Change in mobility function and its causes in adults with cerebral palsy by Gross Motor Function Classification System level: A cross-sectional questionnaire study.

PubMed

Himuro, Nobuaki; Mishima, Reiko; Seshimo, Takashi; Morishima, Toshibumi; Kosaki, Keisuke; Ibe, Shigeharu; Asagai, Yoshimi; Minematsu, Koji; Kurita, Kazuhiro; Okayasu, Tsutomu; Shimura, Tsukasa; Hoshino, Kotaro; Suzuki, Toshiro; Yanagizono, Taiichiro

2018-04-07

The prognosis for mobility function by Gross Motor Function Classification System (GMFCS) level is vital as a guide to rehabilitation for people with cerebral palsy. This study sought to investigate change in mobility function and its causes in adults with cerebral palsy by GMFCS level. We conducted a cross-sectional questionnaire study. A total of 386 participants (26 y 8 m, SD 5 y 10 m) with cerebral palsy were analyzed. Participant numbers by GMFCS level were: I (53), II (139), III (74) and IV (120). The median age of participants with peak mobility function in GMFCS level III was younger than that in the other levels. 48% had experienced a decline in mobility. A Kaplan-Meier plot showed the risk of mobility decline increased in GMFCS level III; the hazard ratio was 1.97 (95% CI, 1.20-3.23) compared with level I. The frequently reported causes of mobility decline were changes in environment, and illness and injury in GMFCS level III, stiffness and deformity in level IV, and reduced physical activity in level II and III. Peak mobility function and mobility decline occurred at a younger age in GMFCS level III, with the cause of mobility decline differing by GMFCS level.

[Relationship between cognitive function and physical activities: a longitudinal study among community-dwelling elderly].

PubMed

Konagaya, Yoko; Watanabe, Tomoyuki; Ohta, Toshiki

2012-01-01

The purpose of this study was to evaluate whether physical activities reduce the risk of cognitive decline in community-dwelling elderly. We investigated correlations between cognitive functions at baseline and physical activities, correlations between cognitive functions at baseline and cognitive decline over 4 years, as well as correlations between physical activity at baseline and cognitive decline over 4 years. At baseline, 2,431 community-dwelling elderly completed the cognitive screening by telephone (TICS-J), and answered the questionnaires about physical activities. Of these, 1,040 subjects again completed the TICS-J over 4 years. Physical activities contained moving ability, walking frequency, walking speed, the exercise frequency. At baseline, 870 elderly (age 75.87±4.96 (mean±SD) years, duration of education 11.05±2.41) showed normal cognitive functions and 170 (79.19±6.22, 9.61±2.23) showed cognitive impairment. The total TICS-J score was significantly higher in cognitive normal subjects compared with that of cognitive impaired subjects (36.02±1.89, 30.19±2.25, respectively, p<0.001). Logistic regression analyses showed that moving ability significantly reduced the risk of cognitive impairment in an unadjusted model, and walking speed also reduced the risk of cognitive impairment at baseline even in an adjusted model. Cognitive function at baseline might be a predictor of cognitive function over 4 years. The longitudinal study revealed that walking speed and exercise frequency significantly correlate with maintenance of cognitive function over 4 years. This study provides that physical activities, especially walking speed have significant correlation with cognitive function.

The influence of vitamins E and C and exercise on brain aging.

PubMed

Mock, J Thomas; Chaudhari, Kiran; Sidhu, Akram; Sumien, Nathalie

2017-08-01

Age-related declines in motor and cognitive function have been associated with increases in oxidative stress. Accordingly, interventions capable of reducing the oxidative burden would be capable of preventing or reducing functional declines occurring during aging. Popular interventions such as antioxidant intake and moderate exercise are often recommended to attain healthy aging and have the capacity to alter redox burden. This review is intended to summarize the outcomes of antioxidant supplementation (more specifically of vitamins C and E) and exercise training on motor and cognitive declines during aging, and on measures of oxidative stress. Additionally, we will address whether co-implementation of these two types of interventions can potentially further their individual benefits. Together, these studies highlight the importance of using translationally-relevant parameters for interventions and to study their combined outcomes on healthy brain aging. Copyright © 2016 Elsevier Inc. All rights reserved.

Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage

PubMed Central

Caplin, Ben; Boruc, Olga; Bruce-Cobbold, Claire; Cutillas, Pedro; Dormann, Dirk; Faull, Peter; Grossman, Rebecca C.; Khadayate, Sanjay; Mas, Valeria R.; Nitsch, Dorothea D.; Wang, Zhen; Norman, Jill T.; Wilcox, Christopher S.; Wheeler, David C.; Leiper, James

2015-01-01

Nitric oxide (NO) production is diminished in many patients with cardiovascular and renal disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis, and elevated plasma levels of ADMA are associated with poor outcomes. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is a methylarginine-metabolizing enzyme that reduces ADMA levels. We reported previously that a DDAH1 gene variant associated with increased renal DDAH1 mRNA transcription and lower plasma ADMA levels, but counterintuitively, a steeper rate of renal function decline. Here, we test the hypothesis that reduced renal-specific ADMA metabolism protects against progressive renal damage. Renal DDAH1 is expressed predominately within the proximal tubule. A novel proximal tubule–specific Ddah1 knockout (Ddah1PT−/−) mouse demonstrated tubular cell accumulation of ADMA and lower NO concentrations, but unaltered plasma ADMA concentrations. Ddah1PT−/− mice were protected from reduced kidney tissue mass, collagen deposition, and profibrotic cytokine expression in two independent renal injury models: folate nephropathy and unilateral ureteric obstruction. Furthermore, a study of two independent kidney transplant cohorts revealed higher levels of human renal allograft methylarginine-metabolizing enzyme gene expression associated with steeper function decline. We also report an association among DDAH1 expression, NO activity, and uromodulin expression supported by data from both animal and human studies, raising the possibility that kidney DDAH1 expression exacerbates renal injury through uromodulin-related mechanisms. Together, these data demonstrate that reduced renal tubular ADMA metabolism protects against progressive kidney function decline. Thus, circulating ADMA may be an imprecise marker of renal methylarginine metabolism, and therapeutic ADMA reduction may even be deleterious to kidney function. PMID:25855779

Kyphosis and Decline in Physical Function Over 15 Years in Older Community-Dwelling Women: The Study of Osteoporotic Fractures

PubMed Central

2013-01-01

Background Maintaining physical function is an important prerequisite for preserving independence in later life. Greater degrees of kyphosis in the thoracic spine are prevalent in older persons and accompanied by reduced physical function in multiple cross-sectional studies. It is unknown whether kyphosis predicts worse physical function over time. Methods. We retrospectively assessed whether greater magnitude of kyphosis is associated with decline in self-reported and objectively measured physical function over 15 years. Digitized Cobb angle kyphosis (T4–T12) was derived from supine lateral thoracic spine radiographs in a cohort of 1,196 women aged 65 and older (mean = 69.3 years [SD = 4.0]). Using regression models, we evaluated associations of baseline kyphosis with both self-reported functional status and objectively measured gait speed, grip strength, and timed chair stands cross-sectionally and as change assessed over 15 years. Results. In cross-sectional multivariate analyses, with each 10-degree increment of kyphosis, grip strength was 0.24kg lower (p = .02), but there were no significant associations between kyphosis and functional status, gait speed, or timed chair stand, likely reflecting the high functioning study participants. In multivariate longitudinal analysis, with each 10-degree increment in baseline kyphosis, there was 0.07 point additional decline in functional status (p = .09), 0.01 m/s more decline in gait speed (p = .07), and 0.32 s greater decline in time to complete five chair stands (p = .004), but no association with decline in grip strength. Conclusions. Greater magnitude of kyphosis may predict worsening lower extremity function over time in older women. Early recognition and preventative measures against kyphosis progression may help preserve physical function over the long term. PMID:23633167

Kyphosis and decline in physical function over 15 years in older community-dwelling women: the Study of Osteoporotic Fractures.

PubMed

Katzman, Wendy B; Huang, Mei-Hua; Lane, Nancy E; Ensrud, Kristine E; Kado, Deborah M

2013-08-01

Maintaining physical function is an important prerequisite for preserving independence in later life. Greater degrees of kyphosis in the thoracic spine are prevalent in older persons and accompanied by reduced physical function in multiple cross-sectional studies. It is unknown whether kyphosis predicts worse physical function over time. We retrospectively assessed whether greater magnitude of kyphosis is associated with decline in self-reported and objectively measured physical function over 15 years. Digitized Cobb angle kyphosis (T4-T12) was derived from supine lateral thoracic spine radiographs in a cohort of 1,196 women aged 65 and older (mean = 69.3 years [SD = 4.0]). Using regression models, we evaluated associations of baseline kyphosis with both self-reported functional status and objectively measured gait speed, grip strength, and timed chair stands cross-sectionally and as change assessed over 15 years. In cross-sectional multivariate analyses, with each 10-degree increment of kyphosis, grip strength was 0.24 kg lower (p = .02), but there were no significant associations between kyphosis and functional status, gait speed, or timed chair stand, likely reflecting the high functioning study participants. In multivariate longitudinal analysis, with each 10-degree increment in baseline kyphosis, there was 0.07 point additional decline in functional status (p = .09), 0.01 m/s more decline in gait speed (p = .07), and 0.32 s greater decline in time to complete five chair stands (p = .004), but no association with decline in grip strength. Greater magnitude of kyphosis may predict worsening lower extremity function over time in older women. Early recognition and preventative measures against kyphosis progression may help preserve physical function over the long term.

Neural and behavioural changes in male periadolescent mice after prolonged nicotine-MDMA treatment.

PubMed

Adeniyi, Philip A; Ishola, Azeez O; Laoye, Babafemi J; Olatunji, Babawale P; Bankole, Oluwamolakun O; Shallie, Philemon D; Ogundele, Olalekan M

2016-02-01

The interaction between MDMA and Nicotine affects multiple brain centres and neurotransmitter systems (serotonin, dopamine and glutamate) involved in motor coordination and cognition. In this study, we have elucidated the effect of prolonged (10 days) MDMA, Nicotine and a combined Nicotine-MDMA treatment on motor-cognitive neural functions. In addition, we have shown the correlation between the observed behavioural change and neural structural changes induced by these treatments in BALB/c mice. We observed that MDMA (2 mg/Kg body weight; subcutaneous) induced a decline in motor function, while Nicotine (2 mg/Kg body weight; subcutaneous) improved motor function in male periadolescent mice. In combined treatment, Nicotine reduced the motor function decline observed in MDMA treatment, thus no significant change in motor function for the combined treatment versus the control. Nicotine or MDMA treatment reduced memory function and altered hippocampal structure. Similarly, a combined Nicotine-MDMA treatment reduced memory function when compared with the control. Ultimately, the metabolic and structural changes in these neural systems were seen to vary for the various forms of treatment. It is noteworthy to mention that a combined treatment increased the rate of lipid peroxidation in brain tissue.

Working memory overload: fronto-limbic interactions and effects on subsequent working memory function.

PubMed

Yun, Richard J; Krystal, John H; Mathalon, Daniel H

2010-03-01

The human working memory system provides an experimentally useful model for examination of neural overload effects on subsequent functioning of the overloaded system. This study employed functional magnetic resonance imaging in conjunction with a parametric working memory task to characterize the behavioral and neural effects of cognitive overload on subsequent cognitive performance, with particular attention to cognitive-limbic interactions. Overloading the working memory system was associated with varying degrees of subsequent decline in performance accuracy and reduced activation of brain regions central to both task performance and suppression of negative affect. The degree of performance decline was independently predicted by three separate factors operating during the overload condition: the degree of task failure, the degree of amygdala activation, and the degree of inverse coupling between the amygdala and dorsolateral prefrontal cortex. These findings suggest that vulnerability to overload effects in cognitive functioning may be mediated by reduced amygdala suppression and subsequent amygdala-prefrontal interaction.

Serum Micronutrient Concentrations and Decline in Physical Function Among Older Persons

PubMed Central

Bartali, Benedetta; Frongillo, Edward A.; Guralnik, Jack M.; Stipanuk, Martha H.; Allore, Heather G.; Cherubini, Antonio; Bandinelli, Stefania; Ferrucci, Luigi; Gill, Thomas M.

2009-01-01

Context Maintaining independence of older persons is a public health priority, and identifying the factors that contribute to decline in physical function is needed to prevent or postpone the disablement process. The potential deleterious effect of poor nutrition on decline in physical function in older persons is unclear. Objective To determine whether a low serum concentration of micronutrients is associated with subsequent decline in physical function among older men and women living in the community. Design, Setting, and Participants Longitudinal study of 698 community-living persons 65 years or older who were randomly selected from a population registry in Tuscany, Italy. Participants completed the baseline examination from November 1, 1998, through May 28, 2000, and the 3-year follow-up assessments from November 1, 2001, through March 30, 2003. Main Outcome Measure Decline in physical function was defined as a loss of at least 1 point in the Short Physical Performance Battery during the 3-year follow-up. Odds ratios (ORs) were calculated for the lowest quartile of each nutrient using the other 3 quartiles combined as the reference group. Two additional and complementary analytical approaches were used to confirm the validity of the results. Results The mean decline in the Short Physical Performance Battery score was 1.1 point. In a logistic regression analysis that was adjusted for potential confounders, only a low concentration of vitamin E (<1.1 μg/mL [<24.9 μmol/L]) was significantly associated with subsequent decline in physical function (OR, 1.62; 95% confidence interval, 1.11-2.36; P=.01 for association of lowest α-tocopherol quartile with at least a 1-point decline in physical function). In a general linear model, the concentration of vitamin E at baseline, when analyzed as a continuous measure, was significantly associated with the Short Physical Performance Battery score at follow-up after adjustment for potential confounders and Short Physical Performance Battery score at baseline (β=.023; P=.01). In a classification and regression tree analysis, age older than 81 years and vitamin E (in participants aged 70-80 years) were identified as the strongest determinants of decline in physical function (physical decline in 84% and 60%, respectively; misclassification error rate, 0.33). Conclusions These results provide empirical evidence that a low serum concentration of vitamin E is associated with subsequent decline in physical function among community-living older adults. Clinical trials may be warranted to determine whether an optimal concentration of vitamin E reduces functional decline and the onset of disability in older persons. PMID:18212315

Predicting cognitive function from clinical measures of physical function and health status in older adults.

PubMed

Bolandzadeh, Niousha; Kording, Konrad; Salowitz, Nicole; Davis, Jennifer C; Hsu, Liang; Chan, Alison; Sharma, Devika; Blohm, Gunnar; Liu-Ambrose, Teresa

2015-01-01

Current research suggests that the neuropathology of dementia-including brain changes leading to memory impairment and cognitive decline-is evident years before the onset of this disease. Older adults with cognitive decline have reduced functional independence and quality of life, and are at greater risk for developing dementia. Therefore, identifying biomarkers that can be easily assessed within the clinical setting and predict cognitive decline is important. Early recognition of cognitive decline could promote timely implementation of preventive strategies. We included 89 community-dwelling adults aged 70 years and older in our study, and collected 32 measures of physical function, health status and cognitive function at baseline. We utilized an L1-L2 regularized regression model (elastic net) to identify which of the 32 baseline measures were strongly predictive of cognitive function after one year. We built three linear regression models: 1) based on baseline cognitive function, 2) based on variables consistently selected in every cross-validation loop, and 3) a full model based on all the 32 variables. Each of these models was carefully tested with nested cross-validation. Our model with the six variables consistently selected in every cross-validation loop had a mean squared prediction error of 7.47. This number was smaller than that of the full model (115.33) and the model with baseline cognitive function (7.98). Our model explained 47% of the variance in cognitive function after one year. We built a parsimonious model based on a selected set of six physical function and health status measures strongly predictive of cognitive function after one year. In addition to reducing the complexity of the model without changing the model significantly, our model with the top variables improved the mean prediction error and R-squared. These six physical function and health status measures can be easily implemented in a clinical setting.

The Impact of a Participatory Care Model on Work Satisfaction of Care Workers and the Functionality, Connectedness, and Mental Health of Community-Dwelling Older People.

PubMed

Bernoth, Maree; Burmeister, Oliver K; Morrison, Mark; Islam, Md Zahidul; Onslow, Fiona; Cleary, Michelle

2016-06-01

This study describes and evaluates an innovative program designed to reduce functional decline among seniors, using a participatory care approach and integrated health teams. The evaluation provides older people and community support workers (CSWs) with the opportunity to share their experiences of being involved with an innovative program to reduce functional decline (mobility, skin integrity, nutrition, mental health, continence) of older, community dwelling adults implemented by a Nursing Service in a major capital city in Australia. As part of the program, CSWs were trained to provide care that aimed to reduce functional decline, and improve the quality of life for the care recipients. Data were collected through in-depth interviews with older people receiving care and a focus group (FG) was conducted with CSWs. Seven themes emerged during data analysis: 1) functionality/independence; 2) prevention; 3) confidence; 4) connection; 5) the approach; 6) care plans; and 7) the role of the CSWs. The relationship built between care giver and receiver and the mutual respect facilitated through adopting a participatory care approach was crucial. This relationship-focused care contributed to improved functionality and consequently quality of life for the older person, and for the CSW professional it contributed to their development, improved satisfaction with their role, and increased pride in the difference they make in the lives of their clients. Opportunities for improvement of the program included ensuring that participants understood the rationale for all aspects of the program, including regular reminders, as well as the use of regular reviews of individual outcomes.

Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage.

PubMed

Tomlinson, James A P; Caplin, Ben; Boruc, Olga; Bruce-Cobbold, Claire; Cutillas, Pedro; Dormann, Dirk; Faull, Peter; Grossman, Rebecca C; Khadayate, Sanjay; Mas, Valeria R; Nitsch, Dorothea D; Wang, Zhen; Norman, Jill T; Wilcox, Christopher S; Wheeler, David C; Leiper, James

2015-12-01

Nitric oxide (NO) production is diminished in many patients with cardiovascular and renal disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis, and elevated plasma levels of ADMA are associated with poor outcomes. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is a methylarginine-metabolizing enzyme that reduces ADMA levels. We reported previously that a DDAH1 gene variant associated with increased renal DDAH1 mRNA transcription and lower plasma ADMA levels, but counterintuitively, a steeper rate of renal function decline. Here, we test the hypothesis that reduced renal-specific ADMA metabolism protects against progressive renal damage. Renal DDAH1 is expressed predominately within the proximal tubule. A novel proximal tubule-specific Ddah1 knockout (Ddah1(PT-/-)) mouse demonstrated tubular cell accumulation of ADMA and lower NO concentrations, but unaltered plasma ADMA concentrations. Ddah1(PT-/-) mice were protected from reduced kidney tissue mass, collagen deposition, and profibrotic cytokine expression in two independent renal injury models: folate nephropathy and unilateral ureteric obstruction. Furthermore, a study of two independent kidney transplant cohorts revealed higher levels of human renal allograft methylarginine-metabolizing enzyme gene expression associated with steeper function decline. We also report an association among DDAH1 expression, NO activity, and uromodulin expression supported by data from both animal and human studies, raising the possibility that kidney DDAH1 expression exacerbates renal injury through uromodulin-related mechanisms. Together, these data demonstrate that reduced renal tubular ADMA metabolism protects against progressive kidney function decline. Thus, circulating ADMA may be an imprecise marker of renal methylarginine metabolism, and therapeutic ADMA reduction may even be deleterious to kidney function. Copyright © 2015 by the American Society of Nephrology.

The natural history of cardiac and pulmonary function decline in patients with duchenne muscular dystrophy.

PubMed

Roberto, Rolando; Fritz, Anto; Hagar, Yolanda; Boice, Braden; Skalsky, Andrew; Hwang, Hosun; Beckett, Laurel; McDonald, Craig; Gupta, Munish

2011-07-01

Retrospective review of scoliosis progression, pulmonary and cardiac function in a series of patients with Duchenne Muscular Dystrophy (DMD). To determine whether operative treatment of scoliosis decreases the rate of pulmonary function loss in patients with DMD. It is generally accepted that surgical intervention should be undertaken in DMD scoliosis once curve sizes reach 35° to allow intervention before critical respiratory decline has occurred. There are conflicting reports, however, regarding the effect of scoliosis stabilization on the rate of pulmonary function decline when compared to nonoperative cohorts. We reviewed spinal radiographs, echocardiograms, and spirometry, hospital, and operative records of all patients seen at our tertiary referral center from July 1, 1992 to June 1, 2007. Data were recorded to Microsoft Excel (Microsoft, Redmond, WA) and analyzed with SAS (SAS Institute, Cary, NC) and R statistical processing software (www.r-project.org). The percent predicted forced vital capacity (PPFVC) decreased 5% per year before operation. The mean PPFVC was 54% (SD = 21%) before operation with a mean postoperative PPFVC of 43% (SD = 14%). Surgical treatment was associated with a 12% decline in PPFVC independent of other treatment variables. PPFVC after operation declined at a rate of 1% per year and while this rate was lower, it was not significantly different than the rate of decline present before operation (P = 0.18). Cardiac function as measured by left ventricular fractional shortening declined at a rate of 1% per year with most individuals exhibiting a left ventricular fractional shortening rate of more than 30 before operation. Operative treatment of scoliosis in DMD using the Luque Galveston method was associated with a reduction of forced vital capacity related to operation. The rate of pulmonary function decline after operation was not significantly reduced when compared with the rate of preoperative forced vital capacity decline.

Pretreatment rate of decay in forced vital capacity predicts long-term response to pirfenidone in patients with idiopathic pulmonary fibrosis.

