maternal or paternal age of onset of CVD, into risk estimate calculators may improve accuracy of identification of high-risk patients in clinical

  7. Systematic analysis of the gerontome reveals links between aging and age-related diseases

    PubMed Central

    Fernandes, Maria; Wan, Cen; Tacutu, Robi; Barardo, Diogo; Rajput, Ashish; Wang, Jingwei; Thoppil, Harikrishnan; Thornton, Daniel; Yang, Chenhao; Freitas, Alex

    2016-01-01

    Abstract In model organisms, over 2,000 genes have been shown to modulate aging, the collection of which we call the ‘gerontome’. Although some individual aging-related genes have been the subject of intense scrutiny, their analysis as a whole has been limited. In particular, the genetic interaction of aging and age-related pathologies remain a subject of debate. In this work, we perform a systematic analysis of the gerontome across species, including human aging-related genes. First, by classifying aging-related genes as pro- or anti-longevity, we define distinct pathways and genes that modulate aging in different ways. Our subsequent comparison of aging-related genes with age-related disease genes reveals species-specific effects with strong overlaps between aging and age-related diseases in mice, yet surprisingly few overlaps in lower model organisms. We discover that genetic links between aging and age-related diseases are due to a small fraction of aging-related genes which also tend to have a high network connectivity. Other insights from our systematic analysis include assessing how using datasets with genes more or less studied than average may result in biases, showing that age-related disease genes have faster molecular evolution rates and predicting new aging-related drugs based on drug-gene interaction data. Overall, this is the largest systems-level analysis of the genetics of aging to date and the first to discriminate anti- and pro-longevity genes, revealing new insights on aging-related genes as a whole and their interactions with age-related diseases. PMID:28175300

  8. Association of extraintestinal manifestations and anaemia with disease outcomes in patients with inflammatory bowel disease.

    PubMed

    Vegh, Zsuzsanna; Kurti, Zsuzsanna; Gonczi, Lorant; Golovics, Petra Anna; Lovasz, Barbara Dorottya; Szita, Istvan; Balogh, Mihaly; Pandur, Tunde; Vavricka, Stephan R; Rogler, Gerhard; Lakatos, Laszlo; Lakatos, Peter Laszlo

    2016-07-01

    The association between extraintestinal manifestations (EIMs) and disease activity suggest a common pathogenetic link with inflammatory bowel disease (IBD). We report on the association of EIMs and anaemia with long-term disease outcomes, including treatment steps, hospitalization, and surgery in the prospective population-based IBD inception cohort from Veszprem province. Data of 678 incident IBD patients (Crohn's disease/ulcerative colitis(CD/UC): 331/347) diagnosed from 1st January 2000 to 31st December 2012 were analyzed (CD: m/f: 176/155, median age at diagnosis: 28, IQR: 21-40 years, disease duration: 6, IQR: 2-9 years; UC: m/f: 200/147, median age at diagnosis: 36, IQR: 26-50 years, duration: 7, IQR: 4-10 years). EIMs were present in 30% of the CD and 17.3% of the UC patients. In CD, female gender (p = 0.02) need for steroid (p  < 0.001) and azathioprine (AZA) (p = 0.02), while in UC, young age at onset (p = 0.03), extensive disease (p = 0.003), female gender (p = 0.07), need for steroids (p < 0.001) and AZA (p = 0.004) and need for IBD-related hospitalization (p = 0.01) were associated with the presence of EIMs. Anaemia was present in 56.7% of the CD and 30.2% of the UC patients. In both CD and UC anaemia was associated with age at onset (pCD = 0.001, pUC = 0.04), disease location/extent (pCD = 0.02, pUC < 0.001), steroid and AZA use (for both pCD,UC < 0.001), need for surgery/colectomy (pCD < 0.001, pUC = 0.002) and hospitalization (pCD = 0.004, pUC < 0.001) and in CD, it was associated with anti TNF therapy(p = 0.002). The presence of EIMs was associated with disease phenotype in UC and with treatment strategy in both CD and UC. Additionally, anaemia was associated with hospitalization and surgery in both CD and UC, suggesting that EIMs and anaemia may be helpful in stratifying disease severity in IBD.

  9. Disease-associated repeat instability and mismatch repair.

    PubMed

    Schmidt, Monika H M; Pearson, Christopher E

    2016-02-01

    Expanded tandem repeat sequences in DNA are associated with at least 40 human genetic neurological, neurodegenerative, and neuromuscular diseases. Repeat expansion can occur during parent-to-offspring transmission, and arise at variable rates in specific tissues throughout the life of an affected individual. Since the ongoing somatic repeat expansions can affect disease age-of-onset, severity, and progression, targeting somatic expansion holds potential as a therapeutic target. Thus, understanding the factors that regulate this mutation is crucial. DNA repair, in particular mismatch repair (MMR), is the major driving force of disease-associated repeat expansions. In contrast to its anti-mutagenic roles, mammalian MMR curiously drives the expansion mutations of disease-associated (CAG)·(CTG) repeats. Recent advances have broadened our knowledge of both the MMR proteins involved in disease repeat expansions, including: MSH2, MSH3, MSH6, MLH1, PMS2, and MLH3, as well as the types of repeats affected by MMR, now including: (CAG)·(CTG), (CGG)·(CCG), and (GAA)·(TTC) repeats. Mutagenic slipped-DNA structures have been detected in patient tissues, and the size of the slip-out and their junction conformation can determine the involvement of MMR. Furthermore, the formation of other unusual DNA and R-loop structures is proposed to play a key role in MMR-mediated instability. A complex correlation is emerging between tissues showing varying amounts of repeat instability and MMR expression levels. Notably, naturally occurring polymorphic variants of DNA repair genes can have dramatic effects upon the levels of repeat instability, which may explain the variation in disease age-of-onset, progression and severity. An increasing grasp of these factors holds prognostic and therapeutic potential. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Alloimmunization is associated with older age of transfused red blood cells in sickle cell disease.

    PubMed

    Desai, Payal C; Deal, Allison M; Pfaff, Emily R; Qaqish, Bahjat; Hebden, Leyna M; Park, Yara A; Ataga, Kenneth I

    2015-08-01

    Red blood cell (RBC) alloimmunization is a significant clinical complication of sickle cell disease (SCD). It can lead to difficulty with cross-matching for future transfusions and may sometimes trigger life-threatening delayed hemolytic transfusion reactions. We conducted a retrospective study to explore the association of clinical complications and age of RBC with alloimmunization in patients with SCD followed at a single institution from 2005 to 2012. One hundred and sixty six patients with a total of 488 RBC transfusions were evaluated. Nineteen patients (11%) developed new alloantibodies following blood transfusions during the period of review. The median age of RBC units was 20 days (interquartile range: 14-27 days). RBC antibody formation was significantly associated with the age of RBC units (P = 0.002), with a hazard ratio of 3.5 (95% CI: 1.71-7.11) for a RBC unit that was 7 days old and 9.8 (95% CI: 2.66-35.97) for a unit that was 35 days old, 28 days after the blood transfusion. No association was observed between RBC alloimmunization and acute vaso-occlusive complications. Although increased echocardiography-derived tricuspid regurgitant jet velocity (TRV) was associated with the presence of RBC alloantibodies (P = 0.02), TRV was not significantly associated with alloimmunization when adjusted for patient age and number of transfused RBC units. Our study suggests that RBC antibody formation is significantly associated with older age of RBCs at the time of transfusion. Prospective studies in patients with SCD are required to confirm this finding. © 2015 Wiley Periodicals, Inc.

  11. Associations of the fatty liver and hepatic steatosis indices with risk of cardiovascular disease: Interrelationship with age.

    PubMed

    Kunutsor, Setor K; Bakker, Stephan J L; Blokzijl, Hans; Dullaart, Robin P F

    2017-03-01

    The fatty liver index (FLI) and the hepatic steatosis index (HSI), are biomarker-based algorithms developed as proxies for non-alcoholic fatty liver disease (NAFLD). We assessed associations of FLI and HSI with cardiovascular disease (CVD) risk. The FLI and HSI were estimated at baseline in the PREVEND cohort involving 6340 participants aged 28-75years without pre-existing CVD. During a median follow-up of 10.5years, 631 CVD events occurred. In age-and sex-adjusted analysis, the hazard ratio (HR) (95% CI) for CVD comparing FLI≥60 versus FLI<30 was 1.53 (1.25-1.88); which was attenuated to 0.89 (0.70-1.13) on adjustment for conventional cardiovascular risk factors. The association remained absent after additional adjustment for potential confounders 0.85 (0.65-1.11). Comparing HSI>36 versus HSI<30, the corresponding adjusted HRs were 1.29 (1.02-1.65), 0.84 (0.65-1.09) and 0.79 (0.55-1.13) respectively. Subgroup analyses suggested a positive association in younger participants (<50years) for FLI and inverse associations in older participants (≥50years) for both indices (P for interaction for all=0.001). Current data suggest age interactions in the association of NAFLD (as assessed by FLI or HSI) with CVD risk in a general Caucasian population. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. MicroRNAs as Peripheral Biomarkers in Aging and Age-Related Diseases.

    PubMed

    Kumar, S; Vijayan, M; Bhatti, J S; Reddy, P H

    2017-01-01

    MicroRNAs (miRNAs) are found in the circulatory biofluids considering the important molecules for biomarker study in aging and age-related diseases. Blood or blood components (serum/plasma) are primary sources of circulatory miRNAs and can release these in cell-free form either bound with some protein components or encapsulated with microvesicle particles, called exosomes. miRNAs are quite stable in the peripheral circulation and can be detected by high-throughput techniques like qRT-PCR, microarray, and sequencing. Intracellular miRNAs could modulate mRNA activity through target-specific binding and play a crucial role in intercellular communications. At a pathological level, changes in cellular homeostasis lead to the modulation of molecular function of cells; as a result, miRNA expression is deregulated. Deregulated miRNAs came out from cells and frequently circulate in extracellular body fluids as part of various human diseases. Most common aging-associated diseases are cardiovascular disease, cancer, arthritis, dementia, cataract, osteoporosis, diabetes, hypertension, and neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Variation in the miRNA signature in a diseased peripheral circulatory system opens up a new avenue in the field of biomarker discovery. Here, we measure the biomarker potential of circulatory miRNAs in aging and various aging-related pathologies. However, further more confirmatory researches are needed to elaborate these findings at the translation level. © 2017 Elsevier Inc. All rights reserved.

  13. Increase of Reproductive Life Span Delays Age of Onset of Parkinson’s Disease

    PubMed Central

    Frentzel, Dominik; Judanin, Grigorij; Borozdina, Olga; Klucken, Jochen; Winkler, Jürgen; Schlachetzki, Johannes C. M.

    2017-01-01

    One striking observation in Parkinson’s disease (PD) is the remarkable gender difference in incidence and prevalence of the disease. Data on gender differences with regard to disease onset, motor and non-motor symptoms, and dopaminergic medication are limited. Furthermore, whether estrogen status affects disease onset and progression of PD is controversially discussed. In this retrospective single center study, we extracted clinical data of 226 ambulatory PD patients and compared age of disease onset, disease stage, motor impairment, non-motor symptoms, and dopaminergic medication between genders. We applied a matched-pairs design to adjust for age and disease duration. To determine the effect of estrogen-related reproductive factors including number of children, age at menarche, and menopause on the age of onset, we applied a standardized questionnaire and performed a regression analysis. The male to female ratio in the present PD cohort was 1.9:1 (147 men vs. 79 women). Male patients showed increased motor impairment than female patients. The levodopa equivalent daily dose was increased by 18.9% in male patients compared to female patients. Matched-pairs analysis confirmed the increased dose of dopaminergic medication in male patients. No differences were observed in age of onset, type of medication, and non-motor symptoms between both groups. Female reproductive factors including number of children, age at menarche, and age at menopause were positively associated with a delay of disease onset up to 30 months. The disease-modifying role of estrogen-related outcome measures warrants further clinical and experimental studies targeting gender differences, specifically hormone-dependent pathways in PD. PMID:28871235

  14. Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset.

    PubMed

    Nichols, W C; Pankratz, N; Marek, D K; Pauciulo, M W; Elsaesser, V E; Halter, C A; Rudolph, A; Wojcieszek, J; Pfeiffer, R F; Foroud, T

    2009-01-27

    To characterize sequence variation within the glucocerebrosidase (GBA) gene in a select subset of our sample of patients with familial Parkinson disease (PD) and then to test in our full sample whether these sequence variants increased the risk for PD and were associated with an earlier onset of disease. We performed a comprehensive study of all GBA exons in one patient with PD from each of 96 PD families, selected based on the family-specific lod scores at the GBA locus. Identified GBA variants were subsequently screened in all 1325 PD cases from 566 multiplex PD families and in 359 controls. Nine different GBA variants, five previously reported, were identified in 21 of the 96 PD cases sequenced. Screening for these variants in the full sample identified 161 variant carriers (12.2%) in 99 different PD families. An unbiased estimate of the frequency of the five previously reported GBA variants in the familial PD sample was 12.6% and in the control sample was 5.3% (odds ratio 2.6; 95% confidence interval 1.5-4.4). Presence of a GBA variant was associated with an earlier age at onset (p = 0.0001). On average, those patients carrying a GBA variant had onset with PD 6.04 years earlier than those without a GBA variant. This study suggests that GBA is a susceptibility gene for familial Parkinson disease (PD) and patients with GBA variants have an earlier age at onset than patients with PD without GBA variants.

  15. Neuroinflamm-aging and neurodegenerative diseases: an overview.

    PubMed

    Pizza, Vincenzo; Agresta, Anella; D'Acunto, Cosimo W; Festa, Michela; Capasso, Anna

    2011-08-01

    Neuroinflammation is considered a chronic activation of the immune response in the central nervous system (CNS) in response to different injuries. This brain immune activation results in various events: circulating immune cells infiltrate the CNS; resident cells are activated; and pro-inflammatory mediators produced and released induce neuroinflammatory brain disease. The effect of immune diffusible mediators on synaptic plasticity might result in CNS dysfunction during neuroinflammatory brain diseases. The CNS dysfunction may induce several human pathological conditions associated with both cognitive impairment and a variable degree of neuroinflammation. Furthermore, age has a powerful effect on enhanced susceptibility to neurodegenerative diseases and age-dependent enhanced neuroinflammatory processes may play an important role in toxin generation that causes death or dysfunction of neurons in neurodegenerative diseases This review will address current understanding of the relationship between ageing, neuroinflammation and neurodegenerative disease by focusing on the principal mechanisms by which the immune system influences the brain plastic phenomena. Also, the present review considers the principal human neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis and psychiatric disorders caused by aging and neuroinflammation.

  16. Nationwide Case-Control Study Examining the Association between Tamoxifen Use and Alzheimer's Disease in Aged Women with Breast Cancer in Taiwan.

    PubMed

    Liao, Kuan-Fu; Lin, Cheng-Li; Lai, Shih-Wei

    2017-01-01

    Background and Objectives: Little is known about the association between tamoxifen use and Alzheimer's disease in women with breast cancer. The study aimed to explore the association between tamoxifen use and Alzheimer's disease in aged women with breast cancer in Taiwan. Methods : We conducted a retrospective nationwide case-control study using the database of the Taiwan National Health Insurance Program. Totally, 173 female subjects with breast cancer aged ≥ 65 years with newly diagnosed Alzheimer's disease from 2000 to 2011 were identified as the cases. Additionally, 684 female subjects with breast cancer aged ≥ 65 years without any type of dementia were selected as the matched controls. The cases and the matched controls were matched with age and comorbidities. Ever use of tamoxifen was defined as subjects who had at least a prescription for tamoxifen before the index date. Never use of tamoxifen was defined as subjects who never had a prescription for tamoxifen before the index date. We used the logistic regression model to calculate the odds ratio (OR) and 95% confidence interval (CI) of Alzheimer's disease associated with tamoxifen use. Results : The OR of Alzheimer's disease was 3.09 for subjects with ever use of tamoxifen (95% CI 2.10, 4.55), compared with never use. The OR of Alzheimer's disease was 1.23 for subjects with increasing cumulative duration of tamoxifen use for every 1 year (95% CI 1.13, 1.34), compared with never use. Conclusion: The increased odds of Alzheimer's disease associated with tamoxifen use may be due to the survival effect, not the toxic effect. That is, the longer the tamoxifen use, the longer the patients survive, and the greater the likelihood that she may have a chance to develop Alzheimer's disease.

  17. Ageing and the border between health and disease.

    PubMed

    MacNee, William; Rabinovich, Roberto A; Choudhury, Gourab

    2014-11-01

    Ageing is associated with a progressive degeneration of the tissues, which has a negative impact on the structure and function of vital organs and is among the most important known risk factors for most chronic diseases. Since the proportion of the world's population aged >60 years will double in the next four decades, this will be accompanied by an increased incidence of chronic age-related diseases that will place a huge burden on healthcare resources. There is increasing evidence that many chronic inflammatory diseases represent an acceleration of the ageing process. Chronic pulmonary diseases represents an important component of the increasingly prevalent multiple chronic debilitating diseases, which are a major cause of morbidity and mortality, particularly in the elderly. The lungs age and it has been suggested that chronic obstructive pulmonary disease (COPD) is a condition of accelerated lung ageing and that ageing may provide a mechanistic link between COPD and many of its extrapulmonary effects and comorbidities. In this article we will describe the physiological changes and mechanisms of ageing, with particular focus on the pulmonary effects of ageing and how these may be relevant to the development of COPD and its major extrapulmonary manifestations. ©ERS 2014.

  18. Age-associated changes in cardiovascular structure and function: a fertile milieu for future disease

    PubMed Central

    Strait, James

    2015-01-01

    Important changes occur in the cardiovascular system with advancing age, even in apparently healthy individuals. Thickening and stiffening of the large arteries develop due to collagen and calcium deposition and loss of elastic fibers in the medial layer. These arterial changes cause systolic blood pressure to rise with age, while diastolic blood pressure generally declines after the sixth decade. In the left ventricle, modest concentric wall thickening occurs due to cellular hypertrophy, but cavity size does not change. Although left ventricular systolic function is preserved across the age span, early diastolic filling rate declines 30–50% between the third and ninth decades. Conversely, an age-associated increase in late diastolic filling due to atrial contraction preserves end-diastolic volume. Aerobic exercise capacity declines approximately 10% per decade in cross-sectional studies; in longitudinal studies, however, this decline is accelerated in the elderly. Reductions in peak heart rate and peripheral oxygen utilization but not stroke volume appear to mediate the age-associated decline in aerobic capacity. Deficits in both cardiac b-adrenergic receptor density and in the efficiency of postsynaptic b-adrenergic signaling contribute significantly to the reduced cardiovascular performance during exercise in older adults. Although these cardiovascular aging changes are considered “normative”, they lower the threshold for the development of cardiovascular disease, which affects the majority of older adults. PMID:21809160

  19. Stressors of School-age Children With Allergic Diseases: A Qualitative Study.

    PubMed

    Iio, Misa; Hamaguchi, Mana; Nagata, Mayumi; Yoshida, Koichi

    2018-05-08

    Most studies of stress in children with chronic diseases have been geared toward parents and caregivers have not considered allergic diseases together. This study aimed to identify the stressors associated with allergic diseases in Japanese school-age children. Stressors associated with allergic diseases of 11 school-age children (seven boys and four girls; age range: 9-12 years) were investigated using semi-structured interviews. In the qualitative thematic analysis of stressors about allergic diseases, two themes: allergic disease-specific stressors and common stressors in chronic diseases, and 12 categories were identified. A thematic map was applied to four domains of stressor: physiological factors, psychological factors, social factors, and environmental factors. The results showed that school-age children with allergic diseases have a variety of stressors. Future studies should aim to develop an allergic disease-specific stress management program with school-age children. In children with allergic diseases, not only is stress management in daily life important, but also stress management for disease-specific matters to control the symptoms and maintain mental health. Stress management should be supported for school-age children with allergic diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases

    PubMed Central

    Davalli, Pierpaola; Mitic, Tijana; Caporali, Andrea; Lauriola, Angela; D'Arca, Domenico

    2016-01-01

    The aging process worsens the human body functions at multiple levels, thus causing its gradual decrease to resist stress, damage, and disease. Besides changes in gene expression and metabolic control, the aging rate has been associated with the production of high levels of Reactive Oxygen Species (ROS) and/or Reactive Nitrosative Species (RNS). Specific increases of ROS level have been demonstrated as potentially critical for induction and maintenance of cell senescence process. Causal connection between ROS, aging, age-related pathologies, and cell senescence is studied intensely. Senescent cells have been proposed as a target for interventions to delay the aging and its related diseases or to improve the diseases treatment. Therapeutic interventions towards senescent cells might allow restoring the health and curing the diseases that share basal processes, rather than curing each disease in separate and symptomatic way. Here, we review observations on ROS ability of inducing cell senescence through novel mechanisms that underpin aging processes. Particular emphasis is addressed to the novel mechanisms of ROS involvement in epigenetic regulation of cell senescence and aging, with the aim to individuate specific pathways, which might promote healthy lifespan and improve aging. PMID:27247702

  1. Glycomics and glycoproteomics focused on aging and age-related diseases--Glycans as a potential biomarker for physiological alterations.

    PubMed

    Miura, Yuri; Endo, Tamao

    2016-08-01

    Since glycosylation depends on glycosyltransferases, glycosidases, and sugar nucleotide donors, it is susceptible to the changes associated with physiological and pathological conditions. Therefore, alterations in glycan structures may be good targets and biomarkers for monitoring health conditions. Since human aging and longevity are affected by genetic and environmental factors such as diseases, lifestyle, and social factors, a scale that reflects various environmental factors is required in the study of human aging and longevity. We herein focus on glycosylation changes elucidated by glycomic and glycoproteomic studies on aging, longevity, and age-related diseases including cognitive impairment, diabetes mellitus, and frailty. We also consider the potential of glycan structures as biomarkers and/or targets for monitoring physiological and pathophysiological changes. Glycan structures are altered in age-related diseases. These glycans and glycoproteins may be involved in the pathophysiology of these diseases and, thus, be useful diagnostic markers. Age-dependent changes in N-glycans have been reported previously in cohort studies, and characteristic N-glycans in extreme longevity have been proposed. These findings may lead to a deeper understanding of the mechanisms underlying aging as well as the factors influencing longevity. Alterations in glycosylation may be good targets and biomarkers for monitoring health conditions, and be applicable to studies on age-related diseases and healthy aging. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Traumatic Brain Injury History is Associated with Earlier Age of Onset of Alzheimer Disease

    PubMed Central

    LoBue, Christian; Wadsworth, Hannah; Wilmoth, Kristin; Clem, Matthew; Hart, John; Womack, Kyle B.; Didehbani, Nyaz; Lacritz, Laura H.; Rossetti, Heidi C.; Cullum, C. Munro

    2016-01-01

    Objective This study examined whether a history of traumatic brain injury (TBI) is associated with earlier onset of Alzheimer disease (AD), independent of apolipoprotein ε4 status (Apoe4) and gender. Method Participants with a clinical diagnosis of AD (n=7625) were obtained from the National Alzheimer’s Coordinating Center Uniform Data Set, and categorized based on self-reported lifetime TBI with loss of consciousness (LOC) (TBI+ vs TBI-) and presence of Apoe4. ANCOVAs, controlling for gender, race, and education were used to examine the association between history of TBI, presence of Apoe4, and an interaction of both risk factors on estimated age of AD onset. Results Estimated AD onset differed by TBI history and Apoe4 independently (p’s <.001). The TBI+ group had a mean age of onset 2.5 years earlier than the TBI- group. Likewise, Apoe4 carriers had a mean age of onset 2.3 years earlier than non-carriers. While the interaction was non-significant (p = .34), participants having both a history of TBI and Apoe4 had the earliest mean age of onset compared to those with a TBI history or Apoe4 alone (MDifference = 2.8 & 2.7 years, respectively). These results remained unchanged when stratified by gender. Conclusions History of self-reported TBI can be associated with an earlier onset of AD-related cognitive decline, regardless of Apoe4 status and gender. TBI may be related to an underlying neurodegenerative process in AD, but the implications of age at time of injury, severity, and repetitive injuries remain unclear. PMID:27855547

  3. Associations of clinical features and prognosis with age at disease onset in patients with systemic lupus erythematosus.

    PubMed

    Feng, X; Zou, Y; Pan, W; Wang, X; Wu, M; Zhang, M; Tao, J; Zhang, Y; Tan, K; Li, J; Chen, Z; Ding, X; Qian, X; Da, Z; Wang, M; Sun, L

    2014-03-01

    The objective of this study is to evaluate the association of clinical features and prognosis with age at disease onset in patients with systemic lupus erythematosus (SLE) in a large, multicenter Chinese cohort. Medical records of 1898 SLE inpatients from 15 hospitals were reviewed and classified into three groups according to their ages at disease presentation. Categorical data were analyzed by chi-square test and potentially associated factors were tested by multinomial logistic regression. Among the patients studied, 259 (13.6%) were juvenile onset (≤18 years), 1444 (76.1%) were early onset (>18 and ≤45 years) and 195 (10.3%) were late onset (>45 years). Whenever manifestations occurred, most patients (>80%) were diagnosed within two years. Juvenile-onset patients were more likely to be untreated before admission (p < 0.001) and have mucocutaneous manifestations (p < 0.001), but musculoskeletal symptoms (p < 0.05) and leukopenia (p < 0.05) were less frequent, while comorbidities were much higher in patients with late-onset SLE (p < 0.001). Neuropsychiatric, cardiopulmonary, renal and gastrointestinal involvement, disease activity index and damage scores were similar among three groups. Anti-Sm antibodies were less prevalent in late-onset patients (p < 0.05) and antimalarial drugs were more often applied to juvenile-onset patients (p < 0.001). As expected, mortality was elevated in the late-onset SLE group (p < 0.05), in which nearly half died of infections, which was much higher than those in the other two groups (p < 0.001). Logistic regression confirmed that patients with juvenile- and early-onset disease were associated with high incidence of being untreated prior to admission, and with low incidence of comorbidities as well as deaths caused by infection compared to patients with late-onset lupus. Interestingly, our data showed that more patients with late-onset disease had a SLEDAI score change of >7 at discharge. In

  4. Aging With Down Syndrome: The Dual Diagnosis: Alzheimer's Disease and Down Syndrome.

    PubMed

    Cipriani, Gabriele; Danti, Sabrina; Carlesi, Cecilia; Di Fiorino, Mario

    2018-06-01

    People with Down syndrome (DS) enjoy a longer life expectancy now than they ever have before and are therefore at greater risk of developing conditions associated with aging, including dementia. To explore the phenomenon of dementia in DS. Medline and Google Scholar searches were conducted for relevant articles, chapters, and books published until 2017. Search terms included Alzheimer's disease, cognitive impairment, dementia, DS, and trisomy 21. Publications found through this indexed search were reviewed for further references. Virtually, all subject aged 35 to 40 show key neuropathologic changes characteristic of Alzheimer's disease, but only a part of them show clinical signs of dementia, usually around the age of 50 years. Early signs of dementia in people with DS may be different from those experienced by the general population. Failure to recognize this can delay diagnosis and subsequent interventions.

  5. Factors associated with mixed dementia vs Alzheimer disease in elderly Mexican adults.

    PubMed

    Moreno Cervantes, C; Mimenza Alvarado, A; Aguilar Navarro, S; Alvarado Ávila, P; Gutiérrez Gutiérrez, L; Juárez Arellano, S; Ávila Funes, J A

    2017-06-01

    Mixed dementia (DMix) refers to dementia resulting from Alzheimer disease in addition to cerebrovascular disease. The study objectives were to determine the clinical and imaging factors associated with Dmix and compare them to those associated with Alzheimer disease. Cross-sectional study including 225 subjects aged 65 years and over from a memory clinic in a tertiary hospital in Mexico City. All patients underwent clinical, neuropsychological, and brain imaging studies. We included patients diagnosed with DMix or Alzheimer disease (AD). A multivariate analysis was used to determine factors associated with DMix. We studied 137 subjects diagnosed with Dmix. Compared to patients with AD, Dmix patients were older and more likely to present diabetes, hypertension, dyslipidaemia, and history of cerebrovascular disease (P<.05). The multivariate analysis showed that hypertension (OR 1.92, CI 1.62-28.82; P=.009), white matter disease (OR 3.61, CI 8.55-159.80; P<.001), and lacunar infarcts (OR 3.35, CI 1.97-412.34; P=.014) were associated with Dmix, whereas a history of successfully treated depression showed an inverse association (OR 0.11, CI 0.02-0-47; P=.004) CONCLUSIONS: DMix may be more frequent than AD. Risk factors such as advanced age and other potentially modifiable factors were associated with this type of dementia. Clinicians should understand and be able to define Dmix. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Association of Coronary Artery Calcium in Adults Aged 32 to 46 Years With Incident Coronary Heart Disease and Death

    PubMed Central

    Jacobs, David R.; Terry, James G.; Shay, Christina M.; Sidney, Stephen; Liu, Kiang; Schreiner, Pamela J.; Lewis, Cora E.; Shikany, James M.; Reis, Jared P.; Goff, David C.

    2017-01-01

    Importance Coronary artery calcium (CAC) is associated with coronary heart disease (CHD) and cardiovascular disease (CVD); however, prognostic data on CAC are limited in younger adults. Objective To determine if CAC in adults aged 32 to 46 years is associated with incident clinical CHD, CVD, and all-cause mortality during 12.5 years of follow-up. Design, Setting, and Participants The Coronary Artery Risk Development in Young Adults (CARDIA) Study is a prospective community-based study that recruited 5115 black and white participants aged 18 to 30 years from March 25, 1985, to June 7, 1986. The cohort has been under surveillance for 30 years, with CAC measured 15 (n = 3043), 20 (n = 3141), and 25 (n = 3189) years after recruitment. The mean follow-up period for incident events was 12.5 years, from the year 15 computed tomographic scan through August 31, 2014. Main Outcomes and Measures Incident CHD included fatal or nonfatal myocardial infarction, acute coronary syndrome without myocardial infarction, coronary revascularization, or CHD death. Incident CVD included CHD, stroke, heart failure, and peripheral arterial disease. Death included all causes. The probability of developing CAC by age 32 to 56 years was estimated using clinical risk factors measured 7 years apart between ages 18 and 38 years. Results At year 15 of the study among 3043 participants (mean [SD] age, 40.3 [3.6] years; 1383 men and 1660 women), 309 individuals (10.2%) had CAC, with a geometric mean Agatston score of 21.6 (interquartile range, 17.3-26.8). Participants were followed up for 12.5 years, with 57 incident CHD events and 108 incident CVD events observed. After adjusting for demographics, risk factors, and treatments, those with any CAC experienced a 5-fold increase in CHD events (hazard ratio [HR], 5.0; 95% CI, 2.8-8.7) and 3-fold increase in CVD events (HR, 3.0; 95% CI, 1.9-4.7). Within CAC score strata of 1-19, 20-99, and 100 or more, the HRs for CHD were 2.6 (95% CI, 1

  7. Low-grade systemic inflammation connects aging, metabolic syndrome and cardiovascular disease.

    PubMed

    Guarner, Verónica; Rubio-Ruiz, Maria Esther

    2015-01-01

    Aging is associated with immunosenescence and accompanied by a chronic inflammatory state which contributes to metabolic syndrome, diabetes and their cardiovascular consequences. Risk factors for cardiovascular diseases (CVDs) and diabetes overlap, leading to the hypothesis that both share an inflammatory basis. Obesity is increased in the elderly population, and adipose tissue induces a state of systemic inflammation partially induced by adipokines. The liver plays a pivotal role in the metabolism of nutrients and exhibits alterations in the expression of genes associated with inflammation, cellular stress and fibrosis. Hepatic steatosis and its related inflammatory state (steatohepatitis) are the main hepatic complications of obesity and metabolic diseases. Aging-linked declines in expression and activity of endoplasmic reticulum molecular chaperones and folding enzymes compromise proper protein folding and the adaptive response of the unfolded protein response. These changes predispose aged individuals to CVDs. CVDs and endothelial dysfunction are characterized by a chronic alteration of inflammatory function and markers of inflammation and the innate immune response, including C-reactive protein, interleukin-6, TNF-α, and several cell adhesion molecules are linked to the occurrence of myocardial infarction and stroke in healthy elderly populations and patients with metabolic diseases. 2015 S. Karger AG, Basel.

  8. The association between personal income and aging: A population-based 13-year longitudinal study.

    PubMed

    Lin, Tzu-Yu; Chen, Chia-Yu; Tsao, Chueh-Yung; Hsu, Kuang-Hung

    Population aging is set to increase the elder dependency ratio, causing a rapid increase in healthcare expenditures and financial burden on the government. This study aims to construct an aging score from age-related diseases and to perform longitudinal analyses to examine the association between personal income and aging. A total of 86,838 subjects drawn from a community with 384,617 residents in northern Taiwan were examined. Personal income and aging-related diseases were measured from the National Health Insurance database during 1997-2010. Multiple linear regression and stratified analyses were used. Our results indicate that subjects with low personal income (defined as monthly income ≤610 USD) can have high aging scores as calculated by selected aging-related diseases. In stratified analyses, moreover, subjects with low personal income tended to have higher aging scores across different anthropometric groups. The association was particularly evident in subjects >60years old, and they were noted across multiple strata, including those of catastrophic illness as well as type of primary care setting. This study found evidence for association between low income and aging in a population with compulsory health insurance program, where accessibility barriers were low in terms of health care resources and personal socioeconomic status. The economic inequity causes difference in aging process, which deserves for future interventions. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Inflammation, chronic obstructive pulmonary disease and aging.

    PubMed

    Provinciali, Mauro; Cardelli, Maurizio; Marchegiani, Francesca

    2011-12-01

    Chronic obstructive pulmonary disease (COPD) is characterized by an abnormal persistent inflammatory response to noxious environmental stimuli, particularly cigarette smoke. The determinants of the dysregulated immune responses, which play a role both in the onset and continuation of COPD, are largely unknown. We examined several molecular mechanisms regulating the inflammatory pathway, such as cytokine polymorphisms, miRNA expression, and DNA methylation in COPD and aging, with the aim to provide evidence supporting the view that aging of the immune system may predispose to COPD. The incidence of COPD increases with age. The pathogenesis of the disease is linked to a chronic inflammation and involves the recruitment and regulation of innate and adaptive immune cells. A chronic systemic inflammation characterizes aging and has been correlated with many diseases, most of them age-related. COPD and aging are associated with significant dysregulation of the immune system that leads to a chronic inflammatory response. The similar molecular mechanisms and the common genetic signature shared by COPD and aging suggest that immunosenescence may contribute to the development of COPD.

  10. iPSCs, aging and age-related diseases.

    PubMed

    Isobe, Ken-Ichi; Cheng, Zhao; Nishio, Naomi; Suganya, Thanasegan; Tanaka, Yuriko; Ito, Sachiko

    2014-09-25

    Human histocompatibility antigens are quite heterogeneous and promote the rejection of transplanted tissue. Recent advances in stem cell research that enable the use of a patient's own stem cells for transplantation are very important because rejection could be avoided. In particular, Yamanaka's group in Japan gave new hope to patients with incurable diseases when they developed induced murine pluripotent stem cells (iPSCs) in 2006 and human iPSCs in 2007. Whereas embryonic stem cells (ESCs) are derived from the inner cell mass and are supported in culture by LIF, iPSCs are derived from fetal or adult somatic cells. Through the application of iPSC technology, adult somatic cells can develop a pluripotent state. One advantage of using iPSCs instead of ESCs in regenerative medicine is that (theoretically) immune rejection could be avoided, although there is some debate about immune rejection of a patient's own iPSCs. Many diseases occur in elderly patients. In order to use regenerative medicine with the elderly, it is important to demonstrate that iPSCs can indeed be generated from older patients. Recent findings have shown that iPSCs can be established from aged mice and aged humans. These iPSCs can differentiate to cells from all three germ layers. However, it is not known whether iPSCs from aged mice or humans show early senescence. Before clinical use of iPSCs, issues related to copy number variation, tumorigenicity and immunogenicity must be resolved. It is particularly important that researchers have succeeded in generating iPSCs that have differentiated to somatic cells related to specific diseases of the elderly, including atherosclerosis, diabetes, Alzheimer's disease and Parkinson's disease. These efforts will facilitate the use of personalized stem cell transplantation therapy for currently incurable diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. The Association of Age With Clinical Presentation and Comorbidities of Pyoderma Gangrenosum.

    PubMed

    Ashchyan, Hovik J; Butler, Daniel C; Nelson, Caroline A; Noe, Megan H; Tsiaras, William G; Lockwood, Stephen J; James, William D; Micheletti, Robert G; Rosenbach, Misha; Mostaghimi, Arash

    2018-04-01

    Pyoderma gangrenosum is an inflammatory neutrophilic dermatosis. Current knowledge of this rare disease is limited owing to a lack of validated diagnostic criteria and large population studies. To evaluate the association of age with the clinical presentation and comorbidities of pyoderma gangrenosum. This was a multicenter retrospective cohort study performed at tertiary academic referral centers in urban settings. Adults (≥18 years) who were evaluated and diagnosed as having pyoderma gangrenosum at the Brigham and Women's and Massachusetts General Hospitals from 2000 to 2015 and the University of Pennsylvania Health System from 2006 to 2016 were included. Patient demographics, clinical features, medical comorbidities, and treatment. Of the 356 validated cases of pyoderma gangrenosum included in the study, 267 (75%) were women and 284 (84.8%) were white. The mean (SD) age at presentation was 51.6 (17.7) years. Pathergy was recorded in 100 patients (28.1%). A total of 238 patients (66.9%) had associated medical comorbidities: inflammatory bowel disease in 146 patients (41.0%); inflammatory arthritis in 73 patients (20.5%); solid organ malignant neoplasms in 23 patients (6.5%); hematologic malignant neoplasms in 21 patients (5.9%); and hematologic disorders, specifically monoclonal gammopathy of undetermined significance, myelodysplastic syndrome, and polycythemia vera in 17 patients (4.8%). When stratified by age, pathergy was more common in patients 65 years or older (36.3% vs 24.3%; P = .02). Inflammatory bowel disease was the only medical comorbidity that was more common in patients younger than 65 years (47.7% vs 26.6%; P < .001), while a number of medical comorbidities were more common in those 65 years or older, including rheumatoid arthritis (13.3% vs 6.2%; P = .03), ankylosing spondylitis (1.8% vs 0%; P = .04), solid organ malignant neoplasms (13.3% vs 3.3%; P < .001), hematologic malignant neoplasms (9.7% vs 4.1%; P = .04), and

  12. Odorant Item Specific Olfactory Identification Deficit May Differentiate Alzheimer Disease From Aging.

    PubMed

    Woodward, Matthew R; Hafeez, Muhammad Ubaid; Qi, Qianya; Riaz, Ahmed; Benedict, Ralph H B; Yan, Li; Szigeti, Kinga

    2018-04-19

    To explore whether the ability to recognize specific odorant items is differentially affected in aging versus Alzheimer disease (AD); to refine olfactory identification deficit (OID) as a biomarker of prodromal and early AD. Prospective multicenter cross-sectional study with a longitudinal arm. Outpatient memory diagnostic clinics in New York and Texas. Adults aged 65 and older with amnestic mild cognitive impairment (aMCI) and AD and healthy aging (HA) subjects in the comparison group. Participants completed the University of Pennsylvania Smell Identification Test (UPSIT) and neuropsychological testing. AD-associated odorants (AD-10) were selected based on a model of ordinal logistic regression. Age-associated odorants (Age-10) were identified using a linear model. For the 841 participants (234 HA, 192 aMCI, 415 AD), AD-10 was superior to Age-10 in separating HA and AD. AD-10 was associated with a more widespread cognitive deficit across multiple domains, in contrast to Age-10. The disease- and age-associated odorants clustered separately in age and AD. AD-10 predicted conversion from aMCI to AD. Nonoverlapping UPSIT items were identified that were individually associated with age and disease. Despite a modest predictive value of the AD-specific items for conversion to AD, the AD-specific items may be useful in enriching samples to better identify those at risk for AD. Further studies are needed with monomolecular and unilateral stimulation and orthogonal biomarker validation to further refine disease- and age-associated signals. Copyright © 2018 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  13. Whole-genome sequencing suggests a chemokine gene cluster that modifies age at onset in familial Alzheimer's disease

    PubMed Central

    Lalli, M A; Bettcher, B M; Arcila, M L; Garcia, G; Guzman, C; Madrigal, L; Ramirez, L; Acosta-Uribe, J; Baena, A; Wojta, K J; Coppola, G; Fitch, R; de Both, M D; Huentelman, M J; Reiman, E M; Brunkow, M E; Glusman, G; Roach, J C; Kao, A W; Lopera, F; Kosik, K S

    2015-01-01

    We have sequenced the complete genomes of 72 individuals affected with early-onset familial Alzheimer's disease caused by an autosomal dominant, highly penetrant mutation in the presenilin-1 (PSEN1) gene, and performed genome-wide association testing to identify variants that modify age at onset (AAO) of Alzheimer's disease. Our analysis identified a haplotype of single-nucleotide polymorphisms (SNPs) on chromosome 17 within a chemokine gene cluster associated with delayed onset of mild-cognitive impairment and dementia. Individuals carrying this haplotype had a mean AAO of mild-cognitive impairment at 51.0±5.2 years compared with 41.1±7.4 years for those without these SNPs. This haplotype thus appears to modify Alzheimer's AAO, conferring a large (~10 years) protective effect. The associated locus harbors several chemokines including eotaxin-1 encoded by CCL11, and the haplotype includes a missense polymorphism in this gene. Validating this association, we found plasma eotaxin-1 levels were correlated with disease AAO in an independent cohort from the University of California San Francisco Memory and Aging Center. In this second cohort, the associated haplotype disrupted the typical age-associated increase of eotaxin-1 levels, suggesting a complex regulatory role for this haplotype in the general population. Altogether, these results suggest eotaxin-1 as a novel modifier of Alzheimer's disease AAO and open potential avenues for therapy. PMID:26324103

  14. Whole-genome sequencing suggests a chemokine gene cluster that modifies age at onset in familial Alzheimer's disease.

    PubMed

    Lalli, M A; Bettcher, B M; Arcila, M L; Garcia, G; Guzman, C; Madrigal, L; Ramirez, L; Acosta-Uribe, J; Baena, A; Wojta, K J; Coppola, G; Fitch, R; de Both, M D; Huentelman, M J; Reiman, E M; Brunkow, M E; Glusman, G; Roach, J C; Kao, A W; Lopera, F; Kosik, K S

    2015-11-01

    We have sequenced the complete genomes of 72 individuals affected with early-onset familial Alzheimer's disease caused by an autosomal dominant, highly penetrant mutation in the presenilin-1 (PSEN1) gene, and performed genome-wide association testing to identify variants that modify age at onset (AAO) of Alzheimer's disease. Our analysis identified a haplotype of single-nucleotide polymorphisms (SNPs) on chromosome 17 within a chemokine gene cluster associated with delayed onset of mild-cognitive impairment and dementia. Individuals carrying this haplotype had a mean AAO of mild-cognitive impairment at 51.0 ± 5.2 years compared with 41.1 ± 7.4 years for those without these SNPs. This haplotype thus appears to modify Alzheimer's AAO, conferring a large (~10 years) protective effect. The associated locus harbors several chemokines including eotaxin-1 encoded by CCL11, and the haplotype includes a missense polymorphism in this gene. Validating this association, we found plasma eotaxin-1 levels were correlated with disease AAO in an independent cohort from the University of California San Francisco Memory and Aging Center. In this second cohort, the associated haplotype disrupted the typical age-associated increase of eotaxin-1 levels, suggesting a complex regulatory role for this haplotype in the general population. Altogether, these results suggest eotaxin-1 as a novel modifier of Alzheimer's disease AAO and open potential avenues for therapy.

  15. Connective tissue disease-associated pulmonary arterial hypertension

    PubMed Central

    Howard, Luke S.

    2015-01-01

    Although rare in its idiopathic form, pulmonary arterial hypertension (PAH) is not uncommon in association with various associated medical conditions, most notably connective tissue disease (CTD). In particular, it develops in approximately 10% of patients with systemic sclerosis and so these patients are increasingly screened to enable early detection. The response of patients with systemic sclerosis to PAH-specific therapy appears to be worse than in other forms of PAH. Survival in systemic sclerosis-associated PAH is inferior to that observed in idiopathic PAH. Potential reasons for this include differences in age, the nature of the underlying pulmonary vasculopathy and the ability of the right ventricle to cope with increased afterload between patients with systemic sclerosis-associated PAH and idiopathic PAH, while coexisting cardiac and pulmonary disease is common in systemic sclerosis-associated PAH. Other forms of connective tissue-associated PAH have been less well studied, however PAH associated with systemic lupus erythematosus (SLE) has a better prognosis than systemic sclerosis-associated PAH and likely responds to immunosuppression. PMID:25705389

  16. Three SNPs in the GSTO1, GSTO2 and PRSS11 genes on chromosome 10 are not associated with age-at-onset of Alzheimer's disease.

    PubMed

    Ozturk, Ayla; Desai, Purnima P; Minster, Ryan L; Dekosky, Steven T; Kamboh, M Ilyas

    2005-01-01

    Linkage studies suggest the presence of putative risk and/or age-at-onset genes for Alzheimer's disease on Chromosome 10. Recently, a genomic converging approach using a combination of linkage, expression and association studies has reported significant associations of the glutathione S-transferase omega 1 and 2 (GSTO1 and GSTO2) genes and possibly the protease serine 11 (PRSS11) gene on chromosome 10 with age-at-onset, but not risk, for Alzheimer's disease (AD) and Parkinson disease. We investigated the association of the reported three polymorphisms in 990 sporadic late-onset AD cases (26% autopsy confirmed) and 735 controls. In our sample, we found no association either with age-at-onset in AD cases or with disease risk in the case-control cohort. However, haplotype analysis revealed a modest association of one haplotype with AD risk (p = 0.04). Additional markers in these genes need to be screened to explore their role in the etiology of AD.

  17. Effects of multiple genetic loci on age at onset in late-onset Alzheimer disease: a genome-wide association study.

    PubMed

    Naj, Adam C; Jun, Gyungah; Reitz, Christiane; Kunkle, Brian W; Perry, William; Park, Yo Son; Beecham, Gary W; Rajbhandary, Ruchita A; Hamilton-Nelson, Kara L; Wang, Li-San; Kauwe, John S K; Huentelman, Matthew J; Myers, Amanda J; Bird, Thomas D; Boeve, Bradley F; Baldwin, Clinton T; Jarvik, Gail P; Crane, Paul K; Rogaeva, Ekaterina; Barmada, M Michael; Demirci, F Yesim; Cruchaga, Carlos; Kramer, Patricia L; Ertekin-Taner, Nilufer; Hardy, John; Graff-Radford, Neill R; Green, Robert C; Larson, Eric B; St George-Hyslop, Peter H; Buxbaum, Joseph D; Evans, Denis A; Schneider, Julie A; Lunetta, Kathryn L; Kamboh, M Ilyas; Saykin, Andrew J; Reiman, Eric M; De Jager, Philip L; Bennett, David A; Morris, John C; Montine, Thomas J; Goate, Alison M; Blacker, Deborah; Tsuang, Debby W; Hakonarson, Hakon; Kukull, Walter A; Foroud, Tatiana M; Martin, Eden R; Haines, Jonathan L; Mayeux, Richard P; Farrer, Lindsay A; Schellenberg, Gerard D; Pericak-Vance, Margaret A; Albert, Marilyn S; Albin, Roger L; Apostolova, Liana G; Arnold, Steven E; Barber, Robert; Barnes, Lisa L; Beach, Thomas G; Becker, James T; Beekly, Duane; Bigio, Eileen H; Bowen, James D; Boxer, Adam; Burke, James R; Cairns, Nigel J; Cantwell, Laura B; Cao, Chuanhai; Carlson, Chris S; Carney, Regina M; Carrasquillo, Minerva M; Carroll, Steven L; Chui, Helena C; Clark, David G; Corneveaux, Jason; Cribbs, David H; Crocco, Elizabeth A; DeCarli, Charles; DeKosky, Steven T; Dick, Malcolm; Dickson, Dennis W; Duara, Ranjan; Faber, Kelley M; Fallon, Kenneth B; Farlow, Martin R; Ferris, Steven; Frosch, Matthew P; Galasko, Douglas R; Ganguli, Mary; Gearing, Marla; Geschwind, Daniel H; Ghetti, Bernardino; Gilbert, John R; Glass, Jonathan D; Growdon, John H; Hamilton, Ronald L; Harrell, Lindy E; Head, Elizabeth; Honig, Lawrence S; Hulette, Christine M; Hyman, Bradley T; Jicha, Gregory A; Jin, Lee-Way; Karydas, Anna; Kaye, Jeffrey A; Kim, Ronald; Koo, Edward H; Kowall, Neil W; Kramer, Joel H; LaFerla, Frank M; Lah, James J; Leverenz, James B; Levey, Allan I; Li, Ge; Lieberman, Andrew P; Lin, Chiao-Feng; Lopez, Oscar L; Lyketsos, Constantine G; Mack, Wendy J; Martiniuk, Frank; Mash, Deborah C; Masliah, Eliezer; McCormick, Wayne C; McCurry, Susan M; McDavid, Andrew N; McKee, Ann C; Mesulam, Marsel; Miller, Bruce L; Miller, Carol A; Miller, Joshua W; Murrell, Jill R; Olichney, John M; Pankratz, Vernon S; Parisi, Joseph E; Paulson, Henry L; Peskind, Elaine; Petersen, Ronald C; Pierce, Aimee; Poon, Wayne W; Potter, Huntington; Quinn, Joseph F; Raj, Ashok; Raskind, Murray; Reisberg, Barry; Ringman, John M; Roberson, Erik D; Rosen, Howard J; Rosenberg, Roger N; Sano, Mary; Schneider, Lon S; Seeley, William W; Smith, Amanda G; Sonnen, Joshua A; Spina, Salvatore; Stern, Robert A; Tanzi, Rudolph E; Thornton-Wells, Tricia A; Trojanowski, John Q; Troncoso, Juan C; Valladares, Otto; Van Deerlin, Vivianna M; Van Eldik, Linda J; Vardarajan, Badri N; Vinters, Harry V; Vonsattel, Jean Paul; Weintraub, Sandra; Welsh-Bohmer, Kathleen A; Williamson, Jennifer; Wishnek, Sarah; Woltjer, Randall L; Wright, Clinton B; Younkin, Steven G; Yu, Chang-En; Yu, Lei

    2014-11-01

    Because APOE locus variants contribute to risk of late-onset Alzheimer disease (LOAD) and to differences in age at onset (AAO), it is important to know whether other established LOAD risk loci also affect AAO in affected participants. To investigate the effects of known Alzheimer disease risk loci in modifying AAO and to estimate their cumulative effect on AAO variation using data from genome-wide association studies in the Alzheimer Disease Genetics Consortium. The Alzheimer Disease Genetics Consortium comprises 14 case-control, prospective, and family-based data sets with data on 9162 participants of white race/ethnicity with Alzheimer disease occurring after age 60 years who also had complete AAO information, gathered between 1989 and 2011 at multiple sites by participating studies. Data on genotyped or imputed single-nucleotide polymorphisms most significantly associated with risk at 10 confirmed LOAD loci were examined in linear modeling of AAO, and individual data set results were combined using a random-effects, inverse variance-weighted meta-analysis approach to determine whether they contribute to variation in AAO. Aggregate effects of all risk loci on AAO were examined in a burden analysis using genotype scores weighted by risk effect sizes. Age at disease onset abstracted from medical records among participants with LOAD diagnosed per standard criteria. Analysis confirmed the association of APOE with earlier AAO (P = 3.3 × 10(-96)), with associations in CR1 (rs6701713, P = 7.2 × 10(-4)), BIN1 (rs7561528, P = 4.8 × 10(-4)), and PICALM (rs561655, P = 2.2 × 10(-3)) reaching statistical significance (P < .005). Risk alleles individually reduced AAO by 3 to 6 months. Burden analyses demonstrated that APOE contributes to 3.7% of the variation in AAO (R(2) = 0.256) over baseline (R(2) = 0.221), whereas the other 9 loci together contribute to 2.2% of the variation (R(2) = 0.242). We confirmed an association of APOE (OMIM 107741) variants with AAO among

  18. Immunohistochemical and ELISA assays for biomarkers of oxidative stress in aging and disease.

    PubMed

    Onorato, J M; Thorpe, S R; Baynes, J W

    1998-11-20

    Oxidative stress is apparent in pathology associated with aging and many age-related, chronic diseases, including atherosclerosis, diabetes mellitus, rheumatoid arthritis, and neurodegenerative diseases. Although it cannot be measured directly in biological systems, several biomarkers have been identified that provide a measure of oxidative damage to biomolecules. These include amino acid oxidation products (methionine sulfoxide, ortho-tyrosine (o-tyr) and dityrosine, chlorotyrosine and nitrotyrosine), as well as chemical modifications of protein following carbohydrate or lipid oxidation, such as N epsilon-(carboxymethyl)lysine and N epsilon-(carboxyethyl)lysine, and malondialdehyde and 4-hydroxynonenal adducts to amino acids. Other biomarkers include the amino acid cross-link pentosidine, the imidazolone adducts formed by reaction of 3-deoxyglucosone or methylglyoxal with arginine, and the imidazolium cross-links formed by the reaction of glyoxal and methylglyoxal with lysine residues in protein. These compounds have been measured in short-lived intracellular proteins, plasma proteins, long-lived extracellular proteins, and in urine, making them valuable tools for monitoring tissue-specific and systemic chemical and oxidative damage to proteins in biological systems. They are normally measured by sensitive high-performance liquid chromatography or gas chromatography-mass spectrometry methods, requiring both complex analytical instrumentation and derivatization procedures. However, sensitive immunohistochemical and ELISA assays are now available for many of these biomarkers. Immunochemical assays should facilitate studies on the role of oxidative stress in aging and chronic disease and simplify the evaluation of therapeutic approaches for limiting oxidative damage in tissues and treating pathologies associated with aging and disease. In this article we summarize recent data and conclusions based on immunohistochemical and ELISA assays, emphasizing the strengths and

  19. Association of rheumatoid arthritis with allergic diseases: A nationwide population-based cohort study.

    PubMed

    Lai, Ning-Sheng; Tsai, Tzung-Yi; Koo, Malcolm; Lu, Ming-Chi

    2015-01-01

    Low-grade inflammation conditions, e.g., type 2 diabetes, have been shown to be associated with an increased risk of rheumatoid arthritis (RA). However, the association between other chronic inflammatory conditions, e.g., asthma, allergic rhinitis, and atopic dermatitis, is still unclear. To investigate the risk of RA in patients with allergic diseases, including asthma, allergic rhinitis, and atopic dermatitis, by using a nationwide health claims database. The Taiwan National Health Insurance Research Database was used to assemble a cohort of 170,570 patients ages 20 years old and older diagnosed with allergic diseases, including asthma, allergic rhinitis, or atopic dermatitis. A comparison cohort of 170,238 patients was constructed from the same data base, with frequency matching for sex, 10-year age group, and year of insurance enrollment. Cox proportional hazards regression analyses were conducted to assess the association between the allergic diseases and incident RA. Asthma (adjusted hazard ratio [AHR] 1.67, [95% confidence interval {CI}], 1.32-2.62) and allergic rhinitis (AHR 1.62 [95% CI, 1.33-1.98]) were significantly associated with the incident RA. These associations remained significant even after excluding patients who had concurrent diagnoses of asthma and allergic rhinitis. Patients with more than one allergic disease had an increased risk of developing RA (AHR 1.98 [95% CI, 1.50-2.62]). Subgroup analysis further indicated that middle-aged and elderly female patients with more than one allergic disease exhibited a high risk of developing RA. Significant associations between common allergic diseases and incident RA was found in this population-based cohort study. Our findings provided support to the hypothesis that allergic diseases and RA might share a similar underlying etiologic pathway related to chronic inflammatory responses.

  20. Hippocampal sclerosis of aging, a prevalent and high-morbidity brain disease

    PubMed Central

    Smith, Charles D.; Abner, Erin L.; Wilfred, Bernard J.; Wang, Wang-Xia; Neltner, Janna H.; Baker, Michael; Fardo, David W.; Kryscio, Richard J.; Scheff, Stephen W.; Jicha, Gregory A.; Jellinger, Kurt A.; Van Eldik, Linda J.; Schmitt, Frederick A.

    2013-01-01

    Hippocampal sclerosis of aging (HS-Aging) is a causative factor in a large proportion of elderly dementia cases. The current definition of HS-Aging rests on pathologic criteria: neuronal loss and gliosis in the hippocampal formation that is out of proportion to AD-type pathology. HS-Aging is also strongly associated with TDP-43 pathology. HS-Aging pathology appears to be most prevalent in the oldest-old: autopsy series indicate that 5–30 % of nonagenarians have HS-Aging pathology. Among prior studies, differences in study design have contributed to the study-to-study variability in reported disease prevalence. The presence of HS-Aging pathology correlates with significant cognitive impairment which is often misdiagnosed as AD clinically. The antemortem diagnosis is further confounded by other diseases linked to hippocampal atrophy including frontotemporal lobar degeneration and cerebrovascular pathologies. Recent advances characterizing the neurocognitive profile of HS-Aging patients have begun to provide clues that may help identify living individuals with HS-Aging pathology. Structural brain imaging studies of research subjects followed to autopsy reveal hippocampal atrophy that is substantially greater in people with eventual HS-Aging pathology, compared to those with AD pathology alone. Data are presented from individuals who were followed with neurocognitive and neuroradiologic measurements, followed by neuropathologic evaluation at the University of Kentucky. Finally, we discuss factors that are hypothesized to cause or modify the disease. We conclude that the published literature on HS-Aging provides strong evidence of an important and under-appreciated brain disease of aging. Unfortunately, there is no therapy or preventive strategy currently available. PMID:23864344

  1. HEALTH CONDITIONS LINKED TO AGE-RELATED MACULAR DEGENERATION ASSOCIATED WITH DARK ADAPTATION.

    PubMed

    Laíns, Inês; Miller, John B; Mukai, Ryo; Mach, Steven; Vavvas, Demetrios; Kim, Ivana K; Miller, Joan W; Husain, Deeba

    2018-06-01

    To determine the association between dark adaption (DA) and different health conditions linked with age-related macular degeneration (AMD). Cross-sectional study, including patients with AMD and a control group. Age-related macular degeneration was graded according to the Age-Related Eye Disease Study (AREDS) classification. We obtained data on medical history, medications, and lifestyle. Dark adaption was assessed with the extended protocol (20 minutes) of AdaptDx (MacuLogix). For analyses, the right eye or the eye with more advanced AMD was selected. Multivariate linear and logistic regressions were performed, accounting for age and AMD stage. Seventy-eight subjects (75.6% AMD; 24.4% controls) were included. Multivariate assessments revealed that body mass index (BMI; β = 0.30, P = 0.045), taking AREDS vitamins (β = 5.51, P < 0.001), and family history of AMD (β = 2.68, P = 0.039) were significantly associated with worse rod intercept times. Abnormal DA (rod intercept time ≥ 6.5 minutes) was significantly associated with family history of AMD (β = 1.84, P = 0.006), taking AREDS supplements (β = 1.67, P = 0.021) and alcohol intake (β = 0.07, P = 0.017). Besides age and AMD stage, a higher body mass index, higher alcohol intake, and a family history of AMD seem to impair DA. In this cohort, the use of AREDS vitamins was also statistically linked with impaired DA, most likely because of an increased severity of disease in subjects taking them.

  2. Investigating the Association Between Periodontal Disease and Risk of Pancreatic Cancer.

    PubMed

    Chang, Jeffrey S; Tsai, Chia-Rung; Chen, Li-Tzong; Shan, Yan-Shen

    2016-01-01

    Periodontal disease (PD) is increasingly recognized as an emerging risk factor for various systemic diseases, including diabetes, cardiovascular diseases, and cancer. The current study examined the association between PD (periodontitis, gingivitis, and others) and pancreatic cancer. A total of 139,805 subjects with PD and 75,085 subjects without PD were identified from the National Health Insurance Research Database of Taiwan. Cox proportional hazards regression was performed to compare the incidence of pancreatic cancer between the 2 groups. Periodontal disease was positively associated with pancreatic cancer risk (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.02-2.33). This positive association occurred predominantly among those aged 65 years or older (HR, 2.17; 95% CI, 1.03-4.57) and was not observed among those aged younger than 65 years (HR, 0.83; 95% CI, 0.52-1.34). Further analysis showed that PD is a risk factor for pancreatic cancer independent of diabetes, hyperlipidemia, allergies, viral hepatitis, peptic ulcer, pancreatitis, chronic obstructive pulmonary disease (as a proxy for cigarette smoking), and alcoholic-related conditions (as a proxy for alcohol drinking). Our results indicated a significantly positive association between PD and risk of pancreatic cancer. The underlying biological mechanisms for the positive association between PD and pancreatic cancer require further investigation.

  3. Membranoproliferative glomerulonephritis associated with autoimmune diseases.

    PubMed

    Zand, Ladan; Fervenza, Fernando C; Nasr, Samih H; Sethi, Sanjeev

    2014-04-01

    Membranoproliferative glomerulonephritis (MPGN) has been classified based on its pathogenesis into immune complex-mediated and complement-mediated MPGN. The immune complex-mediated type is secondary to chronic infections, autoimmune diseases or monoclonal gammopathy. There is a paucity of data on MPGN associated with autoimmune diseases. We reviewed the Mayo Clinic database over a 10-year period and identified 12 patients with MPGN associated with autoimmune diseases, after exclusion of systemic lupus erythematosus. The autoimmune diseases included rheumatoid arthritis, primary Sjögren's syndrome, undifferentiated connective tissue disease, primary sclerosing cholangitis and Graves' disease. Nine of the 12 patients were female, and the mean age was 57.9 years. C4 levels were decreased in nine of 12 patients tested. The serum creatinine at time of renal biopsy was 2.2 ± 1.0 mg/dl and the urinary protein was 2,850 ± 3,543 mg/24 h. Three patients required dialysis at the time of renal biopsy. Renal biopsy showed an MPGN in all cases, with features of cryoglobulins in six cases; immunoglobulin (Ig)M was the dominant Ig, and both subendothelial and mesangial electron dense deposits were noted. Median follow-up was 10.9 months. Serum creatinine and proteinuria improved to 1.6 ± 0.8 mg/dl and 428 ± 677 mg/24 h, respectively, except in 3 patients with end-stage renal disease. In summary, this study describes the clinical features, renal biopsy findings, laboratory evaluation, treatment and prognosis of MPGN associated with autoimmune diseases.

  4. Analytical approaches to the diagnosis and treatment of aging and aging-related disease: redox status and proteomics.

    PubMed

    Calabrese, V; Dattilo, S; Petralia, A; Parenti, R; Pennisi, M; Koverech, G; Calabrese, V; Graziano, A; Monte, I; Maiolino, L; Ferreri, T; Calabrese, E J

    2015-05-01

    Basal levels of oxidants are indispensible for redox signaling to produce adaptive cellular responses such as vitagenes linked to cell survival; however, at higher levels, they are detrimental to cells, contributing to aging and to the pathogenesis of numerous age-related diseases. Aging is a complex systemic process and the major gap in aging research reminds the insufficient knowledge about pathways shifting from normal "healthy" aging to disease-associated pathological aging. The major complication of normal "healthy" aging is in fact the increasing risk of age-related diseases such as cardiovascular diseases, diabetes mellitus, and neurodegenerative pathologies that can adversely affect the quality of life in general, with enhanced incidences of comorbidities and mortality. In this context, global "omics" approaches may help to dissect and fully study the cellular and molecular mechanisms of aging and age-associated processes. The proteome, being more close to the phenotype than the transcriptome and more stable than the metabolome, represents the most promising "omics" field in aging research. In the present study, we exploit recent advances in the redox biology of aging and discuss the potential of proteomics approaches as innovative tools for monitoring at the proteome level the extent of protein oxidative insult and related modifications with the identification of targeted proteins.

  5. Genome-wide association studies in Alzheimer disease.

    PubMed

    Waring, Stephen C; Rosenberg, Roger N

    2008-03-01

    The genetics of Alzheimer disease (AD) to date support an age-dependent dichotomous model whereby earlier age of disease onset (< 60 years) is explained by 3 fully penetrant genes (APP [NCBI Entrez gene 351], PSEN1 [NCBI Entrez gene 5663], and PSEN2 [NCBI Entrez gene 5664]), whereas later age of disease onset (> or = 65 years) representing most cases of AD has yet to be explained by a purely genetic model. The APOE gene (NCBI Entrez gene 348) is the strongest genetic risk factor for later onset, although it is neither sufficient nor necessary to explain all occurrences of disease. Numerous putative genetic risk alleles and genetic variants have been reported. Although all have relevance to biological mechanisms that may be associated with AD pathogenesis, they await replication in large representative populations. Genome-wide association studies have emerged as an increasingly effective tool for identifying genetic contributions to complex diseases and represent the next frontier for furthering our understanding of the underlying etiologic, biological, and pathologic mechanisms associated with chronic complex disorders. There have already been success stories for diseases such as macular degeneration and diabetes mellitus. Whether this will hold true for a genetically complex and heterogeneous disease such as AD is not known, although early reports are encouraging. This review considers recent publications from studies that have successfully applied genome-wide association methods to investigations of AD by taking advantage of the currently available high-throughput arrays, bioinformatics, and software advances. The inherent strengths, limitations, and challenges associated with study design issues in the context of AD are presented herein.

  6. Oropharyngeal Dysphagia in Dermatomyositis: Associations with Clinical and Laboratory Features Including Autoantibodies

    PubMed Central

    Mugii, Naoki; Hasegawa, Minoru; Matsushita, Takashi; Hamaguchi, Yasuhito; Oohata, Sacihe; Okita, Hirokazu; Yahata, Tetsutarou; Someya, Fujiko; Inoue, Katsumi; Murono, Shigeyuki; Fujimoto, Manabu; Takehara, Kazuhiko

    2016-01-01

    Objective Dysphagia develops with low frequency in patients with dermatomyositis. Our objective was to determine the clinical and laboratory features that can estimate the development of dysphagia in dermatomyositis. Methods This study included 92 Japanese patients with adult-onset dermatomyositis. The associations between dysphagia and clinical and laboratory features including disease-specific autoantibodies determined by immunoprecipitation assays were analyzed. Results Videofluoroscopy swallow study (VFSS) was performed for all patients with clinical dysphagia (n = 13, 14.1%) but not for patients without clinical dysphagia. Typical findings of dysphagia (pharyngeal pooling, n = 11 and/or nasal regurgitation, n = 4) was detected by VFSS in all patients with clinical dysphagia. Eleven patients with dysphagia (84.6%) had anti-transcription intermediary factor 1γ (TIF-1γ) antibody. By univariate analysis, the average age and the male to female ratio, internal malignancy, and anti-TIF-1γ antibody were significantly higher and the frequency of interstitial lung diseases and manual muscle testing (MMT) scores of sternomastoid and dertoid muscles were significantly lower in patients with dysphagia than in patients without dysphagia. Among patients with anti-TIF-1γ antibody, the mean age, the ratios of male to female and internal malignancy were significantly higher and mean MMT scores of sternomastoid muscle were significantly lower in patients with dysphagia compared with patients without dysphagia. By multivariable analysis, the risk of dysphagia was strongly associated with the existence of internal malignancy and ant-TIF-1γ antibody and was also associated with reduced scores of manual muscle test of sternomastoid muscle. Dysphagia was markedly improved after the treatment against myositis in all 13 patients. Conclusion These findings indicate that dysphagia can develop frequently in patients with internal malignancy, anti-TIF-1γ antibody, or severe muscle

  7. Oropharyngeal Dysphagia in Dermatomyositis: Associations with Clinical and Laboratory Features Including Autoantibodies.

    PubMed

    Mugii, Naoki; Hasegawa, Minoru; Matsushita, Takashi; Hamaguchi, Yasuhito; Oohata, Sacihe; Okita, Hirokazu; Yahata, Tetsutarou; Someya, Fujiko; Inoue, Katsumi; Murono, Shigeyuki; Fujimoto, Manabu; Takehara, Kazuhiko

    2016-01-01

    Dysphagia develops with low frequency in patients with dermatomyositis. Our objective was to determine the clinical and laboratory features that can estimate the development of dysphagia in dermatomyositis. This study included 92 Japanese patients with adult-onset dermatomyositis. The associations between dysphagia and clinical and laboratory features including disease-specific autoantibodies determined by immunoprecipitation assays were analyzed. Videofluoroscopy swallow study (VFSS) was performed for all patients with clinical dysphagia (n = 13, 14.1%) but not for patients without clinical dysphagia. Typical findings of dysphagia (pharyngeal pooling, n = 11 and/or nasal regurgitation, n = 4) was detected by VFSS in all patients with clinical dysphagia. Eleven patients with dysphagia (84.6%) had anti-transcription intermediary factor 1γ (TIF-1γ) antibody. By univariate analysis, the average age and the male to female ratio, internal malignancy, and anti-TIF-1γ antibody were significantly higher and the frequency of interstitial lung diseases and manual muscle testing (MMT) scores of sternomastoid and dertoid muscles were significantly lower in patients with dysphagia than in patients without dysphagia. Among patients with anti-TIF-1γ antibody, the mean age, the ratios of male to female and internal malignancy were significantly higher and mean MMT scores of sternomastoid muscle were significantly lower in patients with dysphagia compared with patients without dysphagia. By multivariable analysis, the risk of dysphagia was strongly associated with the existence of internal malignancy and ant-TIF-1γ antibody and was also associated with reduced scores of manual muscle test of sternomastoid muscle. Dysphagia was markedly improved after the treatment against myositis in all 13 patients. These findings indicate that dysphagia can develop frequently in patients with internal malignancy, anti-TIF-1γ antibody, or severe muscle weakness of sternomastoid muscle.

  8. Primary hypertension is a disease of premature vascular aging associated with neuro-immuno-metabolic abnormalities.

    PubMed

    Litwin, Mieczysław; Feber, Janusz; Niemirska, Anna; Michałkiewicz, Jacek

    2016-02-01

    There is an increasing amount of data indicating that primary hypertension (PH) is not only a hemodynamic phenomenon but also a complex syndrome involving abnormal fat tissue distribution, over-activity of the sympathetic nervous system (SNS), metabolic abnormalities, and activation of the immune system. In children, PH usually presents with a typical phenotype of disturbed body composition, accelerated biological maturity, and subtle immunological and metabolic abnormalities. This stage of the disease is potentially reversible. However, long-lasting over-activity of the SNS and immuno-metabolic alterations usually lead to an irreversible stage of cardiovascular disease. We describe an intermediate phenotype of children with PH, showing that PH is associated with accelerated development, i.e., early premature aging of the immune, metabolic, and vascular systems. The associations and determinants of hypertensive organ damage, the principles of treatment, and the possibility of rejuvenation of the cardiovascular system are discussed.

  9. Genetic variants associated with neurodegenerative Alzheimer disease in natural models.

    PubMed

    Salazar, Claudia; Valdivia, Gonzalo; Ardiles, Álvaro O; Ewer, John; Palacios, Adrián G

    2016-02-26

    The use of transgenic models for the study of neurodegenerative diseases has made valuable contributions to the field. However, some important limitations, including protein overexpression and general systemic compensation for the missing genes, has caused researchers to seek natural models that show the main biomarkers of neurodegenerative diseases during aging. Here we review some of these models-most of them rodents, focusing especially on the genetic variations in biomarkers for Alzheimer diseases, in order to explain their relationships with variants associated with the occurrence of the disease in humans.

  10. Age at onset in Huntington's disease: replication study on the association of HAP1.

    PubMed

    Karadima, Georgia; Dimovasili, Christina; Koutsis, Georgios; Vassilopoulos, Demetris; Panas, Marios

    2012-11-01

    In recent years two association studies investigating the HAP1 T441M (rs4523977) polymorphism as a potential modifying factor of the age at onset (AAO) of Huntington's disease (HD), have been reported. Initially evidence for association was found between the M441 risk allele and the AAO. Subsequently, a second study, although failing to replicate these findings, found evidence for association between the same risk allele and AAO of motor symptoms (mAAO). In the present study, the role of the HAP1 T441M polymorphism as a modifier of the AAO in HD was investigated in a cohort of 298 Greek HD patients. In this cohort the CAG repeat number accounted for 55% of the variance in AAO. No association was found between the HAP1 T441M polymorphism and the AAO of HD. © 2012 Elsevier Ltd. All rights reserved.

  11. Disease drivers of aging

    PubMed Central

    Hodes, Richard J.; Sierra, Felipe; Austad, Steven N.; Epel, Elissa; Neigh, Gretchen N.; Erlandson, Kristine M.; Schafer, Marissa J.; LeBrasseur, Nathan K.; Wiley, Christopher; Campisi, Judith; Sehl, Mary E.; Scalia, Rosario; Eguchi, Satoru; Kasinath, Balakuntalam S.; Halter, Jeffrey B.; Cohen, Harvey Jay; Demark-Wahnefried, Wendy; Ahles, Tim A.; Barzilai, Nir; Hurria, Arti; Hunt, Peter W.

    2017-01-01

    It has long been known that aging, at both the cellular and organismal levels, contributes to the development and progression of the pathology of many chronic diseases. However, much less research has examined the inverse relationship—the contribution of chronic diseases and their treatments to the progression of aging-related phenotypes. Here, we discuss the impact of three chronic diseases (cancer, HIV/AIDS, and diabetes) and their treatments on aging, putative mechanisms by which these effects are mediated, and the open questions and future research directions required to understand the relationships between these diseases and aging. PMID:27943360

  12. Exercise counteracts declining hippocampal function in aging and Alzheimer's disease.

    PubMed

    Intlekofer, Karlie A; Cotman, Carl W

    2013-09-01

    Alzheimer's disease (AD) afflicts more than 5.4 million Americans and ranks as the most common type of dementia (Thies and Bleiler, 2011), yet effective pharmacological treatments have not been identified. Substantial evidence indicates that physical activity enhances learning and memory for people of all ages, including individuals that suffer from cognitive impairment. The mechanisms that underlie these benefits have been explored using animal models, including transgenic models of AD. Accumulating research shows that physical activity reinstates hippocampal function by enhancing the expression of brain-derived neurotrophic factor (BDNF) and other growth factors that promote neurogenesis, angiogenesis, and synaptic plasticity. In addition, several studies have found that physical activity counteracts age- and AD-associated declines in mitochondrial and immune system function. A growing body of evidence also suggests that exercise interventions hold the potential to reduce the pathological features associated with AD. Taken together, animal and human studies indicate that exercise provides a powerful stimulus that can countervail the molecular changes that underlie the progressive loss of hippocampal function in advanced age and AD. 2012 Published by Elsevier Inc

  13. Association Studies of Sporadic Parkinson’s Disease in the Genomic Era

    PubMed Central

    Labbé, Catherine; Ross, Owen A

    2014-01-01

    Parkinson’s disease is a common age-related progressive neurodegenerative disorder. Over the last 10 years, advances have been made in our understanding of the etiology of the disease with the greatest insights perhaps coming from genetic studies, including genome-wide association approaches. These large scale studies allow the identification of genomic regions harboring common variants associated to disease risk. Since the first genome-wide association study on sporadic Parkinson’s disease performed in 2005, improvements in study design, including the advent of meta-analyses, have allowed the identification of ~21 susceptibility loci. The first loci to be nominated were previously associated to familial PD (SNCA, MAPT, LRRK2) and these have been extensively replicated. For other more recently identified loci (SREBF1, SCARB2, RIT2) independent replication is still warranted. Cumulative risk estimates of associated variants suggest that more loci are still to be discovered. Additional association studies combined with deep re-sequencing of known genome-wide association study loci are necessary to identify the functional variants that drive disease risk. As each of these associated genes and variants are identified they will give insight into the biological pathways involved the etiology of Parkinson’s disease. This will ultimately lead to the identification of molecules that can be used as biomarkers for diagnosis and as targets for the development of better, personalized treatment. PMID:24653658

  14. Age-Specific Associations of Renal Impairment With Magnetic Resonance Imaging Markers of Cerebral Small Vessel Disease in Transient Ischemic Attack and Stroke

    PubMed Central

    Liu, Bian; Lau, Kui Kai; Li, Linxin; Lovelock, Caroline; Liu, Ming; Kuker, Wilhelm

    2018-01-01

    Background and Purpose— It has been hypothesized that cerebral small vessel disease (SVD) and chronic renal impairment may be part of a multisystem small-vessel disorder, but their association may simply be as a result of shared risk factors (eg, hypertension) rather than to a systemic susceptibility to premature SVD. However, most previous studies were hospital based, most had inadequate adjustment for hypertension, many were confined to patients with lacunar stroke, and none stratified by age. Methods— In a population-based study of transient ischemic attack and ischemic stroke (OXVASC [Oxford Vascular Study]), we evaluated the magnetic resonance imaging markers of cerebral SVD, including lacunes, white matter hyperintensities, cerebral microbleeds, and enlarged perivascular space. We studied the age-specific associations of renal impairment (estimated glomerular filtration rate <60 mL/min per 1.73 m2) and total SVD burden (total SVD score) adjusting for age, sex, vascular risk factors, and premorbid blood pressure (mean blood pressure during 15 years preevent). Results— Of 1080 consecutive patients, 1028 (95.2%) had complete magnetic resonance imaging protocol and creatinine measured at baseline. Renal impairment was associated with total SVD score (odds ratio [OR], 2.16; 95% confidence interval [CI], 1.69–2.75; P<0.001), but only at age <60 years (<60 years: OR, 3.97; 95% CI, 1.69–9.32; P=0.002; 60–79 years: OR, 1.01; 95% CI, 0.72–1.41; P=0.963; ≥80 years: OR, 0.95; 95% CI, 0.59–1.54; P=0.832). The overall association of renal impairment and total SVD score was also attenuated after adjustment for age, sex, history of hypertension, diabetes mellitus, and premorbid average systolic blood pressure (adjusted OR, 0.76; 95% CI, 0.56–1.02; P=0.067), but the independent association of renal impairment and total SVD score at age <60 years was maintained (adjusted OR, 3.11; 95% CI, 1.21–7.98; P=0.018). Associations of renal impairment and SVD were

  15. Age-Specific Associations of Renal Impairment With Magnetic Resonance Imaging Markers of Cerebral Small Vessel Disease in Transient Ischemic Attack and Stroke.