PubMed

Biondini, Davide; Balestro, Elisabetta; Lacedonia, Donato; Cerri, Stefania; Milaneschi, Rosanna; Luppi, Fabrizio; Cocconcelli, Elisabetta; Bazzan, Erica; Clini, Enrico; Foschino Barbaro, Maria Pia; Gregori, Dario; Cosio, Manuel G; Saetta, Marina; Spagnolo, Paolo

2018-04-13

Pirfenidone reduces functional decline in patients with Idiopathic Pulmonary Fibrosis (IPF). However, response to treatment is highly heterogeneous. We sought to evaluate whether response to pirfenidone is influenced by the pretreatment rate of forced vital capacity (FVC) decline. Fifty-six IPF patients were categorized as rapid (RP) or slow progressors (SP) based on whether their FVC decline in the year preceding pirfenidone treatment was > or ≤ 10% predicted. Following pirfenidone treatment patients were followed-up every 6 months and up to 24 months. In the entire population, pirfenidone reduced significantly FVC decline from 231 to 49 ml/year at 6 months (T6) (p = 0.003) and this effect was maintained at the 12-, 18- and 24-month time points (p value for trend n.s.). In RP, the reduction of FVC decline was evident at 6 months (36 vs 706 ml/year pretreatment; p = 0.002) and maintained, though to a lesser degree, at 12 (106 ml/year), 18 (176 ml/year) and 24 months (162 ml/year; p value for trend n.s). Among SP, the reduction in FVC decline was not significant at any of the time points analyzed. In conclusion, pirfenidone reduces FVC decline in IPF patients. However, its beneficial effect is more pronounced in patients with rapidly progressive disease.

Low health literacy predicts decline in physical function among older adults: findings from the LitCog cohort study

PubMed Central

Smith, Samuel G; O'Conor, Rachel; Curtis, Laura M; Waite, Katie; Deary, Ian J; Paasche-Orlow, Michael; Wolf, Michael S

2015-01-01

Background Limited health literacy is associated with worse physical function in cross-sectional studies. We aimed to determine if health literacy is a risk factor for decline in physical function among older adults. Methods A longitudinal cohort of 529 community-dwelling American adults aged 55–74 years were recruited from an academic general internal medicine clinic and federally qualified health centres in 2008–2011. Health literacy (Newest Vital Sign), age, gender, race, education, chronic conditions, body mass index, alcohol consumption, smoking status and exercise frequency were included in multivariable analyses. The 10-item PROMIS (Patient-Reported Outcomes Measurement Information System) physical function scale was assessed at baseline and follow-up (mean=3.2 years, SD=0.39). Results Nearly half of the sample (48.2%) had either marginal (25.5%) or low health literacy (22.7%). Average physical function at baseline was 83.2 (SD=16.6) of 100, and health literacy was associated with poorer baseline physical function in multivariable analysis (p=0.004). At follow-up, physical function declined to 81.9 (SD=17.3; p=0.006) and 20.5% experienced a meaningful decline (>0.5 SD of baseline score). In multivariable analyses, participants with marginal (OR 2.62; 95%CI 1.38 to 4.95; p=0.003) and low (OR 2.57; 95%CI 1.22 to 5.44; p=0.013) health literacy were more likely to experience meaningful decline in physical function than the adequate health literacy group. Entering cognitive abilities to these models did not substantially attenuate effect sizes. Health literacy attenuated the relationship between black race and decline in physical function by 32.6%. Conclusions Lower health literacy increases the risk of exhibiting faster physical decline over time among older adults. Strategies that reduce literacy disparities should be designed and evaluated. PMID:25573701

DNA-PK Promotes the Mitochondrial, Metabolic, and Physical Decline that Occurs During Aging.

PubMed

Park, Sung-Jun; Gavrilova, Oksana; Brown, Alexandra L; Soto, Jamie E; Bremner, Shannon; Kim, Jeonghan; Xu, Xihui; Yang, Shutong; Um, Jee-Hyun; Koch, Lauren G; Britton, Steven L; Lieber, Richard L; Philp, Andrew; Baar, Keith; Kohama, Steven G; Abel, E Dale; Kim, Myung K; Chung, Jay H

2017-05-02

Hallmarks of aging that negatively impact health include weight gain and reduced physical fitness, which can increase insulin resistance and risk for many diseases, including type 2 diabetes. The underlying mechanism(s) for these phenomena is poorly understood. Here we report that aging increases DNA breaks and activates DNA-dependent protein kinase (DNA-PK) in skeletal muscle, which suppresses mitochondrial function, energy metabolism, and physical fitness. DNA-PK phosphorylates threonines 5 and 7 of HSP90α, decreasing its chaperone function for clients such as AMP-activated protein kinase (AMPK), which is critical for mitochondrial biogenesis and energy metabolism. Decreasing DNA-PK activity increases AMPK activity and prevents weight gain, decline of mitochondrial function, and decline of physical fitness in middle-aged mice and protects against type 2 diabetes. In conclusion, DNA-PK is one of the drivers of the metabolic and fitness decline during aging, and therefore DNA-PK inhibitors may have therapeutic potential in obesity and low exercise capacity. Published by Elsevier Inc.

Longitudinal decline in speech production in Parkinson's disease spectrum disorders.

PubMed

Ash, Sharon; Jester, Charles; York, Collin; Kofman, Olga L; Langey, Rachel; Halpin, Amy; Firn, Kim; Dominguez Perez, Sophia; Chahine, Lama; Spindler, Meredith; Dahodwala, Nabila; Irwin, David J; McMillan, Corey; Weintraub, Daniel; Grossman, Murray

2017-08-01

We examined narrative speech production longitudinally in non-demented (n=15) and mildly demented (n=8) patients with Parkinson's disease spectrum disorder (PDSD), and we related increasing impairment to structural brain changes in specific language and motor regions. Patients provided semi-structured speech samples, describing a standardized picture at two time points (mean±SD interval=38±24months). The recorded speech samples were analyzed for fluency, grammar, and informativeness. PDSD patients with dementia exhibited significant decline in their speech, unrelated to changes in overall cognitive or motor functioning. Regression analysis in a subset of patients with MRI scans (n=11) revealed that impaired language performance at Time 2 was associated with reduced gray matter (GM) volume at Time 1 in regions of interest important for language functioning but not with reduced GM volume in motor brain areas. These results dissociate language and motor systems and highlight the importance of non-motor brain regions for declining language in PDSD. Copyright © 2017 Elsevier Inc. All rights reserved.

A Larger Social Network Enhances Novel Object Location Memory and Reduces Hippocampal Microgliosis in Aged Mice.

PubMed

Smith, Bryon M; Yao, Xinyue; Chen, Kelly S; Kirby, Elizabeth D

2018-01-01

The mammalian hippocampus shows marked decline in function with aging across many species, including humans and laboratory rodent models. This decline frequently manifests in memory impairments that occur even in the absence of dementia pathology. In humans, a number of factors correlate with preserved hippocampal memory in aging, such as exercise, cognitive stimulation and number of social ties. While interventional studies and animal models clearly indicate that exercise and cognitive stimulation lead to hippocampal preservation, there is relatively little research on whether a decline in social ties leads to cognitive decline or vice versa. Even in animal studies of environmental enrichment in aging, the focus typically falls on physical enrichment such as a rotating cast of toys, rather than the role of social interactions. The present studies investigated the hypothesis that a greater number of social ties in aging mice would lead to improved hippocampal function. Aged, female C57/Bl6 mice were housed for 3 months in pairs or large groups (7 mice per cage). Group-housed mice showed greater novel object location memory and stronger preference for a spatial navigation strategy in the Barnes maze, though no difference in escape latency, compared to pair-housed mice. Group-housed mice did not differ from pair-housed mice in basal corticosterone levels or adult hippocampal neurogenesis. Group-housed mice did, however, show reduced numbers of Iba1/CD68+ microglia in the hippocampus. These findings suggest that group housing led to better memory function and reduced markers of neuroinflammation in aged mice. More broadly, they support a causative link between social ties and hippocampal function, suggesting that merely having a larger social network can positively influence the aging brain. Future research should address the molecular mechanisms by which a greater number of social ties alters hippocampal function.

A Larger Social Network Enhances Novel Object Location Memory and Reduces Hippocampal Microgliosis in Aged Mice

PubMed Central

Smith, Bryon M.; Yao, Xinyue; Chen, Kelly S.; Kirby, Elizabeth D.

2018-01-01

The mammalian hippocampus shows marked decline in function with aging across many species, including humans and laboratory rodent models. This decline frequently manifests in memory impairments that occur even in the absence of dementia pathology. In humans, a number of factors correlate with preserved hippocampal memory in aging, such as exercise, cognitive stimulation and number of social ties. While interventional studies and animal models clearly indicate that exercise and cognitive stimulation lead to hippocampal preservation, there is relatively little research on whether a decline in social ties leads to cognitive decline or vice versa. Even in animal studies of environmental enrichment in aging, the focus typically falls on physical enrichment such as a rotating cast of toys, rather than the role of social interactions. The present studies investigated the hypothesis that a greater number of social ties in aging mice would lead to improved hippocampal function. Aged, female C57/Bl6 mice were housed for 3 months in pairs or large groups (7 mice per cage). Group-housed mice showed greater novel object location memory and stronger preference for a spatial navigation strategy in the Barnes maze, though no difference in escape latency, compared to pair-housed mice. Group-housed mice did not differ from pair-housed mice in basal corticosterone levels or adult hippocampal neurogenesis. Group-housed mice did, however, show reduced numbers of Iba1/CD68+ microglia in the hippocampus. These findings suggest that group housing led to better memory function and reduced markers of neuroinflammation in aged mice. More broadly, they support a causative link between social ties and hippocampal function, suggesting that merely having a larger social network can positively influence the aging brain. Future research should address the molecular mechanisms by which a greater number of social ties alters hippocampal function. PMID:29904345

Physical Exercise-Induced Adult Neurogenesis: A Good Strategy to Prevent Cognitive Decline in Neurodegenerative Diseases?

PubMed Central

Yau, Suk-yu; Christie, Brian R.; So, Kwok-fai

2014-01-01

Cumulative evidence has indicated that there is an important role for adult hippocampal neurogenesis in cognitive function. With the increasing prevalence of cognitive decline associated with neurodegenerative diseases among the ageing population, physical exercise, a potent enhancer of adult hippocampal neurogenesis, has emerged as a potential preventative strategy/treatment to reduce cognitive decline. Here we review the functional role of adult hippocampal neurogenesis in learning and memory, and how this form of structural plasticity is altered in neurodegenerative diseases known to involve cognitive impairment. We further discuss how physical exercise may contribute to cognitive improvement in the ageing brain by preserving adult neurogenesis, and review the recent approaches for measuring changes in neurogenesis in the live human brain. PMID:24818140

Clinically important FEV1 declines among coal miners: an exploration of previously unrecognised determinants

PubMed Central

Wang, M. L.; Petsonk, E. L.; Beeckman, L. A.; Wagner, G. R.

1999-01-01

OBJECTIVES: The relation between occupational exposure to dust and loss of ventilatory lung function is now well established. However, many exposures during work and other activities might also have important roles in determining clinically important losses of lung function. In this study, we attempted to explore additional plausible determinants of exposures and other potential risk factors for clinically important decline in forced expiratory volume in 1 second (FEV1) during work in dusty trades. METHODS: The study was performed in 264 underground coal miners whose lung function had been followed up for an average of 11 years. With an extensive follow up questionnaire, miners were asked about their occupational and non-occupational exposures, smoking, personal and family medical history, and living conditions during childhood. RESULTS: Several variables of the mine environment (as well as previously recognised effects of mining work and region) were found to be associated with excess decline in FEV1, including work in roof bolting, exposure to explosive blasting, and to control dust spraying water that had been stored in holding tanks. Use of respiratory protection seemed to reduce the risk of decline in FEV1. Other factors that were found to be associated with declines in pulmonary function included smoking, body mass, weight gain, childhood pneumonia, and childhood exposure in the home to passive tobacco smoke and possibly smoke due to wood and coal fuels. Miners with excessive decline in FEV1 were less likely to be working in mining jobs at follow up. CONCLUSIONS: These findings suggest the existence of additional risk factors for decline in lung function in dusty trades, and may be useful in developing additional approaches to the prevention of chronic respiratory disease.   PMID:10658541

ACETOGENIC AND SULPHATE-REDUCING BACTERIA INHABITING THE RHIZOPLANE AND DEEP CORTEX CELLS OF THE SEAGRASS HALODULE WRIGHTII

EPA Science Inventory

Recent declines in sea grass distribution underscore the importance of understanding microbial community structure-function relationships in sea grass rhizosphere that might affect the viability of these plants. Phospholipid fatty acid analyses showed that sulfate-reducing bacter...

Short-term memory deficits correlate with hippocampal-thalamic functional connectivity alterations following acute sleep restriction.

PubMed

Chengyang, Li; Daqing, Huang; Jianlin, Qi; Haisheng, Chang; Qingqing, Meng; Jin, Wang; Jiajia, Liu; Enmao, Ye; Yongcong, Shao; Xi, Zhang

2017-08-01

Acute sleep restriction heavily influences cognitive function, affecting executive processes such as attention, response inhibition, and memory. Previous neuroimaging studies have suggested a link between hippocampal activity and short-term memory function. However, the specific contribution of the hippocampus to the decline of short-term memory following sleep restriction has yet to be established. In the current study, we utilized resting-state functional magnetic resonance imaging (fMRI) to examine the association between hippocampal functional connectivity (FC) and the decline of short-term memory following total sleep deprivation (TSD). Twenty healthy adult males aged 20.9 ± 2.3 years (age range, 18-24 years) were enrolled in a within-subject crossover study. Short-term memory and FC were assessed using a Delay-matching short-term memory test and a resting-state fMRI scan before and after TSD. Seed-based correlation analysis was performed using fMRI data for the left and right hippocampus to identify differences in hippocampal FC following TSD. Subjects demonstrated reduced alertness and a decline in short-term memory performance following TSD. Moreover, fMRI analysis identified reduced hippocampal FC with the superior frontal gyrus (SFG), temporal regions, and supplementary motor area. In addition, an increase in FC between the hippocampus and bilateral thalamus was observed, the extent of which correlated with short-term memory performance following TSD. Our findings indicate that the disruption of hippocampal-cortical connectivity is linked to the decline in short-term memory observed after acute sleep restriction. Such results provide further evidence that support the cognitive impairment model of sleep deprivation.

Cognitive Decline and Its Risk Factors in Prevalent Hemodialysis Patients.

PubMed

Drew, David A; Weiner, Daniel E; Tighiouart, Hocine; Duncan, Sarah; Gupta, Aditi; Scott, Tammy; Sarnak, Mark J

2017-06-01

Cognitive impairment is common in patients treated with hemodialysis. The trajectory of cognitive function and risk factors for cognitive decline remain uncertain in this population. Longitudinal cohort. 314 prevalent hemodialysis patients. Age, sex, race, education level, hemodialysis vintage, cause of end-stage renal disease, and baseline history of cardiovascular disease. Cognitive function as determined by a comprehensive neurocognitive battery, administered at baseline and yearly when possible. Individual cognitive test results were reduced into 2 domain scores using principal components analysis, representing memory and executive function, which were used as our coprimary outcomes and by definition have a mean of zero and SD of 1. Mean age was 63 years; 54% were men, 22% were black, and 90% had at least a high school education. During a median follow-up of 2.1 (IQR, 0.9-4.2) years, 196 had at least 1 follow-up test, 156 died, and 43 received a kidney transplant. Linear mixed models and joint models, which accounted for competing risks from death, dropout, or kidney transplantation, showed nearly identical results. The joint model demonstrated a decline in executive function (-0.09 [95% CI, -0.13 to -0.05] SD per year), whereas memory improved slightly (0.05 [95% CI, 0.02 to 0.08] SD per year). A significant yearly decline was also seen in the Mini-Mental State Examination score (median change, -0.41; 95% CI, -0.57 to -0.25). Older age was the only significant risk factor for steeper executive function decline (-0.04 [95% CI, -0.06 to -0.02] SD steeper annual decline for each 10 years of age). Prevalent hemodialysis patients only, limited follow-up testing due to high mortality rate, and exclusion of participants with severe cognitive deficits or dementia. Prevalent hemodialysis patients demonstrate significant cognitive decline, particularly within tests of executive function. Older age was the only statistically significant risk factor for steeper cognitive decline, which may have important clinical consequences for patient management and education. Future studies should evaluate strategies to maintain or improve cognitive function. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

The beneficial role of anti-inflammatory dietary ingredients in attenuating markers of chronic low-grade inflammation in aging.

PubMed

Panickar, Kiran S; Jewell, Dennis E

2015-08-01

Aging in humans is associated with chronic low-grade inflammation (systemic), and this condition is sometimes referred to as "inflammaging". In general, canines also age similarly to humans, and such aging is associated with a decline in mobility, joint problems, weakened muscles and bones, reduced lean body mass, cancer, increased dermatological problems, decline in cognitive ability, reduced energy, decreased immune function, decreased renal function, and urinary incontinence. Each of these conditions is also associated with an increase in pro-inflammatory cytokines. An inflammatory state characterized by an increase in pro-inflammatory markers including but not restricted to tumor necrosis factor-α, interleukin-6, IL-1β, and C-reactive protein (CRP) is believed to contribute to or worsen a general decline in biological mechanisms responsible for physical function with aging. Nutritional management of inflammation in aging dogs is important in maintaining health. In particular, natural botanicals have bioactive components that appear to have robust anti-inflammatory effects and, when included in the diet, may contribute to a reduction in inflammation. While there are scientific data to support the anti-inflammatory effects and the efficacy of such bioactive molecules from botanicals, the clinical data are limited and more studies are needed to validate the efficacy of these ingredients. This review will summarize the role of dietary ingredients in reducing inflammatory molecules as well as review the evidence available to support the role of diet and nutrition in reducing chronic low-grade systemic inflammation in animal and human studies with a special reference to canines, where possible.

Life-long calorie restriction in Fischer 344 rats attenuates age-related loss in skeletal muscle-specific force and reduces extracellular space.

PubMed

Payne, Anthony M; Dodd, Stephen L; Leeuwenburgh, Christiaan

2003-12-01

The decline in muscle function is associated with an age-related decrease in muscle mass and an age-related decline in strength. However, decreased strength is not solely due to decreased muscle mass. The age-related decline in muscle-specific force (force/muscle cross-sectional area), a measure of intrinsic muscle function, also contributes to age-related strength decline, and the mechanisms by which this occurs are only partially known. Moreover, changes in the extracellular space could have a profound effect on skeletal muscle function. Life-long calorie restriction in rodents has shown to be a powerful anti-aging intervention. In this study, we examine whether calorie restriction is able to attenuate the loss of muscle function and elevations in extracellular space associated with aging. We hypothesize that calorie restriction attenuates the age-associated decline in specific force and increases in extracellular space. Measurements of in vitro contractile properties of the extensor digitorum longus (type II) and soleus (type I) muscles from 12-mo and 26- to 28-mo-old ad libitum-fed, as well as 27- to 28-mo-old life-long calorie-restricted male Fischer 344 rats, were performed. We found that calorie restriction attenuated the age-associated decline in muscle mass-to-body mass ratio (mg/g) and strength-to-body mass ratio (N/kg) in the extensor digitorum longus muscle (P < 0.05) but not in the soleus muscle (P > 0.05). Importantly, muscle-specific force (N/cm2) in the extensor digitorum longus, but not in the soleus muscle, of the old calorie-restricted rats was equal to that of the young 12-mo-old animals. Moreover, the age-associated increase in extracellular space was reduced in the fast-twitch extensor digitorum longus muscle (P < 0.05) but not in the soleus muscle with calorie restriction. We also found a significant correlation between the extracellular space and the muscle-specific force in the extensor digitorum longus (r = -0.58; P < 0.05) but not in the soleus muscle (r = -0.38; P > 0.05). Hence, this study shows a loss of muscle function with age and suggests that long-term calorie restriction is an effective intervention against the loss of muscle function with age.

Effects of grain dust on lungs prior to and following dust remediation.

PubMed

Pahwa, Punam; Dosman, James A; McDuffie, Helen H

2008-12-01

To determine longitudinal estimates of pulmonary function decline in Canadian grain elevator workers before and after dust control by analyzing data collected from five regions of Canada over 15 years. Declines in forced expired volume in one second and forced vital capacity before and after dust control were estimated by using a generalized estimating equations approach. For grain workers who were in the grain industry for 20 or more years both before and after dust control: the mean annual loss of forced expired volume in one second was greatest among current smoking grain workers followed by ex-smokers and nonsmokers, respectively. Similar results were obtained for forced vital capacity. Grain dust control was effective in reducing decline in the lung function measurements among grain workers in all smoking and exposure categories.

Dietary strawberry improves cognition in older adults: a randomized, double-blind, placebo-controlled study

USDA-ARS?s Scientific Manuscript database

Older adults experience a variety of functional changes that decrease their quality of life with age-related cognitive decline and reduced mobility being of particular concern. Pre-clinical research indicates that berry fruit offer a promising dietary approach to preserving nervous system function, ...

Optimizing management of chronic obstructive pulmonary disease in the upcoming decade.

PubMed

Russell, Richard; Anzueto, Antonio; Weisman, Idelle

2011-01-10

Chronic obstructive pulmonary disease (COPD) is a leading cause of disability and mortality. Caring for patients with COPD, particularly those with advanced disease who experience frequent exacerbations, places a significant burden on health care budgets, and there is a global need to reduce the financial and personal burden of COPD. Evolving scientific evidence on the natural history and clinical course of COPD has fuelled a fundamental shift in our approach to the disease. The emergence of data highlighting the heterogeneity in rate of lung function decline has altered our perception of disease progression in COPD and our understanding of appropriate strategies for the management of stable disease. These data have demonstrated that early, effective, and prolonged bronchodilation has the potential to slow the rate of decline in lung function and to reduce the frequency of exacerbations that contribute to functional decline. The goals of therapy for COPD are no longer confined to controlling symptoms, reducing exacerbations, and maintaining quality of life, and slowing disease progression is now becoming an achievable aim. A challenge for the future will be to capitalize on these observations by improving the identification and diagnosis of patients with COPD early in the course of their disease, so that effective interventions can be introduced before the more advanced, disabling, and costly stages of the disease. Here we critically review emerging data that underpin the advances in our understanding of the clinical course and management of COPD, and evaluate both current and emerging pharmacologic options for effective maintenance treatment.

Nicotinamide Forestalls Pathology and Cognitive Decline in Alzheimer Mice: Evidence for Improved Neuronal Bioenergetics and Autophagy Procession

PubMed Central

Liu, Dong; Pitta, Michael; Jiang, Haiyang; Lee, Jong-Hwan; Zhang, Guofeng; Chen, Xinzhi; Kawamoto, Elisa M.; Mattson, Mark P.

2012-01-01

Impaired brain energy metabolism and oxidative stress are implicated in cognitive decline and the pathological accumulations of amyloid β-peptide (Aβ) and hyperphosphorylated Tau (p-Tau) in Alzheimer's disease (AD). To determine whether improving brain energy metabolism will forestall disease progress in AD, the impact of the NAD+ precursor nicotinamide on brain cell mitochondrial function and macroautophagy, bioenergetics-related signaling and cognitive performance were studied in cultured neurons and in a mouse model of AD. Oxidative stress resulted in decreased mitochondrial mass, mitochondrial degeneration and autophagosome accumulation in neurons. Nicotinamide preserved mitochondrial integrity and autophagy function, and reduced neuronal vulnerability to oxidative/metabolic insults and Aβ toxicity. NAD+ biosynthesis, autophagy and PI3K signaling were required for the neuroprotective action of nicotinamide. Treatment of 3xTgAD mice with nicotinamide for 8 months resulted in improved cognitive performance, and reduced Aβ and p-Tau pathologies in hippocampus and cerebral cortex. Nicotinamide treatment preserved mitochondrial integrity, and improved autophagy-lysosome procession by enhancing lysosome/autolysosome acidification to reduce autophagosome accumulation. Treatment of 3xTgAD mice with nicotinamide resulted in elevated levels of activated neuroplasticity-related kinases (Akt and ERKs) and the transcription factor cyclic AMP response element-binding protein in the hippocampus and cerebral cortex. Thus, nicotinamide suppresses AD pathology and cognitive decline in a mouse model of AD by a mechanism involving improved brain bioenergetics with preserved functionality of mitochondria and the autophagy system. PMID:23273573

Sustained Effects of Sirolimus on Lung Function and Cystic Lung Lesions in Lymphangioleiomyomatosis

PubMed Central

Yao, Jianhua; Jones, Amanda M.; Julien-Williams, Patricia; Stylianou, Mario; Moss, Joel

2014-01-01

Rationale: Sirolimus therapy stabilizes lung function and reduces the size of chylous effusions and lymphangioleiomyomas in patients with lymphangioleiomyomatosis. Objectives: To determine whether sirolimus has beneficial effects on lung function, cystic areas, and adjacent lung parenchyma; whether these effects are sustained; and whether sirolimus is well tolerated by patients. Methods: Lung function decline over time, lung volume occupied by cysts (cyst score), and lung tissue texture in the vicinity of the cysts were quantified with a computer-aided diagnosis system in 38 patients. Then we compared cyst scores from the last study on sirolimus with studies done on sirolimus therapy. In 12 patients, we evaluated rates of change in lung function and cyst scores off and on sirolimus. Measurements and Main Results: Sirolimus reduced yearly declines in FEV1 (−2.3 ± 0.1 vs. 1.0 ± 0.3% predicted; P < 0.001) and diffusing capacity of carbon monoxide (−2.6 ± 0.1 vs. 0.9 ± 0.2% predicted; P < 0.001). Cyst scores 1.2 ± 0.8 years (30.5 ± 11.9%) and 2.5 ± 2 years (29.7 ± 12.1%) after initiating sirolimus were not significantly different from pretreatment values (28.4 ± 12.5%). In 12 patients followed for 5 years, a significant reduction in rates of yearly decline in FEV1 (−1.4 ± 0.2 vs. 0.3 ± 0.4% predicted; P = 0.025) was observed. Analyses of 104 computed tomography scans showed a nonsignificant (P = 0.23) reduction in yearly rates of change of cyst scores (1.8 ± 0.2 vs. 0.3 ± 0.3%; P = 0.23) and lung texture features. Despite adverse events, most patients were able to continue sirolimus therapy. Conclusions: Sirolimus therapy slowed down lung function decline and increase in cystic lesions. Most patients were able to tolerate sirolimus therapy. PMID:25329516

Predictors of Renal Function Decline in Chinese Patients with Type 2 Diabetes Mellitus and in a Subgroup of Normoalbuminuria: A Retrospective Cohort Study.

PubMed

Hu, Ping; Zhou, Xiang-Hai; Wen, Xin; Ji, Linong

2016-10-01

Risk factors related to renal function decline in type 2 diabetes mellitus (T2DM) remain uncertain. This study aimed to investigate risk factors in relation to renal function decline in patients with T2DM and in a subgroup of patients with normoalbuminuria. This study was a retrospective cohort study, which included 451 patients with T2DM aged 63 ± 14 years admitted to a tertiary hospital in Beijing, China, between April and December 2010 and followed up for 6-60 months. Endpoint was renal function decline, defined as estimated glomerular filtration rate less than 60 mL/min 1.73 m 2 or at least twofold increase of serum creatinine. Cox proportional hazards analysis was used to estimate hazard ratios (HRs) for candidate risk factors of renal function decline. After a median follow-up of 3.3 years, 94 (20.8%) patients developed renal function decline. Increased age (HR, 1.045; 95% CI, 1.020-1.070), albuminuria (HR, 1.956; 95%CI, 1.271-3.011), mild renal dysfunction (HR, 4.521; 95%CI, 2.734-7.476), hyperfiltration (HR, 3.897; 95%CI, 1.572-9.663), and increased hemoglobin A1c (HR, 1.128; 95%CI, 1.020-1.249) were identified as major risk factors. Among a subgroup of 344 patients with normoalbuminuria at baseline, 53 (15.4%) patients developed renal function decline. Increased age (HR, 1.089; 95%CI, 1.050-1.129), mild renal dysfunction (HR, 4.667; 95%CI, 2.391-9.107), hyperfiltration (HR, 5.677; 95%CI, 1.544-20.872), smoking (HR, 2.886; 95%CI, 1.370-6.082), higher pulse pressure (HR, 1.022; 95%CI, 1.004-1.040), and increased fasting glucose (HR, 1.104; 95%CI, 1.020-1.194) were major risk factors. Risk factors of diabetic renal impairment in T2DM should be screened and evaluated at an early stage of diabetes. Albuminuria, mild renal dysfunction, hyperfiltration, increased blood glucose, increased pulse pressure, and smoking were all predictors for diabetic renal impairment and interventions that focus on these risk factors may reduce further decline in renal function.

Lung function impairment in women exposed to biomass fuels during cooking compared to cleaner fuels in Uttar Pradesh, India.

PubMed

Bihari, Vipin; Iqbal, S M; Srivastava, L P; Kesavachandran, C; Siddique, M J A

2013-11-01

A national survey has shown that approximately 75-80% use of fire wood and chips, 10% of dung cake rural women in Uttar Pradesh, India. Considering the respiratory health risk of biomass fuel exposure to women, a cross sectional study was conducted to elucidate the relationship between cooking smoke and lung function impairments. The present study showed significant decline in air flow limitation based on reduced PEFR (3.69 | sec(-1)) and FEV1 (1.34 | sec(-1)) in women cooking with biomass fuels compared to PEFR (4.26 | sec(-1)) and FEV1 (1.73 | sec(-1)) in women cooking with cleaner fuels. The noxious gases and particles generated from biomass fuels during cooking reported in earlier studies may be the reason for the slight decline in airway status PEFR (3.69 | sec(-1)) and lung volumes FEV1 (1.34 | sec(-1)). The higher mean bio-fuels exposure index (52.5 hr-yrs) can attribute to reduced lung function in rural women.

Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity.

PubMed

Seals, Douglas R; Justice, Jamie N; LaRocca, Thomas J

2016-04-15

Most nations of the world are undergoing rapid and dramatic population ageing, which presents great socio-economic challenges, as well as opportunities, for individuals, families, governments and societies. The prevailing biomedical strategy for reducing the healthcare impact of population ageing has been 'compression of morbidity' and, more recently, to increase healthspan, both of which seek to extend the healthy period of life and delay the development of chronic diseases and disability until a brief period at the end of life. Indeed, a recently established field within biological ageing research, 'geroscience', is focused on healthspan extension. Superimposed on this background are new attitudes and demand for 'optimal longevity' - living long, but with good health and quality of life. A key obstacle to achieving optimal longevity is the progressive decline in physiological function that occurs with ageing, which causes functional limitations (e.g. reduced mobility) and increases the risk of chronic diseases, disability and mortality. Current efforts to increase healthspan centre on slowing the fundamental biological processes of ageing such as inflammation/oxidative stress, increased senescence, mitochondrial dysfunction, impaired proteostasis and reduced stress resistance. We propose that optimization of physiological function throughout the lifespan should be a major emphasis of any contemporary biomedical policy addressing global ageing. Effective strategies should delay, reduce in magnitude or abolish reductions in function with ageing (primary prevention) and/or improve function or slow further declines in older adults with already impaired function (secondary prevention). Healthy lifestyle practices featuring regular physical activity and ideal energy intake/diet composition represent first-line function-preserving strategies, with pharmacological agents, including existing and new pharmaceuticals and novel 'nutraceutical' compounds, serving as potential complementary approaches. Future research efforts should focus on defining the temporal patterns of functional declines with ageing, identifying the underlying mechanisms and modulatory factors involved, and establishing the most effective lifestyle practices and pharmacological options for maintaining function. Continuing development of effective behavioural approaches for enhancing adherence to healthy ageing practices in diverse populations, and ongoing analysis of the socio-economic costs and benefits of healthspan extension will be important supporting goals. To meet the demands created by rapid population ageing, a new emphasis in physiological geroscience is needed, which will require the collaborative, interdisciplinary efforts of investigators working throughout the translational research continuum from basic science to public health. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Antibody-directed myostatin inhibition in 21-mo-old mice reveals novel roles for myostatin signaling in skeletal muscle structure and function.

PubMed

Murphy, Kate T; Koopman, René; Naim, Timur; Léger, Bertrand; Trieu, Jennifer; Ibebunjo, Chikwendu; Lynch, Gordon S

2010-11-01

Sarcopenia is the progressive loss of skeletal muscle mass and function with advancing age, leading to reduced mobility and quality of life. We tested the hypothesis that antibody-directed myostatin inhibition would attenuate the decline in mass and function of muscles of aged mice and that apoptosis would be reduced. Eighteen-month-old C57BL/6 mice were treated for 14 wk with a once-weekly injection of saline (control, n=9) or a mouse chimera of anti-human myostatin antibody (PF-354, 10 mg/kg; n=12). PF-354 prevented the age-related reduction in body mass and increased soleus, gastrocnemius, and quadriceps muscle mass (P<0.05). PF-354 increased fiber cross-sectional area by 12% and enhanced maximum in situ force of tibialis anterior (TA) muscles by 35% (P<0.05). PF-354 increased the proportion of type IIa fibers by 114% (P<0.01) and enhanced activity of oxidative enzymes (SDH) by 39% (P<0.01). PF-354 reduced markers of apoptosis in TA muscle cross-sections by 56% (P<0.03) and reduced caspase3 mRNA by 65% (P<0.04). Antibody-directed myostatin inhibition attenuated the decline in mass and function of muscles of aging mice, in part, by reducing apoptosis. These observations identify novel roles for myostatin in regulation of muscle mass and highlight the therapeutic potential of antibody-directed myostatin inhibition for sarcopenia.

Cognitive function and brain structure in persons with type 2 diabetes mellitus after intensive lowering of blood pressure and lipid levels: a randomized clinical trial.

PubMed

Williamson, Jeff D; Launer, Lenore J; Bryan, R Nick; Coker, Laura H; Lazar, Ronald M; Gerstein, Hertzel C; Murray, Anne M; Sullivan, Mark D; Horowitz, Karen R; Ding, Jingzhong; Marcovina, Santica; Lovato, Laura; Lovato, James; Margolis, Karen L; Davatzikos, Christos; Barzilay, Joshua; Ginsberg, Henry N; Linz, Peter E; Miller, Michael E

2014-03-01

Persons with type 2 diabetes mellitus (T2DM) are at increased risk for decline in cognitive function, reduced brain volume, and increased white matter lesions in the brain. Poor control of blood pressure (BP) and lipid levels are risk factors for T2DM-related cognitive decline, but the effect of intensive treatment on brain function and structure is unknown. To examine whether intensive therapy for hypertension and combination therapy with a statin plus a fibrate reduces the risk of decline in cognitive function and total brain volume (TBV) in patients with T2DM. A North American multicenter clinical trial including 2977 participants without baseline clinical evidence of cognitive impairment or dementia and with hemoglobin A1c (HbA1c) levels less than 7.5% randomized to a systolic BP goal of less than 120 vs less than 140 mm Hg (n = 1439) or to a fibrate vs placebo in patients with low-density lipoprotein cholesterol levels less than 100 mg/dL (n = 1538). Participants were recruited from August 1, 2003, through October 31, 2005, with the final follow-up visit by June 30, 2009. Cognition was assessed at baseline and 20 and 40 months. A subset of 503 participants underwent baseline and 40-month brain magnetic resonance imaging to assess for change in TBV and other structural measures of brain health. Baseline mean HbA1c level was 8.3%; mean age, 62 years; and mean duration of T2DM, 10 years. At 40 months, no differences in cognitive function were found in the intensive BP-lowering trial or in the fibrate trial. At 40 months, TBV had declined more in the intensive vs standard BP-lowering group (difference, -4.4 [95% CI, -7.8 to -1.1] cm(3); P = .01). Fibrate therapy had no effect on TBV compared with placebo. In participants with long-standing T2DM and at high risk for cardiovascular events, intensive BP control and fibrate therapy in the presence of controlled low-density lipoprotein cholesterol levels did not produce a measurable effect on cognitive decline at 40 months of follow-up. Intensive BP control was associated with greater decline in TBV at 40 months relative to standard therapy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00000620.

Role of oxidants/inflammation in declining renal function in chronic kidney disease and normal aging.

PubMed

Vlassara, Helen; Torreggiani, Massimo; Post, James B; Zheng, Feng; Uribarri, Jaime; Striker, Gary E

2009-12-01

Oxidant stress (OS) and inflammation increase in normal aging and in chronic kidney disease (CKD), as observed in human and animal studies. In cross-sectional studies of the US population, these changes are associated with a decrease in renal function, which is exhibited by a significant proportion of the population. However, since many normal adults have intact renal function, and longitudinal studies show that some persons maintain normal renal function with age, the link between OS, inflammation, and renal decline is not clear. In aging mice, greater oxidant intake is associated with increased age-related CKD and mortality, which suggests that interventions that reduce OS and inflammation may be beneficial for older individuals. Both OS and inflammation can be readily lowered in normal subjects and patients with CKD stage 3-4 by a simple dietary modification that lowers intake and results in reduced serum and tissue levels of advanced glycation end products. Diabetic patients, including those with microalbuminuria, have a decreased ability to metabolize and excrete oxidants prior to observable changes in serum creatinine. Thus, OS and inflammation may occur in the diabetic kidney at an early time. We review the evidence that oxidants in the diet directly lead to increased serum levels of OS and inflammatory mediators in normal aging and in CKD. We also discuss a simple dietary intervention that helps reduce OS and inflammation, an important and achievable therapeutic goal for patients with CKD and aging individuals with reduced renal function.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sundar, Isaac K.; Hwang, Jae-Woong; Wu, Shaoping

Research highlights: {yields} Vitamin D deficiency is linked to accelerated decline in lung function. {yields} Levels of vitamin D receptor (VDR) are decreased in lungs of patients with COPD. {yields} VDR knock-out mouse showed increased lung inflammation and emphysema. {yields} This was associated with decline in lung function and increased MMPs. {yields} VDR knock-out mouse model is useful for studying the mechanisms of lung diseases. -- Abstract: Deficiency of vitamin D is associated with accelerated decline in lung function. Vitamin D is a ligand for nuclear hormone vitamin D receptor (VDR), and upon binding it modulates various cellular functions. Themore » level of VDR is reduced in lungs of patients with chronic obstructive pulmonary disease (COPD) which led us to hypothesize that deficiency of VDR leads to significant alterations in lung phenotype that are characteristics of COPD/emphysema associated with increased inflammatory response. We found that VDR knock-out (VDR{sup -/-}) mice had increased influx of inflammatory cells, phospho-acetylation of nuclear factor-kappaB (NF-{kappa}B) associated with increased proinflammatory mediators, and up-regulation of matrix metalloproteinases (MMPs) MMP-2, MMP-9, and MMP-12 in the lung. This was associated with emphysema and decline in lung function associated with lymphoid aggregates formation compared to WT mice. These findings suggest that deficiency of VDR in mouse lung can lead to an early onset of emphysema/COPD because of chronic inflammation, immune dysregulation, and lung destruction.« less

Geriatric Conditions in Acutely Hospitalized Older Patients: Prevalence and One-Year Survival and Functional Decline

PubMed Central

Buurman, Bianca M.; Hoogerduijn, Jita G.; de Haan, Rob J.; Abu-Hanna, Ameen; Lagaay, A. Margot; Verhaar, Harald J.; Schuurmans, Marieke J.; Levi, Marcel; de Rooij, Sophia E.

2011-01-01

Background To study the prevalence of eighteen geriatric conditions in older patients at admission, their reporting rate in discharge summaries and the impact of these conditions on mortality and functional decline one year after admission. Method A prospective multicenter cohort study conducted between 2006 and 2008 in two tertiary university teaching hospitals and one regional teaching hospital in the Netherlands. Patients of 65 years and older, acutely admitted and hospitalized for at least 48 hours, were invited to participate. Eighteen geriatric conditions were assessed at hospital admission, and outcomes (mortality, functional decline) were assessed one year after admission. Results 639 patients were included, with a mean age of 78 years. IADL impairment (83%), polypharmacy (61%), mobility difficulty (59%), high levels of primary caregiver burden (53%), and malnutrition (52%) were most prevalent. Except for polypharmacy and cognitive impairment, the reporting rate of the geriatric conditions in discharge summaries was less than 50%. One year after admission, 35% had died and 33% suffered from functional decline. A high Charlson comorbidity index score, presence of malnutrition, high fall risk, presence of delirium and premorbid IADL impairment were associated with mortality and overall poor outcome (mortality or functional decline). Obesity lowered the risk for mortality. Conclusion Geriatric conditions were highly prevalent and associated with poor health outcomes after admission. Early recognition of these conditions in acutely hospitalized older patients and improving the handover to the general practitioner could lead to better health outcomes and reduce the burden of hospital admission for older patients. PMID:22110598

Altered Odor-Induced Brain Activity as an Early Manifestation of Cognitive Decline in Patients With Type 2 Diabetes.

PubMed

Zhang, Zhou; Zhang, Bing; Wang, Xin; Zhang, Xin; Yang, Qing X; Qing, Zhao; Lu, Jiaming; Bi, Yan; Zhu, Dalong

2018-05-01

Type 2 diabetes is reported to be associated with olfactory dysfunction and cognitive decline. However, whether and how olfactory neural circuit abnormalities involve cognitive impairment in diabetes remains uncovered. This study thus aimed to investigate olfactory network alterations and the associations of odor-induced brain activity with cognitive and metabolic parameters in type 2 diabetes. Participants with normal cognition, including 51 patients with type 2 diabetes and 41 control subjects without diabetes, underwent detailed cognitive assessment, olfactory behavior tests, and odor-induced functional MRI measurements. Olfactory brain regions showing significantly different activation between the two groups were selected for functional connectivity analysis. Compared with the control subjects, patients with diabetes demonstrated significantly lower olfactory threshold score, decreased brain activation, and disrupted functional connectivity in the olfactory network. Positive associations of the disrupted functional connectivity with decreased neuropsychology test scores and reduced pancreatic function were observed in patients with diabetes. Notably, the association between pancreatic function and executive function was mediated by olfactory behavior and olfactory functional connectivity. Our results suggested the alteration of olfactory network is present before clinically measurable cognitive decrements in type 2 diabetes, bridging the gap between the central olfactory system and cognitive decline in diabetes. © 2018 by the American Diabetes Association.

Assessment and management of nutrition in older people and its importance to health.

PubMed

Ahmed, Tanvir; Haboubi, Nadim

2010-08-09

Nutrition is an important element of health in the older population and affects the aging process. The prevalence of malnutrition is increasing in this population and is associated with a decline in: functional status, impaired muscle function, decreased bone mass, immune dysfunction, anemia, reduced cognitive function, poor wound healing, delayed recovery from surgery, higher hospital readmission rates, and mortality. Older people often have reduced appetite and energy expenditure, which, coupled with a decline in biological and physiological functions such as reduced lean body mass, changes in cytokine and hormonal level, and changes in fluid electrolyte regulation, delay gastric emptying and diminish senses of smell and taste. In addition pathologic changes of aging such as chronic diseases and psychological illness all play a role in the complex etiology of malnutrition in older people. Nutritional assessment is important to identify and treat patients at risk, the Malnutrition Universal Screening Tool being commonly used in clinical practice. Management requires a holistic approach, and underlying causes such as chronic illness, depression, medication and social isolation must be treated. Patients with physical or cognitive impairment require special care and attention. Oral supplements or enteral feeding should be considered in patients at high risk or in patients unable to meet daily requirements.

Hypersensitivity pneumonitis in a cluster of sawmill workers: a 10-year follow-up of exposure, symptoms, and lung function

PubMed Central

Færden, Karl; Lund, May Brit; Aaløkken, Trond Mogens; Eduard, Wijnand; Søstrand, Per; Langård, Sverre; Kongerud, Johny

2014-01-01

Background: The long-term prognosis of repeated acute episodes of hypersensitivity pneumonitis (HP) is not well described. We report on a 10-year follow-up of a 10-person cluster from a Norwegian sawmill who had all experienced relapsing episodes of HP. Objectives: To evaluate the health symptoms, work-related sick-leave, and lung function of 10 workers exposed to mold in a Norwegian sawmill. Methods: Participants were evaluated at baseline and 10 years later at follow-up. A structured interview, measurement of serum IgG antibodies to Rhizopus microsporus (R. microsporus) antigens, lung function tests, high resolution computed tomography (HRCT) of the chest, and personal measurements of exposure to mold spores and dust were completed for each participant. Results: At baseline, nearly all workers reported acute episodes of HP more than twice a month. At follow-up, both the frequency and intensity of symptoms had declined. Sick-leave was reduced and gas diffusing capacity improved – paralleling the gradually reduced air levels of mold spores. Conclusions: In spite of an initially high occurrence of symptoms, long-term clinical and physiological outcome was good. With reduced exposure to mold spores, symptoms declined and lung function was restored. PMID:24999852

Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity

PubMed Central

Justice, Jamie N.; LaRocca, Thomas J.