    PubMed

    Liu, Bian; Lau, Kui Kai; Li, Linxin; Lovelock, Caroline; Liu, Ming; Kuker, Wilhelm; Rothwell, Peter M

    2018-04-01

    It has been hypothesized that cerebral small vessel disease (SVD) and chronic renal impairment may be part of a multisystem small-vessel disorder, but their association may simply be as a result of shared risk factors (eg, hypertension) rather than to a systemic susceptibility to premature SVD. However, most previous studies were hospital based, most had inadequate adjustment for hypertension, many were confined to patients with lacunar stroke, and none stratified by age. In a population-based study of transient ischemic attack and ischemic stroke (OXVASC [Oxford Vascular Study]), we evaluated the magnetic resonance imaging markers of cerebral SVD, including lacunes, white matter hyperintensities, cerebral microbleeds, and enlarged perivascular space. We studied the age-specific associations of renal impairment (estimated glomerular filtration rate <60 mL/min per 1.73 m 2 ) and total SVD burden (total SVD score) adjusting for age, sex, vascular risk factors, and premorbid blood pressure (mean blood pressure during 15 years preevent). Of 1080 consecutive patients, 1028 (95.2%) had complete magnetic resonance imaging protocol and creatinine measured at baseline. Renal impairment was associated with total SVD score (odds ratio [OR], 2.16; 95% confidence interval [CI], 1.69-2.75; P <0.001), but only at age <60 years (<60 years: OR, 3.97; 95% CI, 1.69-9.32; P =0.002; 60-79 years: OR, 1.01; 95% CI, 0.72-1.41; P =0.963; ≥80 years: OR, 0.95; 95% CI, 0.59-1.54; P =0.832). The overall association of renal impairment and total SVD score was also attenuated after adjustment for age, sex, history of hypertension, diabetes mellitus, and premorbid average systolic blood pressure (adjusted OR, 0.76; 95% CI, 0.56-1.02; P =0.067), but the independent association of renal impairment and total SVD score at age <60 years was maintained (adjusted OR, 3.11; 95% CI, 1.21-7.98; P =0.018). Associations of renal impairment and SVD were consistent for each SVD marker at age <60 years but

  16. Preferential degradation of cognitive networks differentiates Alzheimer's disease from ageing.

    PubMed

    Chhatwal, Jasmeer P; Schultz, Aaron P; Johnson, Keith A; Hedden, Trey; Jaimes, Sehily; Benzinger, Tammie L S; Jack, Clifford; Ances, Beau M; Ringman, John M; Marcus, Daniel S; Ghetti, Bernardino; Farlow, Martin R; Danek, Adrian; Levin, Johannes; Yakushev, Igor; Laske, Christoph; Koeppe, Robert A; Galasko, Douglas R; Xiong, Chengjie; Masters, Colin L; Schofield, Peter R; Kinnunen, Kirsi M; Salloway, Stephen; Martins, Ralph N; McDade, Eric; Cairns, Nigel J; Buckles, Virginia D; Morris, John C; Bateman, Randall; Sperling, Reisa A

    2018-05-01

    Converging evidence from structural, metabolic and functional connectivity MRI suggests that neurodegenerative diseases, such as Alzheimer's disease, target specific neural networks. However, age-related network changes commonly co-occur with neuropathological cascades, limiting efforts to disentangle disease-specific alterations in network function from those associated with normal ageing. Here we elucidate the differential effects of ageing and Alzheimer's disease pathology through simultaneous analyses of two functional connectivity MRI datasets: (i) young participants harbouring highly-penetrant mutations leading to autosomal-dominant Alzheimer's disease from the Dominantly Inherited Alzheimer's Network (DIAN), an Alzheimer's disease cohort in which age-related comorbidities are minimal and likelihood of progression along an Alzheimer's disease trajectory is extremely high; and (ii) young and elderly participants from the Harvard Aging Brain Study, a cohort in which imaging biomarkers of amyloid burden and neurodegeneration can be used to disambiguate ageing alone from preclinical Alzheimer's disease. Consonant with prior reports, we observed the preferential degradation of cognitive (especially the default and dorsal attention networks) over motor and sensory networks in early autosomal-dominant Alzheimer's disease, and found that this distinctive degradation pattern was magnified in more advanced stages of disease. Importantly, a nascent form of the pattern observed across the autosomal-dominant Alzheimer's disease spectrum was also detectable in clinically normal elderly with clear biomarker evidence of Alzheimer's disease pathology (preclinical Alzheimer's disease). At the more granular level of individual connections between node pairs, we observed that connections within cognitive networks were preferentially targeted in Alzheimer's disease (with between network connections relatively spared), and that connections between positively coupled nodes

  17. Mitochondria, Cybrids, Aging, and Alzheimer’s Disease

    PubMed Central

    Swerdlow, Russell H.; Koppel, Scott; Weidling, Ian; Hayley, Clay; Ji, Yan; Wilkins, Heather M.

    2018-01-01

    Mitochondrial and bioenergetic function change with advancing age and may drive aging phenotypes. Mitochondrial and bioenergetic changes are also documented in various age-related neurodegenerative diseases, including Alzheimer’s disease (AD). In some instances AD mitochondrial and bioenergetic changes are reminiscent of those observed with advancing age, but are greater in magnitude. Mitochondrial and bioenergetic dysfunction could, therefore, link neurodegeneration to brain aging. Interestingly, mitochondrial defects in AD patients are not brain-limited, and mitochondrial function can be linked to classic AD histologic changes including amyloid precursor protein processing to beta amyloid. Also, transferring mitochondria from AD subjects to cell lines depleted of endogenous mitochondrial DNA (mtDNA) creates cytoplasmic hybrid (cybrid) cell lines that recapitulate specific biochemical, molecular, and histologic AD features. Such findings have led to the formulation of a “mitochondrial cascade hypothesis” that places mitochondrial dysfunction at the apex of the AD pathology pyramid. Data pertinent to this premise are reviewed. PMID:28253988

  18. Young Age at Diagnosis of Type 1 Diabetes Is Associated with the Development of Celiac Disease-Associated Antibodies in Children Living in Newfoundland and Labrador, Canada.

    PubMed

    Pall, Harpreet; Newhook, Leigh A; Aaron, Hillary; Curtis, Joseph; Randell, Ed

    2015-10-14

    The objectives of this study were to establish the prevalence of positive antibodies to endomysium (EMA) and tissue transglutaminase (tTG) in children with type 1 diabetes living in Newfoundland and Labrador (NL), and to examine clinical features associated with positive antibodies. Patients were recruited from the pediatric diabetes clinic. One hundred sixty-seven children with type 1 diabetes from the 280 children followed at the clinic were prospectively screened for celiac disease using EMA and tTG. The variables of Irish descent, age at onset of diabetes, duration of diabetes, sex, family history of celiac disease, hemoglobin A1C (A1C), ferritin, gastrointestinal symptoms, and body mass index were compiled for all patients. The group of patients with positive antibodies to EMA and/or tTG was compared to the group with negative antibodies. The prevalence of patients with positive antibodies to EMA and/or tTG was 16.8% (n = 28). One patient had also been previously diagnosed with symptomatic celiac disease. The two statistically significant variables with positive antibodies were an earlier age at onset of diabetes (Mann-Whitney U two-tailed test: mean difference 3.2 years, 95% CI 1.7-4.8 years, p < 0.0001) and longer duration of diabetes (Mann-Whitney U two-tailed test: mean difference 2.9 years, 95% CI 1.3-4.4 years, p < 0.0001). Irish descent was associated with positive antibodies but did not reach statistical significance. On logistic regression analysis performed with these three variables together, only age at onset of diabetes remained significant. There is a high prevalence of celiac disease-associated antibodies in children living in NL with type 1 diabetes. Unlike other clinical features, an earlier age at onset of diabetes was predictive for positive antibodies. As the majority of children with positive antibodies did not have signs or symptoms of celiac disease, routine screening for celiac disease in type 1 diabetes is recommended.

  19. Older Age and Steroid Use Are Associated with Increasing Polypharmacy and Potential Medication Interactions Among Patients with Inflammatory Bowel Disease

    PubMed Central

    Parian, Alyssa

    2015-01-01

    Background: Comorbidity and polypharmacy, more prevalent among older persons, may impact the treatment of patients with inflammatory bowel disease (IBD). The aims of this study were to assess the frequency of polypharmacy and medication interactions within a cohort of older patients with IBD and describe IBD treatment patterns. Methods: Cohort study of 190 patients with IBD 65 years or older followed at a tertiary IBD referral center from 2006 to 2012. Data collected included demographics, IBD-specific characteristics including disease activity, and comorbidity. Medication histories were extracted from medical records, and data were used to classify polypharmacy, frequency, and severity of potential medication interactions and inappropriate medication use. Results: Older patients with IBD were prescribed an average of 9 routine medications. Severe polypharmacy (≥10 routine medications) was present in 43.2% of studied patients and associated with increasing age, greater comorbidity, and steroid use. Overall, 73.7% of patients had at least 1 potential medication interaction, including 40% of patients with potential IBD medication-associated interactions. Chronic steroids were prescribed to 40% of the older patients including 24% who were in remission or with mild disease activity. Only 39.5% of patients were on immunomodulators and 21.1% on biologics. Approximately, 35% of patients were given at least 1 Beers inappropriate medication and almost 10% were receiving chronic narcotics. Conclusions: Older patients with IBD are at increased risk for severe polypharmacy and potential major medication interactions especially with increasing comorbidity and chronic steroid use. Steroid-maintenance therapies are prevalent among the older patients with IBD with lower utilization of steroid-sparing regimens. PMID:25856768

  20. Mechanisms and consequences of oxidative stress in lung disease: therapeutic implications for an aging populace.

    PubMed

    Hecker, Louise

    2018-04-01

    The rapid expansion of the elderly population has led to the recent epidemic of age-related diseases, including increased incidence and mortality of chronic and acute lung diseases. Numerous studies have implicated aging and oxidative stress in the pathogenesis of various pulmonary diseases; however, despite recent advances in these fields, the specific contributions of aging and oxidative stress remain elusive. This review will discuss the consequences of aging on lung morphology and physiology, and how redox imbalance with aging contributes to lung disease susceptibility. Here, we focus on three lung diseases for which aging is a significant risk factor: acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). Preclinical and clinical development for redox- and senescence-altering therapeutic strategies are discussed, as well as scientific advancements that may direct current and future therapeutic development. A deeper understanding of how aging impacts normal lung function, redox balance, and injury-repair processes will inspire the development of new therapies to prevent and/or reverse age-associated pulmonary diseases, and ultimately increase health span and longevity. This review is intended to encourage basic, clinical, and translational research that will bridge knowledge gaps at the intersection of aging, oxidative stress, and lung disease to fuel the development of more effective therapeutic strategies for lung diseases that disproportionately afflict the elderly.

  1. Vulnerable Populations and the Association between Periodontal and Chronic Kidney Disease

    PubMed Central

    Plantinga, Laura C.; Crews, Deidra C.; Bibbins-Domingo, Kirsten; Saran, Rajiv; Heung, Michael; Patel, Priti R.; Burrows, Nilka Ríos; Ernst, Kristina L.; Powe, Neil R.

    2011-01-01

    Summary Background and objectives Recent studies suggest an overall association between chronic kidney disease (CKD) and periodontal disease, but it is unknown whether this association is similar across various subpopulations. Design, setting, participants, & measurements This study was a cross-sectional analysis of 2001 to 2004 National Health and Nutrition Examination Survey data. CKD was defined as a urinary albumin-to-creatinine ratio ≥30 mg/g or estimated GFR of 15 to 59 ml/min per 1.73 m2. Adjusted odds ratios were calculated using multivariable logistic regression with U.S. population-based weighting. Results These analyses included 6199 dentate adult participants (aged 21 to 75 years) with periodontal exams. The estimated prevalences of moderate/severe periodontal disease and CKD were 5.3% and 10.6%, respectively. Periodontal disease was associated with >2-fold higher risk of CKD that was moderately attenuated after adjustment for age, gender, race/ethnicity, tobacco use, hypertension, diabetes, educational attainment, poverty index ratio, and dental care use. There were no statistically significant interactions between periodontal disease and race/ethnicity, educational attainment, or poverty status. Less-than-recommended dental care use was associated with periodontal disease and CKD and was increasingly prevalent among nonwhites, lower educational attainment, and lower poverty status. Conclusions The association between periodontal disease and CKD is not significantly different among subgroups. However, because nonwhites, those with a lower educational level, and the poor less frequently report use of recommended dental care, the association between periodontal disease and kidney function over time may become stronger among these groups and warrants further investigation. PMID:21350109

  2. The Protective Effect of Lipoic Acid on Selected Cardiovascular Diseases Caused by Age-Related Oxidative Stress

    PubMed Central

    Goraca, Anna

    2015-01-01

    Oxidative stress is considered to be the primary cause of many cardiovascular diseases, including endothelial dysfunction in atherosclerosis and ischemic heart disease, hypertension, and heart failure. Oxidative stress increases during the aging process, resulting in either increased reactive oxygen species (ROS) production or decreased antioxidant defense. The increase in the incidence of cardiovascular disease is directly related to age. Aging is also associated with oxidative stress, which in turn leads to accelerated cellular senescence and organ dysfunction. Antioxidants may help lower the incidence of some pathologies of cardiovascular diseases and have antiaging properties. Lipoic acid (LA) is a natural antioxidant which is believed to have a beneficial effect on oxidative stress parameters in relation to diseases of the cardiovascular system. PMID:25949771

  3. The National Institute on Aging and the Alzheimer's Association Research Framework for Alzheimer's disease: Perspectives from the Research Roundtable.

    PubMed

    Knopman, David S; Haeberlein, Samantha Budd; Carrillo, Maria C; Hendrix, James A; Kerchner, Geoff; Margolin, Richard; Maruff, Paul; Miller, David S; Tong, Gary; Tome, Maria B; Murray, Melissa E; Nelson, Peter T; Sano, Mary; Mattsson, Niklas; Sultzer, David L; Montine, Thomas J; Jack, Clifford R; Kolb, Hartmuth; Petersen, Ronald C; Vemuri, Prashanthi; Canniere, Megan Zoschg; Schneider, Julie A; Resnick, Susan M; Romano, Gary; van Harten, Argonde Corien; Wolk, David A; Bain, Lisa J; Siemers, Eric

    2018-04-01

    The Alzheimer's Association's Research Roundtable met in November 2017 to explore the new National Institute on Aging and the Alzheimer's Association Research Framework for Alzheimer's disease. The meeting allowed experts in the field from academia, industry, and government to provide perspectives on the new National Institute on Aging and the Alzheimer's Association Research Framework. This review will summarize the "A, T, N System" (Amyloid, Tau, and Neurodegeneration) using biomarkers and how this may be applied to clinical research and drug development. In addition, challenges and barriers to the potential adoption of this new framework will be discussed. Finally, future directions for research will be proposed. Copyright © 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  4. Outbreaks associated to large open air festivals, including music festivals, 1980 to 2012.

    PubMed

    Botelho-Nevers, E; Gautret, P

    2013-03-14

    In the minds of many, large scale open air festivals have become associated with spring and summer, attracting many people, and in the case of music festivals, thousands of music fans. These festivals share the usual health risks associated with large mass gatherings, including transmission of communicable diseases and risk of outbreaks. Large scale open air festivals have however specific characteristics, including outdoor settings, on-site housing and food supply and the generally young age of the participants. Outbreaks at large scale open air festivals have been caused by Cryptosporium parvum, Campylobacter spp., Escherichia coli, Salmonella enterica, Shigella sonnei, Staphylococcus aureus, hepatitis A virus, influenza virus, measles virus, mumps virus and norovirus. Faecal-oral and respiratory transmissions of pathogens result from non-compliance with hygiene rules, inadequate sanitation and insufficient vaccination coverage. Sexual transmission of infectious diseases may also occur and is likely to be underestimated and underreported. Enhanced surveillance during and after festivals is essential. Preventive measures such as immunisations of participants and advice on-site and via social networks should be considered to reduce outbreaks at these large scale open air festivals.

  5. Breast-feeding does not protect against allergic sensitization in early childhood and allergy-associated disease at age 7 years.

    PubMed

    Jelding-Dannemand, Ea; Malby Schoos, Ann-Marie; Bisgaard, Hans

    2015-11-01

    Extended breast-feeding is recommended for newborn children at risk of allergy-associated diseases, but the evidence of a protective effect on sensitization and these diseases remains elusive. The aim of this study was to investigate the effects of the duration of exclusive breast-feeding on the development of sensitization in preschool children. Information on breast-feeding was gathered by interviews involving 335 children aged 1, 6, and 12 months from the Copenhagen Prospective Study on Asthma in Childhood2000 birth cohort born to mothers with a history of asthma. Skin prick test responses and specific IgE levels against 12 common inhalant and 10 food allergens were assessed longitudinally at ages ½ year, 1½ years, 4 years, and 6 years. Eczema, wheeze/asthma, and allergic rhinitis were diagnosed at the Copenhagen Prospective Studies on Asthma in Childhood clinic at 7 years of age, strictly adhering to predefined algorithms. Associations between duration of exclusive breast-feeding and outcomes were analyzed by logistic regression. We found no significant association between duration of exclusive breast-feeding and development of sensitization in the first 6 years of life (odds ratio [OR]: ½ year, 1.10 [95% CI, 0.90-1.36]; 1½ years, 1.15 [95% CI, 0.97-1.36]; 4 years, 1.08 [95% CI, 0.93-1.25]; and 6 years, 0.96 [95% CI, 0.84-1.10]) or with current eczema, wheeze/asthma, and allergic rhinitis at age 7 years (OR, 1.07 [95% CI, 0.92-1.24]; OR, 0.97 [95% CI, 0.82-1.14]; and OR, 1.02 [95% CI, 0.84-1.23], respectively). Adjusting for reverse causation by excluding children with eczema, wheeze, or a positive skin prick test response before ending exclusive breast-feeding did not alter the results. Exclusive breast-feeding does not affect sensitization in early childhood or associated diseases at 7 years of age in at-risk children. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  6. Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1·25 million people.

    PubMed

    Rapsomaniki, Eleni; Timmis, Adam; George, Julie; Pujades-Rodriguez, Mar; Shah, Anoop D; Denaxas, Spiros; White, Ian R; Caulfield, Mark J; Deanfield, John E; Smeeth, Liam; Williams, Bryan; Hingorani, Aroon; Hemingway, Harry

    2014-05-31

    The associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared. In this study, we aimed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease. We used linked electronic health records from 1997 to 2010 in the CALIBER (CArdiovascular research using LInked Bespoke studies and Electronic health Records) programme to assemble a cohort of 1·25 million patients, 30 years of age or older and initially free from cardiovascular disease, a fifth of whom received blood pressure-lowering treatments. We studied the heterogeneity in the age-specific associations of clinically measured blood pressure with 12 acute and chronic cardiovascular diseases, and estimated the lifetime risks (up to 95 years of age) and cardiovascular disease-free life-years lost adjusted for other risk factors at index ages 30, 60, and 80 years. This study is registered at ClinicalTrials.gov, number NCT01164371. During 5·2 years median follow-up, we recorded 83,098 initial cardiovascular disease presentations. In each age group, the lowest risk for cardiovascular disease was in people with systolic blood pressure of 90-114 mm Hg and diastolic blood pressure of 60-74 mm Hg, with no evidence of a J-shaped increased risk at lower blood pressures. The effect of high blood pressure varied by cardiovascular disease endpoint, from strongly positive to no effect. Associations with high systolic blood pressure were strongest for intracerebral haemorrhage (hazard ratio 1·44 [95% CI 1·32-1·58]), subarachnoid haemorrhage (1·43 [1·25-1·63]), and stable angina (1·41 [1·36-1·46]), and weakest for abdominal aortic aneurysm (1·08 [1·00-1·17]). Compared with diastolic blood pressure, raised systolic blood pressure had a greater effect on angina, myocardial infarction, and peripheral arterial disease, whereas raised diastolic blood pressure had a greater effect on

  7. Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1·25 million people

    PubMed Central

    Rapsomaniki, Eleni; Timmis, Adam; George, Julie; Pujades-Rodriguez, Mar; Shah, Anoop D; Denaxas, Spiros; White, Ian R; Caulfield, Mark J; Deanfield, John E; Smeeth, Liam; Williams, Bryan; Hingorani, Aroon; Hemingway, Harry

    2014-01-01

    Summary Background The associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared. In this study, we aimed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease. Methods We used linked electronic health records from 1997 to 2010 in the CALIBER (CArdiovascular research using LInked Bespoke studies and Electronic health Records) programme to assemble a cohort of 1·25 million patients, 30 years of age or older and initially free from cardiovascular disease, a fifth of whom received blood pressure-lowering treatments. We studied the heterogeneity in the age-specific associations of clinically measured blood pressure with 12 acute and chronic cardiovascular diseases, and estimated the lifetime risks (up to 95 years of age) and cardiovascular disease-free life-years lost adjusted for other risk factors at index ages 30, 60, and 80 years. This study is registered at ClinicalTrials.gov, number NCT01164371. Findings During 5·2 years median follow-up, we recorded 83 098 initial cardiovascular disease presentations. In each age group, the lowest risk for cardiovascular disease was in people with systolic blood pressure of 90–114 mm Hg and diastolic blood pressure of 60–74 mm Hg, with no evidence of a J-shaped increased risk at lower blood pressures. The effect of high blood pressure varied by cardiovascular disease endpoint, from strongly positive to no effect. Associations with high systolic blood pressure were strongest for intracerebral haemorrhage (hazard ratio 1·44 [95% CI 1·32–1·58]), subarachnoid haemorrhage (1·43 [1·25–1·63]), and stable angina (1·41 [1·36–1·46]), and weakest for abdominal aortic aneurysm (1·08 [1·00–1·17]). Compared with diastolic blood pressure, raised systolic blood pressure had a greater effect on angina, myocardial infarction, and peripheral arterial disease, whereas raised

  8. Common diseases as determinants of menopausal age.

    PubMed

    Li, Jingmei; Eriksson, Mikael; Czene, Kamila; Hall, Per; Rodriguez-Wallberg, Kenny A

    2016-12-01

    Can the diagnosis of common diseases before menopause influence age at natural menopause (ANM) onset? Polycystic ovary syndrome (PCOS) and depression were observed to delay menopause. It has been observed that women who undergo early menopause experience a higher burden of health problems related to metabolic syndromes, heart disease and depression, but whether ANM can be influenced by common adult diseases has not been studied extensively. All women attending mammography screening or clinical mammography at four hospitals in Sweden were invited to participate in the Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA) study. Between January 2011 and March 2013, 70 877 women were recruited. Information from the baseline questionnaire filled out upon enrollment was used in this cross-sectional analysis on predictors of ANM onset. We limited our analyses to 61 936 women with complete data on ANM and covariates and a follow-up time (from birth to menopause or censoring) of at least 35 years. Premenopausal diagnoses of depression, anorexia, bulimia, PCOS, ovarian cyst, heart failure, myocardial infarction, angina pectoris, stroke, preeclampsia, diabetes, hypertension and hyperlipidemia were examined as time-dependent variables in multivariable Cox regression analyses, adjusting for reproductive factors (age at menarche, menstrual cycle regularity in adult life, number of children and premenopausal oral contraceptive use) and risk factors of common diseases (education, physical activity at 18 years and information at the time of questionnaire including BMI, ever smoking and alcohol consumption). Women with PCOS and depression were independently associated with later menopause (hazard ratio (95% CI): 0.44 (0.28-0.71) and 0.95 (0.91-1.00), respectively), compared to women with no such histories. The associations remained significant in a subset of women who had never received gynecological surgery or hormone treatment (n = 32313, 0.21 (0

  9. Association between periodontal disease and non-communicable diseases

    PubMed Central

    Lee, Jae-Hong; Oh, Jin-Young; Youk, Tae-Mi; Jeong, Seong-Nyum; Kim, Young-Taek; Choi, Seong-Ho

    2017-01-01

    Abstract The National Health Insurance Service–Health Examinee Cohort during 2002 to 2013 was used to investigate the associations between periodontal disease (PD) and the following non-communicable diseases (NCDs): hypertension, diabetes mellitus, osteoporosis, cerebral infarction, angina pectoris, myocardial infarction, and obesity. Univariate and multivariate logistic regression analyses adjusting for potential confounders during the follow-up period—including age, sex, household income, insurance status, residence area, health status, and comorbidities—were used to estimated odds ratios (ORs) with 95% confidence intervals (CIs) in order to assess the associations between PD and NCDs. We enrolled 200,026 patients with PD and 154,824 subjects with a healthy oral status. Statistically, significant associations were found between PD and the investigated NCDs except for cerebral and myocardial infarction after adjusting for sociodemographic and comorbidity factors (P < .05). In particular, obesity (OR = 1.30, 95% CI = 1.04–1.63, P = .022), osteoporosis (OR = 1.22, 95% CI = 1.18–1.27, P < .001), and angina pectoris (OR = 1.22, 95% CI = 1.17–1.27, P < .001) were significantly and positively associated with PD. This longitudinal cohort study has provided evidence that patients with PD are at increased risk of NCDs. Further studies are required to confirm the reliability of this association and elucidate the role of the inflammatory pathway in periodontitis pathogenesis as a triggering and mediating mechanism. PMID:28658175

  10. Cardiorespiratory Fitness is Associated with Reduced Risk of Respiratory Diseases in Middle-Aged Caucasian Men: A Long-Term Prospective Cohort Study.

    PubMed

    Kunutsor, Setor K; Laukkanen, Tanjaniina; Laukkanen, Jari A

    2017-10-01

    Cardiorespiratory fitness (CRF), an index of cardiac and respiratory functioning, is strongly associated with a reduced risk of adverse health outcomes. We aimed to assess the prospective association of CRF with the risk of respiratory diseases (defined as chronic obstructive pulmonary disease, pneumonia, or asthma). Cardiorespiratory fitness, as measured by maximal oxygen uptake, was assessed in 1974 middle-aged men. During a median follow-up of 25.7 years, 382 hospital diagnosed respiratory diseases were recorded. Cardiorespiratory fitness was linearly associated with risk of respiratory diseases. In analysis adjusted for several established and potential risk factors, the hazard ratio (HR) (95% CI) for respiratory diseases was 0.63 (0.45-0.88), when comparing extreme quartiles of CRF levels. The corresponding multivariate adjusted HR (95% CI) for pneumonia was 0.67 (0.48-0.95). Our findings indicate a graded inverse and independent association between CRF and the future risk of respiratory diseases in a general male Caucasian population.

  11. Disease-related microglia heterogeneity in the hippocampus of Alzheimer's disease, dementia with Lewy bodies, and hippocampal sclerosis of aging.

    PubMed

    Bachstetter, Adam D; Van Eldik, Linda J; Schmitt, Frederick A; Neltner, Janna H; Ighodaro, Eseosa T; Webster, Scott J; Patel, Ela; Abner, Erin L; Kryscio, Richard J; Nelson, Peter T

    2015-05-23

    Neuropathological, genetic, and biochemical studies have provided support for the hypothesis that microglia participate in Alzheimer's disease (AD) pathogenesis. Despite the extensive characterization of AD microglia, there are still many unanswered questions, and little is known about microglial morphology in other common forms of age-related dementia: particularly, dementia with Lewy bodies (DLB) and hippocampal sclerosis of aging (HS-Aging). In addition, no prior studies have attempted to compare and contrast the microglia morphology in the hippocampus of various neurodegenerative conditions. Here we studied cases with pathologically-confirmed AD (n = 7), HS-Aging (n = 7), AD + HS-aging (n = 4), DLB (n = 12), and normal (cognitively intact) controls (NC) (n = 9) from the University of Kentucky Alzheimer's Disease Center autopsy cohort. We defined five microglia morphological phenotypes in the autopsy samples: ramified, hypertrophic, dystrophic, rod-shaped, and amoeboid. The Aperio ScanScope digital neuropathological tool was used along with two well-known microglial markers: IBA1 (a marker for both resting and activated microglia) and CD68 (a lysosomal marker in macrophages/microglia associated with phagocytic cells). Hippocampal staining analyses included studies of subregions within the hippocampal formation and nearby white matter. Using these tools and methods, we describe variation in microglial characteristics that show some degree of disease specificity, including, (1) increased microglia density and number in HS-aging and AD + HS-aging; (2) low microglia density in DLB; (3) increased number of dystrophic microglia in HS-aging; and (4) increased proportion of dystrophic to all microglia in DLB. We conclude that variations in morphologies among microglial cells, and cells of macrophage lineage, can help guide future work connecting neuroinflammatory mechanisms with specific neurodegenerative disease subtypes.

  12. Age-related and disease-related muscle loss: the effect of diabetes, obesity, and other diseases

    PubMed Central

    Kalyani, Rita Rastogi; Corriere, Mark; Ferrucci, Luigi

    2014-01-01

    The term sarcopenia refers to the loss of muscle mass that occurs with ageing. On the basis of study results showing that muscle mass is only moderately related to functional outcomes, international working groups have proposed that loss of muscle strength or physical function should also be included in the definition. Irrespective of how sarcopenia is defined, both low muscle mass and poor muscle strength are clearly highly prevalent and important risk factors for disability and potentially mortality in individuals as they age. Many chronic diseases, in addition to ageing, could also accelerate decrease of muscle mass and strength, and this effect could be a main underlying mechanism by which chronic diseases cause physical disability. In this Review, we address both age-related and disease-related muscle loss, with a focus on diabetes and obesity but including other disease states, and potential common mechanisms and treatments. Development of treatments for age-related and disease-related muscle loss might improve active life expectancy in older people, and lead to substantial health-care savings and improved quality of life. PMID:24731660

  13. [Sense of smell, physiological ageing and neurodegenerative diseases: II. Ageing and neurodegenerative diseases].

    PubMed

    Fusari, A; Molina, J A

    The sense of smell, which was once studied because of its biological and evolutionary significance, is today one of the centres of interest in research on normal and pathological ageing. The latest scientific developments point to an inversely proportional relationship between age and olfactory sensitivity. In certain neurodegenerative diseases this sensory decline is one of the first symptoms of the disorder and is correlated with the progression of the disease. In this work we are going to review the scientific knowledge on loss of sense of smell in ageing and in neurodegenerative diseases, with special attention given to Alzheimer's and Parkinson's diseases. A survey of studies that have examined the olfactory deficits in ageing and in some neurodegenerative diseases offers conclusive results about the presence of these impairments in the early stages of these disorders and even among healthy elderly persons. Although a number of causes contribute to these sensory losses in physiological ageing, a common neurological foundation has been proposed for Alzheimer's and Parkinson's diseases. Nevertheless, despite certain initial similarities, the olfactory deficits shown in these disorders seem to be qualitatively different.

  14. Inflammation and premature aging in advanced chronic kidney disease.

    PubMed

    Kooman, Jeroen P; Dekker, Marijke J; Usvyat, Len A; Kotanko, Peter; van der Sande, Frank M; Schalkwijk, Casper G; Shiels, Paul G; Stenvinkel, Peter

    2017-10-01

    Systemic inflammation in end-stage renal disease is an established risk factor for mortality and a catalyst for other complications, which are related to a premature aging phenotype, including muscle wasting, vascular calcification, and other forms of premature vascular disease, depression, osteoporosis, and frailty. Uremic inflammation is also mechanistically related to mechanisms involved in the aging process, such as telomere shortening, mitochondrial dysfunction, and altered nutrient sensing, which can have a direct effect on cellular and tissue function. In addition to uremia-specific causes, such as abnormalities in the phosphate-Klotho axis, there are remarkable similarities between the pathophysiology of uremic inflammation and so-called "inflammaging" in the general population. Potentially relevant, but still somewhat unexplored in this respect, are abnormal or misplaced protein structures, as well as abnormalities in tissue homeostasis, which evoke danger signals through damage-associated molecular patterns, as well as the senescence-associated secretory phenotype. Systemic inflammation, in combination with the loss of kidney function, can impair the resilience of the body to external and internal stressors by reduced functional and structural tissue reserves, and by impairing normal organ crosstalk, thus providing an explanation for the greatly increased risk of homeostatic breakdown in this population. In this review, the relationship between uremic inflammation and a premature aging phenotype, as well as potential causes and consequences, are discussed. Copyright © 2017 the American Physiological Society.

  15. Kidney disease and aging: A reciprocal relation.

    PubMed

    Kooman, Jeroen P; van der Sande, Frank M; Leunissen, Karel M L

    2017-01-01

    Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are overrepresented in elderly patients. This provides specific challenges for the treatment, as the start of dialysis in vulnerable elderly patients may be associated with a rapid decline in functional performance. However, prognosis in elderly patients with ESRD is quite variable and related to the presence of comorbidity and geriatric impairments. The decision to start dialysis in elderly patients should always be based on shared decision making, which may be aided by the use of prediction models which should however not be used to withhold dialysis treatment. The treatment of ESRD in elderly patients should be based on a multidimensional treatment plan with a role for active rehabilitation. Moreover, there also appears to be a reciprocal relationship between aging and CKD, as the presence of geriatric complications is also high in younger patients with ESRD. This has led to the hypothesis of a premature aging process associated with CKD, resulting in different phenotypes such as premature vascular aging, muscle wasting, bone disease, cognitive dysfunction and frailty. Prevention and treatment of this phenotype is based on optimal treatment of CKD, associated comorbidities, and lifestyle factors by established treatments. For the future, interventions, which are developed to combat the aging process in general, might also have relevance for the treatment of patients with CKD, but their role should always be investigated in adequately powered clinical trials, as results obtained in experimental trials may not be directly translatable to the clinical situation of elderly patients. In the meantime, physical exercise is a very important intervention, by improving both physical capacity and functional performance, as well as by a direct effect on the aging process. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Environmental stress, ageing and glial cell senescence: a novel mechanistic link to Parkinson's disease?

    PubMed

    Chinta, S J; Lieu, C A; Demaria, M; Laberge, R-M; Campisi, J; Andersen, J K

    2013-05-01

    Exposure to environmental toxins is associated with a variety of age-related diseases including cancer and neurodegeneration. For example, in Parkinson's disease (PD), chronic environmental exposure to certain toxins has been linked to the age-related development of neuropathology. Neuronal damage is believed to involve the induction of neuroinflammatory events as a consequence of glial cell activation. Cellular senescence is a potent anti-cancer mechanism that occurs in a number of proliferative cell types and causes the arrest of proliferation of cells at risk of malignant transformation following exposure to potentially oncogenic stimuli. With age, senescent cells accumulate and express a senescence-associated secretory phenotype (SASP; that is the robust secretion of many inflammatory cytokines, growth factors and proteases). Whereas cell senescence in peripheral tissues has been causally linked to a number of age-related pathologies, little is known about the induction of cellular senescence and the SASP in the brain. On the basis of recently reported findings, we propose that environmental stressors associated with PD may act in part by eliciting senescence and the SASP within non neuronal glial cells in the ageing brain, thus contributing to the characteristic decline in neuronal integrity that occurs in this disorder. © 2013 The Association for the Publication of the Journal of Internal Medicine.

  17. High Aerobic Capacity Mitigates Changes in the Plasma Metabolomic Profile Associated with Aging.

    PubMed

    Falegan, Oluyemi S; Vogel, Hans J; Hittel, Dustin S; Koch, Lauren G; Britton, Steven L; Hepple, Russ T; Shearer, Jane

    2017-02-03

    Advancing age is associated with declines in maximal oxygen consumption. Declines in aerobic capacity not only contribute to the aging process but also are an independent risk factor for morbidity, cardiovascular disease, and all-cause mortality. Although statistically convincing, the relationships between aerobic capacity, aging, and disease risk remain largely unresolved. To this end, we employed sensitive, system-based metabolomics approach to determine whether enhanced aerobic capacity could mitigate some of the changes seen in the plasma metabolomic profile associated with aging. Metabolomic profiles of plasma samples obtained from young (13 month) and old (26 month) rats bred for low (LCR) or high (HCR) running capacity using proton nuclear magnetic resonance spectroscopy ( 1 H NMR) were examined. Results demonstrated strong profile separation in old and low aerobic capacity rats, whereas young and high aerobic capacity rat models were less predictive. Significantly differential metabolites between the groups include taurine, acetone, valine, and trimethylamine-N-oxide among other metabolites, specifically citrate, succinate, isovalerate, and proline, were differentially increased in older HCR animals compared with their younger counterparts. When interactions between age and aerobic capacity were examined, results demonstrated that enhanced aerobic capacity could mitigate some but not all age-associated alterations in the metabolomic profile.

  18. Central systolic blood pressure is associated with ethnicity and cardiovascular disease risk factors in Chinese middle-aged population.

    PubMed

    Wang, Zengwu; Hao, Guang; Zhang, Linfeng; Chen, Zuo; Wang, Xin; Guo, Min; Tian, Ye; Shao, Lan; Zhu, Manlu

    2016-02-01

    Central systolic blood pressure (CSBP) is a useful prognostic aid in the reduction and prevention of cardiovascular diseases. However, data regarding the distribution of CSBP in China are not available. The study aimed at assessing the distribution of CSBP and examining its relationship with potential cardiovascular risk factors in the Chinese middle-aged population. A cross-sectional study. A cross-sectional survey on cardiovascular risk factors across China was conducted in 2009-2010. CSBP levels were estimated using the non-invasive BPro device with A-Pulse central aortic systolic pressure software. The study population included 9113 individuals (mean age 49.84 years; 53.37% women). The CSBP levels (mean (standard deviation)) were 119.46 (17.51) mmHg in men and 119.81 (19.29) mmHg in women. CSBP levels were higher in rural than urban and lower in the southern than the northern populations (both P < 0.05). The Han ethnic group had higher CSBP levels than the Tibetans (P < 0.05) but similar to those in the Mongolian, Uyghur, Kazak and Akha groups. Irrespective of gender, the mean CSBP level was higher in individuals with diabetes and hypertension than in those without these disorders (P < 0.05). CSBP was positively associated with cardiovascular risk factors such as age, female gender, body mass index, systolic and diastolic blood pressure, and negatively associated with heart rate. CSBP estimated using the BPro device correlates with various cardiovascular risk factors. Our results may help establish future reference values in the Chinese middle-aged population. © The European Society of Cardiology 2015.

  19. APOE associated hemispheric asymmetry of entorhinal cortical thickness in aging and Alzheimer’s disease

    PubMed Central

    Donix, Markus; Burggren, Alison C.; Scharf, Maria; Marschner, Kira; Suthana, Nanthia A.; Siddarth, Prabha; Krupa, Allison K.; Jones, Michael; Martin-Harris, Laurel; Ercoli, Linda M.; Miller, Karen J.; Werner, Annett; von Kummer, Rüdiger; Sauer, Cathrin; Small, Gary W.; Holthoff, Vjera A.; Bookheimer, Susan Y.

    2013-01-01

    Across species structural and functional hemispheric asymmetry is a fundamental feature of the brain. Environmental and genetic factors determine this asymmetry during brain development and modulate its interaction with brain disorders. The e4 allele of the apolipoprotein E gene (APOE-4) is a risk factor for Alzheimer’s disease, associated with regionally specific effects on brain morphology and function during the life span. Furthermore, entorhinal and hippocampal hemispheric asymmetry could be modified by pathology during Alzheimer’s disease development. Using high-resolution magnetic resonance imaging and a cortical unfolding technique we investigated whether carrying the APOE-4 allele influences hemispheric asymmetry in the entorhinal cortex and the hippocampus among patients with Alzheimer’s disease as well as in middle-aged and older cognitively healthy individuals. APOE-4 carriers showed a thinner entorhinal cortex in the left hemisphere when compared with the right hemisphere across all participants. Non-carriers of the allele showed this asymmetry only in the patient group. Cortical thickness in the hippocampus did not vary between hemispheres among APOE-4 allele carriers and non-carriers. The APOE-4 allele modulates hemispheric asymmetry in entorhinal cortical thickness. Among Alzheimer’s disease patients, this asymmetry might be less dependent on the APOE genotype and a more general marker of incipient disease pathology. PMID:24080518

  20. The association between etanercept serum concentration and psoriasis severity is highly age-dependent.

    PubMed

    Detrez, Iris; Van Steen, Kristel; Segaert, Siegfried; Gils, Ann

    2017-06-01

    The association between etanercept serum concentration and psoriasis disease severity is poorly investigated, and currently etanercept serum concentration monitoring that is aiming to optimize the psoriasis treatment lacks evidence. In this prospective study, we investigated the relation between etanercept exposure and disease severity via measuring etanercept concentrations at five consecutive time points in 56 psoriasis patients. Disease severity assessments included the Psoriasis Area and Severity Index (PASI), body surface area (BSA) and Physician Global Assessment (PGA), and etanercept and anti-etanercept antibody concentrations were determined every 3 months for a period of 1 year. The present study demonstrated that the association between etanercept concentration and psoriasis severity is age-dependent: when patients were stratified into three groups, patients in the youngest age group (-50 years) showed a lower PASI at a higher etanercept concentration (β = -0.26), whereas patients in the oldest age group (+59 years) showed the opposite trend (β =0.22). Similar age effects were observed in the relation of etanercept concentration with BSA ( P =0.02) and PGA ( P =0.02). The influence of age and length of time in therapy on the etanercept concentration-disease severity relation was unaffected by body mass index (BMI) or any other possible confounder. Incidence of anti-etanercept antibodies was low (2%). The age-dependent relation between etanercept serum concentrations is both unexpected and intriguing and needs further investigation. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  1. Advanced patient age at diagnosis of diffuse large B-cell lymphoma is associated with molecular characteristics including ABC-subtype and high expression of MYC.

    PubMed

    Paul, Ulrike; Richter, Julia; Stuhlmann-Laiesz, Christiane; Kreuz, Markus; Nagel, Inga; Horn, Heike; Staiger, Annette M; Aukema, Sietse M; Hummel, Michael; Ott, German; Spang, Rainer; Rosenwald, Andreas; Feller, Alfred C; Cogliatti, Sergio; Stein, Harald; Hansmann, Martin-Leo; Moller, Peter; Szczepanowski, Monika; Burkhardt, Birgit; Pfreundschuh, Michael; Schmitz, Norbert; Loeffler, Markus; Trümper, Lorenz; Siebert, Reiner; Klapper, Wolfram

    2018-05-01

    The incidence of diffuse large B-cell lymphoma (DLBCL) increases with age being patient age at diagnosis an adverse prognostic factor. However, elderly patients are often underrepresented in common studies. To investigate the effect between age and biological characteristics in DLBCL, we analyzed data of 1534 patients encompassing all adult age groups, enriched for the age ≥75 years. Follicular lymphoma (FL) grade 3B with histopathological characteristics of DLBCLs were included. Gender, centroblastic cytology, FL grade 3B morphology, CD10 expression, and ABC/non-GCB-subtype were significantly associated with age after correction for multiple testing and after adjusting for cohorts. Analysis of a subgroup points towards an association of MYC expression with age. Our data indicate that biological features of DLBCL and FL grade 3B are associated with increasing age among adult patients. The prevalence of the ABC/non-GCB-subtype in elderly patients suggests that therapies targeting this molecular subtype should be specifically explored in this subgroup.

  2. Increased brain-predicted aging in treated HIV disease

    PubMed Central

    Underwood, Jonathan; Caan, Matthan W.A.; De Francesco, Davide; van Zoest, Rosan A.; Leech, Robert; Wit, Ferdinand W.N.M.; Portegies, Peter; Geurtsen, Gert J.; Schmand, Ben A.; Schim van der Loeff, Maarten F.; Franceschi, Claudio; Sabin, Caroline A.; Majoie, Charles B.L.M.; Winston, Alan; Reiss, Peter; Sharp, David J.

    2017-01-01

    Objective: To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. Methods: A large sample of virologically suppressed HIV-positive adults (n = 162, age 45–82 years) and highly comparable HIV-negative controls (n = 105) were recruited as part of the Comorbidity in Relation to AIDS (COBRA) collaboration. Using T1-weighted MRI scans, a machine-learning model of healthy brain aging was defined in an independent cohort (n = 2,001, aged 18–90 years). Neuroimaging data from HIV-positive and HIV-negative individuals were then used to estimate brain-predicted age; then brain-predicted age difference (brain-PAD = brain-predicted brain age − chronological age) scores were calculated. Neuropsychological and clinical assessments were also carried out. Results: HIV-positive individuals had greater brain-PAD score (mean ± SD 2.15 ± 7.79 years) compared to HIV-negative individuals (−0.87 ± 8.40 years; b = 3.48, p < 0.01). Increased brain-PAD score was associated with decreased performance in multiple cognitive domains (information processing speed, executive function, memory) and general cognitive performance across all participants. Brain-PAD score was not associated with age, duration of HIV infection, or other HIV-related measures. Conclusion: Increased apparent brain aging, predicted using neuroimaging, was observed in HIV-positive adults, despite effective viral suppression. Furthermore, the magnitude of increased apparent brain aging related to cognitive deficits. However, predicted brain age difference did not correlate with chronological age or duration of HIV infection, suggesting that HIV disease may accentuate rather than accelerate brain aging. PMID:28258081

  3. Increased brain-predicted aging in treated HIV disease.

    PubMed

    Cole, James H; Underwood, Jonathan; Caan, Matthan W A; De Francesco, Davide; van Zoest, Rosan A; Leech, Robert; Wit, Ferdinand W N M; Portegies, Peter; Geurtsen, Gert J; Schmand, Ben A; Schim van der Loeff, Maarten F; Franceschi, Claudio; Sabin, Caroline A; Majoie, Charles B L M; Winston, Alan; Reiss, Peter; Sharp, David J

    2017-04-04

    To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. A large sample of virologically suppressed HIV-positive adults (n = 162, age 45-82 years) and highly comparable HIV-negative controls (n = 105) were recruited as part of the Comorbidity in Relation to AIDS (COBRA) collaboration. Using T1-weighted MRI scans, a machine-learning model of healthy brain aging was defined in an independent cohort (n = 2,001, aged 18-90 years). Neuroimaging data from HIV-positive and HIV-negative individuals were then used to estimate brain-predicted age; then brain-predicted age difference (brain-PAD = brain-predicted brain age - chronological age) scores were calculated. Neuropsychological and clinical assessments were also carried out. HIV-positive individuals had greater brain-PAD score (mean ± SD 2.15 ± 7.79 years) compared to HIV-negative individuals (-0.87 ± 8.40 years; b = 3.48, p < 0.01). Increased brain-PAD score was associated with decreased performance in multiple cognitive domains (information processing speed, executive function, memory) and general cognitive performance across all participants. Brain-PAD score was not associated with age, duration of HIV infection, or other HIV-related measures. Increased apparent brain aging, predicted using neuroimaging, was observed in HIV-positive adults, despite effective viral suppression. Furthermore, the magnitude of increased apparent brain aging related to cognitive deficits. However, predicted brain age difference did not correlate with chronological age or duration of HIV infection, suggesting that HIV disease may accentuate rather than accelerate brain aging. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  4. Targeting aging for disease modification in osteoarthritis.

    PubMed

    Collins, John A; Diekman, Brian O; Loeser, Richard F

    2018-01-01

    Age is a key risk factor for the development of osteoarthritis and age-related changes within the joint might represent targets for therapy. The recent literature was reviewed to find studies that provide new insight into the role of aging in osteoarthritis, with a focus on the potential for disease modification. Preclinical studies using isolated cells and animal models provide evidence that two hallmarks of aging (cellular senescence and mitochondrial dysfunction) contribute to the development of osteoarthritis. Senescent cells secrete pro-inflammatory mediators and matrix degrading enzymes, and killing these cells with 'senolytic' compounds has emerged as a potential disease-modifying therapy. Mitochondrial dysfunction is associated with increased levels of reactive oxygen species (ROS) that can promote osteoarthritis by disrupting homeostatic intracellular signaling. Reducing ROS production in the mitochondria, stimulating antioxidant gene expression through Nrf2 activation, or inhibiting specific redox-sensitive signaling proteins represent additional approaches to disease modification in osteoarthritis that require further investigation. Although no human clinical trials for osteoarthritis have specifically targeted aging, preclinical studies suggest that targeting cellular senescence and/or mitochondrial dysfunction and the effects of excessive ROS may lead to novel interventions that could slow the progression of osteoarthritis.

  5. Pathology of the Aging Brain in Domestic and Laboratory Animals, and Animal Models of Human Neurodegenerative Diseases.

    PubMed

    Youssef, S A; Capucchio, M T; Rofina, J E; Chambers, J K; Uchida, K; Nakayama, H; Head, E

    2016-03-01

    According to the WHO, the proportion of people over 60 years is increasing and expected to reach 22% of total world's population in 2050. In parallel, recent animal demographic studies have shown that the life expectancy of pet dogs and cats is increasing. Brain aging is associated not only with molecular and morphological changes but also leads to different degrees of behavioral and cognitive dysfunction. Common age-related brain lesions in humans include brain atrophy, neuronal loss, amyloid plaques, cerebrovascular amyloid angiopathy, vascular mineralization, neurofibrillary tangles, meningeal osseous metaplasia, and accumulation of lipofuscin. In aging humans, the most common neurodegenerative disorder is Alzheimer's disease (AD), which progressively impairs cognition, behavior, and quality of life. Pathologic changes comparable to the lesions of AD are described in several other animal species, although their clinical significance and effect on cognitive function are poorly documented. This review describes the commonly reported age-associated neurologic lesions in domestic and laboratory animals and the relationship of these lesions to cognitive dysfunction. Also described are the comparative interspecies similarities and differences to AD and other human neurodegenerative diseases including Parkinson's disease and progressive supranuclear palsy, and the spontaneous and transgenic animal models of these diseases. © The Author(s) 2016.

  6. Polarization sensitive changes in the human macula associated with normal aging and age-related macular degeneration

    NASA Astrophysics Data System (ADS)

    VanNasdale, Dean Allan, Jr.

    2011-12-01

    The human macula occupies a relatively small, but crucial retinal area, as it is the location responsible for our most acute spatial vision and best color discrimination. Localizing important landmarks in the retina is difficult even in normal eyes where morphological inter-individual variability is high. This becomes even more challenging in the presence of sight-threatening pathology. With respect to the human macula, there remains a significant gap in the understanding of normal structure and function. Even less is known about the pathological mechanisms that occur in sight-threatening diseases including age-related macular degeneration. Because relatively little is known about normal aging changes, it is also difficult to differentiate those changes from changes associated with retinal disease. To better understand normal and pathological changes in the macula, imaging techniques using specific optical signatures are required. Structural features in the macula can be distinguished based on their intrinsic properties using specific light/tissue interactions. Because of the high degree of structural regularity in the macula, polarization sensitive imaging is potentially a useful tool for evaluating the morphology and integrity of the cellular architecture for both normal individuals and those affected by disease. In our investigations, we used polarization sensitive imaging to determining normal landmarks that are important clinically and for research investigations. We found that precision and accuracy in localizing the central macula was greatly improved through the use of polarization sensitive imaging. We also found that specific polarization alterations can be used to demonstrate systematic changes as a function of age, disproportionately affecting the central macular region. When evaluating patients with age-related macular degeneration, we found that precision and accuracy of localizing the central macula was also improved, even when significant pathology

  7. [Valvular heart disease associated with coronary artery disease].

    PubMed

    Yildirir, Aylin

    2009-07-01

    Nowadays, age-related degenerative etiologies have largely replaced the rheumatic ones and as a natural result of this etiologic change, coronary artery disease has become associated with valvular heart disease to a greater extent. Degenerative aortic valve disease has an important pathophysiological similarity to atherosclerosis and is the leader in this association. There is a general consensus that severely stenotic aortic valve should be replaced during bypass surgery for severe coronary artery disease. For moderate degree aortic stenosis, aortic valve replacement is usually performed during coronary bypass surgery. Ischemic mitral regurgitation has recently received great attention from both diagnostic and therapeutic points of view. Ischemic mitral regurgitation significantly alters the prognosis of the patient with coronary artery disease. Severe ischemic mitral regurgitation should be corrected during coronary bypass surgery and mitral valve repair should be preferred to valve replacement. For moderate degree ischemic mitral regurgitation, many authors prefer valve surgery with coronary bypass surgery. In this review, the main characteristics of patients with coronary artery disease accompanying valvular heart disease and the therapeutic options based on individual valve pathology are discussed.

  8. Phospholipase A2 - nexus of aging, oxidative stress, neuronal excitability, and functional decline of the aging nervous system? Insights from a snail model system of neuronal aging and age-associated memory impairment.

    PubMed

    Hermann, Petra M; Watson, Shawn N; Wildering, Willem C

    2014-01-01

    The aging brain undergoes a range of changes varying from subtle structural and physiological changes causing only minor functional decline under healthy normal aging conditions, to severe cognitive or neurological impairment associated with extensive loss of neurons and circuits due to age-associated neurodegenerative disease conditions. Understanding how biological aging processes affect the brain and how they contribute to the onset and progress of age-associated neurodegenerative diseases is a core research goal in contemporary neuroscience. This review focuses on the idea that changes in intrinsic neuronal electrical excitability associated with (per)oxidation of membrane lipids and activation of phospholipase A2 (PLA2) enzymes are an important mechanism of learning and memory failure under normal aging conditions. Specifically, in the context of this special issue on the biology of cognitive aging we portray the opportunities offered by the identifiable neurons and behaviorally characterized neural circuits of the freshwater snail Lymnaea stagnalis in neuronal aging research and recapitulate recent insights indicating a key role of lipid peroxidation-induced PLA2 as instruments of aging, oxidative stress and inflammation in age-associated neuronal and memory impairment in this model system. The findings are discussed in view of accumulating evidence suggesting involvement of analogous mechanisms in the etiology of age-associated dysfunction and disease of the human and mammalian brain.

  9. Falls and age in patients with Alzheimer's disease.

    PubMed

    Bassiony, Medhat M; Rosenblatt, Adam; Baker, Alva; Steinberg, Martin; Steele, Cynthia D; Sheppard, Jeanie-Marie E; Lyketsos, Constantine G

    2004-08-01

    The study's objective was to estimate the prevalence of falls in community-residing patients with Alzheimer's disease (AD) and to investigate the relationship between falls and age in AD. This was a study of 326 community-residing patients with AD according to National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria. The patients and their caregivers were asked about falls, behavioral disturbances, and medication use within the last 2 weeks. The patients were also rated on standardized measures of cognitive impairment, stage of dementia, depression, daily activities, general health, and extrapyramidal symptoms. Falls occurred in 24 (7.4%) patients with AD during the last 2 weeks. Using multiple logistic regression analyses, falls were independently associated with old age (odds ratio = 1.2; p = .03; 95% confidence interval = 1.0 to 1.4) but not with other variables examined. The authors conclude that falls in community-residing patients with AD are significantly associated with old age. Population-based prospective studies are needed to investigate further the risk factors for falls in AD.

  10. NAD+ Deficits in Age-Related Diseases and Cancer.

    PubMed

    Garrido, Amanda; Djouder, Nabil

    2017-08-01

    The phenomenon of aging has gained widespread attention in recent times. Although significant advances have been made to better understand aging and its related pathologies including cancer, there is not yet a clear mechanism explaining why diseases and cancer are inherent parts of the aging process. Finding a unifying equation that could bridge aging and its related diseases would allow therapeutic development and solve an immense human health problem to live longer and better. In this review, we discuss NAD + reduction as the central mechanism that may connect aging to its related pathologies and cancer. NAD + boosters would ensure and ameliorate health quality during aging. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Burden of disease associated with lower levels of income among US adults aged 65 and older.

    PubMed

    Lubetkin, Erica I; Jia, Haomiao

    2017-01-16

    Persons aged 65 years and older represent a heterogeneous group whose prevalence in the USA is expected to markedly increase. Few investigations have examined the total burden of disease attributable to lower levels of income in a single number that accounts for morbidity and mortality. We ascertained respondents' health-related quality of life (HRQOL) scores and mortality status from the 2003 to 2004, 2005 to 2006, 2007 to 2008 and 2009 to 2010 cohorts of the National Health and Nutrition Examination Survey (NHANES) with mortality follow-up through 31 December 2011. A mapping algorithm based on respondents' age and answers to the 4 core Healthy Days questions was used to obtain values of a preference-based measure of HRQOL, the EuroQol five dimensions questionnaire (EQ-5D) index, which enables quality-adjusted life years (QALYs) to be calculated. We included only respondents aged 65 years and older at the baseline, yielding a total sample size of 4952. We estimated mean QALYs according to different categories of income based on the percentage of Federal Poverty Level (FPL). After adjusting for age, gender and education, the remaining QALYs decreased with each successive decrement of category of income, ranging from 18.4 QALY (≥500% FPL) to 8.6 QALY (<100% FPL). Compared with participants with a mean income of ≥250% FPL, participants with an income <250% FPL had significant losses in QALY for most of the sociodemographic groups examined. In contrast, persons with a lower educational attainment did not show a corresponding loss in QALY according to income category. This study confirmed the association between lower income category and greater burden of disease, as measured by QALYs lost, among the US population aged 65 years and older. Our findings provide additional evidence of the role played by other key determinants of health and how factors not traditionally addressed by the healthcare system impact the life cycle of individuals and communities

  12. Factors Associated with Periodontal Disease in Pregnant Diabetic Women.

    PubMed

    Anwar, N; Zaman, N; Nimmi, N; Chowdhury, T A; Khan, M H

    2016-04-01

    There have been an association between systemic diseases and hormonal changes particularly diabetes which has been cited as a risk factor in the progression of periodontitis in pregnant women. The incidence and severity of periodontal diseases are increasing at a higher rate and a common condition in pregnant diabetic women among Bangladeshi population. This cross sectional study included 200 pregnant women who were selected from gynecological department and examined at the dental unit. The clinical parameters used were the Silness and Loe plaque index (PI), gingival scores and periodontal status and any relationship to socio demographic variables (age, occupation, level of education and urban or rural residence) and clinical variables (gestation period, previous pregnancy, type of diabetes and periodontal maintenance) were evaluated. The results showed that these clinical parameters increased concomitantly with an increase in the stage of pregnancy and in women with multiple pregnancies. Increased age, lower level of education, unemployment and patients residing in rural areas were associated with significantly higher gingival scores and periodontal measures. Women with increased age and multiple pregnancies usually have less interest to frequent periodontal maintenance showing a significant statistical relation between an increased age and changes in gingival and periodontal status; however no significant association was found between increased age and plaque index. It is concluded that gingival inflammatory symptoms are aggravated during pregnancy in diabetic women and are related to different clinical and demographic variables.

  13. Vitamin D status and age of onset of demyelinating disease.

    PubMed

    Brenton, J Nicholas; Koenig, Scott; Goldman, Myla D

    2014-11-01

    To evaluate the prevalence of and associated factors impacting vitamin D insufficiency and deficiency in childhood versus adult-onset demyelinating disease. We conducted a retrospective, cross-sectional, chart-review, cohort study on geographically-similar pediatric, young adult, and adult patients with a diagnosis of demyelinating disease identified at the University of Virginia from 2008 to 2013. Group prevalence of vitamin D insufficiency and deficiency as well as relevant factors associated with vitamin D status was analyzed and compared. We identified 24 childhood-onset (CO), 33 young adult-onset (Y-AO), and 59 adult-onset (AO) cases. There was no difference in the prevalence of vitamin D insufficiency or deficiency between the cohorts. Non-Caucasian race and elevated body mass index were significantly associated with low vitamin D levels, regardless of age of onset. In regression models, race and obesity were independent predictors of vitamin D status. The prevalence of obesity was significantly higher in the childhood-onset cohort (CO=58.5%; Y-AO=31%; AO=34%; p=0.02). Our findings demonstrate no difference in the prevalence of vitamin D insufficiency/deficiency between childhood and adult-onset demyelinating disease, suggesting age at disease onset is irrelevant to vitamin D status in demyelinating disease. Both race and obesity are independent factors associated with vitamin D insufficiency/deficiency, regardless of age of disease onset. Obesity, independent of gender, is significantly higher in children compared to adult patients diagnosed with multiple sclerosis and may have a role in the development of childhood-onset demyelinating disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Analysis of alternative splicing associated with aging and neurodegeneration in the human brain

    PubMed Central

    Tollervey, James R.; Wang, Zhen; Hortobágyi, Tibor; Witten, Joshua T.; Zarnack, Kathi; Kayikci, Melis; Clark, Tyson A.; Schweitzer, Anthony C.; Rot, Gregor; Curk, Tomaž; Zupan, Blaž; Rogelj, Boris; Shaw, Christopher E.; Ule, Jernej

    2011-01-01

    Age is the most important risk factor for neurodegeneration; however, the effects of aging and neurodegeneration on gene expression in the human brain have most often been studied separately. Here, we analyzed changes in transcript levels and alternative splicing in the temporal cortex of individuals of different ages who were cognitively normal, affected by frontotemporal lobar degeneration (FTLD), or affected by Alzheimer's disease (AD). We identified age-related splicing changes in cognitively normal individuals and found that these were present also in 95% of individuals with FTLD or AD, independent of their age. These changes were consistent with increased polypyrimidine tract binding protein (PTB)–dependent splicing activity. We also identified disease-specific splicing changes that were present in individuals with FTLD or AD, but not in cognitively normal individuals. These changes were consistent with the decreased neuro-oncological ventral antigen (NOVA)–dependent splicing regulation, and the decreased nuclear abundance of NOVA proteins. As expected, a dramatic down-regulation of neuronal genes was associated with disease, whereas a modest down-regulation of glial and neuronal genes was associated with aging. Whereas our data indicated that the age-related splicing changes are regulated independently of transcript-level changes, these two regulatory mechanisms affected expression of genes with similar functions, including metabolism and DNA repair. In conclusion, the alternative splicing changes identified in this study provide a new link between aging and neurodegeneration. PMID:21846794

  15. Investigation of Genetic Variants Associated with Alzheimer Disease in Parkinson Disease Cognition.

    PubMed

    Barrett, Matthew J; Koeppel, Alexander F; Flanigan, Joseph L; Turner, Stephen D; Worrall, Bradford B

    2016-01-01

    Meta-analysis of genome-wide association studies have implicated multiple single nucleotide polymorphisms (SNPs) and associated genes with Alzheimer disease. The role of these SNPs in cognitive impairment in Parkinson disease (PD) remains incompletely evaluated. The objective of this study was to test alleles associated with risk of Alzheimer disease for association with cognitive impairment in Parkinson disease (PD). Two datasets with PD subjects accessed through the NIH database of Genotypes and Phenotypes contained both single nucleotide polymorphism (SNP) arrays and mini-mental state exam (MMSE) scores. Genetic data underwent rigorous quality control and we selected SNPs for genes associated with AD other than APOE. We constructed logistic regression and ordinal regression models, adjusted for sex, age at MMSE, and duration of PD, to assess the association between selected SNPs and MMSE score. In one dataset, PICALM rs3851179 was associated with cognitive impairment (MMSE <  24) in PD subjects > 70 years old (OR = 2.3; adjusted p-value = 0.017; n = 250) but not in PD subjects ≤ 70 years old. Our finding suggests that PICALM rs3851179 could contribute to cognitive impairment in older patients with PD. It is important that future studies consider the interaction of age and genetic risk factors in the development of cognitive impairment in PD.

  16. The role of inflammation in age-related disease

    PubMed Central

    Howcroft, T. Kevin; Campisi, Judith; Louis, Germaine Buck; Smith, Martyn T.; Wise, Bradley; Wyss-Coray, Tony; Augustine, Alison Deckhut; McElhaney, Janet E.; Kohanski, Ron; Sierra, Felipe

    2013-01-01

    The National Institutes of Health (NIH) Geroscience Interest Group (GSIG) sponsored workshop, The Role of Inflammation in Age-Related Disease, was held September 6th-7th, 2012 in Bethesda, MD. It is now recognized that a mild pro-inflammatory state is correlated with the major degenerative diseases of the elderly. The focus of the workshop was to better understand the origins and consequences of this low level chronic inflammation in order to design appropriate interventional studies aimed at improving healthspan. Four sessions explored the intrinsic, environmental exposures and immune pathways by which chronic inflammation are generated, sustained, and lead to age-associated diseases. At the conclusion of the workshop recommendations to accelerate progress toward understanding the mechanistic bases of chronic disease were identified. PMID:23474627

  17. The epigenetic landscape of age-related diseases: the geroscience perspective.

    PubMed

    Gensous, Noémie; Bacalini, Maria Giulia; Pirazzini, Chiara; Marasco, Elena; Giuliani, Cristina; Ravaioli, Francesco; Mengozzi, Giacomo; Bertarelli, Claudia; Palmas, Maria Giustina; Franceschi, Claudio; Garagnani, Paolo

    2017-08-01

    In this review, we summarize current knowledge regarding the epigenetics of age-related diseases, focusing on those studies that have described DNA methylation landscape in cardio-vascular diseases, musculoskeletal function and frailty. We stress the importance of adopting the conceptual framework of "geroscience", which starts from the observation that advanced age is the major risk factor for several of these pathologies and aims at identifying the mechanistic links between aging and age-related diseases. DNA methylation undergoes a profound remodeling during aging, which includes global hypomethylation of the genome, hypermethylation at specific loci and an increase in inter-individual variation and in stochastic changes of DNA methylation values. These epigenetic modifications can be an important contributor to the development of age-related diseases, but our understanding on the complex relationship between the epigenetic signatures of aging and age-related disease is still poor. The most relevant results in this field come from the use of the so called "epigenetics clocks" in cohorts of subjects affected by age-related diseases. We report these studies in final section of this review.

  18. Complex and differential glial responses in Alzheimer's disease and ageing.

    PubMed

    Rodríguez, José J; Butt, Arthur M; Gardenal, Emanuela; Parpura, Vladimir; Verkhratsky, Alexei

    2016-01-01

    Glial cells and their association with neurones are fundamental for brain function. The emergence of complex neurone-glial networks assures rapid information transfer, creating a sophisticated circuitry where both types of neural cells work in concert, serving different activities. All glial cells, represented by astrocytes, oligodendrocytes, microglia and NG2-glia, are essential for brain homeostasis and defence. Thus, glia are key not only for normal central nervous system (CNS) function, but also to its dysfunction, being directly associated with all forms of neuropathological processes. Therefore, the progression and outcome of neurological and neurodegenerative diseases depend on glial reactions. In this review, we provide a concise account of recent data obtained from both human material and animal models demonstrating the pathological involvement of glia in neurodegenerative processes, including Alzheimer's disease (AD), as well as physiological ageing.

  19. College Students' Ageist Behavior: The Role of Aging Knowledge and Perceived Vulnerability to Disease

    ERIC Educational Resources Information Center

    Stahl, Sarah T.; Metzger, Aaron

    2013-01-01

    This cross-sectional study examined the associations among perceived vulnerability to disease, aging knowledge, and ageism (positive and negative) in a sample of undergraduate students enrolled in a human development course (N = 649; M age = 19.94 years, SD = 2.84 years). Perceived vulnerability to disease and aging knowledge were associated with…

  20. Gene therapy for Stargardt disease associated with ABCA4 gene.

    PubMed

    Han, Zongchao; Conley, Shannon M; Naash, Muna I

    2014-01-01

    Mutations in the photoreceptor-specific flippase ABCA4 lead to accumulation of the toxic bisretinoid A2E, resulting in atrophy of the retinal pigment epithelium (RPE) and death of the photoreceptor cells. Many blinding diseases are associated with these mutations including Stargardt's disease (STGD1), cone-rod dystrophy, retinitis pigmentosa (RP), and increased susceptibility to age-related macular degeneration. There are no curative treatments for any of these dsystrophies. While the monogenic nature of many of these conditions makes them amenable to treatment with gene therapy, the ABCA4 cDNA is 6.8 kb and is thus too large for the AAV vectors which have been most successful for other ocular genes. Here we review approaches to ABCA4 gene therapy including treatment with novel AAV vectors, lentiviral vectors, and non-viral compacted DNA nanoparticles. Lentiviral and compacted DNA nanoparticles in particular have a large capacity and have been successful in improving disease phenotypes in the Abca4 (-/-) murine model. Excitingly, two Phase I/IIa clinical trials are underway to treat patients with ABCA4-associated Startgardt's disease (STGD1). As a result of the development of these novel technologies, effective therapies for ABCA4-associated diseases may finally be within reach.

  1. Association of Insulin Resistance With Cerebral Glucose Uptake in Late Middle-Aged Adults at Risk for Alzheimer Disease.

    PubMed

    Willette, Auriel A; Bendlin, Barbara B; Starks, Erika J; Birdsill, Alex C; Johnson, Sterling C; Christian, Bradley T; Okonkwo, Ozioma C; La Rue, Asenath; Hermann, Bruce P; Koscik, Rebecca L; Jonaitis, Erin M; Sager, Mark A; Asthana, Sanjay

    2015-09-01

    Converging evidence suggests that Alzheimer disease (AD) involves insulin signaling impairment. Patients with AD and individuals at risk for AD show reduced glucose metabolism, as indexed by fludeoxyglucose F 18-labeled positron emission tomography (FDG-PET). To determine whether insulin resistance predicts AD-like global and regional glucose metabolism deficits in late middle-aged participants at risk for AD and to examine whether insulin resistance-predicted variation in regional glucose metabolism is associated with worse cognitive performance. This population-based, cross-sectional study included 150 cognitively normal, late middle-aged (mean [SD] age, 60.7 [5.8] years) adults from the Wisconsin Registry for Alzheimer's Prevention (WRAP) study, a general community sample enriched for AD parental history. Participants underwent cognitive testing, fasting blood draw, and FDG-PET at baseline. We used the homeostatic model assessment of peripheral insulin resistance (HOMA-IR). Regression analysis tested the statistical effect of HOMA-IR on global glucose metabolism. We used a voxelwise analysis to determine whether HOMA-IR predicted regional glucose metabolism. Finally, predicted variation in regional glucose metabolism was regressed against cognitive factors. Covariates included age, sex, body mass index, apolipoprotein E ε4 genotype, AD parental history status, and a reference region used to normalize regional uptake. Regional glucose uptake determined using FDG-PET and neuropsychological factors. Higher HOMA-IR was associated with lower global glucose metabolism (β = -0.29; P < .01) and lower regional glucose metabolism across large portions of the frontal, lateral parietal, lateral temporal, and medial temporal lobes (P < .05, familywise error corrected). The association was especially robust in the left medial temporal lobe (R2 = 0.178). Lower glucose metabolism in the left medial temporal lobe predicted by HOMA-IR was significantly related

  2. Age-specific association between blood pressure and vascular and non-vascular chronic diseases in 0·5 million adults in China: a prospective cohort study.

    PubMed

    Lacey, Ben; Lewington, Sarah; Clarke, Robert; Kong, Xiang Ling; Chen, Yiping; Guo, Yu; Yang, Ling; Bennett, Derrick; Bragg, Fiona; Bian, Zheng; Wang, Shaojie; Zhang, Hua; Chen, Junshi; Walters, Robin G; Collins, Rory; Peto, Richard; Li, Liming; Chen, Zhengming

    2018-06-01

    The age-specific association between blood pressure and vascular disease has been studied mostly in high-income countries, and before the widespread use of brain imaging for diagnosis of the main stroke types (ischaemic stroke and intracerebral haemorrhage). We aimed to investigate this relationship among adults in China. 512 891 adults (59% women) aged 30-79 years were recruited into a prospective study from ten areas of China between June 25, 2004, and July 15, 2008. Participants attended assessment centres where they were interviewed about demographic and lifestyle characteristics, and their blood pressure, height, and weight were measured. Incident disease was identified through linkage to local mortality records, chronic disease registries, and claims to the national health insurance system. We used Cox regression analysis to produce adjusted hazard ratios (HRs) relating systolic blood pressure to disease incidence. HRs were corrected for regression dilution to estimate associations with long-term average (usual) systolic blood pressure. During a median follow-up of 9 years (IQR 8-10), there were 88 105 incident vascular and non-vascular chronic disease events (about 90% of strokes events were diagnosed using brain imaging). At ages 40-79 years (mean age at event 64 years [SD 9]), usual systolic blood pressure was continuously and positively associated with incident major vascular disease throughout the range 120-180 mm Hg: each 10 mm Hg higher usual systolic blood pressure was associated with an approximately 30% higher risk of ischaemic heart disease (HR 1·31 [95% CI 1·28-1·34]) and ischaemic stroke (1·30 [1·29-1·31]), but the association with intracerebral haemorrhage was about twice as steep (1·68 [1·65-1·71]). HRs for vascular disease were twice as steep at ages 40-49 years than at ages 70-79 years. Usual systolic blood pressure was also positively associated with incident chronic kidney disease (1·40 [1·35-1·44]) and diabetes (1·14 [1

  3. Sex, the aging immune system, and chronic disease.

    PubMed

    Gubbels Bupp, Melanie R

    2015-04-01

    The immune systems of men and women differ in significant ways, especially after puberty. In particular, females are generally more prone to autoimmunity, but experience lower rates of infections and chronic inflammatory disease. Sex hormones, genes encoded on the sex chromosomes, and gender-specific behaviors likely contribute to these differences. The aging process is associated with changes in the composition and function of the immune system and these changes may occur at an accelerated rate in men as compared to women. Moreover, after the age of menopause, the incidence of chronic inflammatory disease in women approaches or exceeds that observed in males. At the same time, the incidence of autoimmunity in post-menopausal women is decreased or equivalent to the rates observed in similarly-aged men. Additional studies addressing the influence of sex on the pathogenesis of chronic and autoimmune diseases in the aged are warranted. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Inverse association between age at the time of radiation exposure and extent of disease in cases of radiation-induced childhood thyroid carcinoma in Belarus.

    PubMed

    Farahati, J; Demidchik, E P; Biko, J; Reiners, C

    2000-03-15

    Increased incidence of childhood thyroid carcinoma, particularly in the youngest children, has been reported from Belarus since the nuclear reactor accident at Chernobyl in 1986. The relation between disease severity and age at the time of the accident, not previously established in this cohort, was analyzed in this study. The authors studied the association between disease severity, expressed by TNM classification, and age at radiation exposure in a cohort of 483 patients younger than 8 years at the time of the Chernobyl accident who have been diagnosed with differentiated thyroid carcinoma since 1986 at the Center for Thyroid Cancer in Minsk. The associations between age at radiation exposure and TNM categories were compared among 4 groups of patients who were ages <2, 2.1-4, 4.1-6, and 6.1-8 years at the time of the accident. Multivariate discriminant analysis was performed to examine the effects of age at the time of the accident, gender, histology, tumor stage, and N classification on the frequency of distant metastasis. Younger age at the time of the Chernobyl accident was associated with greater extrathyroidal tumor extension (P<0.01) and more lymph node involvement (P<0.0001) and tended to be associated with more distant metastases (P = 0.09). Compared with patients who were ages 6.1-8 years at the time of the accident, patients who were younger than 2 years had significantly more extrathyroidal tumor invasion (P = 0.004), lymph node involvement (P = 0.004), and distant metastases (P = 0.05). The age at diagnosis increased with older age at the time of radiation exposure (linear regression analysis; correlation coefficient = 0. 67; P<0.001). Multivariate analysis revealed that younger age at the time of the accident (P = 0.001) and advanced locoregional tumor extension (P<0.001) were the only powerful factors influencing the risk for distant metastasis of this malignancy. The severity of disease was associated inversely with age at the time of radiation

  5. Oxysterol Signatures Distinguish Age-Related Macular Degeneration from Physiologic Aging.

    PubMed

    Lin, Jonathan B; Sene, Abdoulaye; Santeford, Andrea; Fujiwara, Hideji; Sidhu, Rohini; Ligon, Marianne M; Shankar, Vikram A; Ban, Norimitsu; Mysorekar, Indira U; Ory, Daniel S; Apte, Rajendra S

    2018-06-11

    Macrophage aging is pathogenic in numerous diseases, including age-related macular degeneration (AMD), a leading cause of blindness in older adults. Although prior studies have explored the functional consequences of macrophage aging, less is known about its cellular basis or what defines the transition from physiologic aging to disease. Here, we show that despite their frequent self-renewal, macrophages from old mice exhibited numerous signs of aging, such as impaired oxidative respiration. Transcriptomic profiling of aged murine macrophages revealed dysregulation of diverse cellular pathways, especially in cholesterol homeostasis, that manifested in altered oxysterol signatures. Although the levels of numerous oxysterols in human peripheral blood mononuclear cells and plasma exhibited age-associated changes, plasma 24-hydroxycholesterol levels were specifically associated with AMD. These novel findings demonstrate that oxysterol levels can discriminate disease from physiologic aging. Furthermore, modulation of cholesterol homeostasis may be a novel strategy for treating age-associated diseases in which macrophage aging is pathogenic. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Taste Bud Homeostasis in Health, Disease, and Aging

    PubMed Central

    2014-01-01

    The mammalian taste bud is an onion-shaped epithelial structure with 50–100 tightly packed cells, including taste receptor cells, supporting cells, and basal cells. Taste receptor cells detect nutrients and toxins in the oral cavity and transmit the sensory information to gustatory nerve endings in the buds. Supporting cells may play a role in the clearance of excess neurotransmitters after their release from taste receptor cells. Basal cells are precursor cells that differentiate into mature taste cells. Similar to other epithelial cells, taste cells turn over continuously, with an average life span of about 8–12 days. To maintain structural homeostasis in taste buds, new cells are generated to replace dying cells. Several recent studies using genetic lineage tracing methods have identified populations of progenitor/stem cells for taste buds, although contributions of these progenitor/stem cell populations to taste bud homeostasis have yet to be fully determined. Some regulatory factors of taste cell differentiation and degeneration have been identified, but our understanding of these aspects of taste bud homoeostasis remains limited. Many patients with various diseases develop taste disorders, including taste loss and taste distortion. Decline in taste function also occurs during aging. Recent studies suggest that disruption or alteration of taste bud homeostasis may contribute to taste dysfunction associated with disease and aging. PMID:24287552

  7. Taste bud homeostasis in health, disease, and aging.

    PubMed

    Feng, Pu; Huang, Liquan; Wang, Hong

    2014-01-01

    The mammalian taste bud is an onion-shaped epithelial structure with 50-100 tightly packed cells, including taste receptor cells, supporting cells, and basal cells. Taste receptor cells detect nutrients and toxins in the oral cavity and transmit the sensory information to gustatory nerve endings in the buds. Supporting cells may play a role in the clearance of excess neurotransmitters after their release from taste receptor cells. Basal cells are precursor cells that differentiate into mature taste cells. Similar to other epithelial cells, taste cells turn over continuously, with an average life span of about 8-12 days. To maintain structural homeostasis in taste buds, new cells are generated to replace dying cells. Several recent studies using genetic lineage tracing methods have identified populations of progenitor/stem cells for taste buds, although contributions of these progenitor/stem cell populations to taste bud homeostasis have yet to be fully determined. Some regulatory factors of taste cell differentiation and degeneration have been identified, but our understanding of these aspects of taste bud homoeostasis remains limited. Many patients with various diseases develop taste disorders, including taste loss and taste distortion. Decline in taste function also occurs during aging. Recent studies suggest that disruption or alteration of taste bud homeostasis may contribute to taste dysfunction associated with disease and aging.