2015-01-01

Abstract Most nations of the world are undergoing rapid and dramatic population ageing, which presents great socio‐economic challenges, as well as opportunities, for individuals, families, governments and societies. The prevailing biomedical strategy for reducing the healthcare impact of population ageing has been ‘compression of morbidity’ and, more recently, to increase healthspan, both of which seek to extend the healthy period of life and delay the development of chronic diseases and disability until a brief period at the end of life. Indeed, a recently established field within biological ageing research, ‘geroscience’, is focused on healthspan extension. Superimposed on this background are new attitudes and demand for ‘optimal longevity’ – living long, but with good health and quality of life. A key obstacle to achieving optimal longevity is the progressive decline in physiological function that occurs with ageing, which causes functional limitations (e.g. reduced mobility) and increases the risk of chronic diseases, disability and mortality. Current efforts to increase healthspan centre on slowing the fundamental biological processes of ageing such as inflammation/oxidative stress, increased senescence, mitochondrial dysfunction, impaired proteostasis and reduced stress resistance. We propose that optimization of physiological function throughout the lifespan should be a major emphasis of any contemporary biomedical policy addressing global ageing. Effective strategies should delay, reduce in magnitude or abolish reductions in function with ageing (primary prevention) and/or improve function or slow further declines in older adults with already impaired function (secondary prevention). Healthy lifestyle practices featuring regular physical activity and ideal energy intake/diet composition represent first‐line function‐preserving strategies, with pharmacological agents, including existing and new pharmaceuticals and novel ‘nutraceutical’ compounds, serving as potential complementary approaches. Future research efforts should focus on defining the temporal patterns of functional declines with ageing, identifying the underlying mechanisms and modulatory factors involved, and establishing the most effective lifestyle practices and pharmacological options for maintaining function. Continuing development of effective behavioural approaches for enhancing adherence to healthy ageing practices in diverse populations, and ongoing analysis of the socio‐economic costs and benefits of healthspan extension will be important supporting goals. To meet the demands created by rapid population ageing, a new emphasis in physiological geroscience is needed, which will require the collaborative, interdisciplinary efforts of investigators working throughout the translational research continuum from basic science to public health. PMID:25639909

Synaptic genes are extensively downregulated across multiple brain regions in normal human aging and Alzheimer’s disease

PubMed Central

Berchtold, Nicole C.; Coleman, Paul D.; Cribbs, David H.; Rogers, Joseph; Gillen, Daniel L.; Cotman, Carl W.

2014-01-01

Synapses are essential for transmitting, processing, and storing information, all of which decline in aging and Alzheimer’s disease (AD). Because synapse loss only partially accounts for the cognitive declines seen in aging and AD, we hypothesized that existing synapses might undergo molecular changes that reduce their functional capacity. Microarrays were used to evaluate expression profiles of 340 synaptic genes in aging (20–99 years) and AD across 4 brain regions from 81 cases. The analysis revealed an unexpectedly large number of significant expression changes in synapse-related genes in aging, with many undergoing progressive downregulation across aging and AD. Functional classification of the genes showing altered expression revealed that multiple aspects of synaptic function are affected, notably synaptic vesicle trafficking and release, neurotransmitter receptors and receptor trafficking, postsynaptic density scaffolding, cell adhesion regulating synaptic stability, and neuromodulatory systems. The widespread declines in synaptic gene expression in normal aging suggests that function of existing synapses might be impaired, and that a common set of synaptic genes are vulnerable to change in aging and AD. PMID:23273601

Pulmonary function test findings in patients with acute inhalation injury caused by smoke bombs

PubMed Central

Cao, Lu; Zhang, Xin-Gang; Wang, Jian-Guo; Wang, Han-Bin; Chen, Yi-Bing; Zhao, Da-Hui; Shi, Wen-Fang

2016-01-01

Background This study aimed to determine the effects of smoke bomb-induced acute inhalation injury on pulmonary function at different stages of lung injury. Methods We performed pulmonary function tests (PFTs) in 15 patients with acute inhalation injury from days 3 to 180 after smoke inhalation. We measured the trace element zinc in whole blood on days 4 and 17, and correlations of zinc levels with PFTs were performed. Results In the acute stage of lung injury (day 3), 3 of 11 patients with mild symptoms had normal pulmonary function and 8 patients with restrictive ventilatory dysfunction and reduced diffusing capacity. Some patients also had mild obstructive ventilatory dysfunction (5 patients) and a decline in small airway function (6 patients). For patients with severe symptoms, PFT results showed moderate to severe restrictive ventilatory dysfunction and reduced diffusing capacity. PaCO2 was significantly higher (P=0.047) in patients with reduced small airway function compared with those with normal small airway function. Whole blood zinc levels in the convalescence stage (day 17) were significantly lower than those in the acute stage (day 4). Zinc in the acute stage was negatively correlated with DLCO/VA on days 3, 10, and 46 (r=−0.633, −0.676, and −0.675 respectively, P<0.05). Conclusions Smoke inhalation injury mainly causes restrictive ventilatory dysfunction and reduced diffusing capacity, and causes mild obstructive ventilatory dysfunction and small airway function decline in some patients. Zinc is negatively correlated with DLCO/VA. Zinc levels may be able to predict prognosis and indicate the degree of lung injury. PMID:28066595

Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial

PubMed Central

Brown, Paul D.; Pugh, Stephanie; Laack, Nadia N.; Wefel, Jeffrey S.; Khuntia, Deepak; Meyers, Christina; Choucair, Ali; Fox, Sherry; Suh, John H.; Roberge, David; Kavadi, Vivek; Bentzen, Soren M.; Mehta, Minesh P.; Watkins-Bruner, Deborah

2013-01-01

Background To determine the protective effects of memantine on cognitive function in patients receiving whole-brain radiotherapy (WBRT). Methods Adult patients with brain metastases received WBRT and were randomized to receive placebo or memantine (20 mg/d), within 3 days of initiating radiotherapy for 24 weeks. Serial standardized tests of cognitive function were performed. Results Of 554 patients who were accrued, 508 were eligible. Grade 3 or 4 toxicities and study compliance were similar in the 2 arms. There was less decline in delayed recall in the memantine arm at 24 weeks (P = .059), but the difference was not statistically significant, possibly because there were only 149 analyzable patients at 24 weeks, resulting in only 35% statistical power. The memantine arm had significantly longer time to cognitive decline (hazard ratio 0.78, 95% confidence interval 0.62–0.99, P = .01); the probability of cognitive function failure at 24 weeks was 53.8% in the memantine arm and 64.9% in the placebo arm. Superior results were seen in the memantine arm for executive function at 8 (P = .008) and 16 weeks (P = .0041) and for processing speed (P = .0137) and delayed recognition (P = .0149) at 24 weeks. Conclusions Memantine was well tolerated and had a toxicity profile very similar to placebo. Although there was less decline in the primary endpoint of delayed recall at 24 weeks, this lacked statistical significance possibly due to significant patient loss. Overall, patients treated with memantine had better cognitive function over time; specifically, memantine delayed time to cognitive decline and reduced the rate of decline in memory, executive function, and processing speed in patients receiving WBRT. RTOG 0614, ClinicalTrials.gov number CT00566852. PMID:23956241

Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial.

PubMed

Brown, Paul D; Pugh, Stephanie; Laack, Nadia N; Wefel, Jeffrey S; Khuntia, Deepak; Meyers, Christina; Choucair, Ali; Fox, Sherry; Suh, John H; Roberge, David; Kavadi, Vivek; Bentzen, Soren M; Mehta, Minesh P; Watkins-Bruner, Deborah

2013-10-01

To determine the protective effects of memantine on cognitive function in patients receiving whole-brain radiotherapy (WBRT). Adult patients with brain metastases received WBRT and were randomized to receive placebo or memantine (20 mg/d), within 3 days of initiating radiotherapy for 24 weeks. Serial standardized tests of cognitive function were performed. Of 554 patients who were accrued, 508 were eligible. Grade 3 or 4 toxicities and study compliance were similar in the 2 arms. There was less decline in delayed recall in the memantine arm at 24 weeks (P = .059), but the difference was not statistically significant, possibly because there were only 149 analyzable patients at 24 weeks, resulting in only 35% statistical power. The memantine arm had significantly longer time to cognitive decline (hazard ratio 0.78, 95% confidence interval 0.62-0.99, P = .01); the probability of cognitive function failure at 24 weeks was 53.8% in the memantine arm and 64.9% in the placebo arm. Superior results were seen in the memantine arm for executive function at 8 (P = .008) and 16 weeks (P = .0041) and for processing speed (P = .0137) and delayed recognition (P = .0149) at 24 weeks. Memantine was well tolerated and had a toxicity profile very similar to placebo. Although there was less decline in the primary endpoint of delayed recall at 24 weeks, this lacked statistical significance possibly due to significant patient loss. Overall, patients treated with memantine had better cognitive function over time; specifically, memantine delayed time to cognitive decline and reduced the rate of decline in memory, executive function, and processing speed in patients receiving WBRT. RTOG 0614, ClinicalTrials.gov number CT00566852.

Prognostic Significance of the Short Physical Performance Battery in Older Patients Discharged from Acute Care Hospitals

PubMed Central

Lattanzio, Fabrizia; Pedone, Claudio; Garasto, Sabrina; Laino, Irma; Bustacchini, Silvia; Pranno, Luigi; Mazzei, Bruno; Passarino, Giuseppe; Incalzi, Raffaele Antonelli

2012-01-01

Abstract We investigated the prognostic role of the Short Physical Performance Battery (SPPB) in elderly patients discharged from the acute care hospital. Our series consisted of 506 patients aged 70 years or more enrolled in a multicenter collaborative observational study. We considered three main outcomes: 1-year survival after discharge, functional decline, and hospitalization during follow-up. Independent predictors/correlates of the outcomes were investigated by Cox regression or logistic regression analysis when appropriate. The diagnostic accuracy of SPPB in relation to study outcomes was investigated by receiver operating characteristic (ROC) curve. SPPB score was associated with reduced mortality (hazard ratio [HR]=0.86, 95% confidence interval [CI] 0.78–0.95). When the analysis was adjusted for functional status at discharge, such an association was still near significant only for SPPB values >8 (HR=0.51; 95% CI 0.30–1.05). An SPPB score<5 could identify patients who died during follow-up with fair sensitivity (0.66), specificity (0.62), and area under the ROC curve (0.66). SPPB also qualified as independent correlate of functional decline (odds ratio [OR]=0.82; 95% CI 0.70–0.96), but not of rehospitalization or combined end-point death or rehospitalization. An SPPB score <5 could identify patients experiencing functional decline during follow-up with lower sensitivity (0.60), but higher specificity (0.69), and area under the ROC curve (0.69) with respect to mortality. In conclusion, SPPB can be considered a valid instrument to identify patients at major risk of functional decline and death after discharge from acute care hospital. However, it could more efficiently target patients at risk of functional decline than those at risk of death. PMID:22004280

Identifying species conservation strategies to reduce disease-associated declines

USGS Publications Warehouse

Gerber, Brian D.; Converse, Sarah J.; Muths, Erin L.; Crockett, Harry J.; Mosher, Brittany A.; Bailey, Larissa L.

2018-01-01

Emerging infectious diseases (EIDs) are a salient threat to many animal taxa, causing local and global extinctions, altering communities and ecosystem function. The EID chytridiomycosis is a prominent driver of amphibian declines, which is caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd). To guide conservation policy, we developed a predictive decision-analytic model that combines empirical knowledge of host-pathogen metapopulation dynamics with expert judgment regarding effects of management actions, to select from potential conservation strategies. We apply our approach to a boreal toad (Anaxyrus boreas boreas) and Bd system, identifying optimal strategies that balance tradeoffs in maximizing toad population persistence and landscape-level distribution, while considering costs. The most robust strategy is expected to reduce the decline of toad breeding sites from 53% to 21% over 50 years. Our findings are incorporated into management policy to guide conservation planning. Our online modeling application provides a template for managers of other systems challenged by EIDs.

An evaluation of longitudinal changes in serum uric acid levels and associated risk of cardio-metabolic events and renal function decline in gout.

PubMed

Desai, Rishi J; Franklin, Jessica M; Spoendlin-Allen, Julia; Solomon, Daniel H; Danaei, Goodarz; Kim, Seoyoung C

2018-01-01

Gout patients have a high burden of co-morbid conditions including diabetes mellitus (DM), chronic kidney disease (CKD), and cardiovascular disease (CVD). We sought to evaluate the association between changes in serum uric acid (SUA) levels over time and the risk of incident DM, CVD, and renal function decline in gout patients. An observational cohort study was conducted among enrollees of private health insurance programs in the US between 2004 and 2015. Gout patients were included on the index date of a SUA measurement ≥6.8 mg/dl. The exposure of interest was cumulative change in SUA levels from baseline. Hazard ratios (HR) and 95% confidence intervals (CI) for incident DM, incident CVD, and renal function decline (≥30% reduction in glomerular filtration rate) were derived using marginal structural models with stabilized inverse probability weights accounting for baseline confounders (age, gender, co-morbidities, co-medications) and time-varying confounders (serum creatinine, blood urea nitrogen, glycated hemoglobin). Among 26,341 patients with gout, the average age was 62, 75% were men, and the median baseline SUA was 8.6 mg/dl (interquartile range 7.7 to 9.5). The incidence rates/100 person-years (95% CI) were 1.63 (1.51-1.75) for DM, 0.77 (0.70-0.84) for CVD, and 4.32 (4.14-4.49) for renal function decline. The adjusted HR (95% CI) per 3 mg/dl reduction in SUA, corresponding on average to achieving the target level of <6 mg/dl in this population, was 1.04 (0.92-1.17) for DM, 1.07 (0.89-1.29) for CVD, and 0.85 (0.78-0.92) for renal function decline. Reduction in SUA in patients with gout may be associated with a reduced risk of renal function decline, but not with DM or CVD.

The Role for Dietary Omega-3 Fatty Acids Supplementation in Older Adults

PubMed Central

Molfino, Alessio; Gioia, Gianfranco; Fanelli, Filippo Rossi; Muscaritoli, Maurizio

2014-01-01

Optimal nutrition is one of the most important determinants of healthier ageing, reducing the risk of disability, maintaining mental and physical functions, and thus preserving and ensuring a better quality of life. Dietary intake and nutrient absorption decline with age, thus increasing the risk of malnutrition, morbidity and mortality. Specific nutrients, particularly long-chain omega-3 polyunsaturated fatty acids (PUFAs), might have the potential of preventing and reducing co-morbidities in older adults. Omega-3 PUFAs are able to modulate inflammation, hyperlipidemia, platelet aggregation, and hypertension. Different mechanisms contribute to these effects, including conditioning cell membrane function and composition, eicosanoid production, and gene expression. The present review analyzes the influence of omega-3 PUFAs status and intake on brain function, cardiovascular system, immune function, muscle performance and bone health in older adults. Omega-3 FAs may have substantial benefits in reducing the risk of cognitive decline in older people. The available data encourage higher intakes of omega-3 PUFAs in the diet or via specific supplements. More studies are needed to confirm the role of omega-3 FAs in maintaining bone health and preventing the loss of muscle mass and function associated with ageing. In summary, omega-3 PUFAs are now identified as potential key nutrients, safe and effective in the treatment and prevention of several negative consequences of ageing. PMID:25285409

Predicting Speech Intelligibility Decline in Amyotrophic Lateral Sclerosis Based on the Deterioration of Individual Speech Subsystems

PubMed Central

Yunusova, Yana; Wang, Jun; Zinman, Lorne; Pattee, Gary L.; Berry, James D.; Perry, Bridget; Green, Jordan R.

2016-01-01

Purpose To determine the mechanisms of speech intelligibility impairment due to neurologic impairments, intelligibility decline was modeled as a function of co-occurring changes in the articulatory, resonatory, phonatory, and respiratory subsystems. Method Sixty-six individuals diagnosed with amyotrophic lateral sclerosis (ALS) were studied longitudinally. The disease-related changes in articulatory, resonatory, phonatory, and respiratory subsystems were quantified using multiple instrumental measures, which were subjected to a principal component analysis and mixed effects models to derive a set of speech subsystem predictors. A stepwise approach was used to select the best set of subsystem predictors to model the overall decline in intelligibility. Results Intelligibility was modeled as a function of five predictors that corresponded to velocities of lip and jaw movements (articulatory), number of syllable repetitions in the alternating motion rate task (articulatory), nasal airflow (resonatory), maximum fundamental frequency (phonatory), and speech pauses (respiratory). The model accounted for 95.6% of the variance in intelligibility, among which the articulatory predictors showed the most substantial independent contribution (57.7%). Conclusion Articulatory impairments characterized by reduced velocities of lip and jaw movements and resonatory impairments characterized by increased nasal airflow served as the subsystem predictors of the longitudinal decline of speech intelligibility in ALS. Declines in maximum performance tasks such as the alternating motion rate preceded declines in intelligibility, thus serving as early predictors of bulbar dysfunction. Following the rapid decline in speech intelligibility, a precipitous decline in maximum performance tasks subsequently occurred. PMID:27148967

Predicting Speech Intelligibility Decline in Amyotrophic Lateral Sclerosis Based on the Deterioration of Individual Speech Subsystems.

PubMed

Rong, Panying; Yunusova, Yana; Wang, Jun; Zinman, Lorne; Pattee, Gary L; Berry, James D; Perry, Bridget; Green, Jordan R

2016-01-01

To determine the mechanisms of speech intelligibility impairment due to neurologic impairments, intelligibility decline was modeled as a function of co-occurring changes in the articulatory, resonatory, phonatory, and respiratory subsystems. Sixty-six individuals diagnosed with amyotrophic lateral sclerosis (ALS) were studied longitudinally. The disease-related changes in articulatory, resonatory, phonatory, and respiratory subsystems were quantified using multiple instrumental measures, which were subjected to a principal component analysis and mixed effects models to derive a set of speech subsystem predictors. A stepwise approach was used to select the best set of subsystem predictors to model the overall decline in intelligibility. Intelligibility was modeled as a function of five predictors that corresponded to velocities of lip and jaw movements (articulatory), number of syllable repetitions in the alternating motion rate task (articulatory), nasal airflow (resonatory), maximum fundamental frequency (phonatory), and speech pauses (respiratory). The model accounted for 95.6% of the variance in intelligibility, among which the articulatory predictors showed the most substantial independent contribution (57.7%). Articulatory impairments characterized by reduced velocities of lip and jaw movements and resonatory impairments characterized by increased nasal airflow served as the subsystem predictors of the longitudinal decline of speech intelligibility in ALS. Declines in maximum performance tasks such as the alternating motion rate preceded declines in intelligibility, thus serving as early predictors of bulbar dysfunction. Following the rapid decline in speech intelligibility, a precipitous decline in maximum performance tasks subsequently occurred.

Musical Experience and the Aging Auditory System: Implications for Cognitive Abilities and Hearing Speech in Noise

PubMed Central

Parbery-Clark, Alexandra; Strait, Dana L.; Anderson, Samira; Hittner, Emily; Kraus, Nina

2011-01-01

Much of our daily communication occurs in the presence of background noise, compromising our ability to hear. While understanding speech in noise is a challenge for everyone, it becomes increasingly difficult as we age. Although aging is generally accompanied by hearing loss, this perceptual decline cannot fully account for the difficulties experienced by older adults for hearing in noise. Decreased cognitive skills concurrent with reduced perceptual acuity are thought to contribute to the difficulty older adults experience understanding speech in noise. Given that musical experience positively impacts speech perception in noise in young adults (ages 18–30), we asked whether musical experience benefits an older cohort of musicians (ages 45–65), potentially offsetting the age-related decline in speech-in-noise perceptual abilities and associated cognitive function (i.e., working memory). Consistent with performance in young adults, older musicians demonstrated enhanced speech-in-noise perception relative to nonmusicians along with greater auditory, but not visual, working memory capacity. By demonstrating that speech-in-noise perception and related cognitive function are enhanced in older musicians, our results imply that musical training may reduce the impact of age-related auditory decline. PMID:21589653

Musical experience and the aging auditory system: implications for cognitive abilities and hearing speech in noise.

PubMed

Parbery-Clark, Alexandra; Strait, Dana L; Anderson, Samira; Hittner, Emily; Kraus, Nina

2011-05-11

Much of our daily communication occurs in the presence of background noise, compromising our ability to hear. While understanding speech in noise is a challenge for everyone, it becomes increasingly difficult as we age. Although aging is generally accompanied by hearing loss, this perceptual decline cannot fully account for the difficulties experienced by older adults for hearing in noise. Decreased cognitive skills concurrent with reduced perceptual acuity are thought to contribute to the difficulty older adults experience understanding speech in noise. Given that musical experience positively impacts speech perception in noise in young adults (ages 18-30), we asked whether musical experience benefits an older cohort of musicians (ages 45-65), potentially offsetting the age-related decline in speech-in-noise perceptual abilities and associated cognitive function (i.e., working memory). Consistent with performance in young adults, older musicians demonstrated enhanced speech-in-noise perception relative to nonmusicians along with greater auditory, but not visual, working memory capacity. By demonstrating that speech-in-noise perception and related cognitive function are enhanced in older musicians, our results imply that musical training may reduce the impact of age-related auditory decline.

Resting-state networks associated with cognitive processing show more age-related decline than those associated with emotional processing.

PubMed

Nashiro, Kaoru; Sakaki, Michiko; Braskie, Meredith N; Mather, Mara

2017-06-01

Correlations in activity across disparate brain regions during rest reveal functional networks in the brain. Although previous studies largely agree that there is an age-related decline in the "default mode network," how age affects other resting-state networks, such as emotion-related networks, is still controversial. Here we used a dual-regression approach to investigate age-related alterations in resting-state networks. The results revealed age-related disruptions in functional connectivity in all 5 identified cognitive networks, namely the default mode network, cognitive-auditory, cognitive-speech (or speech-related somatosensory), and right and left frontoparietal networks, whereas such age effects were not observed in the 3 identified emotion networks. In addition, we observed age-related decline in functional connectivity in 3 visual and 3 motor/visuospatial networks. Older adults showed greater functional connectivity in regions outside 4 out of the 5 identified cognitive networks, consistent with the dedifferentiation effect previously observed in task-based functional magnetic resonance imaging studies. Both reduced within-network connectivity and increased out-of-network connectivity were correlated with poor cognitive performance, providing potential biomarkers for cognitive aging. Copyright © 2017 Elsevier Inc. All rights reserved.