  8. Neuroimaging of Cerebrovascular Disease in the Aging Brain

    PubMed Central

    Gupta, Ajay; Nair, Sreejit; Schweitzer, Andrew D.; Kishore, Sirish; Johnson, Carl E.; Comunale, Joseph P.; Tsiouris, Apostolos J.; Sanelli, Pina C.

    2012-01-01

    Cerebrovascular disease remains a significant public health burden with its greatest impact on the elderly population. Advances in neuroimaging techniques allow detailed and sophisticated evaluation of many manifestations of cerebrovascular disease in the brain parenchyma as well as in the intracranial and extracranial vasculature. These tools continue to contribute to our understanding of the multifactorial processes that occur in the age-dependent development of cerebrovascular disease. Structural abnormalities related to vascular disease in the brain and vessels have been well characterized with CT and MRI based techniques. We review some of the pathophysiologic mechanisms in the aging brain and cerebral vasculature and the related structural abnormalities detectable on neuroimaging, including evaluation of age-related white matter changes, atherosclerosis of the cerebral vasculature, and cerebral infarction. In addition, newer neuroimaging techniques, such as diffusion tensor imaging, perfusion techniques, and assessment of cerebrovascular reserve, are also reviewed, as these techniques can detect physiologic alterations which complement the morphologic changes that cause cerebrovascular disease in the aging brain.Further investigation of these advanced imaging techniques has potential application to the understanding and diagnosis of cerebrovascular disease in the elderly. PMID:23185721

  9. HIGHER SERUM TOTAL CHOLESTEROL LEVELS IN LATE MIDDLE AGE ARE ASSOCIATED WITH GLUCOSE HYPOMETABOLISM IN BRAIN REGIONS AFFECTED BY ALZHEIMER’S DISEASE AND NORMAL AGING

    PubMed Central

    Reiman, Eric M.; Chen, Kewei; Langbaum, Jessica B.S.; Lee, Wendy; Reschke, Cole; Bandy, Daniel; Alexander, Gene E.; Caselli, Richard J.

    2010-01-01

    Epidemiological studies suggest that higher midlife serum total cholesterol levels are associated with an increased risk of Alzheimer’s disease (AD). Using fluorodeoxyglucose positron emission tomography (PET) in the study of cognitively normal late-middle-aged people, we demonstrated an association between apolipoprotein E (APOE) ε4 gene dose, the major genetic risk factor for late-onset AD, and lower measurements of the cerebral metabolic rate for glucose (CMRgl) in AD-affected brain regions, we proposed using PET as a presymptomatic endophenotype to evaluate other putative AD risk modifiers, and we then used it to support an aggregate cholesterol-related genetic risk score in the risk of AD. In the present study, we used PET to investigate the association between serum total cholesterol levels and cerebral metabolic rate for glucose metabolism (CMRgl) in 117 cognitively normal late middle-aged APOE ε4 homozygotes, heterozygotes and noncarriers. Higher serum total cholesterol levels were associated with lower CMRgl bilaterally in precuneus, parietotemporal and prefrontal regions previously found to be preferentially affected by AD, and in additional frontal regions previously found to be preferentially affected by normal aging. The associations were greater in APOE ε4 carriers than non-carriers in some of the AD-affected brain regions. We postulate the higher midlife serum total cholesterol levels accelerate brain processes associated with normal aging and conspire with other risk factors in the predisposition to AD. We propose using PET in proof-of-concept randomized controlled trials to rapidly evaluate the effects of midlife cholesterol-lowering treatments on the brain changes associated with normal aging and AD. PMID:19631758

  10. Age exacerbates HIV-associated white matter abnormalities.

    PubMed

    Seider, Talia R; Gongvatana, Assawin; Woods, Adam J; Chen, Huaihou; Porges, Eric C; Cummings, Tiffany; Correia, Stephen; Tashima, Karen; Cohen, Ronald A

    2016-04-01

    Both HIV disease and advanced age have been associated with alterations to cerebral white matter, as measured with white matter hyperintensities (WMH) on fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI), and more recently with diffusion tensor imaging (DTI). This study investigates the combined effects of age and HIV serostatus on WMH and DTI measures, as well as the relationships between these white matter measures, in 88 HIV seropositive (HIV+) and 49 seronegative (HIV-) individuals aged 23-79 years. A whole-brain volumetric measure of WMH was quantified from FLAIR images using a semi-automated process, while fractional anisotropy (FA) was calculated for 15 regions of a whole-brain white matter skeleton generated using tract-based spatial statistics (TBSS). An age by HIV interaction was found indicating a significant association between WMH and older age in HIV+ participants only. Similarly, significant age by HIV interactions were found indicating stronger associations between older age and decreased FA in the posterior limbs of the internal capsules, cerebral peduncles, and anterior corona radiata in HIV+ vs. HIV- participants. The interactive effects of HIV and age were stronger with respect to whole-brain WMH than for any of the FA measures. Among HIV+ participants, greater WMH and lower anterior corona radiata FA were associated with active hepatitis C virus infection, a history of AIDS, and higher current CD4 cell count. Results indicate that age exacerbates HIV-associated abnormalities of whole-brain WMH and fronto-subcortical white matter integrity.

  11. Presbyphagia and Sarcopenic Dysphagia: Association between Aging, Sarcopenia, and Deglutition Disorders.

    PubMed

    Wakabayashi, H

    2014-01-01

    Presbyphagia refers to age-related changes in the swallowing mechanism in the elderly associated with a frailty in swallowing. Presbyphagia is different from dysphagia. Sarcopenic dysphagia is difficulty swallowing due to sarcopenia of generalized skeletal muscles and swallowing muscles. Age-related loss of swallowing muscle mass becomes evident in the geniohyoid muscle and tongue. Elderly subjects with both sarcopenia and dysphagia may have not only disease-related dysphagia but also sarcopenic dysphagia. In cases of aspiration pneumonia, deterioration in activity-, disease-, and nutrition-related sarcopenia of generalized skeletal muscles and swallowing muscles may develop into sarcopenic dysphagia. Assessment of sarcopenic dysphagia includes evaluation of both dysphagia and sarcopenia. The 10-item Eating Assessment Tool (EAT-10) and a water test combined with pulse oximetry are useful for dysphagia screening. Assessment of the multi-factorial causes of sarcopenia including nutritional review is important, because rehabilitation of sarcopenic dysphagia differs depending on its etiology. Consensus diagnostic criteria for sarcopenic dysphagia were proposed at the 19th Annual Meeting of the Japanese Society of Dysphagia Rehabilitation. Rehabilitation for sarcopenic dysphagia includes treatment of both dysphagia and sarcopenia. The core components of dysphagia rehabilitation are oral health care, rehabilitative techniques, and food modification. The causes of adult malnutrition may also contribute to the etiology of secondary sarcopenia and sarcopenic dysphagia. Therefore, nutrition management is indispensable for sarcopenic dysphagia rehabilitation. In cases of sarcopenia with numerous complicating causes, treatment should include pharmaceutical therapies for age-related sarcopenia and comorbid chronic diseases, resistance training, early ambulation, nutrition management, protein and amino acid supplementation, and non-smoking.

  12. Reprint of "iPSCs, aging and age-related diseases".

    PubMed

    Isobe, Ken-ichi; Cheng, Zhao; Nishio, Naomi; Suganya, Thanasegan; Tanaka, Yuriko; Ito, Sachiko

    2015-01-25

    Human histocompatibility antigens are quite heterogeneous and promote the rejection of transplanted tissue. Recent advances in stem cell research that enable the use of a patient's own stem cells for transplantation are very important because rejection could be avoided. In particular, Yamanaka’s group in Japan gave new hope to patients with incurable diseases when they developed induced murine pluripotent stem cells (iPSCs) in 2006 and human iPSCs in 2007. Whereas embryonic stem cells (ESCs) are derived from the inner cell mass and are supported in culture by LIF, iPSCs are derived from fetal or adult somatic cells. Through the application of iPSC technology, adult somatic cells can develop a pluripotent state. One advantage of using iPSCs instead of ESCs in regenerative medicine is that (theoretically) immune rejection could be avoided, although there is some debate about immune rejection of a patient's own iPSCs. Many diseases occur in elderly patients. In order to use regenerative medicine with the elderly, it is important to demonstrate that iPSCs can indeed be generated from older patients. Recent findings have shown that iPSCs can be established from aged mice and aged humans. These iPSCs can differentiate to cells from all three germ layers. However, it is not known whether iPSCs from aged mice or humans show early senescence. Before clinical use of iPSCs, issues related to copy number variation, tumorigenicity and immunogenicity must be resolved. It is particularly important that researchers have succeeded in generating iPSCs that have differentiated to somatic cells related to specific diseases of the elderly, including atherosclerosis, diabetes, Alzheimer's disease and Parkinson's disease. These efforts will facilitate the use of personalized stem cell transplantation therapy for currently incurable diseases.

  13. Inference of domain-disease associations from domain-protein, protein-disease and disease-disease relationships.

    PubMed

    Zhang, Wangshu; Coba, Marcelo P; Sun, Fengzhu

    2016-01-11

    Protein domains can be viewed as portable units of biological function that defines the functional properties of proteins. Therefore, if a protein is associated with a disease, protein domains might also be associated and define disease endophenotypes. However, knowledge about such domain-disease relationships is rarely available. Thus, identification of domains associated with human diseases would greatly improve our understanding of the mechanism of human complex diseases and further improve the prevention, diagnosis and treatment of these diseases. Based on phenotypic similarities among diseases, we first group diseases into overlapping modules. We then develop a framework to infer associations between domains and diseases through known relationships between diseases and modules, domains and proteins, as well as proteins and disease modules. Different methods including Association, Maximum likelihood estimation (MLE), Domain-disease pair exclusion analysis (DPEA), Bayesian, and Parsimonious explanation (PE) approaches are developed to predict domain-disease associations. We demonstrate the effectiveness of all the five approaches via a series of validation experiments, and show the robustness of the MLE, Bayesian and PE approaches to the involved parameters. We also study the effects of disease modularization in inferring novel domain-disease associations. Through validation, the AUC (Area Under the operating characteristic Curve) scores for Bayesian, MLE, DPEA, PE, and Association approaches are 0.86, 0.84, 0.83, 0.83 and 0.79, respectively, indicating the usefulness of these approaches for predicting domain-disease relationships. Finally, we choose the Bayesian approach to infer domains associated with two common diseases, Crohn's disease and type 2 diabetes. The Bayesian approach has the best performance for the inference of domain-disease relationships. The predicted landscape between domains and diseases provides a more detailed view about the disease

  14. Developing a patient and family research advisory panel to include people with significant disease, multimorbidity and advanced age.

    PubMed

    Portalupi, Laura B; Lewis, Carmen L; Miller, Carl D; Whiteman-Jones, Kerry L; Sather, Kay A; Nease, Donald E; Matlock, Daniel D

    2017-06-01

    People who have experienced illness due to significant disease, multimorbidity and/or advanced age are high utilizers of the health care system. Yet this population has had little formal opportunity to participate in guiding the health care research agenda, and few mechanisms exist for researchers to engage this population in an efficient way. We describe the process of developing a standing patient and family advisory panel to incorporate this population's voice into research in the USA. The panel was created at the University of Colorado. Preliminary panel development consisted of a needs assessment, information gathering and participant recruitment. We collected feedback from researchers who consulted with the panel and from panel members in order to better understand the experience from the patient and family member perspective. The patient and family research advisory panel consists of eight advisors who have experience with significant disease, multimorbidity and/or advanced age, two physicians and a program manager. The panel meets every other month for 2 hours with the main purpose of advising diverse researchers on health care studies. People with significant disease, multimorbidity and/or advanced age represent a growing demographic in the USA, and their engagement in research is essential as the model of health care delivery moves from volume to value. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Prevalence of periodontal disease, its association with systemic diseases and prevention

    PubMed Central

    Nazir, Muhammad Ashraf

    2017-01-01

    Periodontal diseases are prevalent both in developed and developing countries and affect about 20-50% of global population. High prevalence of periodontal disease in adolescents, adults, and older individuals makes it a public health concern. Several risk factors such as smoking, poor oral hygiene, diabetes, medication, age, hereditary, and stress are related to periodontal diseases. Robust evidence shows the association of periodontal diseases with systemic diseases such as cardiovascular disease, diabetes, and adverse pregnancy outcomes. Periodontal disease is likely to cause 19% increase in the risk of cardiovascular disease, and this increase in relative risk reaches to 44% among individuals aged 65 years and over. Type 2 diabetic individuals with severe form of periodontal disease have 3.2 times greater mortality risk compared with individuals with no or mild periodontitis. Periodontal therapy has been shown to improve glycemic control in type 2 diabetic subjects. Periodontitis is related to maternal infection, preterm birth, low birth weight, and preeclampsia. Oral disease prevention strategies should be incorporated in chronic systemic disease preventive initiatives to curtail the burden of disease in populations. The reduction in the incidence and prevalence of periodontal disease can reduce its associated systemic diseases and can also minimize their financial impact on the health-care systems. It is hoped that medical, dental practitioners, and other health-care professionals will get familiar with perio-systemic link and risk factors, and need to refer to the specialized dental or periodontal care. PMID:28539867

  16. Prevalence of periodontal disease, its association with systemic diseases and prevention.

    PubMed

    Nazir, Muhammad Ashraf

    2017-01-01

    Periodontal diseases are prevalent both in developed and developing countries and affect about 20-50% of global population. High prevalence of periodontal disease in adolescents, adults, and older individuals makes it a public health concern. Several risk factors such as smoking, poor oral hygiene, diabetes, medication, age, hereditary, and stress are related to periodontal diseases. Robust evidence shows the association of periodontal diseases with systemic diseases such as cardiovascular disease, diabetes, and adverse pregnancy outcomes. Periodontal disease is likely to cause 19% increase in the risk of cardiovascular disease, and this increase in relative risk reaches to 44% among individuals aged 65 years and over. Type 2 diabetic individuals with severe form of periodontal disease have 3.2 times greater mortality risk compared with individuals with no or mild periodontitis. Periodontal therapy has been shown to improve glycemic control in type 2 diabetic subjects. Periodontitis is related to maternal infection, preterm birth, low birth weight, and preeclampsia. Oral disease prevention strategies should be incorporated in chronic systemic disease preventive initiatives to curtail the burden of disease in populations. The reduction in the incidence and prevalence of periodontal disease can reduce its associated systemic diseases and can also minimize their financial impact on the health-care systems. It is hoped that medical, dental practitioners, and other health-care professionals will get familiar with perio-systemic link and risk factors, and need to refer to the specialized dental or periodontal care.

  17. Sex hormones, aging, and Alzheimer’s disease

    PubMed Central

    Barron, Anna M.; Pike, Christian J.

    2012-01-01

    A promising strategy to delay and perhaps prevent Alzheimer’s disease (AD) is to identify the age-related changes that put the brain at risk for the disease. A significant normal age change known to result in tissue-specific dysfunction is the depletion of sex hormones. In women, menopause results in a relatively rapid loss of estradiol and progesterone. In men, aging is associated with a comparatively gradual yet significant decrease in testosterone. We review a broad literature that indicates age-related losses of estrogens in women and testosterone in men are risk factors for AD. Both estrogens and androgens exert a wide range of protective actions that improve multiple aspects of neural health, suggesting that hormone therapies have the potential to combat AD pathogenesis. However, translation of experimental findings into effective therapies has proven challenging. One emerging treatment option is the development of novel hormone mimetics termed selective estrogen and androgen receptor modulators. Continued research of sex hormones and their roles in the aging brain is expected to yield valuable approaches to reducing the risk of AD. PMID:22201929

  18. Vital capacity and selected metabolic diseases in middle-aged Japanese men

    PubMed Central

    Sakuta, Hidenari; Suzuki, Takashi; Yasuda, Hiroko; Ito, Teizo

    2006-01-01

    OBJECTIVE To elucidate the association between vital capacity and the presence of selected metabolic diseases in middle-aged Japanese men. METHODS A cross-sectional analysis of the associations among forced vital capacity (FVC), static vital capacity as a percentage of that predicted (%VC) and the presence of metabolic diseases was performed. RESULTS In a univariate linear regression analysis, FVC and %VC were inversely associated with poor vegetable intake, cigarette smoking and body mass index, but not with physical activity or ethanol consumption. In a logistic regression analysis adjusted for lifestyle factors, body mass index and age, the odds ratios for the presence of metabolic disease per 0.54 L (1 SD) decrease in FVC were 1.24 (95% CI 1.03 to 1.50) for type II diabetes, 1.21 (95% CI 1.02 to 1.42) for hypertension, 1.34 (95% CI 1.11 to 1.63) for hypertriglyceridemia, 1.23 (95% CI 1.03 to 1.46) for high gamma-glutamyl transferase levels and 1.63 (95% CI 1.10 to 2.41) for an episode of cardiovascular disease. FVC did not correlate with hyperhomocysteinemia, hypercholesterolemia or high white blood cell count. Similar results were also obtained for the association between %VC and metabolic diseases. CONCLUSIONS A decrease in FVC or %VC was associated with the presence of some metabolic diseases. The association may partly explain the reported association between low FVC and cardiovascular disease. PMID:16550264

  19. Food insecurity is associated with chronic disease among low-income NHANES participants.

    PubMed

    Seligman, Hilary K; Laraia, Barbara A; Kushel, Margot B

    2010-02-01

    Food insecurity refers to the inability to afford enough food for an active, healthy life. Numerous studies have shown associations between food insecurity and adverse health outcomes among children. Studies of the health effects of food insecurity among adults are more limited and generally focus on the association between food insecurity and self-reported disease. We therefore examined the association between food insecurity and clinical evidence of diet-sensitive chronic disease, including hypertension, hyperlipidemia, and diabetes. Our population-based sample included 5094 poor adults aged 18-65 y participating in the NHANES (1999-2004 waves). We estimated the association between food insecurity (assessed by the Food Security Survey Module) and self-reported or laboratory/examination evidence of diet-sensitive chronic disease using Poisson regression. We adjusted the models to account for differences in age, gender, race, educational attainment, and income. Food insecurity was associated with self-reported hypertension [adjusted relative risk (ARR) 1.20; 95% CI, 1.04-1.38] and hyperlipidemia (ARR 1.30; 95% CI, 1.09-1.55), but not diabetes (ARR 1.19; 95% CI, 0.89-1.58). Food insecurity was associated with laboratory or examination evidence of hypertension (ARR 1.21; 95% CI, 1.04-1.41) and diabetes (ARR 1.48; 95% CI, 0.94-2.32). The association with laboratory evidence of diabetes did not reach significance in the fully adjusted model unless we used a stricter definition of food insecurity (ARR 2.42; 95% CI, 1.44-4.08). These data show that food insecurity is associated with cardiovascular risk factors. Health policy discussions should focus increased attention on ability to afford high-quality foods for adults with or at risk for chronic disease.

  20. Association between Daytime Napping and Chronic Diseases in China.

    PubMed

    Zhou, Junmin; Kessler, Asia Sikora; Su, Dejun

    2016-03-01

    To explore the relationship between daytime napping and incidence of chronic diseases over the past 6 months among adults in China. Based on data collected from 13,469 respondents over age 40 in the Chinese Family Panel Studies in 2010, logistic regression models were estimated to examine the association between daytime napping and the incidence of any chronic diseases and 3 specific chronic diseases (hypertension, diabetes, and heart disease) after adjusting for confounders. Differences of risks by sex and age were also investigated. In the sample, 50.8% were women and 32.2% were over 60 years old. Adjusted estimates show respondents with daytime napping had elevated odds of developing any chronic diseases, hypertension, and diabetes compared to those who did not nap; having over 60 minutes of daytime napping had weaker association compared with shorter duration of daytime napping. The association between daytime napping and hypertension was found in women but not in men. Daytime napping appears to be associated with elevated risk of incidence of any chronic diseases, hypertension, and diabetes.

  1. Brain aging, Alzheimer's disease, and mitochondria

    PubMed Central

    Swerdlow, Russell H.

    2011-01-01

    The relationship between brain aging and Alzheimer’s disease (AD) is contentious. One view holds AD results when brain aging surpasses a threshold. The other view postulates AD is not a consequence of brain aging. This review discusses this conundrum from the perspective of different investigative lines that have tried to address it, as well as from the perspective of the mitochondrion, an organelle that appears to play a role in both AD and brain aging. Specific issues addressed include the question of whether AD and brain aging should be conceptually lumped or split, the extent to which AD and brain aging potentially share common molecular mechanisms, whether beta amyloid should be primarily considered a marker of AD or simply brain aging, and the definition of AD itself. PMID:21920438

  2. Prevalence and factors associated with rheumatic diseases and chronic joint symptoms in the elderly.

    PubMed

    Falsarella, Gláucia R; Coimbra, Ibsen B; Barcelos, Caroline C; Costallat, Lilian Tl; Carvalho, Olga Mf; Coimbra, Arlete Mv

    2013-10-01

    In the elderly population, rheumatic conditions are major causes of pain that restrict participation in activities and mobility, and cause difficulties in the execution of self-care tasks. The present study aimed to analyze the prevalence and factors associated with the self-reported rheumatic diseases and chronic joint symptoms of the elderly. This transversal epidemiological survey involved 2209 older adults (aged ≥ 60 years). The investigation included sociodemographic factors, anthropometrics, activities of daily living, chronic conditions, medication and quality of life. Univariate and multivariate regression analysis were used for statistical procedures, P ≤ 0.05. The prevalence of rheumatism was 22.7%. Multivariate analysis showed that rheumatism was correlated with the following: female sex (OR = 1.91), high income (OR = 2.34), cardiovascular disease (OR = 1.42), cataracts (OR = 1.39), glucocorticoids (OR = 5.24), other anti-inflammatory medications (OR = 2.24) and pain (OR = 0.983). After adjusting for age and glucocorticoids, an association between cataracts and rheumatism was detected (OR = 1.32). The prevalence of symptoms was 45.6%. Multivariate regression results for symptoms included the following: female sex (OR = 1.40), body mass index ≥ 30.0 kg/m(2) (OR = 3.31), functional capacity (OR = 0.990), general health (OR = 0.993) and pain (OR = 0.981). After adjustment for age and glucocorticoids, an association between cataracts and symptoms was detected (OR = 1.26). There was a significant association of rheumatism and symptoms with women and high incomes. Obesity was associated with joint symptoms, which in turn were associated with an impaired quality of life. Cataracts and cardiovascular disease were associated with rheumatism. The identification of these characteristics in the elderly will contribute to a better understanding of this systemic disease and should be used to plan effective preventive measures. © 2013 Japan Geriatrics Society.

  3. HIV-associated cellular senescence: A contributor to accelerated aging.

    PubMed

    Cohen, Justin; Torres, Claudio

    2017-07-01

    Due to the advent of antiretroviral therapy HIV is no longer a terminal disease and the HIV infected patients are becoming increasingly older. While this is a major success, with increasing age comes an increased risk for disease. The age-related comorbidities that HIV infected patients experience suggest that they suffer from accelerated aging. One possible contributor to this accelerated aging is cellular senescence, an age-associated response that can occur prematurely in response to stress, and that is emerging as a contributor to disease and aging. HIV patients experience several stressors such as the virus itself, antiretroviral drugs and to a lesser extent, substance abuse that can induce cellular senescence. This review summarizes the current knowledge of senescence induction in response to these stressors and their relation to the comorbidities in HIV patients. Cellular senescence may be a possible therapeutic target for these comorbidities. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Association between cardiovascular disease and socioeconomic level in Portugal.

    PubMed

    Ribeiro, Sónia; Furtado, Cláudia; Pereira, João

    2013-11-01

    Cardiovascular disease is the leading cause of morbidity, mortality and disability in Portugal. Socioeconomic level is known to influence health status but there is scant evidence on socioeconomic inequalities in cardiovascular disease in Portugal. To analyze the distribution of cardiovascular disease in the Portuguese population according to socioeconomic status. We conducted a cross-sectional study using data from the fourth National Health Survey on a representative sample of the Portuguese population. Socioeconomic inequalities in cardiovascular disease, risk factors and number of medical visits were analyzed using odds ratios according to socioeconomic status (household equivalent income) in the adult population (35-74 years). Comparisons focused on the top and bottom 50% and 10% of household income distribution. Of the 21 807 individuals included, 53.3% were female, and mean age was 54 ± 11 years. Cardiovascular disease, stroke, ischemic heart disease, hypertension, diabetes, obesity and physical inactivity were associated with lower socioeconomic status, while smoking was associated with higher status; number of medical visits and psychological distress showed no association. When present, inequality was greater at the extremes of income distribution. The results reveal an association between morbidity, lifestyle and socioeconomic status. They also suggest that besides improved access to effective medical intervention, there is a need for a comprehensive strategy for health promotion and disease prevention that takes account of individual, cultural and socioeconomic characteristics. Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  5. Association between periodontal disease and pregnancy outcomes.

    PubMed

    Soroye, M; Ayanbadejo, P; Savage, K; Oluwole, A

    2015-12-01

    To evaluate the association between periodontal disease and pregnancy outcomes like preterm birth and low birth weight. Interviewer-administered questionnaires were completed by the subjects who attended the antenatal clinic of the Lagos University Teaching Hospital, Lagos. Information obtained included; maternal age, gestational age, marital status, educational status, occupation and expected date of delivery. After delivery, the questionnaire was completed with baby's weight at birth and the actual date of delivery. Clinical assessment of the periodontium was done using Oral Hygiene Index (OHI) and Community Periodontal Index of Treatment Needs (CPITN). Participants were divided into three groups: Test, Control I and Control II groups. Scaling and polishing were done for all patients with periodontal disease before (Test group) and after delivery (Control I). All Control II participants (those without periodontal disease) were given Oral hygiene instructions. Descriptive and comparative analyses were done using Epi info version 2008. Four hundred and fifty women received the questionnaire but the response rate was 94%, giving an actual sample size of 423 participants. Maternal age range was between 18 and 34 years with mean age of 29.67 (± 3.37). Gestational age at the point of recruitment was between 10 weeks and 26 weeks with mean of 23.34 (± 4.05). The prevalence of periodontal disease among the study group was 33.38%. About 71% of the participants attained tertiary level of education; only 0.7% had no formal education. There was 9.9% use of alcohol among the participants. The mean oral hygiene score for the participants was 1.94 (± 1.31). The prevalences for preterm deliveries, low birth weight and spontaneous abortion were 12.5%, 12.1% and 1.42% respectively. This study confirms periodontal disease as a probable risk for adverse pregnancy outcomes such as preterm delivery and low birth weight. Therefore, health workers should be encouraged to promote good

  6. Association of central blood pressure and cardiovascular diseases in diabetic patients with hypertension.

    PubMed

    Yang, Lei; Qin, Bo; Zhang, Xiaojuan; Chen, Yanrong; Hou, Jian

    2017-10-01

    To evaluate association of central blood pressure (BP) and cardiovascular disease (CVD) in diabetic patients with hypertension.This was a cross-section study and 360 participants were enrolled. Baseline characteristics were collected and indices of central BP including central systolic/diastolic BP (SBP/DBP), augmentation index adjusted for 75 beats per minute of heart rate (AIx@75) were measured. Participants were separated into with and without CVD groups and between-group differences were assessed. Linear regression analysis was used to evaluate potential risk factors for increased AIx@75. Logistic regression analysis was used to evaluate association between central SBP and AIx@75 with CVD.Mean age was 50.6 years and male participants accounted for 57.8%. Thirty-five and 43 participants had coronary heart disease and ischemic stroke. Compared with participants without CVD, those with CVD were more likely to be male and smokers and had higher glycated hemoglobin level. Additionally, participants with CVD had significantly higher central SBP and AIx@75 compared with those without CVD. Ageing, male gender, and presence of coronary heart disease and ischemic stroke were associated with increased AIx@75, whereas renin-angiotensin-axis inhibitor was associated with reduced AIx@75. After adjusted for traditional risk factors including brachial SBP, both central SBP, and AIx@75 remained significantly associated with CVD, with odds ratio and 95% confidence interval of 1.09 (1.08-1.31) and 1.20 (1.15-1.42), respectively.Diabetic patients with hypertension, ageing, male gender, and presence of CVD are independent risk factors of central BP increase; and increased central SBP and AIx@75 are significantly associated with CVD.

  7. Systemic disease manifestations associated with epilepsy in tuberous sclerosis complex.

    PubMed

    Jeong, Anna; Wong, Michael

    2016-09-01

    Epilepsy is one of the most disabling symptoms of tuberous sclerosis complex (TSC) and is a leading cause of morbidity and mortality in affected individuals. The relationship between systemic disease manifestations and the presence of epilepsy has not been thoroughly investigated. This study utilizes a multicenter TSC Natural History Database including 1,816 individuals to test the hypothesis that systemic disease manifestations of TSC are associated with epilepsy. Univariate analysis was used to identify patient characteristics (e.g., age, gender, race, and TSC mutation status) associated with the presence of epilepsy. Individual logistic regression models were built to examine the association between epilepsy and each candidate systemic or neurologic disease variable, controlling for the patient characteristics found to be significant on univariate analysis. Finally, a multivariable logistic regression model was constructed, using the variables found to be significant on the individual analyses as well as the patient characteristics that were significant on univariate analysis. Nearly 88% of our cohort had a history of epilepsy. After adjusting for age, gender, and TSC mutation status, multiple systemic disease manifestations including cardiac rhabdomyomas (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.3-3.9, p = 0.002), retinal hamartomas (OR 2.1, CI 1.0-4.3, p = 0.04), renal cysts (OR 2.1, CI 1.3-3.4, p = 0.002), renal angiomyolipomas (OR 3.0, CI 1.8-5.1, p < 0.001), shagreen patches (OR 1.7, CI 1.0-2.7, p = 0.04), and facial angiofibromas (OR 1.7, CI 1.1-2.9, p = 0.03) were associated with a higher likelihood of epilepsy. In the multivariable logistic regression model, cardiac rhabdomyomas (OR 1.9, CI 1.0-3.5, p = 0.04) remained significantly associated with the presence of epilepsy. The identification of systemic disease manifestations such as cardiac rhabdomyomas that confer a higher risk of epilepsy development in TSC could contribute to disease

  8. Is diverticular disease associated with colonic malignancy?

    PubMed

    Ekbom, Anders

    2012-01-01

    Colon cancer and diverticular disease have common characteristics; there are increases in the incidences in both disease entities and these diseases are more common in the westernized world. There is also an increase in the age-specific incidence with advancing age. Similar dietary features have been implicated for both diseases and already during the 1960s it was postulated by Burkitt that there is an association. Observational studies initially were able to demonstrate that patients with a history of diverticular disease of the colon had an increased risk of colon cancer, especially in the left side. However, the results from these studies have not been consistent, and problems like selection bias and confounding by indication have been major drawbacks in order to interpret the results and infer causality. Recent studies, which have had a better assessment of diverticular disease by new diagnostic methods, do not support such an association to the same extent as previously. Moreover, surveillance bias has become an increasing problem as patients with diverticular disease of the colon are subjected to a higher diagnostic intensity than other individuals in a population-based setting. A critical evaluation of the studies published so far therefore clearly indicates that the proposed association between diverticular disease and colonic malignancy is not evidence based, which should have an impact on clinical practice as well as on how to deal with these patient groups within the realms of a screening program. Copyright © 2012 S. Karger AG, Basel.

  9. Age- and disease-dependent increase of the mitophagy marker phospho-ubiquitin in normal aging and Lewy body disease.

    PubMed

    Hou, Xu; Fiesel, Fabienne C; Truban, Dominika; Castanedes Casey, Monica; Lin, Wen-Lang; Soto, Alexandra I; Tacik, Pawel; Rousseau, Linda G; Diehl, Nancy N; Heckman, Michael G; Lorenzo-Betancor, Oswaldo; Ferrer, Isidre; Arbelo, José M; Steele, John C; Farrer, Matthew J; Cornejo-Olivas, Mario; Torres, Luis; Mata, Ignacio F; Graff-Radford, Neill R; Wszolek, Zbigniew K; Ross, Owen A; Murray, Melissa E; Dickson, Dennis W; Springer, Wolfdieter

    2018-06-27

    Although exact causes of Parkinson disease (PD) remain enigmatic, mitochondrial dysfunction is increasingly appreciated as a key determinant of dopaminergic neuron susceptibility in both familial and sporadic PD. Two genes associated with recessive, early-onset PD encode the ubiquitin (Ub) kinase PINK1 and the E3 Ub ligase PRKN/PARK2/Parkin, which together orchestrate a protective mitochondrial quality control (mitoQC) pathway. Upon stress, both enzymes cooperatively identify and decorate damaged mitochondria with phosphorylated poly-Ub (p-S65-Ub) chains. This specific label is subsequently recognized by autophagy receptors that further facilitate mitochondrial degradation in lysosomes (mitophagy). Here, we analyzed human post-mortem brain specimens and identified distinct pools of p-S65-Ub-positive structures that partially colocalized with markers of mitochondria, autophagy, lysosomes and/or granulovacuolar degeneration bodies. We further quantified levels and distribution of the 'mitophagy tag' in 2 large cohorts of brain samples from normal aging and Lewy body disease (LBD) cases using unbiased digital pathology. Somatic p-S65-Ub structures independently increased with age and disease in distinct brain regions and enhanced levels in LBD brain were age- and Braak tangle stage-dependent. Additionally, we observed significant correlations of p-S65-Ub with LBs and neurofibrillary tangle levels in disease. The degree of co-existing p-S65-Ub signals and pathological PD hallmarks increased in the pre-mature stage, but decreased in the late stage of LB or tangle aggregation. Altogether, our study provides further evidence for a potential pathogenic overlap among different forms of PD and suggests that p-S65-Ub can serve as a biomarker for mitochondrial damage in aging and disease.

  10. Association of GSK3B With Alzheimer Disease and Frontotemporal Dementia

    PubMed Central

    Schaffer, Barbara A. J.; Bertram, Lars; Miller, Bruce L.; Mullin, Kristina; Weintraub, Sandra; Johnson, Nancy; Bigio, Eileen H.; Mesulam, Marsel; Wiedau-Pazos, Martina; Jackson, George R.; Cummings, Jeffrey L.; Cantor, Rita M.; Levey, Allan I.; Tanzi, Rudolph E.; Geschwind, Daniel H.

    2009-01-01

    Background Deposits of abnormally hyperphosphorylated tau are a hallmark of several dementias, including Alzheimer disease (AD), and about 10% of familial frontotemporal dementia (FTD) cases are caused by mutations in the tau gene. As a known tau kinase, GSK3B is a promising candidate gene in the remaining cases of FTD and in AD, for which tau mutations have not been found. Objective To examine the promoter of GSK3B and all 12 exons, including the surrounding intronic sequence, in patients with FTD, patients with AD, and aged healthy subjects to identify single-nucleotide polymorphisms associated with disease. Design, Setting, and Participants Single-nucleotide polymorphism frequency was examined in a case-control cohort of 48 patients with probable AD, 102 patients with FTD, 38 patients with primary progressive aphasia, and 85 aged healthy subjects. Results were followed up in 2 independent AD family samples consisting of 437 multiplex families with AD (National Institute of Mental Health Genetics Initiative AD Study) or 150 sibships discordant for AD (Consortium on Alzheimer’s Genetics Study). Results Several rare sequence variants in GSK3B were identified in the case-control study. An intronic polymorphism (IVS2−68G>A) occurred at more than twice the frequency among patients with FTD (10.8%) and patients with AD (14.6%) than in aged healthy subjects (4.1%). The polymorphism showed association with disease in both follow-up samples independently, although only the Consortium on Alzheimer’s Genetics sample showed the same direction of association as the case-control sample. Conclusions To our knowledge, this is the first evidence that a gene known to be involved in tau phosphorylation, GSK3B, is associated with risk for primary neurodegenerative dementias. This supports previous work in animal models suggesting that such genes are therapeutic targets. PMID:18852354

  11. Myelin content changes in probable Alzheimer's disease and mild cognitive impairment: Associations with age and severity of neuropsychiatric impairment.

    PubMed

    Kavroulakis, Eleftherios; Simos, Panagiotis G; Kalaitzakis, Georgios; Maris, Thomas G; Karageorgou, Dimitra; Zaganas, Ioannis; Panagiotakis, Simeon; Basta, Maria; Vgontzas, Alexandros; Papadaki, Efrosini

    2018-05-01

    Existing indices of white matter integrity such as fractional anisotropy and magnetization transfer ratio may not provide optimal specificity to myelin content. In contrast, myelin water fraction (MWF) derived from the multiecho T 2 relaxation time technique may serve as a more direct measure of myelin content. The goal of the present study was to identify markers of regional demyelination in patients with probable Alzheimer's disease (AD) and mild cognitive impairment (MCI) in relation to age and severity of neuropsychiatric impairment. The sample included patients diagnosed with probable AD (n = 25) or MCI (n = 43), and cognitively intact elderly controls (n = 33). Long T 2 , short T 2 , and MWF values were measured with a 1.5T scanner in periventricular and deep normal-appearing white matter (NAWM), serving as indices of intra/extracellular water content and myelin content. A comprehensive neuropsychological and neuropsychiatric assessment was administered to all participants. AD patients displayed higher age-adjusted long and short T 2 values and reduced MWF values in left temporal/parietal and bilateral periventricular NAWM than controls and MCI patients (P < 0.004; one-way analysis of covariance [ANCOVA] tests). Short T 2 /MWF values in temporal, frontal, and periventricular NAWM of controls and/or MCI patients were significantly associated with episodic and semantic memory performance and depressive symptomatology (P < 0.004; partial correlation indices). The impact of age on memory performance was significantly (P < 0.01; mediated linear regression analyses) mediated by age-related changes in short T 2 and MWF values in these regions. Age-related demyelination is associated with memory impairment (especially in prodromal dementia states) and symptoms of depression in an anatomically specific manner. 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1359-1372. © 2017 International Society for Magnetic Resonance in Medicine.

  12. Environmental stress, ageing and glial cell senescence: a novel mechanistic link to Parkinson’s disease?

    PubMed Central

    Chinta, Shankar J; Lieu, Christopher A; DeMaria, Marco; Laberge, Remi-Martin; Campisi, Judith; Andersen, Julie K

    2013-01-01

    Exposure to environmental toxins is associated with a variety of age-related diseases including cancer and neurodegeneration. For example, in Parkinson’s disease (PD), chronic environmental exposure to certain toxins has been linked to the age-related development of neuropathology. Neuronal damage is believed to involve the induction of neuroinflammatory events as a consequence of glial cell activation. Cellular senescence is a potent anti-cancer mechanism that occurs in a number of proliferative cell types and causes the arrest of proliferation of cells at risk of malignant transformation following exposure to potentially oncogenic stimuli. With age, senescent cells accumulate and express a senescence-associated secretory phenotype (SASP; i.e. the robust secretion of many inflammatory cytokines, growth factors and proteases). Whereas cell senescence in peripheral tissues has been causally linked to a number of age-related pathologies, little is known about the induction of cellular senescence and the SASP in the brain. Based on recently reported findings, we propose that environmental stressors associated with PD may act in part by eliciting senescence and the SASP within non-neuronal glial cells in the ageing brain, thus contributing to the characteristic decline in neuronal integrity that occurs in this disorder. PMID:23600398

  13. A Disease or Not a Disease? Aging As a Pathology.

    PubMed

    Gladyshev, Timothy V; Gladyshev, Vadim N

    2016-12-01

    The debate on the relationship between aging and disease is centered on whether aging is a normal/natural/physiological process or it represents a pathology. Considering this relationship from medical, molecular, social, and historical perspectives, we argue that aging is neither a disease, nor a non-disease. Instead, it combines all age-related diseases and their preclinical forms, in addition to other pathological changes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Is complexity of work associated with risk of dementia? The Canadian Study of Health And Aging.

    PubMed

    Kröger, Edeltraut; Andel, Ross; Lindsay, Joan; Benounissa, Zohra; Verreault, René; Laurin, Danielle

    2008-04-01

    The authors evaluated the association of complexity of work with data, people, and things with the incidence of dementia, Alzheimer's disease, and vascular dementia in the Canadian Study of Health and Aging, while adjusting for work-related physical activity. The Canadian Study of Health and Aging is a 10-year population study, from 1991 to 2001, of a representative sample of persons aged 65 years or older. Lifetime job history allowed application of complexity scores and classification of work-related physical activity. Analyses included 3,557 subjects, of whom 400 were incident dementia cases, including 299 with Alzheimer's disease and 93 with vascular dementia. In fully adjusted Cox regression models, high complexity of work with people or things reduced risk of dementia (hazard ratios were 0.66 (95% confidence interval: 0.44, 0.98) and 0.72 (95% confidence interval: 0.52, 0.99), respectively) but not Alzheimer's disease. For vascular dementia, hazard ratios were 0.36 (95% confidence interval: 0.15, 0.90) for high complexity of work with people and 0.50 (95% confidence interval: 0.25, 1.00) for high complexity of work with things. Subgroup analyses according to median duration (23 years) of principal occupation showed that associations with complexity varied according to duration of employment. High complexity of work appears to be associated with risk of dementia, but effects may vary according to subtype.

  15. Age, Predisposing Diseases, and Ultrasonographic Findings in Determining Clinical Outcome of Acute Acalculous Inflammatory Gallbladder Diseases in Children

    PubMed Central

    2016-01-01

    We evaluated clinical factors such as age, gender, predisposing diseases and ultrasonographic findings that determine clinical outcome of acute acalculous inflammatory gallbladder diseases in children. The patients were divided into the four age groups. From March 2004 through February 2014, clinical data from 131 children diagnosed as acute acalculous inflammatory gallbladder disease by ultrasonography were retrospectively reviewed. Systemic infectious diseases were the most common etiology of acute inflammatory gallbladder disease in children and were identified in 50 patients (38.2%). Kawasaki disease was the most common predisposing disease (28 patients, 21.4%). The incidence was highest in infancy and lowest in adolescence. The age groups were associated with different predisposing diseases; noninfectious systemic disease was the most common etiology in infancy and early childhood, whereas systemic infectious disease was the most common in middle childhood and adolescence (P = 0.001). Gallbladder wall thickening was more commonly found in malignancy (100%) and systemic infection (94.0%) (P = 0.002), whereas gallbladder distension was more frequent in noninfectious systemic diseases (60%) (P = 0.000). Ascites seen on ultrasonography was associated with a worse clinical course compared with no ascites (77.9% vs. 37.7%, P = 0.030), and the duration of hospitalization was longer in patients with ascites (11.6 ± 10.7 vs. 8.0 ± 6.6 days, P = 0.020). In conclusion, consideration of age and predisposing disease in addition to ultrasonographic gallbladder findings in children suspected of acute acalculous inflammatory gallbladder disease might result in better outcomes. PMID:27550491

  16. [Prevalence of severe periodontal disease and its association with respiratory disease in hospitalized adult patients in a tertiary care center].

    PubMed

    Fernández-Plata, Rosario; Olmedo-Torres, Daniel; Martínez-Briseño, David; García-Sancho, Cecilia; Franco-Marina, Francisco; González-Cruz, Herminia

    2015-01-01

    Severe periodontal disease is a chronic inflammatory gingival process associated with systemic diseases. To determine the prevalence of severe periodontal disease and its association with respiratory diseases among hospitalized patients at the Institute of Respiratory Diseases "Ismael Cosio Villegas" (INER) in 2011. A cross-sectional study was developed. The severe periodontal disease was diagnosed by the Department of Stomatology. The International Classification of Diseases 10th revision was used. A multinomial logistic was fit to estimate relative-risk. Three thousand and fifty-nine patients were included; 772/3,059 (25.2%) had severe periodontal disease. After controlling for age, sex, inpatient days, death, and socioeconomic status, the infectious respiratory diseases that were significantly associated with severe periodontal disease were: HIV/AIDS (RR: 10.6; 95% CI: 9.1-23.3; p < 0.0001); pneumonia (RR: 2.6; 95% CI: 2.2-5.7; p < 0.0001); pulmonary tuberculosis and its sequels (RR: 2.1; 95% CI: 1.6-4.9; p < 0.0001); and lung abscess (RR: 2.6; 95% CI: 1.6-7.8; p = 0.002). Lung cancer and pleural diseases were also significantly associated with severe periodontal disease. High prevalence of severe periodontal disease was observed in the different respiratory diseases. Severe periodontal disease was associated with both infectious and non-infectious respiratory diseases. It is important to study an oral health intervention.

  17. A 2-d classification of diseases based on age-specific death rates

    NASA Astrophysics Data System (ADS)

    Richmond, Peter; Roehner, Bertrand M.

    2018-02-01

    Age specific mortality curves exhibit an age tc (about 10 years) which plays a crucial role in that the mortality curve decreases hyperbolically in the age interval A before tc and increases exponentially in the interval B following tc. For those familiar with reliability theory, region A is called the "burn in" phase and B is the "wear out" phase. Using the exponents of the hyperbolic and exponential phases, we introduce a new 2 dimensional map of diseases. This permits the classification of diseases into three broad classes: AS1, AS2 and S. Class AS1 includes all diseases arising from congenital malformations which dominate infant and child mortality; class AS2 includes degenerative diseases such as dementia and Alzheimer's which dominate old age mortality. In class S, which includes most infectious and metabolic diseases, the exponents from both aging phases contribute to positions on the map. Cancer is one of these mixed cases but is closer to class AS2 than AS1. A second line classification is needed to resolve S cases and to this end we introduce a 3rd dimension, namely (calendar) time. Using historical data we show that in their response to treatment (particularly vaccination), S diseases fall into three sub-classes. (i) Class E diseases (e.g. measles or meningococcal disease) which have been almost eliminated at all ages (ii) class C diseases (e.g. tuberculosis) which can be cured but whose cure becomes less effective at old age. (iii) Class U diseases for which radical cures are still unknown. Regarding the future, the fact that the wear-out process of numerous diseases already starts around the age of 25 means that a major extension of the human lifespan beyond 120 certainly also requires to uncover the secret of the "elixir of eternal youth" which has driven timeless human efforts and still seems unlikely in the foreseeable future.

  18. Association between rheumatic diseases and cancer: results from a clinical practice cohort study.

    PubMed

    Bellan, Mattia; Boggio, Enrico; Sola, Daniele; Gibbin, Antonello; Gualerzi, Alessandro; Favretto, Serena; Guaschino, Giulia; Bonometti, Ramona; Pedrazzoli, Roberta; Pirisi, Mario; Sainaghi, Pier Paolo

    2017-08-01

    The association between cancer and immune-mediated rheumatic conditions is controversial, especially as far as polymyalgia rheumatica (PMR) is concerned. Furthermore, no clinical feature has been shown to be suggestive of a paraneoplastic rheumatic syndrome. With the present study, we aim to address both these issues. The study population comprised N = 1750 patients, including N = 100 with PMR, who attended our tertiary immuno-rheumatology clinic between January 1, 2005 and November 30, 2012. A rheumatic disease was deemed paraneoplastic if cancer had been diagnosed in the 2 years preceding or following its onset. The probability of a significant association between a specific rheumatic disease and cancer was evaluated by computing the odds ratio (OR): N = 702 patients with osteoarthritis serving as controls. Furthermore, clinical features distinguishing paraneoplastic rheumatic diseases were searched for by univariate and multivariate analysis. Sjogren's syndrome (SS) [OR 3.6 (CI 95% 1.7-7.5)], PMR (OR 5.1 CI 95% 2.9-8.9), dermatomyositis/polymyositis [OR 12.09 (CI 95% 2.6-55.8)] and vasculitis [OR 3.70 (CI 95% 1.81-7.52)] are associated with cancer. At multivariate analysis, older age is associated with cancer among SS patients (p = 0.03), while in the PMR group, older age, male gender, and ≥6 tender joints are independent predictors of paraneoplastic PMR (p < 0.0004). Cancer frequently either heralds or follows rheumatic manifestations, including PMR. Older age, male gender and a more extensive joint involvement should be considered red flags for paraneoplastic PMR.

  19. No Association Between CALHM1 Variation and Risk of Alzheimer Disease

    PubMed Central

    Minster, Ryan L.; Demirci, F. Yesim; DeKosky, Steven T.; Kamboh, M. Ilyas

    2010-01-01

    A polymorphism in the calcium homeostasis modulator 1 gene (CALHM1) has recently been associated with risk of late-onset Alzheimer disease. We examined this variant (rs2986017) in 945 Caucasian Americans with late-onset Alzheimer disease and 875 age-matched Caucasian American controls. No association with risk of late-onset Alzheimer disease (p = 0.368 for genotypes; p = 0.796 for alleles) was observed in our sample. However, a potential modest association of minor allele homozygosity (TT) with an earlier age-at-onset was seen (p = 0.034). PMID:19191331

  20. No association between CALHM1 variation and risk of Alzheimer disease.

    PubMed

    Minster, Ryan L; Demirci, F Yesim; DeKosky, Steven T; Kamboh, M Ilyas

    2009-04-01

    A polymorphism in the calcium homeostasis modulator 1 gene (CALHM1) has recently been associated with risk of late-onset Alzheimer disease. We examined this variant (rs2986017) in 945 Caucasian Americans with late-onset Alzheimer disease and 875 age-matched Caucasian American controls. No association with risk of late-onset Alzheimer disease (p=0.368 for genotypes; p=0.796 for alleles) was observed in our sample. However, a potential modest association of minor allele homozygosity (TT) with an earlier age-at-onset was seen (p=0.034). (c) 2009 Wiley-Liss, Inc.

  1. Perceptions of competence: age moderates views of healthy aging and Alzheimer's disease.

    PubMed

    Berry, Jane M; Williams, Helen L; Thomas, Kevin D; Blair, Jamie

    2015-01-01

    BACKGROUND/STUDY CONTEXT: Older adults have more complex and differentiated views of aging than do younger adults, but less is known about age-related perceptions of Alzheimer's disease. This study investigated age-related perceptions of competence of an older adult labeled as "in good health" (healthy) or "has Alzheimer's disease" (AD), using a person-perception paradigm. It was predicted that older adults would provide more differentiated assessments of the two targets than would younger adults. Younger (n=86; 18-36 years) and older (n=66; 61-95 years) adults rated activities of daily living (ADL), instrumental activities of daily living (IADL), and memory abilities of a female target aged 75 years, described as healthy or with AD. Data on anxiety about aging, knowledge of and experience with aging and AD, knowledge of memory aging, and positive and negative biases toward aging and AD were also collected. Older adults perceived the healthy target as more capable of cognitively effortful activities (e.g., managing finances) and as possessing better memory abilities than the AD target. As predicted, these differences were greater than differences between targets perceived by younger adults. The interaction effect remained significant after statistically controlling for relevant variables, including education and gender. Additionally, exploratory analyses revealed that older adults held less positively biased views of AD than younger adults, but negatively biased views were equivalent between age groups. The results demonstrate that mere labels of "healthy" and "Alzheimer's disease" produce significant and subtle age differences in perceived competencies of older adults, and that biases towards AD vary by age group and valence. Our findings extend the person-perception paradigm to an integrative analysis of aging and AD, are consistent with models of adult development, and complement current research and theory on stereotypes of aging. Future directions for research

  2. Associations between labial and whole salivary flow rates, systemic diseases and medications in a sample of older people.

    PubMed

    Smidt, Dorte; Torpet, Lis Andersen; Nauntofte, Birgitte; Heegaard, Karen Margrethe; Pedersen, Anne Marie Lynge

    2010-10-01

    To investigate the associations between age, gender, systemic diseases, medications and labial and whole salivary flow rates in older people. Unstimulated labial (LS) and unstimulated (UWS) and chewing-stimulated (SWS) whole salivary flow rates were measured in 389 randomly selected community-dwelling Danish women and 279 men aged 65-97 years. Systemic diseases, medications (coded according to the Anatomical Therapeutic Chemical (ATC) Classification System), tobacco and alcohol consumption were registered. The number of diseases and medications was higher and UWS lower in the older age groups. On average, women were slightly older, had more diseases, higher medication intake and lower UWS, SWS and LS than men. High number of diseases and medications was associated with low UWS, SWS and LS. In the healthy (14%) and nonmedicated (19%) participants, flow rates were not associated with age and gender, apart from SWS being lower in nonmedicated women. Low UWS were associated with psychiatric and respiratory disorders, type 2 diabetes and intake of psycholeptics, psychoanaleptics (especially SRRIs), respiratory agents, oral antidiabetics (particularly sulfonylureas), magnesium-hydroxide, cardiac agents, quinine, thiazides, calcium channel blockers, statins, urinary antispasmodics, glucosamine, NSAIDs, opioids and ophthalmologicals. SWS were lower in participants with ophthalmological disorders using ophthalmologicals (especially antiglaucoma agents and miotics), but also in those taking antidepressants, cardiac agents (mostly digitalis glycosides) and calcium channel blockers. Cardiovascular diseases and intake of anti-thrombotics (mainly low dose aspirins), calcium channel blockers and oral antidiabetics were associated with low LS. In older people, low salivary flow rates are associated with specific and high number of diseases and medications, but neither with age and gender per se nor with tobacco and alcohol consumption. Low UWS are associated with more diseases and

  3. Sex differences in the effect of aging on dry eye disease.

    PubMed

    Ahn, Jong Ho; Choi, Yoon-Hyeong; Paik, Hae Jung; Kim, Mee Kum; Wee, Won Ryang; Kim, Dong Hyun

    2017-01-01

    Aging is a major risk factor in dry eye disease (DED), and understanding sexual differences is very important in biomedical research. However, there is little information about sex differences in the effect of aging on DED. We investigated sex differences in the effect of aging and other risk factors for DED. This study included data of 16,824 adults from the Korea National Health and Nutrition Examination Survey (2010-2012), which is a population-based cross-sectional survey. DED was defined as the presence of frequent ocular dryness or a previous diagnosis by an ophthalmologist. Basic sociodemographic factors and previously known risk factors for DED were included in the analyses. Linear regression modeling and multivariate logistic regression modeling were used to compare the sex differences in the effect of risk factors for DED; we additionally performed tests for interactions between sex and other risk factors for DED in logistic regression models. In our linear regression models, the prevalence of DED symptoms in men increased with age ( R =0.311, P =0.012); however, there was no association between aging and DED in women ( P >0.05). Multivariate logistic regression analyses showed that aging in men was not associated with DED (DED symptoms/diagnosis: odds ratio [OR] =1.01/1.04, each P >0.05), while aging in women was protectively associated with DED (DED symptoms/diagnosis: OR =0.94/0.91, P =0.011/0.003). Previous ocular surgery was significantly associated with DED in both men and women (men/women: OR =2.45/1.77 [DED symptoms] and 3.17/2.05 [DED diagnosis], each P <0.001). Tests for interactions of sex revealed significantly different aging × sex and previous ocular surgery × sex interactions ( P for interaction of sex: DED symptoms/diagnosis - 0.044/0.011 [age] and 0.012/0.006 [previous ocular surgery]). There were distinct sex differences in the effect of aging on DED in the Korean population. DED following ocular surgery also showed sexually different

  4. Association Between Atopic Disease and Anemia in US Children.

    PubMed

    Drury, Kerry E; Schaeffer, Matt; Silverberg, Jonathan I

    2016-01-01

    Atopic disease is associated with chronic inflammation, food allergen avoidance, and use of systemic immunosuppressant medications. All these factors have been shown to be associated with anemia. To investigate whether atopic disease is associated with increased risk of childhood anemia. A cross-sectional survey and laboratory assessment were conducted using data from the 1997-2013 US National Health Interview Survey (NHIS) that included 207,007 children and adolescents and the 1999-2012 National Health and Nutrition Examination Survey (NHANES) that included 30,673 children and adolescents. Analysis of the data was conducted between August 1, 2014, and August 28, 2015. Caregiver-reported history of eczema, asthma, hay fever, and/or food allergy. Anemia was defined by caregiver report in the NHIS and by hemoglobin levels for age and sex in the NHANES. Data were collected on 207,007 children and adolescents from NHIS, representing all pediatric age, sex, racial/ethnic, household educational level, and income groups. The US prevalence was 9.5% (95% CI, 9.4%-9.7%) from all years of the NHIS for health care-diagnosed eczema, 12.8% (95% CI, 12.6%-13.0%) for asthma, 17.1% (95% CI, 16.9%-17.3%) for hay fever, 4.2% (95% CI, 4.1%-4.3%) for food allergy, and 1.1% (95% CI, 1.1%-1.2%) for anemia. In multivariable logistic regression models controlling for age, sex, race/ethnicity, annual household income, highest educational level in the family, insurance coverage, number of persons in the household, birthplace in the United States, and history of asthma, hay fever, and food allergy, anemia was associated with eczema in 14 of 17 studies, asthma in 11, hay fever in 12, and food allergy in 12. In multivariable analysis across the NHIS (with results reported as adjusted odds ratios [95% CIs]), children with any eczema (1.83; 1.58-2.13), asthma (1.31; 1.14-1.51), hay fever (1.57; 1.36-1.81), and food allergy (2.08; 1.71-2.52) had higher odds of anemia (P < .001 for all). In the

  5. Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer

    PubMed Central

    Farrell, James J; Zhang, Lei; Zhou, Hui; Chia, David; Elashoff, David; Akin, David; Paster, Bruce J; Joshipura, Kaumudi; Wong, David T W

    2012-01-01

    Objective The associations between oral diseases and increased risk of pancreatic cancer have been reported in several prospective cohort studies. In this study, we measured variations of salivary microbiota and evaluated their potential associations with pancreatic cancer and chronic pancreatitis. Methods This study was divided into three phases: (1) microbial profiling using the Human Oral Microbe Identification Microarray to investigate salivary microbiota variation between 10 resectable patients with pancreatic cancer and 10 matched healthy controls, (2) identification and verification of bacterial candidates by real-time quantitative PCR (qPCR) and (3) validation of bacterial candidates by qPCR on an independent cohort of 28 resectable pancreatic cancer, 28 matched healthy control and 27 chronic pancreatitis samples. Results Comprehensive comparison of the salivary microbiota between patients with pancreatic cancer and healthy control subjects revealed a significant variation of salivary microflora. Thirty-one bacterial species/clusters were increased in the saliva of patients with pancreatic cancer (n=10) in comparison to those of the healthy controls (n=10), whereas 25 bacterial species/clusters were decreased. Two out of six bacterial candidates (Neisseria elongata and Streptococcus mitis) were validated using the independent samples, showing significant variation (p<0.05, qPCR) between patients with pancreatic cancer and controls (n=56). Additionally, two bacteria (Granulicatella adiacens and S mitis) showed significant variation (p<0.05, qPCR) between chronic pancreatitis samples and controls (n=55). The combination of two bacterial biomarkers (N elongata and S mitis) yielded a receiver operating characteristic plot area under the curve value of 0.90 (95% CI 0.78 to 0.96, p<0.0001) with a 96.4% sensitivity and 82.1% specificity in distinguishing patients with pancreatic cancer from healthy subjects. Conclusions The authors observed associations between

  6. Deregulation of CRTCs in Aging and Age-related Disease Risk

    PubMed Central

    Escoubas, Caroline C.; Silva-García, Carlos G.; Mair, William B.

    2017-01-01

    Advances in public health in the last century have seen a sharp increase in human life expectancy. With these changes have come increased incidence of age-related pathologies and health burdens in the elderly. Patient age is the biggest risk factor for multiple chronic conditions that often occur simultaneously within one individual. An alternative to disease centric therapeutic approaches is that of ‘geroscience’, which aims to define molecular mechanisms that link age to overall disease risk. One such mechanism is deregulation of CREB-regulated transcriptional coactivators, CRTCs. Initially identified for their role in modulating CREB transcription, the last five years has seen an expansion in knowledge of new cellular regulators and roles of CRTCs beyond CREB. CRTCs have been shown to modulate organismal aging in C. elegans and to impact age-related diseases in humans. Here, we discuss CRTC deregulation as a new driver of aging, and integrating link between age and disease risk. PMID:28365140

  7. Association between allergic disease, sleep-disordered breathing, and childhood nocturnal enuresis: a population-based case-control study.

    PubMed

    Tsai, Jeng-Dau; Chen, Hsuan-Ju; Ku, Min-Sho; Chen, Shan-Ming; Hsu, Chih-Chuan; Tung, Min-Che; Lin, Che-Chen; Chang, Hsing-Yi; Sheu, Ji-Nan

    2017-12-01

    Little is known about the associations between allergic disease, sleep-disordered breathing (SDB), and childhood nocturnal enuresis (NE). We examined whether allergic disease and SDB were associated with childhood NE. Data were assessed from the 2007-2012 Taiwan National Health Insurance Research Database. We enrolled 4308 children aged 5-18 years having NE diagnosis and age- and sex-matched 4308 children as the control group. The odds ratios of NE were calculated to determine an association with preexisting allergic disease and SDB. A total of 8616 children were included in the analysis. Prevalence of allergic diseases and SDB was significantly higher for the NE group than the control group (all p < 0.001). After adjusting odds ratios for potential confounding factors, except asthma, children with allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and obstructive sleep apnea (OSA) had significantly higher odds of NE compared with children never diagnosed. With stratification for sex, girls with allergic rhinitis, atopic dermatitis, allergic conjunctivitis, OSA, and snoring had significantly higher odds of NE, compared with girls never diagnosed. Only boys with allergic rhinitis and OSA were associated with increased odds of NE. With stratification for age, children aged 5-12 years with allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and OSA had significantly higher odds of NE compared with those never diagnosed. Odds of NE increased with the number of comorbid allergic diseases. Allergic diseases and SDB are associated with increased odds of childhood NE. The odds of NE increased with the number of comorbid allergic diseases present.

  8. Cystic neutrophilic granulomatous mastitis associated with Corynebacterium including Corynebacterium kroppenstedtii.

    PubMed

    Johnstone, Kate J; Robson, Jennifer; Cherian, Sarah G; Wan Sai Cheong, Jenny; Kerr, Kris; Bligh, Judith F

    2017-06-01

    Granulomatous (lobular) mastitis is a rare inflammatory breast disease affecting parous reproductive-aged women. Once considered idiopathic, there is growing evidence of an association with corynebacteria infection, especially in the setting of a distinct histological pattern termed cystic neutrophilic granulomatous mastitis (CNGM). We describe 15 cases with histological features either confirming (n = 12) or suggesting (n = 3) CNGM, and concurrent microbiological evidence of Corynebacterium species. The organism was detected by culture or 16S rRNA gene sequencing of specimens obtained at surgery or fine needle aspiration. In seven cases, Gram-positive organisms were seen within vacuolated spaces. Speciation was performed in nine cases, with Corynebacterium kroppenstedtii subsequently identified. These cases provide further evidence in support of this association and in doing so highlight the importance of recognising these histological clues as well as the limitations of Gram stain and microbiological culture in detecting this previously under-recognised disease process. Copyright © 2017 Royal College of Pathologists of Australasia. All rights reserved.

  9. Association of chronic obstructive pulmonary disease and hemorrhoids

    PubMed Central

    Lin, Lih-Hwa; Siu, Justin Ji-Yuen; Liao, Po-Chi; Chiang, Jen-Huai; Chou, Pei-Chi; Chen, Huey-Yi; Ho, Tsung-Jung; Tsai, Ming-Yen; Chen, Yung-Hsiang; Chen, Wen-Chi

    2017-01-01

    Abstract According to traditional Chinese medicine (TCM) theory, a specific physiological and pathological relationship exists between the lungs and the large intestine. The aim of this study is to delineate the association of chronic obstructive pulmonary disease (COPD) and hemorrhoids in order to verify the “interior–exterior” relationship between the lungs and the large intestine. A retrospective cohort study is conceived from the National Health Insurance Research Database, Taiwan. The 2 samples (COPD cohort and non-COPD cohort) were selected from the 2000 to 2003 beneficiaries of the NHI, representing patients age 20 and older in Taiwan, with the follow-up ending on December 31, 2011. The COPD cohort (n = 51,506) includes every patient newly diagnosed as having Chronic Obstructive Pulmonary Disease (COPD, ICD-9-CM: 490–492, 494, 496), who have made at least 2 confirmed visits to the hospital/clinic. The non-COPD cohort (n = 103,012) includes patients without COPD and is selected via a 1:2 (COPD: non-COPD) matching by age group (per 5 years), gender, and index date (diagnosis date of COPD for the COPD cohort). Compared with non-COPD cohorts, patients with COPD have a higher likelihood of having hemorrhoids and the age-, gender- and comorbidies-adjusted hazard ratio (HR) for hemorrhoids is 1.56 (95% confidence intervals [CI]:1.50–1.62). The adjusted HR of hemorrhoids for females is 0.79 (95% CI: 0.77–0.83), which is significantly less than that for males. The elderly groups, 40 to 59 years and aged 60 or above, have higher adjusted HRs than younger age groups (20–39 years), 1.19 (95% CI: 1.14–1.26), and 1.18 (95% CI: 1.12–1.24), respectively. Patients with COPD may have a higher likelihood to have hemorrhoids in this retrospective cohort study. This study verifies the fundamental theorem of TCM that there is a definite pathogenic association between the lungs and large intestine. PMID:28272246

  10. Between destiny and disease: genetics and molecular pathways of human central nervous system aging.

    PubMed

    Glorioso, Christin; Sibille, Etienne

    2011-02-01

    Aging of the human brain is associated with "normal" functional, structural, and molecular changes that underlie alterations in cognition, memory, mood and motor function, amongst other processes. Normal aging also imposes a robust constraint on the onset of many neurological diseases, ranging from late onset neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's diseases (PD), to early onset psychiatric disorders, such as bipolar disorder (BPD) and schizophrenia (SCZ). The molecular mechanisms and genetic underpinnings of age-related changes in the brain are understudied, and, while they share some overlap with peripheral mechanisms of aging, many are unique to the largely non-mitotic brain. Hence, understanding mechanisms of brain aging and identifying associated modulators may have profound consequences for the prevention and treatment of age-related impairments and diseases. Here we review current knowledge on age-related functional and structural changes, their molecular and genetic underpinnings, and discuss how these pathways may contribute to the vulnerability to develop age-related neurological diseases. We highlight recent findings from human post-mortem brain microarray studies, which we hypothesize, point to a potential genetically controlled transcriptional program underlying molecular changes and age-gating of neurological diseases. Finally, we discuss the implications of this model for understanding basic mechanisms of brain aging and for the future investigation of therapeutic approaches. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Variant of TREM2 Associated with the Risk of Alzheimer’s Disease

    PubMed Central

    Jonsson, Thorlakur; Stefansson, Hreinn; Steinberg, Stacy; Jonsdottir, Ingileif; Jonsson, Palmi V.; Snaedal, Jon; Bjornsson, Sigurbjorn; Huttenlocher, Johanna; Levey, Allan I.; Lah, James J.; Rujescu, Dan; Hampel, Harald; Giegling, Ina; Andreassen, Ole A.; Engedal, Knut; Ulstein, Ingun; Djurovic, Srdjan; Ibrahim-Verbaas, Carla; Hofman, Albert; Ikram, M. Arfan; van Duijn, Cornelia M; Thorsteinsdottir, Unnur; Kong, Augustine; Stefansson, Kari

    2013-01-01

    BACKGROUND Sequence variants, including the ε4 allele of apolipoprotein E, have been associated with the risk of the common late-onset form of Alzheimer’s disease. Few rare variants affecting the risk of late-onset Alzheimer’s disease have been found. METHODS We obtained the genome sequences of 2261 Icelanders and identified sequence variants that were likely to affect protein function. We imputed these variants into the genomes of patients with Alzheimer’s disease and control participants and then tested for an association with Alzheimer’s disease. We performed replication tests using case–control series from the United States, Norway, the Netherlands, and Germany. We also tested for a genetic association with cognitive function in a population of unaffected elderly persons. RESULTS A rare missense mutation (rs75932628-T) in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2), which was predicted to result in an R47H substitution, was found to confer a significant risk of Alzheimer’s disease in Iceland (odds ratio, 2.92; 95% confidence interval [CI], 2.09 to 4.09; P = 3.42×10−10). The mutation had a frequency of 0.46% in controls 85 years of age or older. We observed the association in additional sample sets (odds ratio, 2.90; 95% CI, 2.16 to 3.91; P = 2.1×10−12 in combined discovery and replication samples). We also found that carriers of rs75932628-T between the ages of 80 and 100 years without Alzheimer’s disease had poorer cognitive function than noncarriers (P = 0.003). CONCLUSIONS Our findings strongly implicate variant TREM2 in the pathogenesis of Alzheimer’s disease. Given the reported antiinflammatory role of TREM2 in the brain, the R47H substitution may lead to an increased predisposition to Alzheimer’s disease through impaired containment of inflammatory processes. (Funded by the National Institute on Aging and others.) PMID:23150908

  12. [Non-pharmacologic therapy of age-related macular degeneration, based on the etiopathogenesis of the disease].

    PubMed

    Fischer, Tamás

    2015-07-12

    It has a great therapeutic significance that the disorder of the vascular endothelium, which supplies the affected ocular structures, plays a major role in the development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfuncition and age-related macular degeneration is accompanied by a general inflammatory response. The vascular wall including those in chorioids may be activated by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic and genetic factors causing a protracted host defence response with a consequent vascular damage, which leads to age-related macular degeneration. Based on this concept, age-related macular degeneration is a local manifestation of the systemic vascular disease. This recognition should have therapeutic implications because restoration of endothelial dysfunction can stabilize the condition of chronic vascular disease including age-related macular degeneration, as well. Restoration of endothelial dysfunction by non-pharmacological or pharmacological interventions may prevent the development or improve endothelial dysfunction resulting in prevention or improvement of age-related macular degeneration. Non-pharmacological interventions which may have beneficial effect in endothelial dysfunction include (1) smoking cessation; (2) reduction of increased body weight; (3) adequate physical activity; (4) appropriate diet (a) proper dose of flavonoids, polyphenols and kurcumin; (b) omega-3 long-chain polyunsaturated fatty acids: docosahexaenoic acid and eicosapentaenoic acid; (c) carotenoids, lutein and zeaxanthins), (d) management of dietary glycemic index, (e) caloric restriction, and (5) elimination of stressful lifestyle. Non-pharmacological interventions should be preferable even if medicaments are also used for the treatment of endothelial dysfunction.

  13. Association between colonic polyps and diverticular disease

    PubMed Central

    Hirata, Tetsuo; Kawakami, Yuko; Kinjo, Nagisa; Arakaki, Susumu; Arakaki, Tetsu; Hokama, Akira; Kinjo, Fukunori; Fujita, Jiro

    2008-01-01

    AIM: To evaluate the association between colonic polyps and diverticular disease in Japan. METHODS: We retrospectively reviewed the medical records of 672 consecutive patients who underwent total colonoscopy between August 2006 and April 2007 at Nishinjo Hospital, Okinawa, Japan. Patients with a history of any of the following were excluded from the study: previous polypectomy, colonic resection, and inflammatory bowel diseases. The association between colonic polyps and diverticular disease was analyzed by logistic regression analysis, adjusted for age and sex. RESULTS: Prevalence of colonic polyps in all patients with diverticular disease was significantly higher than that in those without diverticular disease (adjusted odds ratio 1.7). CONCLUSION: Our data showed that patients with diverticular disease have a higher risk of colonic polyps compared to those without. PMID:18416471

  14. CD4/CD8 ratio, age, and risk of serious non-communicable diseases in HIV-infected adults on antiretroviral therapy

    PubMed Central

    CASTILHO, Jessica L.; SHEPHERD, Bryan E.; KOETHE, John; TURNER, Megan; BEBAWY, Sally; LOGAN, James; ROGERS, William B.; RAFFANTI, Stephen; STERLING, Timothy R.

    2015-01-01

    Objective In virologically suppressed HIV-infected adults, non-communicable diseases (NCDs) have been associated with immune senescence and low CD4/CD8 lymphocyte ratio. Age differences in the relationship between CD4/CD8 ratio and NCDs have not been described. Design Observational cohort study. Methods We assessed CD4/CD8 ratio and incident NCDs (cardiovascular, cancer, liver, and renal diseases) in HIV-infected adults started on antiretroviral therapy between 1998–2012. Study inclusion began once patients maintained virologic suppression for 12 months (defined as baseline). We examined age and baseline CD4/CD8 ratio and used Cox proportional hazard models to assess baseline CD4/CD8 ratio and NCDs. Results This study included 2,006 patients. Low baseline CD4/CD8 ratio was associated with older age, male sex, and low CD4 lymphocyte counts. In models adjusting for CD4 lymphocyte count, CD4/CD8 ratio was inversely associated with age (p <0.01). Among all patients, 182 had incident NCDs, including 46 with coronary artery disease (CAD) events. CD4/CD8 ratio was inversely associated with risk of CAD events (adjusted HR per 0.1 increase in CD4/CD8 ratio = 0.87, 95% CI: 0.76–0.99, p=0.03). This association was driven by those under age 50 years (adjusted HR 0.83 [0.70–0.97], p = 0.02) versus those over age 50 years (adjusted HR = 0.96 [0.79–1.18], p = 0.71). CD4/CD8 ratio was not significantly associated with incident non-cardiac NCDs. Conclusions Higher CD4/CD8 ratio after one year of HIV virologic suppression was independently predictive of decreased CAD risk, particularly among younger adults. Advanced immune senescence may contribute to CAD events in younger HIV patients on antiretroviral therapy. PMID:26959354

  15. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases.

    PubMed

    Franceschi, Claudio; Campisi, Judith

    2014-06-01

    Human aging is characterized by a chronic, low-grade inflammation, and this phenomenon has been termed as "inflammaging." Inflammaging is a highly significant risk factor for both morbidity and mortality in the elderly people, as most if not all age-related diseases share an inflammatory pathogenesis. Nevertheless, the precise etiology of inflammaging and its potential causal role in contributing to adverse health outcomes remain largely unknown. The identification of pathways that control age-related inflammation across multiple systems is therefore important in order to understand whether treatments that modulate inflammaging may be beneficial in old people. The session on inflammation of the Advances in Gerosciences meeting held at the National Institutes of Health/National Institute on Aging in Bethesda on October 30 and 31, 2013 was aimed at defining these important unanswered questions about inflammaging. This article reports the main outcomes of this session. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Large-Scale Discovery of Disease-Disease and Disease-Gene Associations

    PubMed Central

    Gligorijevic, Djordje; Stojanovic, Jelena; Djuric, Nemanja; Radosavljevic, Vladan; Grbovic, Mihajlo; Kulathinal, Rob J.; Obradovic, Zoran

    2016-01-01

    Data-driven phenotype analyses on Electronic Health Record (EHR) data have recently drawn benefits across many areas of clinical practice, uncovering new links in the medical sciences that can potentially affect the well-being of millions of patients. In this paper, EHR data is used to discover novel relationships between diseases by studying their comorbidities (co-occurrences in patients). A novel embedding model is designed to extract knowledge from disease comorbidities by learning from a large-scale EHR database comprising more than 35 million inpatient cases spanning nearly a decade, revealing significant improvements on disease phenotyping over current computational approaches. In addition, the use of the proposed methodology is extended to discover novel disease-gene associations by including valuable domain knowledge from genome-wide association studies. To evaluate our approach, its effectiveness is compared against a held-out set where, again, it revealed very compelling results. For selected diseases, we further identify candidate gene lists for which disease-gene associations were not studied previously. Thus, our approach provides biomedical researchers with new tools to filter genes of interest, thus, reducing costly lab studies. PMID:27578529

  17. Association between dyslipidemia and chronic kidney disease: a cross-sectional study in the middle-aged and elderly Chinese population.

    PubMed

    Liu, Dong-Wei; Wan, Jia; Liu, Zhang-Suo; Wang, Pei; Cheng, Gen-Yang; Shi, Xue-Zhong

    2013-04-01

    Dyslipidemia, a well-known risk factor for cardiovascular disease, is common in patients with kidney disease. Recent studies discerned that dyslipidemias play a critical role in renal damage progression in renal diseases, but the association between dyslipidemias and chronic kidney disease (CKD) in the general population remains unknown. Thus, we assessed whether the growing prevalence of dyslipidemia could increase the risk of CKD. A total of 4779 middle-aged and elderly participants participated in this study. Dyslipidemias were defined by the 2007 Guidelines in Chinese Adults. Incident CKD was defined as albuminuria and/or reduced estimated glomerular filtration rate (eGFR, < 60 ml×min(-1)×1.73 m(-2)). Regression analysis was used to evaluate the association between dyslipidemia and albuminuria/reduced eGFR. Participants with hypercholesterolemia exhibited a greater prevalence of albuminuria and reduced eGFR (10.0% vs. 6.1%, P = 0.001; 4.0% vs. 2.4%, P = 0.028, respectively). Both hypercholesterolemia and low high density lipoprotein cholesterol (HDL-C) were independently associated with albuminuria (odds ratio (OR) 1.49; 95% confidence interval (CI) 1.08 - 2.07 and OR 1.53; 95%CI 1.13 - 2.09, respectively). The multivariable adjusted OR of reduced eGFR in participants with hypercholesterolemia was 1.65 (95%CI 1.03 - 2.65). As the number of dyslipidemia components increased, so did the OR of CKD: 0.87 (95%CI 0.65 - 1.15), 1.29 (95%CI, 0.83 - 2.01), and 7.87 (95%CI, 3.75 - 16.50) for albuminuria, and 0.38 (95%CI 0.21 - 0.69), 1.92 (95%CI 1.14 - 3.25), and 5.85 (95%CI 2.36 - 14.51) for reduced eGFR, respectively. Our findings indicate that dyslipidemias increase the risk of CKD in the middle-aged and elderly Chinese population. Hypercholesterolemia plays an important role in reducing total eGFR. Both low HDL-C and hypercholesterolemia are associated with an increased risk for albuminuria.

  18. Colonic Crohn's Disease Is Associated with Less Aggressive Disease Course Than Ileal or Ileocolonic Disease.

    PubMed

    Arora, Umang; Kedia, Saurabh; Garg, Prerna; Bopanna, Sawan; Jain, Saransh; Yadav, Dawesh P; Goyal, Sandeep; Gupta, Vipin; Sahni, Peush; Pal, Sujoy; Dash, Nihar Ranjan; Madhusudhan, Kumble Seetharama; Sharma, Raju; Makharia, Govind; Ahuja, Vineet

    2018-06-01

    The literature on disease characteristics of colonic Crohn's disease (CD) is sparse, especially from Asia, where the burden of inflammatory bowel disease is on the rise. The present study aims to describe the disease characteristics of colonic CD, and compare it with that of ileal/ileocolonic disease. This retrospective study included adult patients of CD (diagnosed by standard criteria, follow-up duration > 6 months) on follow-up between August 2004 and January 2016. The disease location was classified by Montreal classification. The data were recorded on demographic characteristics, smoking status, disease phenotype, disease course, treatment received, hospitalization and surgeries. Of 406 CD patients, 123 had colonic [mean age (at onset) 30.4 ± 13.2 years, 59.3% males] and 265 had ileal/ileocolonic disease [mean age (at onset) 32.9 ± 13.8 years, 61.5% males] while 18 patients had isolated upper GI disease. The frequency of inflammatory behavior (B1 phenotype; 61.8 vs. 46.4%, p = 0.003), perianal disease (23.6 vs. 4.5%, p < 0.001), and extra-intestinal manifestation (42.3 vs. 30.2%, p = 0.019) was higher in colonic than ileal/ileocolonic CD. Though not statistically significant, requirement of atleast one course of steroid was lower in colonic CD (72.7 vs. 84.2%, p = 0.098). Although there was no difference in the frequency of hospitalization (30.1 vs. 27.1%, p = 0.45), the overall requirement for surgery was significantly lower in colonic CD (17.1 vs. 26.1%, p = 0.032) and patients with colonic disease had a lower cumulative probability of first surgery in the first 10 years of follow-up [Hazard ratio 0.556 (95% CI 0.313-0.985), p = 0.045]. Colonic CD was associated with less aggressive disease behavior and lower requirement of surgery as compared to ileal/ileocolonic CD.

  19. Ageing, metabolism and cardiovascular disease.

    PubMed

    Costantino, Sarah; Paneni, Francesco; Cosentino, Francesco

    2016-04-15

    Age is one of the major risk factors associated with cardiovascular disease (CVD). About one-fifth of the world population will be aged 65 or older by 2030, with an exponential increase in CVD prevalence. It is well established that environmental factors (overnutrition, smoking, pollution, sedentary lifestyles) may lead to premature defects in mitochondrial functionality, insulin signalling, endothelial homeostasis and redox balance, fostering early senescent features. Over the last few years, molecular investigations have unveiled common signalling networks which may link the ageing process with deterioration of cardiovascular homeostasis and metabolic disturbances, namely insulin resistance. These different processes seem to be highly interconnected and their interplay may favour adverse vascular and cardiac phenotypes responsible for myocardial infarction, stroke and heart failure. In the present review, we carefully describe novel molecular cues underpinning ageing, metabolism and CVD. In particular, we describe a dynamic interplay between emerging pathways such as FOXOs, AMPK, SIRT1, p66(Shc) , JunD and NF-kB. This overview will provide the background for attractive molecular targets to prevent age-driven pathology in the vasculature and the heart. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  20. Molecular mechanism of endothelial and vascular aging: implications for cardiovascular disease.

    PubMed

    Camici, Giovanni G; Savarese, Gianluigi; Akhmedov, Alexander; Lüscher, Thomas F

    2015-12-21

    Western societies are aging due to an increasing life span, decreased birth rates, and improving social and health conditions. On the other hand, the prevalence of cardiovascular (CV) and cerebrovascular (CBV) diseases rises with age. Thus, in view of the ongoing aging pandemic, it is appropriate to better understand the molecular pathways of aging as well as age-associated CV and CBV diseases. Oxidative stress contributes to aging of organs and the whole body by an accumulation of reactive oxygen species promoting oxidative damage. Indeed, increased oxidative stress produced in the mitochondria and cytosol of heart and brain is a common denominator to almost all CV and CBV diseases. The mitochondrial adaptor protein p66(Shc) and the family of deacetylase enzymes, the sirtuins, regulate the aging process, determine lifespan of many species and are involved in CV diseases. GDF11, a member of TGFβ superfamily with homology to myostatin also retards the aging process via yet unknown mechanisms. Recent evidence points towards a promising role of this novel 'rejuvenation' factor in reducing age-related heart disease. Finally, telomere length is also involved in aging and the development of age-related CV dysfunction. This review focuses on the latest scientific advances in understanding age-related changes of the CV and CBV system, as well as delineating potential novel therapeutic targets derived from aging research for CV and CBV diseases. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  1. HIV/HCV Co-infection, Liver Disease Progression, and Age-Related IGF-1 Decline.

    PubMed

    Quinn, Jeffrey; Astemborski, Jacquie; Mehta, Shruti H; Kirk, Gregory D; Thomas, David L; Balagopal, Ashwin

    2017-01-01

    We have previously reported that persons co-infected with HIV and hepatitis C virus (HCV) had liver disease stages similar to HIV-uninfected individuals who were approximately 10 years older. Insulin-like growth factor 1(IGF-1) levels have long been known to decline with advancing age in humans and non-humans alike. We examined whether HIV infection affects the expected decline in IGF-1 in persons with chronic hepatitis C virus (HCV) infection and if that alteration in IGF-1 decline contributes to the link between HIV, aging, and liver disease progression. A total of 553 individuals with HCV infection were studied from the AIDS Linked to the Intravenous Experience (ALIVE) cohort for whom more than 10 years of follow-up was available. Serum IGF-1 levels were determined by ELISA and evaluated according to baseline characteristics and over time by HIV status and liver disease progression. Linear regression with generalized estimating equations was used to determine whether IGF-1 decline over time was independently associated with liver disease progression. Baseline IGF-1 levels were strongly associated with age ( P < 0.0001) but not with gender or HIV infection. Levels of IGF-1 declined at a rate of -1.75 ng/mL each year in HCV mono-infected individuals and at a rate of -1.23 ng/mL each year in HIV/HCV co-infected individuals ( P < 0.05). In a multivariable linear regression model, progression of liver fibrosis was associated with HIV infection and age, as well as with a slower rate of IGF-1 decline ( P = 0.001); however, the rate of IGF-1 decline did not alter the strength of the associations between HIV, liver disease, and age. The normal decline in IGF-1 levels with age was attenuated in HIV/HCV co-infected individuals compared to those with HCV mono-infection, and slower IGF-1 decline was independently associated with liver disease progression.

  2. Free triiodothyronine levels are positively associated with non-alcoholic fatty liver disease in euthyroid middle-aged subjects.

    PubMed

    Liu, Guoli; Zheng, Xiao; Guan, Liying; Jiang, Zhi; Lin, Haiyan; Jiang, Qiang; Zhang, Nan; Zhang, Yikun; Zhang, Xu; Yu, Chunxiao; Guan, Qingbo

    2015-01-01

    Studies on the relationship between thyroid function and non-alcoholic fatty liver disease (NAFLD) among euthyroid subjects have produced conflicting results. The aim of this study was to investigate the association between thyroid function and the presence of NAFLD in a large-sample middle-aged euthyroid subjects. A total of 2576 euthyroid subjects who underwent health check-up were included. NAFLD was diagnosed by hepatic ultrasonography. Conventional risk factors for NAFLD were assessed as well as serum levels of TSH, FT3 and FT4. Levels of FT3 were significantly higher in NAFLD group (5.12 ± 0.58 versus 4.84 ± 0.58 pmol/L, adjusted p = 0.000) than non-NAFLD group, while levels of TSH and FT4 were comparable between NAFLD and non-NAFLD groups (TSH: 2.13 ± 0.90 versus 2.20 ± 0.93 mIU/L, adjusted p = 0.190; FT4: 16.41 ± 2.04 versus 16.18 ± 2.06 pmol/L, adjusted p = 0.146, respectively). Levels of FT3 were positively correlated with components of metabolic syndrome. Multivariate logistic regression analysis revealed that high level of FT3 was an independent predictor for NAFLD (odds ratio: 1.253, p = 0.040). The relationship between FT4 and NAFLD in women was different according to menopausal status, with negative association in pre-menopausal women (OR: 0.777, 95% CI: 0.617-0.979, p = 0.032) and null association in post-menopausal women (OR: 1.037, 95% CI: 0.841-1.277, p = 0.736). Our findings suggested that high levels of FT3 were significantly associated with NAFLD among middle-aged euthyroid subjects independently of known metabolic risk factors. A negative correlation of serum FT4 level with NAFLD was only observed in pre-menopausal women.

  3. Are Lung Disease and Function Related to Age-related Macular Degeneration?

    PubMed Central

    Moorthy, Sonia; Cheung, Ning; Klein, Ronald; Shahar, E; Wong, Tien Y

    2010-01-01

    Purpose To describe the relationship of lung disease and function with early age-related macular degeneration (AMD) in a population-based study. Design A population-based, cross-sectional study of 12,596 middle-aged participants from the Atherosclerosis Risk in Communities Study. Methods Lung function was assessed by spirometry. Physician diagnosis of asthma and lung disease was ascertained from a standardized questionnaire. AMD signs were graded from fundus photographs according to the Wisconsin grading protocol. Results Of our study population, 587 (4.7%) had early AMD, 638 (5.1%) had asthma and 581 (4.6%) had lung disease. After adjusting for age, gender, smoking and hypertension, each litre increase in predicted forced expiratory volume in one second (FEV1) (odds ratio [OR]: 1.27; 95% confidence interval [CI]: 0.89, 1.80), forced vital capacity (FVC) (OR 1.18; 95% CI: 0.93, 1.51) and peak expiratory flow rate (OR 1.12; 95% CI: 0.95, 1.33) were not significantly associated with early AMD. FEV1/FVC ratio (second quartile OR 1.61; 95%CI 0.88–2.93, third quartile OR 1.65; CI 0.90–3.03, fourth quartile OR 1.28; 95%CI 0.68–2.40) was not significantly associated with early AMD. Similarly, asthma (OR 1.06; 95% CI: 0.86, 1.27) and other lung diseases (OR 1.08; 95% CI: 0.90, 1.29) were not associated with early AMD. Conclusion Our data do not support a cross-sectional association between lung disease and risk of early AMD. PMID:21168814

  4. ABCC9 gene polymorphism is associated with hippocampal sclerosis of aging pathology

    PubMed Central

    Estus, Steven; Abner, Erin L.; Parikh, Ishita; Malik, Manasi; Neltner, Janna H.; Ighodaro, Eseosa; Wang, Wang-Xia; Wilfred, Bernard R.; Wang, Li-San; Kukull, Walter A.; Nandakumar, Kannabiran; Farman, Mark L.; Poon, Wayne W.; Corrada, Maria M.; Kawas, Claudia H.; Cribbs, David H.; Bennett, David A.; Schneider, Julie A.; Larson, Eric B.; Crane, Paul K.; Valladares, Otto; Schmitt, Frederick A.; Kryscio, Richard J.; Jicha, Gregory A.; Smith, Charles D.; Scheff, Stephen W.; Sonnen, Joshua A.; Haines, Jonathan L.; Pericak-Vance, Margaret A.; Mayeux, Richard; Farrer, Lindsay A.; Van Eldik, Linda J.; Horbinski, Craig; Green, Robert C.; Gearing, Marla; Poon, Leonard W.; Kramer, Patricia L.; Woltjer, Randall L.; Montine, Thomas J.; Partch, Amanda B.; Rajic, Alexander J.; Richmire, KatieRose; Monsell, Sarah E.; Schellenberg, Gerard D.

    2014-01-01

    Hippocampal sclerosis of aging (HS-Aging) is a high-morbidity brain disease in the elderly but risk factors are largely unknown. We report the first genome-wide association study (GWAS) with HS-Aging pathology as an endophenotype. In collaboration with the Alzheimer’s Disease Genetics Consortium, data were analyzed from large autopsy cohorts: (#1) National Alzheimer’s Coordinating Center (NACC); (#2) Rush University Religious Orders Study and Memory and Aging Project; (#3) Group Health Research Institute Adult Changes in Thought study; (#4) University of California at Irvine 90+ Study; and (#5) University of Kentucky Alzheimer’s Disease Center. Altogether, 363 HS-Aging cases and 2,303 controls, all pathologically confirmed, provided statistical power to test for risk alleles with large effect size. A two-tier study design included GWAS from cohorts #1–3 (Stage I) to identify promising SNP candidates, followed by focused evaluation of particular SNPs in cohorts #4–5 (Stage II). Polymorphism in the ATP-binding cassette, sub-family C member 9 (ABCC9) gene, also known as sulfonylurea receptor 2, was associated with HS-Aging pathology. In the meta-analyzed Stage I GWAS, ABCC9 polymorphisms yielded the lowest p values, and factoring in the Stage II results, the meta-analyzed risk SNP (rs704178:G) attained genome-wide statistical significance (p = 1.4 × 10−9), with odds ratio (OR) of 2.13 (recessive mode of inheritance). For SNPs previously linked to hippocampal sclerosis, meta-analyses of Stage I results show OR = 1.16 for rs5848 (GRN) and OR = 1.22 rs1990622 (TMEM106B), with the risk alleles as previously described. Sulfonylureas, a widely prescribed drug class used to treat diabetes, also modify human ABCC9 protein function. A subsample of patients from the NACC database (n = 624) were identified who were older than age 85 at death with known drug history. Controlling for important confounders such as diabetes itself, exposure to a sulfonylurea drug was

  5. Solar radiation is inversely associated with inflammatory bowel disease admissions.

    PubMed

    Jaime, Francisca; Riutort, Maria C; Alvarez-Lobos, Manuel; Hoyos-Bachiloglu, Rodrigo; Camargo, Carlos A; Borzutzky, Arturo

    To explore the associations between latitude and solar radiation with inflammatory bowel disease admission rates in Chile, the country with the largest variation in solar radiation in the world. This is an ecological study, which included data on all hospital-admitted population for inflammatory bowel disease between 2001 and 2012, according to different latitudes and solar radiation exposures in Chile. The data were acquired from the national hospital discharge database from the Department of Health Statistics and Information of the Chilean Ministry of Health. Between 2001 and 2012 there were 12,869 admissions due to inflammatory bowel disease (69% ulcerative colitis, 31% Crohn's disease). Median age was 36 years (IQR: 25-51); 57% were female. The national inflammatory bowel disease admission rate was 6.52 (95% CI: 6.40-6.63) per 100,000 inhabitants with increasing rates over the 12-year period. In terms of latitude, the highest admission rates for pediatric ulcerative colitis and Crohn's disease, as well as adult ulcerative colitis, were observed in the southernmost region with lowest annual solar radiation. Linear regression analysis showed that regional solar radiation was inversely associated with inflammatory bowel disease admissions in Chile (β: -.44, p = .03). Regional solar radiation was inversely associated with inflammatory bowel disease admission rates in Chile; inflammatory bowel disease admissions were highest in the southernmost region with lowest solar radiation. Our results support the potential role of vitamin D deficiency on inflammatory bowel disease flares.

  6. [The age-related macular degeneration as a vascular disease/part of systemic vasculopathy: contributions to its pathogenesis].

    PubMed

    Fischer, Tamás

    2015-03-01

    The wall of blood vessels including those in choroids may be harmed by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic, and genetic impacts (risk factors), which may trigger a protracted response, the so-called host defense response. As a consequence, pathological changes resulting in vascular injury (e. g. atherosclerosis, age-related macular degeneration) may be evolved. Risk factors can also act directly on the endothelium through an increased production of reactive oxygen species promoting an endothelial activation, which leads to endothelial dysfunction, the onset of vascular disease. Thus, endothelial dysfunction is a link between the harmful stimulus and vascular injury; any kind of harmful stimuli may trigger the defensive chain that results in inflammation that may lead to vascular injury. It has been shown that even early age-related macular degeneration is associated with the presence of diffuse arterial disease and patients with early age-related macular degeneration demonstrate signs of systemic and retinal vascular alterations. Chronic inflammation, a feature of AMD, is tightly linked to diseases associated with ED: AMD is accompanied by a general inflammatory response, in the form of complement system activation, similar to that observed in degenerative vascular diseases such as atherosclerosis. All these facts indicate that age-related macular degeneration may be a vascular disease (or part of a systemic vasculopathy). This recognition could have therapeutic implications because restoration of endothelial dysfunction may prevent the development or improve vascular disease resulting in prevention or improvement of age-related macular degeneration as well.

  7. Factors associated with coronary artery disease and stroke in adults with congenital heart disease.

    PubMed

    Bokma, Jouke P; Zegstroo, Ineke; Kuijpers, Joey M; Konings, Thelma C; van Kimmenade, Roland R J; van Melle, Joost P; Kiès, Philippine; Mulder, Barbara J M; Bouma, Berto J

    2018-04-01

    To determine factors associated with coronary artery disease (CAD) and ischaemic stroke in ageing adult congenital heart disease (ACHD) patients. We performed a multicentre case-control study, using data from the national CONgenital CORvitia (CONCOR) registry to identify ACHD patients within five participating centres. Patients with CAD were matched (1:2 ratio) with ACHD patients without CAD on age, CHD defect group and gender. Patients with ischaemic stroke (or transient ischaemic attack) were matched similarly. Medical charts were reviewed and a standardised questionnaire was used to determine presence of risk factors. Of 6904 ACHD patients, a total of 55 cases with CAD (80% male, mean age 55.1±12.4 years) and 56 cases with stroke (46% male, mean age 46.9±15.2) were included and matched with control patients. In multivariable logistic regression analysis, traditional atherosclerotic risk factors (hypertension (OR 2.45; 95% CI 1.15 to 5.23), hypercholesterolaemia (OR 3.99; 95% CI 1.62 to 9.83) and smoking (OR 2.25; 95% CI 1.09 to 4.66)) were associated with CAD. In contrast, these risk factors were not associated with ischaemic stroke. In multivariable analysis, stroke was associated with previous shunt operations (OR 4.20; 95% CI 1.36 to 12.9), residual/unclosed septal defects (OR 2.38; 95% CI 1.03 to 5.51) and left-sided mechanical valves (OR 2.67; 95% CI 1.09 to 6.50). Traditional atherosclerotic risk factors were associated with CAD in ACHD patients. In contrast, ischaemic stroke was related to factors (previous shunts, septal defects, mechanical valves) suggesting a cardioembolic aetiology. These findings may inform surveillance and prevention strategies. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. Association of Amyloid Pathology With Myelin Alteration in Preclinical Alzheimer Disease.

    PubMed

    Dean, Douglas C; Hurley, Samuel A; Kecskemeti, Steven R; O'Grady, J Patrick; Canda, Cristybelle; Davenport-Sis, Nancy J; Carlsson, Cynthia M; Zetterberg, Henrik; Blennow, Kaj; Asthana, Sanjay; Sager, Mark A; Johnson, Sterling C; Alexander, Andrew L; Bendlin, Barbara B

    2017-01-01

    The accumulation of aggregated β-amyloid and tau proteins into plaques and tangles is a central feature of Alzheimer disease (AD). While plaque and tangle accumulation likely contributes to neuron and synapse loss, disease-related changes to oligodendrocytes and myelin are also suspected of playing a role in development of AD dementia. Still, to our knowledge, little is known about AD-related myelin changes, and even when present, they are often regarded as secondary to concomitant arteriosclerosis or related to aging. To assess associations between hallmark AD pathology and novel quantitative neuroimaging markers while being sensitive to white matter myelin content. Magnetic resonance imaging was performed at an academic research neuroimaging center on a cohort of 71 cognitively asymptomatic adults enriched for AD risk. Lumbar punctures were performed and assayed for cerebrospinal fluid (CSF) biomarkers of AD pathology, including β-amyloid 42, total tau protein, phosphorylated tau 181, and soluble amyloid precursor protein. We measured whole-brain longitudinal and transverse relaxation rates as well as the myelin water fraction from each of these individuals. Automated brain mapping algorithms and statistical models were used to evaluate the relationships between age, CSF biomarkers of AD pathology, and quantitative magnetic resonance imaging relaxometry measures, including the longitudinal and transverse relaxation rates and the myelin water fraction. The mean (SD) age for the 19 male participants and 52 female participants in the study was 61.6 (6.4) years. Widespread age-related changes to myelin were observed across the brain, particularly in late myelinating brain regions such as frontal white matter and the genu of the corpus callosum. Quantitative relaxometry measures were negatively associated with levels of CSF biomarkers across brain white matter and in areas preferentially affected in AD. Furthermore, significant age-by-biomarker interactions were

  9. Understanding ageing: fear of chronic diseases later in life.

    PubMed

    Awang, Halimah; Mansor, Norma; Nai Peng, Tey; Nik Osman, Nik Ainoon

    2018-01-01

    Objectives Ageing is often associated with deteriorating mental and physical health and the need for long-term care, creating a fear of ageing. We investigated what people fear most in terms of disabling chronic diseases and their concerns regarding having long-term illnesses. Methods Data were obtained from an online survey of 518 respondents aged 40 years and older residing in Malaysia, which was based on a convenience sample collected in May 2015 to January 2016. Data were analyzed using chi-squared tests and multinomial logistic regression. Results Of the most dreaded diseases, heart disease and cancer are life-threatening; however, dementia, diabetes, and hypertension persist and have a disabling effect for a long time. While there were variations in the diseases feared most across sex, ethnicity, and place of residence, the biggest worry for all respondents with regard to having a long-term illness was that they would become a burden to their family, a concern that superseded fear of dying. Conclusions We found our survey respondents had a fear of chronic diseases and placing a burden on others. Thus, there is a need to provide motivation for people to adopt a healthy lifestyle, to remain healthy.

  10. Disease spread in age structured populations with maternal age effects.

    PubMed

    Clark, Jessica; Garbutt, Jennie S; McNally, Luke; Little, Tom J

    2017-04-01

    Fundamental ecological processes, such as extrinsic mortality, determine population age structure. This influences disease spread when individuals of different ages differ in susceptibility or when maternal age determines offspring susceptibility. We show that Daphnia magna offspring born to young mothers are more susceptible than those born to older mothers, and consider this alongside previous observations that susceptibility declines with age in this system. We used a susceptible-infected compartmental model to investigate how age-specific susceptibility and maternal age effects on offspring susceptibility interact with demographic factors affecting disease spread. Our results show a scenario where an increase in extrinsic mortality drives an increase in transmission potential. Thus, we identify a realistic context in which age effects and maternal effects produce conditions favouring disease transmission. © 2017 The Authors Ecology Letters published by CNRS and John Wiley & Sons Ltd.

  11. The association between eGFR in the normal or mildly impaired range and incident cadiovascular disease: Age and sex analysis.

    PubMed

    Eisen, Alon; Porter, Avital; Hoshen, Moshe; Balicer, Ran D; Reges, Orna; Rabi, Yardena; Leibowitz, Morton; Iakobishvili, Zaza; Hasdai, David

    2018-05-14

    Worse renal function, even in the normal or mildly impaired range, is associated with incident cardiovascular disease (CVD). Whether this association exists in both sexes across all ages is not known. A population based cohort of individuals >22 years with no prior CVD and with an eGFR 60-130 ml/min/1.73 m 2 . eGFR was calculated using the CKD-EPI formula. Incident CVD was defined as either myocardial infarction, unstable angina pectoris, coronary revascularization, or cerebrovascular event. Incident CVD was examined separately in men and women in 3 age-groups (young, 22-40 years; middle-aged, 41-60 years; and elderly, ≥61 years), during a median follow-up of 96.0 months. Among 1,341,400 individuals (57% women, mean age 49.2 ± 16.6 years), men had more incident CVD as compared to women (34,968 vs. 23,515 total incident CVD) in all age-groups (0.6% vs. 0.2% in young; 6.2% vs. 2.0% in middle-aged; 13.4% vs. 8.4% in elderly, respectively). After adjustment for CVD risk factors, an increment of 10 units in eGFR was independently associated with a decrease of 5.4%, 3.4% and 5.4% in incident CVD in young, middle-aged and elderly men (p < 0.001 for each) and a decrease of 6.3%, 3.4% and 6.8% in the same age-groups in women (p < 0.001 for each). There was no significant age-sex interaction in the association between eGFR and incident CVD. Although incident CVD differs in men and women, as well as in different age-groups, a higher eGFR even in the normal or mildly impaired range is associated with lesser incident CVD in men and women of all ages. Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  12. Hydrogen sulfide ameliorates aging-associated changes in the kidney.

    PubMed

    Lee, Hak Joo; Feliers, Denis; Barnes, Jeffrey L; Oh, Sae; Choudhury, Goutam Ghosh; Diaz, Vivian; Galvan, Veronica; Strong, Randy; Nelson, James; Salmon, Adam; Kevil, Christopher G; Kasinath, Balakuntalam S

    2018-04-01

    Aging is associated with replacement of normal kidney parenchyma by fibrosis. Because hydrogen sulfide (H 2 S) ameliorates kidney fibrosis in disease models, we examined its status in the aging kidney. In the first study, we examined kidney cortical H 2 S metabolism and signaling pathways related to synthesis of proteins including matrix proteins in young and old male C57BL/6 mice. In old mice, increase in renal cortical content of matrix protein involved in fibrosis was associated with decreased H 2 S generation and AMPK activity, and activation of insulin receptor (IR)/IRS-2-Akt-mTORC1-mRNA translation signaling axis that can lead to increase in protein synthesis. In the second study, we randomized 18-19 month-old male C57BL/6 mice to receive 30 μmol/L sodium hydrosulfide (NaHS) in drinking water vs. water alone (control) for 5 months. Administration of NaHS increased plasma free sulfide levels. NaHS inhibited the increase in kidney cortical content of matrix proteins involved in fibrosis and ameliorated glomerulosclerosis. NaHS restored AMPK activity and inhibited activation of IR/IRS-2-Akt-mTORC1-mRNA translation axis. NaHS inhibited age-related increase in kidney cortical content of p21, IL-1β, and IL-6, components of the senescence-associated secretory phenotype. NaHS abolished increase in urinary albumin excretion seen in control mice and reduced serum cystatin C levels suggesting improved glomerular clearance function. We conclude that aging-induced changes in the kidney are associated with H 2 S deficiency. Administration of H 2 S ameliorates aging-induced kidney changes probably by inhibiting signaling pathways leading to matrix protein synthesis.

  13. Pharmacologic Approaches Against Advanced Glycation End Products (AGEs) in Diabetic Cardiovascular Disease.

    PubMed

    Nenna, Antonio; Nappi, Francesco; Avtaar Singh, Sanjeet Singh; Sutherland, Fraser W; Di Domenico, Fabio; Chello, Massimo; Spadaccio, Cristiano

    2015-05-01

    Advanced Glycation End-Products (AGEs) are signaling proteins associated to several vascular and neurological complications in diabetic and non-diabetic patients. AGEs proved to be a marker of negative outcome in both diabetes management and surgical procedures in these patients. The reported role of AGEs prompted the development of pharmacological inhibitors of their effects, giving rise to a number of both preclinical and clinical studies. Clinical trials with anti-AGEs drugs have been gradually developed and this review aimed to summarize most relevant reports. Evidence acquisition process was performed using PubMed and ClinicalTrials.gov with manually checked articles. Pharmacological approaches in humans include aminoguanidine, pyridoxamine, benfotiamine, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, statin, ALT-711 (alagebrium) and thiazolidinediones. The most recent promising anti-AGEs agents are statins, alagebrium and thiazolidinediones. The role of AGEs in disease and new compounds interfering with their effects are currently under investigation in preclinical settings and these newer anti-AGEs drugs would undergo clinical evaluation in the next years. Compounds with anti-AGEs activity but still not available for clinical scenarios are ALT-946, OPB-9195, tenilsetam, LR-90, TM2002, sRAGE and PEDF. Despite most studies confirm the efficacy of these pharmacological approaches, other reports produced conflicting evidences; in almost any case, these drugs were well tolerated. At present, AGEs measurement has still not taken a precise role in clinical practice, but its relevance as a marker of disease has been widely shown; therefore, it is important for clinicians to understand the value of new cardiovascular risk factors. Findings from the current and future clinical trials may help in determining the role of AGEs and the benefits of anti-AGEs treatment in cardiovascular disease.

  14. Accelerated Age-Dependent Hippocampal Volume Loss in Parkinson Disease With Mild Cognitive Impairment.

    PubMed

    Schneider, Christine B; Donix, Markus; Linse, Katharina; Werner, Annett; Fauser, Mareike; Klingelhoefer, Lisa; Löhle, Matthias; von Kummer, Rüdiger; Reichmann, Heinz; Storch, Alexander

    2017-09-01

    Patients with Parkinson disease are at high risk of developing dementia. During the course of the disease, a substantial number of patients will experience a cognitive decline, indicating the dynamics of the underlying neuropathology. Magnetic resonance imaging (MRI) has become increasingly useful for identifying structural characteristics in radiological brain anatomy existing prior to clinical symptoms. Whether these changes reflect pathology, whether they are aging related, or both often remains unclear. We hypothesized that aging-associated brain structural changes would be more pronounced in the hippocampal region among patients with Parkinson disease having mild cognitive deficits relative to cognitively unimpaired patients. Using MRI, we investigated 30 cognitively healthy patients with Parkinson disease and 33 patients with nondemented Parkinson disease having mild cognitive impairment. All participants underwent structural MRI scanning and extensive clinical and neuropsychological assessments. Irrespective of the study participants' cognitive status, older age was associated with reduced cortical thickness in various neocortical regions. Having mild cognitive impairment was not associated with an increased rate of cortical thinning or volume loss in these regions, except in the hippocampus bilaterally. Patients with Parkinson disease having mild cognitive impairment show an accelerated age-dependent hippocampal volume loss when compared with cognitively healthy patients with Parkinson disease. This may indicate pathological processes in a key region for memory functioning in patients with Parkinson disease at risk of developing dementia. Structural MRI of the hippocampal region could potentially contribute to identifying patients who should receive early treatment aimed at delaying the clinical onset of dementia.

  15. R2* mapping for brain iron: associations with cognition in normal aging.

    PubMed

    Ghadery, Christine; Pirpamer, Lukas; Hofer, Edith; Langkammer, Christian; Petrovic, Katja; Loitfelder, Marisa; Schwingenschuh, Petra; Seiler, Stephan; Duering, Marco; Jouvent, Eric; Schmidt, Helena; Fazekas, Franz; Mangin, Jean-Francois; Chabriat, Hugues; Dichgans, Martin; Ropele, Stefan; Schmidt, Reinhold

    2015-02-01

    Brain iron accumulates during aging and has been associated with neurodegenerative disorders including Alzheimer's disease. Magnetic resonance (MR)-based R2* mapping enables the in vivo detection of iron content in brain tissue. We investigated if during normal brain aging iron load relates to cognitive impairment in region-specific patterns in a community-dwelling cohort of 336 healthy, middle aged, and older adults from the Austrian Stroke Prevention Family Study. MR imaging and R2* mapping in the basal ganglia and neocortex were done at 3T. Comprehensive neuropsychological testing assessed memory, executive function, and psychomotor speed. We found the highest iron concentration in the globus pallidus, and pallidal and putaminal iron was significantly and inversely associated with cognitive performance in all cognitive domains, except memory. These associations were iron load dependent. Vascular brain lesions and brain volume did not mediate the relationship between iron and cognitive performance. We conclude that higher R2*-determined iron in the basal ganglia correlates with cognitive impairment during brain aging independent of concomitant brain abnormalities. The prognostic significance of this finding needs to be determined. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Late-life factors associated with healthy aging in older men.

    PubMed

    Bell, Christina L; Chen, Randi; Masaki, Kamal; Yee, Priscilla; He, Qimei; Grove, John; Donlon, Timothy; Curb, J David; Willcox, D Craig; Poon, Leonard W; Willcox, Bradley J

    2014-05-01

    To identify potentially modifiable late-life biological, lifestyle, and sociodemographic factors associated with overall and healthy survival to age 85. Prospective longitudinal cohort study with 21 years of follow-up (1991-2012). Hawaii Lifespan Study. American men of Japanese ancestry (mean age 75.7, range 71-82) without baseline major clinical morbidity and functional impairments (N = 1,292). Overall survival and healthy survival (free from six major chronic diseases and without physical or cognitive impairment) to age 85. Factors were measured at late-life baseline examinations (1991-1993). Of 1,292 participants, 1,000 (77%) survived to 85 (34% healthy) and 309 (24%) to 95 (<1% healthy). Late-life factors associated with survival and healthy survival included biological (body mass index, ankle-brachial index, cognitive score, blood pressure, inflammatory markers), lifestyle (smoking, alcohol use, physical activity), and sociodemographic factors (education, marital status). Cumulative late-life baseline risk factor models demonstrated that age-standardized (at 70) probability of survival to 95 ranged from 27% (no factors) to 7% (≥ 5 factors); probability of survival to 100 ranged from 4% (no factors) to 0.1% (≥ 5 factors). Age-standardized (at 70) probability of healthy survival to 90 ranged from 4% (no factors) to 0.01% (≥ 5 factors). There were nine healthy survivors at 95 and one healthy survivor at 100. Several potentially modifiable risk factors in men in late life (mean age 75.7) were associated with markedly greater probability of subsequent healthy survival and longevity. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

  17. Small Vessel Disease/White Matter Disease of the Brain and Its Association With Osteoporosis

    PubMed Central

    Alagiakrishnan, Kannayiram; Hsueh, Jenny; Zhang, Edwin; Khan, Khurshid; Senthilselvan, Ambikaipakan

    2015-01-01

    Background Evidence now suggests the role of neural effect on bone mass control. The effect of small vessel disease of the brain on osteoporosis has not been studied. The aim of this study was to investigate the association of white matter disease (WMD) of the brain with osteoporosis in the elderly. Methods In this retrospective cross-sectional study, 780 consecutive patient charts between 2010 and 2011 were reviewed in the Senior’s Outpatient Clinic at the University of Alberta Hospital. Subjects with brain computerized tomography (CT) were included in the study. Subjects with incomplete information, intracranial hemorrhage, acute stroke, cerebral edema, and/or normal pressure hydrocephalus on the CT were excluded. WMD was quantified on CT using Wahlund’s scoring protocol. Osteoporosis information was obtained from the chart, which has been diagnosed based on bone mineral density (BMD) information. Logistic regression analysis was done to determine the association of WMD severity with osteoporosis after controlling for confounding vascular risk factors. Results Of the 505 subjects who were included in the study, 188 (37%) had osteoporosis and 171 (91%) of these osteoporotic subjects were females. The mean age was 79.8 ± 7.04 years. The prevalence of WMD in osteoporosis subjects was 73%. In the unadjusted logistic regression analysis, there was a significant association between WMD severity and osteoporosis (odds ratio (OR): 1.10; 95% confidence interval (CI): 1.05 - 1.14; P < 0.001) and the significance remained in the adjusted model, after correcting for age, sex and all vascular risk factors (OR: 1.11; 95% CI: 1.05 - 1.18; P < 0.001). Conclusion WMD severity of the brain was associated with osteoporosis in the elderly. PMID:25780476

  18. Cognitive Reserve in Healthy Aging and Alzheimer's Disease: A Meta-Analysis of fMRI Studies.

    PubMed

    Colangeli, Stefano; Boccia, Maddalena; Verde, Paola; Guariglia, Paola; Bianchini, Filippo; Piccardi, Laura

    2016-08-01

    Cognitive reserve (CR) has been defined as the ability to optimize or maximize performance through differential recruitment of brain networks. In the present study, we aimed at providing evidence for a consistent brain network underpinning CR in healthy and pathological aging. To pursue this aim, we performed a coordinate-based meta-analysis of 17 functional magnetic resonance imaging studies on CR proxies in healthy aging, Alzheimer's disease (AD), and mild cognitive impairment (MCI). We found that different brain areas were associated with CR proxies in healthy and pathological aging. A wide network of areas, including medial and lateral frontal areas, that is, anterior cingulate cortex and dorsolateral prefrontal cortex, as well as precuneus, was associated with proxies of CR in healthy elderly patients. The CR proxies in patients with AD and amnesic-MCI were associated with activation in the anterior cingulate cortex. These results were discussed hypothesizing the existence of possible compensatory mechanisms in healthy and pathological aging. © The Author(s) 2016.

  19. Epidemiology of inflammatory bowel disease: Is there a shift towards onset at a younger age?

    PubMed

    Braegger, Christian P; Ballabeni, Pierluigi; Rogler, Daniela; Vavricka, Stephan R; Friedt, Michael; Pittet, Valérie

    2011-08-01

    Increasing numbers of paediatric and adolescent patients with Crohn disease (CD) and ulcerative colitis (UC) are reported. To determine whether this observation is a consequence of a shift towards onset at a younger age, we analysed retrospective data from patients enrolled in the Swiss IBD Cohort Study (SIBDCS). The SIBDCS is a disease-based cohort in Switzerland, which collects retrospective and prospective data on a large sample of patients with inflammatory bowel disease (IBD). Patients, diagnosed from 1980, were stratified according to diagnosis of CD and UC. Age at disease onset (age at first symptoms and age at diagnosis) was analysed in relation to calendar year of disease onset. Data were extracted from physician and patient questionnaires. Linear regressions of age at disease onset by calendar year of disease onset adjusted by sex, country of birth, and education were performed. Adjusted regression coefficients for CD and UC were significantly positive, that is, age at disease onset has increased with time. Male sex was associated with an increase in age at disease onset, and birth in Switzerland with a decrease. These associations were statistically significant. The results from the SIBDCS do not support the hypothesis that disease onset of both CD and UC occur today at a younger age. On the contrary, our results show that there is a significant trend for age at disease onset occurring at an older age today as compared with recent decades. We conclude that the observation of increasing numbers of paediatric and adolescent patients with IBD is not caused by a trend towards disease onset at a younger age, but that this may rather be a consequence of the overall increasing incidence of these conditions.

  20. Global Distribution of Outbreaks of Water-Associated Infectious Diseases

    PubMed Central

    Yang, Kun; LeJeune, Jeffrey; Alsdorf, Doug; Lu, Bo; Shum, C. K.; Liang, Song

    2012-01-01

    Background Water plays an important role in the transmission of many infectious diseases, which pose a great burden on global public health. However, the global distribution of these water-associated infectious diseases and underlying factors remain largely unexplored. Methods and Findings Based on the Global Infectious Disease and Epidemiology Network (GIDEON), a global database including water-associated pathogens and diseases was developed. In this study, reported outbreak events associated with corresponding water-associated infectious diseases from 1991 to 2008 were extracted from the database. The location of each reported outbreak event was identified and geocoded into a GIS database. Also collected in the GIS database included geo-referenced socio-environmental information including population density (2000), annual accumulated temperature, surface water area, and average annual precipitation. Poisson models with Bayesian inference were developed to explore the association between these socio-environmental factors and distribution of the reported outbreak events. Based on model predictions a global relative risk map was generated. A total of 1,428 reported outbreak events were retrieved from the database. The analysis suggested that outbreaks of water-associated diseases are significantly correlated with socio-environmental factors. Population density is a significant risk factor for all categories of reported outbreaks of water-associated diseases; water-related diseases (e.g., vector-borne diseases) are associated with accumulated temperature; water-washed diseases (e.g., conjunctivitis) are inversely related to surface water area; both water-borne and water-related diseases are inversely related to average annual rainfall. Based on the model predictions, “hotspots” of risks for all categories of water-associated diseases were explored. Conclusions At the global scale, water-associated infectious diseases are significantly correlated with socio

  1. Low-burden TP53 mutations in chronic phase of myeloproliferative neoplasms: association with age, hydroxyurea administration, disease type and JAK2 mutational status

    PubMed Central

    Kubesova, B; Pavlova, S; Malcikova, J; Kabathova, J; Radova, L; Tom, N; Tichy, B; Plevova, K; Kantorova, B; Fiedorova, K; Slavikova, M; Bystry, V; Kissova, J; Gisslinger, B; Gisslinger, H; Penka, M; Mayer, J; Kralovics, R; Pospisilova, S; Doubek, M

    2018-01-01

    The multistep process of TP53 mutation expansion during myeloproliferative neoplasm (MPN) transformation into acute myeloid leukemia (AML) has been documented retrospectively. It is currently unknown how common TP53 mutations with low variant allele frequency (VAF) are, whether they are linked to hydroxyurea (HU) cytoreduction, and what disease progression risk they carry. Using ultra-deep next-generation sequencing, we examined 254 MPN patients treated with HU, interferon alpha-2a or anagrelide and 85 untreated patients. We found TP53 mutations in 50 cases (0.2–16.3% VAF), regardless of disease subtype, driver gene status and cytoreduction. Both therapy and TP53 mutations were strongly associated with older age. Over-time analysis showed that the mutations may be undetectable at diagnosis and slowly increase during disease course. Although three patients with TP53 mutations progressed to TP53-mutated or TP53-wild-type AML, we did not observe a significant age-independent impact on overall survival during the follow-up. Further, we showed that complete p53 inactivation alone led to neither blast transformation nor HU resistance. Altogether, we revealed patient's age as the strongest factor affecting low-burden TP53 mutation incidence in MPN and found no significant age-independent association between TP53 mutations and hydroxyurea. Mutations may persist at low levels for years without an immediate risk of progression. PMID:28744014

  2. Genome-wide association study of the age of onset of childhood asthma.

    PubMed

    Forno, Erick; Lasky-Su, Jessica; Himes, Blanca; Howrylak, Judie; Ramsey, Clare; Brehm, John; Klanderman, Barbara; Ziniti, John; Melén, Erik; Pershagen, Goran; Wickman, Magnus; Martinez, Fernando; Mauger, Dave; Sorkness, Christine; Tantisira, Kelan; Raby, Benjamin A; Weiss, Scott T; Celedón, Juan C

    2012-07-01

    Childhood asthma is a complex disease with known heritability and phenotypic diversity. Although an earlier onset has been associated with more severe disease, there has been no genome-wide association study of the age of onset of asthma in children. We sought to identify genetic variants associated with earlier onset of childhood asthma. We conducted the first genome-wide association study of the age of onset of childhood asthma among participants in the Childhood Asthma Management Program (CAMP) and used 3 independent cohorts from North America, Costa Rica, and Sweden for replication. Two single nucleotide polymorphisms (SNPs) were associated with earlier onset of asthma in the combined analysis of CAMP and the replication cohorts: rs9815663 (Fisher P= 2.31 × 10(-8)) and rs7927044 (P= 6.54 × 10(-9)). Of these 2 SNPs, rs9815663 was also significantly associated with earlier asthma onset in an analysis including only the replication cohorts. Ten SNPs in linkage disequilibrium with rs9815663 were also associated with earlier asthma onset (2.24 × 10(-7) associated with lower lung function and higher asthma medication use during 4 years of follow-up in CAMP. We have identified 2 SNPs associated with earlier onset of childhood asthma in 4 independent cohorts. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  3. Periodontal disease and metabolic syndrome: A qualitative critical review of their association

    PubMed Central

    Watanabe, Keiko; Cho, Yale D.

    2014-01-01

    Background Metabolic syndrome (MetS) is a conglomerate of several physical conditions/diseases that, as a group, increases the risk of mortality resulting from development of T2DM and cardiovascular diseases (CVD). These conditions/diseases include glucose intolerance/insulin resistance, hypertension, obesity, and dyslipidemia. The results from epidemiological studies suggest that there is an association between metabolic syndrome (MetS) and periodontitis, it is therefore important to understand the current status of the association and a possible contribution of periodontitis to MetS. Objective This review will qualitatively analyze published papers on the association of MetS and periodontitis/periodontal disease to clarify the current status of the association and suggest future directions for studies which may unravel the causal relationship between them. Results Of 309 papers related to MetS and periodontitis, 26 are original research papers that investigated the relationship/association between periodontal disease and MetS. Criteria used to assess periodontitis and MetS as well as overall study designs and patient recruitment criteria varied greatly among these studies. Conclusion All these studies demonstrated a positive association between periodontal disease and MetS. However, due to the heterogeneity of criteria to assess periodontitis and MetS and also paucity of longitudinal studies, it is difficult to determine the relative contribution of periodontitis to MetS. Age and the number of positive components of MetS appear to strengthen the relationship, however, incidence of each disease entity increases with ageing. Thus, mechanistic studies are also necessary to unravel the inter-relationship between periodontitis and MetS. In this regard, a use of animal models will be helpful as they are more uniform in regards to genetic background and have minimum confounding factors. Finally, development of accurate, quantitative assessment of gingival inflammation

  4. Clinical Characteristics and Associated Systemic Diseases in Patients With Esophageal "Absent Contractility"-A Clinical Algorithm.

    PubMed

    Laique, Sobia; Singh, Tavankit; Dornblaser, David; Gadre, Abhishek; Rangan, Vikram; Fass, Ronnie; Kirby, Donald; Chatterjee, Soumya; Gabbard, Scott

    2018-01-19

    This study was carried out to assess the clinical characteristics and associated systemic diseases seen in patients diagnosed with absent contractility as per the Chicago Classification version 3.0, allowing us to propose a diagnostic algorithm for their etiologic testing. The Chicago Classification version 3.0 has redefined major and minor esophageal motility disorders using high-resolution esophageal manometry. There is a dearth of publications based on research on absent contractility, which historically has been associated with myopathic processes such as systemic sclerosis (SSc). We conducted a retrospective, multicenter study. Data of patients diagnosed with absent contractility were pooled from Cleveland Clinic, Cleveland, OH (January 2006 to July 2016) and Metrohealth Medical Center, Cleveland, OH (July 2014 to July 2016) and included: age, gender, associated medical conditions, surgical history, medications, and specific antibody testing. A total of 207 patients, including 57 male individuals and 150 female individuals, with mean age of 56.1 and 60.0 years, respectively, were included. Disease distribution was as follows: SSc (diffuse or limited cutaneous) 132, overlap syndromes 7, systemic lupus erythematosus17, Sjögren syndrome 4, polymyositis 3, and dermatomyositis 3. Various other etiologies including gastroesophageal reflux disease, postradiation esophagitis, neuromuscular disorders, and surgical complications were seen in the remaining cohort. Most practitioners use the term "absent contractility" interchangeably with "scleroderma esophagus"; however, only 63% of patients with absent contractility had SSc. Overall, 20% had another systemic autoimmune rheumatologic disease and 16% had a nonrheumatologic etiology for absent contractility. Therefore, alternate diagnosis must be sought in these patients. We propose an algorithm for their etiologic evaluation.

  5. Effect of Aging on Periodontal Inflammation, Microbial Colonization, and Disease Susceptibility.

    PubMed

    Wu, Y; Dong, G; Xiao, W; Xiao, E; Miao, F; Syverson, A; Missaghian, N; Vafa, R; Cabrera-Ortega, A A; Rossa, C; Graves, D T

    2016-04-01

    Periodontitis is a chronic inflammatory disease induced by a biofilm that forms on the tooth surface. Increased periodontal disease is associated with aging. We investigated the effect of aging on challenge by oral pathogens, examining the host response, colonization, and osteoclast numbers in aged versus young mice. We also compared the results with mice with lineage-specific deletion of the transcription factor FOXO1, which reduces dendritic cell (DC) function. Periodontitis was induced by oral inoculation of Porphyromonas gingivalis and Fusobacterium nucleatum in young (4 to 5 mo) and aged (14 to 15 mo) mice. Aged mice as well as mice with reduced DC function had decreased numbers of DCs in lymph nodes, indicative of a diminished host response. In vitro studies suggest that reduced DC numbers in lymph nodes of aged mice may involve the effect of advanced glycation end products on DC migration. Surprisingly, aged mice but not mice with genetically altered DC function had greater production of antibody to P. gingivalis, greater IL-12 expression, and more plasma cells in lymph nodes following oral inoculation as compared with young mice. The greater adaptive immune response in aged versus young mice was linked to enhanced levels of P. gingivalis and reduced bacterial diversity. Thus, reduced bacterial diversity in aged mice may contribute to increased P. gingivalis colonization following inoculation and increased periodontal disease susceptibility, reflected by higher TNF levels and osteoclast numbers in the periodontium of aged versus young mice. © International & American Associations for Dental Research 2016.

  6. Age and disability drive cognitive impairment in multiple sclerosis across disease subtypes.

    PubMed

    Ruano, Luis; Portaccio, Emilio; Goretti, Benedetta; Niccolai, Claudia; Severo, Milton; Patti, Francesco; Cilia, Sabina; Gallo, Paolo; Grossi, Paola; Ghezzi, Angelo; Roscio, Marco; Mattioli, Flavia; Stampatori, Chiara; Trojano, Maria; Viterbo, Rosa Gemma; Amato, Maria Pia

    2017-08-01

    There is limited and inconsistent information on the clinical determinants of cognitive impairment (CI) in multiple sclerosis (MS). The aim of this study was to compare the prevalence and profile of CI across MS disease subtypes and assess its clinical determinants. Cognitive performance was assessed through the Brief Repeatable Battery and the Stroop test in consecutive patients with MS referred to six Italian centers. CI was defined as impairment in ⩾ 2 cognitive domains. A total of 1040 patients were included, 167 with clinically isolated syndrome (CIS), 759 with relapsing remitting (RR), 74 with secondary progressive (SP), and 40 with primary progressive (PP) disease course. The overall prevalence of CI was 46.3%; 34.5% in CIS, 44.5% in RR, 79.4% in SP, and 91.3% in PP. The severity of impairment and the number of involved domains were significantly higher in SP and primary progressive multiple sclerosis (PPMS) than in CIS and RR. In multivariable logistic regression analysis, the presence of CI was significantly associated with higher Expanded Disability Status Scale (EDSS) and older age. CI is present in all MS subtypes since the clinical onset and its frequency is increased in the progressive forms, but these differences seem to be more associated with patient age and physical disability than to disease subtype per se.

  7. The mouse age phenome knowledgebase and disease-specific inter-species age mapping.

    PubMed

    Geifman, Nophar; Rubin, Eitan

    2013-01-01

    Similarities between mice and humans lead to generation of many mouse models of human disease. However, differences between the species often result in mice being unreliable as preclinical models for human disease. One difference that might play a role in lowering the predictivity of mice models to human diseases is age. Despite the important role age plays in medicine, it is too often considered only casually when considering mouse models. We developed the mouse-Age Phenotype Knowledgebase, which holds knowledge about age-related phenotypic patterns in mice. The knowledgebase was extensively populated with literature-derived data using text mining techniques. We then mapped between ages in humans and mice by comparing the age distribution pattern for 887 diseases in both species. The knowledgebase was populated with over 9800 instances generated by a text-mining pipeline. The quality of the data was manually evaluated, and was found to be of high accuracy (estimated precision >86%). Furthermore, grouping together diseases that share similar age patterns in mice resulted in clusters that mirror actual biomedical knowledge. Using these data, we matched age distribution patterns in mice and in humans, allowing for age differences by shifting either of the patterns. High correlation (r(2)>0.5) was found for 223 diseases. The results clearly indicate a difference in the age mapping between different diseases: age 30 years in human is mapped to 120 days in mice for Leukemia, but to 295 days for Anemia. Based on these results we generated a mice-to-human age map which is publicly available. We present here the development of the mouse-APK, its population with literature-derived data and its use to map ages in mice and human for 223 diseases. These results present a further step made to bridging the gap between humans and mice in biomedical research.

  8. Parent-of-origin specific allelic associations among 106 genomic loci for age at menarche

    PubMed Central

    Thompson, Deborah J; Ferreira, Teresa; He, Chunyan; Chasman, Daniel I; Esko, Tõnu; Thorleifsson, Gudmar; Albrecht, Eva; Ang, Wei Q; Corre, Tanguy; Cousminer, Diana L; Feenstra, Bjarke; Franceschini, Nora; Ganna, Andrea; Johnson, Andrew D; Kjellqvist, Sanela; Lunetta, Kathryn L; McMahon, George; Nolte, Ilja M; Paternoster, Lavinia; Porcu, Eleonora; Smith, Albert V; Stolk, Lisette; Teumer, Alexander; Tšernikova, Natalia; Tikkanen, Emmi; Ulivi, Sheila; Wagner, Erin K; Amin, Najaf; Bierut, Laura J; Byrne, Enda M; Hottenga, Jouke-Jan; Koller, Daniel L; Mangino, Massimo; Pers, Tune H; Yerges-Armstrong, Laura M; Zhao, Jing Hua; Andrulis, Irene L; Anton-Culver, Hoda; Atsma, Femke; Bandinelli, Stefania; Beckmann, Matthias W; Benitez, Javier; Blomqvist, Carl; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Brauch, Hiltrud; Brenner, Hermann; Buring, Julie E; Chang-Claude, Jenny; Chanock, Stephen; Chen, Jinhui; Chenevix-Trench, Georgia; Collée, J. Margriet; Couch, Fergus J; Couper, David; Coveillo, Andrea D; Cox, Angela; Czene, Kamila; D’adamo, Adamo Pio; Smith, George Davey; De Vivo, Immaculata; Demerath, Ellen W; Dennis, Joe; Devilee, Peter; Dieffenbach, Aida K; Dunning, Alison M; Eiriksdottir, Gudny; Eriksson, Johan G; Fasching, Peter A; Ferrucci, Luigi; Flesch-Janys, Dieter; Flyger, Henrik; Foroud, Tatiana; Franke, Lude; Garcia, Melissa E; García-Closas, Montserrat; Geller, Frank; de Geus, Eco EJ; Giles, Graham G; Gudbjartsson, Daniel F; Gudnason, Vilmundur; Guénel, Pascal; Guo, Suiqun; Hall, Per; Hamann, Ute; Haring, Robin; Hartman, Catharina A; Heath, Andrew C; Hofman, Albert; Hooning, Maartje J; Hopper, John L; Hu, Frank B; Hunter, David J; Karasik, David; Kiel, Douglas P; Knight, Julia A; Kosma, Veli-Matti; Kutalik, Zoltan; Lai, Sandra; Lambrechts, Diether; Lindblom, Annika; Mägi, Reedik; Magnusson, Patrik K; Mannermaa, Arto; Martin, Nicholas G; Masson, Gisli; McArdle, Patrick F; McArdle, Wendy L; Melbye, Mads; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L; Nevanlinna, Heli; Neven, Patrick; Nohr, Ellen A; Oldehinkel, Albertine J; Oostra, Ben A; Palotie, Aarno; Peacock, Munro; Pedersen, Nancy L; Peterlongo, Paolo; Peto, Julian; Pharoah, Paul DP; Postma, Dirkje S; Pouta, Anneli; Pylkäs, Katri; Radice, Paolo; Ring, Susan; Rivadeneira, Fernando; Robino, Antonietta; Rose, Lynda M; Rudolph, Anja; Salomaa, Veikko; Sanna, Serena; Schlessinger, David; Schmidt, Marjanka K; Southey, Mellissa C; Sovio, Ulla; Stampfer, Meir J; Stöckl, Doris; Storniolo, Anna M; Timpson, Nicholas J; Tyrer, Jonathan; Visser, Jenny A; Vollenweider, Peter; Völzke, Henry; Waeber, Gerard; Waldenberger, Melanie; Wallaschofski, Henri; Wang, Qin; Willemsen, Gonneke; Winqvist, Robert; Wolffenbuttel, Bruce HR; Wright, Margaret J; Boomsma, Dorret I; Econs, Michael J; Khaw, Kay-Tee; Loos, Ruth JF; McCarthy, Mark I; Montgomery, Grant W; Rice, John P; Streeten, Elizabeth A; Thorsteinsdottir, Unnur; van Duijn, Cornelia M; Alizadeh, Behrooz Z; Bergmann, Sven; Boerwinkle, Eric; Boyd, Heather A; Crisponi, Laura; Gasparini, Paolo; Gieger, Christian; Harris, Tamara B; Ingelsson, Erik; Järvelin, Marjo-Riitta; Kraft, Peter; Lawlor, Debbie; Metspalu, Andres; Pennell, Craig E; Ridker, Paul M; Snieder, Harold; Sørensen, Thorkild IA; Spector, Tim D; Strachan, David P; Uitterlinden, André G; Wareham, Nicholas J; Widen, Elisabeth; Zygmunt, Marek; Murray, Anna; Easton, Douglas F

    2014-01-01

    Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality1. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation2,3, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P<5×10−8) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1/WDR25, MKRN3/MAGEL2 and KCNK9) demonstrating parent-of-origin specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and gamma-aminobutyric acid-B2 receptor signaling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition. PMID:25231870

  9. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

    PubMed

    Perry, John Rb; Day, Felix; Elks, Cathy E; Sulem, Patrick; Thompson, Deborah J; Ferreira, Teresa; He, Chunyan; Chasman, Daniel I; Esko, Tõnu; Thorleifsson, Gudmar; Albrecht, Eva; Ang, Wei Q; Corre, Tanguy; Cousminer, Diana L; Feenstra, Bjarke; Franceschini, Nora; Ganna, Andrea; Johnson, Andrew D; Kjellqvist, Sanela; Lunetta, Kathryn L; McMahon, George; Nolte, Ilja M; Paternoster, Lavinia; Porcu, Eleonora; Smith, Albert V; Stolk, Lisette; Teumer, Alexander; Tšernikova, Natalia; Tikkanen, Emmi; Ulivi, Sheila; Wagner, Erin K; Amin, Najaf; Bierut, Laura J; Byrne, Enda M; Hottenga, Jouke-Jan; Koller, Daniel L; Mangino, Massimo; Pers, Tune H; Yerges-Armstrong, Laura M; Zhao, Jing Hua; Andrulis, Irene L; Anton-Culver, Hoda; Atsma, Femke; Bandinelli, Stefania; Beckmann, Matthias W; Benitez, Javier; Blomqvist, Carl; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Brauch, Hiltrud; Brenner, Hermann; Buring, Julie E; Chang-Claude, Jenny; Chanock, Stephen; Chen, Jinhui; Chenevix-Trench, Georgia; Collée, J Margriet; Couch, Fergus J; Couper, David; Coveillo, Andrea D; Cox, Angela; Czene, Kamila; D'adamo, Adamo Pio; Smith, George Davey; De Vivo, Immaculata; Demerath, Ellen W; Dennis, Joe; Devilee, Peter; Dieffenbach, Aida K; Dunning, Alison M; Eiriksdottir, Gudny; Eriksson, Johan G; Fasching, Peter A; Ferrucci, Luigi; Flesch-Janys, Dieter; Flyger, Henrik; Foroud, Tatiana; Franke, Lude; Garcia, Melissa E; García-Closas, Montserrat; Geller, Frank; de Geus, Eco Ej; Giles, Graham G; Gudbjartsson, Daniel F; Gudnason, Vilmundur; Guénel, Pascal; Guo, Suiqun; Hall, Per; Hamann, Ute; Haring, Robin; Hartman, Catharina A; Heath, Andrew C; Hofman, Albert; Hooning, Maartje J; Hopper, John L; Hu, Frank B; Hunter, David J; Karasik, David; Kiel, Douglas P; Knight, Julia A; Kosma, Veli-Matti; Kutalik, Zoltan; Lai, Sandra; Lambrechts, Diether; Lindblom, Annika; Mägi, Reedik; Magnusson, Patrik K; Mannermaa, Arto; Martin, Nicholas G; Masson, Gisli; McArdle, Patrick F; McArdle, Wendy L; Melbye, Mads; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L; Nevanlinna, Heli; Neven, Patrick; Nohr, Ellen A; Oldehinkel, Albertine J; Oostra, Ben A; Palotie, Aarno; Peacock, Munro; Pedersen, Nancy L; Peterlongo, Paolo; Peto, Julian; Pharoah, Paul Dp; Postma, Dirkje S; Pouta, Anneli; Pylkäs, Katri; Radice, Paolo; Ring, Susan; Rivadeneira, Fernando; Robino, Antonietta; Rose, Lynda M; Rudolph, Anja; Salomaa, Veikko; Sanna, Serena; Schlessinger, David; Schmidt, Marjanka K; Southey, Mellissa C; Sovio, Ulla; Stampfer, Meir J; Stöckl, Doris; Storniolo, Anna M; Timpson, Nicholas J; Tyrer, Jonathan; Visser, Jenny A; Vollenweider, Peter; Völzke, Henry; Waeber, Gerard; Waldenberger, Melanie; Wallaschofski, Henri; Wang, Qin; Willemsen, Gonneke; Winqvist, Robert; Wolffenbuttel, Bruce Hr; Wright, Margaret J; Boomsma, Dorret I; Econs, Michael J; Khaw, Kay-Tee; Loos, Ruth Jf; McCarthy, Mark I; Montgomery, Grant W; Rice, John P; Streeten, Elizabeth A; Thorsteinsdottir, Unnur; van Duijn, Cornelia M; Alizadeh, Behrooz Z; Bergmann, Sven; Boerwinkle, Eric; Boyd, Heather A; Crisponi, Laura; Gasparini, Paolo; Gieger, Christian; Harris, Tamara B; Ingelsson, Erik; Järvelin, Marjo-Riitta; Kraft, Peter; Lawlor, Debbie; Metspalu, Andres; Pennell, Craig E; Ridker, Paul M; Snieder, Harold; Sørensen, Thorkild Ia; Spector, Tim D; Strachan, David P; Uitterlinden, André G; Wareham, Nicholas J; Widen, Elisabeth; Zygmunt, Marek; Murray, Anna; Easton, Douglas F; Stefansson, Kari; Murabito, Joanne M; Ong, Ken K

    2014-10-02

    Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.

  10. Association of Parkinson Disease Risk Loci With Mild Parkinsonian Signs in Older Persons

    PubMed Central

    Shulman, Joshua M.; Yu, Lei; Buchman, Aron S.; Evans, Denis A.; Schneider, Julie A.; Bennett, David A.; De Jager, Philip L.

    2014-01-01

    IMPORTANCE Parkinsonian motor signs are common in the aging population and are associated with adverse health outcomes. Compared with Parkinson disease (PD), potential genetic risk factors for mild parkinsonian signs have been largely unexplored. OBJECTIVE To determine whether PD susceptibility loci are associated with parkinsonism or substantia nigra pathology in a large community-based cohort of older persons. DESIGN, SETTING, AND PARTICIPANTS Eighteen candidate single-nucleotide polymorphisms from PD genome-wide association studies were evaluated in a joint clinicopathologic cohort. Participants included 1698 individuals and a nested autopsy collection of 821 brains from the Religious Orders Study and the Rush Memory and Aging Project, 2 prospective community-based studies. MAIN OUTCOMES AND MEASURES The primary outcomes were a quantitative measure of global parkinsonism or component measures of bradykinesia, rigidity, tremor, and gait impairment that were based on the motor Unified Parkinson’s Disease Rating Scale. In secondary analyses, we examined associations with additional quantitative motor traits and postmortem indices, including substantia nigra Lewy bodies and neuronal loss. RESULTS Parkinson disease risk alleles in the MAPT (rs2942168; P = .0006) and CCDC62 (rs12817488; P = .004) loci were associated with global parkinsonism, and these associations remained after exclusion of patients with a PD diagnosis. Based on motor Unified Parkinson’s Disease Rating Scale subscores, MAPT (P = .0002) and CCDC62 (P = .003) were predominantly associated with bradykinesia, and we further discovered associations between SREBF1 (rs11868035; P = .005) and gait impairment, SNCA (rs356220; P = .04) and rigidity, and GAK (rs1564282; P = .03) and tremor. In the autopsy cohort, only NMD3 (rs34016896; P = .03) was related to nigral neuronal loss, and no associations were detected with Lewy bodies. CONCLUSIONS AND RELEVANCE In addition to the established link to PD

  11. Age at menarche and age at natural menopause in East Asian women: a genome-wide association study.

    PubMed

    Shi, Jiajun; Zhang, Ben; Choi, Ji-Yeob; Gao, Yu-Tang; Li, Huaixing; Lu, Wei; Long, Jirong; Kang, Daehee; Xiang, Yong-Bing; Wen, Wanqing; Park, Sue K; Ye, Xingwang; Noh, Dong-Young; Zheng, Ying; Wang, Yiqin; Chung, Seokang; Lin, Xu; Cai, Qiuyin; Shu, Xiao-Ou

    2016-12-01

    Age at menarche (AM) and age at natural menopause (ANM) are complex traits with a high heritability. Abnormal timing of menarche or menopause is associated with a reduced span of fertility and risk for several age-related diseases including breast, endometrial and ovarian cancer, cardiovascular disease, and osteoporosis. To identify novel genetic loci for AM or ANM in East Asian women and to replicate previously identified loci primarily in women of European ancestry by genome-wide association studies (GWASs), we conducted a two-stage GWAS. Stage I aimed to discover promising novel AM and ANM loci using GWAS data of 8073 women from Shanghai, China. The Stage II replication study used the data from another Chinese GWAS (n = 1230 for AM and n = 1458 for ANM), a Korean GWAS (n = 4215 for AM and n = 1739 for ANM), and de novo genotyping of 2877 additional Chinese women. Previous GWAS-identified loci for AM and ANM were also evaluated. We identified two suggestive menarcheal age loci tagged by rs79195475 at 10q21.3 (beta = -0.118 years, P = 3.4 × 10 -6 ) and rs1023935 at 4p15.1 (beta = -0.145 years, P = 4.9 × 10 -6 ) and one menopausal age locus tagged by rs3818134 at 22q12.2 (beta = -0.276 years, P = 8.8 × 10 -6 ). These suggestive loci warrant a further validation in independent populations. Although limited by low statistical power, we replicated 19 of the 98 menarche loci and 5 of the 20 menopause loci previously identified in women of European ancestry in East Asian women, suggesting a shared genetic architecture for these two traits across populations.

  12. Nutrition and age-related eye diseases

    USDA-ARS?s Scientific Manuscript database

    Vision loss among the elderly is an important health problem. Approximately one person in three has some form of vision-reducing eye disease by the age of 65 [1]. Age-related cataract, age-related macular degeneration (AMD), diabetic retinopathy and glaucoma are the major diseases resulting in visu...

  13. Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases

    PubMed Central

    DeBalsi, Karen L.; Hoff, Kirsten E.; Copeland, William C.

    2016-01-01

    As regulators of bioenergetics in the cell and the primary source of endogenous reactive oxygen species (ROS), dysfunctional mitochondria have been implicated for decades in the process of aging and age-related diseases. Mitochondrial DNA (mtDNA) is replicated and repaired by nuclear-encoded mtDNA polymerase γ (Pol γ) and several other associated proteins, which compose the mtDNA replication machinery. Here, we review evidence that errors caused by this replication machinery and failure to repair these mtDNA errors results in mtDNA mutations. Clonal expansion of mtDNA mutations results in mitochondrial dysfunction, such as decreased electron transport chain (ETC) enzyme activity and impaired cellular respiration. We address the literature that mitochondrial dysfunction, in conjunction with altered mitochondrial dynamics, is a major driving force behind aging and age-related diseases. Additionally, interventions to improve mitochondrial function and attenuate the symptoms of aging are examined. PMID:27143693

  14. Atherosclerosis is associated with erectile function and lower urinary tract symptoms, especially nocturia, in middle-aged men.

    PubMed

    Tsujimura, Akira; Hiramatsu, Ippei; Aoki, Yusuke; Shimoyama, Hirofumi; Mizuno, Taiki; Nozaki, Taiji; Shirai, Masato; Kobayashi, Kazuhiro; Kumamoto, Yoshiaki; Horie, Shigeo

    2017-06-01

    Atherosclerosis is a systematic disease in which plaque builds up inside the arteries that can lead to serious problems related to quality of life (QOL). Lower urinary tract symptoms (LUTS), erectile dysfunction (ED), and late-onset hypogonadism (LOH) are highly prevalent in aging men and are significantly associated with a reduced QOL. However, few questionnaire-based studies have fully examined the relation between atherosclerosis and several urological symptoms. The study comprised 303 outpatients who visited our clinic with symptoms of LOH. Several factors influencing atherosclerosis, including serum concentrations of triglyceride, fasting blood sugar, and total testosterone measured by radioimmunoassay, were investigated. We also measured brachial-ankle pulse wave velocity (baPWV) and assessed symptoms by specific questionnaires, including the Sexual Health Inventory for Men (SHIM), Erection Hardness Score (EHS), International Prostate Symptom Score (IPSS), QOL index, and Aging Male Symptoms rating scale (AMS). Stepwise associations between the ratio of measured/age standard baPWV and clinical factors including laboratory data and the scores of the questionnaires were compared using the Jonckheere-Terpstra test for trend. The associations between the ratio of measured/age standard baPWV and each IPSS score were assessed in a multivariate linear regression model after adjustment for serum triglyceride, fasting blood sugar, and total testosterone. Regarding ED, a higher level of the ratio of measured/age standard baPWV was associated with a lower EHS, whereas no association was found with SHIM. Regarding LUTS, a higher ratio of measured/age standard baPWV was associated with a higher IPSS and QOL index. However, there was no statistically significant difference between the ratio of measured/age standard baPWV and AMS. A multivariate linear regression model showed only nocturia to be associated with the ratio of measured/age standard baPWV for each IPSS score

  15. Association of HTRA1 rs11200638 with age-related macular degeneration (AMD) in Brazilian patients.

    PubMed

    Lana, Tamires Prates; da Silva Costa, Sueli Matilde; Ananina, Galina; Hirata, Fábio Endo; Rim, Priscila Hae Hyun; Medina, Flávio MacCord; de Vasconcellos, José Paulo Cabral; de Melo, Mônica Barbosa

    2018-01-01

    Age-related macular degeneration is a multifactorial disease that can lead to vision impairment in older individuals. Although the etiology of age-related macular degeneration remains unknown, risk factors include age, ethnicity, smoking, hypertension, obesity, and genetic factors. Two main loci have been identified through genome-wide association studies, on chromosomes 1 and 10. Among the variants located at the 10q26 region, rs11200638, located at the HTRA1 gene promoter, has been associated with age-related macular degeneration in several populations and is considered the main polymorphism. We conducted a replication case-control study to analyze the frequency and participation of rs11200638 in the etiology of age-related macular degeneration in a sample of patients and controls from the State of São Paulo, Brazil, through polymerase chain reaction and enzymatic digestion. The frequency of the A allele was 57.60% in patients with age-related macular degeneration and 36.45% in controls (p value < 1e-07), representing a 2.369-fold higher risk factor for the disease. Both the AA and AG genotypes were observed more frequently in the age-related macular degeneration group compared to the control group (p = 1.21 e-07 and 0.0357, respectively). No statistically significant results were observed after stratification in dry versus wet types or advanced versus non-advanced forms. To our knowledge, this is the first time the association between rs11200638 and overall age-related macular degeneration has been reported in South America.

  16. [Pathogenetic associations of periodontal diseases with somatic therapeutic pathology, comorbid conditions in patients of advanced and senile age: state-of-the-art review. Part 1. Associations of periodontal diseases with somatic therapeutic pathology in patients of advanced and senile age].

    PubMed

    Ar'eva, G T; Solov'ev, M M; Ar'ev, A L; Ryzhak, G A

    2014-01-01

    The state-of-the-art review of literature on existing views on the association of periodontal diseases with somatic therapeutic pathology (first part of the review) and comorbid conditions (second part of the review) is submitted. The conclusion about need of carrying out the further multicenter researches which purpose is development of new integrated indicators, in a complex and comprehensively characterizing not only the periodontal status, but also set of available somatic therapeutic pathology, especially at pa- tients of advanced and senile age is drawn.

  17. Parkinson's disease as a result of aging

    PubMed Central

    Rodriguez, Manuel; Rodriguez-Sabate, Clara; Morales, Ingrid; Sanchez, Alberto; Sabate, Magdalena

    2015-01-01

    It is generally considered that Parkinson's disease is induced by specific agents that degenerate a clearly defined population of dopaminergic neurons. Data commented in this review suggest that this assumption is not as clear as is often thought and that aging may be critical for Parkinson's disease. Neurons degenerating in Parkinson's disease also degenerate in normal aging, and the different agents involved in the etiology of this illness are also involved in aging. Senescence is a wider phenomenon affecting cells all over the body, whereas Parkinson's disease seems to be restricted to certain brain centers and cell populations. However, reviewed data suggest that Parkinson's disease may be a local expression of aging on cell populations which, by their characteristics (high number of synaptic terminals and mitochondria, unmyelinated axons, etc.), are highly vulnerable to the agents promoting aging. The development of new knowledge about Parkinson's disease could be accelerated if the research on aging and Parkinson's disease were planned together, and the perspective provided by gerontology gains relevance in this field. PMID:25677794

  18. Paternal Age Effect Mutations and Selfish Spermatogonial Selection: Causes and Consequences for Human Disease

    PubMed Central

    Goriely, Anne; Wilkie, Andrew O.M.

    2012-01-01

    Advanced paternal age has been associated with an increased risk for spontaneous congenital disorders and common complex diseases (such as some cancers, schizophrenia, and autism), but the mechanisms that mediate this effect have been poorly understood. A small group of disorders, including Apert syndrome (caused by FGFR2 mutations), achondroplasia, and thanatophoric dysplasia (FGFR3), and Costello syndrome (HRAS), which we collectively term “paternal age effect” (PAE) disorders, provides a good model to study the biological and molecular basis of this phenomenon. Recent evidence from direct quantification of PAE mutations in sperm and testes suggests that the common factor in the paternal age effect lies in the dysregulation of spermatogonial cell behavior, an effect mediated molecularly through the growth factor receptor-RAS signal transduction pathway. The data show that PAE mutations, although arising rarely, are positively selected and expand clonally in normal testes through a process akin to oncogenesis. This clonal expansion, which is likely to take place in the testes of all men, leads to the relative enrichment of mutant sperm over time—explaining the observed paternal age effect associated with these disorders—and in rare cases to the formation of testicular tumors. As regulation of RAS and other mediators of cellular proliferation and survival is important in many different biological contexts, for example during tumorigenesis, organ homeostasis and neurogenesis, the consequences of selfish mutations that hijack this process within the testis are likely to extend far beyond congenital skeletal disorders to include complex diseases, such as neurocognitive disorders and cancer predisposition. PMID:22325359

  19. Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson's Disease.

    PubMed

    Sepe, Sara; Milanese, Chiara; Gabriels, Sylvia; Derks, Kasper W J; Payan-Gomez, Cesar; van IJcken, Wilfred F J; Rijksen, Yvonne M A; Nigg, Alex L; Moreno, Sandra; Cerri, Silvia; Blandini, Fabio; Hoeijmakers, Jan H J; Mastroberardino, Pier G

    2016-05-31

    The underlying relation between Parkinson's disease (PD) etiopathology and its major risk factor, aging, is largely unknown. In light of the causative link between genome stability and aging, we investigate a possible nexus between DNA damage accumulation, aging, and PD by assessing aging-related DNA repair pathways in laboratory animal models and humans. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER) capacity and that Ercc1 mutant mice with mildly compromised NER exhibit typical PD-like pathological alterations, including decreased striatal dopaminergic innervation, increased phospho-synuclein levels, and defects in mitochondrial respiration. Ercc1 mouse mutants are also more sensitive to the prototypical PD toxin MPTP, and their transcriptomic landscape shares important similarities with that of PD patients. Our results demonstrate that specific defects in DNA repair impact the dopaminergic system and are associated with human PD pathology and might therefore constitute an age-related risk factor for PD. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  20. A culture-brain link: Negative age stereotypes predict Alzheimer's disease biomarkers.

    PubMed

    Levy, Becca R; Ferrucci, Luigi; Zonderman, Alan B; Slade, Martin D; Troncoso, Juan; Resnick, Susan M

    2016-02-01

    Although negative age stereotypes have been found to predict adverse outcomes among older individuals, it was unknown whether the influence of stereotypes extends to brain changes associated with Alzheimer's disease. To consider this possibility, we drew on dementia-free participants, in the Baltimore Longitudinal Study of Aging, whose age stereotypes were assessed decades before yearly magnetic resonance images and brain autopsies were performed. Those holding more-negative age stereotypes earlier in life had significantly steeper hippocampal-volume loss and significantly greater accumulation of neurofibrillary tangles and amyloid plaques, adjusting for relevant covariates. These findings suggest a new pathway to identifying mechanisms and potential interventions related to the pathology of Alzheimer's disease. (c) 2016 APA, all rights reserved).

  1. Human podocyte depletion in association with older age and hypertension.

    PubMed

    Puelles, Victor G; Cullen-McEwen, Luise A; Taylor, Georgina E; Li, Jinhua; Hughson, Michael D; Kerr, Peter G; Hoy, Wendy E; Bertram, John F

    2016-04-01

    Podocyte depletion plays a major role in the development and progression of glomerulosclerosis. Many kidney diseases are more common in older age and often coexist with hypertension. We hypothesized that podocyte depletion develops in association with older age and is exacerbated by hypertension. Kidneys from 19 adult Caucasian American males without overt renal disease were collected at autopsy in Mississippi. Demographic data were obtained from medical and autopsy records. Subjects were categorized by age and hypertension as potential independent and additive contributors to podocyte depletion. Design-based stereology was used to estimate individual glomerular volume and total podocyte number per glomerulus, which allowed the calculation of podocyte density (number per volume). Podocyte depletion was defined as a reduction in podocyte number (absolute depletion) or podocyte density (relative depletion). The cortical location of glomeruli (outer or inner cortex) and presence of parietal podocytes were also recorded. Older age was an independent contributor to both absolute and relative podocyte depletion, featuring glomerular hypertrophy, podocyte loss, and thus reduced podocyte density. Hypertension was an independent contributor to relative podocyte depletion by exacerbating glomerular hypertrophy, mostly in glomeruli from the inner cortex. However, hypertension was not associated with podocyte loss. Absolute and relative podocyte depletion were exacerbated by the combination of older age and hypertension. The proportion of glomeruli with parietal podocytes increased with age but not with hypertension alone. These findings demonstrate that older age and hypertension are independent and additive contributors to podocyte depletion in white American men without kidney disease. Copyright © 2016 the American Physiological Society.