Multi-modal intervention to reduce cardiovascular risk among hypertensive older adults: Design of a randomized clinical trial

PubMed Central

Buford, Thomas W.; Anton, Stephen D.; Bavry, Anthony; Carter, Christy S.; Daniels, Michael J.; Pahor, Marco

2015-01-01

Persons aged over 65 years account for over 75% of healthcare expenditures and deaths attributable to cardiovascular disease (CVD). Accordingly, reducing CVD risk among older adults is an important public health priority. Functional status, determined by measures of physical performance, is an important predictor of cardiovascular outcomes in older adults and declines more rapidly in seniors with hypertension. To date, physical exercise is the primary strategy for attenuating declines in functional status. Yet despite the general benefits of training, exercise alone appears to be insufficient for preventing this decline. Thus, alternative or adjuvant strategies are needed to preserve functional status among seniors with hypertension. Prior data suggest that angiotensin converting enzyme inhibitors (ACEi) may be efficacious in enhancing exercise-derived improvements in functional status yet this hypothesis has not been tested in a randomized controlled trial. The objective of this randomized, double-masked pilot trial is to gather preliminary efficacy and safety data necessary for conducting a full-scale trial to test this hypothesis. Sedentary men and women ≥ 65 years of age with functional limitations and hypertension are being recruited into this 24 week intervention study. Participants are randomly assigned to one of three conditions: (1) ACEi plus exercise training, (2) thiazide diuretic plus exercise training, or (3) AT1 receptor antagonist plus exercise training. The primary outcome is change in walking speed and secondary outcomes consist of other indices of CV risk including exercise capacity, body composition, as well as circulating indices of metabolism, inflammation and oxidative stress. PMID:26115878

BRAIN FUEL METABOLISM, AGING AND ALZHEIMER’S DISEASE

PubMed Central

Cunnane, SC; Nugent, S; Roy, M; Courchesne-Loyer, A; Croteau, E; Tremblay, S; Castellano, A; Pifferi, F; Bocti, C; Paquet, N; Begdouri, H; Bentourkia, M; Turcotte, E; Allard, M; Barberger-Gateau, P; Fulop, T; Rapoport, S

2012-01-01

Lower brain glucose metabolism is present before the onset of clinically-measurable cognitive decline in two groups of people at risk of Alzheimer’s disease (AD) - carriers of apoE4, and in those with a maternal family history of AD. Supported by emerging evidence from in vitro and animal studies, these reports suggest that brain hypometabolism may precede and contribute to the neuropathological cascade leading cognitive decline in AD. The reason for brain hypometabolism is unclear but may include defects in glucose transport at the blood-brain barrier, glycolysis, and/or mitochondrial function. Methodological issues presently preclude knowing with certainty whether or not aging in the absence of cognitive impairment is necessarily associated with lower brain glucose metabolism. Nevertheless, aging appears to increase the risk of deteriorating systemic control of glucose utilization which, in turn, may increase the risk of declining brain glucose uptake, at least in some regions. A contributing role of deteriorating glucose availability to or metabolism by the brain in AD does not exclude the opposite effect, i.e. that neurodegenerative processes in AD further decrease brain glucose metabolism because of reduced synaptic functionality and, hence, reduced energy needs, thereby completing a vicious cycle. Strategies to reduce the risk of AD by breaking this cycle should aim to – (i) improve insulin sensitivity by improving systemic glucose utilization, or (ii) bypass deteriorating brain glucose metabolism using approaches that safely induce mild, sustainable ketonemia. PMID:21035308

[Advances in the research of effects of glutamine on immune function of burn patients].

PubMed

Liu, Y H; Guo, P F; Chen, G Y; Bo, Y C; Ma, Y; Cui, Z J

2018-04-20

Glutamine is the most abundant amino acid found in plasma and cells. It is the preferred fuel for enterocytes in the small intestine, macrophages, and lymphocytes. After serious burn, increased requirement of glutamine by the gastrointestinal tract, kidney and lymphocytes, and relatively insufficient self synthesis likely contribute to the rapid decline of glutamine in circulation and cells. Glutamine supplementation can not only protect intestinal mucosa, maintain normal intestinal barrier function, reduce bacterial translocation, and enhance the intestinal immune function, but also increase the number of lymphocytes, enhance the phagocytic function of macrophage, promote the synthesis of immunoglobulin, and reduce the body's inflammatory response, so as to enhance the immune function. Therefore, glutamine supplementation can improve and enhance the immune function, reduce complications and promote the prognosis of severely burned patients.

The Verriest Lecture: Short-wave-sensitive cone pathways across the life span

PubMed Central

Werner, John S.

2017-01-01

Structurally and functionally, the short-wave-sensitive (S) cone pathways are thought to decline more rapidly with normal aging than the middle- and long-wave-sensitive cone pathways. This would explain the celebrated results by Verriest and others demonstrating that the largest age-related color discrimination losses occur for stimuli on a tritan axis. Here, we challenge convention, arguing from psychophysical data that selective S-cone pathway losses do not cause declines in color discrimination. We show substantial declines in chromatic detection and discrimination, as well as in temporal and spatial vision tasks, that are mediated by S-cone pathways. These functional losses are not, however, unique to S-cone pathways. Finally, despite reduced photon capture by S cones, their postreceptoral pathways provide robust signals for the visual system to renormalize itself to maintain nearly stable color perception across the life span. PMID:26974914

Ingestion of Lactobacillus strain reduces anxiety and improves cognitive function in the hyperammonemia rat.

PubMed

Luo, Jia; Wang, Tao; Liang, Shan; Hu, Xu; Li, Wei; Jin, Feng

2014-03-01

Evidence suggests that the hyperammonemia (HA)-induced neuroinflammation and alterations in the serotonin (5-HT) system may contribute to cognitive decline and anxiety disorder during hepatic encephalopathy (HE). Probiotics that maintain immune system homeostasis and regulate the 5-HT system may be potential treatment for HA-mediated neurological disorders in HE. In this study, we tested the efficacy of probiotic Lactobacillus helveticus strain NS8 in preventing cognitive decline and anxiety-like behavior in HA rats. Chronic HA was induced by intraperitoneal injection of ammonium acetate for four weeks in male Sprague-Dawley rats. HA rats were then given Lactobacillus helveticus strain NS8 (10(9) CFU mL(-1)) in drinking water as a daily supplementation. The Morris water maze task assessed cognitive function, and the elevated plus maze test evaluated anxiety-like behavior. Neuroinflammation was assessed by measuring the inflammatory markers: inducible nitric oxide synthase, prostaglandin E2, and interleukin-1 β in the brain. 5-HT system activity was evaluated by measuring 5-HT and its metabolite, 5-HIAA, and the 5-HT precursor, tryptophan. Probiotic treatment of HA rats significantly reduced the level of inflammatory markers, decreased 5-HT metabolism, restored cognitive function and improved anxiety-like behavior. These results indicate that probiotic L. helveticus strain NS8 is beneficial for the treatment of cognitive decline and anxiety-like behavior in HA rats.

Enriched childhood experiences moderate age-related motor and cognitive decline

PubMed Central

Metzler, Megan J.; Saucier, Deborah M.; Metz, Gerlinde A.

2012-01-01

Aging is associated with deterioration of skilled manual movement. Specifically, aging corresponds with increased reaction time, greater movement duration, segmentation of movement, increased movement variability, and reduced ability to adapt to external forces and inhibit previously learned sequences. Moreover, it is thought that decreased lateralization of neural function in older adults may point to increased neural recruitment as a compensatory response to deterioration of key frontal and intra-hemispheric networks, particularly of callosal structures. However, factors that mediate age-related motor decline are not well understood. Here we show that music training in childhood is associated with reduced age-related decline of bimanual and unimanual motor skills in a MIDI keyboard motor learning task. Compared to older adults without music training, older adults with more than a year of music training demonstrated proficient bimanual and unimanual movement, evidenced by enhanced speed and decreased movement errors. Further, this group demonstrated significantly better implicit learning in the weather prediction task, a non-motor task. The performance of older adults with music training in those tasks was comparable to young adults. Older adults, however, displayed greater verbal ability compared to young adults irrespective of a past history of music training. Our results indicate that music training early in life may reduce age-associated decline of neural motor and cognitive networks. PMID:23423702

Brain plasticity and functional losses in the aged: scientific bases for a novel intervention.

PubMed

Mahncke, Henry W; Bronstone, Amy; Merzenich, Michael M

2006-01-01

Aging is associated with progressive losses in function across multiple systems, including sensation, cognition, memory, motor control, and affect. The traditional view has been that functional decline in aging is unavoidable because it is a direct consequence of brain machinery wearing down over time. In recent years, an alternative perspective has emerged, which elaborates on this traditional view of age-related functional decline. This new viewpoint--based upon decades of research in neuroscience, experimental psychology, and other related fields--argues that as people age, brain plasticity processes with negative consequences begin to dominate brain functioning. Four core factors--reduced schedules of brain activity, noisy processing, weakened neuromodulatory control, and negative learning--interact to create a self-reinforcing downward spiral of degraded brain function in older adults. This downward spiral might begin from reduced brain activity due to behavioral change, from a loss in brain function driven by aging brain machinery, or more likely from both. In aggregate, these interrelated factors promote plastic changes in the brain that result in age-related functional decline. This new viewpoint on the root causes of functional decline immediately suggests a remedial approach. Studies of adult brain plasticity have shown that substantial improvement in function and/or recovery from losses in sensation, cognition, memory, motor control, and affect should be possible, using appropriately designed behavioral training paradigms. Driving brain plasticity with positive outcomes requires engaging older adults in demanding sensory, cognitive, and motor activities on an intensive basis, in a behavioral context designed to re-engage and strengthen the neuromodulatory systems that control learning in adults, with the goal of increasing the fidelity, reliability, and power of cortical representations. Such a training program would serve a substantial unmet need in aging adults. Current treatments directed at age-related functional losses are limited in important ways. Pharmacological therapies can target only a limited number of the many changes believed to underlie functional decline. Behavioral approaches focus on teaching specific strategies to aid higher order cognitive functions, and do not usually aspire to fundamentally change brain function. A brain-plasticity-based training program would potentially be applicable to all aging adults with the promise of improving their operational capabilities. We have constructed such a brain-plasticity-based training program and conducted an initial randomized controlled pilot study to evaluate the feasibility of its use by older adults. A main objective of this initial study was to estimate the effect size on standardized neuropsychological measures of memory. We found that older adults could learn the training program quickly, and could use it entirely unsupervised for the majority of the time required. Pre- and posttesting documented a significant improvement in memory within the training group (effect size 0.41, p<0.0005), with no significant within-group changes in a time-matched computer using active control group, or in a no-contact control group. Thus, a brain-plasticity-based intervention targeting normal age-related cognitive decline may potentially offer benefit to a broad population of older adults.

Ovarian fluid mediates the temporal decline in sperm viability in a fish with sperm storage.

PubMed

Gasparini, Clelia; Evans, Jonathan P

2013-01-01

A loss of sperm viability and functionality during sperm transfer and storage within the female reproductive tract can have important fitness implications by disrupting fertilization and impairing offspring development and survival. Consequently, mechanisms that mitigate the temporal decline in sperm function are likely to be important targets of selection. In many species, ovarian fluid is known to regulate and maintain sperm quality. In this paper, we use the guppy Poecilia reticulata, a highly polyandrous freshwater fish exhibiting internal fertilization and sperm storage, to determine whether ovarian fluid (OF) influences the decline in sperm viability (the proportion of live sperm in the ejaculate) over time and whether any observed effects depend on male sexual ornamentation. To address these questions we used a paired experimental design in which ejaculates from individual males were tested in vitro both in presence and absence of OF. Our results revealed that the temporal decline in sperm viability was significantly reduced in the presence of OF compared to a saline control. This finding raises the intriguing possibility that OF may play a role in mediating the decline in sperm quality due to the deleterious effects of sperm ageing, although other possible explanations for this observation are discussed. Interestingly, we also show that the age-related decline in sperm viability was contingent on male sexual ornamentation; males with relatively high levels of iridescence (indicating higher sexual attractiveness) exhibited a more pronounced decline in sperm viability over time than their less ornamented counterparts. This latter finding offers possible insights into the functional basis for the previously observed trade-off between these key components of pre- and postcopulatory sexual selection.

T-Tau is Associated with Objective Memory Decline Over Two Years in Persons Seeking Help for Subjective Cognitive Decline: A Report from the Gothenburg-Oslo MCI Study.

PubMed

Hessen, Erik; Nordlund, Arto; Stålhammar, Jacob; Eckerström, Marie; Bjerke, Maria; Eckerström, Carl; Göthlin, Mattias; Fladby, Tormod; Reinvang, Ivar; Wallin, Anders

2015-01-01

There is a need to find very early markers for pre-clinical Alzheimer's disease as interventions early in the disease process are thought to be most effective. The present study aimed to address the potential relation between cerebrospinal fluid (CSF) biomarkers and reduced cognitive function in a relatively young cohort of memory clinic patients with subjective cognitive decline. 122 patients (mean age 63 years) with subjective cognitive decline were recruited from two university memory clinics and followed for two years. The main finding was that the subgroup with objective memory decline during the study period had significantly higher T-tau at baseline than the group with improved memory. Baseline CSF variables showed a trend toward more pathological values in the patients with memory decline compared to those who improved or remained stable. The baseline memory score of those who declined was significantly better than the baseline score of those who improved over two years. The general trend for the whole group was improved memory and executive test scores. There were no differences in cognitive scores based on CSF quartiles at baseline, nor were there differences in cognitive outcome for patients with early amnestic mild cognitive impairment versus average cognitive function at baseline. The main finding that T-tau rather than amyloid-β was associated with memory decline do not support the prevailing opinion about the chain of events assumed to take place in Alzheimer's disease. In addition, memory decline was not associated with poor baseline memory score. Thus, a memory cut-off indicating low baseline memory would not would have identified the declining group.

Thioredoxin-2 Inhibits Mitochondrial ROS Generation and ASK1 Activity to Maintain Cardiac Function

PubMed Central

Huang, Qunhua; Zhou, Huanjiao Jenny; Zhang, Haifeng; Huang, Yan; Hinojosa-Kirschenbaum, Ford; Fan, Peidong; Yao, Lina; Belardinelli, Luiz; Tellides, George; Giordano, Frank J.; Budas, Grant R.; Min, Wang

2015-01-01

Background Thioredoxin 2 (Trx2) is a key mitochondrial protein which regulates cellular redox and survival by suppressing mitochondrial ROS generation and by inhibiting apoptosis stress kinase-1 (ASK1)-dependent apoptotic signaling. To date, the role of the mitochondrial Trx2 system in heart failure pathogenesis has not been investigated. Methods and Results Western blot and histological analysis revealed that Trx2 protein expression levels were reduced in hearts from patients with dilated cardiomyopathy (DCM), with a concomitant increase in increased ASK1 phosphorylation/activity. Cardiac-specific Trx2 knockout mice (Trx2-cKO). Trx2-cKO mice develop spontaneous DCM at 1 month of age with increased heart size, reduced ventricular wall thickness, and a progressive decline in left ventricular (LV) contractile function, resulting in mortality due to heart failure by ~4 months of age. The progressive decline in cardiac function observed in Trx2-cKO mice was accompanied by disruption of mitochondrial ultrastructure, mitochondrial membrane depolarization, increased mitochondrial ROS generation and reduced ATP production, correlating with increased ASK1 signaling and increased cardiomyocyte apoptosis. Chronic administration of a highly selective ASK1 inhibitor improved cardiac phenotype and reduced maladaptive LV remodeling with significant reductions in oxidative stress, apoptosis, fibrosis and cardiac failure. Cellular data from Trx2-deficient cardiomyocytes demonstrated that ASK1 inhibition reduced apoptosis and reduced mitochondrial ROS generation. Conclusions Our data support an essential role for mitochondrial Trx2 in preserving cardiac function by suppressing mitochondrial ROS production and ASK1-dependent apoptosis. Inhibition of ASK1 represents a promising therapeutic strategy for the treatment of dilated cardiomyopathy and heart failure. PMID:25628390

Lung Function and Incidence of Chronic Obstructive Pulmonary Disease after Improved Cooking Fuels and Kitchen Ventilation: A 9-Year Prospective Cohort Study

PubMed Central

Zhou, Yumin; Zou, Yimin; Li, Xiaochen; Chen, Shuyun; Zhao, Zhuxiang; He, Fang; Zou, Weifeng; Luo, Qiuping; Li, Wenxi; Pan, Yiling; Deng, Xiaoliang; Wang, Xiaoping; Qiu, Rong; Liu, Shiliang; Zheng, Jingping; Zhong, Nanshan; Ran, Pixin

2014-01-01

Background Biomass smoke is associated with the risk of chronic obstructive pulmonary disease (COPD), but few studies have elaborated approaches to reduce the risk of COPD from biomass burning. The purpose of this study was to determine whether improved cooking fuels and ventilation have effects on pulmonary function and the incidence of COPD. Methods and Findings A 9-y prospective cohort study was conducted among 996 eligible participants aged at least 40 y from November 1, 2002, through November 30, 2011, in 12 villages in southern China. Interventions were implemented starting in 2002 to improve kitchen ventilation (by providing support and instruction for improving biomass stoves or installing exhaust fans) and to promote the use of clean fuels (i.e., biogas) instead of biomass for cooking (by providing support and instruction for installing household biogas digesters); questionnaire interviews and spirometry tests were performed in 2005, 2008, and 2011. That the interventions improved air quality was confirmed via measurements of indoor air pollutants (i.e., SO2, CO, CO2, NO2, and particulate matter with an aerodynamic diameter of 10 µm or less) in a randomly selected subset of the participants' homes. Annual declines in lung function and COPD incidence were compared between those who took up one, both, or neither of the interventions. Use of clean fuels and improved ventilation were associated with a reduced decline in forced expiratory volume in 1 s (FEV1): decline in FEV1 was reduced by 12 ml/y (95% CI, 4 to 20 ml/y) and 13 ml/y (95% CI, 4 to 23 ml/y) in those who used clean fuels and improved ventilation, respectively, compared to those who took up neither intervention, after adjustment for confounders. The combined improvements of use of clean fuels and improved ventilation had the greatest favorable effects on the decline in FEV1, with a slowing of 16 ml/y (95% CI, 9 to 23 ml/y). The longer the duration of improved fuel use and ventilation, the greater the benefits in slowing the decline of FEV1 (p<0.05). The reduction in the risk of COPD was unequivocal after the fuel and ventilation improvements, with an odds ratio of 0.28 (95% CI, 0.11 to 0.73) for both improvements. Conclusions Replacing biomass with biogas for cooking and improving kitchen ventilation are associated with a reduced decline in FEV1 and risk of COPD. Trial Registration Chinese Clinical Trial Register ChiCTR-OCH-12002398 Please see later in the article for the Editors' Summary PMID:24667834

Hypertension is associated with cognitive decline in elderly people at high risk for dementia.

PubMed

Wysocki, Michael; Luo, Xiaodong; Schmeidler, James; Dahlman, Karen; Lesser, Gerson T; Grossman, Hillel; Haroutunian, Vahram; Beeri, Michal Schnaider

2012-02-01

Cardiovascular risk factors including hypertension (HTN) have been shown to increase the risk of Alzheimer disease. The current study investigated whether individuals with HTN are more susceptible to increased cognitive decline and whether the influence of HTN on cognitive decline varied as a function of dementia severity. A total of 224 nursing home and assisted living residents, with a mean age of 84.9 (±7.6) years, were assessed longitudinally with Mini Mental State Exams (MMSEs) and Clinical Dementia Ratings (CDR). Baseline dementia status was defined by the CDR score. As described in , MMSE scores in persons with HTN and questionable dementia (CDR = 0.5) declined significantly faster than nonhypertensive questionably demented persons. Hypertensive participants did not decline significantly faster than nonhypertensive participants in persons with intact cognition (CDR = 0) or frank dementia (CDR ≥ 1). These results suggest an increased risk of subsequent cognitive decline in hypertensive individuals who are especially vulnerable to developing dementia and raises the possibility that avoiding or controlling HTN might reduce the rate of cognitive decline in cognitively vulnerable individuals, potentially delaying their conversion to full-fledged dementia.

The NAD+/PARP1/SIRT1 Axis in Aging.

PubMed

Mendelsohn, Andrew R; Larrick, James W

2017-06-01

NAD+ levels decline with age in diverse animals from Caenorhabditis elegans to mice. Raising NAD+ levels by dietary supplementation with NAD+ precursors, nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN), improves mitochondrial function and muscle and neural and melanocyte stem cell function in mice, as well as increases murine life span. Decreased NAD+ levels with age reduce SIRT1 function and reduce the mitochondrial unfolded protein response, which can be overcome by NR supplementation. Decreased NAD+ levels cause NAD+-binding protein DBC1 to form a complex with PARP1, inhibiting poly(adenosine diphosphate-ribose) polymerase (PARP) catalytic activity. Old mice have increased amounts of DBC1-PARP1 complexes, lower PARP activity, increased DNA damage, and reduced nonhomologous end joining and homologous recombination repair. DBC1-PARP1 complexes in old mice can be broken by increasing NAD+ levels through treatment with NMN, reducing DNA damage and restoring PARP activity to youthful levels. The mechanism of declining NAD+ levels and its fundamental importance to aging are yet to be elucidated. There is a correlation of PARP activity with mammalian life span that suggests that NAD+/SIRT1/PARP1 may be more significant than the modest effects on life span observed for NR supplementation in old mice. The NAD+/PARP1/SIRT1 axis may link NAD+ levels and DNA damage with the apparent epigenomic DNA methylation clocks that have been described.

Improvements and decline in the physical functioning of Israeli older adults.