  2. Impact of aging, Alzheimer's disease and Parkinson's disease on the blood-brain barrier transport of therapeutics.

    PubMed

    Pan, Yijun; Nicolazzo, Joseph A

    2018-04-14

    Older people are at a greater risk of medicine-induced toxicity resulting from either increased drug sensitivity or age-related pharmacokinetic changes. The scenario is further complicated with the two most prevalent age-related neurodegenerative diseases, Alzheimer's disease (AD) and Parkinson's disease (PD). With aging, AD and PD, there is growing evidence of altered structure and function of the blood-brain barrier (BBB), including modifications to tight junctions and efflux transporters, such as P-glycoprotein. The subsequent impact on CNS drug exposure and risk of neurotoxicity from systemically-acting medicines is less well characterized. The purpose of this review, therefore, is to provide an overview of the multiple changes that occur to the BBB as a result of aging, AD and PD, and the impact that such changes have on CNS exposure of drugs, based on studies conducted in aged rodents or rodent models of disease, and in elderly people with and without AD or PD. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  3. Risk factor studies of age-at-onset in a sample ascertained for Parkinson disease affected sibling pairs: a cautionary tale

    PubMed Central

    Wilk, Jemma B; Lash, Timothy L

    2007-01-01

    An association between exposure to a risk factor and age-at-onset of disease may reflect an effect on the rate of disease occurrence or an acceleration of the disease process. The difference in age-at-onset arising from case-only studies, however, may also reflect secular trends in the prevalence of exposure to the risk factor. Comparisons of age-at-onset associated with risk factors are commonly performed in case series enrolled for genetic linkage analysis of late onset diseases. We describe how the results of age-at-onset studies of environmental risk factors reflect the underlying structure of the source population, rather than an association with age-at-onset, by contrasting the effects of coffee drinking and cigarette smoking on Parkinson disease age-at-onset with the effects on age-at-enrollment in a population based study sample. Despite earlier evidence to suggest a protective association of coffee drinking and cigarette smoking with Parkinson disease risk, the age-at-onset results are comparable to the patterns observed in the population sample, and thus a causal inference from the age-at-onset effect may not be justified. Protective effects of multivitamin use on PD age-at-onset are also shown to be subject to a bias from the relationship between age and multivitamin initiation. Case-only studies of age-at-onset must be performed with an appreciation for the association between risk factors and age and ageing in the source population. PMID:17408493

  4. Serum calcification propensity is independently associated with disease activity in systemic lupus erythematosus

    PubMed Central

    Chalikias, George; Tziakas, Dimitrios; Chizzolini, Carlo; Ribi, Camillo; Trendelenburg, Marten; Eisenberger, Ute; Hauser, Thomas; Pasch, Andreas; Huynh-Do, Uyen; Arampatzis, Spyridon

    2018-01-01

    Background Systemic lupus erythematosus (SLE) is associated with severe cardiovascular complications. The T50 score is a novel functional blood test quantifying calcification propensity in serum. High calcification propensity (or low T50) is a strong and independent determinant of all-cause mortality in various patient populations. Methods A total of 168 patients with ≥ 4 American College of Rheumatology (ACR) diagnostic criteria from the Swiss Systemic lupus erythematosus Cohort Study (SSCS) were included in this analysis. Serum calcification propensity was assessed using time-resolved nephelometry. Results The cohort mainly consisted of female (85%), middle-aged (43±14 years) Caucasians (77%). The major determinants of T50 levels included hemoglobin, serum creatinine and serum protein levels explaining 43% of the variation at baseline. Integrating disease activity (SELENA-SLEDAI) into this multivariate model revealed a significant association between disease activity and T50 levels. In a subgroup analysis considering only patients with active disease (SELENA-SLEDAI score ≥4) we found a negative association between T50 and SELENA-SLEDAI score at baseline (Spearman’s rho -0.233, P = 0.02). Conclusions Disease activity and T50 are closely associated. Moreover, T50 levels identify a subgroup of SLE patients with ongoing systemic inflammation as mirrored by increased disease activity. T50 could be a promising biomarker reflecting SLE disease activity and might offer an earlier detection tool for high-risk patients. PMID:29364894

  5. Bioactive Nutrients and Nutrigenomics in Age-Related Diseases.

    PubMed

    Rescigno, Tania; Micolucci, Luigina; Tecce, Mario F; Capasso, Anna

    2017-01-08

    The increased life expectancy and the expansion of the elderly population are stimulating research into aging. Aging may be viewed as a multifactorial process that results from the interaction of genetic and environmental factors, which include lifestyle. Human molecular processes are influenced by physiological pathways as well as exogenous factors, which include the diet. Dietary components have substantive effects on metabolic health; for instance, bioactive molecules capable of selectively modulating specific metabolic pathways affect the development/progression of cardiovascular and neoplastic disease. As bioactive nutrients are increasingly identified, their clinical and molecular chemopreventive effects are being characterized and systematic analyses encompassing the "omics" technologies (transcriptomics, proteomics and metabolomics) are being conducted to explore their action. The evolving field of molecular pathological epidemiology has unique strength to investigate the effects of dietary and lifestyle exposure on clinical outcomes. The mounting body of knowledge regarding diet-related health status and disease risk is expected to lead in the near future to the development of improved diagnostic procedures and therapeutic strategies targeting processes relevant to nutrition. The state of the art of aging and nutrigenomics research and the molecular mechanisms underlying the beneficial effects of bioactive nutrients on the main aging-related disorders are reviewed herein.

  6. Coronary Artery Disease and Reticular Macular Disease, a Subphenotype of Early Age-Related Macular Degeneration.

    PubMed

    Cymerman, Rachel M; Skolnick, Adam H; Cole, William J; Nabati, Camellia; Curcio, Christine A; Smith, R Theodore

    2016-11-01

    Reticular macular disease (RMD) is the highest risk form of early age-related macular degeneration and also specifically confers decreased longevity. However, because RMD requires advanced retinal imaging for adequate detection of its characteristic subretinal drusenoid deposits (SDD), it has not yet been completely studied with respect to coronary artery disease (CAD), the leading cause of death in the developed world. Because CAD appears in middle age, our purpose was to screen patients aged 45-80 years, documented either with or without CAD, to determine if CAD is associated with RMD. A prospective cohort study of patients with documented CAD status and no known retinal disease in a clinical practice setting at one institution. Subjects and Controls: A number of 76 eyes from 38 consecutive patients (23 with documented CAD, 15 controls documented without CAD; 47.4% female; mean age 66.7 years). Patients were imaged with near-infrared reflectance/spectral domain optical coherence tomography and assessed in masked fashion by two graders for the presence of SDD lesions of RMD and soft drusen. Presence or absence of RMD/SDD and soft drusen. RMD was more frequent in patients with CAD versus those without (Relative Risk [RR] = 2.1, CI = 1.08-3.95, P = 0.03). There was no association of CAD with soft drusen. A specific relationship between CAD and RMD suggests common systemic causes for both and warrants further study.

  7. Alzheimer disease biomarkers are associated with body mass index

    PubMed Central

    Vidoni, E.D.; Townley, R.A.; Honea, R.A.

    2011-01-01

    Objective: Both low and high body mass index (BMI) has been associated with cognitive impairment and dementia risk, including Alzheimer disease (AD). We examined the relationship of BMI with potential underlying biological substrates for cognitive impairment. Methods: We analyzed cross-sectional data from participants enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI) with PET imaging using Pittsburgh Compound B (PiB, n = 101) or CSF analyses (n = 405) for β-amyloid peptide (Aβ) and total tau. We assessed the relationship of CSF biomarkers and global PiB uptake with BMI using linear regression controlling for age and sex. We also assessed BMI differences between those who were and were not considered biomarker positive. Finally, we assessed BMI change over 2 years in relationship to AD biomarkers. Results: No dementia, mild cognitive impairment (MCI), and AD groups were not different in age, education, or BMI. In the overall sample, CSF Aβ (β = 0.181, p < 0.001), tau (β = −0.179, p < 0.001), tau/Aβ ratio (β = −0.180, p < 0.001), and global PiB uptake (β = −0.272, p = 0.005) were associated with BMI, with markers of increased AD burden associated with lower BMI. Fewer overweight individuals had biomarker levels indicative of pathophysiology (p < 0.01). These relationships were strongest in the MCI and no dementia groups. Conclusions: The presence and burden of in vivo biomarkers of cerebral amyloid and tau are associated with lower BMI in cognitively normal and MCI individuals. This supports previous findings of systemic change in the earliest phases of the disease. Further, MCI in those who are overweight may be more likely to result from heterogeneous pathophysiology. PMID:22105948

  8. The lysosomal storage disease continuum with ageing-related neurodegenerative disease.

    PubMed

    Lloyd-Evans, Emyr; Haslett, Luke J

    2016-12-01

    Lysosomal storage diseases and diseases of ageing share many features both at the physiological level and with respect to the mechanisms that underlie disease pathogenesis. Although the exact pathophysiology is not exactly the same, it is astounding how many similar pathways are altered in all of these diseases. The aim of this review is to provide a summary of the shared disease mechanisms, outlining the similarities and differences and how genetics, insight into rare diseases and functional research has changed our perspective on the causes underlying common diseases of ageing. The lysosome should no longer be considered as just the stomach of the cell or as a suicide bag, it has an emerging role in cellular signalling, nutrient sensing and recycling. The lysosome is of fundamental importance in the pathophysiology of diseases of ageing and by comparing against the LSDs we not only identify common pathways but also therapeutic targets so that ultimately more effective treatments can be developed for all neurodegenerative diseases. Copyright © 2016. Published by Elsevier B.V.

  9. Diarrhea-Predominant Irritable Bowel Syndrome Is Associated With Diverticular Disease: A Population-Based Study

    PubMed Central

    Jung, Hye-kyung; Choung, Rok Seon; Locke, G. Richard; Schleck, Cathy D.; Zinsmeister, Alan R.; Talley, Nicholas J.

    2010-01-01

    OBJECTIVES A subset of patients with colonic diverticular disease have chronic gastrointestinal symptoms, and some have a clinical diagnosis of irritable bowel syndrome (IBS), but whether IBS and diverticular disease are linked is uncertain. We aimed to evaluate this association in the community. METHODS A population-based, cross-sectional survey was conducted by mailing a valid symptom questionnaire to the eligible residents of Olmsted County, MN, aged 30 –95 years. Colonic diverticular disease (diverticulosis and diverticulitis) was ascertained through a review of the complete medical history of all responders. Subjects with at least one relevant test (colonoscopy, computed tomography (CT) scan, CT colonography, or barium enema) were included. IBS was defined using Rome II criteria. RESULTS Among 2,267 eligible respondents, there were 1,712 subjects who had undergone colon testing (76%): 919 women (54%); mean (±s.d.) age 65 (±11 years). Colonic diverticular disease was identified in 44.4% (95% confidence interval (CI) 42.1–46.8) of the subject. IBS was reported by 8.8% (95% CI 6.9 –11.0) of men and 17.0% (95% CI 14.6 –19.6) of women. After adjusting for age and gender, the presence of IBS was associated with an increased odds for diverticulosis (odds ratio (OR) = 1.8, 95% CI 1.3 – 2.4) but not diverticulitis (OR = 1.7, 95% CI 0.9 –3.2). In those 65 years of age or older, the presence of IBS was associated with a ninefold higher odds for diverticulosis (OR = 9.4, 95% CI 5.8–15.1). Relative to the non-IBS subgroup, diarrhea-predominant IBS and mixed IBS were significantly associated with an increased odds for diverticular disease (OR = 1.9, 95% CI 1.1–3.2; OR = 2.6, 95% CI 1.0 –6.4, respectively). CONCLUSIONS There is a significantly increased odds for colonic diverticulosis in subjects with IBS (relative to those without IBS). These results suggest that IBS and colonic diverticular disease may be connected. PMID:19861955

  10. Patient and Disease Characteristics Associated with Activation for Self-Management in Patients with Diabetes, Chronic Obstructive Pulmonary Disease, Chronic Heart Failure and Chronic Renal Disease: A Cross-Sectional Survey Study

    PubMed Central

    Bos-Touwen, Irene; Schuurmans, Marieke; Monninkhof, Evelyn M.; Korpershoek, Yvonne; Spruit-Bentvelzen, Lotte; Ertugrul-van der Graaf, Inge; de Wit, Niek; Trappenburg, Jaap

    2015-01-01

    A substantial proportion of chronic disease patients do not respond to self-management interventions, which suggests that one size interventions do not fit all, demanding more tailored interventions. To compose more individualized strategies, we aim to increase our understanding of characteristics associated with patient activation for self-management and to evaluate whether these are disease-transcending. A cross-sectional survey study was conducted in primary and secondary care in patients with type-2 Diabetes Mellitus (DM-II), Chronic Obstructive Pulmonary Disease (COPD), Chronic Heart Failure (CHF) and Chronic Renal Disease (CRD). Using multiple linear regression analysis, we analyzed associations between self-management activation (13-item Patient Activation Measure; PAM-13) and a wide range of socio-demographic, clinical, and psychosocial determinants. Furthermore, we assessed whether the associations between the determinants and the PAM were disease-transcending by testing whether disease was an effect modifier. In addition, we identified determinants associated with low activation for self-management using logistic regression analysis. We included 1154 patients (53% response rate); 422 DM-II patients, 290 COPD patients, 223 HF patients and 219 CRD patients. Mean age was 69.6±10.9. Multiple linear regression analysis revealed 9 explanatory determinants of activation for self-management: age, BMI, educational level, financial distress, physical health status, depression, illness perception, social support and underlying disease, explaining a variance of 16.3%. All associations, except for social support, were disease transcending. This study explored factors associated with varying levels of activation for self-management. These results are a first step in supporting clinicians and researchers to identify subpopulations of chronic disease patients less likely to be engaged in self-management. Increased scientific efforts are needed to explain the greater

  11. Association between endothelin type A receptor haplotypes and mortality in coronary heart disease.

    PubMed

    Ellis, Katrina L; Pilbrow, Anna P; Potter, Howard C; Frampton, Chris M; Doughty, Rob N; Whalley, Gillian A; Ellis, Chris J; Palmer, Barry R; Skelton, Lorraine; Yandle, Tim G; Troughton, Richard W; Richards, A Mark; A Cameron, Vicky

    2012-05-01

    The endothelin type A receptor, encoded by EDNRA, mediates the effects of endothelin-1 to promote vasoconstriction, vascular cell growth, adhesion, fibrosis and thrombosis. We investigated the association between EDNRA haplotype and cardiovascular outcomes in patients with coronary artery disease. Coronary disease patients (n = 1007) were genotyped for the His323His (rs5333) variant and one tag SNP from each of the major EDNRA haplotype blocks (rs6537484, rs1568136, rs5335 and rs10003447). EDNRA haplotype associations with clinical history, natriuretic peptides cardiac function and cardiovascular outcomes were tested over a median 3.8 years. Univariate analysis identified a 'low-risk' EDNRA haplotype associated with later age of Type 2 diabetes onset (p = 0.004) smaller BMI (p = 0.021), and reduced mortality (log rank p = 0.001). Cox proportional hazards analysis including established cardiovascular risk factors revealed an independent association between haplotype and mortality (p < 0.0001). These data highlight the potential importance of the endothelin system, and in particular EDNRA in coronary disease.

  12. Toxic Inhalational Injury-Associated Interstitial Lung Disease in Children

    PubMed Central

    Lee, Eun; Seo, Ju-Hee; Kim, Hyung Young; Yu, Jinho; Jhang, Won-Kyoung; Park, Seong-Jong; Kwon, Ji-Won; Kim, Byoung-Ju; Do, Kyung-Hyun; Cho, Young Ah; Kim, Sun-A; Jang, Se Jin

    2013-01-01

    Interstitial lung disease in children (chILD) is a group of disorders characterized by lung inflammation and interstitial fibrosis. In the past recent years, we noted an outbreak of child in Korea, which is possibly associated with inhalation toxicity. Here, we report a series of cases involving toxic inhalational injury-associated chILD with bronchiolitis obliterans pattern in Korean children. This study included 16 pediatric patients confirmed by lung biopsy and chest computed tomography, between February 2006 and May 2011 at Asan Medical Center Children's Hospital. The most common presenting symptoms were cough and dyspnea. The median age at presentation was 26 months (range: 12-47 months), with high mortality (44%). Histopathological analysis showed bronchiolar destruction and centrilobular distribution of alveolar destruction by inflammatory and fibroproliferative process with subpleural sparing. Chest computed tomography showed ground-glass opacities and consolidation in the early phase and diffuse centrilobular nodular opacity in the late phase. Air leak with severe respiratory difficulty was associated with poor prognosis. Although respiratory chemicals such as humidifier disinfectants were strongly considered as a cause of this disease, further studies are needed to understand the etiology and pathophysiology of the disease to improve the prognosis and allow early diagnosis and treatment. PMID:23772158

  13. Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels.

    PubMed

    Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F; Eszes, Marika; Faull, Richard L M; Curtis, Maurice A; Waldvogel, Henry J; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V; Coppola, Giovanni; Yang, X William

    2016-07-01

    Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=-0.41, p=5.5×10-8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels.

  14. Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels

    PubMed Central

    Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F.; Eszes, Marika; Faull, Richard L.M.; Curtis, Maurice A.; Waldvogel, Henry J.; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V.; Coppola, Giovanni; Yang, X. William

    2016-01-01

    Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=−0.41, p=5.5×10−8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels. PMID:27479945

  15. Are APOE ɛ genotype and TOMM40 poly-T repeat length associations with cognitive ageing mediated by brain white matter tract integrity?

    PubMed

    Lyall, D M; Harris, S E; Bastin, M E; Muñoz Maniega, S; Murray, C; Lutz, M W; Saunders, A M; Roses, A D; Valdés Hernández, M del C; Royle, N A; Starr, J M; Porteous, D J; Wardlaw, J M; Deary, I J

    2014-09-23

    Genetic polymorphisms in the APOE ɛ and TOMM40 '523' poly-T repeat gene loci have been associated with significantly increased risk of Alzheimer's disease. This study investigated the independent effects of these polymorphisms on human cognitive ageing, and the extent to which nominally significant associations with cognitive ageing were mediated by previously reported genetic associations with brain white matter tract integrity in this sample. Most participants in the Lothian Birth Cohort 1936 completed a reasoning-type intelligence test at age 11 years, and detailed cognitive/physical assessments and structural diffusion tensor brain magnetic resonance imaging at a mean age of 72.70 years (s.d.=0.74). Participants were genotyped for APOE ɛ2/ɛ3/ɛ4 status and TOMM40 523 poly-T repeat length. Data were available from 758-814 subjects for cognitive analysis, and 522-543 for mediation analysis with brain imaging data. APOE genotype was significantly associated with performance on several different tests of cognitive ability, including general factors of intelligence, information processing speed and memory (raw P-values all<0.05), independently of childhood IQ and vascular disease history. Formal tests of mediation showed that several significant APOE-cognitive ageing associations--particularly those related to tests of information processing speed--were partially mediated by white matter tract integrity. TOMM40 523 genotype was not associated with cognitive ageing. A range of brain phenotypes are likely to form the anatomical basis for significant associations between APOE genotype and cognitive ageing, including white matter tract microstructural integrity.

  16. Associations between cardiovascular disease and its risk factors with hearing loss-A cross-sectional analysis.

    PubMed

    Tan, H E; Lan, N S R; Knuiman, M W; Divitini, M L; Swanepoel, D W; Hunter, M; Brennan-Jones, C G; Hung, J; Eikelboom, R H; Santa Maria, P L

    2018-02-01

    To investigate the relationship between hearing loss and cardiovascular disease risk factors. Cross-sectional study. Participants were recruited between May 2010 and December 2015 and answered a health and risk factor questionnaire. Physical and biochemical assessments were performed. A community-based population. A total of 5107 participants born within the years 1946-1964 enrolled in the Busselton Healthy Ageing Study. Hearing was assessed behaviourally through the best ear pure-tone average (500, 1000, 2000, 4000 Hz), low-frequency average (250, 500, 1000 Hz) and high-frequency average (4000, 8000 Hz). Self-reported hearing loss, tinnitus and hyperacusis were assessed via questionnaire. Cardiovascular risk factors were assessed via a patient-completed questionnaire and objective measurements including blood pressure, body mass index, waist circumference, lipid profile and glycated haemoglobin. Of the participants, 54% were female, with the mean age of 58 years (range 45-69 years). Age, sex and family history of hearing loss were consistently strong determinants of hearing loss outcomes. After adjusting for these, obesity, current smoking, peripheral arterial disease and history of cardiovascular disease were significantly associated with pure-tone, low-frequency and high-frequency hearing loss. In addition, high blood pressure, triglyceride and glycated haemoglobin were significantly associated with low-frequency hearing loss. There was a graded association between hearing loss and Framingham Risk Score for cardiovascular risk (P<0.001). Established cardiovascular disease and individual and combined cardiovascular disease risk factors were found to be associated with hearing loss. Future research should prospectively investigate whether targeting cardiovascular disease can prevent hearing loss. © 2017 John Wiley & Sons Ltd.

  17. Correlations between sleep patterns and cardiovascular diseases in a Chinese middle-aged population.

    PubMed

    Wang, Chuangshi; Hao, Guang; Bo, Jian; Li, Wei

    2017-01-01

    Epidemiological and animal studies have suggested an association between habitual sleep patterns and cardiovascular (CV) disease, but the results are still controversial. Therefore, the aims of this study are to investigate the relationships between habitual sleep patterns and CV disease based on Prospective Urban Rural Epidemiology (PURE) China study. PURE China study recruited 46 285 participants, aged 35-70, from 12 provinces and 115 communities in China. Habitual sleep patterns and CV disease were self-reported. Multilevel logistic regression was used in our analysis. In this study, 39 515 participants were eligible in our analysis, including 23 345 (59.1%) women and 16 170 (40.9%) men. Sleeping ≥9 h per day was associated with increased odds of CV disease (OR = 1.16, 95% CI: 1.01-1.32, p = 0.033) compared with sleeping 7-8 h per day. Taking daytime naps was also associated with an increased odds of CV disease, and the CV odds increased with increasing napping duration (p for trend < 0.001). For the sleeping < 6 h per day, we only found an association with coronary artery disease (CAD) (OR = 1.58, 95% CI: 1.01-2.48, p = 0.046). Participants with only 7-8 h sleep per night had lowest prevalence of CV disease (OR = 0.77, 95% CI: 0.65-0.90, p = 0.001) compared with other sleep patterns. Napping, long and short duration of habitual sleep may increase the odds of CV disease. Only participants sleeping 7-8 hours at night are recommended in this study, and large longitudinal studies are needed to confirm these results.

  18. Tocotrienols: constitutional effects in aging and disease.

    PubMed

    Schaffer, Sebastian; Müller, Walter E; Eckert, Gunter P

    2005-02-01

    Tocotrienols, a class of vitamin E analogs, modulate several mechanisms associated with the aging process and aging-related diseases. Most studies compare the activities of tocotrienols with those of tocopherols ("classical vitamin E"). However, some biological effects were found to be unique for tocotrienols. Although the absorption mechanisms are essentially the same for all vitamin E analogs, tocotrienols are degraded to a greater extent than tocopherols. The levels of tocotrienols in the plasma of animals and humans were estimated to reach low micromolar concentrations. One hallmark in the origin of disease and aging is the overproduction of reactive oxygen species (ROS). Tocotrienols possess excellent antioxidant activity in vitro and have been suggested to suppress ROS production more efficiently than tocopherols. In addition, tocotrienols show promising nonantioxidant activities in various in vitro and in vivo models. Most notable are the interactions of tocotrienols with the mevalonate pathway leading to the lowering of cholesterol levels, the prevention of cell adhesion to endothelial cells, and the suppression of tumor cell growth. Furthermore, glutamate-induced neurotoxicity is suppressed in the presence of tocotrienols. This review summarizes the main antioxidant and nonantioxidant effects of tocotrienols and assesses their potential as health-maintaining compounds.

  19. Are risk factors associated with invasive pneumococcal disease according to different serotypes?

    PubMed

    Ciruela, Pilar; Soldevila, Núria; Selva, Laura; Hernández, Sergi; Garcia-Garcia, Juan Jose; Moraga, Fernando; de Sevilla, Mariona F; Codina, Gemma; Planes, Ana Maria; Esteva, Cristina; Coll, Francis; Cardeñosa, Neus; Jordan, Iolanda; Batalla, Joan; Salleras, Luis; Muñoz-Almagro, Carmen; Domínguez, Angela

    2013-03-01

    The aim of this study was to investigate risk factors for the most common serotypes of invasive pneumococcal disease (IPD). A total of 293 IPD cases were analyzed in children aged 3-59 mo in a community with intermediate vaccination coverage with the 7-valent pneumococcal vaccine (PCV7). IPD cases were reviewed during 2007-2009 in two pediatric hospitals in Catalonia (Spain). A multivariate analysis using unconditional logistic regression was performed to estimate the adjusted odds ratio. PCV7 coverage was 45.4%. Pneumonia with empyema (64.5%) was the most frequent clinical manifestation. The most common serotypes were: serotype 1 (21.2%), 19A (16.0%), 3 (12.6%) and 7F/A (6.8%). 70.0% of serotypes found were included in the 13-valent conjugate vaccine (PCV13), 39.2% in the 10-valent conjugate vaccine and 8.1% in the PCV7. PCV7 was protective in IPD cases due to PCV7-serotypes (aOR: 0.15, 95% CI:0.04-0.55). Serotype 1 was positively associated with attending day care or school (aOR: 3.55, 95% CI: 1.21-10.38) and age 24-59 mo (aOR: 7.70, 95% CI:2.70-21.98). Serotype 19A was positively associated with respiratory infection in the previous month (aOR: 2.26, 95% CI: 1.03-4.94), non-penicillin susceptible IPD (aOR: 1.89, 95% CI:1.13-3.16) and negatively associated with age 24-59 mo (aOR: 0.19, 95% CI:0.09-0.41). Serotype 3 was positively associated with vaccination (aOR: 4.87, 95% CI:2.05-11.59). No factors were associated with serotype 7F/A. Vaccination with pneumococcal vaccines including more serotypes may reduce the risk of disease in our setting.

  20. Association between dietary fats and age-related macular degeneration (AMD) in the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women’s Health Initiative123

    PubMed Central

    Parekh, Niyati; Voland, Rickie P.; Moeller, Suzen M.; Blodi, Barbara A.; Ritenbaugh, Cheryl; Chappell, Richard J.; Wallace, Robert B.; Mares, Julie A.

    2011-01-01

    Objective Evaluating relationships of amount and type of dietary fat to intermediate AMD. Design Women, ages 50–79, from the Women’s Health Initiative-Observational Study, with high and low lutein intakes, were recruited into the Carotenoids in Age-Related Eye Disease Study (CAREDS). Fat intake in 1994–1998 was estimated using food frequency questionnaires. AMD was assessed in 2001–2004 from stereoscopic fundus photographs. Results Intakes of omega-6 and omega-3 polyunsaturated fats (ω-6 and ω-3 PUFA), which were highly correlated (r=0.8), were associated with higher prevalence of intermediate AMD. Significant age-interactions were noted for associations with total fat, monounsaturated and saturated fat (p= 0.01–0.02). In women <75 years (n=1,325), diets high in total fat (% energy) were associated with increased prevalence of AMD (OR (95% CI) for quintile five vs. one = 1.73 (1.02–2.7; p-trend=0.10); the association was reversed in older women. Monounsaturated fat (MUFA) intakes in quintiles three through five vs. one were associated with lower prevalence of AMD in the whole population. Conclusions Overall associations of dietary fat to AMD differed by type of fat and, often, by age in this cohort. These findings contribute insights about sources of inconsistencies of fat to AMD in epidemiological studies. PMID:19901214

  1. Autism risk associated with parental age and with increasing difference in age between the parents.

    PubMed

    Sandin, S; Schendel, D; Magnusson, P; Hultman, C; Surén, P; Susser, E; Grønborg, T; Gissler, M; Gunnes, N; Gross, R; Henning, M; Bresnahan, M; Sourander, A; Hornig, M; Carter, K; Francis, R; Parner, E; Leonard, H; Rosanoff, M; Stoltenberg, C; Reichenberg, A

    2016-05-01

    Advancing paternal and maternal age have both been associated with risk for autism spectrum disorders (ASD). However, the shape of the association remains unclear, and results on the joint associations is lacking. This study tests if advancing paternal and maternal ages are independently associated with ASD risk and estimates the functional form of the associations. In a population-based cohort study from five countries (Denmark, Israel, Norway, Sweden and Western Australia) comprising 5 766 794 children born 1985-2004 and followed up to the end of 2004-2009, the relative risk (RR) of ASD was estimated by using logistic regression and splines. Our analyses included 30 902 cases of ASD. Advancing paternal and maternal age were each associated with increased RR of ASD after adjusting for confounding and the other parent's age (mothers 40-49 years vs 20-29 years, RR=1.15 (95% confidence interval (CI): 1.06-1.24), P-value<0.001; fathers⩾50 years vs 20-29 years, RR=1.66 (95% CI: 1.49-1.85), P-value<0.001). Younger maternal age was also associated with increased risk for ASD (mothers <20 years vs 20-29 years, RR=1.18 (95% CI: 1.08-1.29), P-value<0.001). There was a joint effect of maternal and paternal age with increasing risk of ASD for couples with increasing differences in parental ages. We did not find any support for a modifying effect by the sex of the offspring. In conclusion, as shown in multiple geographic regions, increases in ASD was not only limited to advancing paternal or maternal age alone but also to differences parental age including younger or older similarly aged parents as well as disparately aged parents.

  2. Senescent Cells: A Novel Therapeutic Target for Aging and Age-Related Diseases

    PubMed Central

    Naylor, RM; Baker, DJ; van Deursen, JM

    2014-01-01

    Aging is the main risk factor for most chronic diseases, disabilities, and declining health. It has been proposed that senescent cells—damaged cells that have lost the ability to divide—drive the deterioration that underlies aging and age-related diseases. However, definitive evidence for this relationship has been lacking. The use of a progeroid mouse model (which expresses low amounts of the mitotic checkpoint protein BubR1) has been instrumental in demonstrating that p16Ink4a-positive senescent cells drive age-related pathologies and that selective elimination of these cells can prevent or delay age-related deterioration. These studies identify senescent cells as potential therapeutic targets in the treatment of aging and age-related diseases. Here, we describe how senescent cells develop, the experimental evidence that causally implicates senescent cells in age-related dysfunction, the chronic diseases and disorders that are characterized by the accumulation of senescent cells at sites of pathology, and the therapeutic approaches that could specifically target senescent cells. PMID:23212104

  3. A Review of the Diagnosis and Treatment of Ochratoxin A Inhalational Exposure Associated with Human Illness and Kidney Disease including Focal Segmental Glomerulosclerosis

    PubMed Central

    Hope, Janette H.; Hope, Bradley E.

    2012-01-01

    Ochratoxin A (OTA) exposure via ingestion and inhalation has been described in the literature to cause kidney disease in both animals and humans. This paper reviews Ochratoxin A and its relationship to human health and kidney disease with a focus on a possible association with focal segmental glomerulosclerosis (FSGS) in humans. Prevention and treatment strategies for OTA-induced illness are also discussed, including cholestyramine, a bile-acid-binding resin used as a sequestrant to reduce the enterohepatic recirculation of OTA. PMID:22253638

  4. Diverticular disease and colon cancer: a real association between the two diseases?

    PubMed

    Del Rio, Paolo; Rossini, Matteo; Papadia, Cinzia; Lorenzo, Viani; Labonia, Domenico; Sianesi, Mario

    2014-01-01

    During the last century the incidence of diverticular disease (DD), as well as the prevalence of colonic adenocarcinoma (ADK), recorded a marked increase in Western populations. In literature has been reported a higher incidence of sigmoid colon carcinoma associated with diverticular disease suggesting a possible sharing of risk factors and pathogens between these two pathologies. We prospectively examined 165 patients undergoing left colonic resection from May 2010 to December 2012 at the operating unit of General Surgery and Organ Transplantation of University Hospital of Parma , dividing them into three groups: affected by left colon cancer (120 cases), affected by complicated diverticular disease (29 cases) and affected by both diseases (16 cases). In this last group the indication for surgery has always been oncology based. All cases have been subjected to a 6 months minimum follow-up. The average age of patients operated for colonic ADK was 69.91 years. The average age of patients operated for ADK and concomitant DD, compared to that of patients treated for single DD, was statistically higher (73.8 ± 6.89 VS 60.9 ± 13.5, p = 0.004). It was found instead a higher diverticular inflammation degree in patients treated for DD compared with those treated for ADK associated with DD. No patient with ADK associated with DD showed hepatic metastases, whereas among patients with just ADK, peritoneal carcinomatosis was recorded in 2.6% of cases and liver metastases, always synchronous, in 11 .5%. The lymph nodes positivity instead, has presented a prevalence of 33.5% in patients with ADK and of 7% in patients with associated DD. In our study and its comparison with literature we found in synthesis multiple clinical evidences of a possible association between the two diseases. The role played by DD would lead to an early diagnosis of colonic ADK. It remains to be analyzed however the possible etiopathogenetic correlation over time between the two clinical entities

  5. Mechanistically linking age-related diseases and dietary carbohydrate via autophagy and the ubiquitin proteolytic systems

    USDA-ARS?s Scientific Manuscript database

    Epidemiological data indicate that consuming diets that deliver sugar to the blood rapidly (called high glycemic index, GI) is associated with enhanced risk for age-related diseases such as cardiovascular disease, type 2 diabetes, cataract and age-related macular degeneration (AMD). These debilities...

  6. Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration

    PubMed Central

    Pearson, Brandon L.; Simon, Jeremy M.; McCoy, Eric S.; Salazar, Gabriela; Fragola, Giulia; Zylka, Mark J.

    2016-01-01

    Environmental factors, including pesticides, have been linked to autism and neurodegeneration risk using retrospective epidemiological studies. Here we sought to prospectively identify chemicals that share transcriptomic signatures with neurological disorders, by exposing mouse cortical neuron-enriched cultures to hundreds of chemicals commonly found in the environment and on food. We find that rotenone, a pesticide associated with Parkinson's disease risk, and certain fungicides, including pyraclostrobin, trifloxystrobin, famoxadone and fenamidone, produce transcriptional changes in vitro that are similar to those seen in brain samples from humans with autism, advanced age and neurodegeneration (Alzheimer's disease and Huntington's disease). These chemicals stimulate free radical production and disrupt microtubules in neurons, effects that can be reduced by pretreating with a microtubule stabilizer, an antioxidant, or with sulforaphane. Our study provides an approach to prospectively identify environmental chemicals that transcriptionally mimic autism and other brain disorders. PMID:27029645

  7. Increased White Matter Inflammation in Aging- and Alzheimer's Disease Brain.

    PubMed

    Raj, Divya; Yin, Zhuoran; Breur, Marjolein; Doorduin, Janine; Holtman, Inge R; Olah, Marta; Mantingh-Otter, Ietje J; Van Dam, Debby; De Deyn, Peter P; den Dunnen, Wilfred; Eggen, Bart J L; Amor, Sandra; Boddeke, Erik

    2017-01-01

    Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer's disease (AD)-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis. Particularly in white matter microglia of 24-month-old mice, abundant expression of phagocytic markers including Mac-2, Axl, CD16/32, Dectin1, CD11c, and CD36 was detected. Interestingly, in white matter of human brain tissue the first signs of inflammatory activity were already detected during middle age. Thus quantification of microglial proteins, such as CD68 (commonly associated with phagocytosis) and HLA-DR (associated with antigen presentation), in postmortem human white matter brain tissue showed an age-dependent increase in immunoreactivity already in middle-aged people (53.2 ± 2.0 years). This early inflammation was also detectable by non-invasive positron emission tomography imaging using [ 11 C]-(R)-PK11195, a ligand that binds to activated microglia. Increased microglia activity was also prominently present in the white matter of human postmortem early-onset AD (EOAD) brain tissue. Interestingly, microglia activity in the white matter of late-onset AD (LOAD) CNS was similar to that of the aged clinically silent AD cases. These data indicate that microglia-induced neuroinflammation is predominant in the white matter of aging mice and humans as well as in EOAD brains. This white matter inflammation may contribute to the progression of neurodegeneration, and have prognostic value for detecting the onset and progression of aging and neurodegeneration.

  8. Association of insulin resistance with cerebral glucose uptake in late middle-aged adults at risk for Alzheimer’s disease

    PubMed Central

    Willette, Auriel A.; Bendlin, Barbara B.; Starks, Erika J.; Birdsill, Alex C.; Johnson, Sterling C.; Christian, Bradley T.; Okonkwo, Ozioma C.; La Rue, Asenath; Hermann, Bruce P.; Koscik, Rebecca L.; Jonaitis, Erin M.; Sager, Mark A.; Asthana, Sanjay

    2015-01-01

    Importance Converging evidence suggests that Alzheimer’s disease (AD) involves insulin signaling impairment. AD patients and people at risk for AD show reduced glucose metabolism, as indexed by F18-fluorodeoxyglucose positron emission tomography ([F18]FDG-PET). Objective To determine if insulin resistance (IR) predicts AD-like global and regional glucose metabolism deficits in late middle-aged participants at risk for AD. A secondary objective was to examine if IR-predicted variation in regional glucose metabolism was associated with worse cognitive performance. Setting A general community sample enriched for AD family history. Participants Population-based, cross-sectional study of 150 cognitively normal, late middle-aged (mean=60.67 years) adults from the Wisconsin Registry for Alzheimer’s Prevention. Design Participants underwent cognitive testing, fasting blood draw, and an [F18]FDG-PET scan at baseline. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was used to assess peripheral insulin resistance. Regression analysis tested the statistical effect of HOMA-IR on global glucose metabolism. A voxel-wise analysis was used to determine if HOMA-IR predicted regional glucose metabolism. Finally, predicted variation in regional glucose metabolism was regressed against cognitive factors. Covariates included age, sex, body mass index, Apolipoprotein E genotype, AD family history status, and a reference region used to normalize regional uptake. Main Outcome Measures Regional glucose uptake determined using [F18]FDG-PET, and neuropsychological factors. Results Higher HOMA-IR was associated with lower global glucose metabolism (β=−0.29, p<.01) and lower regional glucose metabolism across large portions of frontal, lateral parietal, lateral temporal, and medial temporal lobe (MTL; p<.05, family-wise error corrected). The association was especially robust in left MTL (R2=0.178). Lower left MTL glucose metabolism predicted by HOMA-IR was significantly

  9. Association of body flexibility and carotid atherosclerosis in Japanese middle-aged men: a cross-sectional study

    PubMed Central

    Imoto, Takayuki; Kida, Akira; Yokochi, Takashi; Iwase, Mitsunori; Kozawa, Kenji

    2018-01-01

    Objective This study examined the associations of body flexibility with carotid arterial remodelling, including intima–media thickness (IMT) and plaque formation in middle-aged men. Methods The subjects of this cross-sectional study included 1354 Japanese men aged 35–59 years without histories of stroke or cardiac diseases. The arm extensibility test, which can estimate flexibility of the upper extremity (composed of shoulder external rotation and forearm supination), and the sit-and-reach test were performed. Common carotid IMT and plaque formation (≥1.1 mm) were estimated by ultrasound. Results The proportion of subjects who fully completed the arm extensibility test was 55.0%, and who had plaques in the common carotid artery was 37.8%. IMT was associated with poor arm extensibility (β=–0.073, 95% CI –0.02224 to –0.00041, P=0.004), while plaque formation was associated with poor sit-and-reach (OR 0.98579, 95% CI 0.97257 to 0.99919, P=0.038) after adjustment by all covariates. Conclusions This study demonstrated that poor upper extremity and trunk flexibility were associated with characteristics of early onset of atherosclerosis. Furthermore, these associations were independent of covariates such as age, blood pressure, blood lipids glucose levels and abdominal fat accumulation, handgrip strength and lifestyle, including sleeping, drinking, exercise and smoking habits. Poor flexibility may reflect subclinical atherosclerosis in middle-aged men. PMID:29306892

  10. Neuropathologic features associated with Alzheimer disease diagnosis

    PubMed Central

    Grinberg, L.T.; Miller, B.; Kawas, C.; Yaffe, K.

    2011-01-01

    Objective: To examine whether the association between clinical Alzheimer disease (AD) diagnosis and neuropathology and the precision by which neuropathology differentiates people with clinical AD from those with normal cognition varies by age. Methods: We conducted a cross-sectional analysis of 2,014 older adults (≥70 years at death) from the National Alzheimer's Coordinating Center database with clinical diagnosis of normal cognition (made ≤1 year before death, n = 419) or AD (at ≥65 years, n = 1,595) and a postmortem neuropathologic examination evaluating AD pathology (neurofibrillary tangles, neuritic plaques) and non-AD pathology (diffuse plaques, amyloid angiopathy, Lewy bodies, macrovascular disease, microvascular disease). We used adjusted logistic regression to analyze the relationship between clinical AD diagnosis and neuropathologic features, area under the receiver operating characteristic curve (c statistic) to evaluate how precisely neuropathology differentiates between cognitive diagnoses, and an interaction to identify effect modification by age group. Results: In a model controlling for coexisting neuropathologic features, the relationship between clinical AD diagnosis and neurofibrillary tangles was significantly weaker with increasing age (p < 0.001 for interaction). The aggregate of all neuropathologic features more strongly differentiated people with clinical AD from those without in younger age groups (70–74 years: c statistic, 95% confidence interval: 0.93, 0.89–0.96; 75–84 years: 0.95, 0.87–0.95; ≥85 years: 0.83, 0.80–0.87). Non-AD pathology significantly improved precision of differentiation across all age groups (p < 0.004). Conclusion: Clinical AD diagnosis was more weakly associated with neurofibrillary tangles among the oldest old compared to younger age groups, possibly due to less accurate clinical diagnosis, better neurocompensation, or unaccounted pathology among the oldest old. PMID:22031532

  11. Cardiac surgery in patients with congenital heart disease is associated with acute kidney injury and the risk of chronic kidney disease.

    PubMed

    Madsen, Nicolas L; Goldstein, Stuart L; Frøslev, Trine; Christiansen, Christian F; Olsen, Morten

    2017-09-01

    Cardiac surgery associated-acute kidney injury (CS-AKI) occurs in 30-50% of patients undergoing surgery for congenital heart disease. Here we determine if CS-AKI is associated with chronic kidney disease (CKD) in patients with congenital heart disease. Using Danish regional population-based registries, our cohort study included patients with congenital heart disease born between 1990-2010 with first cardiac surgery between 2005 and 2010 (under 15 years of age). Utilizing in- and out-patient laboratory serum creatinine data, we identified individuals fulfilling KDIGO stages of AKI within 5 days of cardiac surgery. A unique personal identifier enabled unambiguous data linkage and virtually complete follow-up. The cumulative incidences of CKD stages 2-5 according to presence of CS-AKI were computed utilizing serum creatinine values and Pottel's formula. Using Cox regression, the corresponding hazard ratios were computed, adjusting for sex, age at first cardiac surgery, calendar period of surgery, and congenital heart disease severity. Of 382 patients with congenital heart disease undergoing cardiac surgery, 127 experienced CS-AKI within 5 days of surgery. Median follow-up was 4.9 years. The five-year cumulative incidence of CKD for patients with CS-AKI was 12% (95% confidence interval 7%-20%), significantly higher than the 3% (1%-5%) for those without CS-AKI with a significant adjusted hazard ratio of 3.8 (1.4-10.4). Thus, CS-AKI in patients with congenital heart disease is common and is associated with an increased risk for CKD. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  12. Histopathological lesions associated with equine periodontal disease.

    PubMed

    Cox, Alistair; Dixon, Padraic; Smith, Sionagh

    2012-12-01

    Equine periodontal disease (EPD) is a common and painful condition, the aetiology and pathology of which are poorly understood. To characterise the histopathological lesions associated with EPD, the skulls of 22 horses were assessed grossly for the presence of periodontal disease, and a standard set of interdental tissues taken from each for histopathological examination. Histological features of EPD included ulceration and neutrophilic inflammation of the gingival epithelium. Mononuclear and eosinophilic inflammation of the gingival lamina propria and submucosa was commonly present irrespective of the presence or degree of periodontal disease. Gingival hyperplasia was present to some degree in all horses, and was only weakly associated with the degree of periodontal disease. In all horses dental plaque was present at the majority of sites examined and was often associated with histological evidence of peripheral cemental erosion. Bacteria (including spirochaetes in four horses) were identified in gingival samples by Gram and silver impregnation techniques and were significantly associated with the presence of periodontal disease. This is the first study to describe histological features of EPD, and the first to identify associated spirochaetes in some cases. Histological features were variable, and there was considerable overlap of some features between the normal and diseased gingiva. Further investigation into the potential role of bacteria in the pathogenesis and progression of EPD is warranted. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Preface: The aging eye: normal changes, age-related diseases, and sight-saving approaches.

    PubMed

    Chader, Gerald J; Taylor, Allen

    2013-12-13

    This volume presents articles based on a workshop held June 14 to 16, 2013 in Rancho Palos Verde, CA sponsored by the Ocular Research Symposia Foundation (ORSF). The mission of the ORSF is to focus attention on unmet needs and current research opportunities in eye research with the objective of accelerating translation of research findings to effective clinical care. In this workshop, the subject of the "The Aging Eye" was addressed, including the prevalence of eye diseases in aging and the economic burden imposed by these diseases. New research work was highlighted on the genetics, biology, biochemistry, neurochemistry, and the impact of nutrition and the environment on function in the older eye. By identifying "low-hanging fruit" (i.e., the best opportunities for successful transition of laboratory research for the prevention of and new treatments and cures for ocular diseases), we seek to spur funding at both the basic research and clinical levels, resulting in sight-saving and sight-restoration measures in the near future.

  14. Aging Microglia—Phenotypes, Functions and Implications for Age-Related Neurodegenerative Diseases

    PubMed Central

    Spittau, Björn

    2017-01-01

    Aging of the central nervous system (CNS) is one of the major risk factors for the development of neurodegenerative pathologies such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). The molecular mechanisms underlying the onset of AD and especially PD are not well understood. However, neuroinflammatory responses mediated by microglia as the resident immune cells of the CNS have been reported for both diseases. The unique nature and developmental origin of microglia causing microglial self-renewal and telomere shortening led to the hypothesis that these CNS-specific innate immune cells become senescent. Age-dependent and senescence-driven impairments of microglia functions and responses have been suggested to play essential roles during onset and progression of neurodegenerative diseases. This review article summarizes the current knowledge of microglia phenotypes and functions in the aging CNS and further discusses the implications of these age-dependent microglia changes for the development and progression of AD and PD as the most common neurodegenerative diseases. PMID:28659790

  15. [Association between single-person households and ambulatory treatment of endocrine and metabolic disease in Japan: analysis of the Comprehensive Survey of Living Conditions].

    PubMed

    Tsukinoki, Rumi; Murakami, Yoshitaka

    2014-01-01

    We examined the association between single-person households and ambulatory treatment of endocrine and metabolic disease in Japan. We used random sample data from the Comprehensive Survey of Living Conditions in 2003. The study included 11,928 participants aged ≥20 years, excluding inpatients and nursing home residents. Household status was categorized in terms of two groups: single-person household or multi-person household. Three age categories were used: 20-49, 50-64, and ≥65 years. Endocrine and metabolic disease was defined as the prevalence of diabetes, obesity, hyperlipidemia, and thyroid diseases. Men and women were analyzed separately. Logistic regression models were used to estimate the odds ratios (ORs) after adjusting for employment status, marital status, disability in activities of daily living, and smoking. The association between age, household, and ambulatory care for endocrine and metabolic disease was examined by a likelihood ratio test. There were 443 male and 529 female outpatients with endocrine and metabolic disease. In male outpatients from single-person households, the ORs for endocrine and metabolic disease were higher than for multi-person households across all age groups [single-person household, 1.62 (95% confidence interval: 1.03-2.56)]. The ORs for outpatients with endocrine and metabolic disease increased with age, and for those aged ≥65 years, these ORs increased gradually. There were no significant associations between age, households, and ambulatory care for endocrine and metabolic disease in men (for the interaction P=0.986). Furthermore, there was no significant association between single-person households and ambulatory care for endocrine and metabolic disease in women. The data from the national survey suggest that single-person households are a risk factor for endocrine and metabolic disease in Japanese men. Our findings indicate the need for management of endocrine and metabolic disease across all age groups.

  16. Modifiable risk factors for Alzheimer disease and subjective memory impairment across age groups.

    PubMed

    Chen, Stephen T; Siddarth, Prabha; Ercoli, Linda M; Merrill, David A; Torres-Gil, Fernando; Small, Gary W

    2014-01-01

    Previous research has identified modifiable risk factors for Alzheimer's disease (AD) in older adults. Research is limited on the potential link between these risk factors and subjective memory impairment (SMI), which may precede AD and other dementias. Examination of these potential relationships may help identify those at risk for AD at a stage when interventions may delay or prevent further memory problems. The objective of this study was to determine whether risk factors for AD are associated with SMI among different age groups. Trained interviewers conducted daily telephone surveys (Gallup-Healthways) of a representative community sample of 18,614 U.S. respondents, including 4,425 younger (age 18 to 39 years), 6,365 middle-aged (40 to 59 years), and 7,824 older (60 to 99 years) adults. The surveyors collected data on demographics, lifestyles, and medical information. Less education, smoking, hypertension, diabetes, less exercise, obesity and depression, and interactions among them, were examined for associations with SMI. Weighted logistic regressions and chi-square tests were used to calculate odds ratios and confidence intervals for SMI with each risk factor and pairwise interactions across age groups. Depression, less education, less exercise, and hypertension were significantly associated with SMI in all three age groups. Several interactions between risk factors were significant in younger and middle-aged adults and influenced their associations with SMI. Frequency of SMI increased with age and number of risk factors. Odds of having SMI increased significantly with just having one risk factor. These results indicate that modifiable risk factors for AD are also associated with SMI, suggesting that these relationships occur in a broad range of ages and may be targeted to mitigate further memory problems. Whether modifying these risk factors reduces SMI and the eventual incidence of AD and other dementias later in life remains to be determined.

  17. Are APOE ɛ genotype and TOMM40 poly-T repeat length associations with cognitive ageing mediated by brain white matter tract integrity?

    PubMed Central

    Lyall, D M; Harris, S E; Bastin, M E; Muñoz Maniega, S; Murray, C; Lutz, M W; Saunders, A M; Roses, A D; Valdés Hernández, M del C; Royle, N A; Starr, J M; Porteous, D J; Wardlaw, J M; Deary, I J

    2014-01-01

    Genetic polymorphisms in the APOE ɛ and TOMM40 ‘523' poly-T repeat gene loci have been associated with significantly increased risk of Alzheimer's disease. This study investigated the independent effects of these polymorphisms on human cognitive ageing, and the extent to which nominally significant associations with cognitive ageing were mediated by previously reported genetic associations with brain white matter tract integrity in this sample. Most participants in the Lothian Birth Cohort 1936 completed a reasoning-type intelligence test at age 11 years, and detailed cognitive/physical assessments and structural diffusion tensor brain magnetic resonance imaging at a mean age of 72.70 years (s.d.=0.74). Participants were genotyped for APOE ɛ2/ɛ3/ɛ4 status and TOMM40 523 poly-T repeat length. Data were available from 758–814 subjects for cognitive analysis, and 522–543 for mediation analysis with brain imaging data. APOE genotype was significantly associated with performance on several different tests of cognitive ability, including general factors of intelligence, information processing speed and memory (raw P-values all<0.05), independently of childhood IQ and vascular disease history. Formal tests of mediation showed that several significant APOE-cognitive ageing associations—particularly those related to tests of information processing speed—were partially mediated by white matter tract integrity. TOMM40 523 genotype was not associated with cognitive ageing. A range of brain phenotypes are likely to form the anatomical basis for significant associations between APOE genotype and cognitive ageing, including white matter tract microstructural integrity. PMID:25247594

  18. White Matter Lipids as a Ketogenic Fuel Supply in Aging Female Brain: Implications for Alzheimer's Disease.

    PubMed

    Klosinski, Lauren P; Yao, Jia; Yin, Fei; Fonteh, Alfred N; Harrington, Michael G; Christensen, Trace A; Trushina, Eugenia; Brinton, Roberta Diaz

    2015-12-01

    White matter degeneration is a pathological hallmark of neurodegenerative diseases including Alzheimer's. Age remains the greatest risk factor for Alzheimer's and the prevalence of age-related late onset Alzheimer's is greatest in females. We investigated mechanisms underlying white matter degeneration in an animal model consistent with the sex at greatest Alzheimer's risk. Results of these analyses demonstrated decline in mitochondrial respiration, increased mitochondrial hydrogen peroxide production and cytosolic-phospholipase-A2 sphingomyelinase pathway activation during female brain aging. Electron microscopic and lipidomic analyses confirmed myelin degeneration. An increase in fatty acids and mitochondrial fatty acid metabolism machinery was coincident with a rise in brain ketone bodies and decline in plasma ketone bodies. This mechanistic pathway and its chronologically phased activation, links mitochondrial dysfunction early in aging with later age development of white matter degeneration. The catabolism of myelin lipids to generate ketone bodies can be viewed as a systems level adaptive response to address brain fuel and energy demand. Elucidation of the initiating factors and the mechanistic pathway leading to white matter catabolism in the aging female brain provides potential therapeutic targets to prevent and treat demyelinating diseases such as Alzheimer's and multiple sclerosis. Targeting stages of disease and associated mechanisms will be critical.

  19. White Matter Lipids as a Ketogenic Fuel Supply in Aging Female Brain: Implications for Alzheimer's Disease

    PubMed Central

    Klosinski, Lauren P.; Yao, Jia; Yin, Fei; Fonteh, Alfred N.; Harrington, Michael G.; Christensen, Trace A.; Trushina, Eugenia; Brinton, Roberta Diaz

    2015-01-01

    White matter degeneration is a pathological hallmark of neurodegenerative diseases including Alzheimer's. Age remains the greatest risk factor for Alzheimer's and the prevalence of age-related late onset Alzheimer's is greatest in females. We investigated mechanisms underlying white matter degeneration in an animal model consistent with the sex at greatest Alzheimer's risk. Results of these analyses demonstrated decline in mitochondrial respiration, increased mitochondrial hydrogen peroxide production and cytosolic-phospholipase-A2 sphingomyelinase pathway activation during female brain aging. Electron microscopic and lipidomic analyses confirmed myelin degeneration. An increase in fatty acids and mitochondrial fatty acid metabolism machinery was coincident with a rise in brain ketone bodies and decline in plasma ketone bodies. This mechanistic pathway and its chronologically phased activation, links mitochondrial dysfunction early in aging with later age development of white matter degeneration. The catabolism of myelin lipids to generate ketone bodies can be viewed as a systems level adaptive response to address brain fuel and energy demand. Elucidation of the initiating factors and the mechanistic pathway leading to white matter catabolism in the aging female brain provides potential therapeutic targets to prevent and treat demyelinating diseases such as Alzheimer's and multiple sclerosis. Targeting stages of disease and associated mechanisms will be critical. PMID:26844268

  20. Long-term exposure to air pollution is associated with biological aging

    PubMed Central

    Ward-Caviness, Cavin K.; Nwanaji-Enwerem, Jamaji C.; Wolf, Kathrin; Wahl, Simone; Colicino, Elena; Trevisi, Letizia; Kloog, Itai; Just, Allan C.; Vokonas, Pantel; Cyrys, Josef; Gieger, Christian; Schwartz, Joel; Baccarelli, Andrea A.; Schneider, Alexandra; Peters, Annette

    2016-01-01

    Long-term exposure to air pollution is associated with age-related diseases. We explored the association between accelerated biological aging and air pollution, a potential mechanism linking air pollution and health. We estimated long-term exposure to PM10, PM2.5, PM2.5 absorbance/black carbon (BC), and NOx via land-use regression models in individuals from the KORA F4 cohort. Accelerated biological aging was assessed using telomere length (TeloAA) and three epigenetic measures: DNA methylation age acceleration (DNAmAA), extrinsic epigenetic age acceleration (correlated with immune cell counts, EEAA), and intrinsic epigenetic age acceleration (independent of immune cell counts, IEAA). We also investigated sex-specific associations between air pollution and biological aging, given the published association between sex and aging measures. In KORA an interquartile range (0.97 μg/m3) increase in PM2.5 was associated with a 0.33 y increase in EEAA (CI = 0.01, 0.64; P = 0.04). BC and NOx (indicators or traffic exposure) were associated with DNAmAA and IEAA in women, while TeloAA was inversely associated with BC in men. We replicated this inverse BC-TeloAA association in the Normative Aging Study, a male cohort based in the USA. A multiple phenotype analysis in KORA F4 combining all aging measures showed that BC and PM10 were broadly associated with biological aging in men. Thus, we conclude that long-term exposure to air pollution is associated with biological aging measures, potentially in a sex-specific manner. However, many of the associations were relatively weak and further replication of overall and sex-specific associations is warranted. PMID:27793020

  1. Long-term exposure to air pollution is associated with biological aging.

    PubMed

    Ward-Caviness, Cavin K; Nwanaji-Enwerem, Jamaji C; Wolf, Kathrin; Wahl, Simone; Colicino, Elena; Trevisi, Letizia; Kloog, Itai; Just, Allan C; Vokonas, Pantel; Cyrys, Josef; Gieger, Christian; Schwartz, Joel; Baccarelli, Andrea A; Schneider, Alexandra; Peters, Annette

    2016-11-15

    Long-term exposure to air pollution is associated with age-related diseases. We explored the association between accelerated biological aging and air pollution, a potential mechanism linking air pollution and health. We estimated long-term exposure to PM10, PM2.5, PM2.5 absorbance/black carbon (BC), and NOx via land-use regression models in individuals from the KORA F4 cohort. Accelerated biological aging was assessed using telomere length (TeloAA) and three epigenetic measures: DNA methylation age acceleration (DNAmAA), extrinsic epigenetic age acceleration (correlated with immune cell counts, EEAA), and intrinsic epigenetic age acceleration (independent of immune cell counts, IEAA). We also investigated sex-specific associations between air pollution and biological aging, given the published association between sex and aging measures. In KORA an interquartile range (0.97 µg/m3) increase in PM2.5 was associated with a 0.33 y increase in EEAA (CI = 0.01, 0.64; P = 0.04). BC and NOx (indicators or traffic exposure) were associated with DNAmAA and IEAA in women, while TeloAA was inversely associated with BC in men. We replicated this inverse BC-TeloAA association in the Normative Aging Study, a male cohort based in the USA. A multiple phenotype analysis in KORA F4 combining all aging measures showed that BC and PM10 were broadly associated with biological aging in men. Thus, we conclude that long-term exposure to air pollution is associated with biological aging measures, potentially in a sex-specific manner. However, many of the associations were relatively weak and further replication of overall and sex-specific associations is warranted.

  2. The Association Between Unhealthy Lifestyle Behaviors and the Prevalence of Chronic Kidney Disease (CKD) in Middle-Aged and Older Men.

    PubMed

    Michishita, Ryoma; Matsuda, Takuro; Kawakami, Shotaro; Kiyonaga, Akira; Tanaka, Hiroaki; Morito, Natsumi; Higaki, Yasuki

    2016-07-05

    This cross-sectional study evaluated the association between unhealthy lifestyle behaviors and the prevalence of chronic kidney disease (CKD) in middle-aged and older men. The subjects included 445 men without a history of cardiovascular disease, stroke, or dialysis treatment, who were not taking medications. Unhealthy lifestyle behaviors were evaluated using a standardized self-administered questionnaire and were defined as follows: 1) lack of habitual moderate exercise, 2) lack of daily physical activity, 3) slow walking speed, 4) fast eating speed, 5) late-night dinner, 6) bedtime snacking, and 7) skipping breakfast. The participants were divided into four categories, which were classified into quartile distributions based on the number of unhealthy lifestyle behaviors (0-1, 2, 3, and ≥4 unhealthy behaviors). According to a multivariate analysis, the odds ratio (OR) for CKD (defined as estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m(2) and/or proteinuria) was found to be significantly higher in the ≥4 group than in the 0-1 group (OR 4.67; 95% confidence interval [CI], 1.51-14.40). Moreover, subjects' lack of habitual moderate exercise (OR 3.06; 95% CI, 1.13-8.32) and presence of late-night dinner (OR 2.84; 95% CI, 1.40-5.75) and bedtime snacking behaviors (OR 2.87; 95% CI, 1.27-6.45) were found to be significantly associated with the prevalence of CKD. These results suggest that an accumulation of unhealthy lifestyle behaviors, especially those related to lack of habitual moderate exercise and presence of late-night dinner and bedtime snacking may be associated with the prevalence of CKD.

  3. Cancer-associated bone disease.

    PubMed

    Rizzoli, R; Body, J-J; Brandi, M-L; Cannata-Andia, J; Chappard, D; El Maghraoui, A; Glüer, C C; Kendler, D; Napoli, N; Papaioannou, A; Pierroz, D D; Rahme, M; Van Poznak, C H; de Villiers, T J; El Hajj Fuleihan, G

    2013-12-01

    Bone is commonly affected in cancer. Cancer-induced bone disease results from the primary disease, or from therapies against the primary condition, causing bone fragility. Bone-modifying agents, such as bisphosphonates and denosumab, are efficacious in preventing and delaying cancer-related bone disease. With evidence-based care pathways, guidelines assist physicians in clinical decision-making. Of the 57 million deaths in 2008 worldwide, almost two thirds were due to non-communicable diseases, led by cardiovascular diseases and cancers. Bone is a commonly affected organ in cancer, and although the incidence of metastatic bone disease is not well defined, it is estimated that around half of patients who die from cancer in the USA each year have bone involvement. Furthermore, cancer-induced bone disease can result from the primary disease itself, either due to circulating bone resorbing substances or metastatic bone disease, such as commonly occurs with breast, lung and prostate cancer, or from therapies administered to treat the primary condition thus causing bone loss and fractures. Treatment-induced osteoporosis may occur in the setting of glucocorticoid therapy or oestrogen deprivation therapy, chemotherapy-induced ovarian failure and androgen deprivation therapy. Tumour skeletal-related events include pathologic fractures, spinal cord compression, surgery and radiotherapy to bone and may or may not include hypercalcaemia of malignancy while skeletal complication refers to pain and other symptoms. Some evidence demonstrates the efficacy of various interventions including bone-modifying agents, such as bisphosphonates and denosumab, in preventing or delaying cancer-related bone disease. The latter includes treatment of patients with metastatic skeletal lesions in general, adjuvant treatment of breast and prostate cancer in particular, and the prevention of cancer-associated bone disease. This has led to the development of guidelines by several societies and

  4. Cancer-associated bone disease

    PubMed Central

    Body, J.-J.; Brandi, M.-L.; Cannata-Andia, J.; Chappard, D.; El Maghraoui, A.; Glüer, C.C.; Kendler, D.; Napoli, N.; Papaioannou, A.; Pierroz, D.D.; Rahme, M.; Van Poznak, C.H.; de Villiers, T.J.; El Hajj Fuleihan, G.

    2016-01-01

    Bone is commonly affected in cancer. Cancer-induced bone disease results from the primary disease, or from therapies against the primary condition, causing bone fragility. Bone-modifying agents, such as bisphosphonates and denosumab, are efficacious in preventing and delaying cancer-related bone disease. With evidence-based care pathways, guidelines assist physicians in clinical decision-making. Of the 57 million deaths in 2008 worldwide, almost two thirds were due to non-communicable diseases, led by cardiovascular diseases and cancers. Bone is a commonly affected organ in cancer, and although the incidence of metastatic bone disease is not well defined, it is estimated that around half of patients who die from cancer in the USA each year have bone involvement. Furthermore, cancer-induced bone disease can result from the primary disease itself, either due to circulating bone resorbing substances or metastatic bone disease, such as commonly occurs with breast, lung and prostate cancer, or from therapies administered to treat the primary condition thus causing bone loss and fractures. Treatment-induced osteoporosis may occur in the setting of glucocorticoid therapy or oestrogen deprivation therapy, chemotherapy-induced ovarian failure and androgen deprivation therapy. Tumour skeletal-related events include pathologic fractures, spinal cord compression, surgery and radiotherapy to bone and may or may not include hypercalcaemia of malignancy while skeletal complication refers to pain and other symptoms. Some evidence demonstrates the efficacy of various interventions including bone-modifying agents, such as bisphosphonates and denosumab, in preventing or delaying cancer-related bone disease. The latter includes treatment of patients with metastatic skeletal lesions in general, adjuvant treatment of breast and prostate cancer in particular, and the prevention of cancer-associated bone disease. This has led to the development of guidelines by several societies and

  5. Genome-Wide Associations Related to Hepatic Histology in Nonalcoholic Fatty Liver Disease in Hispanic Boys.

    PubMed

    Wattacheril, Julia; Lavine, Joel E; Chalasani, Naga P; Guo, Xiuqing; Kwon, Soonil; Schwimmer, Jeffrey; Molleston, Jean P; Loomba, Rohit; Brunt, Elizabeth M; Chen, Yii-Der Ida; Goodarzi, Mark O; Taylor, Kent D; Yates, Katherine P; Tonascia, James; Rotter, Jerome I

    2017-11-01

    To identify genetic loci associated with features of histologic severity of nonalcoholic fatty liver disease in a cohort of Hispanic boys. There were 234 eligible Hispanic boys age 2-17 years with clinical, laboratory, and histologic data enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network included in the analysis of 624 297 single nucleotide polymorphisms (SNPs). After the elimination of 4 outliers and 22 boys with cryptic relatedness, association analyses were performed on 208 DNA samples with corresponding liver histology. Logistic regression analyses were carried out for qualitative traits and linear regression analyses were applied for quantitative traits. The median age and body mass index z-score were 12.0 years (IQR, 11.0-14.0) and 2.4 (IQR, 2.1-2.6), respectively. The nonalcoholic fatty liver disease activity score (scores 1-4 vs 5-8) was associated with SNP rs11166927 on chromosome 8 in the TRAPPC9 region (P = 8.7 -07 ). Fibrosis stage was associated with SNP rs6128907 on chromosome 20, near actin related protein 5 homolog (p = 9.9 -07 ). In comparing our results in Hispanic boys with those of previously reported SNPs in adult nonalcoholic steatohepatitis, 2 of 26 susceptibility loci were associated with nonalcoholic fatty liver disease activity score and 2 were associated with fibrosis stage. In this discovery genome-wide association study, we found significant novel gene effects on histologic traits associated with nonalcoholic fatty liver disease activity score and fibrosis that are distinct from those previously recognized by adult nonalcoholic fatty liver disease genome-wide association studies. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease

    PubMed Central

    Mora, Ana L.; Rojas, Mauricio; Pardo, Annie; Selman, Moises

    2018-01-01

    Idiopathic pulmonary fibrosis (IPF) is a fatal age-associated disease that is characterized by progressive and irreversible scarring of the lung. The pathogenesis of IPF is not completely understood and current therapies are limited to those that reduce the rate of functional decline in patients with mild-to-moderate disease. In this context, new therapeutic approaches that substantially improve the survival time and quality of life of these patients are urgently needed. Our incomplete understanding of the pathogenic mechanisms of IPF and the lack of appropriate experimental models that reproduce the key characteristics of the human disease are major challenges. As ageing is a major risk factor for IPF, age-related cell perturbations such as telomere attrition, senescence, epigenetic drift, stem cell exhaustion, loss of proteostasis and mitochondrial dysfunction are becoming targets of interest for IPF therapy. In this Review, we discuss current and emerging therapies for IPF, particularly those targeting age-related mechanisms, and discuss future therapeutic approaches. PMID:29081515

  7. Combined effects of age and polymorphisms in Notch3 in the pathogenesis of cerebral infarction disease.

    PubMed

    Zhu, Chun-Yu; Wang, Yue; Zeng, Qing-Xuan; Qian, Yu; Li, Huan; Yang, Zi-Xia; Yang, Ya-Mei; Zhang, Qiong; Li, Fei-Feng; Liu, Shu-Lin

    2016-10-01

    Cerebral infarction disease is a severe hypoxic ischemic tissue necrosis in the brain, often leading to long-term functional disability and residual impairments. The Notch signaling pathway plays key roles in proliferation and survival of the stem/progenitor cells of the central and peripheral nervous systems. Notch3 is an important member of the pathway, but the relationships between the genetic abnormalities and cerebral infarction disease still remain unclear. The aim of this work was to evaluate variations in Notch3 gene for their possible associations with the cerebral infarction disease. We sequenced the Notch3 gene for 260 patients with cerebral infarction disease, 300 normal controls with old ages and 300 normal controls with younger ages, and identified the variations. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 19.0). The Hardy-Weinberg equilibrium test of the population was carried out using the online software OEGE. Six variations, including rs1044116, rs1044009, rs1044006, rs10408676, rs1043996 and rs16980398 within or near the Notch3 gene, were found. The genetic heterozygosity of rs1044116, rs1044009, rs1044006, and rs1043996 was very high, whereas that of rs10408676 and rs16980398 was very low. Statistical analyses showed that rs1044009 and rs1044006 were associated with the risk of cerebral infarction disease in the Chinese Han agedness population. The SNPs rs1044009 and rs1044006 in the Notch3 gene were associated with the risk of cerebral infarction diseases in the Chinese Han agedness population.

  8. The association of aspirin use with age-related macular degeneration.

    PubMed

    Liew, Gerald; Mitchell, Paul; Wong, Tien Yin; Rochtchina, Elena; Wang, Jie Jin

    2013-02-25

    To determine whether regular aspirin use is associated with a higher risk for developing age-related macular degeneration (AMD) by using analyzed data from a 15-year prospective cohort. A prospective analysis was conducted of data from an Australian population-based cohort with 4 examinations during a 15-year period (1992-1994 to 2007-2009). Participants completed a detailed questionnaire at baseline assessing aspirin use, cardiovascular disease status, and AMD risk factors. Age-related macular degeneration was graded side-by-side from retinal photographs taken at each study visit to assess the incidence of neovascular (wet) AMD and geographic atrophy (dry AMD) according to the international AMD classification. Of 2389 baseline participants with follow-up data available, 257 individuals (10.8%) were regular aspirin users and 63 of the 2389 developed neovascular AMD. Persons who were regular aspirin users were more likely to have incident neovascular AMD: the 15-year cumulative incidence was 9.3% in users and 3.7% in nonusers. After adjustment for age, sex, smoking, history of cardiovascular disease, systolic blood pressure, and body mass index, persons who were regular aspirin users had a higher risk of developing neovascular AMD (odds ratio [OR], 2.46; 95% CI, 1.25-4.83). The association showed a dose-response effect (multivariate-adjusted P = .01 for trend). Aspirin use was not associated with the incidence of geographic atrophy (multivariate-adjusted OR, 0.99; 95% CI, 0.59-1.65). Regular aspirin use is associated with increased risk of incident neovascular AMD, independent of a history of cardiovascular disease and smoking.

  9. In patient's with Parkinson disease, autonomic symptoms are frequent and associated with other non-motor symptoms.

    PubMed

    Arnao, Valentina; Cinturino, Antonio; Valentino, Francesca; Perini, Valentina; Mastrilli, Sergio; Bellavia, Gabriele; Savettieri, Giovanni; Realmuto, Sabrina; D'Amelio, Marco

    2015-10-01

    Autonomic symptoms and sleep disorders are common non-motor symptoms of Parkinson disease (PD), which are correlated with poor quality of life for patients. To assess the frequency of autonomic symptoms in a consecutive series of PD patients and to correlate them with other motor and non-motor symptoms. All consecutive non-demented PD patients who underwent an extensive evaluation including Hoehn and Yahr staging, Unified Parkinson's Disease Rating Scale, Beck's Depression Inventory, Neuropsychiatric Inventory, PDQ-39 Scale, the Parkinson's diseases Sleep Scale, the Epworth Sleepiness Scale and SCOPA-AUT scale were enrolled. Comorbidity has been also considered. Supine to standing position blood pressure and cardiac frequency changes were also measured. 135 PD patients were included (mean age at interview 67.7; mean disease duration: 5.3 years). Patients were stratified according to mean SCOPA-AUT scale score (13.1). Those with higher SCOPA-AUT scale score were significantly older, had longer disease duration, worse disease stage, worse quality of sleep, were more severely affected, and were also taking a higher dosage of levodopa. At multivariate analysis, older age, longer disease duration, and worse quality of sleep were independently associated with higher SCOPA-AUT scale scores. Our results remark the role of autonomic symptoms in PD. In our patient population, characterized by mild to moderate disease severity, most of the patients complained of autonomic nervous system involvement (84%). A significant association between autonomic symptoms and sleep disorders was also observed.

  10. [Disease perception in patients with wet age-related macular degeneration].

    PubMed

    Kostadinov, F; Valmaggia, C

    2015-04-01

    The disease perception of the patients treated with intravitreal injections of anti-vascular endothelial growth factor due to wet age-related macular degeneration was investigated. 177 questionnaires focusing on the development of the perceived visual acuity and the quality of life were evaluated. The subgroup 1 included 125 patients (70.6%) with a unilateral wet age-related macular degeneration. The subgroup 2 included 52 patients (29.4%) with a bilateral wet age-related macular degeneration. Patients would almost always recommend the therapy to a friend (97.2%). The critical remarks are related to the uncertain course of the disease (22.8%) and the uncertain duration of the treatment (19%). There was a discrepancy between the measured visual outcome and the perceived one in 5.6% in the subgroup 1, and in 38.5% in the subgroup 2. This difference was statistically significant (chi-square test with p<0.01). The treatment of wet age-related macular degeneration with intravitreal injections of anti-vascular endothelial growth factor is judged positively. Binocular affected patients have a higher disease perception and therefore a poorer self-assessment of their visual acuity and their quality of life compared with monocular affected patients. Georg Thieme Verlag KG Stuttgart · New York.

  11. Serum levels of advanced glycation end-products (AGEs) and the decoy soluble receptor for AGEs (sRAGE) can identify non-alcoholic fatty liver disease in age-, sex- and BMI-matched normo-glycemic adults.

    PubMed

    Palma-Duran, Susana A; Kontogianni, Meropi D; Vlassopoulos, Antonis; Zhao, Shudong; Margariti, Aikaterini; Georgoulis, Michael; Papatheodoridis, George; Combet, Emilie

    2018-06-01

    Non-alcoholic fatty liver disease (NAFLD) is a serious health problem affecting ~25% of the global population. While NAFLD pathogenesis is still unclear, multiple NAFLD parameters, including reduced insulin sensitivity, impaired glucose metabolism and increased oxidative stress are hypothesised to foster the formation of advanced glycation end-products (AGEs). Given the link of AGEs with end organ damage, there is scope to examine the role of the AGE/RAGE axis activation in liver injury and NAFLD. Age, sex and body mass index matched normo-glycemic NAFLD adults (n = 58) and healthy controls (n = 58) were enrolled in the study. AGEs were analysed by liquid chromatography-mass spectrometry (CML, CEL), fluorescence (pentosidine, AGE fluorescence), colorimetry (fructosamine) and ELISA (sRAGE). Their association with liver function, inflammation, fibrosis and stage of NAFLD was examined. Early and advanced glycation end-products, except N ε -carboxymethyl-L-lysine (CML), were 10-30% higher, sRAGE levels 1.7-fold lower, and glycation/sRAGE ratios 4-fold higher in the NAFLD cases compared to controls. While AGEs presented weak to moderate correlations with indices of liver function and damage (AST/ALT, HOMA-IR, TNF-α and TGF-β1), including sRAGE to characterize the AGEs/sRAGE axis strengthened the associations observed. High glycation/sRAGE ratios were associated with 1.3 to 14-fold likelihood of lower AST/ALT ratios. The sum of AGEs/sRAGE ratios accurately distinguished between healthy controls and NAFLD patients (area under the curve of 0.85). Elevated AGEs/sRAGE (>7.8 mmol/pmol) was associated with a 12-fold likelihood of the presence of NAFLD. These findings strengthen the involvement of AGEs-RAGE axis in liver injury and the pathogenesis of NAFLD. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Cumulative psychological stress and cardiovascular disease risk in middle aged and older women: Rationale, design, and baseline characteristics.

    PubMed

    Albert, Michelle A; Durazo, Eva M; Slopen, Natalie; Zaslavsky, Alan M; Buring, Julie E; Silva, Ted; Chasman, Daniel; Williams, David R

    2017-10-01

    Although a growing body of evidence indicates strong links between psychological stress (stress) and untoward cardiovascular disease (CVD) outcomes, comprehensive examination of these effects remains lacking. The "Cumulative Psychological Stress and Cardiovascular Disease Risk in Middle Aged and Older Women" study is embedded within the landmark Women's Health Study (WHS) follow-up cohort and seeks to evaluate the individual and joint effects of stressors (cumulative stress) on incident CVD risk, including myocardial infarction, stroke, coronary revascularization and CVD death. GWAS data will be used for exploratory analyses to identify any genes associated with stress and CVD. This study prospectively follows 25,335 women (mean age 72.2 ± 6.04 years) without CVD who returned a short mailed stress questionnaire at baseline and 3 years of follow-up inquiring about their experiences with stress including perceived stress, work stress, work-family spillover, financial stress, traumatic and major life events, discrimination and neighborhood environment/stressors. Other domains ascertained were sleep, anger, cynical hostility, depression, anxiety, social support, intimate partner relations, and volunteer and social activities. Higher levels of cumulative stress were associated with younger age and black race/ethnicity, divorced or separated marital status, increased prevalence of obesity, smoking, diabetes, depression and anxiety (p<0.001 for each). Findings from this study will provide clinically important, new information about associations of cumulative stress, environmental, lifestyle and genetic factors with incident CVD risk in aging women. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. The use of satellite data to measure ultraviolet-B penetrance and its potential association with age of multiple sclerosis onset.

    PubMed

    Amram, Ofer; Schuurman, Nadine; Randall, Ellen; Zhu, Feng; Saeedi, Jameelah; Rieckmann, Peter; Yee, Irene; Tremlett, Helen

    2018-04-01

    Studies have indicated an association between low Ultraviolet B (UVB) exposure and an increased risk of developing multiple sclerosis (MS). Few studies, however, have explored whether UVB exposure is associated with the age at MS symptom onset. We investigated the potential association between cumulative early life ambient UVB exposure and age at MS onset, using satellite data to measure ambient UVB exposure. Adult onset MS patients were selected from the University of British Columbia's MS genetic database (1980-2005). Patients' places of residence from birth to age 18 years were geocoded (latitude and longitude) and assigned UVB values using NASA's Total Ozone Mapping Spectrometer (TOMS) dataset. Linear regression was used to explore the relationship between cumulative UVB exposure (measured for age periods 0-6, 7-12, 13-18, 0-12, and 0-18) and age at MS onset. 3226 patients were included in the analysis. Of these, 74% were female, with an overall mean symptom onset age of 33.3 years. At onset, a total of 2944 (91%) had a relapsing-remitting disease course, 254 (8%) had primary progressive and the disease course for 28 (1%) was unknown. No significant associations between cumulative early life ambient UVB exposure and age at MS onset were observed. Patient sex, MS phenotype, and immigration to Canada after age 18 were significantly associated with age of onset (p < 0.01). Early life ambient UVB, as measured by satellite imagery, was not significantly associated with the age at MS onset. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Traumatic brain injury history is associated with an earlier age of dementia onset in autopsy-confirmed Alzheimer's disease.