PubMed

Spalter, Tal; Brodsky, Jenny; Shnoor, Yitschak

2014-12-01

The current study depicts improvement and decline in functioning among 3 population groups of Israeli older adults: Jews and veteran immigrants, former Soviet Union immigrants, and Arabs. Using longitudinal data from 2005 and 2010 Survey of Health and Retirement (SHARE) in Israel (n = 982), we examined 4 functional changes in late life in mobility, movement, activities of daily living (ADL), and instrumental ADL, as a function of sociodemographic, health, and social variables The findings reveal that physical functioning among older adults can decline as well as improve over time. Older age, higher number of diseases and comorbidity, living with others (not the spouse) compared with living alone, receiving informal help and formal help with homemaking, and declined mental health and cognitive status predict deterioration in physical functioning. Also, Arab older adults are at higher risk of deterioration over time compared with Jewish older adults. Findings imply that noncompatible assistance to older adults may "save them the hassle" of doing things by themselves and thus, weakens a potential functional rehabilitation process. There is a need to guide not only professional personnel but also nonprofessional home care workers and family members on how to encourage and retain older adults' functions as much as possible in order to improve their quality of life. Another implication of investing in rehabilitation is that it might reduce the disability rate among older adults and thus save health expenditures on long-term care at the macrosocial level. © The Author 2013. 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.

ESTROGENS AND AGE-RELATED MEMORY DECLINE IN RODENTS: WHAT HAVE WE LEARNED AND WHERE DO WE GO FROM HERE?

PubMed Central

Frick, Karyn M.

2009-01-01

The question of whether ovarian hormone therapy can prevent or reduce age-related memory decline in menopausal women has been the subject of much recent debate. Although numerous studies have demonstrated a beneficial effect of estrogen and/or progestin therapy for certain types of memory in menopausal women, recent clinical trials suggest that such therapy actually increases the risk of cognitive decline and dementia. Because rodent models have been frequently used to examine the effects of age and/or ovarian hormone deficiency on mnemonic function, rodent models of age-related hormone and memory decline may be useful in helping to resolve this issue. This review will focus on evidence suggesting that estradiol modulates memory, particularly hippocampal-dependent memory, in young and aging female rats and mice. Various factors affecting the mnemonic response to estradiol in aging females will be highlighted to illustrate the complications inherent to studies of estrogen therapy in aging females. Avenues for future development of estradiol-based therapies will also be discussed, and it is argued that an approach to drug development based on identifying the molecular mechanisms underlying estrogenic modulation of memory may lead to promising future treatments for reducing age-related mnemonic decline. PMID:18835561

Cognitive Function and Brain Structure in Persons With Type 2 Diabetes Mellitus After Intensive Lowering of Blood Pressure and Lipid Levels

PubMed Central

Williamson, Jeff D.; Launer, Lenore J.; Bryan, R. Nick; Coker, Laura H.; Lazar, Ronald M.; Gerstein, Hertzel C.; Murray, Anne M.; Sullivan, Mark D.; Horowitz, Karen R.; Ding, Jingzhong; Marcovina, Santica; Lovato, Laura; Lovato, James; Margolis, Karen L.; Davatzikos, Christos; Barzilay, Joshua; Ginsberg, Henry N.; Linz, Peter E.; Miller, Michael E.

2015-01-01

IMPORTANCE Persons with type 2 diabetes mellitus (T2DM) are at increased risk for decline in cognitive function, reduced brain volume, and increased white matter lesions in the brain. Poor control of blood pressure (BP) and lipid levels are risk factors for T2DM-related cognitive decline, but the effect of intensive treatment on brain function and structure is unknown. OBJECTIVE To examine whether intensive therapy for hypertension and combination therapy with a statin plus a fibrate reduces the risk of decline in cognitive function and total brain volume (TBV) in patients with T2DM. DESIGN, SETTING, AND PARTICIPANTS A North American multicenter clinical trial including 2977 participants without baseline clinical evidence of cognitive impairment or dementia and with hemoglobin A1c (HbA1c) levels less than 7.5% randomized to a systolic BP goal of less than 120 vs less than 140 mm Hg (n = 1439) or to a fibrate vs placebo in patients with low-density lipoprotein cholesterol levels less than 100 mg/dL (n = 1538). Participants were recruited from August 1, 2003, through October 31, 2005, with the final follow-up visit by June 30, 2009. MAIN OUTCOME MEASURES Cognition was assessed at baseline and 20 and 40 months. A subset of 503 participants underwent baseline and 40-month brain magnetic resonance imaging to assess for change in TBV and other structural measures of brain health. RESULTS Baseline mean HbA1c level was 8.3%; mean age, 62 years; and mean duration of T2DM, 10 years. At 40 months, no differences in cognitive function were found in the intensive BP-lowering trial or in the fibrate trial. At 40 months, TBV had declined more in the intensive vs standard BP-lowering group (difference, −4.4 [95% CI, −7.8 to −1.1] cm3; P = .01). Fibrate therapy had no effect on TBV compared with placebo. CONCLUSIONS AND RELEVANCE In participants with long-standing T2DM and at high risk for cardiovascular events, intensive BP control and fibrate therapy in the presence of controlled low-density lipoprotein cholesterol levels did not produce a measurable effect on cognitive decline at 40 months of follow-up. Intensive BP control was associated with greater decline in TBV at 40 months relative to standard therapy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00000620 PMID:24493100

Going outdoors daily predicts long-term functional and health benefits among ambulatory older people.

PubMed

Jacobs, Jeremy M; Cohen, Aaron; Hammerman-Rozenberg, Robert; Azoulay, Daniel; Maaravi, Yoram; Stessman, Jochanan

2008-04-01

This article examines the association between frequency of going out of the house and health and functional status among older people. A randomly chosen cohort of ambulatory participants born in 1920 or 1921 from the Jerusalem Longitudinal Study underwent assessments for health, functional, and psychosocial variables at ages 70 and 77. Twelve-year mortality data were collected. Women went out daily less than did men. Participants going out daily at age 70 reported significantly fewer new complaints at age 77 of musculoskeletal pain, sleep problems, urinary incontinence, and decline in activities of daily living (ADLs). Logistic regression analysis indicated that not going out daily at age 70 was predictive of subsequent dependence in ADL, poor self-rated health, and urinary incontinence at age 77. Going out daily is beneficial among independent older people, correlating with reduced functional decline and improved health measures.

Longitudinal Modeling of Functional Decline Associated with Pathologic Alzheimer's Disease in Older Persons without Cognitive Impairment.

PubMed

Wang, Dai; Schultz, Tim; Novak, Gerald P; Baker, Susan; Bennett, David A; Narayan, Vaibhav A

2018-01-01

Therapeutic research on Alzheimer's disease (AD) has moved to intercepting the disease at the preclinical phase. Most drugs in late development have focused on the amyloid hypothesis. To understand the magnitude of amyloid-related functional decline and to identify the functional domains sensitive to decline in a preclinical AD population. Data were from the Religious Orders Study and the Rush Memory and Aging Project. Cognitive decline was measured by a modified version of the Alzheimer's Disease Cooperative Study Preclinical Alzheimer Cognitive Composite. The trajectories of functional decline, as measured by the instrumental and basic activities of daily living, were longitudinally modeled in 484 participants without cognitive impairment at baseline and having both a final clinical and a postmortem neuropathology assessment of AD. Individuals with different final clinical diagnoses had different trajectories of cognitive and functional decline. Individuals with AD dementia, minor cognitive impairment, and no cognitive impairment had the most, intermediate, and least declines. While individuals with pathologic AD had significantly more cognitive decline over time than those without, the magnitude of difference in functional decline between these two groups was small. Functional domains such as handling finance and handling medications were more sensitive to decline. Demonstrating the functional benefit of an amyloid-targeting drug represents a significant challenge as elderly people experience functional decline due to a wide range of reasons with limited manifestation attributable to AD neuropathology. More sensitive functional scales focusing on the functional domains sensitive to decline in preclinical AD are needed.

The non-linear relationship between body size and function in parrotfishes

NASA Astrophysics Data System (ADS)

Lokrantz, J.; Nyström, M.; Thyresson, M.; Johansson, C.

2008-12-01

Parrotfishes are a group of herbivores that play an important functional role in structuring benthic communities on coral reefs. Increasingly, these fish are being targeted by fishermen, and resultant declines in biomass and abundance may have severe consequences for the dynamics and regeneration of coral reefs. However, the impact of overfishing extends beyond declining fish stocks. It can also lead to demographic changes within species populations where mean body size is reduced. The effect of reduced mean body size on population dynamics is well described in literature but virtually no information exists on how this may influence important ecological functions. The study investigated how one important function, scraping (i.e., the capacity to remove algae and open up bare substratum for coral larval settlement), by three common species of parrotfishes ( Scarus niger, Chlorurus sordidus, and Chlorurus strongylocephalus) on coral reefs at Zanzibar (Tanzania) was influenced by the size of individual fishes. There was a non-linear relationship between body size and scraping function for all species examined, and impact through scraping was also found to increase markedly when fish reached a size of 15 20 cm. Thus, coral reefs which have a high abundance and biomass of parrotfish may nonetheless be functionally impaired if dominated by small-sized individuals. Reductions in mean body size within parrotfish populations could, therefore, have functional impacts on coral reefs that previously have been overlooked.

Antiproteinuric effect of pirfenidone in a rat model of anti-glomerular basement membrane glomerulonephritis.

PubMed

Takakura, Koji; Mizukami, Kazuhiko; Mitori, Hikaru; Noto, Takahisa; Tomura, Yuichi

2014-08-15

While pirfenidone has been established as an effective anti-fibrosis remedy, whether or not its antifibrotic effect contributes to a reduction of proteinuria remains unclear. We investigated the renoprotective properties of pirfenidone in an anti-glomerular basement membrane (GBM) glomerulonephritis model both prophylactically and therapeutically to determine its profile against proteinuria. In the prophylactic regimen, pirfenidone was treated immediately after anti-serum injection. We observed a significant reduction in the progression of proteinuria (P<0.05) and decline in renal function (P<0.01) and also noted histological improvement in renal injury. These effects appeared to be due to the maintained expression of nephrin and podocin on podocytes as well as the reduced expression of profibrotic factors like transforming growth factor-β (TGF-β). The expression of nephrin mRNA was strongly negatively correlated with the amount of urinary protein excretion (R=-0.84, P<0.001), implicating podocyte damage in the outcome of proteinuria (R(2)=0.70). These results suggest that preservation of podocytes with the pirfenidone treatment may have resulted in the decrease of proteinuria. In contrast, when the therapeutic regimen was initiated 2 weeks after nephritis induction, pirfenidone had little effect on the progression of proteinuria, although the decline of renal function and fibrosis were suppressed. Taken together, present findings suggested that pirfenidone prevented the progression of proteinuria only when administered prophylactically but was still able to ameliorate the decline of renal function independent of proteinuria. In conclusion, pirfenidone as a prophylactic regimen reduces proteinuria in anti-GBM nephritis via preservation of podocytes with markedly reduced efficacy when administered as a therapeutic regimen. Copyright © 2014 Elsevier B.V. All rights reserved.

Age-Related Decline in Anticipatory Motor Planning and Its Relation to Cognitive and Motor Skill Proficiency.

PubMed

Stöckel, Tino; Wunsch, Kathrin; Hughes, Charmayne M L

2017-01-01

Anticipatory motor planning abilities mature as children grow older, develop throughout childhood and are likely to be stable till the late sixties. In the seventh decade of life, motor planning performance dramatically declines, with anticipatory motor planning abilities falling to levels of those exhibited by children. At present, the processes enabling successful anticipatory motor planning in general, as do the cognitive processes mediating these age-related changes, remain elusive. Thus, the aim of the present study was (a) to identify cognitive and motor functions that are most affected by normal aging and (b) to elucidate key (cognitive and motor) factors that are critical for successful motor planning performance in young ( n = 40, mean age = 23.1 ± 2.6 years) and older adults ( n = 37, mean age = 73.5 ± 7.1 years). Results indicate that normal aging is associated with a marked decline in all aspects of cognitive and motor functioning tested. However, age-related declines were more apparent for fine motor dexterity, processing speed and cognitive flexibility. Furthermore, up to 64% of the variance in motor planning performance across age groups could be explained by the cognitive functions processing speed, response planning and cognitive flexibility. It can be postulated that anticipatory motor planning abilities are strongly influenced by cognitive control processes, which seem to be key mechanisms to compensate for age-related decline. These findings support the general therapeutic and preventive value of cognitive-motor training programs to reduce adverse effects associated with high age.

Longitudinal assessment of spirometry in the World Trade Center medical monitoring program.

PubMed

Skloot, Gwen S; Schechter, Clyde B; Herbert, Robin; Moline, Jacqueline M; Levin, Stephen M; Crowley, Laura E; Luft, Benjamin J; Udasin, Iris G; Enright, Paul L

2009-02-01

Multiple studies have demonstrated an initial high prevalence of spirometric abnormalities following World Trade Center (WTC) disaster exposure. We assessed prevalence of spirometric abnormalities and changes in spirometry between baseline and first follow-up evaluation in participants in the WTC Worker and Volunteer Medical Monitoring Program. We also determined the predictors of spirometric change between the two examinations. Prebronchodilator and postbronchodilator spirometry, demographics, occupational history, smoking status, and respiratory symptoms and exposure onset were obtained at both examinations (about 3 years apart). At the second examination, 24.1% of individuals had abnormal spirometry findings. The predominant defect was a low FVC without obstruction (16.1%). Between examinations, the majority of individuals did not have a greater-than-expected decline in lung function. The mean declines in prebronchodilator FEV(1) and FVC were 13 mL/yr and 2 mL/yr, respectively (postbronchodilator results were similar and not reported). Significant predictors of greater average decline between examinations were lack of bronchodilator responsiveness at examination 1 and weight gain [corrected]. Elevated rates of spirometric abnormalities were present at both examinations, with reduced FVC most common. Although the majority had a normal decline in lung function, lack of bronchodilator response at examination 1 and weight gain were significantly associated with greater-than-normal lung function declines [corrected]. Due to the presence of spirometric abnormalities > 5 years after the disaster in many exposed individuals, longer-term monitoring of WTC responders is essential.

Is the Mediterranean diet a feasible approach to preserving cognitive function and reducing risk of dementia for older adults in Western countries? New insights and future directions.

PubMed

Knight, Alissa; Bryan, Janet; Murphy, Karen

2016-01-01

The rise in the ageing population has resulted in increased incident rates of cognitive impairment and dementia. The subsequent financial and societal burden placed on an already strained public health care system is of increasing concern. Evidence from recent studies has revealed modification of lifestyle and dietary behaviours is, at present, the best means of prevention. Some of the most important findings, in relation to the Mediterranean diet (MedDiet) and the contemporary Western diet, and potential molecular mechanisms underlying the effects of these two diets on age-related cognitive function, are discussed in this review. A major aim of this review was to discuss whether or not a MedDiet intervention would be a feasible preventative approach against cognitive decline for older adults living in Western countries. Critical appraisal of the literature does somewhat support this idea. Demonstrated evidence highlights the MedDiet as a potential strategy to reduce cognitive decline in older age, and suggests the Western diet may play a role in the aetiology of cognitive decline. However, strong intrinsic Western socio-cultural values, traditions and norms may impede on the feasibility of this notion. Copyright © 2015 Elsevier B.V. All rights reserved.

Species-specific impacts of suspended sediments on gill structure and function in coral reef fishes.

PubMed

Hess, Sybille; Prescott, Leteisha J; Hoey, Andrew S; McMahon, Shannon A; Wenger, Amelia S; Rummer, Jodie L

2017-11-15

Reduced water quality, in particular increases in suspended sediments, has been linked to declines in fish abundance on coral reefs. Changes in gill structure induced by suspended sediments have been hypothesized to impair gill function and may provide a mechanistic basis for the observed declines; yet, evidence for this is lacking. We exposed juveniles of three reef fish species ( Amphiprion melanopus , Amphiprion percula and Acanthochromis polyacanthus ) to suspended sediments (0-180 mg l -1 ) for 7 days and examined changes in gill structure and metabolic performance (i.e. oxygen consumption). Exposure to suspended sediments led to shorter gill lamellae in A. melanopus and A. polyacanthus and reduced oxygen diffusion distances in all three species. While A. melanopus exhibited impaired oxygen uptake after suspended sediment exposure, i.e. decreased maximum and increased resting oxygen consumption rates resulting in decreased aerobic scope, the oxygen consumption rates of the other two species remained unaffected. These findings imply that species sensitive to changes in gill structure such as A. melanopus may decline in abundance as reefs become more turbid, whereas species that are able to maintain metabolic performance despite suspended sediment exposure, such as A. polyacanthus or A. percula , may be able to persist or gain a competitive advantage. © 2017 The Author(s).

Effects of weightlessness on human baroreflex function

NASA Technical Reports Server (NTRS)

Fritsch, Janice M.; Eckberg, Dwain L.

1992-01-01

Impaired cardiovascular function, characterized by orthostatic intolerance and reduced exercise capacity, is a result of space travel. We hypothesized that postflight baroreflex dysfunction may contribute. We studied the vagally mediated carotid baroreceptor-cardiac reflex response of 6 astronauts before, during, and after the ten day SLS-l mission. A series of R-waves triggered pressure and suction steps (from 40 to minus 65 mmHg) were delivered to a neck chamber during held expirtation. Resulting R-R interval changes were plotted against carotid distending pressure (systolic - neck pressure), and curve parameters calculated. After an initial rise, the operational point declined consistently during the flight and reached a nadir on landing day, but had recovered to preflight levels by L + 4. Slope and range of the response declined throughout the flight, were slightly recovered by the time measurements were made on landing day, but still were reduced on L + 4. These data indicate that space flight results in a significant impairment of the carotid baroreceptor cardiac reflex response.

Specific ablation of Nampt in adult neural stem cells recapitulates their functional defects during aging

PubMed Central

Stein, Liana R; Imai, Shin-ichiro

2014-01-01

Neural stem/progenitor cell (NSPC) proliferation and self-renewal, as well as insult-induced differentiation, decrease markedly with age. The molecular mechanisms responsible for these declines remain unclear. Here, we show that levels of NAD+ and nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme in mammalian NAD+ biosynthesis, decrease with age in the hippocampus. Ablation of Nampt in adult NSPCs reduced their pool and proliferation in vivo. The decrease in the NSPC pool during aging can be rescued by enhancing hippocampal NAD+ levels. Nampt is the main source of NSPC NAD+ levels and required for G1/S progression of the NSPC cell cycle. Nampt is also critical in oligodendrocytic lineage fate decisions through a mechanism mediated redundantly by Sirt1 and Sirt2. Ablation of Nampt in the adult NSPCs in vivo reduced NSPC-mediated oligodendrogenesis upon insult. These phenotypes recapitulate defects in NSPCs during aging, giving rise to the possibility that Nampt-mediated NAD+ biosynthesis is a mediator of age-associated functional declines in NSPCs. PMID:24811750

Changing dynamics of Caribbean reef carbonate budgets: emergence of reef bioeroders as critical controls on present and future reef growth potential.

PubMed

Perry, Chris T; Murphy, Gary N; Kench, Paul S; Edinger, Evan N; Smithers, Scott G; Steneck, Robert S; Mumby, Peter J

2014-12-07

Coral cover has declined rapidly on Caribbean reefs since the early 1980s, reducing carbonate production and reef growth. Using a cross-regional dataset, we show that widespread reductions in bioerosion rates-a key carbonate cycling process-have accompanied carbonate production declines. Bioerosion by parrotfish, urchins, endolithic sponges and microendoliths collectively averages 2 G (where G = kg CaCO3 m(-2) yr(-1)) (range 0.96-3.67 G). This rate is at least 75% lower than that reported from Caribbean reefs prior to their shift towards their present degraded state. Despite chronic overfishing, parrotfish are the dominant bioeroders, but erosion rates are reduced from averages of approximately 4 to 1.6 G. Urchin erosion rates have declined further and are functionally irrelevant to bioerosion on most reefs. These changes demonstrate a fundamental shift in Caribbean reef carbonate budget dynamics. To-date, reduced bioerosion rates have partially offset carbonate production declines, limiting the extent to which more widespread transitions to negative budget states have occurred. However, given the poor prognosis for coral recovery in the Caribbean and reported shifts to coral community states dominated by slower calcifying taxa, a continued transition from production to bioerosion-controlled budget states, which will increasingly threaten reef growth, is predicted. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Variation in lung function is associated with worse clinical outcomes in cystic fibrosis

PubMed Central

Heinzmann-Filho, João Paulo; Pinto, Leonardo Araujo; Marostica, Paulo José Cauduro; Donadio, Márcio Vinícius Fagundes

2015-01-01

ABSTRACT OBJECTIVE: To determine whether the variation in lung function over one year is associated with worse clinical outcomes, as well as with a decline in lung function in the following years, in patients with cystic fibrosis (CF). METHODS: This was a retrospective study involving CF patients (4-19 years of age), evaluated over a three-year period. We evaluated demographic characteristics, chronic Pseudomonas aeruginosa infection, antibiotic use, hospitalization, six-minute walk distance (6MWD), and lung function. The inclusion criterion was having undergone pulmonary function testing at least three times in the first year and at least once in each of the next two years. RESULTS: We evaluated 35 CF patients. The variation in FEV1 in the first year (ΔFEV1) was greater among those who, in the third year, showed reduced FEV1, had a below-average 6MWD, or were hospitalized than among those with normal FEV1, normal 6MWD, or no hospital admissions, in that same year (p < 0.05), although no such difference was found for antibiotic use in the third year. Subjects showing a ΔFEV1 ≥ 10% also showed a greater decline in FEV1 over the two subsequent years (p = 0.04). The ΔFEV1 also showed an inverse correlation with absolute FEV1 in the third year (r = −0.340, p = 0.04) and with the rate of FEV1 decline (r = −0.52, p = 0.001). Linear regression identified ΔFEV1 as a predictor of FEV1 decline (coefficient of determination, 0.27). CONCLUSIONS: Significant variation in lung function over one year seems to be associated with a higher subsequent rate of FEV1 decline and worse clinical outcomes in CF patients. Short-term ΔFEV1 might prove useful as a predictor of CF progression in clinical practice. PMID:26785959

Whole genome prediction and heritability of childhood asthma phenotypes.

PubMed

McGeachie, Michael J; Clemmer, George L; Croteau-Chonka, Damien C; Castaldi, Peter J; Cho, Michael H; Sordillo, Joanne E; Lasky-Su, Jessica A; Raby, Benjamin A; Tantisira, Kelan G; Weiss, Scott T

2016-12-01

While whole genome prediction (WGP) methods have recently demonstrated successes in the prediction of complex genetic diseases, they have not yet been applied to asthma and related phenotypes. Longitudinal patterns of lung function differ between asthmatics, but these phenotypes have not been assessed for heritability or predictive ability. Herein, we assess the heritability and genetic predictability of asthma-related phenotypes. We applied several WGP methods to a well-phenotyped cohort of 832 children with mild-to-moderate asthma from CAMP. We assessed narrow-sense heritability and predictability for airway hyperresponsiveness, serum immunoglobulin E, blood eosinophil count, pre- and post-bronchodilator forced expiratory volume in 1 sec (FEV 1 ), bronchodilator response, steroid responsiveness, and longitudinal patterns of lung function (normal growth, reduced growth, early decline, and their combinations). Prediction accuracy was evaluated using a training/testing set split of the cohort. We found that longitudinal lung function phenotypes demonstrated significant narrow-sense heritability (reduced growth, 95%; normal growth with early decline, 55%). These same phenotypes also showed significant polygenic prediction (areas under the curve [AUCs] 56% to 62%). Including additional demographic covariates in the models increased prediction 4-8%, with reduced growth increasing from 62% to 66% AUC. We found that prediction with a genomic relatedness matrix was improved by filtering available SNPs based on chromatin evidence, and this result extended across cohorts. Longitudinal reduced lung function growth displayed extremely high heritability. All phenotypes with significant heritability showed significant polygenic prediction. Using SNP-prioritization increased prediction across cohorts. WGP methods show promise in predicting asthma-related heritable traits.

Cognition and Depression Following Deep Brain Stimulation of the Subthalamic Nucleus and Globus Pallidus Pars Internus in Parkinson's Disease: A Meta-Analysis.

PubMed

Combs, Hannah L; Folley, Bradley S; Berry, David T R; Segerstrom, Suzanne C; Han, Dong Y; Anderson-Mooney, Amelia J; Walls, Brittany D; van Horne, Craig

2015-12-01

Parkinson's disease (PD) is a common, degenerative disorder of the central nervous system. Individuals experience predominantly extrapyramidal symptoms including resting tremor, rigidity, bradykinesia, gait abnormalities, cognitive impairment, depression, and neurobehavioral concerns. Cognitive impairments associated with PD are diverse, including difficulty with attention, processing speed, executive functioning, memory recall, visuospatial functions, word-retrieval, and naming. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) is FDA approved and has been shown to be effective in reducing motor symptoms of PD. Studies have found that stimulating STN and GPi are equally effective at improving motor symptoms and dyskinesias; however, there has been discrepancy as to whether the cognitive, behavioral, and mood symptoms are affected differently between the two targets. The present study used random-effects meta-analytic models along with a novel p-curve analytic procedure to compare the potential cognitive and emotional impairments associated with STN-DBS in the current literature to those associated with GPi-DBS. Forty-one articles were reviewed with an aggregated sample size of 1622 patients. Following STN-DBS, small declines were found in psychomotor speed, memory, attention, executive functions, and overall cognition; and moderate declines were found in both semantic and phonemic fluency. However, GPi-DBS resulted in fewer neurocognitive declines than STN-DBS (small declines in attention and small-moderate declines in verbal fluency). With regards to its effect on depression symptomatology, both GPi-DBS and STN-DBS resulted in lower levels of depressive symptoms post-surgery. From a neurocognitive standpoint, both GPi-DBS and STN-DBS produce subtle cognitive declines but appears to be relatively well tolerated.

Enteral tube feeding in adults with cystic fibrosis; patient choice and impact on long term outcomes.

PubMed

White, H; Morton, A M; Conway, S P; Peckham, D G

2013-12-01

Enteral tube feeding (ETF) has been evaluated in paediatric and mixed child and adult populations with cystic fibrosis, demonstrating positive outcomes from 6 months to 2 years post insertion. No studies have examined the longer term nutritional and clinical outcomes in an exclusively adult population with cystic fibrosis or compared the outcomes for those who meet standard criteria and opt to undertake or decline ETF. Twenty three out of 380 patients attending the Leeds Regional Adult CF unit fulfilled the standard criteria for commencing ETF (CF Trust, 2002) between 2004 and 2008. Weight, BMI, FEV1, FVC, CFRD, and number of intravenous antibiotic treatment days were collected at 1 year pre baseline, at baseline, and at 1, 2, and 3 years post baseline for all these patients whether they accepted or declined ETF. Seventeen of the 23 patients agreed to accept a programme of ETF, two of whom died within the first year of ETF. In the remaining patients (n=15), weight increased by 19.5% from baseline (p<0.001), BMI increased to within the normal range and lung function stabilised. There was no reduction in the requirement for intravenous antibiotic treatment. The six patients who declined ETF had a decline in lung function and no weight gain. Supplemental enteral tube feeding improves clinical outcomes when administered over 3 years, resulting in significant weight gain, a normal BMI and stabilisation of lung function. It does not reduce intravenous antibiotic treatment days. In contrast those patients eligible for, but who declined ETF, showed a deterioration in lung function and a failure to gain weight and to achieve normal BMI status. Copyright © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Normal cognitive decline or dementia?

PubMed

Ebmeier, Klaus P

2010-01-01

Cognitive speed, inhibitory function, and memory decline with age while crystallised, particularly verbal, abilities remain largely intact. Poor health, fewer years of education, lower activity, the presence of the APOE E4 allele, and high BP appear to predict faster cognitive decline. Dementia is diagnosed in the presence of objective cognitive impairment, both long- and short-term memory, plus at least one additional (cortical) cognitive deficit, such as dysphasia, dyspraxia, agnosia, or disturbance in executive functioning. In addition, patients have to show significant impairment in social or occupational functioning and a significant decline from previous levels. Both smoking and diabetes increase the risk of all types of dementia, not smoking or even stopping smoking reduces this risk, but better control of type 2 diabetes does not appear to have a measurable effect. Drinking small to moderate amounts of alcohol appears to confer some benefit in ameliorating cognitive decline. There is some evidence that HRT, DHEA, BP lowering in patients without prior cerebrovascular disease, statins, vitamin B6 and procaine are NOT helpful. There is insufficient evidence to establish or refute a beneficial effect for exercise, treatment of type 2 diabetes, omega-3 fatty acids, folic acid with/without vitamin B12, antioxidant vitamins, or ginkgo biloba. Depressive symptoms are more prevalent than dementia. Clinical (major) depression can present with cognitive deterioration, often associated with subjective complaints. Patients with subjective or objective memory impairment, but without functional deterioration, can be referred to the local memory clinic, while demented patients eligible for acetylcholinesterase inhibitor treatment, patients whose diagnosis is unclear and who may need some specific investigations, as well as patients who may benefit from a combined approach with psychotropic drugs and behavioural support should be referred to the local mental health team.

Assistive technologies to overcome sarcopenia in ageing.

PubMed

Scott, Rachel A; Callisaya, Michele L; Duque, Gustavo; Ebeling, Peter R; Scott, David

2018-06-01

Sarcopenia is an age-related decline in skeletal muscle mass and function that results in disability and loss of independence. It affects up to 30% of older adults. Exercise (particularly progressive resistance training) and nutrition are key strategies in preventing and reversing declines in muscle mass, strength and power during ageing, but many sarcopenic older adults fail to meet recommended levels of both physical activity and dietary nutrient intake. Assistive technology (AT) describes devices or systems used to maintain or improve physical functioning. These may help sarcopenic older adults to maintain independence, and also to achieve adequate physical activity and nutrition. There is a paucity of research exploring the use of AT in sarcopenic patients, but there is evidence that AT, including walking aids, may reduce functional decline in other populations with disability. Newer technologies, such as interactive and virtual reality games, as well as wearable devices and smartphone applications, smart homes, 3D printed foods, exoskeletons and robotics, and neuromuscular electrical stimulation also hold promise for improving engagement in physical activity and nutrition behaviours to prevent further functional declines. While AT may be beneficial for sarcopenic patients, clinicians should be aware of its potential limitations. In particular, there are high rates of patient abandonment of AT, which may be minimised by appropriate training and monitoring of use. Clinicians should preferentially prescribe AT devices which promote physical activity. Further research is required in sarcopenic populations to identify strategies for effective use of current and emerging AT devices. Copyright © 2018 Elsevier B.V. All rights reserved.

Long-term impact of liver transplantation on respiratory function and nutritional status in children and adults with cystic fibrosis.

PubMed

Dowman, J K; Watson, D; Loganathan, S; Gunson, B K; Hodson, J; Mirza, D F; Clarke, J; Lloyd, C; Honeybourne, D; Whitehouse, J L; Nash, E F; Kelly, D; van Mourik, I; Newsome, P N

2012-04-01

Early liver transplant (LT) has been advocated for patients with cystic fibrosis liver disease (CFLD) and evidence of deterioration in nutritional state and respiratory function to prevent further decline. However, the impact of single LT on long-term respiratory function and nutritional status has not been adequately addressed. We performed a retrospective analysis of the outcomes of 40 (21 adult/19 pediatric) patients with CFLD transplanted between 1987 and 2009 with median follow-up of 47.8 months (range 4-180). One and five-year actuarial survival rates were 85%/64% for adult and 90%/85% for pediatric LT cohorts, respectively. Lung function remained stable until 4 years (FEV(1) % predicted; pretransplant 48.4% vs. 45.9%, 4 years posttransplant) but declined by 5 years (42.4%). Up to 4 years posttransplant mean annual decline in FEV(1) % was lower (0.74%; p = 0.04) compared with the predicted 3% annual decline in CF patients with comorbidity including diabetes. Number of courses of intravenous antibiotics was reduced following LT, from 3.9/year pretransplant to 1.1/year, 5 years posttransplant. Body mass index was preserved posttransplant; 18.0 kg/m(2) (range 15-24.3) pretransplant versus 19.6 kg/m(2) (range 16.4-22.7) 5 years posttransplant. In conclusion, LT is an effective treatment for selected patients with cirrhosis due to CFLD, stabilizing aspects of long-term lung function and preserving nutritional status. © Copyright 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

Amblyopia: The Thalamus Is a No-Go Area for Visual Acuity.

PubMed

Seignette, Koen; Levelt, Christiaan N

2018-06-18

When one eye does not function well during development, the visual cortex becomes less responsive to it and visual acuity declines. New research suggests that reduced response strength and deteriorating acuity occur in separate circuits. Copyright © 2018 Elsevier Ltd. All rights reserved.

Asthma Is a Risk Factor for Respiratory Exacerbations Without Increased Rate of Lung Function Decline: Five-Year Follow-up in Adult Smokers From the COPDGene Study.

PubMed

Hayden, Lystra P; Hardin, Megan E; Qiu, Weiliang; Lynch, David A; Strand, Matthew J; van Beek, Edwin J; Crapo, James D; Silverman, Edwin K; Hersh, Craig P

2018-02-01

Previous investigations in adult smokers from the COPDGene Study have shown that early-life respiratory disease is associated with reduced lung function, COPD, and airway thickening. Using 5-year follow-up data, we assessed disease progression in subjects who had experienced early-life respiratory disease. We hypothesized that there are alternative pathways to reaching reduced FEV 1 and that subjects who had childhood pneumonia, childhood asthma, or asthma-COPD overlap (ACO) would have less lung function decline than subjects without these conditions. Subjects returning for 5-year follow-up were assessed. Childhood pneumonia was defined by self-reported pneumonia at < 16 years. Childhood asthma was defined as self-reported asthma diagnosed by a health professional at < 16 years. ACO was defined as subjects with COPD who self-reported asthma diagnosed by a health-professional at ≤ 40 years. Smokers with and those without these early-life respiratory diseases were compared on measures of disease progression. Follow-up data from 4,915 subjects were examined, including 407 subjects who had childhood pneumonia, 323 subjects who had childhood asthma, and 242 subjects with ACO. History of childhood asthma or ACO was associated with an increased exacerbation frequency (childhood asthma, P < .001; ACO, P = .006) and odds of severe exacerbations (childhood asthma, OR, 1.41; ACO, OR, 1.42). History of childhood pneumonia was associated with increased exacerbations in subjects with COPD (absolute difference [β], 0.17; P = .04). None of these early-life respiratory diseases were associated with an increased rate of lung function decline or progression on CT scans. Subjects who had early-life asthma are at increased risk of developing COPD and of having more active disease with more frequent and severe respiratory exacerbations without an increased rate of lung function decline over a 5-year period. ClinicalTrials.gov; No. NCT00608764; https://clinicaltrials.gov. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Decline in physical performance among women with a recent transient ischemic attack or ischemic stroke: opportunities for functional preservation a report of the Women's Estrogen Stroke Trial.

PubMed

Kernan, Walter N; Viscoli, Catherine M; Brass, Lawrence M; Gill, Thomas M; Sarrel, Philip M; Horwitz, Ralph I

2005-03-01

Physical performance for walking, reaching, turning, and other common tasks is a major determinant of functional independence after stroke. Current strategies to preserve physical performance focus on prevention of recurrent stroke. Loss of physical performance, however, may occur in the absence of recurrence. To examine this possibility, we measured change in physical performance, independent of subsequent stroke, among women with a recent ischemic stroke or transient ischemic attack (TIA). Among 664 postmenopausal women who participated in a clinical trial of estrogen therapy after stroke or TIA, we administered the Physical Performance Test (PPT) at baseline (mean 58 days from the cerebrovascular event) and annually. Women who died or had a stroke during follow-up were censored. Decline or improvement in physical performance was defined as a change in the PPT score from baseline of at least 3 points. Sustained decline or improvement was defined as 2 consecutive years during which the score had declined or improved, respectively, relative to the baseline score. With each year of follow-up, a smaller proportion of the cohort demonstrated improvement (16% in year 1, 6% in year 5) and a larger proportion demonstrated decline (15% in year 1, 35% in year 5). In an analysis restricted to 259 women with 3 years of follow-up, 46 (18%) experienced a nonsustained decline in physical performance, and 39 (15%) experienced a sustained decline. Decline in physical performance is common after an ischemic stroke or TIA even in the absence of a recurrent neurological event. Our findings suggest that specific interventions to maintain and improve physical performance may be important for reducing long-term disability.

Predictive abilities of cardiovascular biomarkers to rapid decline of renal function in Chinese community-dwelling population: a 5-year prospective analysis.

PubMed

Fu, Shihui; Liu, Chunling; Luo, Leiming; Ye, Ping

2017-11-09

Predictive abilities of cardiovascular biomarkers to renal function decline are more significant in Chinese community-dwelling population without glomerular filtration rate (GFR) below 60 ml/min/1.73m 2 , and long-term prospective study is an optimal choice to explore this problem. Aim of this analysis was to observe this problem during the follow-up of 5 years. In a large medical check-up program in Beijing, there were 948 participants with renal function evaluated at baseline and follow-up of 5 years. Physical examinations were performed by well-trained physicians. Blood samples were analyzed by qualified technicians in central laboratory. Median rate of renal function decline was 1.46 (0.42-2.91) mL/min/1.73m 2 /year. Rapid decline of renal function had a prevalence of 23.5% (223 participants). Multivariate linear and Logistic regression analyses confirmed that age, sex, baseline GFR, homocysteine and N-terminal pro B-type natriuretic peptide (NT-proBNP) had independently predictive abilities to renal function decline rate and rapid decline of renal function (p < 0.05 for all). High-sensitivity cardiac troponin T (hs-cTnT), carotid femoral pulse wave velocity and central augmentation index had no statistically independent association with renal function decline rate and rapid decline of renal function (p > 0.05 for all). Homocysteine and NT-proBNP rather than hs-cTnT had independently predictive abilities to rapid decline of renal function in Chinese community-dwelling population without GFR below 60 ml/min/1.73m 2 . Baseline GFR was an independent factor predicting the rapid decline of renal function. Arterial stiffness and compliance had no independent effect on rapid decline of renal function. This analysis has a significant implication for public health, and changing the homocysteine and NT-proBNP levels might slow the rapid decline of renal function.

Exercise Prescriptions for Active Seniors: A Team Approach for Maximizing Adherence.

ERIC Educational Resources Information Center

Brennan, Fred H., Jr.

2002-01-01

Exercise is an important "medication" that healthcare providers can prescribe for their geriatric patients. Increasing physical fitness by participating in regular exercise can reduce the effects of aging that lead to functional declines and poor health. Modest regular exercise can substantially lower the risk of death from coronary…

The Effects of Group Work with Institutionalized Elderly Persons

ERIC Educational Resources Information Center

Duyan, Veli; Sahin-Kara, Gülay; Camur Duyan, Gülsüm; Özdemir, Burcu; Megahead, Hamido A.

2017-01-01

Objectives: This research article aims to measure the effects of group therapy on institutionalized elderly in terms of reducing depression and improving psychosocial functioning. Methods: Thirty elderly nursing home residents were recruited, and 16 of them elected to receive group treatment for depression and 14 declined treatment. The…

Age-Related Decline in Anticipatory Motor Planning and Its Relation to Cognitive and Motor Skill Proficiency

PubMed Central

Stöckel, Tino; Wunsch, Kathrin; Hughes, Charmayne M. L.

2017-01-01

Anticipatory motor planning abilities mature as children grow older, develop throughout childhood and are likely to be stable till the late sixties. In the seventh decade of life, motor planning performance dramatically declines, with anticipatory motor planning abilities falling to levels of those exhibited by children. At present, the processes enabling successful anticipatory motor planning in general, as do the cognitive processes mediating these age-related changes, remain elusive. Thus, the aim of the present study was (a) to identify cognitive and motor functions that are most affected by normal aging and (b) to elucidate key (cognitive and motor) factors that are critical for successful motor planning performance in young (n = 40, mean age = 23.1 ± 2.6 years) and older adults (n = 37, mean age = 73.5 ± 7.1 years). Results indicate that normal aging is associated with a marked decline in all aspects of cognitive and motor functioning tested. However, age-related declines were more apparent for fine motor dexterity, processing speed and cognitive flexibility. Furthermore, up to 64% of the variance in motor planning performance across age groups could be explained by the cognitive functions processing speed, response planning and cognitive flexibility. It can be postulated that anticipatory motor planning abilities are strongly influenced by cognitive control processes, which seem to be key mechanisms to compensate for age-related decline. These findings support the general therapeutic and preventive value of cognitive-motor training programs to reduce adverse effects associated with high age. PMID:28928653

Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex.

PubMed

Jeong, Da Un; Oh, Jin Hwan; Lee, Ji Eun; Lee, Jihyeon; Cho, Zang Hee; Chang, Jin Woo; Chang, Won Seok

2016-01-01

Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by ¹⁸F-2-fluoro-2-deoxyglucose positron emission tomography. During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.

Water Transport Properties of the Grape Pedicel during Fruit Development: Insights into Xylem Anatomy and Function Using Microtomography.

PubMed

Knipfer, Thorsten; Fei, Jiong; Gambetta, Gregory A; McElrone, Andrew J; Shackel, Kenneth A; Matthews, Mark A

2015-08-01

Xylem flow of water into fruits declines during fruit development, and the literature indicates a corresponding increase in hydraulic resistance in the pedicel. However, it is unknown how pedicel hydraulics change developmentally in relation to xylem anatomy and function. In this study on grape (Vitis vinifera), we determined pedicel hydraulic conductivity (kh) from pressure-flow relationships using hydrostatic and osmotic forces and investigated xylem anatomy and function using fluorescent light microscopy and x-ray computed microtomography. Hydrostatic kh (xylem pathway) was consistently 4 orders of magnitude greater than osmotic kh (intracellular pathway), but both declined before veraison by approximately 40% and substantially over fruit development. Hydrostatic kh declined most gradually for low (less than 0.08 MPa) pressures and for water inflow and outflow conditions. Specific kh (per xylem area) decreased in a similar fashion to kh despite substantial increases in xylem area. X-ray computed microtomography images provided direct evidence that losses in pedicel kh were associated with blockages in vessel elements, whereas air embolisms were negligible. However, vessel elements were interconnected and some remained continuous postveraison, suggesting that across the grape pedicel, a xylem pathway of reduced kh remains functional late into berry ripening. © 2015 American Society of Plant Biologists. All Rights Reserved.

Water Transport Properties of the Grape Pedicel during Fruit Development: Insights into Xylem Anatomy and Function Using Microtomography1[OPEN

PubMed Central

Fei, Jiong; McElrone, Andrew J.; Shackel, Kenneth A.; Matthews, Mark A.

2015-01-01

Xylem flow of water into fruits declines during fruit development, and the literature indicates a corresponding increase in hydraulic resistance in the pedicel. However, it is unknown how pedicel hydraulics change developmentally in relation to xylem anatomy and function. In this study on grape (Vitis vinifera), we determined pedicel hydraulic conductivity (kh) from pressure-flow relationships using hydrostatic and osmotic forces and investigated xylem anatomy and function using fluorescent light microscopy and x-ray computed microtomography. Hydrostatic kh (xylem pathway) was consistently 4 orders of magnitude greater than osmotic kh (intracellular pathway), but both declined before veraison by approximately 40% and substantially over fruit development. Hydrostatic kh declined most gradually for low (less than 0.08 MPa) pressures and for water inflow and outflow conditions. Specific kh (per xylem area) decreased in a similar fashion to kh despite substantial increases in xylem area. X-ray computed microtomography images provided direct evidence that losses in pedicel kh were associated with blockages in vessel elements, whereas air embolisms were negligible. However, vessel elements were interconnected and some remained continuous postveraison, suggesting that across the grape pedicel, a xylem pathway of reduced kh remains functional late into berry ripening. PMID:26077763

Role of Physical Therapists in Reducing Hospital Readmissions: Optimizing Outcomes for Older Adults During Care Transitions From Hospital to Community

PubMed Central

Burke, Robert E.; Malone, Daniel; Ridgeway, Kyle J.; McManus, Beth M.; Stevens-Lapsley, Jennifer E.