    PubMed

    Schaffert, Jeff; LoBue, Christian; White, Charles L; Chiang, Hsueh-Sheng; Didehbani, Nyaz; Lacritz, Laura; Rossetti, Heidi; Dieppa, Marisara; Hart, John; Cullum, C Munro

    2018-05-01

    To evaluate whether a history of traumatic brain injury (TBI) with reported loss of consciousness (LOC) is a risk factor for earlier onset of Alzheimer's disease (AD) in an autopsy-confirmed sample. Data from 2,133 participants with autopsy-confirmed AD (i.e., at least Braak neurofibrillary tangle stages III to VI and CERAD neuritic plaque score moderate to frequent) were obtained from the National Alzheimer's Coordinating Center (NACC). Participants were categorized by presence/absence of self-reported remote (i.e., >1 year prior to their first Alzheimer's Disease Center visit) history of TBI with LOC (TBI+ vs. TBI-). Analyses of Covariance (ANCOVA) controlling for sex, education, and race compared groups on clinician-estimated age of symptom onset and age of diagnosis. Average age of onset was 2.34 years earlier (p = .01) for the TBI+ group (n = 194) versus the TBI- group (n = 1900). Dementia was diagnosed on average 2.83 years earlier (p = .002) in the TBI+ group (n = 197) versus the TBI- group (n = 1936). Using more stringent neuropathological criteria (i.e., Braak stages V-VI and CERAD frequent), both age of AD onset and diagnosis were 3.6 years earlier in the TBI+ group (both p's < .001). History of TBI with reported LOC appears to be a risk factor for earlier AD onset. This is the first study to use autopsy-confirmed cases, supporting previous investigations that used clinical criteria for the diagnosis of AD. Further investigation as to possible underlying mechanisms of association is needed. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  15. Dermatological disease in the older age group: a cross-sectional study in aged care facilities.

    PubMed

    Deo, Maneka S; Kerse, Ngaire; Vandal, Alain C; Jarrett, Paul

    2015-12-23

    To estimate the prevalence of dermatological disease in aged care facilities, and the relationship between cognitive or physical disability and significant disease. 2 large aged care facilities in Auckland, New Zealand, each providing low and high level care. All 161 residents of the facilities were invited to participate. The only exclusion criterion was inability to obtain consent from the individual or designated guardian. 88 participants were recruited-66 females (75%), 22 males (25%) with average age 87.1 years (SD 5.5 years). Primary--presence of significant skin disease (defined as that which in the opinion of the investigators needed treatment or was identified as a patient concern) diagnosed clinically on full dermatological examination by a dermatologist or dermatology trainee. Secondary--functional and cognitive status (Rehabilitation Complexity Scale and Abbreviated Mental Test Score). 81.8% were found to have at least one significant condition. The most common disorders were onychomycosis 42 (47.7%), basal cell carcinoma 13 (14.8%), asteototic eczema 11 (12.5%) and squamous cell carcinoma in situ 9 (10.2%). Other findings were invasive squamous cell carcinoma 7 (8%), bullous pemphigoid 2 (2.3%), melanoma 2 (2.3%), lichen sclerosus 2 (2.3%) and carcinoma of the breast 1 (1.1%). Inflammatory disease was more common in those with little physical disability compared with those with serious physical disability (OR 3.69; 95% CI 1.1 to 12.6, p=0.04). No significant association was found between skin disease and cognitive impairment. A high rate of dermatological disease was found. Findings ranged from frequent but not life-threatening conditions (eg, onychomycosis), to those associated with a significant morbidity (eg, eczema, lichen sclerosus and bullous pemphigoid), to potentially life-threatening (eg, squamous cell carcinoma, melanoma and breast cancer). Those with less significant physical impairment were found to be at greater risk of inflammatory

  16. Association of Endodontic Lesions with Coronary Artery Disease.

    PubMed

    Liljestrand, J M; Mäntylä, P; Paju, S; Buhlin, K; Kopra, K A E; Persson, G R; Hernandez, M; Nieminen, M S; Sinisalo, J; Tjäderhane, L; Pussinen, P J

    2016-11-01

    An endodontic lesion (EL) is a common manifestation of endodontic infection where Porphyromonas endodontalis is frequently encountered. EL may associate with increased risk for coronary artery disease (CAD) via similar pathways as marginal periodontitis. The aim of this cross-sectional study was to delineate the associations between EL and CAD. Subgingival P. endodontalis, its immune response, and serum lipopolysaccharide were examined as potential mediators between these 2 diseases. The Finnish Parogene study consists of 508 patients (mean age, 62 y) who underwent coronary angiography and extensive clinical and radiographic oral examination. The cardiovascular outcomes included no significant CAD ( n = 123), stable CAD ( n = 184), and acute coronary syndrome (ACS; n = 169). EL was determined from a panoramic tomography. We combined data of widened periapical spaces (WPSs) and apical rarefactions to a score of EL: 1, no EL ( n = 210); 2, ≥1 WPS per 1 apical rarefaction ( n = 222); 3, ≥2 apical rarefactions ( n = 76). Subgingival P. endodontalis was defined by checkerboard DNA-DNA hybridization analysis, and corresponding serum antibodies were determined by ELISA. In our population, 50.4% had WPSs, and 22.8% apical rarefactions. A total of 51.2% of all teeth with apical rarefactions had received endodontic procedures. Subgingival P. endodontalis levels and serum immunoglobulin G were associated with a higher EL score. In the multiadjusted model (age, sex, smoking, diabetes, body mass index, alveolar bone loss, and number of teeth), having WPSs associated with stable CAD (odds ratio [OR] = 1.94, 95% confidence interval [95% CI] = 1.13 to 3.32, P = 0.016) and highest EL score were associated with ACS (OR = 2.46, 95% CI = 1.09 to 5.54, P = 0.030). This association was especially notable in subjects with untreated teeth with apical rarefactions ( n = 59, OR = 2.72, 95% CI = 1.16 to 6.40, P = 0.022). Our findings support the hypothesis that ELs are independently

  17. Aging, neurodegenerative disease, and traumatic brain injury: the role of neuroimaging.

    PubMed

    Esopenko, Carrie; Levine, Brian

    2015-02-15

    Traumatic brain injury (TBI) is a highly prevalent condition with significant effects on cognition and behavior. While the acute and sub-acute effects of TBI recover over time, relatively little is known about the long-term effects of TBI in relation to neurodegenerative disease. This issue has recently garnered a great deal of attention due to publicity surrounding chronic traumatic encephalopathy (CTE) in professional athletes, although CTE is but one of several neurodegenerative disorders associated with a history of TBI. Here, we review the literative on neurodegenerative disorders linked to remote TBI. We also review the evidence for neuroimaging changes associated with unhealthy brain aging in the context of remote TBI. We conclude that neuroimaging biomarkers have significant potential to increase understanding of the mechanisms of unhealthy brain aging and neurodegeneration following TBI, with potential for identifying those at risk for unhealthy brain aging prior to the clinical manifestation of neurodegenerative disease.

  18. Exploring the Association Between Rosacea and Parkinson Disease: A Danish Nationwide Cohort Study.

    PubMed

    Egeberg, Alexander; Hansen, Peter Riis; Gislason, Gunnar H; Thyssen, Jacob P

    2016-05-01

    The pathogenesis of rosacea is unclear, but increased matrix metalloproteinase target tissue activity appears to play an important role. Parkinson disease and other neurodegenerative disorders also display increased matrix metalloproteinase activity that contribute to neuronal loss. To investigate the risk of incident (new-onset) Parkinson disease in patients with rosacea. A nationwide cohort study of the Danish population was conducted using individual-level linkage of administrative registers. All Danish citizens 18 years or older from January 1, 1997, to December 31, 2011 (N = 5 472 745), were included. Data analysis was conducted from June 26 to July 27, 2015. The main outcome was a diagnosis of Parkinson disease. Incidence rates (IRs) per 10 000 person-years were calculated, and incidence rate ratios (IRRs) adjusted for age, sex, socioeconomic status, smoking, alcohol abuse, medication, and comorbidity were estimated by Poisson regression models. A total of 5 404 692 individuals were included in the reference population; of these, 22 387 individuals (9812 [43.8%] women; mean [SD] age at diagnosis, 75.9 [10.2] years) received a diagnosis of Parkinson disease during the study period and 68 053 individuals (45 712 [67.2%] women; mean age, 42.2 [16.5] years) were registered as having rosacea. The IRs of Parkinson disease per 10 000 person-years were 3.54 (95% CI, 3.49-3.59) in the reference population and 7.62 (95% CI, 6.78-8.57) in patients with rosacea. The adjusted IRR of Parkinson disease was 1.71 (95%, CI 1.52-1.92) in patients with rosacea compared with the reference population. There was a 2-fold increased risk of Parkinson disease in patients classified as having ocular rosacea (adjusted IRR, 2.03 [95% CI, 1.67-2.48]), and tetracycline therapy appeared to reduce the risk of Parkinson disease (adjusted IRR, 0.98 [95% CI, 0.97-0.99]). Rosacea constitutes an independent risk factor for Parkinson disease. This association could be due to shared

  19. Association of Cancer History with Alzheimer's Disease Dementia and Neuropathology.

    PubMed

    Yarchoan, Mark; James, Bryan D; Shah, Raj C; Arvanitakis, Zoe; Wilson, Robert S; Schneider, Julie; Bennett, David A; Arnold, Steven E

    2017-01-01

    Cancer and Alzheimer's disease (AD) are common diseases of aging and share many risk factors. Surprisingly, however, epidemiologic data from several recent independent cohort studies suggest that there may be an inverse association between these diseases. To determine the relationship between history of cancer and odds of dementia proximate to death and neuropathological indices of AD. Using data from two separate clinical-pathologic cohort studies of aging and AD, the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP), we compared odds of AD dementia proximate to death among participants with and without a history of cancer. We then examined the relation of history of cancer with measures of AD pathology at autopsy, i.e., paired helical filament tau (PHFtau) neurofibrillary tangles and amyloid-β load. Participants reporting a history of cancer had significantly lower odds of AD (OR 0.70 [0.55-0.89], p = 0.0040) proximate to death as compared to participants reporting no prior history of cancer. The results remained significant after adjusting for multiple risk factors including age, sex, race, education, and presence of an APOEɛ4 allele. At autopsy, participants with a history of cancer had significantly fewer PHFtau tangles (p < 0.001) than participants without a history of cancer, but similar levels of amyloid-β. Cancer survivors have reduced odds of developing AD and a lower burden of neurofibrillary tangle deposition.

  20. Age-related epigenetic drift and phenotypic plasticity loss: implications in prevention of age-related human diseases

    PubMed Central

    Li, Yuanyuan; Tollefsbol, Trygve O

    2016-01-01

    Aging is considered as one of the most important developmental processes in organisms and is closely associated with global deteriorations of epigenetic markers such as aberrant methylomic patterns. This altered epigenomic state, referred to ‘epigenetic drift’, reflects deficient maintenance of epigenetic marks and contributes to impaired cellular and molecular functions in aged cells. Epigenetic drift-induced abnormal changes during aging are scantily repaired by epigenetic modulators. This inflexibility in the aged epigenome may lead to an age-related decline in phenotypic plasticity at the cellular and molecular levels due to epigenetic drift. This perspective aims to provide novel concepts for understanding epigenetic effects on the aging process and to provide insights into epigenetic prevention and therapeutic strategies for age-related human disease. PMID:27882781

  1. The application of information theory for the research of aging and aging-related diseases.

    PubMed

    Blokh, David; Stambler, Ilia

    2017-10-01

    This article reviews the application of information-theoretical analysis, employing measures of entropy and mutual information, for the study of aging and aging-related diseases. The research of aging and aging-related diseases is particularly suitable for the application of information theory methods, as aging processes and related diseases are multi-parametric, with continuous parameters coexisting alongside discrete parameters, and with the relations between the parameters being as a rule non-linear. Information theory provides unique analytical capabilities for the solution of such problems, with unique advantages over common linear biostatistics. Among the age-related diseases, information theory has been used in the study of neurodegenerative diseases (particularly using EEG time series for diagnosis and prediction), cancer (particularly for establishing individual and combined cancer biomarkers), diabetes (mainly utilizing mutual information to characterize the diseased and aging states), and heart disease (mainly for the analysis of heart rate variability). Few works have employed information theory for the analysis of general aging processes and frailty, as underlying determinants and possible early preclinical diagnostic measures for aging-related diseases. Generally, the use of information-theoretical analysis permits not only establishing the (non-linear) correlations between diagnostic or therapeutic parameters of interest, but may also provide a theoretical insight into the nature of aging and related diseases by establishing the measures of variability, adaptation, regulation or homeostasis, within a system of interest. It may be hoped that the increased use of such measures in research may considerably increase diagnostic and therapeutic capabilities and the fundamental theoretical mathematical understanding of aging and disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. The prevalence of diabetes mellitus (DM) type II among Iranian elderly population and its association with other age-related diseases, 2012.

    PubMed

    Taheri Tanjani, Parisa; Moradinazar, Mehdi; Esmail Mottlagh, Mohammad; Najafi, Farid

    2015-01-01

    DM type II is one of the most common chronic diseases. The objective of this study is to investigate the prevalence of DM and its association with other age-related diseases in Iran, 2012. In this cross-sectional study, people aged 60 years and over were selected using multistage sampling method. Mini-Nutritional Assessment (MNA), Activity of Daily Living (ADL), and Geriatric Depression Scale (GDS-15 items) questionnaires were used. History of common disorders was taken through self-report, medical records and the results of clinical examinations. A total of 1350 old people were studied. DM type II was found in 297 (22.0%) subjects and 371 (27.5%) of subjects were not aware of their DM status. Hypertension (55.6%), high serum cholesterol (51.8%), malnutrition (40.1%), Alzheimer's disease (16.9%), weight loss within past year (16.1%), weight gain within past year (11.7%), frailty (64.6%), insomnia (50.1%), and vision problems (62.6%) were significantly more common in diabetics. Those who were not aware of their status of DM either were between diabetics and non-diabetics or more similar to non-diabetics. Considering high prevalence of age-related diseases among Iranian elderly people, in particular women and those with DM type II, preventive measures are recommended so as to decrease and control DM type II and its consequent complications. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. White matter disease severity of the brain and its association with geriatric syndromes.

    PubMed

    Alagiakrishnan, Kannayiram; Hsueh, Jenny; Zhang, Edwin; Khan, Khurshid; Senthilselvan, Ambikaipakan

    2013-11-01

    White matter disease (WMD) of the brain is considered to be secondary to small vessel ischemia and can be a single unifying risk factor for the development of geriatric syndromes. The aim of our study was to investigate the association of the global and regional severity of WMD in the brain with geriatric syndromes burden. In our retrospective study, consecutive outpatient charts from patients seen between January 2010 and June 2011 at University of Alberta Hospital Seniors Clinic were reviewed. Subjects with brain computed tomography (CT) scans were included in the study. Subjects with incomplete information or with diseases that confounded WMD assessment on CT were excluded. White matter disease was quantified on CT using Wahlund scoring. A multiple linear regression analysis was conducted to determine the association of WMD severity with geriatric syndromes burden after controlling for confounding vascular risk factors. Of the 505 subjects, 326 (64.6%) were women. Mean age of the study patients was 79.8 years (SD ± 7.04), prevalence of WMD disease was 79.4%, and mean WMD score was 5.1 (SD ± 4.4). In subjects aged < and > 80 years, the mean number of geriatric syndromes was 2.83 (standard error of the mean [SE] 0.08) and 3.22 (SE 0.08), respectively. In the adjusted regression analysis, there was a significant association between WMD severity, globally (regression coefficient (β) = 0.457, SE 0.155; P = 0.003), as well as WMD in specific regions: frontal (P < 0.001), parieto-occipital (P = 0.004), and infratentorial regions (P = 0.04) with geriatric syndromes burden. The association remains even after correcting for age, sex, and all vascular risk factors. In our study, there was a significant association between the severity of global and selected regional WMD of the brain with geriatric syndromes burden, thus raising the possibility of a shared biologic association through vascular pathology of the brain.

  4. [Association between adverse experiences in childhood and risk of chronic diseases in adulthood].

    PubMed

    Nie, Junyan; Yu, Honghui; Wang, Zhiqiang; Wang, Leilei; Han, Juan; Wang, Youjie; Du, Yukai; Shen, Min

    2015-09-01

    To analyze the prevalence and characteristics of childhood adverse experiences among adults aged 18-59 years and understand the association between childhood adverse experiences and risk of chronic diseases in adulthood. A cross-sectional study was conducted with a questionnaire among adults aged 18-59 years selected through cluster random sampling from 3 communities in Macheng, Hubei province. Uinivariate and multivariate logistic regression analyses were conducted to evaluate the association between adverse experiences in childhood and the risk of chronic diseases in adulthood. A total of 1 767 adults aged 18-59 years were surveyed and 1 501 valid questionnaires were returned. The average age was (36.32± 10.20) years for males and (35.72±9.08) years for females. The prevalence rate of childhood adverse experiences was 66.22%. The risk of chronic disease in adults increased with the increase of the score indicating childhood adverse experiences (Z=-5.902 1, P<0.000 1). Multivariate logistic regression analysis showed that being physically abused (OR=1.93, 95% CI: 1.41-2.64), substance abuse in family (OR=2.82, 95% CI: 1.16-6.80), being bullied (OR=2.59, 95% CI: 1.39-4.80) and parents separation/divorce (OR=1.51, 95% CI: 1.09-2.09) were significantly associated with risk of chronic diseases in adulthood. The prevalence of adverse childhood experiences was high in adults aged 18-59 years, which was significantly associated with the risk of chronic diseases in adulthood. Early prevention of chronic diseases should be conducted in childhood.

  5. Astrocytes in physiological aging and Alzheimer's disease.

    PubMed

    Rodríguez-Arellano, J J; Parpura, V; Zorec, R; Verkhratsky, A

    2016-05-26

    Astrocytes are fundamental for homoeostasis, defence and regeneration of the central nervous system. Loss of astroglial function and astroglial reactivity contributes to the aging of the brain and to neurodegenerative diseases. Changes in astroglia in aging and neurodegeneration are highly heterogeneous and region-specific. In animal models of Alzheimer's disease (AD) astrocytes undergo degeneration and atrophy at the early stages of pathological progression, which possibly may alter the homeostatic reserve of the brain and contribute to early cognitive deficits. At later stages of AD reactive astrocytes are associated with neurite plaques, the feature commonly found in animal models and in human diseased tissue. In animal models of the AD reactive astrogliosis develops in some (e.g. in the hippocampus) but not in all regions of the brain. For instance, in entorhinal and prefrontal cortices astrocytes do not mount gliotic response to emerging β-amyloid deposits. These deficits in reactivity coincide with higher vulnerability of these regions to AD-type pathology. Astroglial morphology and function can be regulated through environmental stimulation and/or medication suggesting that astrocytes can be regarded as a target for therapies aimed at the prevention and cure of neurodegenerative disorders. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Age-related impairments of mobility associated with cobalt and other heavy metals: Data from NHANES 1999-2004

    PubMed Central

    Lang, Iain A; Scarlett, Alan; Guralnik, Jack; Depledge, Michael H; Melzer, David; Galloway, Tamara S

    2012-01-01

    Introduction Exposure to heavy metals can promote oxidative stress and damage to cellular components, and may accelerate age-related disease and disability.. Physical mobility is a validated biomarker of age-related disability and is predictive of hospitalization and mortality. Aim To examine associations between selected heavy metals and impaired lower limb mobility in a representative older human population. Methods Data for 1615 adults aged ≥60 years from the National Health and Nutrition Examination Survey (NHANES) 1999 to 2004 were used to identify associations between urinary concentrations of 10 metals with self-reported and measured walking impairments (at p<0.01). Models were adjusted for confounding factors, including smoking. Results In models adjusted for age, sex and ethnicity, elevated levels of cadmium, cobalt and uranium were associated with impairment of the ability to walk a quarter mile. In fully adjusted models, cobalt was the only metal that remained associated: the odds ratio for reporting walking problems with a 1-unit increase in logged cobalt concentration (μg L-1) was 1.43 (95% CI 1.12 to 1.84). Cobalt was also the only metal associated with an increased measured time to walk a 20 foot course (p=0.008). In analyses of disease categories to explain the mobility finding, cobalt was associated with physician diagnosed arthritis (1-unit increase OR=1.22 (95% CI 1.00 to 1.49, p=0.045). Conclusions Low level cobalt exposure, assessed through urinary concentrations of this essential heavy metal may be a risk factor for age-related physical impairments. Independent replication is needed to confirm this association. PMID:19199147

  7. Lung Disease Including Asthma and Adult Vaccination

    MedlinePlus

    ... Vaccine-Preventable Adult Diseases Resources Lung Disease including Asthma and Adult Vaccination Language: English (US) Español (Spanish) ... are hospitalized, and some even die. People with asthma or COPD are at higher risk for serious ...

  8. A Culture-Brain Link: Negative Age Stereotypes Predict Alzheimer’s-disease Biomarkers

    PubMed Central

    Levy, Becca R.; Ferrucci, Luigi; Zonderman, Alan B.; Slade, Martin D.; Troncoso, Juan; Resnick, Susan M.

    2016-01-01

    Although negative age stereotypes have been found to predict adverse outcomes among older individuals, it was unknown whether the influence of stereotypes extends to brain changes associated with Alzheimer’s disease. To consider this possibility, we drew on the age stereotypes of dementia-free participants in the Baltimore Longitudinal Study of Aging that had been measured decades before yearly MRIs and brain autopsies were performed. Those with more negative age stereotypes earlier in life had significantly steeper hippocampal-volume loss, and significantly greater accumulation of neurofibrillary tangles and amyloid plaques at autopsy, adjusting for relevant covariates. These findings suggest a new pathway to identifying mechanisms and potential interventions related to the neuropathology of Alzheimer’s disease. PMID:26641877

  9. Association between chronic azotemic kidney disease and the severity of periodontal disease in dogs.

    PubMed

    Glickman, Lawrence T; Glickman, Nita W; Moore, George E; Lund, Elizabeth M; Lantz, Gary C; Pressler, Barrak M

    2011-05-01

    Naturally occurring periodontal disease affects >75% of dogs and has been associated with cardiac lesions and presumptive endocarditis. However, the relationships between periodontal disease and chronic kidney disease (CKD) in dogs have not been studied. In a retrospective longitudinal study the incidence of azotemic CKD was compared between a cohort of 164,706 dogs with periodontal disease and a cohort of age-matched dogs with no periodontal disease from a national primary care practice. These dogs contributed 415,971 dog-years of follow-up from 2002 to 2008. Hazard ratios and 95% confidence intervals from Cox regression were used to compare the incidence of azotemic CKD in dogs with stage 1, 2, or 3/4 periodontal disease to dogs with no periodontal disease. The hazard ratio for azotemic CKD increased with increasing severity of periodontal disease (stage 1 hazard ratio=1.8, 95% confidence interval: 1.6, 2.1; stage 2 hazard ratio=2.0, 95% confidence interval: 1.7, 2.3; stage 3/4 hazard ratio=2.7, 95% confidence interval: 2.3, 3.0; P(trend)=<0.0001) after adjustment for age, gender, neuter status, breed, body weight, number of hospital visits, and dental procedures. Increasing severity of periodontal disease was also associated with serum creatinine >1.4 mg/dl and blood urea nitrogen >36 mg/dl, independent of a veterinarian's clinical diagnosis of CKD. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Periodontal disease associates with higher brain amyloid load in normal elderly

    PubMed Central

    Kamer, Angela R.; Pirraglia, Elizabeth; Tsui, Wai; Rusinek, Henry; Vallabhajosula, Shankar; Mosconi, Lisa; Yi, Li; McHugh, Pauline; Craig, Ronald G.; Svetcov, Spencer; Linker, Ross; Shi, Chen; Glodzik, Lidia; Williams, Schantel; Corby, Patricia; Saxena, Deepak; de Leon, Mony J.

    2015-01-01

    Background The accumulation of amyloid β plaques (Aβ) is a central feature of Alzheimer’s disease (AD). First reported in animal models, it remains uncertain if peripheral inflammatory/infectious conditions in humans can promote Aβ brain accumulation. Periodontal disease, a common chronic infection, has been previously reported to be associated with AD. Methods Thirty-eight cognitively normal, healthy, community residing elderly (mean age 61; 68% female) were examined in an Alzheimer’s Disease research center and a University-based Dental School. Linear regression models (adjusted for age, ApoE and smoking) were used to test the hypothesis that periodontal disease assessed by clinical attachment loss was associated with brain Aβ load using 11C-PIB PET imaging. Results After adjusting for confounders, clinical attachment loss (≥ 3mm), representing a history of periodontal inflammatory/infectious burden, was associated with increased 11C-PIB uptake in Aβ vulnerable brain regions (p=0.002). Conclusion We show for the first time in humans an association between periodontal disease and brain Aβ load. These data are consistent with prior animal studies showing that peripheral inflammation/infections are sufficient to produce brain Aβ accumulations. PMID:25491073

  11. Anxiety and depression in adult outpatients with bronchiectasis: Associations with disease severity and health-related quality of life.

    PubMed

    Gao, Yong-Hua; Guan, Wei-Jie; Zhu, Ya-Nan; Chen, Rong-Chang; Zhang, Guo-Jun

    2018-04-01

    Anxiety and depression might frequently affect bronchiectasis patients, but data in Chinese patients, including their association with disease severity assessed with Bronchiectasis Severity Index (BSI) and FACED score, are limited. To investigate the rate, risk factors, association with disease severity and impact of anxiety and depression on health-related quality of life (HRQoL) in adult outpatients with steady-state bronchiectasis. This cross-sectional study included 163 outpatients (102 females; mean age, 45.8 years) and 80 healthy subjects (47 females; mean age, 47.1 years). Demographic, clinical indices, radiology, spirometry, aetiology, sputum bacteriology, Hospital Anxiety and Depression Scales (HADS), Pittsburgh Sleep Quality Index (PSQI) and St. George's Respiratory Questionnaire (SGRQ) were assessed. Patients with steady-state bronchiectasis had a higher rate of depression (HADS-depression >7) (30.1% vs 10.0%, P = .001) and anxiety (HADS-anxiety >7; 39.9% vs 6.3%, P < .001) compared with healthy subjects. Notably, no significant differences in the rate of anxiety and depression were found across different disease severity, assessed with BSI and FACED score (all P > .05). In multivariate model, factors associated with anxiety included younger age (OR = 1.05), education below college graduate (OR = 4.55) and sleep disturbance (PSQI ≥ 6; OR = 2.95); whereas sleep disturbance was the sole factor associated with depression (OR = 5.98). Patients with either depression or anxiety had more markedly impaired HRQoL affecting most domains than those without. Anxiety and depression are common in bronchiectasis and can negatively affect HRQoL, but not related to disease severity. Prompt assessment and treatment of these mental disorders, regardless of bronchiectasis severity, are advocated and might improve HRQoL. © 2017 John Wiley & Sons Ltd.

  12. Angiotensin II Type 1 Receptor-Associated Protein Regulates Kidney Aging and Lifespan Independent of Angiotensin.

    PubMed

    Uneda, Kazushi; Wakui, Hiromichi; Maeda, Akinobu; Azushima, Kengo; Kobayashi, Ryu; Haku, Sona; Ohki, Kohji; Haruhara, Kotaro; Kinguchi, Sho; Matsuda, Miyuki; Ohsawa, Masato; Minegishi, Shintaro; Ishigami, Tomoaki; Toya, Yoshiyuki; Atobe, Yoshitoshi; Yamashita, Akio; Umemura, Satoshi; Tamura, Kouichi

    2017-07-27

    The kidney is easily affected by aging-associated changes, including glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Particularly, renal tubulointerstitial fibrosis is a final common pathway in most forms of progressive renal disease. Angiotensin II type 1 receptor (AT1R)-associated protein (ATRAP), which was originally identified as a molecule that binds to AT1R, is highly expressed in the kidney. Previously, we have shown that ATRAP suppresses hyperactivation of AT1R signaling, but does not affect physiological AT1R signaling. We hypothesized that ATRAP has a novel functional role in the physiological age-degenerative process, independent of modulation of AT1R signaling. ATRAP-knockout mice were used to study the functional involvement of ATRAP in the aging. ATRAP-knockout mice exhibit a normal age-associated appearance without any evident alterations in physiological parameters, including blood pressure and cardiovascular and metabolic phenotypes. However, in ATRAP-knockout mice compared with wild-type mice, the following takes place: (1) age-associated renal function decline and tubulointerstitial fibrosis are more enhanced; (2) renal tubular mitochondrial abnormalities and subsequent increases in the production of reactive oxygen species are more advanced; and (3) life span is 18.4% shorter (median life span, 100.4 versus 123.1 weeks). As a key mechanism, age-related pathological changes in the kidney of ATRAP-knockout mice correlated with decreased expression of the prosurvival gene, Sirtuin1 . On the other hand, chronic angiotensin II infusion did not affect renal sirtuin1 expression in wild-type mice. These results indicate that ATRAP plays an important role in inhibiting kidney aging, possibly through sirtuin1-mediated mechanism independent of blocking AT1R signaling, and further protecting normal life span. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  13. Influenza-Associated Disease Burden in Kenya: A Systematic Review of Literature

    PubMed Central

    Emukule, Gideon O.; Paget, John; van der Velden, Koos; Mott, Joshua A.

    2015-01-01

    Background In Kenya data on the burden of influenza disease are needed to inform influenza control policies. Methods We conducted a systematic review of published data describing the influenza disease burden in Kenya using surveillance data collected until December 2013. We included studies with laboratory confirmation of influenza, well-defined catchment populations, case definitions used to sample patients for testing and a description of the laboratory methods used for influenza testing. Studies with or without any adjustments on the incidence rates were included. Results Ten studies reporting the incidence of medically-attended and non-medically attended influenza were reviewed. For all age groups, the influenza positive proportion ranged from 5–10% among hospitalized patients, and 5–27% among all medically-attended patients (a combination of in- and outpatients). The adjusted incidence rate of hospitalizations with influenza among children <5 years ranged from 2.7–4.7 per 1,000 [5.7 per 1,000 in children <6 months old], and were 7–10 times higher compared to persons aged ≥5 years. The adjusted incidence of all medically-attended influenza among children aged <5 years ranged from 13.0–58.0 per 1,000 compared to 4.3–26.0 per 1,000 among persons aged ≥5 years. Conclusions Our review shows an expanding set of literature on disease burden associated with influenza in Kenya, with a substantial burden in children under five years of age. Hospitalizations with influenza in these children were 2–3 times higher than reported in the United States. These findings highlight the possible value of an influenza vaccination program in Kenya, with children <5 years and pregnant women being potentially important targets. PMID:26398196

  14. Association of body flexibility and carotid atherosclerosis in Japanese middle-aged men: a cross-sectional study.

    PubMed

    Suwa, Masataka; Imoto, Takayuki; Kida, Akira; Yokochi, Takashi; Iwase, Mitsunori; Kozawa, Kenji

    2018-01-05

    This study examined the associations of body flexibility with carotid arterial remodelling, including intima-media thickness (IMT) and plaque formation in middle-aged men. The subjects of this cross-sectional study included 1354 Japanese men aged 35-59 years without histories of stroke or cardiac diseases. The arm extensibility test, which can estimate flexibility of the upper extremity (composed of shoulder external rotation and forearm supination), and the sit-and-reach test were performed. Common carotid IMT and plaque formation (≥1.1 mm) were estimated by ultrasound. The proportion of subjects who fully completed the arm extensibility test was 55.0%, and who had plaques in the common carotid artery was 37.8%. IMT was associated with poor arm extensibility (β=-0.073, 95% CI -0.02224 to - 0.00041, P=0.004), while plaque formation was associated with poor sit-and-reach (OR 0.98579, 95% CI 0.97257 to 0.99919, P=0.038) after adjustment by all covariates. This study demonstrated that poor upper extremity and trunk flexibility were associated with characteristics of early onset of atherosclerosis. Furthermore, these associations were independent of covariates such as age, blood pressure, blood lipids glucose levels and abdominal fat accumulation, handgrip strength and lifestyle, including sleeping, drinking, exercise and smoking habits. Poor flexibility may reflect subclinical atherosclerosis in middle-aged men. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. The effects of infographics and several quantitative versus qualitative formats for cardiovascular disease risk, including heart age, on people's risk understanding.

    PubMed

    Damman, Olga C; Vonk, Suzanne I; van den Haak, Maaike J; van Hooijdonk, Charlotte M J; Timmermans, Danielle R M

    2018-03-11

    To study how comprehension of cardiovascular disease (CVD) risk is influenced by: (1) infographics about qualitative risk information, with/without risk numbers; (2) which qualitative risk dimension is emphasized; (3) heart age vs. traditional risk format. For aim 1, a 2 (infographics versus text) x 2 (risk number versus no risk number) between-subjects design was used. For aim 2, three pieces of information were tested within-subjects. Aim 3 used a simple comparison group. Participants (45-65 yrs old) were recruited through an online access panel; low educated people were oversampled. They received hypothetical risk information (20%/61yrs). Primary outcomes: recall, risk appraisals, subjective/objective risk comprehension. behavioral intentions, information evaluations. Infographics of qualitative risk dimensions negatively affected recall, subjective risk comprehension and information evaluations. No effect of type of risk dimension was found on risk perception. Heart age influenced recall, comprehension, evaluations and affective risk appraisals. Infographics of hypothetical CVD risk information had detrimental effects on measures related to risk perception/comprehension, but effects were mainly seen in undereducated participants. Heart age influenced perceptions/comprehension of hypothetical risk in a way that seemed to support understanding. Heart age seems a fruitful risk communication approach in disease risk calculators. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Association Studies of 22 Candidate SNPs with Late-Onset Alzheimer's Disease

    PubMed Central

    Figgins, Jessica A.; Minster, Ryan L.; Demirci, F. Yesim; DeKosky, Steven T.; Kamboh, M. Ilyas

    2009-01-01

    Alzheimer's disease (AD) is a complex and multifactorial disease with the possible involvement of several genes. With the exception of the APOE gene as a susceptibility marker, no other genes have been shown consistently to be associated with late-onset AD (LOAD). A recent genome-wide association study of 17,343 gene-based putative functional single nucleotide polymorphisms (SNPs) found 19 significant variants, including 3 linked to APOE, showing association with LOAD (Hum Mol Genet 2007; 16:865–873). We have set out to replicate the 16 new significant associations in a large case-control cohort of American Whites. Additionally, we examined six variants present in positional and/or biological candidate genes for AD. We genotyped the 22 SNPs in up to 1,009 Caucasian Americans with LOAD and up to 1,010 age-matched healthy Caucasian Americans, using 5′ nuclease assays. We did not observe a statistically significant association between the SNPs and the risk of AD, either individually or stratified by APOE. Our data suggest that the association of the studied variants with LOAD risk, if it exists, is not statistically significant in our sample. PMID:18780302

  17. Changes in Circulating B Cell Subsets Associated with Aging and Acute SIV Infection in Rhesus Macaques.

    PubMed

    Chang, W L William; Gonzalez, Denise F; Kieu, Hung T; Castillo, Luis D; Messaoudi, Ilhem; Shen, Xiaoying; Tomaras, Georgia D; Shacklett, Barbara L; Barry, Peter A; Sparger, Ellen E

    2017-01-01

    Aging and certain viral infections can negatively impact humoral responses in humans. To further develop the nonhuman primate (NHP) model for investigating B cell dynamics in human aging and infectious disease, a flow cytometric panel was developed to characterize circulating rhesus B cell subsets. Significant differences between human and macaque B cells included the proportions of cells within IgD+ and switched memory populations and a prominent CD21-CD27+ unswitched memory population detected only in macaques. We then utilized the expanded panel to analyze B cell alterations associated with aging and acute simian immunodeficiency virus (SIV) infection in the NHP model. In the aging study, distinct patterns of B cell subset frequencies were observed for macaques aged one to five years compared to those between ages 5 and 30 years. In the SIV infection study, B cell frequencies and absolute number were dramatically reduced following acute infection, but recovered within four weeks of infection. Thereafter, the frequencies of activated memory B cells progressively increased; these were significantly correlated with the magnitude of SIV-specific IgG responses, and coincided with impaired maturation of anti-SIV antibody avidity, as previously reported for HIV-1 infection. These observations further validate the NHP model for investigation of mechanisms responsible for B cells alterations associated with immunosenescence and infectious disease.

  18. A rat model system to study complex disease risks, fitness, aging, and longevity.

    PubMed

    Koch, Lauren Gerard; Britton, Steven L; Wisløff, Ulrik

    2012-02-01

    The association between low exercise capacity and all-cause morbidity and mortality is statistically strong yet mechanistically unresolved. By connecting clinical observation with a theoretical base, we developed a working hypothesis that variation in capacity for oxygen metabolism is the central mechanistic determinant between disease and health (aerobic hypothesis). As an unbiased test, we show that two-way artificial selective breeding of rats for low and high intrinsic endurance exercise capacity also produces rats that differ for numerous disease risks, including the metabolic syndrome, cardiovascular complications, premature aging, and reduced longevity. This contrasting animal model system may prove to be translationally superior relative to more widely used simplistic models for understanding geriatric biology and medicine. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Dynamic network communication as a unifying neural basis for cognition, development, aging, and disease.

    PubMed

    Voytek, Bradley; Knight, Robert T

    2015-06-15

    Perception, cognition, and social interaction depend upon coordinated neural activity. This coordination operates within noisy, overlapping, and distributed neural networks operating at multiple timescales. These networks are built upon a structural scaffolding with intrinsic neuroplasticity that changes with development, aging, disease, and personal experience. In this article, we begin from the perspective that successful interregional communication relies upon the transient synchronization between distinct low-frequency (<80 Hz) oscillations, allowing for brief windows of communication via phase-coordinated local neuronal spiking. From this, we construct a theoretical framework for dynamic network communication, arguing that these networks reflect a balance between oscillatory coupling and local population spiking activity and that these two levels of activity interact. We theorize that when oscillatory coupling is too strong, spike timing within the local neuronal population becomes too synchronous; when oscillatory coupling is too weak, spike timing is too disorganized. Each results in specific disruptions to neural communication. These alterations in communication dynamics may underlie cognitive changes associated with healthy development and aging, in addition to neurological and psychiatric disorders. A number of neurological and psychiatric disorders-including Parkinson's disease, autism, depression, schizophrenia, and anxiety-are associated with abnormalities in oscillatory activity. Although aging, psychiatric and neurological disease, and experience differ in the biological changes to structural gray or white matter, neurotransmission, and gene expression, our framework suggests that any resultant cognitive and behavioral changes in normal or disordered states or their treatment are a product of how these physical processes affect dynamic network communication. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights

  20. Cognitive reserve in ageing and Alzheimer's disease

    PubMed Central

    Stern, Yaakov

    2012-01-01

    The concept of reserve accounts for individual differences in susceptibility to age-related brain changes or Alzheimer's disease-related pathology. There is evidence that some people can tolerate more of these changes than others and still maintain function. Epidemiologic studies suggest that lifetime exposures including educational and occupational attainment, and leisure activities in late life, can increase this reserve. For example, there is a reduced risk of developing Alzheimer's disease in individuals with higher educational or occupational attainment. It is convenient to think of two types of reserve: brain reserve, which refers to actual differences in the brain itself that may increase tolerance of pathology, and cognitive reserve. Cognitive reserve refers to individual differences in how tasks are performed that may allow some people to be more resilient than others. The concept of cognitive reserve holds out the promise of interventions that could slow cognitive aging or reduce the risk of dementia. PMID:23079557

  1. Association between physical fitness, cardiovascular risk factors, and Parkinson's disease.

    PubMed

    Müller, Jan; Myers, Jonathan

    2018-01-01

    Objective Exercise is a cornerstone of therapy for Parkinson's disease. This study addressed the association between physical fitness and the onset of Parkinson's disease and association with cardiovascular risk factors. Patients and methods Male veterans ( N = 7347, 59.0 ± 11.2 years) from the Veterans Exercise Testing Study cohort were evaluated. Physical fitness was measured objectively by maximal exercise testing. Onset of Parkinson's disease was abstracted from the Veterans Affairs computerized patient records system. Results After a mean follow-up of 12.5 ± 6.3 years, a total of 94 (1.3%) developed Parkinson's disease. Incidence was 86 cases per 100,000 person-years. The strongest multivariate factors associated with incidence of Parkinson's disease were higher age (hazard ratio: 1.067, 95% confidence interval (CI): 1.043-1.093, p < .001), current smoking (hazard ratio: 0.511, 95% CI: 0.274-0.953, p = .035) and physical fitness (high vs. low: hazard ratio: 0.239, 95% CI: 0.079-0.725, p = .011). Compared with patients with no or only one of these risk factors, patients with two risk factors had a 3.7-fold ( p < .001) increased risk for incidence of Parkinson's disease; those with all three risk factors had a 7.8-fold ( p < .001) higher risk. Conclusions High physical fitness, current smoking and younger age were associated with a lower incidence of Parkinson's disease. These findings parallel those of several epidemiological studies focusing on physical activity and the onset of Parkinson's disease. Together, these observations provide strong support for recommending physical activity to diminish risk of Parkinson's disease.

  2. The Association Between Unhealthy Lifestyle Behaviors and the Prevalence of Chronic Kidney Disease (CKD) in Middle-Aged and Older Men

    PubMed Central

    Michishita, Ryoma; Matsuda, Takuro; Kawakami, Shotaro; Kiyonaga, Akira; Tanaka, Hiroaki; Morito, Natsumi; Higaki, Yasuki

    2016-01-01

    Background This cross-sectional study evaluated the association between unhealthy lifestyle behaviors and the prevalence of chronic kidney disease (CKD) in middle-aged and older men. Methods The subjects included 445 men without a history of cardiovascular disease, stroke, or dialysis treatment, who were not taking medications. Unhealthy lifestyle behaviors were evaluated using a standardized self-administered questionnaire and were defined as follows: 1) lack of habitual moderate exercise, 2) lack of daily physical activity, 3) slow walking speed, 4) fast eating speed, 5) late-night dinner, 6) bedtime snacking, and 7) skipping breakfast. The participants were divided into four categories, which were classified into quartile distributions based on the number of unhealthy lifestyle behaviors (0–1, 2, 3, and ≥4 unhealthy behaviors). Results According to a multivariate analysis, the odds ratio (OR) for CKD (defined as estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2 and/or proteinuria) was found to be significantly higher in the ≥4 group than in the 0–1 group (OR 4.67; 95% confidence interval [CI], 1.51–14.40). Moreover, subjects’ lack of habitual moderate exercise (OR 3.06; 95% CI, 1.13–8.32) and presence of late-night dinner (OR 2.84; 95% CI, 1.40–5.75) and bedtime snacking behaviors (OR 2.87; 95% CI, 1.27–6.45) were found to be significantly associated with the prevalence of CKD. Conclusions These results suggest that an accumulation of unhealthy lifestyle behaviors, especially those related to lack of habitual moderate exercise and presence of late-night dinner and bedtime snacking may be associated with the prevalence of CKD. PMID:26947951

  3. Molecular circuitry of stem cell fate in skeletal muscle regeneration, ageing, and disease

    PubMed Central

    Almada, Albert E.; Wagers, Amy J.

    2016-01-01

    Satellite cells are adult myogenic stem cells that function to repair damaged muscle. The enduring capacity for muscle regeneration requires efficient satellite cell expansion after injury, differentiation to produce myoblasts that can reconstitute damaged fibers, and self-renewal to replenish the muscle stem cell pool for subsequent rounds of injury and repair. Emerging studies indicate that misregulations of satellite cell fate and function contribute to age-associated muscle dysfunction and influence the severity of muscle diseases, including Duchenne Muscular Dystrophy (DMD). It has also become apparent that satellite cell fate during muscle regeneration, aging, and in the context of DMD is governed by an intricate network of intrinsic and extrinsic regulators. Targeted manipulation of this network may offer unique opportunities for muscle regenerative medicine. PMID:26956195

  4. Increased White Matter Inflammation in Aging- and Alzheimer’s Disease Brain

    PubMed Central

    Raj, Divya; Yin, Zhuoran; Breur, Marjolein; Doorduin, Janine; Holtman, Inge R.; Olah, Marta; Mantingh-Otter, Ietje J.; Van Dam, Debby; De Deyn, Peter P.; den Dunnen, Wilfred; Eggen, Bart J. L.; Amor, Sandra; Boddeke, Erik

    2017-01-01

    Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer’s disease (AD)-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis. Particularly in white matter microglia of 24-month-old mice, abundant expression of phagocytic markers including Mac-2, Axl, CD16/32, Dectin1, CD11c, and CD36 was detected. Interestingly, in white matter of human brain tissue the first signs of inflammatory activity were already detected during middle age. Thus quantification of microglial proteins, such as CD68 (commonly associated with phagocytosis) and HLA-DR (associated with antigen presentation), in postmortem human white matter brain tissue showed an age-dependent increase in immunoreactivity already in middle-aged people (53.2 ± 2.0 years). This early inflammation was also detectable by non-invasive positron emission tomography imaging using [11C]-(R)-PK11195, a ligand that binds to activated microglia. Increased microglia activity was also prominently present in the white matter of human postmortem early-onset AD (EOAD) brain tissue. Interestingly, microglia activity in the white matter of late-onset AD (LOAD) CNS was similar to that of the aged clinically silent AD cases. These data indicate that microglia-induced neuroinflammation is predominant in the white matter of aging mice and humans as well as in EOAD brains. This white matter inflammation may contribute to the progression of neurodegeneration, and have prognostic value for detecting the onset and progression of aging and neurodegeneration. PMID:28713239

  5. Specific and combined subjective responses to noise and their association with cardiovascular diseases.

    PubMed

    Vandasova, Zdenka; Vencálek, Ondřej; Puklová, Vladimíra

    2016-01-01

    Noise is one of the most extensive environmental factors affecting the general population. The present study is focused on the association between discomfort caused by noise and the incidence of certain diseases (ischaemic heart disease, stroke and hypertension). This cross-sectional questionnaire study, conducted in 10 cities in the Czech Republic, comprises two stages with 3592 obtained questionnaires in the first phase and 762 in the second phase. Twelve variables describe subjective responses to noise from different sources at different times of day. The intensity of the associations between variables was measured by correlation coefficient. Logistic regression was used for fitting models of morbidity, and confounders such as age and socio-economic status were included. The hypotheses from the first phase were independently validated using data from the second phase. The general rates of noise annoyance/sleep disturbance had greater correlation with traffic noise variables than with neighbourhood noise variables. Factors significantly associated with diseases are: for hypertension - annoyance by traffic noise (the elderly, odds ratio (OR) 1.4) and sleep disturbance by traffic and neighbourhood noise (the elderly, OR 1.6); for ischaemic heart disease - the general rate of noise annoyance (all respondents, OR 1.5 and the adults 30-60 years, OR 1.8) and the general rate of annoyance and sleep disturbance (all respondents, OR 1.3); for stroke - annoyance and sleep disturbance by traffic and neighbourhood noise (all respondents, OR 1.8). Factors that include multiple sources of noise or non-specific noise are associated with the studied diseases more frequently than the source-specific factors.

  6. Cumulative Lifetime Marijuana Use and Incident Cardiovascular Disease in Middle Age: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

    PubMed

    Reis, Jared P; Auer, Reto; Bancks, Michael P; Goff, David C; Lewis, Cora E; Pletcher, Mark J; Rana, Jamal S; Shikany, James M; Sidney, Stephen

    2017-04-01

    To investigate the effects of marijuana in the development of incident cardiovascular and cerebrovascular outcomes. Participants were 5113 adults aged 18 to 30 years at baseline (1985-1986) from the Coronary Artery Risk Development in Young Adults study, who were followed for more than 25 years. We estimated cumulative lifetime exposure to marijuana using repeated assessments collected at examinations every 2 to 5 years. The primary outcome was incident cardiovascular disease (CVD) through 2013. A total of 84% (n = 4286) reported a history of marijuana use. During a median 26.9 years (131 990 person-years), we identified 215 CVD events, including 62 strokes or transient ischemic attacks, 104 cases of coronary heart disease, and 50 CVD deaths. Compared with no marijuana use, cumulative lifetime and recent marijuana use showed no association with incident CVD, stroke or transient ischemic attacks, coronary heart disease, or CVD mortality. Marijuana use was not associated with CVD when stratified by age, gender, race, or family history of CVD. Neither cumulative lifetime nor recent use of marijuana is associated with the incidence of CVD in middle age.

  7. [Factors associated with the frailty of elderly people with chronic kidney disease on hemodialysis].

    PubMed

    Gesualdo, Gabriela Dutra; Zazzetta, Marisa Silvana; Say, Karina Gramani; Orlandi, Fabiana de Souza

    2016-11-01

    The scope of this article is to identify sociodemographic and clinical factors associated with the frailty of elderly people with chronic kidney disease on hemodialysis. This involved a correlational, cross-sectional study conducted in a dialysis center in the state of São Paulo. The sample consisted of 60 participants. The Participant Characterization Instrument was used for extracting sociodemographic and clinical data and the Edmonton Frail Scale was used to evaluate the level of frailty. Multivariate logistic regression was used to identify the factors associated with frailty. The mean age of the 60 patients included was 71.1 (± 6.9) years, predominantly male (70%), of which 36.7% were classified as frail. With respect to the factors associated with frailty among the variables of gender, age, self-reported skin color, schooling, monthly per capita income, hemodialysis time, number of associated diseases, falls in the year, hematocrit level, parathyroid hormone and use of calcitriol, it was found that only the monthly per capita income was significantly associated with frailty (OR = 0.44; 95% CI 0.1-0.9; p = 0.04). There was an association between frailty and income, showing that the elderly most at risk of frailty were those with lower income.

  8. Racial Differences in Associations of Blood Pressure Components in Young Adulthood With Incident Cardiovascular Disease by Middle Age: Coronary Artery Risk Development in Young Adults (CARDIA) Study.

    PubMed

    Yano, Yuichiro; Reis, Jared P; Tedla, Yacob G; Goff, David C; Jacobs, David R; Sidney, Stephen; Ning, Hongyan; Liu, Kiang; Greenland, Philip; Lloyd-Jones, Donald M

    2017-04-01

    Data are sparse regarding which blood pressure (BP) components in young adulthood optimally determine cardiovascular disease (CVD) by middle age. To assess which BP components best determine incident CVD events in young adults and determine whether these associations vary by race and age at BP measurement. Using data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, this study assessed the longitudinal race-stratified associations between BP and cardiovascular outcomes. CARDIA is a community-based cohort that recruited black and white individuals (age range, 18-30 years) from March 26, 1985, through June 7, 1986. CARDIA followed up participants for up to 28 years, and 94% of the surviving cohort completed at least 1 telephone interview or examination from August 2009 through August 2014. Blood pressures measubred at baseline (Y0) and 15 years later (Y15). Composite CVD events, including coronary heart disease, stroke, heart failure, and other vascular diseases. A total of 4880 participants participated in the study (mean [SD] age, 24.9 [3.6] years at Y0 and 25.0 [3.6] years at Y15; 2223 male [45.6%] at Y0 and 1800 [44.2%] at Y15; 2657 female [54.4%] at Y0 and 2277 [55.8%] at Y0; 2473 black individuals [50.7%] at Y0 and 1994 [48.9%] at Y15; and 2407 white individuals [49.3%] at Y0 and 2083 [51.1%] at Y15). The mean SBP/DBP was 112/69 mm Hg in blacks and 109/68 mm Hg in whites at Y0 and 117/77 mm Hg in blacks and 110/72 mm Hg in whites at Y15. During a 25-year follow-up from Y0, 210 CVD events occurred (twice as many events in blacks [n = 140] compared with whites), of which 131 (87 in blacks) occurred after Y15. With adjustments for covariates, results from Cox proportional hazards models, including SBP and DBP, jointly suggested that, at Y0, SBP (hazard ratio [HR] per 1-SD increase, 1.32; 95% CI, 1.09-1.61) but not DBP (HR, 1.05; 95% CI, 0.88-1.26) was associated with CVD risk in blacks, whereas DBP (HR, 1.74; 95% CI, 1.21-2.50) but not

  9. Cancer-disease associations: A visualization and animation through medical big data.

    PubMed

    Iqbal, Usman; Hsu, Chun-Kung; Nguyen, Phung Anh Alex; Clinciu, Daniel Livius; Lu, Richard; Syed-Abdul, Shabbir; Yang, Hsuan-Chia; Wang, Yao-Chin; Huang, Chu-Ya; Huang, Chih-Wei; Chang, Yo-Cheng; Hsu, Min-Huei; Jian, Wen-Shan; Li, Yu-Chuan Jack

    2016-04-01

    Cancer is the primary disease responsible for death and disability worldwide. Currently, prevention and early detection represents the best hope for cure. Knowing the expected diseases that occur with a particular cancer in advance could lead to physicians being able to better tailor their treatment for cancer. The aim of this study was to build an animated visualization tool called as Cancer Associations Map Animation (CAMA), to chart the association of cancers with other disease over time. The study population was collected from the Taiwan National Health Insurance Database during the period January 2000 to December 2002, 782 million outpatient visits were used to compute the associations of nine major cancers with other diseases. A motion chart was used to quantify and visualize the associations between diseases and cancers. The CAMA motion chart that was built successfully facilitated the observation of cancer-disease associations across ages and genders. The CAMA system can be accessed online at http://203.71.86.98/web/runq16.html. The CAMA animation system is an animated medical data visualization tool which provides a dynamic, time-lapse, animated view of cancer-disease associations across different age groups and gender. Derived from a large, nationwide healthcare dataset, this exploratory data analysis tool can detect cancer comorbidities earlier than is possible by manual inspection. Taking into account the trajectory of cancer-specific comorbidity development may facilitate clinicians and healthcare researchers to more efficiently explore early stage hypotheses, develop new cancer treatment approaches, and identify potential effect modifiers or new risk factors associated with specific cancers. Copyright © 2016. Published by Elsevier Ireland Ltd.

  10. Association between periodontal diseases and systemic illnesses: A survey among internal medicine residents in Nigeria.

    PubMed

    Umeizudike, Kehinde A; Iwuala, Sandra O; Ozoh, Obianuju B; Ayanbadejo, Patricia O; Fasanmade, Olufemi A

    2016-01-01

    To assess internal medicine residents' knowledge of associations between periodontal disease and systemic illnesses, and attitudes toward patients' periodontal health. A cross-sectional survey using a self-administered questionnaire was conducted among internal medicine residents attending the Faculty of Internal Medicine 2014 Update Course organized by the National Postgraduate Medical College of Nigeria. Participants came from all over the country. Data on respondents' demographic characteristics, periodontal disease knowledge, knowledge of associations between periodontal disease and systemic illnesses, and attitudes toward patients' periodontal health were collected. Data were analyzed using Epi INFO software. The Pearson chi square test was used to measure significant association between categorical variables such as the knowledge of periodontal disease and gender, age group and designation of the participants (p ⩽ 0.05). Of 150 questionnaires distributed, 123 were returned (82% response rate); 109 questionnaires were completed properly and included in the analysis. The most common source of residents' information on oral health was television (59.4%). Only 11.2% of respondents were aware that gingival bleeding was the earliest sign of periodontal disease. Respondents correctly identified periodontal disease as a risk factor for coronary heart disease (45.9%), stroke (43.5%), hospital-acquired pneumonia (53.2%), diabetes mellitus (13.8%), and preterm birth (11%). Increased age (p = 0.032) and male gender (p = 0.022) were associated significantly with knowledge of periodontal disease as a risk factor for stroke. Higher designation (p = 0.002) and longer duration in residency training (p = 0.004) were associated significantly with knowledge of periodontal disease as risk factor for peripheral arterial disease. The majority (90.9%) of respondents had positive attitudes toward the referral of their patients for regular periodontal care. Knowledge of

  11. Association between periodontal diseases and systemic illnesses: A survey among internal medicine residents in Nigeria

    PubMed Central

    Umeizudike, Kehinde A.; Iwuala, Sandra O.; Ozoh, Obianuju B.; Ayanbadejo, Patricia O.; Fasanmade, Olufemi A.

    2015-01-01

    Objective To assess internal medicine residents’ knowledge of associations between periodontal disease and systemic illnesses, and attitudes toward patients’ periodontal health. Methods A cross-sectional survey using a self-administered questionnaire was conducted among internal medicine residents attending the Faculty of Internal Medicine 2014 Update Course organized by the National Postgraduate Medical College of Nigeria. Participants came from all over the country. Data on respondents’ demographic characteristics, periodontal disease knowledge, knowledge of associations between periodontal disease and systemic illnesses, and attitudes toward patients’ periodontal health were collected. Data were analyzed using Epi INFO software. The Pearson chi square test was used to measure significant association between categorical variables such as the knowledge of periodontal disease and gender, age group and designation of the participants (p ⩽ 0.05). Results Of 150 questionnaires distributed, 123 were returned (82% response rate); 109 questionnaires were completed properly and included in the analysis. The most common source of residents’ information on oral health was television (59.4%). Only 11.2% of respondents were aware that gingival bleeding was the earliest sign of periodontal disease. Respondents correctly identified periodontal disease as a risk factor for coronary heart disease (45.9%), stroke (43.5%), hospital-acquired pneumonia (53.2%), diabetes mellitus (13.8%), and preterm birth (11%). Increased age (p = 0.032) and male gender (p = 0.022) were associated significantly with knowledge of periodontal disease as a risk factor for stroke. Higher designation (p = 0.002) and longer duration in residency training (p = 0.004) were associated significantly with knowledge of periodontal disease as risk factor for peripheral arterial disease. The majority (90.9%) of respondents had positive attitudes toward the referral of their patients for

  12. Neuroglia in ageing and disease.

    PubMed

    Verkhratsky, Alexei; Rodríguez, José J; Parpura, Vladimir

    2014-08-01

    The proper operation of the mammalian brain requires dynamic interactions between neurones and glial cells. Various types of glial cells are susceptible to morpho-functional changes in a variety of brain pathological states, including toxicity, neurodevelopmental, neurodegenerative and psychiatric disorders. Morphological modifications include a change in the glial cell size and shape; the latter is evident by changes of the appearance and number of peripheral processes. The most blatant morphological change is associated with the alteration of the sheer number of neuroglia cells in the brain. Functionally, glial cells can undergo various metabolic and biochemical changes, the majority of which reflect upon homeostasis of neurotransmitters, in particular that of glutamate, as well as on defence mechanisms provided by neuroglia. Not only glial cells exhibit changes associated with the pathology of the brain but they also change with brain aging.

  13. The association of coffee intake with liver cancer incidence and chronic liver disease mortality in male smokers.

    PubMed

    Lai, G Y; Weinstein, S J; Albanes, D; Taylor, P R; McGlynn, K A; Virtamo, J; Sinha, R; Freedman, N D

    2013-09-03

    Coffee intake is associated with reduced risk of liver cancer and chronic liver disease as reported in previous studies, including prospective ones conducted in Asian populations where hepatitis B viruses (HBVs) and hepatitis C viruses (HCVs) are the dominant risk factors. Yet, prospective studies in Western populations with lower HBV and HCV prevalence are sparse. Also, although preparation methods affect coffee constituents, it is unknown whether different methods affect disease associations. We evaluated the association of coffee intake with incident liver cancer and chronic liver disease mortality in 27,037 Finnish male smokers, aged 50-69, in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, who recorded their coffee consumption and were followed up to 24 years for incident liver cancer or chronic liver disease mortality. Multivariate relative risks (RRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazard models. Coffee intake was inversely associated with incident liver cancer (RR per cup per day=0.82, 95% CI: 0.73-0.93; P-trend across categories=0.0007) and mortality from chronic liver disease (RR=0.55, 95% CI: 0.48-0.63; P-trend<0.0001). Inverse associations persisted in those without diabetes, HBV- and HCV-negative cases, and in analyses stratified by age, body mass index, alcohol and smoking dose. We observed similar associations for those drinking boiled or filtered coffee. These findings suggest that drinking coffee may have benefits for the liver, irrespective of whether coffee was boiled or filtered.

  14. Peripheral Changes Associated With Delayed Dark Adaptation in Age-related Macular Degeneration.

    PubMed

    Laíns, Inês; Park, Dong Ho; Mukai, Ryo; Silverman, Rebecca; Oellers, Patrick; Mach, Steven; Kim, Ivana K; Vavvas, Demetrios G; Miller, Joan W; Miller, John B; Husain, Deeba

    2018-06-01

    To study the association between peripheral changes in age-related macular degeneration (AMD) and dark adaptation (DA). Prospective, cross-sectional study. We recruited patients with AMD and a control group (>50 years) without any vitreoretinal disease. Ultra-widefield (UWF) pseudocolor and fundus autofluorescence (FAF) were obtained, and were assessed by 2 graders for the presence of several peripheral changes in perimacular, midperipheral, and far-peripheral zones. All participants were also imaged with 7-field color fundus photographs used for AMD staging (Age-Related Eye Disease Study classification system). Both eyes of study participants were tested with a dark adaptation (DA) extended protocol (20 minutes). Multilevel mixed-effect models (accounting for correlated outcomes between 2 eyes) were used for analyses. We included 128 eyes (n = 72 patients), 75% with AMD and the remainder controls. The presence of reticular pigmentary changes in the midperipheral (ß = 4.3, P = .012) and far-peripheral zones (ß = 8.4, P < .001) was associated with delayed rod-intercept times (RITs), even after adjusting for confounding factors. The presence, number, and extent of peripheral classic drusen did not show a similar association (P ≥ .148). The presence of a mottled decreased FAF pattern in the midperipheral zone was also associated with prolonged RITs (β = 4.4, P = .031). Our results suggest an association between DA and the presence of peripheral reticular pigmentary changes, as well as the presence of a peripheral mottled decreased FAF pattern. This provides new insights on the clinical significance of peripheral changes in AMD, and their contribution to impairments on DA. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Percentage and severity of periodontal diseases in Turkish adults aged 35+ years, 2009-10.

    PubMed

    Ilhan, Duygu; Oktay, Inci; Nur, Burcu; Fisekcioglu, Erdogan; Lim, Sungwoo; Lepkowski, James M; Ismail, Amid I

    2017-09-01

    This article presents data on the burden of periodontal diseases in Turkish adults aged 35 years or older. Within each region of Turkey, a rural and an urban area or city were selected in 2009-10 using a probability proportional to size method. In the selected towns, local officials who were familiar with their communities assisted in recruiting subjects. Loss of Attachment (LOA) was measured at six sites around each tooth present in the mouth, excluding third molars. Additionally, the Community Periodontal Index was used to assess the severity of periodontal diseases around 12 index teeth. Self-reported data on key risk factors were also collected. Weights were computed using a raking ratio adjustment procedure and used in all analyses. Almost all examined adults had some loss of periodontal attachment. The proportion of those with more than 3 mm LOA ranged from 43 percent in 35-44 year olds to 91 percent in those aged 65+ years. Among females, older age, low education status, smoking 11-40+ cigarettes a day, being employed, and presence of high number of missing tooth surfaces were associated with LOA > 3 mm. Among males LOA >3 mm was associated with older age, use of alcohol, and unemployment. The CPI data did not yield the same associations with periodontal diseases and risk factors. Periodontal diseases in Turkish adults are highly prevalent. A tailored common risk factor health promotion program is recommended to reduce the burden of periodontal infection in Turkey. © 2017 American Association of Public Health Dentistry.

  16. Disease prevention and health promotion in the aging with a traditional system of natural medicine: Maharishi Vedic Medicine.

    PubMed

    Schneider, Robert H; Alexander, Charles N; Salerno, John W; Robinson, Donald K; Fields, Jeremy Z; Nidich, Sanford I

    2002-02-01

    This review focuses on a comprehensive, sophisticated system of natural medicine that appears to hold promise for prevention of chronic diseases and disabilities, loss of independence, suffering, and health care costs often associated with "usual" aging. The authors discuss the negative impact of usual aging on our society, with its rapidly growing percentage of elderly, and the challenge of promoting "successful aging." Emphasis is given to research literature suggesting that Maharishi Vedic Medicine (MVM) is particularly effective in retarding usual aging. Proposed mechanisms for the antiaging effects of MVM include reductions in physiological and psychological stress and enhancement of homeostatic and self-repair processes. The authors conclude that this set of innovative strategies may help society achieve recommended health objectives for disease prevention and health promotion in older adults and that widespread implementation of this self-empowering, prevention-oriented approach in the elderly is feasible, cost effective, and timely.

  17. Mitochondrial base excision repair in mouse synaptosomes during normal aging and in a model of Alzheimer’s disease

    PubMed Central

    Gredilla, Ricardo; Weissman, Lior; Yang, Jenq-Lin; Bohr, Vilhelm A.; Stevnsner, Tinna

    2010-01-01

    Brain aging is associated with synaptic decline and cognitive impairment. Increased levels of oxidative DNA base damage and accumulation of mitochondrial DNA (mtDNA) mutations or deletions lead to mitochondrial dysfunction, playing an important role in the aging process and the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD). In mitochondria, base excision repair (BER) is the main DNA repair pathway for base modifications such as deamination and oxidation, and constitutes an important mechanism to avoid accumulation of mtDNA mutations. Synaptic function is highly dependent on mitochondria, and in the current study we have investigated BER in synaptosomes of mouse brain during normal aging and in an AD model. Synaptosomes are isolated synapses in membranous structures produced by subcellular fractionation of brain tissue. They include the whole presynaptic terminal as well as portions of the postsynaptic terminal. Synaptosomes contain the molecular machinery necessary for uptake, storage, and release of neurotransmitters, including synaptic vesicles and mitochondria. BER activities were measured in synaptosomal fractions from young and old mice and from pre-symptomatic and symptomatic AD mice harboring mutated APP, Tau and PS1 (3xTgAD). During normal aging, a reduction in the BER capacity was observed in the synaptosomal fraction, which was associated with a decrease in the level of BER proteins. However, we did not observe changes between the synaptosomal BER activities of pre-symptomatic and symptomatic AD mice. Our findings suggest that the age-related reduction in BER capacity in the synaptosomal fraction might contribute to mitochondrial and synaptic dysfunction during aging. The development of AD-like pathology in the 3xTgAD mouse model was, however, not associated with deficiencies of the BER mechanisms in the synaptosomal fraction when the whole brain was analyzed. PMID:20708822

  18. Delaying aging and the aging-associated decline in protein homeostasis by inhibition of tryptophan degradation

    PubMed Central

    van der Goot, Annemieke T.; Zhu, Wentao; Vázquez-Manrique, Rafael P.; Seinstra, Renée I.; Dettmer, Katja; Michels, Helen; Farina, Francesca; Krijnen, Jasper; Melki, Ronald; Buijsman, Rogier C.; Ruiz Silva, Mariana; Thijssen, Karen L.; Kema, Ido P.; Neri, Christian; Oefner, Peter J.; Nollen, Ellen A. A.

    2012-01-01

    Toxicity of aggregation-prone proteins is thought to play an important role in aging and age-related neurological diseases like Parkinson and Alzheimer’s diseases. Here, we identify tryptophan 2,3-dioxygenase (tdo-2), the first enzyme in the kynurenine pathway of tryptophan degradation, as a metabolic regulator of age-related α-synuclein toxicity in a Caenorhabditis elegans model. Depletion of tdo-2 also suppresses toxicity of other heterologous aggregation-prone proteins, including amyloid-β and polyglutamine proteins, and endogenous metastable proteins that are sensors of normal protein homeostasis. This finding suggests that tdo-2 functions as a general regulator of protein homeostasis. Analysis of metabolite levels in C. elegans strains with mutations in enzymes that act downstream of tdo-2 indicates that this suppression of toxicity is independent of downstream metabolites in the kynurenine pathway. Depletion of tdo-2 increases tryptophan levels, and feeding worms with extra l-tryptophan also suppresses toxicity, suggesting that tdo-2 regulates proteotoxicity through tryptophan. Depletion of tdo-2 extends lifespan in these worms. Together, these results implicate tdo-2 as a metabolic switch of age-related protein homeostasis and lifespan. With TDO and Indoleamine 2,3-dioxygenase as evolutionarily conserved human orthologs of TDO-2, intervening with tryptophan metabolism may offer avenues to reducing proteotoxicity in aging and age-related diseases. PMID:22927396

  19. Associations between factors related to atopic disease and glaucoma in the National Health and Nutrition Examination Survey.

    PubMed

    Tseng, Victoria L; Lee, Janet; Yu, Fei; Sirsy, Omar; Coleman, Anne L

    2018-05-01

    Previous studies have suggested associations between glaucoma and serum sensitization to specific allergens. The purpose of this study was to examine associations between inciting factors for atopic disease, atopic diseases and symptoms, and glaucoma in the 2005-2006 National Health and Nutrition Examination Survey. The study population included adult participants of National Health and Nutrition Examination Survey 2005-2006. Inciting factors for atopic disease included pet ownership, mildew/musty smell in home, cockroaches in home, use of water treatment devices, and crowded living conditions. Atopic diseases and symptoms included hay fever, eczema, any allergy, sneezing problems, and sinus infections. The outcome was glaucoma defined by the Rotterdam criteria. Covariates included age, gender, ethnicity, and allergy-related medication use. Logistic regression was used to examine associations between each exposure and glaucoma prevalence, controlling for all covariates. Statistical analyses were weighted by the National Health and Nutrition Examination Survey multistage sampling design. The weighted study population included 83,205,587 subjects, of whom 2,657,336 (3.2%) had glaucoma. After adjusting for covariates, factors associated with increased glaucoma included cat ownership (odds ratio =1.99, 95% confidence interval = 1.02-3.87) and mildew/musty smell in home (odds ratio = 1.95, 95% confidence interval = 0.99-3.84; borderline significance), while history of eczema was associated with decreased glaucoma (odds ratio = 0.27, 95% confidence interval = 0.02-0.99). In National Health and Nutrition Examination Survey, self-reported cat ownership is associated with increased glaucoma prevalence, while a mildew/musty smell in home may have a borderline association with increased glaucoma prevalence. These findings are possibly related to laboratory associations identified in the same population and further studies are needed to identify potential

  20. Potential genetic modifiers of disease risk and age at onset in patients with frontotemporal lobar degeneration and GRN mutations: a genome-wide association study.

    PubMed

    Pottier, Cyril; Zhou, Xiaolai; Perkerson, Ralph B; Baker, Matt; Jenkins, Gregory D; Serie, Daniel J; Ghidoni, Roberta; Benussi, Luisa; Binetti, Giuliano; López de Munain, Adolfo; Zulaica, Miren; Moreno, Fermin; Le Ber, Isabelle; Pasquier, Florence; Hannequin, Didier; Sánchez-Valle, Raquel; Antonell, Anna; Lladó, Albert; Parsons, Tammee M; Finch, NiCole A; Finger, Elizabeth C; Lippa, Carol F; Huey, Edward D; Neumann, Manuela; Heutink, Peter; Synofzik, Matthis; Wilke, Carlo; Rissman, Robert A; Slawek, Jaroslaw; Sitek, Emilia; Johannsen, Peter; Nielsen, Jørgen E; Ren, Yingxue; van Blitterswijk, Marka; DeJesus-Hernandez, Mariely; Christopher, Elizabeth; Murray, Melissa E; Bieniek, Kevin F; Evers, Bret M; Ferrari, Camilla; Rollinson, Sara; Richardson, Anna; Scarpini, Elio; Fumagalli, Giorgio G; Padovani, Alessandro; Hardy, John; Momeni, Parastoo; Ferrari, Raffaele; Frangipane, Francesca; Maletta, Raffaele; Anfossi, Maria; Gallo, Maura; Petrucelli, Leonard; Suh, EunRan; Lopez, Oscar L; Wong, Tsz H; van Rooij, Jeroen G J; Seelaar, Harro; Mead, Simon; Caselli, Richard J; Reiman, Eric M; Noel Sabbagh, Marwan; Kjolby, Mads; Nykjaer, Anders; Karydas, Anna M; Boxer, Adam L; Grinberg, Lea T; Grafman, Jordan; Spina, Salvatore; Oblak, Adrian; Mesulam, M-Marsel; Weintraub, Sandra; Geula, Changiz; Hodges, John R; Piguet, Olivier; Brooks, William S; Irwin, David J; Trojanowski, John Q; Lee, Edward B; Josephs, Keith A; Parisi, Joseph E; Ertekin-Taner, Nilüfer; Knopman, David S; Nacmias, Benedetta; Piaceri, Irene; Bagnoli, Silvia; Sorbi, Sandro; Gearing, Marla; Glass, Jonathan; Beach, Thomas G; Black, Sandra E; Masellis, Mario; Rogaeva, Ekaterina; Vonsattel, Jean-Paul; Honig, Lawrence S; Kofler, Julia; Bruni, Amalia C; Snowden, Julie; Mann, David; Pickering-Brown, Stuart; Diehl-Schmid, Janine; Winkelmann, Juliane; Galimberti, Daniela; Graff, Caroline; Öijerstedt, Linn; Troakes, Claire; Al-Sarraj, Safa; Cruchaga, Carlos; Cairns, Nigel J; Rohrer, Jonathan D; Halliday, Glenda M; Kwok, John B; van Swieten, John C; White, Charles L; Ghetti, Bernardino; Murell, Jill R; Mackenzie, Ian R A; Hsiung, Ging-Yuek R; Borroni, Barbara; Rossi, Giacomina; Tagliavini, Fabrizio; Wszolek, Zbigniew K; Petersen, Ronald C; Bigio, Eileen H; Grossman, Murray; Van Deerlin, Vivianna M; Seeley, William W; Miller, Bruce L; Graff-Radford, Neill R; Boeve, Bradley F; Dickson, Dennis W; Biernacka, Joanna M; Rademakers, Rosa

    2018-06-01

    Loss-of-function mutations in GRN cause frontotemporal lobar degeneration (FTLD). Patients with GRN mutations present with a uniform subtype of TAR DNA-binding protein 43 (TDP-43) pathology at autopsy (FTLD-TDP type A); however, age at onset and clinical presentation are variable, even within families. We aimed to identify potential genetic modifiers of disease onset and disease risk in GRN mutation carriers. The study was done in three stages: a discovery stage, a replication stage, and a meta-analysis of the discovery and replication data. In the discovery stage, genome-wide logistic and linear regression analyses were done to test the association of genetic variants with disease risk (case or control status) and age at onset in patients with a GRN mutation and controls free of neurodegenerative disorders. Suggestive loci (p<1 × 10 -5 ) were genotyped in a replication cohort of patients and controls, followed by a meta-analysis. The effect of genome-wide significant variants at the GFRA2 locus on expression of GFRA2 was assessed using mRNA expression studies in cerebellar tissue samples from the Mayo Clinic brain bank. The effect of the GFRA2 locus on progranulin concentrations was studied using previously generated ELISA-based expression data. Co-immunoprecipitation experiments in HEK293T cells were done to test for a direct interaction between GFRA2 and progranulin. Individuals were enrolled in the current study between Sept 16, 2014, and Oct 5, 2017. After quality control measures, statistical analyses in the discovery stage included 382 unrelated symptomatic GRN mutation carriers and 1146 controls free of neurodegenerative disorders collected from 34 research centres located in the USA, Canada, Australia, and Europe. In the replication stage, 210 patients (67 symptomatic GRN mutation carriers and 143 patients with FTLD without GRN mutations pathologically confirmed as FTLD-TDP type A) and 1798 controls free of neurodegenerative diseases were recruited

  1. Redefining meaningful age groups in the context of disease.

    PubMed

    Geifman, Nophar; Cohen, Raphael; Rubin, Eitan

    2013-12-01

    Age is an important factor when considering phenotypic changes in health and disease. Currently, the use of age information in medicine is somewhat simplistic, with ages commonly being grouped into a small number of crude ranges reflecting the major stages of development and aging, such as childhood or adolescence. Here, we investigate the possibility of redefining age groups using the recently developed Age-Phenome Knowledge-base (APK) that holds over 35,000 literature-derived entries describing relationships between age and phenotype. Clustering of APK data suggests 13 new, partially overlapping, age groups. The diseases that define these groups suggest that the proposed divisions are biologically meaningful. We further show that the number of different age ranges that should be considered depends on the type of disease being evaluated. This finding was further strengthened by similar results obtained from clinical blood measurement data. The grouping of diseases that share a similar pattern of disease-related reports directly mirrors, in some cases, medical knowledge of disease-age relationships. In other cases, our results may be used to generate new and reasonable hypotheses regarding links between diseases.

  2. Mule deer spatial association patterns and potential implications for transmission of an epizootic disease.

    PubMed

    Mejía-Salazar, María Fernanda; Goldizen, Anne W; Menz, Clementine S; Dwyer, Ross G; Blomberg, Simon P; Waldner, Cheryl L; Cullingham, Catherine I; Bollinger, Trent K

    2017-01-01

    Animal social behaviour can have important effects on the long-term dynamics of diseases. In particular, preferential spatial relationships between individuals can lead to differences in the rates of disease spread within a population. We examined the concurrent influence of genetic relatedness, sex, age, home range overlap, time of year, and prion disease status on proximal associations of adult Rocky Mountain mule deer (Odocoileus hemionus hemionus) in a chronic wasting disease endemic area. We also quantified the temporal stability of these associations across different sex, age, and disease status classes. We used three years of high frequency telemetry data from 74 individuals to record encounters within 25 m of each other, and to calculate seasonal home range overlap measured by volume of intersection (VI). The strength of pairwise spatial association between adult mule deer was independent of genetic relatedness, age and disease status. Seasonal variation in association strength was not consistent across years, perhaps due to annual changes in weather conditions. The influence of home range overlap on association strength varied seasonally, whereby associations were stronger in pre-rut and fawning than in the rest of the seasons. The sexes of individuals also interacted with both VI and season. At increasing levels of VI, associations were stronger between females than between males and between females and males. The strongest associations in pre-rut were between males, while the strongest in rut were between females and males. The temporal stability of associations was markedly dependant on the sex and the diagnosis of the associating pair. Our findings highlight the importance of considering concurrent effects of biological and environmental factors when seeking to understand the role of social preference in behavioural ecology and disease spread. Applying this knowledge in epidemiological modelling will shed light on the dynamics of disease transmission

  3. Mule deer spatial association patterns and potential implications for transmission of an epizootic disease

    PubMed Central

    Goldizen, Anne W.; Menz, Clementine S.; Dwyer, Ross G.; Blomberg, Simon P.; Waldner, Cheryl L.; Cullingham, Catherine I.; Bollinger, Trent K.

    2017-01-01

    Animal social behaviour can have important effects on the long-term dynamics of diseases. In particular, preferential spatial relationships between individuals can lead to differences in the rates of disease spread within a population. We examined the concurrent influence of genetic relatedness, sex, age, home range overlap, time of year, and prion disease status on proximal associations of adult Rocky Mountain mule deer (Odocoileus hemionus hemionus) in a chronic wasting disease endemic area. We also quantified the temporal stability of these associations across different sex, age, and disease status classes. We used three years of high frequency telemetry data from 74 individuals to record encounters within 25 m of each other, and to calculate seasonal home range overlap measured by volume of intersection (VI). The strength of pairwise spatial association between adult mule deer was independent of genetic relatedness, age and disease status. Seasonal variation in association strength was not consistent across years, perhaps due to annual changes in weather conditions. The influence of home range overlap on association strength varied seasonally, whereby associations were stronger in pre-rut and fawning than in the rest of the seasons. The sexes of individuals also interacted with both VI and season. At increasing levels of VI, associations were stronger between females than between males and between females and males. The strongest associations in pre-rut were between males, while the strongest in rut were between females and males. The temporal stability of associations was markedly dependant on the sex and the diagnosis of the associating pair. Our findings highlight the importance of considering concurrent effects of biological and environmental factors when seeking to understand the role of social preference in behavioural ecology and disease spread. Applying this knowledge in epidemiological modelling will shed light on the dynamics of disease transmission

  4. Effect of Aging on Periodontal Inflammation, Microbial Colonization, and Disease Susceptibility

    PubMed Central

    Wu, Y.; Dong, G.; Xiao, W.; Xiao, E.; Miao, F.; Syverson, A.; Missaghian, N.; Vafa, R.; Cabrera-Ortega, A.A.; Rossa, C.; Graves, D.T.

    2016-01-01

    Periodontitis is a chronic inflammatory disease induced by a biofilm that forms on the tooth surface. Increased periodontal disease is associated with aging. We investigated the effect of aging on challenge by oral pathogens, examining the host response, colonization, and osteoclast numbers in aged versus young mice. We also compared the results with mice with lineage-specific deletion of the transcription factor FOXO1, which reduces dendritic cell (DC) function. Periodontitis was induced by oral inoculation of Porphyromonas gingivalis and Fusobacterium nucleatum in young (4 to 5 mo) and aged (14 to 15 mo) mice. Aged mice as well as mice with reduced DC function had decreased numbers of DCs in lymph nodes, indicative of a diminished host response. In vitro studies suggest that reduced DC numbers in lymph nodes of aged mice may involve the effect of advanced glycation end products on DC migration. Surprisingly, aged mice but not mice with genetically altered DC function had greater production of antibody to P. gingivalis, greater IL-12 expression, and more plasma cells in lymph nodes following oral inoculation as compared with young mice. The greater adaptive immune response in aged versus young mice was linked to enhanced levels of P. gingivalis and reduced bacterial diversity. Thus, reduced bacterial diversity in aged mice may contribute to increased P. gingivalis colonization following inoculation and increased periodontal disease susceptibility, reflected by higher TNF levels and osteoclast numbers in the periodontium of aged versus young mice. PMID:26762510

  5. Graves' Disease Pharmacotherapy in Women of Reproductive Age.

    PubMed

    Prunty, Jeremy J; Heise, Crystal D; Chaffin, David G

    2016-01-01

    Graves' disease is an autoimmune disorder in which inappropriate stimulation of the thyroid gland results in unregulated secretion of thyroid hormones resulting in hyperthyroidism. Graves' disease is the most common cause of autoimmune hyperthyroidism during pregnancy. Treatment options for Graves' disease include thioamide therapy, partial or total thyroidectomy, and radioactive iodine. In this article, we review guideline recommendations for Graves' disease treatment in women of reproductive age including the recent guideline from the American College of Obstetricians and Gynecologists. Controversy regarding appropriate thioamide therapy before, during, and after pregnancy is reviewed. Surgical and radioactive iodine therapy considerations in this patient population are also reviewed. In patients who may find themselves pregnant during therapy or develop Graves' disease during their pregnancy, consideration should be given to the most appropriate treatment course for the mother and fetus. Thioamide therapy should be used with either propylthiouracil or methimazole at appropriate doses that target the upper range of normal to slightly hyperthyroid to avoid creating hypothyroidism in the fetus. Consideration should also be given to the adverse effects of thioamide, such as agranulocytosis and hepatotoxicity, with appropriate patient consultation regarding signs and symptoms. Individuals who wish to breastfeed their infants while taking thioamide should receive the lowest effective dose. Surgery should be reserved for extreme cases and limited to the second trimester, if possible. Radioactive iodine therapy may be used in nonpregnant individuals, with limited harm to future fertility. Radioactive iodine therapy should be withheld in pregnant women and those who are actively breastfeeding. Clinicians should keep abreast of developments in clinical trials and evidence-based recommendations regarding Graves' disease in reproductive-age women for any changes in evidence

  6. Association of Marine Omega-3 Fatty Acid Levels With Telomeric Aging in Patients With Coronary Heart Disease

    PubMed Central

    Farzaneh-Far, Ramin; Lin, Jue; Epel, Elissa S.; Harris, William S.; Blackburn, Elizabeth H.; Whooley, Mary A.

    2010-01-01

    Context Increased dietary intake of marine omega-3 fatty acids is associated with prolonged survival in patients with coronary heart disease. However, the mechanisms underlying this protective effect are poorly understood. Objective To investigate the association of omega-3 fatty acid blood levels with temporal changes in telomere length, an emerging marker of biological age. Design, Setting, and Participants Prospective cohort study of 608 ambulatory outpatients in California with stable coronary artery disease recruited from the Heart and Soul Study between September 2000 and December 2002 and followed up to January 2009 (median, 6.0 years; range, 5.0-8.1 years). Main Outcome Measures We measured leukocyte telomere length at baseline and again after 5 years of follow-up. Multivariable linear and logistic regression models were used to investigate the association of baseline levels of omega-3 fatty acids (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]) with subsequent change in telomere length. Results Individuals in the lowest quartile of DHA3EPA experienced the fastest rate of telomere shortening (0.13 telomere-to-single-copy gene ratio [T/S] units over 5 years; 95% confidence interval [CI], 0.09-0.17), whereas those in the highest quartile experienced the slowest rate of telomere shortening (0.05 T/S units over 5 years; 95% CI, 0.02-0.08; P<.001 for linear trend across quartiles). Levels of DHA+EPA were associated with less telomere shortening before (unadjusted β coefficient × 10−3=0.06; 95% CI, 0.02-0.10) and after (adjusted β coefficient × 10−3=0.05; 95% CI, 0.01-0.08) sequential adjustment for established risk factors and potential confounders. Each 1-SD increase in DHA+EPA levels was associated with a 32% reduction in the odds of telomere shortening (adjusted odds ratio, 0.68; 95% CI, 0.47-0.98). Conclusion Among this cohort of patients with coronary artery disease, there was an inverse relationship between baseline blood levels of

  7. Metabolomics of human brain aging and age-related neurodegenerative diseases.

    PubMed

    Jové, Mariona; Portero-Otín, Manuel; Naudí, Alba; Ferrer, Isidre; Pamplona, Reinald

    2014-07-01

    Neurons in the mature human central nervous system (CNS) perform a wide range of motor, sensory, regulatory, behavioral, and cognitive functions. Such diverse functional output requires a great diversity of CNS neuronal and non-neuronal populations. Metabolomics encompasses the study of the complete set of metabolites/low-molecular-weight intermediates (metabolome), which are context-dependent and vary according to the physiology, developmental state, or pathologic state of the cell, tissue, organ, or organism. Therefore, the use of metabolomics can help to unravel the diversity-and to disclose the specificity-of metabolic traits and their alterations in the brain and in fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of aging and neurodegenerative diseases. Here, we review the current applications of metabolomics in studies of CNS aging and certain age-related neurodegenerative diseases such as Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Neurometabolomics will increase knowledge of the physiologic and pathologic functions of neural cells and will place the concept of selective neuronal vulnerability in a metabolic context.

  8. Associates of School Absenteeism in Adolescents With Sickle Cell Disease

    PubMed Central

    Schwartz, Lisa A.; Radcliffe, Jerilynn; Barakat, Lamia P.

    2009-01-01

    Background Despite high rates of school absenteeism in adolescents with sickle cell disease (SCD), the issue remains understudied. Potential associates of school absenteeism in adolescents with SCD include demographic (age, income), psychosocial (IQ, self-efficacy, competence, internalizing symptoms, negative thinking), and health-related (hemoglobin, health-care utilization, pain, disease knowledge). Procedure Forty participants ages 12–18 completed measures of psychosocial functioning, IQ, and pain. Medical chart reviews identified other health-related variables. A subsample also completed an assessment of goals. Using school records, absenteeism was the percent of school days missed in the previous year. Correlations tested associates of absenteeism and linear regression tested a model of absenteeism. Results Participants missed an average of 12% of the school year and more than 35% missed at least 1 month of school. Health-related and psychosocial variables, but not demographic variables, correlated with absenteeism. Attendance at clinic appointments and parent-reported teen pain frequency were significant associates of absenteeism in the regression model. For those who completed goal assessment, over 40% of goals identified were academically focused. Absenteeism was positively related to current academic goals and health-related hindrance of academic goals, and negatively related to future-oriented academic goals. Conclusions School absenteeism is a significant problem for adolescents with SCD despite the presence of academic goals. Collaboration between schools, parents, patients, and providers to understand and manage the impact of SCD on school attendance is recommended. PMID:19006248

  9. Role of macrophage migration inhibitory factor in age-related lung disease

    PubMed Central

    Sauler, Maor; Bucala, Richard

    2015-01-01

    The prevalence of many common respiratory disorders, including pneumonia, chronic obstructive lung disease, pulmonary fibrosis, and lung cancer, increases with age. Little is known of the host factors that may predispose individuals to such diseases. Macrophage migration inhibitory factor (MIF) is a potent upstream regulator of the immune system. MIF is encoded by variant alleles that occur commonly in the population. In addition to its role as a proinflammatory cytokine, a growing body of literature demonstrates that MIF influences diverse molecular processes important for the maintenance of cellular homeostasis and may influence the incidence or clinical manifestations of a variety of chronic lung diseases. This review highlights the biological properties of MIF and its implication in age-related lung disease. PMID:25957294

  10. Mechanisms of lung aging.

    PubMed

    Brandenberger, Christina; Mühlfeld, Christian

    2017-03-01

    Lung aging is associated with structural remodeling, a decline of respiratory function and a higher susceptibility to acute and chronic lung diseases. Individual factors that modulate pulmonary aging include basic genetic configuration, environmental exposure, life-style and biography of systemic diseases. However, the actual aging of the lung takes place in pulmonary resident cells and is closely linked to aging of the immune system (immunosenescence). Therefore, this article reviews the current knowledge about the impact of aging on pulmonary cells and the immune system, without analyzing those factors that may accelerate the aging process in depth. Hallmarks of aging include alterations at molecular, cellular and cell-cell interaction levels. Because of the great variety of cell types in the lung, the consequences of aging display a broad spectrum of phenotypes. For example, aging is associated with more collagen and less elastin production by fibroblasts, thus increasing pulmonary stiffness and lowering compliance. Decreased sympathetic airway innervation may increase the constriction status of airway smooth muscle cells. Aging of resident and systemic immune cells leads to a pro-inflammatory milieu and reduced capacity of fighting infectious diseases. The current review provides an overview of cellular changes occurring with advancing age in general and in several cell types of the lung as well as of the immune system. Thereby, this survey not only aims at providing a better understanding of the mechanisms of pulmonary aging but also to identify gaps in knowledge that warrant further investigations.

  11. Optimal Levels of All Major Cardiovascular Risk Factors in Younger Age and Functional Disability in Older Age: The Chicago Heart Association Detection Project in Industry 32-Year Follow-Up Health Survey.

    PubMed

    Vu, Thanh-Huyen T; Lloyd-Jones, Donald M; Liu, Kiang; Stamler, Jeremiah; Garside, Daniel B; Daviglus, Martha L

    2016-07-01

    The associations of optimal levels of all major cardiovascular disease risk factors, that is, low risk, in younger age with subsequent cardiovascular disease morbidity and mortality have been well documented. However, little is known about associations of low-risk profiles in younger age with functional disability in older age. The sample included 6014 participants from the Chicago Heart Association Detection Project in Industry Study. Low-risk status, defined as untreated systolic/diastolic blood pressure ≤120/≤80 mm Hg, untreated serum total cholesterol <5.18 mmol/l, not smoking, body mass index < 25 kg/m(2), and no diabetes mellitus, was assessed at baseline (1967 to 1973). Functional disability, categorized as (1) any disability in activities of daily living (ADLs), (2) any disability in instrumental ADLs but not in ADL, or (3) no disability, was assessed from the 2003 health survey. There were 39% women, 4% Black, with a mean age of 43 years and 6% low-risk status at baseline. After 32 years, 7% reported having limitations in performing any ADL and 11% in any instrumental ADL only. The prevalence of any ADL limitation was lowest in low-risk people and increased in a graded fashion with less-favorable risk factor groups (P trend <0.001). Compared with those with 2+ high-risk factors, the multivariable-adjusted odds of having any disability in ADLs versus no disability in people with low risk, any moderate risk, and 1 high-risk factor at baseline were lower by 58%, 48%, and 37%, respectively. Results were similar for instrumental ADLs, in both men and women. Having an optimal cardiovascular disease risk factor profile at younger age is associated with the lowest rate of functional disability in older age. © 2016 American Heart Association, Inc.

  12. Association of Amyloid Pathology With Myelin Alteration in Preclinical Alzheimer Disease

    PubMed Central

    Dean, Douglas C.; Hurley, Samuel A.; Kecskemeti, Steven R.; O’Grady, J. Patrick; Canda, Cristybelle; Davenport-Sis, Nancy J.; Carlsson, Cynthia M.; Zetterberg, Henrik; Blennow, Kaj; Asthana, Sanjay; Sager, Mark A.; Johnson, Sterling C.; Alexander, Andrew L.; Bendlin, Barbara B.

    2016-01-01

    IMPORTANCE The accumulation of aggregated β-amyloid and tau proteins into plaques and tangles is a central feature of Alzheimer disease (AD). While plaque and tangle accumulation likely contributes to neuron and synapse loss, disease-related changes to oligodendrocytes and myelin are also suspected of playing a role in development of AD dementia. Still, to our knowledge, little is known about AD-related myelin changes, and even when present, they are often regarded as secondary to concomitant arteriosclerosis or related to aging. OBJECTIVE To assess associations between hallmark AD pathology and novel quantitative neuroimaging markers while being sensitive to white matter myelin content. DESIGN, SETTING, AND PARTICIPANTS Magnetic resonance imaging was performed at an academic research neuroimaging center on a cohort of 71 cognitively asymptomatic adults enriched for AD risk. Lumbar punctures were performed and assayed for cerebrospinal fluid (CSF) biomarkers of AD pathology, including β-amyloid 42, total tau protein, phosphorylated tau 181, and soluble amyloid precursor protein. We measured whole-brain longitudinal and transverse relaxation rates as well as the myelin water fraction from each of these individuals. MAIN OUTCOMES AND MEASURES Automated brain mapping algorithms and statistical models were used to evaluate the relationships between age, CSF biomarkers of AD pathology, and quantitative magnetic resonance imaging relaxometry measures, including the longitudinal and transverse relaxation rates and the myelin water fraction. RESULTS The mean (SD) age for the 19 male participants and 52 female participants in the study was 61.6 (6.4) years. Widespread age-related changes to myelin were observed across the brain, particularly in late myelinating brain regions such as frontal white matter and the genu of the corpus callosum. Quantitative relaxometry measures were negatively associated with levels of CSF biomarkers across brain white matter and in areas

  13. Are risk factors associated with invasive pneumococcal disease according to different serotypes?

    PubMed Central

    Ciruela, Pilar; Soldevila, Núria; Selva, Laura; Hernández, Sergi; Garcia-Garcia, Juan Jose; Moraga, Fernando; de Sevilla, Mariona F.; Codina, Gemma; Planes, Ana Maria; Esteva, Cristina; Coll, Francis; Cardeñosa, Neus; Jordan, Iolanda; Batalla, Joan; Salleras, Luis; Muñoz-Almagro, Carmen; Domínguez, Angela

    2013-01-01

    The aim of this study was to investigate risk factors for the most common serotypes of invasive pneumococcal disease (IPD). A total of 293 IPD cases were analyzed in children aged 3–59 mo in a community with intermediate vaccination coverage with the 7-valent pneumococcal vaccine (PCV7). IPD cases were reviewed during 2007–2009 in two pediatric hospitals in Catalonia (Spain). A multivariate analysis using unconditional logistic regression was performed to estimate the adjusted odds ratio. PCV7 coverage was 45.4%. Pneumonia with empyema (64.5%) was the most frequent clinical manifestation. The most common serotypes were: serotype 1 (21.2%), 19A (16.0%), 3 (12.6%) and 7F/A (6.8%). 70.0% of serotypes found were included in the 13-valent conjugate vaccine (PCV13), 39.2% in the 10-valent conjugate vaccine and 8.1% in the PCV7. PCV7 was protective in IPD cases due to PCV7-serotypes (aOR: 0.15, 95% CI:0.04–0.55). Serotype 1 was positively associated with attending day care or school (aOR: 3.55, 95% CI: 1.21–10.38) and age 24–59 mo (aOR: 7.70, 95% CI:2.70–21.98). Serotype 19A was positively associated with respiratory infection in the previous month (aOR: 2.26, 95% CI: 1.03–4.94), non-penicillin susceptible IPD (aOR: 1.89, 95% CI:1.13–3.16) and negatively associated with age 24–59 mo (aOR: 0.19, 95% CI:0.09–0.41). Serotype 3 was positively associated with vaccination (aOR: 4.87, 95% CI:2.05–11.59). No factors were associated with serotype 7F/A. Vaccination with pneumococcal vaccines including more serotypes may reduce the risk of disease in our setting. PMID:23295982

  14. Symptoms to pollen and fruits early in life and allergic disease at 4 years of age.

    PubMed

    Mai, X-M; Neuman, A; Ostblom, E; Pershagen, G; Nordvall, L; Almqvist, C; van Hage, M; Wickman, M

    2008-11-01

    The predictive value of reported early symptoms to pollen or fruits on later allergic disease is unclear. Our aim is to evaluate if symptoms to pollen and/or to fruits early in life are associated with allergic disease and sensitization to pollen at 4 years. The study included 3619 children from the Barn (Children), Allergy, Milieu, Stockholm, Epidemiology project (BAMSE) birth cohort. Reported symptoms of wheeze, sneeze or rash to birch, grass or weed, symptoms (vomiting, diarrhea, rash, facial edema, sneeze, or wheeze) to fruits including tree-nuts at 1 or 2 years of age, and definitions of asthma, rhinitis and eczema at 4 years were derived from questionnaire data. Sensitization to pollen allergens was defined as allergen-specific IgE-antibodies to any pollen (birch/timothy/mugwort) > or =0.35 kU(A)/l. At 1 or 2 years of age, 6% of the children were reported to have pollen-related symptoms, 6% had symptoms to fruits, and 1.4% to both pollen and fruits. Children with symptoms to both pollen and fruits at 1 or 2 years of age had an increased risk for sensitization to any pollen allergen at age 4 (OR(adj) = 4.4, 95% CI = 2.1-9.2). This group of children also had a substantially elevated risk for developing any allergic disease (asthma, rhinitis, or eczema) at 4 years irrespective of sensitization to pollen (OR(adj) = 8.6, 95% CI = 4.5-16.4). The prevalence of reported symptoms to pollen and fruits is very low in early childhood. However, children with early symptoms to both pollen and fruits appear to have a markedly elevated risk for allergic disease.

  15. The Role of Free Radicals in the Aging Brain and Parkinson’s Disease: Convergence and Parallelism

    PubMed Central

    Kumar, Hemant; Lim, Hyung-Woo; More, Sandeep Vasant; Kim, Byung-Wook; Koppula, Sushruta; Kim, In Su; Choi, Dong-Kug

    2012-01-01

    Free radical production and their targeted action on biomolecules have roles in aging and age-related disorders such as Parkinson’s disease (PD). There is an age-associated increase in oxidative damage to the brain, and aging is considered a risk factor for PD. Dopaminergic neurons show linear fallout of 5–10% per decade with aging; however, the rate and intensity of neuronal loss in patients with PD is more marked than that of aging. Here, we enumerate the common link between aging and PD at the cellular level with special reference to oxidative damage caused by free radicals. Oxidative damage includes mitochondrial dysfunction, dopamine auto-oxidation, α-synuclein aggregation, glial cell activation, alterations in calcium signaling, and excess free iron. Moreover, neurons encounter more oxidative stress as a counteracting mechanism with advancing age does not function properly. Alterations in transcriptional activity of various pathways, including nuclear factor erythroid 2-related factor 2, glycogen synthase kinase 3β, mitogen activated protein kinase, nuclear factor kappa B, and reduced activity of superoxide dismutase, catalase and glutathione with aging might be correlated with the increased incidence of PD. PMID:22949875

  16. Sporadic inclusion-body myositis: conformational multifactorial ageing-related degenerative muscle disease associated with proteasomal and lysosomal inhibition, endoplasmic reticulum stress, and accumulation of amyloid-β42 oligomers and phosphorylated tau.

    PubMed

    Askanas, Valerie; Engel, W King

    2011-04-01

    The pathogenesis of sporadic inclusion-body myositis (s-IBM), the most common muscle disease of older persons, is complex and multifactorial. Both the muscle fiber degeneration and the mononuclear-cell inflammation are components of the s-IBM pathology, but how each relates to the pathogenesis remains unsettled. We consider that the intramuscle fiber degenerative component plays the primary and the major pathogenic role leading to muscle fiber destruction and clinical weakness. In this article we review the newest research advances that provide a better understanding of the s-IBM pathogenesis. Cellular abnormalities occurring in s-IBM muscle fibers are discussed, including: several proteins that are accumulated in the form of aggregates within muscle fibers, including amyloid-β42 and its oligomers, and phosphorylated tau in the form of paired helical filaments, and we consider their putative detrimental influence; cellular mechanisms leading to protein misfolding and aggregation, including evidence of their inadequate disposal; pathogenic importance of endoplasmic reticulum stress and the unfolded protein response demonstrated in s-IBM muscle fibers; and decreased deacetylase activity of SIRT1. All these factors are combined with, and perhaps provoked by, an ageing intracellular milieu. Also discussed are the intriguing phenotypic similarities between s-IBM muscle fibers and the brains of Alzheimer and Parkinson's disease patients, the two most common neurodegenerative diseases associated with ageing. Muscle biopsy diagnostic criteria are also described and illustrated. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  17. Reptile-associated salmonellosis in children aged under 5 years in South West England.

    PubMed

    Murphy, Dan; Oshin, Femi

    2015-04-01

    To determine the proportion of Salmonella cases in children aged <5 years that were reptile-associated salmonellosis (RAS) and to compare the severity of illness. To analyse all cases of salmonellosis reported to public health authorities in children aged under 5 years in the South West of the UK from January 2010 to December 2013 for reptile exposure, age, serotype, hospitalisation and invasive disease. 48 of 175 (27%) Salmonella cases had exposure to reptiles. The median age of RAS cases was significantly lower than non-RAS cases (0.5 vs 1.0 year). RAS cases were 2.5 times more likely to be hospitalised (23/48) compared with non-RAS cases (25/127; p=0.0002). This trend continued in cases aged under 12 months, with significantly more RAS cases hospitalised (19/38) than non-RAS cases (8/42; p=0.003). Significantly more RAS cases had invasive disease (8/48: 5 bacteraemia, 2 meningitis, 1 colitis) than non-RAS cases (4/127: 3 bacteraemia, 1 meningitis). Reptile exposure was found in over a quarter of all reported Salmonella cases in children under 5 years of age. RAS is associated with young age, hospitalisation and invasive disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  18. Connective tissue diseases, multimorbidity and the ageing lung.

    PubMed

    Spagnolo, Paolo; Cordier, Jean-François; Cottin, Vincent

    2016-05-01

    Connective tissue diseases encompass a wide range of heterogeneous disorders characterised by immune-mediated chronic inflammation often leading to tissue damage, collagen deposition and possible loss of function of the target organ. Lung involvement is a common complication of connective tissue diseases. Depending on the underlying disease, various thoracic compartments can be involved but interstitial lung disease is a major contributor to morbidity and mortality. Interstitial lung disease, pulmonary hypertension or both are found most commonly in systemic sclerosis. In the elderly, the prevalence of connective tissue diseases continues to rise due to both longer life expectancy and more effective and better-tolerated treatments. In the geriatric population, connective tissue diseases are almost invariably accompanied by age-related comorbidities, and disease- and treatment-related complications, which contribute to the significant morbidity and mortality associated with these conditions, and complicate treatment decision-making. Connective tissue diseases in the elderly represent a growing concern for healthcare providers and an increasing burden of global health resources worldwide. A better understanding of the mechanisms involved in the regulation of the immune functions in the elderly and evidence-based guidelines specifically designed for this patient population are instrumental to improving the management of connective tissue diseases in elderly patients. Copyright ©ERS 2016.

  19. Age-related differences in associative memory: Empirical evidence and theoretical perspectives.

    PubMed

    Naveh-Benjamin, Moshe; Mayr, Ulrich

    2018-02-01

    Systematic research and anecdotal evidence both indicate declines in episodic memory in older adults in good health without dementia-related disorders. Several hypotheses have been proposed to explain these age-related changes in episodic memory, some of which attribute such declines to a deterioration in associative memory. The current special issue of Psychology and Aging on Age-Related Differences in Associative Memory includes 16 articles by top researchers in the area of memory and aging. Their contributions provide a wealth of empirical work that addresses different aspects of aging and associative memory, including different mediators and predictors of age-related declines in binding and associative memory, cognitive, noncognitive, genetic, and neuro-related ones. The contributions also address the processing phases where these declines manifest themselves and look at ways to ameliorate these age-related declines. Furthermore, the contributions in this issue draw on different theoretical perspectives to explain age-related changes in associative memory and provide a wealth of varying methodologies to assess older and younger adults' performance. Finally, although most of the studies focus on normative/healthy aging, some of them contain insights that are potentially applicable to disorders and pathologies. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  20. Age and rate of cognitive decline in Alzheimer disease: implications for clinical trials.

    PubMed

    Bernick, Charles; Cummings, Jeffrey; Raman, Rema; Sun, Xiaoying; Aisen, Paul

    2012-07-01

    Factors that affect the rate of progression of Alzheimer disease (AD) need to be considered in the clinical trial designs of potential disease-modifying therapies. To determine the influence of age on AD course in a clinical trial setting. Pooled cohort study from 3 AD clinical trials of 18-month duration conducted by the Alzheimer Disease Cooperative Study group. Alzheimer disease research centers from across the United States. Four hundred seventy-one subjects with mild to moderate AD assigned to the placebo arm of 3 clinical trials. The relationships between baseline age and rate of change in the Alzheimer Disease Assessment Scale–cognitive subscale (ADAS-cog) 11, Mini-Mental State Examination, Clinical Dementia Rating scale Sum of Boxes score, Alzheimer Disease Cooperative Study–activities of daily living scale, and Neuropsychiatric Inventory were analyzed using a mixed-effect regression model. Sample size calculation for possible future AD clinical trials lasting 18 months using the results of the change in ADAS-cog 11 by tertiles of age groups. Older age at baseline was associated with a slower rate of decline in the ADAS-cog 11 and the Mini-Mental State Examination scores. Almost twice as many subjects aged 80 years and older compared with those aged younger than 70 years would be required to demonstrate a 30% treatment effect on the ADAS-cog 11 in an 18-month AD trial. Subject age is an important factor to consider when defining the study population in and analyzing data from AD trials of potential disease-modifying therapies.

  1. [Chronic kidney disease in Primary Health Care: prevalence and associated risk factors].

    PubMed

    Salvador González, Betlem; Rodríguez Pascual, Mercedes; Ruipérez Guijarro, Laura; Ferré González, Antonia; Cunillera Puertolas, Oriol; Rodríguez Latre, Luisa M

    2015-04-01

    To determine the prevalence of chronic kidney disease and associated risk factors in subjects over 60 years of age, as well as its staging by determining the glomerular filtration rate (GFR). Cross-sectional observational study. Primary Health Care. Patients≥60 years of age who were seen in 40 Primary Health Care centres with serum creatinine measured in a central laboratory between January 1 and December 31, 2010. kidney transplant, home care. Social-demographic and anthropometric data, cardiovascular risk factors, and diseases established according to electronic clinical records. Serum creatinine was measured using standardised Jaffe kinetic method, and GFR estimated with MDRD-4-IDMS and CKD-EPI. A total of 97,665 subjects (57.3% women, median age 70.0 years [Q1: 65.0, Q3: 77.0]). GFR-MDRD prevalence<60=15.1% (16.6% in women, 13.2% in men; P<.001) and increased with age. Multivariate analysis showed a positive association between GFR-MDRD<60 and age (OR=1.74; 95% CI 1.70 to 1.77), hypertension (OR=2.18; 95% CI 2.08 to 2.30), heart failure (OR=2.03; 95% CI 1.83 to 2.25), atrial fibrillation (OR=1.57; 95% CI 1.41 to 1.76), ischaemic heart disease (OR=1.40; 95% CI 1.30 to 1.50), peripheral arterial disease (OR=1.31; 95% CI 1.09 to 1.57), dyslipidaemia (OR=1.28; 95% CI 1.23 to 1.33), diabetes (OR=1.26; 95% CI 1.17 to 1.34), and stroke (OR=1.17; 95% CI 1.09 to 1.25). The GFR-CKD-EPI model showed an increase in OR with age and male sex, that became significant as a chronic kidney disease risk factor. Chronic kidney disease has considerable prevalence in subjects≥60 years seen in Primary Health Care, more in women, and increasing with age. Hypertension, more than diabetes, was the main associated cardiovascular risk factor. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  2. Health and disease phenotyping in old age using a cluster network analysis.

    PubMed

    Valenzuela, Jesus Felix; Monterola, Christopher; Tong, Victor Joo Chuan; Ng, Tze Pin; Larbi, Anis

    2017-11-15

    Human ageing is a complex trait that involves the synergistic action of numerous biological processes that interact to form a complex network. Here we performed a network analysis to examine the interrelationships between physiological and psychological functions, disease, disability, quality of life, lifestyle and behavioural risk factors for ageing in a cohort of 3,270 subjects aged ≥55 years. We considered associations between numerical and categorical descriptors using effect-size measures for each variable pair and identified clusters of variables from the resulting pairwise effect-size network and minimum spanning tree. We show, by way of a correspondence analysis between the two sets of clusters, that they correspond to coarse-grained and fine-grained structure of the network relationships. The clusters obtained from the minimum spanning tree mapped to various conceptual domains and corresponded to physiological and syndromic states. Hierarchical ordering of these clusters identified six common themes based on interactions with physiological systems and common underlying substrates of age-associated morbidity and disease chronicity, functional disability, and quality of life. These findings provide a starting point for indepth analyses of ageing that incorporate immunologic, metabolomic and proteomic biomarkers, and ultimately offer low-level-based typologies of healthy and unhealthy ageing.

  3. Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks

    PubMed Central

    Aung, Theingi; Halsey, Jim; Kromhout, Daan; Gerstein, Hertzel C.; Marchioli, Roberto; Tavazzi, Luigi; Geleijnse, Johanna M.; Rauch, Bernhard; Ness, Andrew; Galan, Pilar; Chew, Emily Y.; Bosch, Jackie; Collins, Rory; Lewington, Sarah; Armitage, Jane

    2018-01-01

    Importance Current guidelines advocate the use of marine-derived omega-3 fatty acids supplements for the prevention of coronary heart disease and major vascular events in people with prior coronary heart disease, but large trials of omega-3 fatty acids have produced conflicting results. Objective To conduct a meta-analysis of all large trials assessing the associations of omega-3 fatty acid supplements with the risk of fatal and nonfatal coronary heart disease and major vascular events in the full study population and prespecified subgroups. Data Sources and Study Selection This meta-analysis included randomized trials that involved at least 500 participants and a treatment duration of at least 1 year and that assessed associations of omega-3 fatty acids with the risk of vascular events. Data Extraction and Synthesis Aggregated study-level data were obtained from 10 large randomized clinical trials. Rate ratios for each trial were synthesized using observed minus expected statistics and variances. Summary rate ratios were estimated by a fixed-effects meta-analysis using 95% confidence intervals for major diseases and 99% confidence intervals for all subgroups. Main Outcomes and Measures The main outcomes included fatal coronary heart disease, nonfatal myocardial infarction, stroke, major vascular events, and all-cause mortality, as well as major vascular events in study population subgroups. Results Of the 77 917 high-risk individuals participating in the 10 trials, 47 803 (61.4%) were men, and the mean age at entry was 64.0 years; the trials lasted a mean of 4.4 years. The associations of treatment with outcomes were assessed on 6273 coronary heart disease events (2695 coronary heart disease deaths and 2276 nonfatal myocardial infarctions) and 12 001 major vascular events. Randomization to omega-3 fatty acid supplementation (eicosapentaenoic acid dose range, 226-1800 mg/d) had no significant associations with coronary heart disease death (rate ratio [RR], 0

  4. Impact of Air Pollutants on Oxidative Stress in Common Autophagy-Mediated Aging Diseases

    PubMed Central

    Numan, Mohamed Saber; Brown, Jacques P.; Michou, Laëtitia

    2015-01-01

    Atmospheric pollution-induced cellular oxidative stress is probably one of the pathogenic mechanisms involved in most of the common autophagy-mediated aging diseases, including neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer’s, disease, as well as Paget’s disease of bone with or without frontotemporal dementia and inclusion body myopathy. Oxidative stress has serious damaging effects on the cellular contents: DNA, RNA, cellular proteins, and cellular organelles. Autophagy has a pivotal role in recycling these damaged non-functional organelles and misfolded or unfolded proteins. In this paper, we highlight, through a narrative review of the literature, that when autophagy processes are impaired during aging, in presence of cumulative air pollution-induced cellular oxidative stress and due to a direct effect on air pollutant, autophagy-mediated aging diseases may occur. PMID:25690002

  5. Early brain response to low-dose radiation exposure involves molecular networks and pathways associated with cognitive functions, advanced aging and Alzheimer's disease.

    PubMed

    Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J

    2009-01-01

    Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy and environmental nuclear contamination as well as for Earth-orbit and space missions. Analyses of transcriptome profiles of mouse brain tissue after whole-body irradiation showed that low-dose exposures (10 cGy) induced genes not affected by high-dose radiation (2 Gy) and that low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues and pathways that were specific for brain tissue. Low-dose genes clustered into a saturated network (P < 10(-53)) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified nine neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose irradiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down-regulated in normal human aging and Alzheimer's disease.

  6. Risk Factors Associated with Age-Related Macular Degeneration

    PubMed Central

    2006-01-01

    Objective: To investigate possible risk factors for age-related macular degeneration (AMD) in participants in the Age-Related Eye Disease Study (AREDS). Design: Case-control study. Participants: Of the 4757 persons enrolled in AREDS, 4519 persons aged 60 to 80 years were included in this study. The lesions associated with AMD ranged from absent in both eyes to advanced in one eye. Main Outcome Measures: Stereoscopic color fundus photographs of the macula were used to place participants into one of five groups, based on the frequency and severity of lesions associated with AMD. Participants with fewer than 15 small drusen served as the control group. Results: Staged model building techniques were used to compare each of the four case groups with the control group. Increased age was a consistent finding of all four of the case groups compared with the control group, and all the following associations were age adjusted. Persons with either intermediate drusen, extensive small drusen, or the pigment abnormalities associated with AMD (group 2) were more likely to be female, more likely to have a history of arthritis, and less likely to have a history of angina. Persons with one or more large drusen or extensive intermediate drusen (group 3) were more likely to use hydrochlorothiazide diuretics and more likely to have arthritis. Hypertension, hyperopia, presence of lens opacities, and white race were also found more frequently in this group as well as in persons with neovascular AMD (group 5). Only persons in group 5 were more likely to have an increased body mass index, whereas persons with geographic atrophy (group 4) as well as those in groups 3 and 5 were more likely to have completed fewer years in school or to be smokers. Those with geographic atrophy were also more likely to use thyroid hormones and antacids. Conclusions: Our findings for smoking and hypertension, which have been noted in previous studies, suggest that two important public health recommendations

  7. Prevalence and severity of ocular involvement in Graves' disease according to sex and age: A clinical study from Babol, Iran.

    PubMed

    Gharib, Sara; Moazezi, Zoleika; Bayani, Mohammad Ali

    2018-01-01

    Thyroid-associated eye disease (TED), previously known as Graves' ophthalmopathy is a cosmetically and functionally debilitating disease that is seen worldwide. The aim of this study was to evaluate the prevalence and clinical severity of ocular manifestations of Graves' disease according to sex, age and duration in northern Iran. Between April 2011 and March 2012, 105 patients with Graves' disease, underwent ophthalmic examination, including ocular motility, exophthalmometry, intraocular pressure (IOP), slit lamp and fundoscopy. Patients received scores according to modified Werner's NO SPECS classification. Ocular involvement was found in 70 patients with established Graves's disease. The mean age was 35.0 years, (SD 13.0, range 15 to 69). The most common ocular findings were exophthalmometric proptosis of more than 20 mm (63.8%), lid lag (55.7%), lid retraction (52.8%) and tearing (38.6%). Almost 70% of patients had bilateral involvement. Elevated IOP was seen in 15 (25.4%) patients, and was significantly related to proptosis (P=0.007). More than half of the patients (n=36, 52.2%) had a modified Werner's NO SPECS score of 3.00. Clinical severity as shown by the increasing number of signs and symptoms per patient was correlated to increasing age (r=0.31, P=0.01) but not to gender (P=0.17). Both functional (ocular motility disorders, increased IOP) and cosmetic (proptosis, periorbital edema) sequels are common ocular presentations in patients with Graves' disease. Proptosis was the most common finding in this study and was associated with elevated IOP. Clinical severity was found to correlate to increasing age.

  8. Direct medical costs associated with atopic diseases among young children in Thailand.

    PubMed

    Ngamphaiboon, Jarungchit; Kongnakorn, Thitima; Detzel, Patrick; Sirisomboonwong, Krittawan; Wasiak, Radek

    2012-01-01

    Allergic diseases are the most common childhood illness in Thailand. Their prevalence has been rising over time, with several studies having revealed substantial economic burden. However, no such study had yet been conducted for Thailand. The aim of this study was to estimate direct medical costs associated with atopic diseases among children aged 0-5 years in Thailand. A cost-of-illness model was constructed to estimate the total direct medical costs of atopic diseases comprising atopic dermatitis, chronic rhinitis, asthma (i.e., recurrent wheeze), and cow's milk allergy. The model employed a prevalence-based approach, considering a total number of atopic cases in 2010. Direct medical costs were estimated using a bottom-up analysis with the estimation of the quantity of healthcare resource use and the unit costs. Epidemiological data were obtained from literature and Thai surveys, whereas treatment unit costs were from either a hospital database or Thai standard cost list. Expert opinion informed type, frequency, and quantity of medical resources utilized. Key limitations included lack of data-driven evidences on severity distribution for this particular age group, indirect costs, and medical resource use associated with each condition. Total direct cost was estimated to be THB 27.8 billion (US$899 million). Treatments contributed largest to the total costs (46%), followed by inpatient care (37%), outpatient care (12%), and monitoring and labs (5%). Costs per treated patient were highest in cow's milk allergy (THB 64,383; US$2077), followed by rhinitis (THB 12,669; US$409), asthma (THB 9633; US$312), and atopic dermatitis (THB 5432; US$175). Atopic diseases in young children are associated with substantial burden in direct medical costs to Thailand. These costs can be diminished through nutritional intervention recognized to effectively decrease the incidence of atopic diseases.

  9. Genome-wide association study identifies four novel loci associated with Alzheimer's endophenotypes and disease modifiers.

    PubMed

    Deming, Yuetiva; Li, Zeran; Kapoor, Manav; Harari, Oscar; Del-Aguila, Jorge L; Black, Kathleen; Carrell, David; Cai, Yefei; Fernandez, Maria Victoria; Budde, John; Ma, Shengmei; Saef, Benjamin; Howells, Bill; Huang, Kuan-Lin; Bertelsen, Sarah; Fagan, Anne M; Holtzman, David M; Morris, John C; Kim, Sungeun; Saykin, Andrew J; De Jager, Philip L; Albert, Marilyn; Moghekar, Abhay; O'Brien, Richard; Riemenschneider, Matthias; Petersen, Ronald C; Blennow, Kaj; Zetterberg, Henrik; Minthon, Lennart; Van Deerlin, Vivianna M; Lee, Virginia Man-Yee; Shaw, Leslie M; Trojanowski, John Q; Schellenberg, Gerard; Haines, Jonathan L; Mayeux, Richard; Pericak-Vance, Margaret A; Farrer, Lindsay A; Peskind, Elaine R; Li, Ge; Di Narzo, Antonio F; Kauwe, John S K; Goate, Alison M; Cruchaga, Carlos

    2017-05-01

    More than 20 genetic loci have been associated with risk for Alzheimer's disease (AD), but reported genome-wide significant loci do not account for all the estimated heritability and provide little information about underlying biological mechanisms. Genetic studies using intermediate quantitative traits such as biomarkers, or endophenotypes, benefit from increased statistical power to identify variants that may not pass the stringent multiple test correction in case-control studies. Endophenotypes also contain additional information helpful for identifying variants and genes associated with other aspects of disease, such as rate of progression or onset, and provide context to interpret the results from genome-wide association studies (GWAS). We conducted GWAS of amyloid beta (Aβ 42 ), tau, and phosphorylated tau (ptau 181 ) levels in cerebrospinal fluid (CSF) from 3146 participants across nine studies to identify novel variants associated with AD. Five genome-wide significant loci (two novel) were associated with ptau 181 , including loci that have also been associated with AD risk or brain-related phenotypes. Two novel loci associated with Aβ 42 near GLIS1 on 1p32.3 (β = -0.059, P = 2.08 × 10 -8 ) and within SERPINB1 on 6p25 (β = -0.025, P = 1.72 × 10 -8 ) were also associated with AD risk (GLIS1: OR = 1.105, P = 3.43 × 10 -2 ), disease progression (GLIS1: β = 0.277, P = 1.92 × 10 -2 ), and age at onset (SERPINB1: β = 0.043, P = 4.62 × 10 -3 ). Bioinformatics indicate that the intronic SERPINB1 variant (rs316341) affects expression of SERPINB1 in various tissues, including the hippocampus, suggesting that SERPINB1 influences AD through an Aβ-associated mechanism. Analyses of known AD risk loci suggest CLU and FERMT2 may influence CSF Aβ 42 (P = 0.001 and P = 0.009, respectively) and the INPP5D locus may affect ptau 181 levels (P = 0.009); larger studies are necessary to verify these results. Together the findings

  10. Takayasu arteritis in childhood: misdiagnoses at disease onset and associated diseases.

    PubMed

    Clemente, Gleice; Silva, Clovis A; Sacchetti, Silvana B; Ferriani, Virginia P L; Oliveira, Sheila K; Sztajnbok, Flavio; Bica, Blanca E R G; Cavalcanti, André; Robazzi, Teresa; Bandeira, Marcia; Terreri, Maria Teresa

    2018-06-01

    Juvenile-Takayasu arteritis (j-TA) is a difficult diagnosis and some patients develop uncommon manifestations and associated diseases that may contribute to the delayed diagnosis. Our aim was to identify the misdiagnoses, the associated diseases and the atypical manifestations observed in a j-TA Brazilian multicentre study. 71 children and adolescents who met the classification criteria for j-TA were included. The misdiagnoses, the associated diseases and the atypical manifestations were evaluated. 19 (26.8%) patients had misdiagnoses. The most common of them was aortic coarctation in six (8.4%) patients, followed by rheumatic fever in five (7.0%) and one patient presented with both former diagnoses. Limb pain (two patients), spondyloarthropathy, juvenile idiopathic arthritis (JIA), spinal arteriovenous malformation, polyarteritis nodosa (PAN) and fever of unknown origin (FUO) were other misdiagnoses. Patients who had misdiagnoses previously to j-TA diagnosis presented a trend to have a longer diagnosis delay. 11 (15.5%) patients had 14 TA-associated diseases, such as pulmonary tuberculosis (5 patients), rheumatic fever (2 patients), spondyloarthropathy, polyarticular JIA, Crohn's disease, Prader-Willi disease, diabetes mellitus, Moyamoya and primary immunodeficiency. 7 (9.9%) patients presented 10 atypical manifestations, such as pyoderma gangrenosum, erythema nodosum, myositis, chorea, enthesitis, episcleritis, uveitis, hepatomegaly, splenomegaly and necrosis of extremities. Our study emphasizes the main misdiagnoses, associated diseases and atypical manifestations that occur in patients with j-TA and warns of the features that may alert paediatricians to this diagnosis, such as constitutional symptoms and elevated inflammatory markers.

  11. Chronic Kidney Disease Is Associated With White Matter Hyperintensity Volume

    PubMed Central

    Khatri, Minesh; Wright, Clinton B.; Nickolas, Thomas L.; Yoshita, Mitsuhiro; Paik, Myunghee C.; Kranwinkel, Grace; Sacco, Ralph L.; DeCarli, Charles

    2010-01-01

    Background and Purpose White matter hyperintensities have been associated with increased risk of stroke, cognitive decline, and dementia. Chronic kidney disease is a risk factor for vascular disease and has been associated with inflammation and endothelial dysfunction, which have been implicated in the pathogenesis of white matter hyperintensities. Few studies have explored the relationship between chronic kidney disease and white matter hyperintensities. Methods The Northern Manhattan Study is a prospective, community-based cohort of which a subset of stroke-free participants underwent MRIs. MRIs were analyzed quantitatively for white matter hyperintensities volume, which was log-transformed to yield a normal distribution (log-white matter hyperintensity volume). Kidney function was modeled using serum creatinine, the Cockcroft-Gault formula for creatinine clearance, and the Modification of Diet in Renal Disease formula for estimated glomerular filtration rate. Creatinine clearance and estimated glomerular filtration rate were trichotomized to 15 to 60 mL/min, 60 to 90 mL/min, and >90 mL/min (reference). Linear regression was used to measure the association between kidney function and log-white matter hyperintensity volume adjusting for age, gender, race–ethnicity, education, cardiac disease, diabetes, homocysteine, and hypertension. Results Baseline data were available on 615 subjects (mean age 70 years, 60% women, 18% whites, 21% blacks, 62% Hispanics). In multivariate analysis, creatinine clearance 15 to 60 mL/min was associated with increased log-white matter hyperintensity volume (β 0.322; 95% CI, 0.095 to 0.550) as was estimated glomerular filtration rate 15 to 60 mL/min (β 0.322; 95% CI, 0.080 to 0.564). Serum creatinine, per 1-mg/dL increase, was also positively associated with log-white matter hyperintensity volume (β 1.479; 95% CI, 1.067 to 2.050). Conclusions The association between moderate–severe chronic kidney disease and white matter

  12. Coeliac disease and C virus-related chronic hepatitis: a non association.

    PubMed

    Gravina, Antonietta Gerarda; Federico, Alessandro; Masarone, Mario; Cuomo, Antonio; Tuccillo, Concetta; Loguercio, Carmelina; Persico, Marcello; Romano, Marco

    2012-09-26

    A higher prevalence of coeliac disease has recently been reported among patients with HCV-related chronic hepatitis. Moreover, development of clinically overt coeliac disease has been described in a number of HCV-related chronic hepatitis patients during α-interferon therapy. This prospective study was designed to evaluate 1) the prevalence of coeliac disease in patients with HCV-related chronic hepatitis; 2) the prevalence of HCV infection in patients with coeliac disease; 3) whether PEG interferon-α treatment might favour the development of coeliac disease in patients with chronic hepatitis C. Two hundred-ten consecutive patients (M/F = 140/70, range of age 35-58 years, median age 46.5 years) with biopsy proven chronic hepatitis C underwent serological screening for antiendomysial and tissue transglutaminase IgA antibodies. One hundred ninety-four coeliac patients (M/F = 52/142, range of age 18-74 years, median age 34 years) were screened for HCV antibodies. Positivity for HCV antibodies in coeliac disease patients was confirmed by detection of serum HCV-RNA by RT-PCR. This work was carried out in accordance to ethical guidelines of Declaration of Helsinki and was approved by Institutional Ethics Committee of the Second University of Naples. All patients gave informed written consent. 1) none of the 210 HCV-related chronic hepatitis patients were positive for coeliac disease serologic screening; 2) prevalence of HCV infection among coeliac patients was 1.54% (3/194) which is comparable to that reported in the Southern Italy population; 3) PEG interferon-α treatment was not associated with development of coeliac disease either clinical or serological. 1) coeliac disease is not associated with HCV infection; 2) PEG interferon-α does not trigger celiac disease.

  13. Cardiac index is associated with brain aging: the Framingham Heart Study.

    PubMed

    Jefferson, Angela L; Himali, Jayandra J; Beiser, Alexa S; Au, Rhoda; Massaro, Joseph M; Seshadri, Sudha; Gona, Philimon; Salton, Carol J; DeCarli, Charles; O'Donnell, Christopher J; Benjamin, Emelia J; Wolf, Philip A; Manning, Warren J

    2010-08-17

    Cardiac dysfunction is associated with neuroanatomic and neuropsychological changes in aging adults with prevalent cardiovascular disease, theoretically because systemic hypoperfusion disrupts cerebral perfusion, contributing to subclinical brain injury. We hypothesized that cardiac function, as measured by cardiac index, would be associated with preclinical brain magnetic resonance imaging (MRI) and neuropsychological markers of ischemia and Alzheimer disease in the community. Brain MRI, cardiac MRI, neuropsychological, and laboratory data were collected on 1504 Framingham Offspring Cohort participants free of clinical stroke, transient ischemic attack, or dementia (age, 61+/-9 years; 54% women). Neuropsychological and brain MRI variables were related to cardiac MRI-assessed cardiac index (cardiac output/body surface area). In multivariable-adjusted models, cardiac index was positively related to total brain volume (P=0.03) and information processing speed (P=0.02) and inversely related to lateral ventricular volume (P=0.048). When participants with clinically prevalent cardiovascular disease were excluded, the relation between cardiac index and total brain volume remained (P=0.02). Post hoc comparisons revealed that participants in the bottom cardiac index tertile (values <2.54) and middle cardiac index tertile (values between 2.54 and 2.92) had significantly lower brain volumes (P=0.04) than participants in the top cardiac index tertile (values >2.92). Although observational data cannot establish causality, our findings are consistent with the hypothesis that decreasing cardiac function, even at normal cardiac index levels, is associated with accelerated brain aging.

  14. Medication for Alzheimer's disease and associated fall hazard: a retrospective cohort study from the Alzheimer's Disease Neuroimaging Initiative.

    PubMed

    Epstein, Noam U; Guo, Rong; Farlow, Martin R; Singh, Jaswinder P; Fisher, Morris

    2014-02-01

    Falls are common in the elderly, especially in those with cognitive impairment. The elderly are often treated with several medications, which may have both beneficial and deleterious effects. The use and type of medication in Alzheimer's disease (AD) patients and association with falls is limited. We examined the association between falls and medication use in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Diagnosis, demographics, medication use, apolipoprotein E4 allele status and functional activity level at baseline were gathered for 810 participants enrolled in the ADNI, including healthy controls and subjects with mild cognitive impairment or Alzheimer's. Reports detailing adverse event falls were tabulated. Baseline characteristics were compared between subjects with and without one or more falls. Cox proportional hazards models were conducted to evaluate the association between subject characteristics and hazard of the first fall. Age (p < 0.0001), Functional Activities Questionnaire (p = 0.035), Beers List (p = 0.0477) and medications for treating cognitive symptoms of Alzheimer's (p = 0.0019) were associated with hazard of fall in the univariate model. In the final multivariate model, after adjusting for covariates, Alzheimer's medication use (p = 0.0005) was associated with hazard of fall. Medication was changed by the clinician after an adverse fall event in 9% of the falls. About 7% of the falls were reported as serious adverse events and 6% were reported to be severe. We found a significant association between the use of symptomatic medication treating cognitive symptoms in AD and hazard of fall after adjusting for age and Beers List medication use. Additional pharmacovigilance of the association between falls and Alzheimer's medication use is warranted.

  15. Effect of young age, positive margins, and triple negative status on disease recurrence after breast conserving therapy

    PubMed Central

    Sakulchairungreung, Bundit; Chirappapha, Prakasit; Suvikapakornkul, Ronnarat; Wasuthit, Yodying; Sukarayothin, Thongchai; Leesombatpaiboon, Montchai; Kongdan, Youwanush

    2016-01-01

    Background To determine the risk factors for disease recurrence after breast conserving therapy (BCT) for breast cancer in a group of South-East Asian women. Methods Medical and pathological records of women who underwent BCT during the 10-year period from 2001 to 2010 were reviewed. Data collected included age ≤35 years defined as the young, type of operation, pathological data, hormonal receptor (HR) status, human epidermal growth factor receptor-2 (HER-2) expression status, and surgical margin status. Data on adjuvant therapy were also collected. Main outcomes were overall breast cancer recurrence, locoregional, and distant recurrence. Risk factors for each type of recurrence were identified using Cox proportional hazards regression models. Results There were 294 BCTs in 290 patients during the study period. The overwhelming majority (91%) had early stage (stages I-II) breast cancers. Young age patients constituted 9% of all patients, and triple negative cancers (HR negative and HER-2 negative) were seen in 19%. Involved margins on initial surgery were found in 9% of cases, and after reoperation, only 2% had involved margins. After a median follow-up of 50 months, and a maximum follow-up of 135 months, there were 30 recurrences and 6 deaths. Of the 30 recurrences, 19 included locoregional, 20 included distant, and 13 had in-breast recurrences. The disease-free survival at 10 years was 82.5% (95% CI: 74.8% to 88.1%), and the cumulative in-breast recurrence was 9.3% (95% CI: 4.9% to 17.2%) at 10 years. Multivariable Cox regression analysis revealed that young age, larger tumor size, involved margins, and no breast irradiation were associated with higher risk of locoregional recurrence. Triple negative status, larger tumor size, more positive nodes, and involved margins were associated with higher risk of distant recurrence. Conclusions We found young age to be a significant prognosticator of locoregional recurrence, and triple negative status of distant

  16. Associations Between Biomarkers and Age in the Presenilin 1 E280A Autosomal Dominant Alzheimer Disease Kindred A Cross-sectional Study

    PubMed Central

    Fleisher, Adam S.; Chen, Kewei; Quiroz, Yakeel T.; Jakimovich, Laura J.; Gomez, Madelyn Gutierrez; Langois, Carolyn M.; Langbaum, Jessica B. S.; Roontiva, Auttawut; Thiyyagura, Pradeep; Lee, Wendy; Ayutyanont, Napatkamon; Lopez, Liliana; Moreno, Sonia; Muñoz, Claudia; Tirado, Victoria; Acosta-Baena, Natalia; Fagan, Anne M.; Giraldo, Margarita; Garcia, Gloria; Huentelman, Matthew J.; Tariot, Pierre N.; Lopera, Francisco; Reiman, Eric M.

    2015-01-01

    IMPORTANCE Age-associated changes in brain imaging and fluid biomarkers are characterized and compared in presenilin 1 (PSEN1) E280A mutation carriers and noncarriers from the world’s largest known autosomal dominant Alzheimer disease (AD) kindred. OBJECTIVE To characterize and compare age-associated changes in brain imaging and fluid biomarkers in PSEN1 E280A mutation carriers and noncarriers. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional measures of 18F-florbetapir positron emission tomography, 18F-fludeoxyglucose positron emission tomography, structural magnetic resonance imaging, cerebrospinal fluid (CSF), and plasma biomarkers of AD were assessed from 54 PSEN1 E280A kindred members (age range, 20-59 years). MAIN OUTCOMES AND MEASURES We used brain mapping algorithms to compare regional cerebral metabolic rates for glucose and gray matter volumes in cognitively unimpaired mutation carriers and noncarriers. We used regression analyses to characterize associations between age and the mean cortical to pontine 18F-florbetapir standard uptake value ratios, precuneus cerebral metabolic rates for glucose, hippocampal gray matter volume, CSF Aβ1-42, total tau and phosphorylated tau181, and plasma Aβ measurements. Age at onset of progressive biomarker changes that distinguish carriers from noncarriers was estimated using best-fitting regression models. RESULTS Compared with noncarriers, cognitively unimpaired mutation carriers had significantly lower precuneus cerebral metabolic rates for glucose, smaller hippocampal volume, lower CSF Aβ1-42, higher CSF total tau and phosphorylated tau181, and higher plasma Aβ1-42 measurements. Sequential changes in biomarkers were seen at age 20 years (95% CI, 14-24 years) for CSF Aβ1-42, age 16 years (95% CI, 11-24 years) for the mean cortical 18F-florbetapir standard uptake value ratio, age 15 years (95% CI, 10-24 years) for precuneus cerebral metabolic rate for glucose, age 15 years (95% CI, 7-20 years) for CSF total tau

  17. Associations between biomarkers and age in the presenilin 1 E280A autosomal dominant Alzheimer disease kindred: a cross-sectional study.

    PubMed

    Fleisher, Adam S; Chen, Kewei; Quiroz, Yakeel T; Jakimovich, Laura J; Gutierrez Gomez, Madelyn; Langois, Carolyn M; Langbaum, Jessica B S; Roontiva, Auttawut; Thiyyagura, Pradeep; Lee, Wendy; Ayutyanont, Napatkamon; Lopez, Liliana; Moreno, Sonia; Muñoz, Claudia; Tirado, Victoria; Acosta-Baena, Natalia; Fagan, Anne M; Giraldo, Margarita; Garcia, Gloria; Huentelman, Matthew J; Tariot, Pierre N; Lopera, Francisco; Reiman, Eric M

    2015-03-01

    Age-associated changes in brain imaging and fluid biomarkers are characterized and compared in presenilin 1 (PSEN1)E280A mutation carriers and noncarriers from the world's largest known autosomal dominant Alzheimer disease (AD) kindred. To characterize and compare age-associated changes in brain imaging and fluid biomarkers in PSEN1 E280A mutation carriers and noncarriers. Cross-sectional measures of 18F-florbetapir positron emission tomography, 18F-fludeoxyglucose positron emission tomography, structural magnetic resonance imaging, cerebrospinal fluid (CSF), and plasma biomarkers of AD were assessed from 54 PSEN1 E280A kindred members (age range, 20-59 years). We used brain mapping algorithms to compare regional cerebral metabolic rates for glucose and gray matter volumes in cognitively unimpaired mutation carriers and noncarriers. We used regression analyses to characterize associations between age and the mean cortical to pontine 18F-florbetapir standard uptake value ratios, precuneus cerebral metabolic rates for glucose, hippocampal gray matter volume, CSF Aβ1-42, total tau and phosphorylated tau181, and plasma Aβ measurements. Age at onset of progressive biomarker changes that distinguish carriers from noncarriers was estimated using best-fitting regression models. Compared with noncarriers, cognitively unimpaired mutation carriers had significantly lower precuneus cerebral metabolic rates for glucose, smaller hippocampal volume, lower CSF Aβ1-42, higher CSF total tau and phosphorylated tau181, and higher plasma Aβ1-42 measurements. Sequential changes in biomarkers were seen at age 20 years (95% CI, 14-24 years) for CSF Aβ1-42, age 16 years (95% CI, 11-24 years) for the mean cortical 18F-florbetapir standard uptake value ratio, age 15 years (95% CI, 10-24 years) for precuneus cerebral metabolic rate for glucose, age 15 years (95% CI, 7-20 years) for CSF total tau, age 13 years (95% CI, 8-19 years) for phosphorylated tau181, and age 6 years (95% CI, 1

  18. Aged monkeys as a partial model for Parkinson's disease

    PubMed Central

    Hurley, P.J.; Elsworth, J.D.; Whittaker, M.C.; Roth, R.H.; Redmond, D.E.

    2011-01-01

    Parkinson's Disease (PD) and the natural aging process share a number of biochemical mechanisms, including reduced function of dopaminergic systems. The present study aims to determine the extent that motor and behavioral changes in aged monkeys resemble parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The behavioral and physiological changes in PD are believed to result largely from selective depletion of dopamine in the nigrostriatal system. In the present study, ten aged female monkeys were compared with three groups: 9 untreated young adult female monkeys, 10 young adult male monkeys and 13 older male monkeys that had been exposed to MPTP. Trained observers, blind as to age and drug condition and without knowledge of the hypotheses, scored the monkeys using the Parkinson's factor score (Parkscore), which has been validated by a high correlation with post mortem striatal dopamine (DA) concentrations. The aged animals had higher scores on the Parkscore compared with the young adults, with most of its component behavioral items showing significance (tremor, eating problems, delayed initiation of movement, and poverty of movement). L-Dopa and DA-agonists did not clearly reverse the principal measure of parkinsonism. DA concentrations post mortem were 63% lower in 3 aged monkeys in the ventral putamen compared with 4 young adults, with greater reductions in putamen than in caudate (45%). We conclude that aged monkeys, unexposed to MPTP, show a similar profile of parkinsonism to that seen after the neurotoxin exposure to MPTP in young adult monkeys. The pattern of greater DA depletion in putamen than in caudate in aged monkeys is the same as in human Parkinson's disease and contrasts with the greater depletion in caudate seen after MPTP. Aged monkeys of this species reflect many facets of Parkinson's disease, but like older humans do not improve with standard dopamine replacement pharmacotherapies. PMID:21620883

  19. Diabetes is Associated with Worse Executive Function in Both Eastern and Western Populations: Shanghai Aging Study and Mayo Clinic Study of Aging.

    PubMed

    Zhao, Qianhua; Roberts, Rosebud O; Ding, Ding; Cha, Ruth; Guo, Qihao; Meng, Haijiao; Luo, Jianfeng; Machulda, Mary M; Shane Pankratz, V; Wang, Bei; Christianson, Teresa J H; Aakre, Jeremiah A; Knopman, David S; Boeve, Bradley F; Hong, Zhen; Petersen, Ronald C

    2015-01-01

    It remains unknown whether the association between diabetes mellitus (DM) and cognitive function differs in Eastern and Western populations. This study aimed to elucidate whether DM is associated with worse cognitive performance in both populations. The Shanghai Aging Study (SAS) and the Mayo Clinic Study of Aging (MCSA) are two population-based studies with similar design and methodology in Shanghai, China and Rochester, MN, USA. Non-demented participants underwent cognitive testing, and DM was assessed from the medical record. Separate analyses were performed in SAS and MCSA regarding the association between DM and cognitive performance. A total of 3,348 Chinese participants in the SAS and 3,734 American subjects in the MCSA were included. Compared with MCSA subjects, SAS participants were younger, less educated, and had lower frequency of vascular disease, APOE ɛ4 carriers and obesity. Participants with DM (compared to non-DM participants) performed significantly worse on all the cognitive domains in both the SAS and MCSA. After adjustment for age, gender, education, and vascular covariates, DM was associated with worse performance in executive function (β=-0.15, p = 0.001 for SAS, and β=-0.10, p = 0.008 for MCSA) in the total sample and in the cognitively normal sub-sample. Furthermore, DM was associated with poor performance in visuospatial skills, language, and memory in the SAS, but not in the MCSA. Diabetes is associated with cognitive dysfunction and, in particular, exerts a negative impact on executive function regardless of race, age, and prevalence of vascular risk factors.

  20. Epidemiology of cognitive aging and Alzheimer's disease: contributions of the cache county utah study of memory, health and aging.

    PubMed

    Hayden, Kathleen M; Welsh-Bohmer, Kathleen A

    2012-01-01

    Epidemiological studies of Alzheimer's disease (AD) provide insights into changing public health trends and their contribution to disease incidence. The current chapter considers how the population-based approach has contributed to our understanding of lifetime exposures that contribute to later disease risk and may act to modify onset of symptoms. We focus on the findings from a recent survey of an exceptionally long-lived population, the Cache County Utah Study of Memory, Health, and Aging. This study is confined to a single geographic population has allowed estimation of the genetic and environmental influences on AD expression across the expected human lifespan of 95+ years. Given the emphasis of this text on the behavioral neurosciences of aging, we highlight within the current chapter the particular contributions of this population-based study to the neuropsychology of aging and AD. We also discuss hypotheses generated from this survey with respect to factors that may either accelerate or delay symptom onset in AD and the conditions that appear to be associated with successful cognitive aging.

  1. A common brain network links development, aging, and vulnerability to disease.

    PubMed

    Douaud, Gwenaëlle; Groves, Adrian R; Tamnes, Christian K; Westlye, Lars Tjelta; Duff, Eugene P; Engvig, Andreas; Walhovd, Kristine B; James, Anthony; Gass, Achim; Monsch, Andreas U; Matthews, Paul M; Fjell, Anders M; Smith, Stephen M; Johansen-Berg, Heidi

    2014-12-09

    Several theories link processes of development and aging in humans. In neuroscience, one model posits for instance that healthy age-related brain degeneration mirrors development, with the areas of the brain thought to develop later also degenerating earlier. However, intrinsic evidence for such a link between healthy aging and development in brain structure remains elusive. Here, we show that a data-driven analysis of brain structural variation across 484 healthy participants (8-85 y) reveals a largely--but not only--transmodal network whose lifespan pattern of age-related change intrinsically supports this model of mirroring development and aging. We further demonstrate that this network of brain regions, which develops relatively late during adolescence and shows accelerated degeneration in old age compared with the rest of the brain, characterizes areas of heightened vulnerability to unhealthy developmental and aging processes, as exemplified by schizophrenia and Alzheimer's disease, respectively. Specifically, this network, while derived solely from healthy subjects, spatially recapitulates the pattern of brain abnormalities observed in both schizophrenia and Alzheimer's disease. This network is further associated in our large-scale healthy population with intellectual ability and episodic memory, whose impairment contributes to key symptoms of schizophrenia and Alzheimer's disease. Taken together, our results suggest that the common spatial pattern of abnormalities observed in these two disorders, which emerge at opposite ends of the life spectrum, might be influenced by the timing of their separate and distinct pathological processes in disrupting healthy cerebral development and aging, respectively.

  2. Microglial dystrophy in the aged and Alzheimer's disease brain is associated with ferritin immunoreactivity.

    PubMed

    Lopes, Kryslaine O; Sparks, D Larry; Streit, Wolfgang J

    2008-08-01

    Degeneration of microglial cells may be important for understanding the pathogenesis of aging-related neurodegeneration and neurodegenerative diseases. In this study, we analyzed the morphological characteristics of microglial cells in the nondemented and Alzheimer's disease (AD) human brain using ferritin immunohistochemistry. The central hypothesis was that expression of the iron storage protein ferritin increases the susceptibility of microglia to degeneration, particularly in the aged brain since senescent microglia might become less efficient in maintaining iron homeostasis and free iron can promote oxidative damage. In a primary set of 24 subjects (age range 34-97 years) examined, microglial cells immunoreactive for ferritin were found to constitute a subpopulation of the larger microglial pool labeled with an antibody for HLA-DR antigens. The majority of these ferritin-positive microglia exhibited aberrant morphological (dystrophic) changes in the aged and particularly in the AD brain. No spatial correlation was found between ferritin-positive dystrophic microglia and senile plaques in AD tissues. Analysis of a secondary set of human postmortem brain tissues with a wide range of postmortem intervals (PMI, average 10.94 +/- 5.69 h) showed that the occurrence of microglial dystrophy was independent of PMI and consequently not a product of tissue autolysis. Collectively, these results suggest that microglial involvement in iron storage and metabolism contributes to their degeneration, possibly through increased exposure of the cells to oxidative stress. We conclude that ferritin immunohistochemistry may be a useful method for detecting degenerating microglia in the human brain. (c) 2008 Wiley-Liss, Inc.

  3. Influence of obesity, age, and comorbidities on the multi-biomarker disease activity test in rheumatoid arthritis.

    PubMed

    Curtis, Jeffrey R; Greenberg, Jeffrey D; Harrold, Leslie R; Kremer, Joel M; Palmer, J Lynn

    2018-02-01

    Traditional markers of inflammation are often required for inclusion in rheumatoid arthritis trials, yet patients with active disease may have normal lab tests. The potential use of the multi-biomarker disease activity (MBDA) test in this setting is unclear, as is understanding of whether it is influenced by patient characteristics (e.g., age, BMI, and comorbidities). Using data from the Corrona registry, we conducted a cross-sectional analysis of RA patients with MBDA tests. Patients were classified as low (<30), moderate (30-44, and high (>44) and by clinical and RA-related factors. Regression was used to evaluate the association between MBDA score and age, body mass index, comorbidities, and RA-related factors. Of 357 eligible patients, 76% (n = 273) had normal CRP (<10mg/L) with high (33%), moderate (45%), and low (22%) disease activity by MBDA. The MBDA score was significantly associated with BMI, age, CDAI, and SJC. There was no association between MBDA score and fibromyalgia, diabetes, smoking, or COPD; none were confounders between MBDA score and either SJC or CDAI. For patients in CDAI remission, older age (2.6 units per decade; p = 0.03) and obesity (β = 10.5 for BMI > 30, referent to <25; p = 0.02) were independently associated with MBDA score. An adjusted MBDA score was proposed that was highly correlated with the original MBDA (r = 0.91). In this real-world analysis, the MBDA score was associated with RA disease activity, obesity, and age, and was negligibly affected by common comorbidities. Almost one-third of patients with normal CRP had high MBDA scores. An adjustment to the MBDA score to account for body mass index and age is proposed. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Association between Dietary Vitamin C Intake and Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study among Middle-Aged and Older Adults.

    PubMed

    Wei, Jie; Lei, Guang-Hua; Fu, Lei; Zeng, Chao; Yang, Tuo; Peng, Shi-Fang

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) has become one of the most prevalent chronic liver disease all over the world. The objective of this study was to evaluate the association between dietary vitamin C intake and NAFLD. Subjects were diagnosed with NAFLD by abdominal ultrasound examination and the consumption of alcohol was less than 40g/day for men or less than 20g/day for women. Vitamin C intake was classified into four categories according to the quartile distribution in the study population: ≤74.80 mg/day, 74.81-110.15 mg/day, 110.16-146.06 mg/day, and ≥146.07 mg/day. The energy and multi-variable adjusted odds ratio (OR), as well as their corresponding 95% confidence interval (CI), were used to determine the relationship between dietary vitamin C intake and NAFLD through logistic regression. The present cross-sectional study included 3471 subjects. A significant inverse association between dietary vitamin C intake and NAFLD was observed in the energy-adjusted and the multivariable model. The multivariable adjusted ORs (95%CI) for NAFLD were 0.69 (95%CI: 0.54-0.89), 0.93 (95%CI: 0.72-1.20), and 0.71 (95%CI: 0.53-0.95) in the second, third and fourth dietary vitamin C intake quartiles, respectively, compared with the lowest (first) quartile. The relative odds of NAFLD was decreased by 0.71 times in the fourth quartile of dietary vitamin C intake compared with the lowest quartile. After stratifying data by sex or the status of obesity, the inverse association remained valid in the male population or non-obesity population, but not in the female population or obesity population. There might be a moderate inverse association between dietary vitamin C intake and NAFLD in middle-aged and older adults, especially for the male population and non-obesity population.

  5. Advanced Glycation End Product (AGE) Accumulation in the Skin is Associated with Depression: The Maastricht Study.

    PubMed

    van Dooren, Fleur E P; Pouwer, Frans; Schalkwijk, Casper G; Sep, Simone J S; Stehouwer, Coen D A; Henry, Ronald M A; Dagnelie, Pieter C; Schaper, Nicolaas C; van der Kallen, Carla J H; Koster, Annemarie; Denollet, Johan; Verhey, Frans R J; Schram, Miranda T

    2017-01-01

    Depression is a highly prevalent disease with a high morbidity and mortality risk. Its pathophysiology is not entirely clear. However, type 2 diabetes is an important risk factor for depression. One mechanism that may explain this association may include the formation of advanced glycation end products (AGEs). We therefore investigated the association of AGEs with depressive symptoms and depressive disorder. In addition, we examined whether the potential association was present for somatic and/or cognitive symptoms of depression. Cross-sectional data were used from the Maastricht Study (N = 862, mean age 59.8 ± 8.5 years, 55% men). AGE accumulation was measured with skin autofluorescence (SAF) by use of the AGE Reader. Plasma levels of protein-bound pentosidine were measured with high-performance liquid chromatography and fluorescence detection. Nε-(carboxymethyl)lysine (CML) and Nε-(carboxyethyl)lysine (CEL) were measured with ultraperformance liquid chromatography and tandem mass spectrometry. Depressive symptoms and depressive disorder were assessed by the nine-item Patient Health Questionnaire and the Mini-International Neuropsychiatric Interview. Higher SAF was associated with depressive symptoms (β = 0.42, 95% CI 0.12-0.73, P = .007) and depressive disorder (OR = 1.42, 95% CI 1.04-1.95, P = .028) after adjustment for age, sex, type 2 diabetes, smoking, BMI, and kidney function. Plasma pentosidine, CML, and CEL were not independently associated with depressive symptoms and depressive disorder. This study shows that AGE accumulation in the skin is independently associated with higher levels of depressive symptoms and depressive disorder. This association is present for both somatic and cognitive symptoms of depression. This might suggest that AGEs are involved in the development of depression. © 2016 Wiley Periodicals, Inc.

  6. Gastroesophageal reflux disease vs. Panayiotopoulos syndrome: an underestimated misdiagnosis in pediatric age?

    PubMed

    Parisi, Pasquale; Pacchiarotti, Claudia; Ferretti, Alessandro; Bianchi, Simona; Paolino, Maria Chiara; Barreto, Mario; Principessa, Luigi; Villa, Maria Pia

    2014-12-01

    Autonomic signs and symptoms could be of epileptic or nonepileptic origin, and the differential diagnosis depends on a number of factors which include the nature of the autonomic manifestations themselves, the occurrence of other nonictal autonomic signs/symptoms, and the age of the patient. Here, we describe twelve children (aged from ten months to six years at the onset of the symptoms) with Panayiotopoulos syndrome misdiagnosed as gastroesophageal reflux disease. Gastroesophageal reflux disease and Panayiotopoulos syndrome may represent an underestimated diagnostic challenge. When the signs/symptoms occur mainly during sleep, a sleep EEG or, if available, a polysomnographic evaluation may be the most useful investigation to make a differential diagnosis between autonomic epileptic and nonepileptic disorders. An early detection can reduce both the high morbidity related to mismanagement and the high costs to the national health service related to the incorrect diagnostic and therapeutic approaches. To decide if antiseizure therapy is required, one should take into account both the frequency and severity of epileptic seizures and the tendency to have potentially lethal autonomic cardiorespiratory involvement. In conclusion, we would emphasize the need to make a differential diagnosis between gastroesophageal reflux disease and Panayiotopoulos syndrome in patients with "an unusual" late-onset picture of GERD and acid therapy-resistant gastroesophageal reflux, especially if associated with other autonomic symptoms and signs. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Factors associated with falling in early, treated Parkinson's disease: The NET-PD LS1 cohort.

    PubMed

    Chou, Kelvin L; Elm, Jordan J; Wielinski, Catherine L; Simon, David K; Aminoff, Michael J; Christine, Chadwick W; Liang, Grace S; Hauser, Robert A; Sudarsky, Lewis; Umeh, Chizoba C; Voss, Tiffini; Juncos, Jorge; Fang, John Y; Boyd, James T; Bodis-Wollner, Ivan; Mari, Zoltan; Morgan, John C; Wills, Anne-Marie; Lee, Stephen L; Parashos, Sotirios A

    2017-06-15

    Recognizing the factors associated with falling in Parkinson's disease (PD) would improve identification of at-risk individuals. To examine frequency of falling and baseline characteristics associated with falling in PD using the National Institute of Neurological Disorders and Stroke (NINDS) Exploratory Trials in PD Long-term Study-1 (NET-PD LS-1) dataset. The LS-1 database included 1741 early treated PD subjects (median 4year follow-up). Baseline characteristics were tested for a univariate association with post-baseline falling during the trial. Significant variables were included in a multivariable logistic regression model. A separate analysis using a negative binomial model investigated baseline factors on fall rate. 728 subjects (42%) fell during the trial, including at baseline. A baseline history of falls was the factor most associated with post-baseline falling. Men had lower odds of post-baseline falling compared to women, but for men, the probability of a post-baseline fall increased with age such that after age 70, men and women had similar odds of falling. Other baseline factors associated with a post-baseline fall and increased fall rate included the Unified PD Rating Scale (UPDRS) Activities of Daily Living (ADL) score, total functional capacity (TFC), baseline ambulatory capacity score and dopamine agonist monotherapy. Falls are common in early treated PD. The biggest risk factor for falls in PD remains a history of falling. Measures of functional ability (UPDRS ADL, TFC) and ambulatory capacity are novel clinical risk factors needing further study. A significant age by sex interaction may help to explain why age has been an inconsistent risk factor for falls in PD. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Free radicals, antioxidants and eye diseases: evidence from epidemiological studies on cataract and age-related macular degeneration.

    PubMed

    Fletcher, A E

    2010-01-01

    Cataract and age-related macular degeneration (AMD) are the major causes of vision impairment and blindness worldwide. Both conditions are strongly age related with earlier signs (usually asymptomatic) occurring in middle age and becoming severer and more prevalent with increasing age. The aetiology of these conditions is thought to fit with the 'free radical theory' of ageing which postulates that ageing and age-related diseases result from the accumulation of cellular damage from reactive oxygen species (ROS). Mitochondrial energy production is a major source of endogenous ROS. External sources of ROS include environmental sources especially solar radiation, biomass fuels and tobacco smoking. There is strong evidence from epidemiological studies that smoking is a risk factor for both cataract and AMD. There is moderate evidence for an association with sunlight and cataract but weak evidence for sunlight and AMD. The few studies that have investigated this suggest an adverse effect of biomass fuels on cataract risk. The antioxidant defence system of the lens and retina include antioxidant vitamins C and E and the carotenoids lutein and zinc, and there is mixed evidence on their associations with cataract and AMD from epidemiological studies. Most epidemiological studies have been conducted in well-nourished western populations but evidence is now emerging from other populations with different dietary patterns and antioxidant levels. Copyright 2010 S. Karger AG, Basel.

  9. Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease in non diabetics

    USDA-ARS?s Scientific Manuscript database

    Epidemiologic studies indicate that the risks for major age-related debilities including coronary heart disease, diabetes, and age-related macular degeneration (AMD) are diminished in people who consume lower glycemic index (GI) diets, but lack of a unifying physiobiochemical mechanism that explains...

  10. Association of Age Related Macular Degeneration and Age Related Hearing Impairment

    PubMed Central

    Ghasemi, Hassan; Pourakbari, Malihe Shahidi; Entezari, Morteza; Yarmohammadi, Mohammad Ebrahim

    2016-01-01

    Purpose: To evaluate the association between age-related macular degeneration (ARMD) and sensory neural hearing impairment (SHI). Methods: In this case-control study, hearing status of 46 consecutive patients with ARMD were compared with 46 age-matched cases without clinical ARMD as a control group. In all patients, retinal involvements were confirmed by clinical examination, fluorescein angiography (FA) and optical coherence tomography (OCT). All participants were examined with an otoscope and underwent audiological tests including pure tone audiometry (PTA), speech reception threshold (SRT), speech discrimination score (SDS), tympanometry, reflex tests and auditory brainstem response (ABR). Results: A significant (P = 0.009) association was present between ARMD, especially with exudative and choroidal neovascularization (CNV) components, and age-related hearing impairment primarily involving high frequencies. Patients had higher SRT and lower SDS against anticipated presbycusis than control subjects. Similar results were detected in exudative, CNV and scar patterns supporting an association between late ARMD with SRT and SDS abnormalities. ABR showed significantly prolonged wave I and IV latency times in ARMD (P = 0.034 and 0.022, respectively). Average latency periods for wave I in geographic atrophy (GA) and CNV, and that for wave IV in drusen patterns of ARMD were significantly higher than controls (P = 0.030, 0.007 and 0.050, respectively). Conclusion: The association between ARMD and age-related SHI may be attributed to common anatomical components such as melanin in these two sensory organs. PMID:27195086

  11. Diffuse Lung Disease in Biopsied Children 2 to 18 Years of Age. Application of the chILD Classification Scheme.

    PubMed

    Fan, Leland L; Dishop, Megan K; Galambos, Csaba; Askin, Frederic B; White, Frances V; Langston, Claire; Liptzin, Deborah R; Kroehl, Miranda E; Deutsch, Gail H; Young, Lisa R; Kurland, Geoffrey; Hagood, James; Dell, Sharon; Trapnell, Bruce C; Deterding, Robin R

    2015-10-01

    Children's Interstitial and Diffuse Lung Disease (chILD) is a heterogeneous group of disorders that is challenging to categorize. In previous study, a classification scheme was successfully applied to children 0 to 2 years of age who underwent lung biopsies for chILD. This classification scheme has not been evaluated in children 2 to 18 years of age. This multicenter interdisciplinary study sought to describe the spectrum of biopsy-proven chILD in North America and to apply a previously reported classification scheme in children 2 to 18 years of age. Mortality and risk factors for mortality were also assessed. Patients 2 to 18 years of age who underwent lung biopsies for diffuse lung disease from 12 North American institutions were included. Demographic and clinical data were collected and described. The lung biopsies were reviewed by pediatric lung pathologists with expertise in diffuse lung disease and were classified by the chILD classification scheme. Logistic regression was used to determine risk factors for mortality. A total of 191 cases were included in the final analysis. Number of biopsies varied by center (5-49 biopsies; mean, 15.8) and by age (2-18 yr; mean, 10.6 yr). The most common classification category in this cohort was Disorders of the Immunocompromised Host (40.8%), and the least common was Disorders of Infancy (4.7%). Immunocompromised patients suffered the highest mortality (52.8%). Additional associations with mortality included mechanical ventilation, worse clinical status at time of biopsy, tachypnea, hemoptysis, and crackles. Pulmonary hypertension was found to be a risk factor for mortality but only in the immunocompetent patients. In patients 2 to 18 years of age who underwent lung biopsies for diffuse lung disease, there were far fewer diagnoses prevalent in infancy and more overlap with adult diagnoses. Immunocompromised patients with diffuse lung disease who underwent lung biopsies had less than 50% survival at time of last follow-up.

  12. Association of homocysteine level and vascular burden and cognitive function in middle-aged and older adults with chronic kidney disease.

    PubMed

    Yeh, Yi-Chun; Huang, Mei-Feng; Hwang, Shang-Jyh; Tsai, Jer-Chia; Liu, Tai-Ling; Hsiao, Shih-Ming; Yang, Yi-Hsin; Kuo, Mei-Chuan; Chen, Cheng-Sheng

    2016-07-01

    Patients with chronic kidney disease (CKD) have been found to have cognitive impairment. However, the core features and clinical correlates of cognitive impairment are still unclear. Elevated homocysteine levels are present in CKD, and this is a risk factor for cognitive impairment and vascular diseases in the general population. Thus, this study investigated the core domains of cognitive impairment and investigated the associations of homocysteine level and vascular burden with cognitive function in patients with CKD. Patients with CKD aged ≥ 50 years and age- and sex-matched normal comparisons were enrolled. The total fasting serum homocysteine level was measured. Vascular burden was assessed using the Framingham Cardiovascular Risk Scale. Cognitive function was evaluated using comprehensive neuropsychological tests. A total of 230 patients with CKD and 92 comparisons completed the study. Memory impairment and executive dysfunction were identified as core features of cognitive impairment in the CKD patients. Among the patients with CKD, higher serum homocysteine levels (β = -0.17, p = 0.035) and higher Framingham Cardiovascular Risk Scale scores (β = -0.18, p = 0.013) were correlated with poor executive function independently. However, an association with memory function was not noted. Our results showed that an elevated homocysteine level and an increased vascular burden were independently associated with executive function, but not memory, in CKD patients. This findings suggested the co-existence of vascular and non-vascular hypotheses regarding executive dysfunction in CKD patients. Meanwhile, other risk factors related to CKD itself should be investigated in the future. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  13. Association of lung function genes with chronic obstructive pulmonary disease.

    PubMed

    Kim, Woo Jin; Lim, Myoung Nam; Hong, Yoonki; Silverman, Edwin K; Lee, Ji-Hyun; Jung, Bock Hyun; Ra, Seung Won; Choi, Hye Sook; Jung, Young Ju; Park, Yong Bum; Park, Myung Jae; Lee, Sei Won; Lee, Jae Seung; Oh, Yeon-Mok; Lee, Sang Do

    2014-08-01

    Spirometric measurements of pulmonary function are important in diagnosing and determining the severity of chronic obstructive pulmonary disease (COPD). We performed this study to determine whether candidate genes identified in genome-wide association studies of spirometric measurements were associated with COPD and if they interacted with smoking intensity. The current analysis included 1,000 COPD subjects and 1,000 controls recruited from 24 hospital-based pulmonary clinics. Thirteen SNPs, chosen based on genome-wide association studies of spirometric measurements in the Korean population cohorts, were genotyped. Genetic association tests were performed, adjusting for age, sex, and smoking intensity, using models including a SNP-by-smoking interaction term. PID1 and FAM13A were significantly associated with COPD susceptibility. There were also significant interactions between SNPs in ACN9 and FAM13A and smoking pack-years, and an association of ACN9 with COPD in the lowest smoking tertile. The risk allele of FAM13A was associated with increased expression of FAM13A in the lung. We have validated associations of FAM13A and PID1 with COPD. ACN9 showed significant interaction with smoking and is a potential candidate gene for COPD. Significant associations of genetic variants of FAM13A with gene expression levels suggest that the associated loci may act as genetic regulatory elements for FAM13A gene expression.

  14. Level of education associated with ophthalmic diseases. The Beijing Eye Study.

    PubMed

    Xu, Liang; Wang, Ya Xing; Jonas, Jost B

    2010-01-01

    To determine associations between educational level and ophthalmic diseases in Chinese. The population-based Beijing Eye Study, performed in 2006, enrolled 3,251 participants (age: 45+ years) out of 4,439 subjects invited to participate (response rate: 73.2%). The participants underwent an interview including questions concerning their educational level, and a detailed ophthalmic examination. Data on the level of education were available for 3,221 (99.1%) subjects, with 1,484 (46.1%) subjects living in the rural region. The mean age was 60.4 +/- 10.1 years (range: 45-89 years). In a multivariate analysis, a higher level of education was significantly associated with myopic refractive error, higher best-corrected visual acuity, lower degree of nuclear cataract, and lower prevalence of angle-closure glaucoma, and with the systemic parameters of lower age, male gender, urban region, taller body height, and lower body mass index. It was not significantly associated with intraocular pressure, amount of subcapsular cataract and cortical cataract, cataract surgery, and the prevalences of diabetes mellitus, retinal vein occlusions, chronic open-angle glaucoma, and age-related macular degeneration, and with the systemic parameters of fasting serum concentrations of glucose, high-density lipoproteins, low-density lipoproteins, cholesterol and triglycerides, systolic and diastolic blood pressure. In the Greater Beijing area, a higher level of education was associated with myopic refractive error, higher best-corrected visual acuity, and lower prevalence of nuclear cataract and angle-closure glaucoma, after adjusting for the systemic parameters of younger age, male gender, urban region, taller body height, lower body mass index less smoking and less alcohol consumption. Educational level was not significantly associated with intraocular pressure, cortical cataract, blood pressure, and frequencies of age-related macular degeneration, retinal vein occlusions and chronic open

  15. Altered prefrontal function with aging: insights into age-associated performance decline.

    PubMed

    Solbakk, Anne-Kristin; Fuhrmann Alpert, Galit; Furst, Ansgar J; Hale, Laura A; Oga, Tatsuhide; Chetty, Sundari; Pickard, Natasha; Knight, Robert T

    2008-09-26

    We examined the effects of aging on visuo-spatial attention. Participants performed a bi-field visual selective attention task consisting of infrequent target and task-irrelevant novel stimuli randomly embedded among repeated standards in either attended or unattended visual fields. Blood oxygenation level dependent (BOLD) responses to the different classes of stimuli were measured using functional magnetic resonance imaging. The older group had slower reaction times to targets, and committed more false alarms but had comparable detection accuracy to young controls. Attended target and novel stimuli activated comparable widely distributed attention networks, including anterior and posterior association cortex, in both groups. The older group had reduced spatial extent of activation in several regions, including prefrontal, basal ganglia, and visual processing areas. In particular, the anterior cingulate and superior frontal gyrus showed more restricted activation in older compared with young adults across all attentional conditions and stimulus categories. The spatial extent of activations correlated with task performance in both age groups, but the regional pattern of association between hemodynamic responses and behavior differed between the groups. Whereas the young subjects relied on posterior regions, the older subjects engaged frontal areas. The results indicate that aging alters the functioning of neural networks subserving visual attention, and that these changes are related to cognitive performance.

  16. Phenotypic, genetic, and single nucleotide polymorphism marker associations between calf diseases and subsequent performance and disease occurrences of first-lactation German Holstein cows.

    PubMed

    Mahmoud, M; Yin, T; Brügemann, K; König, S

    2017-03-01

    A total of 31,396 females born from 2010 to 2013 in 43 large-scale Holstein-Friesian herds were phenotyped for calf and cow disease traits using a veterinarian diagnosis key. Calf diseases were general disease status (cGDS), calf diarrhea (cDIA), and calf respiratory disease (cRD) recorded from birth to 2 mo of age. Incidences were 0.48 for cGDS, 0.28 for cRD, and 0.21 for cDIA. Cow disease trait recording focused on the early period directly after calving in first parity, including the interval from 10 d before calving to 200 d in lactation. For cows, at least one entry for the respective disease implied a score = 1 (sick); otherwise, score = 0 (healthy). Corresponding cow diseases were first-lactation general disease status (flGDS), first-lactation diarrhea (flDIA), and first-lactation respiratory disease (flRD). Additional cow disease categories included mastitis (flMAST), claw disorders (flCLAW), female fertility disorders (flFF), and metabolic disorders (flMET). A further cow trait category considered first-lactation test-day production traits from official test-days 1 and 2 after calving. The genotype data set included 41,256 single nucleotide polymorphisms (SNP) from 9,388 females with phenotypes. Linear and generalized linear mixed models with a logit link-function were applied to Gaussian and categorical cow traits, respectively, considering the calf disease as a fixed effect. Most of the calf diseases were not significantly associated with the occurrence of any cow disease. By trend, increasing risks for the occurrence of cow diseases were observed for healthy calves, indicating mechanisms of disease resistance with aging. Also by trend, occurrence of calf diseases was associated with decreasing milk, protein, and fat yields. Univariate linear and threshold animal models were used to estimate heritabilities and breeding values (EBV) for all calf and cow traits. Heritabilities for cGDS and cRD were 0.06 and 0.07 for cDIA. Genetic correlations among all

  17. Rare case of Takayasu's arteritis associated with Crohn's disease.

    PubMed

    Kusunoki, Ryusaku; Ishihara, Shunji; Sato, Mariko; Sumita, Yoshiko; Mishima, Yoshiyuki; Okada, Mayumi; Tada, Yasumasa; Oka, Akihiko; Fukuba, Nobuhiko; Oshima, Naoki; Moriyama, Ichiro; Yuki, Takafumi; Sato, Shuichi; Amano, Yuji; Murakawa, Yohko; Kinoshita, Yoshikazu

    2011-01-01

    Takayasu's arteritis (TA) and Crohn's disease (CD) are chronic inflammatory diseases of uncertain etiology. Although co-existence of these rare diseases is estimated to occur in 1 in 10 billion individuals, a theoretically unexpected association has been reported in several patients and it is suggested that those associations may have been more than an unusual coincidence. Herein, we report a case of TA associated with clinically inactive CD. A Japanese woman was diagnosed with colonic CD at the age of 15, developed aortic valve regurgitation at 19, and then presented with general fatigue, low grade fever, and painful sensations in her left arm at 25. She was diagnosed with TA based on computed tomography scanning and magnetic resonance angiography findings, and treatments with prednisolone and cyclosporine were started. Thereafter, valve replacement and right coronary artery bypass graft surgery were performed. The possible pathophysiological mechanism responsible for concurrent existence of TA and CD may be associated with immune disorders. Early diagnosis of vascular lesions for patients with inflammatory bowel disease is highly encouraged.

  18. Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study

    PubMed Central

    Cleynen, Isabelle; Boucher, Gabrielle; Jostins, Luke; Schumm, L Philip; Zeissig, Sebastian; Ahmad, Tariq; Andersen, Vibeke; Andrews, Jane M; Annese, Vito; Brand, Stephan; Brant, Steven R; Cho, Judy H; Daly, Mark J; Dubinsky, Marla; Duerr, Richard H; Ferguson, Lynnette R; Franke, Andre; Gearry, Richard B; Goyette, Philippe; Hakonarson, Hakon; Halfvarson, Jonas; Hov, Johannes R; Huang, Hailang; Kennedy, Nicholas A; Kupcinskas, Limas; Lawrance, Ian C; Lee, James C; Satsangi, Jack; Schreiber, Stephan; Théâtre, Emilie; van der Meulen-de Jong, Andrea E; Weersma, Rinse K; Wilson, David C; Parkes, Miles; Vermeire, Severine; Rioux, John D; Mansfield, John; Silverberg, Mark S; Radford-Smith, Graham; McGovern, Dermot P B; Barrett, Jeffrey C; Lees, Charlie W

    2016-01-01

    Summary Background Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. Methods This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34 819 patients (19 713 with Crohn's disease, 14 683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype–phenotype associations across 156 154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile. Findings After quality control, the primary analysis included 29 838 patients (16 902 with Crohn's disease, 12 597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for

  19. Systematic mapping review about costs and economic evaluations of skin conditions and diseases in the aged.

    PubMed

    Lichterfeld-Kottner, Andrea; Hahnel, Elisabeth; Blume-Peytavi, Ulrike; Kottner, Jan

    2017-02-01

    Skin conditions and dermatological diseases associated with advanced age (e.g. fungal infection, dry skin and itch) receive increasingly attention in clinical practice and research. Cost and economic evaluations are important sources to inform priority setting and ressource allocation decisions in healthcare. The economics of skin conditions in aged populations has not been systematically reviewed so far. The aim of this mapping review was to summarize the economic evidence of selected skin conditions in the aged (65 + years). A mapping literature review and evidence summary was conducted. Searches were conducted in data bases Medline and Embase via OVID. Cinahl was searched using EBSCO. References lists of potential eligible studies, reviews, guidelines or other sources were screened for additional literature. For evaluation of methodological quality of full economic analyses the Consensus on Health Economic Criteria (CHEC) checklist was used. Database searches resulted in 1388 records. A total of 270 articles were read in full-text. Thirty-five publications were finally included in the data analysis reporting 38 economic analyses. Ten cost of illness analyses and 26 cost-effectiveness analyses reporting about pressure ulcers, skin tears, pressure ulcers, incontinence associated dermatitis and intertrigo/contact dermatitis/candidiasis treatment and prevention and onychomycosis testing were identified. Limited evidence indicated that low air loss beds were more cost effective than standard beds for prevention of pressure ulcers. Standardized skin care regimens seem to lower the incidence of pressure ulcers, skin tears and IAD but a cost saving effect was not always observed. Findings of this mapping review indicate that there is a paucity of high quality evidence regarding the economic impact of age-associated skin conditions and diseases. Substantial heterogeneity in terms of study design, evaluation perspective, time period, and way of cost estimation was

  20. Blue Journal Conference. Aging and Susceptibility to Lung Disease

    PubMed Central

    Thannickal, Victor J.; Murthy, Mahadev; Balch, William E.; Chandel, Navdeep S.; Meiners, Silke; Eickelberg, Oliver; Selman, Moisés; Pardo, Annie; White, Eric S.; Levy, Bruce D.; Busse, Paula J.; Tuder, Rubin M.; Antony, Veena B.; Sznajder, Jacob I.

    2015-01-01

    The aging of the population in the United States and throughout the developed world has increased morbidity and mortality attributable to lung disease, while the morbidity and mortality from other prevalent diseases has declined or remained stable. Recognizing the importance of aging in the development of lung disease, the American Thoracic Society (ATS) highlighted this topic as a core theme for the 2014 annual meeting. The relationship between aging and lung disease was discussed in several oral symposiums and poster sessions at the annual ATS meeting. In this article, we used the input gathered at the conference to develop a broad framework and perspective to stimulate basic, clinical, and translational research to understand how the aging process contributes to the onset and/or progression of lung diseases. A consistent theme that emerged from the conference was the need to apply novel, systems-based approaches to integrate a growing body of genomic, epigenomic, transcriptomic, and proteomic data and elucidate the relationship between biologic hallmarks of aging, altered lung function, and increased susceptibility to lung diseases in the older population. The challenge remains to causally link the molecular and cellular changes of aging with age-related changes in lung physiology and disease susceptibility. The purpose of this review is to stimulate further research to identify new strategies to prevent or treat age-related lung disease. PMID:25590812

  1. Cellular aging and restorative processes: subjective sleep quality and duration moderate the association between age and telomere length in a sample of middle-aged and older adults.

    PubMed

    Cribbet, Matthew R; Carlisle, McKenzie; Cawthon, Richard M; Uchino, Bert N; Williams, Paula G; Smith, Timothy W; Gunn, Heather E; Light, Kathleen C

    2014-01-01

    To examine whether subjective sleep quality and sleep duration moderate the association between age and telomere length (TL). Participants completed a demographic and sleep quality questionnaire, followed by a blood draw. Social Neuroscience Laboratory. One hundred fifty-four middle-aged to older adults (age 45-77 y) participated. Participants were excluded if they were on immunosuppressive treatment and/or had a disease with a clear immunologic (e.g., cancer) component. N/A. Subjective sleep quality and sleep duration were assessed using the Pittsburgh Sleep Quality Index (PSQI) and TL was determined using peripheral blood mononuclear cells (PBMCs). There was a significant first-order negative association between age and TL. Age was also negatively associated with the self-reported sleep quality item and sleep duration component of the PSQI. A significant age × self-reported sleep quality interaction revealed that age was more strongly related to TL among poor sleepers, and that good sleep quality attenuated the association between age and TL. Moreover, adequate subjective sleep duration among older adults (i.e. greater than 7 h per night) was associated with TL comparable to that in middle-aged adults, whereas sleep duration was unrelated to TL for the middle-aged adults in our study. The current study provides evidence for an association between sleep quality, sleep duration, and cellular aging. Among older adults, better subjective sleep quality was associated with the extent of cellular aging, suggesting that sleep duration and sleep quality may be added to a growing list of modifiable behaviors associated with the adverse effects of aging.

  2. Tau and β-Amyloid Are Associated with Medial Temporal Lobe Structure, Function, and Memory Encoding in Normal Aging

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Marks, Shawn M.; Lockhart, Samuel N.; Baker, Suzanne L.

    Normal aging is associated with a decline in episodic memory and also with aggregation of the β-amyloid (Aβ) and tau proteins and atrophy of medial temporal lobe (MTL) structures crucial to memory formation. Although some evidence suggests that Aβ is associated with aberrant neural activity, the relationships among these two aggregated proteins, neural function, and brain structure are poorly understood. Using in vivo human Aβ and tau imaging, we demonstrate that increased Aβ and tau are both associated with aberrant fMRI activity in the MTL during memory encoding in cognitively normal older adults. This pathological neural activity was in turnmore » associated with worse memory performance and atrophy within the MTL. A mediation analysis revealed that the relationship with regional atrophy was explained by MTL tau. These findings broaden the concept of cognitive aging to include evidence of Alzheimer’s disease-related protein aggregation as an underlying mechanism of age-related memory impairment.« less

  3. Gene-based association study of genes linked to hippocampal sclerosis of aging neuropathology: GRN, TMEM106B, ABCC9, and KCNMB2

    PubMed Central

    Katsumata, Yuriko; Nelson, Peter T.; Ellingson, Sally R.; Fardo, David W.

    2017-01-01

    Hippocampal sclerosis of aging (HS-Aging) is a common neurodegenerative condition associated with dementia. To learn more about genetic risk of HS-Aging pathology, we tested gene-based associations of the GRN, TMEM106B, ABCC9, and KCNMB2 genes, which were reported to be associated with HS-Aging pathology in previous studies. Genetic data were obtained from the Alzheimer’s Disease Genetics Consortium (ADGC), linked to autopsy-derived neuropathological outcomes from the National Alzheimer’s Coordinating Center (NACC). Of the 3,251 subjects included in the study, 271 (8.3%) were identified as an HS-Aging case. The significant gene-based association between the ABCC9 gene and HS-Aging appeared to be driven by a region in which a significant haplotype-based association was found. We tested this haplotype as an expression Quantitative Trait Locus (eQTL) using two different public-access brain gene expression databases. The HS-Aging pathology protective ABCC9 haplotype was associated with decreased ABCC9 expression, indicating a possible toxic gain of function. PMID:28131462

  4. An Update on Inflamm-Aging: Mechanisms, Prevention, and Treatment

    PubMed Central

    Wu, Junzhen

    2016-01-01

    Inflamm-aging is a challenging and promising new branch of aging-related research fields that includes areas such as immunosenescence. Increasing evidence indicates that inflamm-aging is intensively associated with many aging diseases, such as Alzheimer's disease, atherosclerosis, heart disease, type II diabetes, and cancer. Mounting studies have focused on the role of inflamm-aging in disease progression and many advances have been made in the last decade. However, the underlying mechanisms by which inflamm-aging affects pathological changes and disease development are still unclear. Here, we review studies of inflamm-aging that explore the concept, pathological features, mechanisms, intervention, and the therapeutic strategies of inflamm-aging in disease progression. PMID:27493973

  5. Associations between polymyalgia rheumatica and giant cell arteritis and 12 cardiovascular diseases.

    PubMed

    Pujades-Rodriguez, Mar; Duyx, Bram; Thomas, Sara L; Stogiannis, Dimitris; Smeeth, Liam; Hemingway, Harry

    2016-03-01

    Evidence of the association of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) with the full range of cardiovascular diseases (CVDs) is limited. We examined their relationship with the first clinical presentation of the 12 most common CVDs in an unselected population-based cohort of men and women. We analysed CArdiovascular disease research using LInked Bespoke studies and Electronic health Records (CALIBER) data, which links primary care and hospital and mortality data in England, from 1997 to 2010. We assembled a cohort of men and women initially free from CVD at baseline and included all patients with PMR and/or GCA (PMR/GCA) diagnosis, matched by age, sex and general practice with up to 10 individuals without PMR/GCA. Random effects Poisson regression analysis was used to study the association between PMR/GCA and the initial presentation of 12 types of CVDs. The analysis included 9776 patients with PMR only, 1164 with GCA only, 627 with PMR and GCA and 105 504 without either condition. During a median of 3.14 years of follow-up 2787 (24.1%) individuals with PMR/GCA and 21 559 (20.4%) without PMR/GCA developed CVDs. Patients with PMR/GCA had lower rates of unheralded coronary death (3.18 vs 3.61/1000 person-years; adjusted incidence ratio 0.79, 95% CI 0.66 to 0.95), transient ischaemic attack (5.11 vs 5.61/1000 person-years; 0.67, 95% CI 0.54 to 0.84) and coronary and death composite (24.17 vs 25.80/1000 person-years; 0.90, 95% CI 0.82 to 0.98). No associations were observed for other CVDs or cerebrovascular diseases, and in patients with only PMR or GCA. No evidence of interaction by age or sex was found. Estimates decreased with longer PMR/GCA duration and findings were robust to multiple sensitivity analyses. In this large contemporary population-based cohort the presence of PMR and/or GCA was not associated with an increased risk of CVDs or cerebrovascular diseases regardless of PMR/GCA duration. Published by the BMJ Publishing Group

  6. Age- and Hypertension-Associated Protein Aggregates in Mouse Heart Have Similar Proteomic Profiles.

    PubMed

    Ayyadevara, Srinivas; Mercanti, Federico; Wang, Xianwei; Mackintosh, Samuel G; Tackett, Alan J; Prayaga, Sastry V S; Romeo, Francesco; Shmookler Reis, Robert J; Mehta, Jawahar L

    2016-05-01

    Neurodegenerative diseases are largely defined by protein aggregates in affected tissues. Aggregates contain some shared components as well as proteins thought to be specific for each disease. Aggregation has not previously been reported in the normal, aging heart or the hypertensive heart. Detergent-insoluble protein aggregates were isolated from mouse heart and characterized on 2-dimensional gels. Their levels increased markedly and significantly with aging and after sustained angiotensin II-induced hypertension. Of the aggregate components identified by high-resolution proteomics, half changed in abundance with age (392/787) or with sustained hypertension (459/824), whereas 30% (273/901) changed concordantly in both, each P<0.05. One fifth of these proteins were previously associated with age-progressive neurodegenerative or cardiovascular diseases, or both (eg, ApoE, ApoJ, ApoAIV, clusterin, complement C3, and others involved in stress-response and protein-homeostasis pathways). Because fibrosis is a characteristic of both aged and hypertensive hearts, we posited that aging of fibroblasts may contribute to the aggregates observed in cardiac tissue. Indeed, as cardiac myofibroblasts "senesced" (approached their replicative limit) in vitro, they accrued aggregates with many of the same constituent proteins observed in vivo during natural aging or sustained hypertension. In summary, we have shown for the first time that compact (detergent-insoluble) protein aggregates accumulate during natural aging, chronic hypertension, and in vitro myofibroblast senescence, sharing many common proteins. Thus, aggregates that arise from disparate causes (aging, hypertension, and replicative senescence) may have common underlying mechanisms of accrual. © 2016 American Heart Association, Inc.

  7. The Implicitome: A Resource for Rationalizing Gene-Disease Associations

    PubMed Central

    van der Horst, Eelke; Kaliyaperumal, Rajaram; Mina, Eleni; Tatum, Zuotian; Laros, Jeroen F. J.; van Mulligen, Erik M.; Schuemie, Martijn; Aten, Emmelien; Li, Tong Shu; Bruskiewich, Richard; Good, Benjamin M.; Su, Andrew I.; Kors, Jan A.; den Dunnen, Johan; van Ommen, Gert-Jan B.; Roos, Marco; ‘t Hoen, Peter A.C.; Mons, Barend; Schultes, Erik A.

    2016-01-01

    High-throughput experimental methods such as medical sequencing and genome-wide association studies (GWAS) identify increasingly large numbers of potential relations between genetic variants and diseases. Both biological complexity (millions of potential gene-disease associations) and the accelerating rate of data production necessitate computational approaches to prioritize and rationalize potential gene-disease relations. Here, we use concept profile technology to expose from the biomedical literature both explicitly stated gene-disease relations (the explicitome) and a much larger set of implied gene-disease associations (the implicitome). Implicit relations are largely unknown to, or are even unintended by the original authors, but they vastly extend the reach of existing biomedical knowledge for identification and interpretation of gene-disease associations. The implicitome can be used in conjunction with experimental data resources to rationalize both known and novel associations. We demonstrate the usefulness of the implicitome by rationalizing known and novel gene-disease associations, including those from GWAS. To facilitate the re-use of implicit gene-disease associations, we publish our data in compliance with FAIR Data Publishing recommendations [https://www.force11.org/group/fairgroup] using nanopublications. An online tool (http://knowledge.bio) is available to explore established and potential gene-disease associations in the context of other biomedical relations. PMID:26919047

  8. Association between history of psychosis and cardiovascular disease in bipolar disorder.

    PubMed

    Prieto, Miguel L; McElroy, Susan L; Hayes, Sharonne N; Sutor, Bruce; Kung, Simon; Bobo, William V; Fuentes, Manuel E; Cuellar-Barboza, Alfredo B; Crow, Scott; Ösby, Urban; Chauhan, Mohit; Westman, Jeanette; Geske, Jennifer R; Colby, Colin L; Ryu, Euijung; Biernacka, Joanna M; Frye, Mark A

    2015-08-01

    To determine whether clinical features of bipolar disorder, such as history of psychosis, and cardiovascular disease (CVD) risk factors contribute to a higher risk of CVD among patients with bipolar disorder. This cross-sectional study included a sample of 988 patients with bipolar I or bipolar II disorder or schizoaffective bipolar type confirmed by the Structured Clinical Interview for DSM-IV-TR disorders (SCID). Medical comorbidity burden was quantified utilizing the Cumulative Illness Severity Rating Scale (CIRS). This 13-item organ-based scale includes cardiac disease severity quantification. Confirmed by medical record review, patients who scored 1 (current mild or past significant problem) or higher in the cardiac item were compared by logistic regression to patients who scored 0 (no impairment), adjusting for CVD risk factors that were selected using a backwards stepwise approach or were obtained from the literature. In a multivariate model, age [odds ratio (OR) = 3.03, 95% confidence interval (CI): 1.66-5.54, p < 0.0001], hypertension (OR = 2.43, 95% CI: 1.69-3.55, p < 0.0001), and history of psychosis (OR = 1.48, 95% CI: 1.03-2.13, p = 0.03) were associated with CVD. When CVD risk factors from the literature were added to the analysis, age (OR = 3.19, 95% CI: 1.67-6.10, p = 0.0005) and hypertension (OR = 2.46, 95% CI: 1.61-3.76, p < 0.01) remained significant, with psychosis being at the trend level (OR = 1.43, 95% CI: 0.96-2.13, p = 0.08). The phenotype of psychotic bipolar disorder may reflect higher illness severity with associated cardiac comorbidity. Further studies are encouraged to clarify the effect of the disease burden (i.e., depression), lifestyle, and treatment interventions (i.e., atypical antipsychotics) on this risk association. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Factors associated with hepatitis C infection among patients with skin diseases.

    PubMed

    Luksamijarulkul, Pipat; Chantavoraluk, Somjai

    2013-12-01

    The present study attempted to assess factors associated with positive anti-HCV among patients with skin diseases. A retrospective analysis of 3,496 subjects' history profiles from the HCV antibody surveillance projects performed from 2000 to 2007. Only 150 subject profiles with skin diseases were included in the analysis of factors associated with positive anti-HCV Patient profiles including socio-demographic parameters, the main risk behavior or risk exposure, types of skin diseases, anti-HIV status, and results of anti-HCV were analyzed using Chi-square test or Fisher's exact test. Results revealed that only 10 from 150 studied patients (6.7%) were positive for anti-HCV antibody. Patient profiles including socio-demographic parameters, the main risk behavior or risk exposure, types of skin diseases, and anti-HIV status among patients with or without anti-HCV were compared and analyzed to assess factors associated with positive anti-HCV. It was found that patient's income, types of skin disease, and anti-HIV status were significantly associated with positive anti-HCV among this group, p = 0.0240, p = 0.0053 and p = 0.0462, respectively. This analysis found three studied factors including patient's income, types of skin disease, and anti-HIV status to be significantly associated with HCV infection in patients with skin diseases. However, a large-scale work should be done to confirm the present study.

  10. Assessment of Olfactory Function in MAPT-Associated Neurodegenerative Disease Reveals Odor-Identification Irreproducibility as a Non-Disease-Specific, General Characteristic of Olfactory Dysfunction.

    PubMed

    Markopoulou, Katerina; Chase, Bruce A; Robowski, Piotr; Strongosky, Audrey; Narożańska, Ewa; Sitek, Emilia J; Berdynski, Mariusz; Barcikowska, Maria; Baker, Matt C; Rademakers, Rosa; Sławek, Jarosław; Klein, Christine; Hückelheim, Katja; Kasten, Meike; Wszolek, Zbigniew K

    2016-01-01

    Olfactory dysfunction is associated with normal aging, multiple neurodegenerative disorders, including Parkinson's disease, Lewy body disease and Alzheimer's disease, and other diseases such as diabetes, sleep apnea and the autoimmune disease myasthenia gravis. The wide spectrum of neurodegenerative disorders associated with olfactory dysfunction suggests different, potentially overlapping, underlying pathophysiologies. Studying olfactory dysfunction in presymptomatic carriers of mutations known to cause familial parkinsonism provides unique opportunities to understand the role of genetic factors, delineate the salient characteristics of the onset of olfactory dysfunction, and understand when it starts relative to motor and cognitive symptoms. We evaluated olfactory dysfunction in 28 carriers of two MAPT mutations (p.N279K, p.P301L), which cause frontotemporal dementia with parkinsonism, using the University of Pennsylvania Smell Identification Test. Olfactory dysfunction in carriers does not appear to be allele specific, but is strongly age-dependent and precedes symptomatic onset. Severe olfactory dysfunction, however, is not a fully penetrant trait at the time of symptom onset. Principal component analysis revealed that olfactory dysfunction is not odor-class specific, even though individual odor responses cluster kindred members according to genetic and disease status. Strikingly, carriers with incipient olfactory dysfunction show poor inter-test consistency among the sets of odors identified incorrectly in successive replicate tests, even before severe olfactory dysfunction appears. Furthermore, when 78 individuals without neurodegenerative disease and 14 individuals with sporadic Parkinson's disease were evaluated twice at a one-year interval using the Brief Smell Identification Test, the majority also showed inconsistency in the sets of odors they identified incorrectly, independent of age and cognitive status. While these findings may reflect the

  11. Loss-of-Function PCSK9 Mutations Are Not Associated With Alzheimer Disease.

    PubMed

    Paquette, Martine; Saavedra, Yascara Grisel Luna; Poirier, Judes; Théroux, Louise; Dea, Doris; Baass, Alexis; Dufour, Robert

    2018-03-01

    Hypercholesterolemia is a major risk factor for the late-onset form of Alzheimer disease (AD). Loss-of-function (LOF) mutations of PCSK9 and PCSK9 inhibitors lower low-density lipoprotein cholesterol (LDL-C) and have been associated with a reduced risk of cardiovascular disease. The aim of this study was to examine the effect of PCSK9 LOF variants on risk and age of onset of AD. A total of 878 participants (410 controls and 468 AD cases) from the Quebec Founder Population were included in the study. Fifty-four (6.2%) participants carried the R46L mutation, whereas 226 (26.2%) participants carried the InsLEU mutation. There was no protective or no deleterious effect of carrying PCSK9 LOF mutations on AD prevalence nor on age of onset, even when stratified by apolipoprotein E epsilon 4 genotype or by gender. Our data indicate that carrying PCSK9 LOF mutations has a neutral effect on neurocognitive health and the prevalence of AD.

  12. Cardiovascular disease and type 1 diabetes: prevalence, prediction and management in an ageing population

    PubMed Central

    Lee, Siang Ing; Patel, Mitesh; Jones, Christopher M.; Narendran, Parth

    2015-01-01

    Cardiovascular disease (CVD) is a major cause of mortality in type 1 diabetes mellitus (T1D). However, evidence of its risks and management is often extrapolated from studies in type 2 diabetic (T2D) patients or the general population. This approach is unsatisfactory given that the underlying pathology, demographics and natural history of the disease differ between T1D and T2D. Furthermore, with a rising life expectancy, a greater number of T1D patients are exposed to the cardiovascular (CV) risk factors associated with an ageing population. The aim of this review is to examine the existing literature around CVD in T1D. We pay particular attention to CVD prevalence, how well we manage risk, potential biomarkers, and whether the studies included the older aged patients (defined as aged over 65). We also discuss approaches to the management of CV risk in the older aged. The available data suggest a significant CVD burden in patients with T1D and poor management of CV risk factors. This is underpinned by a poor evidence base for therapeutic management of CV risk specifically for patients with T1D, and in the most relevant population – the older aged patients. We would suggest that important areas remain to be addressed, particularly exploring the risks and benefits of therapeutic approaches to CVD management in the older aged. PMID:26568811

  13. Markers of Oxidant Stress that are Clinically Relevant in Aging and Age-related Disease

    PubMed Central

    Jacob, Kimberly D.; Hooten, Nicole Noren; Trzeciak, Andrzej R.; Evans, Michele K.

    2013-01-01

    Despite the long held hypothesis that oxidant stress results in accumulated oxidative damage to cellular macromolecules and subsequently to aging and age-related chronic disease, it has been difficult to consistently define and specifically identify markers of oxidant stress that are consistently and directly linked to age and disease status. Inflammation because it is also linked to oxidant stress, aging, and chronic disease also plays an important role in understanding the clinical implications of oxidant stress and relevant markers. Much attention has focused on identifying specific markers of oxidative stress and inflammation that could be measured in easily accessible tissues and fluids (lymphocytes, plasma, serum). The purpose of this review is to discuss markers of oxidant stress used in the field as biomarkers of aging and age-related diseases, highlighting differences observed by race when data is available. We highlight DNA, RNA, protein, and lipid oxidation as measures of oxidative stress, as well as other well-characterized markers of oxidative damage and inflammation and discuss their strengths and limitations. We present the current state of the literature reporting use of these markers in studies of human cohorts in relation to age and age-related disease and also with a special emphasis on differences observed by race when relevant. PMID:23428415

  14. Association between daily mortality from respiratory and cardiovascular diseases and air pollution in Taiwan.

    PubMed

    Liang, Wen-Miin; Wei, Hsing-Yu; Kuo, Hsien-Wen

    2009-01-01

    Many studies have investigated the effects of air pollutants on disease and mortality. However, the results remain inconsistent and inconclusive. We thought that the impact of different seasons or ages of people may explain these differences. Measurement of the five pollutants (particulate matter <10 microm in aerodynamic diameter (PM(10)), SO(2), NO(2), O(3), and CO) was monitored by automated measuring units at five different stations. Monitoring stations were provided by the Taiwan Environmental Protection Agency (EPA) from 1997 to 1999. The subjects in the study were classified in two groups: those 65 years of age and older, and those of all ages (including the subjects in the > or =65 group). Data on daily mortality caused by respiratory disease, cardiovascular disease, and all other causes including the two aforementioned was collected by the Taiwan Department of Health (DOH). A time-series regression model was used to analyze the relative risk of respiratory and cardiovascular diseases due to air pollution in the summer and winter seasons. Risk of death from all causes and mortality from cardiovascular diseases during winter was significantly positively correlated with levels of SO(2), CO, and NO(2) for both groups of subjects and additionally with PM(10) for the elderly (> or =65 years old) group. There were significant positive correlations with respiratory diseases and levels of O(3) for both groups. However, the only significant positive correlation was with O(3) (RR=1.283) for the elderly group during summer. No other parameters showed significance for either group. Our findings contribute to the evidence of an association between SO(2), CO, NO(2), and PM(10) and mortality from respiratory and cardiovascular diseases, especially among elderly people during the winter season.

  15. Factors associated with resistance to dementia despite high Alzheimer disease pathology.

    PubMed

    Erten-Lyons, D; Woltjer, R L; Dodge, H; Nixon, R; Vorobik, R; Calvert, J F; Leahy, M; Montine, T; Kaye, J

    2009-01-27

    Autopsy series have shown that some elderly people remain with normal cognitive function during life despite having high burdens of pathologic lesions associated with Alzheimer disease (AD) at death. Understanding why these individuals show no cognitive decline, despite high AD pathologic burdens, may be key to discovery of neuroprotective mechanisms. A total of 36 subjects who on autopsy had Braak stage V or VI and moderate or frequent neuritic plaque scores based on Consortium to Establish a Registry for Alzheimer's Disease (CERAD) standards were included. Twelve had normal cognitive function and 24 a diagnosis of AD before death. Demographic characteristics, clinical and pathologic data, as well as antemortem brain volumes were compared between the groups. In multiple regression analysis, antemortem hippocampal and total brain volumes were significantly larger in the group with normal cognitive function after adjusting for gender, age at MRI, time from MRI to death, Braak stage, CERAD neuritic plaque score, and overall presence of vascular disease. Larger brain and hippocampal volumes were associated with preserved cognitive function during life despite a high burden of Alzheimer disease (AD) pathologic lesions at death. A better understanding of processes that lead to preservation of brain volume may provide important clues for the discovery of mechanisms that protect the elderly from AD.

  16. Association between sleep bruxism and gastroesophageal reflux disease.

    PubMed

    Mengatto, Cristiane Machado; Dalberto, Charlene da Silveira; Scheeren, Betina; Barros, Sérgio Gabriel Silva de

    2013-11-01

    Rhythmic masticatory muscle activity, including sleep bruxism (SB), can be induced in healthy individuals by experimental esophageal acidification, which plays an important role in the pathogenesis of gastroesophageal reflux disease (GERD). However, no robust evidence supports the association between SB and GERD. The purpose of this study was to investigate the association between SB and GERD. Forty-five individuals were eligible to participate in this observational transversal study at the Gastroenterology Service of the Clinical Hospital of Porto Alegre, Brazil. The participants were classified into 2 groups, those with and without GERD, according to the Montreal Criteria and pH-metry/endoscopy findings. The diagnosis of SB was not assessed in a sleep laboratory but was based on self-report plus clinical inspection, according to the minimal diagnostic criteria of the American Academy of Sleep Medicine. The Lipp Stress Symptom Inventory was used to evaluate self-perceived stress. Univariate and multiple logistic regression analyses were performed with SB as dependent variable and GERD, sex, age, body mass index, and stress as predictors (α=.05; 90% power). The study population included individuals with SB without GERD (13.3%) and individuals with SB with GERD (31.1%). In participants with GERD, the prevalence of SB was 73.7%. Only the variable GERD was significantly associated with SB (P=.017; odds ratio 6.58; 95% confidence interval 1.40-30.98), although adjusted for stress and age. Sleep bruxism is prevalent in GERD patients, and GERD is highly associated with SB. Copyright © 2013 Editorial Council for the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.

  17. Coeliac Disease With Rheumatoid Arthritis: An Unusual Association.

    PubMed

    Warjri, Synrang Batngen; Ete, Tony; Beyong, Taso; Barman, Bhupen; Lynrah, Kyrshanlang G; Nobin, Hage; Perme, Obang

    2015-02-01

    Coeliac disease has a significant association with many autoimmune disorders. It shares many common genetic and immunological features with other autoimmune diseases. Gluten, a gut-derived antigen, is the driver of the autoimmunity seen in coeliac disease. The altered intestinal permeability found in coeliac patients, coupled with a genetic predisposition and altered immunological response, may result in a systemic immune response that is directed against sites other than the gut. Gut-derived antigens may have a role in the pathogenesis of other autoimmune disorders including rheumatoid arthritis. Here we report a case of adult coeliac disease associated with rheumatoid arthritis.

  18. Belching during gastroscopy and its association with gastroesophageal reflux disease.

    PubMed

    Lee, B S; Lee, S H; Jang, D K; Chung, K H; Hwang, J H; Jang, S E; Cha, B H; Ryu, J K; Kim, Y-T

    2016-05-01

    Belching may result from transient lower esophageal sphincter relaxation; therefore, it has been proposed that belching may be a manifestation of gastroesophageal reflux disease (GERD). This study was conducted to investigate the frequency of belching during esophagogastroduodenoscopy (EGD) and its association with GERD. A retrospective review was performed on prospectively collected clinical and endoscopic data from 404 subjects who underwent EGD without sedation from December 2012 to May 2013 in a training hospital in Korea. All detectable belching events during endoscopy were counted. Frequency and severity of belching events were compared between the group with and without GERD using an ordinal logistic regression model. There were 145 GERD patients (26 erosive reflux disease and 119 nonerosive reflux disease [NERD]). In the multivariable analysis, GERD was significantly associated with a higher frequency of belching events (odds ratio = 6.59, P < 0.001). Central obesity, female, and younger age were also risk factors for frequent belching during EGD. Subgroup analyses were performed in subjects without erosive reflux disease (n = 378) and NERD (n = 293). NERD was also a predictive factor for frequent belching during EGD (odds ratio = 6.61, P < 0.001), and the frequency of belching was significantly correlated with GERD severity according to the Los Angeles classification (P < 0.05). Frequent belching during EGD was associated with GERD, including NERD. Future research should focus on its adjuvant role in the diagnosis of GERD/NERD and the necessity for applying differentiated endoscopy strategies for GERD patients, leading to less discomfort during EGD in patients at risk for intolerability. © 2015 International Society for Diseases of the Esophagus.

  19. Effects of early age at natural menopause on coronary heart disease and stroke in Chinese women.

    PubMed

    Shen, Lijun; Song, Lulu; Liu, Bingqing; Li, Hui; Zheng, Xiaoxuan; Zhang, Lina; Yuan, Jing; Liang, Yuan; Wang, Youjie

    2017-08-15

    Menopause is identified as a risk factor for cardiovascular disease because of the change of estrogen. The objective of the study was to explore the associations between early age at natural menopause (menopause at an age≤45years) and the presence of CHD and stroke. The study subjects were from the first follow-up survey of the Dongfeng-Tongji cohort study. A total of 16,515 postmenopausal women were included for the analysis. Logistic regression models were used to examine the associations between age at natural menopause (≤45, 45-52, >52years) and the presence of CHD and stroke adjusted for sociodemographic characteristics, lifestyle, reproductive history and metabolic factors. In the fully adjusted model, for each 1-year delay in menopausal age, the prevalence of CHD and stroke was reduced by 3% (OR, 0.97; 95% CI, 0.95-0.98) and 5% (OR, 0.95; 95% CI, 0.92-0.98), respectively. Women with early menopause (≤45years) had a higher prevalence of CHD (OR, 1.33; 95% CI, 1.13-1.57) compared with those with menopause at ages 45-52years. Similarly, women with early menopause (≤45years) was associated with higher prevalence of stroke (OR, 1.69; 95% CI, 1.25-2.30) compared with those with menopause at ages 45-52years. Early age at natural menopause is significantly associated with the presence of CHD and stroke among Chinese women. Copyright © 2017. Published by Elsevier B.V.

  20. The influence of age on the distribution of self-rated health, burnout and their associations with psychosocial work conditions.

    PubMed

    Cheng, Yawen; Chen, I-Shin; Chen, Chiou-Jong; Burr, Hermann; Hasselhorn, Hans Martin

    2013-03-01

    Self-rated health (SRH) and burnout are commonly used health indicators. This study was designed to examine the age-specific patterns of SRH and burnout and their correlations with self-reported disease symptoms, and to investigate the moderating effects of age on the associations of psychosocial work conditions with these two health measures. Study subjects were 20,454 male and 16,875 female employees from 2 representative surveys conducted in 2007 and 2010 in Taiwan. SRH was assessed by a single item and burnout was assessed by the general burnout subscale of the Copenhagen Burnout Inventory (CBI). Psychosocial work conditions including working hours, psychological and physical job demands, job control, job insecurity and workplace justice were assessed by a validated questionnaire. Older workers were at higher risk for poor SRH which was correlated with the presence of multiple disease symptoms. In contrast, employees aged 30-40 years had higher burnout which was strongly correlated with emotional disturbance. Among all the examined work factors, low workplace justice was found to be the most predominant predictor for poor SRH and high burnout, and the associations were more profound in younger workers than in older workers. SRH and burnout were differentially related to age, and there were evidences of moderating effects of age on the associations between psychosocial work conditions and health. Researchers and health practitioners should pay attention to the influence of age when using the measures of SRH and burnout as indicators to detect health risk in association with adverse psychosocial work conditions. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Chronic Obstructive Pulmonary Disease (COPD) as a disease of early aging: Evidence from the EpiChron Cohort.

    PubMed

    Divo, Miguel J; Celli, Bartolome R; Poblador-Plou, Beatriz; Calderón-Larrañaga, Amaia; de-Torres, Juan Pablo; Gimeno-Feliu, Luis A; Bertó, Juan; Zulueta, Javier J; Casanova, Ciro; Pinto-Plata, Victor M; Cabrera-Lopez, Carlos; Polverino, Francesca; Carmona Píréz, Jonás; Prados-Torres, Alexandra; Marin, Jose M

    2018-01-01

    Aging is an important risk factor for most chronic diseases. Patients with COPD develop more comorbidities than non-COPD subjects. We hypothesized that the development of comorbidities characteristically affecting the elderly occur at an earlier age in subjects with the diagnosis of COPD. We included all subjects carrying the diagnosis of COPD (n = 27,617), and a similar number of age and sex matched individuals without the diagnosis, extracted from the 727,241 records of individuals 40 years and older included in the EpiChron Cohort (Aragon, Spain). We compared the cumulative number of comorbidities, their prevalence and the mortality risk between both groups. Using network analysis, we explored the connectivity between comorbidities and the most influential comorbidities in both groups. We divided the groups into 5 incremental age categories and compared their comorbidity networks. We then selected those comorbidities known to affect primarily the elderly and compared their prevalence across the 5 age groups. In addition, we replicated the analysis in the smokers' subgroup to correct for the confounding effect of cigarette smoking. Subjects with COPD had more comorbidities and died at a younger age compared to controls. Comparison of both cohorts across 5 incremental age groups showed that the number of comorbidities, the prevalence of diseases characteristic of aging and network's density for the COPD group aged 56-65 were similar to those of non-COPD 15 to 20 years older. The findings persisted after adjusting for smoking. Multimorbidity increases with age but in patients carrying the diagnosis of COPD, these comorbidities are seen at an earlier age.

  2. Cardiac Aging: From Molecular Mechanisms to Significance in Human Health and Disease

    PubMed Central

    Dai, Dao-Fu; Chen, Tony; Johnson, Simon C.; Szeto, Hazel

    2012-01-01

    Abstract Cardiovascular diseases (CVDs) are the major causes of death in the western world. The incidence of cardiovascular disease as well as the rate of cardiovascular mortality and morbidity increase exponentially in the elderly population, suggesting that age per se is a major risk factor of CVDs. The physiologic changes of human cardiac aging mainly include left ventricular hypertrophy, diastolic dysfunction, valvular degeneration, increased cardiac fibrosis, increased prevalence of atrial fibrillation, and decreased maximal exercise capacity. Many of these changes are closely recapitulated in animal models commonly used in an aging study, including rodents, flies, and monkeys. The application of genetically modified aged mice has provided direct evidence of several critical molecular mechanisms involved in cardiac aging, such as mitochondrial oxidative stress, insulin/insulin-like growth factor/PI3K pathway, adrenergic and renin angiotensin II signaling, and nutrient signaling pathways. This article also reviews the central role of mitochondrial oxidative stress in CVDs and the plausible mechanisms underlying the progression toward heart failure in the susceptible aging hearts. Finally, the understanding of the molecular mechanisms of cardiac aging may support the potential clinical application of several “anti-aging” strategies that treat CVDs and improve healthy cardiac aging. PMID:22229339

  3. 'Leukodystrophy-like' phenotype in children with myelin oligodendrocyte glycoprotein antibody-associated disease.

    PubMed

    Hacohen, Yael; Rossor, Thomas; Mankad, Kshitij; Chong, Wk 'Kling'; Lux, Andrew; Wassmer, Evangeline; Lim, Ming; Barkhof, Frederik; Ciccarelli, Olga; Hemingway, Cheryl

    2018-04-01

    To review the demographics and clinical and paraclinical parameters of children with myelin oligodendrocyte glycoprotein (MOG) antibody-associated relapsing disease. In this UK-based, multicentre study, 31 children with MOG antibody-associated relapsing disease were studied retrospectively. Of the 31 children studied, 14 presented with acute disseminated encephalomyelitis (ADEM); they were younger (mean 4.1y) than the remainder (mean 8.5y) who presented with optic neuritis and/or transverse myelitis (p<0.001). Similarly, children who had an abnormal brain magnetic resonance imaging (MRI) at onset (n=20) were younger than patients with normal MRI at onset (p=0.001) or at follow-up (p<0.001). 'Leukodystrophy-like' MRI patterns of confluent largely symmetrical lesions was seen during the course of the disease in 7 out of 14 children with a diagnosis of ADEM, and was only seen in children younger than 7 years of age. Their disability after a 3-year follow-up was mild to moderate, and most patients continued to relapse, despite disease-modifying treatments. MOG antibody should be tested in children presenting with relapsing neurological disorders associated with confluent, bilateral white matter changes, and distinct enhancement pattern. Children with MOG antibody-associated disease present with age-related differences in phenotypes, with a severe leukoencephalopathy phenotype in the very young and normal intracranial MRI in the older children. This finding suggests a susceptibility of the very young and myelinating brain to MOG antibody-mediated mechanisms of damage. Myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination manifest with an age-related phenotype. Children with MOG antibody and 'leukodystrophy-like' imaging patterns tend to have poor response to second-line immunotherapy. © 2017 Mac Keith Press.

  4. Components of family history associated with women's disease perceptions for cancer: a report from the Family Healthware™ Impact Trial.

    PubMed

    Rubinstein, Wendy S; O'neill, Suzanne M; Rothrock, Nan; Starzyk, Erin J; Beaumont, Jennifer L; Acheson, Louise S; Wang, Catharine; Gramling, Robert; Galliher, James M; Ruffin, Mack T

    2011-01-01

    To determine the specific components of family history and personal characteristics related to disease perceptions about breast, colon, and ovarian cancers. Baseline, cross-sectional data on 2,505 healthy women aged 35-65 years enrolled from 41 primary care practices in the cluster-randomized Family Healthware™ Impact Trial, assessed for detailed family history and perceived risk, perceived severity, worry, and perceived control over getting six common diseases including breast, colon, and ovarian cancers. Participants provided family history information on 41,841 total relatives. We found evidence of underreporting of paternal family history and lower perceived breast cancer risk with cancer in the paternal versus maternal lineage. We observed cancer-specific perceived risks and worry for individual family history elements and also found novel "spillover" effects where a family history of one cancer was associated with altered disease perceptions of another. Having a mother with early-onset breast or ovarian cancer was strongly associated with perceived risk of breast cancer. Age, parenthood, and affected lineage were associated with disease perceptions and ran counter to empiric risks. Understanding patients' formulation of risk for multiple diseases is important for public health initiatives that seek to inform risk appraisal, influence disease perceptions, or match preventive interventions to existing risk perceptions.

  5. Components of family history associated with women's disease perceptions for cancer: A report from the Family Healthware™ Impact Trial

    PubMed Central

    Rubinstein, Wendy S.; O'Neill, Suzanne M.; Rothrock, Nan; Starzyk, Erin J.; Beaumont, Jennifer L.; Acheson, Louise S.; Wang, Catharine; Gramling, Robert; Galliher, James M.; Ruffin, Mack T.

    2014-01-01

    Purpose To determine the specific components of family history and personal characteristics related to disease perceptions about breast, colon, and ovarian cancers. Methods Baseline, cross-sectional data on 2,505 healthy women aged 35–65 years enrolled from 41 primary care practices in the cluster-randomized Family Healthware™ Impact Trial, assessed for detailed family history and perceived risk, perceived severity, worry, and perceived control over getting six common diseases including breast, colon, and ovarian cancers. Results Participants provided family history information on 41,841 total relatives. We found evidence of underreporting of paternal family history and lower perceived breast cancer risk with cancer in the paternal versus maternal lineage. We observed cancer-specific perceived risks and worry for individual family history elements and also found novel “spillover” effects where a family history of one cancer was associated with altered disease perceptions of another. Having a mother with early-onset breast or ovarian cancer was strongly associated with perceived risk of breast cancer. Age, parenthood, and affected lineage were associated with disease perceptions and ran counter to empiric risks. Conclusions Understanding patients' formulation of risk for multiple diseases is important for public health initiatives that seek to inform risk appraisal, influence disease perceptions, or match preventive interventions to existing risk perceptions. PMID:21150785

  6. Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study.

    PubMed

    Hensman Moss, Davina J; Pardiñas, Antonio F; Langbehn, Douglas; Lo, Kitty; Leavitt, Blair R; Roos, Raymund; Durr, Alexandra; Mead, Simon; Holmans, Peter; Jones, Lesley; Tabrizi, Sarah J

    2017-09-01

    Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008-11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003-13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10 -10 ) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10 -8 DHFR p=8·37 × 10 -7 MTRNR2L2 p=2·15 × 10 -9 ) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10 -4 DHFR p=8·45 × 10 -4 MTRNR2L2 p=1·20 × 10 -3 ). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome

  7. Mitochondrial and Ubiquitin Proteasome System Dysfunction in Ageing and Disease: Two Sides of the Same Coin?

    PubMed Central

    Ross, Jaime M.; Olson, Lars; Coppotelli, Giuseppe

    2015-01-01

    Mitochondrial dysfunction and impairment of the ubiquitin proteasome system have been described as two hallmarks of the ageing process. Additionally, both systems have been implicated in the etiopathogenesis of many age-related diseases, particularly neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease. Interestingly, these two systems are closely interconnected, with the ubiquitin proteasome system maintaining mitochondrial homeostasis by regulating organelle dynamics, the proteome, and mitophagy, and mitochondrial dysfunction impairing cellular protein homeostasis by oxidative damage. Here, we review the current literature and argue that the interplay of the two systems should be considered in order to better understand the cellular dysfunction observed in ageing and age-related diseases. Such an approach may provide valuable insights into molecular mechanisms underlying the ageing process, and further discovery of treatments to counteract ageing and its associated diseases. Furthermore, we provide a hypothetical model for the heterogeneity described among individuals during ageing. PMID:26287188

  8. The Potential of Chitosan and Its Derivatives in Prevention and Treatment of Age-Related Diseases

    PubMed Central

    Kerch, Garry

    2015-01-01

    Age-related, diet-related and protein conformational diseases, such as atherosclerosis, diabetes mellitus, cancer, hypercholesterolemia, cardiovascular and neurodegenerative diseases are common in the elderly population. The potential of chitosan, chitooligosaccharides and their derivatives in prevention and treatment of age-related dysfunctions is reviewed and discussed in this paper. The influence of oxidative stress, low density lipoprotein oxidation, increase of tissue stiffness, protein conformational changes, aging-associated chronic inflammation and their pathobiological significance have been considered. The chitosan-based functional food also has been reviewed. PMID:25871293

  9. The Intersection of Aging Biology and the Pathobiology of Lung Diseases: A Joint NHLBI/NIA Workshop

    PubMed Central

    Budinger, GR Scott; Kohanski, Ronald A; Gan, Weiniu; Kobor, Michael S; Amaral, Luis A; Armanios, Mary; Kelsey, Karl T; Pardo, Annie; Tuder, Rubin; Macian, Fernando; Chandel, Navdeep; Vaughan, Douglas; Rojas, Mauricio; Mora, Ana L; Kovacs, Elizabeth; Duncan, Steven R; Finkel, Toren; Choi, Augustine; Eickelberg, Oliver; Chen, Danica; Agusti, Alvar; Selman, Moises; Balch, William E; Busse, Paula; Lin, Anning; Morimoto, Richard; Sznajder, Jacob I; Thannickal, Victor J

    2017-01-01

    Abstract Death from chronic lung disease is increasing and chronic obstructive pulmonary disease has become the third leading cause of death in the United States in the past decade. Both chronic and acute lung diseases disproportionately affect elderly individuals, making it likely that these diseases will become more frequent and severe as the worldwide population ages. Chronic lung diseases are associated with substantial morbidity, frequently resulting in exercise limiting dyspnea, immobilization, and isolation. Therefore, effective strategies to prevent or treat lung disease are likely to increase healthspan as well as life span. This review summarizes the findings of a joint workshop sponsored by the NIA and NHLBI that brought together investigators focused on aging and lung biology. These investigators encouraged the use of genetic systems and aged animals in the study of lung disease and the development of integrative systems-based platforms that can dynamically incorporate data sets that describe the genomics, transcriptomics, epigenomics, metabolomics, and proteomics of the aging lung in health and disease. Further research was recommended to integrate benchmark biological hallmarks of aging in the lung with the pathobiology of acute and chronic lung diseases with divergent pathologies for which advanced age is the most important risk factor. PMID:28498894

  10. Reactive oxygen species and oxidative stress in osteoclastogenesis, skeletal aging and bone diseases.

    PubMed

    Callaway, Danielle A; Jiang, Jean X

    2015-07-01

    Osteoclasts are cells derived from bone marrow macrophages and are important in regulating bone resorption during bone homeostasis. Understanding what drives osteoclast differentiation and activity is important when studying diseases characterized by heightened bone resorption relative to formation, such as osteoporosis. In the last decade, studies have indicated that reactive oxygen species (ROS), including superoxide and hydrogen peroxide, are crucial components that regulate the differentiation process of osteoclasts. However, there are still many unanswered questions that remain. This review will examine the mechanisms by which ROS can be produced in osteoclasts as well as how it may affect osteoclast differentiation and activity through its actions on osteoclastogenesis signaling pathways. In addition, the contribution of ROS to the aging-associated disease of osteoporosis will be addressed and how targeting ROS may lead to the development of novel therapeutic treatment options.

  11. Genome-wide association study identifies four novel loci associated with Alzheimer’s endophenotypes and disease modifiers

    PubMed Central

    Deming, Yuetiva; Li, Zeran; Kapoor, Manav; Harari, Oscar; Del-Aguila, Jorge L.; Black, Kathleen; Carrell, David; Cai, Yefei; Fernandez, Maria Victoria; Budde, John; Ma, Shengmei; Saef, Benjamin; Howells, Bill; Huang, Kuanlin; Bertelsen, Sarah; Fagan, Anne M.; Holtzman, David M.; Morris, John C.; Kim, Sungeun; Saykin, Andrew J.; De Jager, Philip L.; Albert, Marilyn; Moghekar, Abhay; O’Brien, Richard; Riemenschneider, Matthias; Petersen, Ronald C.; Blennow, Kaj; Zetterberg, Henrik; Minthon, Lennart; Van Deerlin, Vivianna M.; Lee, Virginia Man-Yee; Shaw, Leslie M.; Trojanowski, John Q.; Schellenberg, Gerard; Haines, Jonathan L.; Mayeux, Richard; Pericak-Vance, Margaret A.; Farrer, Lindsay A.; Peskind, Elaine R.; Li, Ge; Di Narzo, Antonio F.; Kauwe, John S. K.; Goate, Alison M.; Cruchaga, Carlos

    2017-01-01

    More than 20 genetic loci have been associated with risk for Alzheimer’s disease (AD), but reported genome-wide significant loci do not account for all the estimated heritability and provide little information about underlying biological mechanisms. Genetic studies using intermediate quantitative traits such as biomarkers, or endophenotypes, benefit from increased statistical power to identify variants that may not pass the stringent multiple test correction in case–control studies. Endophenotypes also contain additional information helpful for identifying variants and genes associated with other aspects of disease, such as rate of progression or onset, and provide context to interpret the results from genome-wide association studies (GWAS). We conducted GWAS of amyloid beta (Aβ42), tau, and phosphorylated tau (ptau181) levels in cerebrospinal fluid (CSF) from 3146 participants across nine studies to identify novel variants associated with AD. Five genome-wide significant loci (two novel) were associated with ptau181, including loci that have also been associated with AD risk or brain-related phenotypes. Two novel loci associated with Aβ42 near GLIS1 on 1p32.3 (β = −0.059, P = 2.08 × 10−8) and within SERPINB1 on 6p25 (β = −0.025, P = 1.72 × 10−8) were also associated with AD risk (GLIS1: OR = 1.105, P = 3.43 × 10−2), disease progression (GLIS1: β = 0.277, P = 1.92 × 10−2), and age at onset (SER-PINB1: β = 0.043, P = 4.62 × 10−3). Bioinformatics indicate that the intronic SERPINB1 variant (rs316341) affects expression of SERPINB1 in various tissues, including the hippocampus, suggesting that SERPINB1 influences AD through an Aβ-associated mechanism. Analyses of known AD risk loci suggest CLU and FERMT2 may influence CSF Aβ42 (P = 0.001 and P = 0.009, respectively) and the INPP5D locus may affect ptau181 levels (P = 0.009); larger studies are necessary to verify these results. Together the findings from this study can be used to inform

  12. Epigenetic Control of Stem Cell Potential During Homeostasis, Aging, and Disease

    PubMed Central

    Beerman, Isabel; Rossi, Derrick J.

    2015-01-01

    Stem cell decline is an important cellular driver of aging-associated pathophysiology in multiple tissues. Epigenetic regulation is central to establishing and maintaining stem cell function, and emerging evidence indicates that epigenetic dysregulation contributes to the altered potential of stem cells during aging. Unlike terminally differentiated cells, the impact of epigenetic dysregulation in stem cells is propagated beyond self; alterations can be heritably transmitted to differentiated progeny, in addition to being perpetuated and amplified within the stem cell pool through self-renewal divisions. This review focuses on recent studies examining epigenetic regulation of tissue-specific stem cells in homeostasis, aging, and aging-related disease. PMID:26046761

  13. Premature Coronary Artery Disease in Indians and its Associated Risk Factors

    PubMed Central

    Sharma, Meenakshi; Ganguly, Nirmal Kumar

    2005-01-01

    Of particular concern to India is not only the high burden of cardiovascular diseases (CVDs), but also the effects of these diseases on the productive workforce aged 35–65 years. Heart diseases are rising in Asian Indians 5–10 years earlier than in other populations around the world. The mean age for first presentation of acute myocardial infarction in Indians is 53 years. Coronary artery disease (CAD) that manifests at a younger age can have devastating consequences for an individual, the family, and society. Prevention of these deaths in young people is a nation's moral responsibility. A strategy involving prevention of CVDs long before their onset will be more cost-effective than providing interventions at a stage when the disease is well established. We review the rising trends in CAD with particular emphasis on prevalence of premature CAD and the associated risk factors in young Indian CAD patients. Action strategies to reduce the risk are suggested. PMID:17319107

  14. Alzheimer's disease is associated with prostate cancer: a population-based study.

    PubMed

    Lin, Herng-Ching; Kao, Li-Ting; Chung, Shiu-Dong; Huang, Chung-Chien; Shia, Ben-Chang; Huang, Chao-Yuan

    2018-01-26

    Alzheimer's disease and cancer are increasingly prevalent with advancing age. However, the association between Alzheimer's disease and prostate cancer remains unclear. The aim of this study was to examine the relationship between prior Alzheimer's disease and subsequent prostate cancer using a population-based dataset in Taiwan. Data for this study were sourced from the Taiwan Longitudinal Health Insurance Database 2005. This case-control study included 2101 prostate cancer patients as cases and 6303 matched controls. We used conditional logistic regression analyses to calculate the odds ratio (OR) and corresponding 95% confidence interval (CI) for Alzheimer's disease between prostate cancer patients and controls. We found that of the 8404 sampled patients, 128 (1.5%) had been diagnosed with Alzheimer's disease prior to the index date. A Chi-squared test showed that there was a significant difference in the prevalences of prior Alzheimer's disease between prostate cancer patients and controls (2.1% vs. 1.3%, p < 0.001). The conditional logistic regression analysis showed that the OR of prior Alzheimer's disease for prostate cancer patients was 1.53 (95% CI: 1.06∼2.21) compared to controls. Furthermore, the OR of prior Alzheimer's disease for prostate cancer patients was 1.52 (95% CI: 1.04∼2.22) compared to controls after adjusting for hypertension, diabetes, coronary heart disease, hyperlipidemia, obesity, prostatitis, gonorrhea or chlamydia infection, testitis or epididymitis, and alcohol abuse/alcohol dependency syndrome. This study revealed an association between prior Alzheimer's disease and prostate cancer. We suggest that clinicians be alert to the increased risk of prostate cancer when caring for elderly individuals with Alzheimer's disease.

  15. Age of child, more than HPV type, is associated with clinical course in recurrent respiratory papillomatosis.

    PubMed

    Buchinsky, Farrel J; Donfack, Joseph; Derkay, Craig S; Choi, Sukgi S; Conley, Stephen F; Myer, Charles M; McClay, John E; Campisi, Paolo; Wiatrak, Brian J; Sobol, Steven E; Schweinfurth, John M; Tsuji, Domingos H; Hu, Fen Z; Rockette, Howard E; Ehrlich, Garth D; Post, J Christopher

    2008-05-28

    RRP is a devastating disease in which papillomas in the airway cause hoarseness and breathing difficulty. The disease is caused by human papillomavirus (HPV) 6 or 11 and is very variable. Patients undergo multiple surgeries to maintain a patent airway and in order to communicate vocally. Several small studies have been published in which most have noted that HPV 11 is associated with a more aggressive course. Papilloma biopsies were taken from patients undergoing surgical treatment of RRP and were subjected to HPV typing. 118 patients with juvenile-onset RRP with at least 1 year of clinical data and infected with a single HPV type were analyzed. HPV 11 was encountered in 40% of the patients. By our definition, most of the patients in the sample (81%) had run an aggressive course. The odds of a patient with HPV 11 running an aggressive course were 3.9 times higher than that of patients with HPV 6 (Fisher's exact p = 0.017). However, clinical course was more closely associated with age of the patient (at diagnosis and at the time of the current surgery) than with HPV type. Patients with HPV 11 were diagnosed at a younger age (2.4y) than were those with HPV 6 (3.4y) (p = 0.014). Both by multiple linear regression and by multiple logistic regression HPV type was only weakly associated with metrics of disease course when simultaneously accounting for age. CONCLUSIONS/SIGNIFICANCE ABSTRACT: The course of RRP is variable and a quarter of the variability can be accounted for by the age of the patient. HPV 11 is more closely associated with a younger age at diagnosis than it is associated with an aggressive clinical course. These data suggest that there are factors other than HPV type and age of the patient that determine disease course.

  16. Association of Anxiety and Depression With All‐Cause Mortality in Individuals With Coronary Heart Disease

    PubMed Central

    Watkins, Lana L.; Koch, Gary G.; Sherwood, Andrew; Blumenthal, James A.; Davidson, Jonathan R.T.; O'Connor, Christopher; Sketch, Michael H.

    2013-01-01

    Background Depression has been related to mortality in coronary heart disease (CHD) patients, but few studies have evaluated the role of anxiety or the role of the co‐occurrence of depression and anxiety. We examined whether anxiety is associated with increased risk of mortality after accounting for depression in individuals with established CHD. Methods and Results The cohort was composed of 934 men and women with confirmed CHD (mean age, 62±11 years) who completed the Hospital Anxiety and Depression scale (HADS) during hospitalization for coronary angiography. Over the 3‐year follow‐up period, there were 133 deaths. Elevated scores on the HADS anxiety subscale (HADS‐A≥8) were associated with increased risk of mortality after accounting for established risk factors including age, congestive heart failure, left ventricular ejection fraction, 3‐vessel disease, and renal disease (hazard ratio [HR], 2.27; 95% CI, 1.55 to 3.33; P<0.001). Elevated scores on the HADS depression subscale (HADS‐D≥8) were also associated with increased risk of mortality (HR, 2.18; 95% CI, 1.47 to 3.22; P<0.001). When both psychosocial factors were included in the model, each maintained an association with mortality (anxiety, HR, 1.83; 95% CI, 1.18 to 2.83; P=0.006; depression, HR, 1.66; 95% CI, 1.06 to 2.58; P=0.025). Estimation of the HR for patients with both anxiety and depression versus those with neither revealed a larger HR than for patients with either factor alone (HR, 3.10; 95% CI, 1.95 to 4.94; P<0.001). Conclusions Anxiety is associated with increased risk of mortality in CHD patients, particularly when comorbid with depression. Future studies should focus on the co‐occurrence of these psychosocial factors as markers of increased mortality risk. PMID:23537805

  17. Role of Stromal Paracrine Signals in Proliferative Diseases of the Aging Human Prostate

    PubMed Central

    Takahashi, Sanai; Sugimura, Yoshiki

    2018-01-01

    Androgens are essential for the development, differentiation, growth, and function of the prostate through epithelial–stromal interactions. However, androgen concentrations in the hypertrophic human prostate decrease significantly with age, suggesting an inverse correlation between androgen levels and proliferative diseases of the aging prostate. In elderly males, age- and/or androgen-related stromal remodeling is spontaneously induced, i.e., increased fibroblast and myofibroblast numbers, but decreased smooth muscle cell numbers in the prostatic stroma. These fibroblasts produce not only growth factors, cytokines, and extracellular matrix proteins, but also microRNAs as stromal paracrine signals that stimulate prostate epithelial cell proliferation. Surgical or chemical castration is the standard systemic therapy for patients with advanced prostate cancer. Androgen deprivation therapy induces temporary remission, but the majority of patients eventually progress to castration-resistant prostate cancer, which is associated with a high mortality rate. Androgen deprivation therapy-induced stromal remodeling may be involved in the development and progression of castration-resistant prostate cancer. In the tumor microenvironment, activated fibroblasts stimulating prostate cancer cell proliferation are called carcinoma-associated fibroblasts. In this review, we summarize the role of stromal paracrine signals in proliferative diseases of the aging human prostate and discuss the potential clinical applications of carcinoma-associated fibroblast-derived exosomal microRNAs as promising biomarkers. PMID:29614830

  18. Mean platelet volume is associated with disease severity in patients with obstructive sleep apnea syndrome

    PubMed Central

    Akyol, Selahattin; Çörtük, Mustafa; Baykan, Ahmet Oytun; Kiraz, Kemal; Börekçi, Abdurrezzak; Şeker, Taner; Gür, Mustafa; Çayli, Murat

    2015-01-01

    OBJECTIVE: Obstructive sleep apnea syndrome is associated with cardiovascular diseases and thromboembolic events. The mean platelet volume (MPV) is a predictor of cardiovascular thromboembolic events. The aim of the present study is to investigate the association between the MPV and disease severity in patients with obstructive sleep apnea syndrome. METHODS: We prospectively included 194 obstructive sleep apnea syndrome patients without cardiovascular disease (mean age 56.5±12.5 years) who were undergoing sleep tests. An overnight full laboratory polisomnography examination was conducted on each patient. The patients were divided into 3 groups according to the apnea-hypopnea index (AHI): (1) AHIlow group: 5≤AHI<15, (2) AHImid group: 1530. RESULTS: The highest MPV values were found in the AHIhigh group compared with other groups (p<0.05 for all). Multiple linear regression analysis indicated that the MPV was associated with the AHI (β=0.500, p<0.001) and the high sensitivity C-reactive protein (hs-CRP) level (β=0.194, p=0.010). CONCLUSION: The MPV is independently associated with both disease severity and inflammation in patients with obstructive sleep apnea syndrome. PMID:26222817

  19. Arterial stiffness is associated with depression in middle-aged men — the Maastricht Study

    PubMed Central

    Onete, Veronica; Henry, Ronald M.; Sep, Simone J.S.; Koster, Annemarie; van der Kallen, Carla J.; Dagnelie, Pieter C.; Schaper, Nicolaas; Köhler, Sebastian; Reesink, Koen; Stehouwer, Coen D.A.

    2018-01-01

    Background Arterial stiffening may underlie the association between depression and cardiovascular disease (CVD), but reported data are inconsistent. We investigated the associations between aortic stiffness and major depressive disorder (MDD) and depressive symptoms, and whether these differed by sex and age. Methods We measured carotid to femoral pulse wave velocity (cfPWV) using applanation tonometry, and we assessed depression using the Mini-International Neuropsychiatric Interview (MINI) and the Patient Health Questionnaire-9 (PHQ-9) in a cohort of participants from The Maastricht Study. Logistic and negative binominal models were adjusted for age, type 2 diabetes mellitus (T2DM), mean arterial pressure (MAP) and CVD risk factors. Results We included 2757 participants in our analyses (48.8% men, mean age 59.8 ± 8.1 yr, 27% T2DM). We found that cfPWV was associated with MDD in men (fully adjusted odds ratio [OR] 2.36, 95% confidence interval [CI] 1.45–3.84), but not in women (OR 1.57, 95% CI 0.93–2.66), aged 60 years or younger. The ORs were not significant in individuals older than 60 years (men: OR 1.03, 95% CI 0.63–1.68; women: OR 0.64, 95% CI 0.32–1.31). Similarly, cfPWV was associated with a higher PHQ-9 score in men (rate ratio 1.28, 95% CI 1.09–1.52), but not in women (rate ratio 1.11, 95% CI 0.99–1.23), aged 60 years or younger. Associations were not significant in individuals older than 60 years (men: rate ratio 0.96, 95% CI 0.84–1.08; women: rate ratio 1.00, 95% CI 0.90–1.12). Limitations We cannot rule out reversed causation in this cross-sectional study. Conclusion Greater aortic stiffness is associated with MDD and depressive symptoms among middle-aged men and to a lesser extent in women, whereas this association was not observed in old age. PMID:29481318

  20. Genome-wide analysis of disease progression in age-related macular degeneration.

    PubMed

    Yan, Qi; Ding, Ying; Liu, Yi; Sun, Tao; Fritsche, Lars G; Clemons, Traci; Ratnapriya, Rinki; Klein, Michael L; Cook, Richard J; Liu, Yu; Fan, Ruzong; Wei, Lai; Abecasis, Gonçalo R; Swaroop, Anand; Chew, Emily Y; Weeks, Daniel E; Chen, Wei

    2018-03-01

    Family- and population-based genetic studies have successfully identified multiple disease-susceptibility loci for Age-related macular degeneration (AMD), one of the first batch and most successful examples of genome-wide association study. However, most genetic studies to date have focused on case-control studies of late AMD (choroidal neovascularization or geographic atrophy). The genetic influences on disease progression are largely unexplored. We assembled unique resources to perform a genome-wide bivariate time-to-event analysis to test for association of time-to-late-AMD with ∼9 million variants on 2721 Caucasians from a large multi-center randomized clinical trial, the Age-Related Eye Disease Study. To our knowledge, this is the first genome-wide association study of disease progression (bivariate survival outcome) in AMD genetic studies, thus providing novel insights to AMD genetics. We used a robust Cox proportional hazards model to appropriately account for between-eye correlation when analyzing the progression time in the two eyes of each participant. We identified four previously reported susceptibility loci showing genome-wide significant association with AMD progression: ARMS2-HTRA1 (P = 8.1 × 10-43), CFH (P = 3.5 × 10-37), C2-CFB-SKIV2L (P = 8.1 × 10-10) and C3 (P = 1.2 × 10-9). Furthermore, we detected association of rs58978565 near TNR (P = 2.3 × 10-8), rs28368872 near ATF7IP2 (P = 2.9 × 10-8) and rs142450006 near MMP9 (P = 0.0006) with progression to choroidal neovascularization but not geographic atrophy. Secondary analysis limited to 34 reported risk variants revealed that LIPC and CTRB2-CTRB1 were also associated with AMD progression (P < 0.0015). Our genome-wide analysis thus expands the genetics in both development and progression of AMD and should assist in early identification of high risk individuals.