2016-01-01

Hospital readmissions in older adult populations are an emerging quality indicator for acute care hospitals. Recent evidence has linked functional decline during and after hospitalization with an elevated risk of hospital readmission. However, models of care that have been developed to reduce hospital readmission rates do not adequately address functional deficits. Physical therapists, as experts in optimizing physical function, have a strong opportunity to contribute meaningfully to care transition models and demonstrate the value of physical therapy interventions in reducing readmissions. Thus, the purposes of this perspective article are: (1) to describe the need for physical therapist input during care transitions for older adults and (2) to outline strategies for expanding physical therapy participation in care transitions for older adults, with an overall goal of reducing avoidable 30-day hospital readmissions. PMID:26939601

Role of Physical Therapists in Reducing Hospital Readmissions: Optimizing Outcomes for Older Adults During Care Transitions From Hospital to Community.

PubMed

Falvey, Jason R; Burke, Robert E; Malone, Daniel; Ridgeway, Kyle J; McManus, Beth M; Stevens-Lapsley, Jennifer E

2016-08-01

Hospital readmissions in older adult populations are an emerging quality indicator for acute care hospitals. Recent evidence has linked functional decline during and after hospitalization with an elevated risk of hospital readmission. However, models of care that have been developed to reduce hospital readmission rates do not adequately address functional deficits. Physical therapists, as experts in optimizing physical function, have a strong opportunity to contribute meaningfully to care transition models and demonstrate the value of physical therapy interventions in reducing readmissions. Thus, the purposes of this perspective article are: (1) to describe the need for physical therapist input during care transitions for older adults and (2) to outline strategies for expanding physical therapy participation in care transitions for older adults, with an overall goal of reducing avoidable 30-day hospital readmissions. © 2016 American Physical Therapy Association.

Patterns of Kidney Function Decline in Autosomal Dominant Polycystic Kidney Disease: A Post Hoc Analysis From the HALT-PKD Trials.

PubMed

Brosnahan, Godela M; Abebe, Kaleab Z; Moore, Charity G; Rahbari-Oskoui, Frederic F; Bae, Kyongtae T; Grantham, Jared J; Schrier, Robert W; Braun, William E; Chapman, Arlene B; Flessner, Michael F; Harris, Peter C; Hogan, Marie C; Perrone, Ronald D; Miskulin, Dana C; Steinman, Theodore I; Torres, Vicente E

2018-05-01

Previous clinical studies of autosomal dominant polycystic kidney disease (ADPKD) reported that loss of kidney function usually follows a steep and relentless course. A detailed examination of individual patterns of decline in estimated glomerular filtration rate (eGFR) has not been performed. Longitudinal post hoc analysis of data collected during the Halt Progression of Polycystic Kidney Disease (HALT-PKD) trials. 494 HALT-PKD Study A participants (younger; preserved eGFR) and 435 Study B participants (older; reduced eGFR) who had more than 3 years of follow-up and 7 or more eGFR assessments. Longitudinal eGFR assessments using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation. Demographic, clinical, laboratory, and imaging features of participants. Probability of linear and nonlinear decline patterns or of stable eGFR calculated for each participant from a Bayesian model of individual eGFR trajectories. Most (62.5% in Study A and 81% in Study B) participants had a linear decline in eGFR during up to 8 years of follow-up. A proportion (22% in Study A and 13% in Study B) of progressors had a nonlinear pattern. 15.5% of participants in Study A and 6% in Study B had a prolonged (≥4.5 years) period of stable eGFRs. These individuals (Study A) had significantly smaller total kidney volumes, higher renal blood flows, lower urinary albumin excretion, and lower body mass index at baseline and study end. In Study B, participants with reduced but stable eGFRs were older than the progressors. Two-thirds of nonprogressors in both studies had PKD1 mutations, with enrichment for weak nontruncating mutations. Relatively short follow-up of a clinical trial population. Although many individuals with ADPKD have a linear decline in eGFR, prolonged intervals of stable GFRs occur in a substantial fraction. Lower body mass index was associated with more stable kidney function in early ADPKD. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Acute Exacerbations and Lung Function Loss in Smokers with and without Chronic Obstructive Pulmonary Disease.

PubMed

Dransfield, Mark T; Kunisaki, Ken M; Strand, Matthew J; Anzueto, Antonio; Bhatt, Surya P; Bowler, Russell P; Criner, Gerard J; Curtis, Jeffrey L; Hanania, Nicola A; Nath, Hrudaya; Putcha, Nirupama; Roark, Sarah E; Wan, Emily S; Washko, George R; Wells, J Michael; Wendt, Christine H; Make, Barry J

2017-02-01

Acute exacerbations of chronic obstructive pulmonary disease (COPD) increase the risk of death and drive healthcare costs, but whether they accelerate loss of lung function remains controversial. Whether exacerbations in subjects with mild COPD or similar acute respiratory events in smokers without airflow obstruction affect lung function decline is unknown. To determine the association between acute exacerbations of COPD (and acute respiratory events in smokers without COPD) and the change in lung function over 5 years of follow-up. We examined data on the first 2,000 subjects who returned for a second COPDGene visit 5 years after enrollment. Baseline data included demographics, smoking history, and computed tomography emphysema. We defined exacerbations (and acute respiratory events in those without established COPD) as acute respiratory symptoms requiring either antibiotics or systemic steroids, and severe events by the need for hospitalization. Throughout the 5-year follow-up period, we collected self-reported acute respiratory event data at 6-month intervals. We used linear mixed models to fit FEV 1 decline based on reported exacerbations or acute respiratory events. In subjects with COPD, exacerbations were associated with excess FEV 1 decline, with the greatest effect in Global Initiative for Chronic Obstructive Lung Disease stage 1, where each exacerbation was associated with an additional 23 ml/yr decline (95% confidence interval, 2-44; P = 0.03), and each severe exacerbation with an additional 87 ml/yr decline (95% confidence interval, 23-151; P = 0.008); statistically significant but smaller effects were observed in Global Initiative for Chronic Obstructive Lung Disease stage 2 and 3 subjects. In subjects without airflow obstruction, acute respiratory events were not associated with additional FEV 1 decline. Exacerbations are associated with accelerated lung function loss in subjects with established COPD, particularly those with mild disease. Trials are needed to test existing and novel therapies in subjects with early/mild COPD to potentially reduce the risk of progressing to more advanced lung disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00608764).

Type 2 Diabetes Mellitus and Impaired Renal Function Are Associated With Brain Alterations and Poststroke Cognitive Decline.

PubMed

Ben Assayag, Einor; Eldor, Roy; Korczyn, Amos D; Kliper, Efrat; Shenhar-Tsarfaty, Shani; Tene, Oren; Molad, Jeremy; Shapira, Itzhak; Berliner, Shlomo; Volfson, Viki; Shopin, Ludmila; Strauss, Yehuda; Hallevi, Hen; Bornstein, Natan M; Auriel, Eitan

2017-09-01

Type 2 diabetes mellitus (T2DM) is associated with diseases of the brain, kidney, and vasculature. However, the relationship between T2DM, chronic kidney disease, brain alterations, and cognitive function after stroke is unknown. We aimed to evaluate the inter-relationship between T2DM, impaired renal function, brain pathology on imaging, and cognitive decline in a longitudinal poststroke cohort. The TABASCO (Tel Aviv brain acute stroke cohort) is a prospective cohort of stroke/transient ischemic attack survivors. The volume and white matter integrity, ischemic lesions, and brain and hippocampal volumes were measured at baseline using 3-T MRI. Cognitive tests were performed on 507 patients, who were diagnosed as having mild cognitive impairment, dementia, or being cognitively intact after 24 months. At baseline, T2DM and impaired renal function (estimated creatinine clearance [eCCl] <60 mL/min) were associated with smaller brain and hippocampal volumes, reduced cortical thickness, and worse white matter microstructural integrity. Two years later, both T2DM and eCCl <60 mL/min were associated with poorer cognitive scores, and 19.7% of the participants developed cognitive decline (mild cognitive impairment or dementia). Multiple analysis, controlling for age, sex, education, and apolipoprotein E4, showed a significant association of both T2DM and eCCl <60 mL/min with cognitive decline. Having both conditions doubled the risk compared with patients with T2DM or eCCl <60 mL/min alone and almost quadrupled the risk compared with patients without either abnormality. T2DM and impaired renal function are independently associated with abnormal brain structure, as well as poorer performance in cognitive tests, 2 years after stroke. The presence of both conditions quadruples the risk for cognitive decline. T2DM and lower eCCl have an independent and additive effect on brain atrophy and the risk of cognitive decline. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01926691. © 2017 American Heart Association, Inc.

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

An Evaluation of the Evidence that Methamphetamine Abuse Causes Cognitive Decline in Humans

PubMed Central

Dean, Andy C; Groman, Stephanie M; Morales, Angelica M; London, Edythe D

2013-01-01

Methamphetamine (MA) is one of the most commonly abused illicit substances worldwide. Among other problems, abuse of the drug has been associated with reduced cognitive function across several domains. However, much of the literature has not attempted to differentiate cognitive difficulties caused by MA abuse from preexisting cognitive difficulties that are likely caused by other factors. Here, we address this question, evaluating evidence for a priori hypotheses pertaining to six lines of research: (a) animal studies; (b) cross-sectional human studies; (c) a twin study; (d) studies of changes in cognition with abstinence from MA; (e) studies of changes in brain structure and function with abstinence from MA; and (f) studies of the relationship between the severity of MA abuse and the extent of cognitive deficits observed. Overall the findings were mixed, with some support for a causal relationship between MA abuse and cognitive decline, and other findings suggesting that there is no relationship. The preponderance of the data, however, does support the possibility that MA abuse causes cognitive decline, of unknown duration, in at least some users of the drug. When averaged across individuals, this decline is likely to be mild in early-to-middle adulthood. However, moderator variables are likely to contribute to the presence and/or severity of cognitive decline exhibited by a given individual. PMID:22948978

Nonstructural leaf carbohydrate dynamics of Pinus edulis during drought-induced tree mortality reveal role for carbon metabolism in mortality mechanism.

PubMed

Adams, Henry D; Germino, Matthew J; Breshears, David D; Barron-Gafford, Greg A; Guardiola-Claramonte, Maite; Zou, Chris B; Huxman, Travis E

2013-03-01

Vegetation change is expected with global climate change, potentially altering ecosystem function and climate feedbacks. However, causes of plant mortality, which are central to vegetation change, are understudied, and physiological mechanisms remain unclear, particularly the roles of carbon metabolism and xylem function. We report analysis of foliar nonstructural carbohydrates (NSCs) and associated physiology from a previous experiment where earlier drought-induced mortality of Pinus edulis at elevated temperatures was associated with greater cumulative respiration. Here, we predicted faster NSC decline for warmed trees than for ambient-temperature trees. Foliar NSC in droughted trees declined by 30% through mortality and was lower than in watered controls. NSC decline resulted primarily from decreased sugar concentrations. Starch initially declined, and then increased above pre-drought concentrations before mortality. Although temperature did not affect NSC and sugar, starch concentrations ceased declining and increased earlier with higher temperatures. Reduced foliar NSC during lethal drought indicates a carbon metabolism role in mortality mechanism. Although carbohydrates were not completely exhausted at mortality, temperature differences in starch accumulation timing suggest that carbon metabolism changes are associated with time to death. Drought mortality appears to be related to temperature-dependent carbon dynamics concurrent with increasing hydraulic stress in P. edulis and potentially other similar species. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

The Nordic Prudent Diet Reduces Risk of Cognitive Decline in the Swedish Older Adults: A Population-Based Cohort Study.

PubMed

Shakersain, Behnaz; Rizzuto, Debora; Larsson, Susanna C; Faxén-Irving, Gerd; Fratiglioni, Laura; Xu, Wei-Li

2018-02-17

Appropriate dietary pattern for preserving cognitive function in northern Europe remains unknown. We aimed to identify a Nordic dietary pattern index associated with slower cognitive decline compared to the Mediterranean-DASH Intervention for Neurodegenerative Delay, Mediterranean Diet, Dietary Approaches to Stop Hypertension, and Baltic Sea Diet indices. A total of 2223 dementia-free adults aged ≥60 were followed for 6 years. Mini-Mental State Examination was administrated at baseline and follow-ups. Dietary intake was assessed by 98-item food frequency questionnaire, and the Nordic Prudent Dietary Pattern (NPDP) was identified. Data were analysed using mixed-effects and parametric survival models and receiver operating characteristic curves with adjustment for potential confounders. Moderate (β = 0.139, 95% CI 0.077-0.201) and high adherence (β = 0.238, 95% CI 0.175-0.300) to NPDP were associated with less cognitive decline compared to other four indices. High adherence to NPDP was also associated with the lowest risk of MMSE decline to ≤24 (HR = 0.176, 95% CI 0.080-0.386) and had the greatest ability to predict such decline (area under the curve = 0.70). Moderate-to-high adherence to the NPDP may predict a better-preserved cognitive function among older adults in Nordic countries. Regional dietary habits should be considered in developing dietary guidelines for the prevention of cognitive impairment and dementia.

Conditional inhibition of autophagy genes in adult Drosophila impairs immunity without compromising longevity.

PubMed

Ren, Chunli; Finkel, Steven E; Tower, John

2009-03-01

Immune function declines with age in Drosophila and humans, and autophagy is implicated in immune function. In addition, autophagy genes are required for life span extension caused by reduced insulin/IGF1-like signaling and dietary restriction in Caenorhabditiselegans. To test if the autophagy pathway might be limiting for immunity and/or life span in adult Drosophila, the Geneswitch system was used to cause conditional inactivation of the autophagy genes Atg5, Atg7 and Atg12 by RNAi. Conditional inhibition of Atg genes in adult flies reduced lysotracker staining of adult tissues, and reduced resistance to injected Escherichia coli, as evidenced by increased bacterial titers and reduced fly survival. However, survival of uninjected flies was unaffected by Atg gene inactivation. The data indicate that Atg gene activity is required for normal immune function in adult flies, and suggest that neither autophagy nor immune function are limiting for adult life span under typical laboratory conditions.

Reduced survival in adult cystic fibrosis despite attenuated lung function decline.

PubMed

Keating, Claire; Poor, Armeen D; Liu, Xinhua; Chiuzan, Codruta; Backenroth, Daniel; Zhang, Yuan; DiMango, Emily

2017-01-01

There is limited data on disease progression and survival in adult diagnosis cystic fibrosis (CF). This study evaluates change of lung function over time and rates of death/lung transplant in adult diagnosis CF. The CF Foundation Patient Registry was reviewed for patients diagnosed 1993-2003. Rate of FEV1 decline was calculated up to 2010 for age groups 6-11, 12-17, and 18 and above. Kaplan Meier method was used for 10 and 15year survival rate calculations for patients diagnosed as adults. Cox Proportional hazards models using predictors affecting disease progression and survival without transplant were run. Between 1993 and 2003, 11,884 patients were diagnosed with CF, of which 2848 were ages 6 and older. Annual rate of change of FEV1% predicted over 5years differed by diagnosis age group: -1.42% per year for ages 6-11, -2.04% for ages 12-17 and -1.13% for ages 18-65 (p<0.0001). Pseudomonas aeruginosa infection was associated with faster rates of lung function decline in all age groups. Survival without transplant for CF patients diagnosed at ≥18years were 76% and 65% by 10 and 15years, respectively. Of adults with FEV1 of >70% predicted at diagnosis, 95% were alive without transplant at 10years, whereas of those with FEV1<40% predicted at diagnosis, 31% were alive without transplant at 10years. Lung function declines at a slower rate in adult diagnosis CF. However, particularly in those with low lung function at diagnosis, rates of death or transplant in adult diagnosis CF after 10 and 15years is not negligible. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Prospective Study on the Impact of Fear of Falling on Functional Decline among Community Dwelling Elderly Women.

PubMed

Choi, Kyungwon; Jeon, Gyeong-Suk; Cho, Sung-Il

2017-04-27

Fear of falling (FOF) is expected to have effects on functional decline in the elderly. In this study, we examined over 2 years the effect of change in FOF on functional decline in community dwelling elderly. We conducted a secondary analysis using data from elderly women, 70 years of age and older, who participated in the Korean Longitudinal Study of Aging (KLoSA). Participants were divided into four categories according to change in FOF between the 2010 and 2012 surveys. Multiple logistic regression analysis was conducted regarding the effects of changes in FOF on functional decline after controlling for variables as known risk factors for functional decline. Rates of functional decline were highest in the "consistently having FOF" group, whereas they were lowest in the "consistently no FOF" group in both 2010 and 2012. Characteristics independently associated with functional decline were change in FOF, depressive symptoms, low frequency of meeting friends, and fear-induced activity avoidance. Longer exposure to FOF was associated with an increased risk of functional decline. FOF is an important health problem that deserves attention in its own right. Public health approaches for elderly persons should address early detection, prevention, and intervention programs for FOF.

Controls on declining carbon balance with leaf age among 10 woody species in Australian woodland: do leaves have zero daily net carbon balances when they die?

PubMed

Reich, Peter B; Falster, Daniel S; Ellsworth, David S; Wright, Ian J; Westoby, Mark; Oleksyn, Jacek; Lee, Tali D

2009-01-01

* Here, we evaluated how increased shading and declining net photosynthetic capacity regulate the decline in net carbon balance with increasing leaf age for 10 Australian woodland species. We also asked whether leaves at the age of their mean life-span have carbon balances that are positive, zero or negative. * The net carbon balances of 2307 leaves on 53 branches of the 10 species were estimated. We assessed three-dimensional architecture, canopy openness, photosynthetic light response functions and dark respiration rate across leaf age sequences on all branches. We used YPLANT to estimate light interception and to model carbon balance along the leaf age sequences. * As leaf age increased to the mean life-span, increasing shading and declining photosynthetic capacity each separately reduced daytime carbon gain by approximately 39% on average across species. Together, they reduced daytime carbon gain by 64% on average across species. * At the age of their mean life-span, almost all leaves had positive daytime carbon balances. These per leaf carbon surpluses were of a similar magnitude to the estimated whole-plant respiratory costs per leaf. Thus, the results suggest that a whole-plant economic framework, including respiratory costs, may be useful in assessing controls on leaf longevity.

Efficacy of pirfenidone for idiopathic pulmonary fibrosis: An Italian real life study.

PubMed

Harari, S; Caminati, A; Albera, C; Vancheri, C; Poletti, V; Pesci, A; Luppi, F; Saltini, C; Agostini, C; Bargagli, E; Sebastiani, A; Sanduzzi, A; Giunta, V; Della Porta, R; Bandelli, G P; Puglisi, S; Tomassetti, S; Biffi, A; Cerri, S; Mari, A; Cinetto, F; Tirelli, F; Farinelli, G; Bocchino, M; Specchia, C; Confalonieri, M

2015-07-01

In this retrospective Italian study, which involved all major national interstitial lung diseases centers, we evaluated the effect of pirfenidone on disease progression in patients with IPF. We retrospectively studied 128 patients diagnosed with mild, moderate or severe IPF, and the decline in lung function monitored during the one-year treatment with pirfenidone was compared with the decline measured during the one-year pre-treatment period. At baseline (first pirfenidone prescription), the mean percentage forced vital capacity (FVC) was 75% (35-143%) of predicted, and the mean percentage diffuse lung capacity (DLCO) was 47% (17-120%) of predicted. Forty-eight patients (37.5%) had mild disease (GAP index stage I), 64 patients (50%) had moderate IPF (stage II), and 8 patients (6.3%) had severe disease (stage III). In the whole population, pirfenidone attenuated the decline in FVC (p = 0.065), but did not influence the decline in DLCO (p = 0.355) in comparison to the pre-treatment period. Stratification of patients into mild and severe disease groups based on %FVC level at baseline (>75% and ≤75%) revealed that attenuation of decline in FVC (p = 0.002) was more pronounced in second group of patients. Stratification of patients according to GAP index at baseline (stage I vs. II/III) also revealed that attenuation of decline in lung function was more pronounced in patients with more severe disease. In this national experience, pirfenidone reduced the rate of annual FVC decline (p = 0.065). Since pirfenidone provided significant treatment benefit for patients with moderate-severe disease, our results suggest that the drug may also be effective in patients with more advanced disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Apolipoprotein E ε2 and functional decline in amnestic mild cognitive impairment and Alzheimer disease.

PubMed

Bonner-Jackson, Aaron; Okonkwo, Ozioma; Tremont, Geoffrey

2012-07-01

Recent work has demonstrated the potentially protective effects of the apolipoprotein E (APOE) ε2 allele on cognitive functioning in individuals at risk for developing Alzheimer disease. However, little is known regarding the effect of ε2 genotype on rate of change in daily functioning over time. The aim of the current study was to examine the relationship between APOE genotype and change over time in ability to perform daily activities. We examined the relationship between APOE genotype and change in the ability to perform activities of daily living at 12- and 24-month intervals in 225 healthy comparison subjects, 381 individuals with amnestic mild cognitive impairment, and 189 individuals with Alzheimer disease who were enrolled in the Alzheimer's Disease Neuroimaging Initiative study. Neuropsychological measures were also collected at each follow-up. Overall, individuals with at least one APOE-ε2 allele showed less functional decline over time and better performance on neuropsychological measures than those without an ε2 allele, even after controlling for potential confounders. When diagnostic groups were examined individually, presence of the ε2 allele continued to be associated with slower functional decline, although the relationship was no longer statistically significant in most cases, likely due to reduced statistical power. Our findings suggest that the APOE-ε2 allele provides a buffer against significant changes in daily functioning over time and is associated with better neuropsychological performance across a number of measures.

Initial elevations in glutamate and dopamine neurotransmission decline with age, as does exploratory behavior, in LRRK2 G2019S knock-in mice

PubMed Central

Kuhlmann, Naila; Kadgien, Chelsie A; Tatarnikov, Igor; Fox, Jesse; Khinda, Jaskaran; Mitchell, Emma; Bergeron, Sabrina; Melrose, Heather

2017-01-01

LRRK2 mutations produce end-stage Parkinson’s disease (PD) with reduced nigrostriatal dopamine, whereas, asymptomatic carriers have increased dopamine turnover and altered brain connectivity. LRRK2 pathophysiology remains unclear, but reduced dopamine and mitochondrial abnormalities occur in aged G2019S mutant knock-in (GKI) mice. Conversely, cultured GKI neurons exhibit increased synaptic transmission. We assessed behavior and synaptic glutamate and dopamine function across a range of ages. Young GKI mice exhibit more vertical exploration, elevated glutamate and dopamine transmission, and aberrant D2-receptor responses. These phenomena decline with age, but are stable in littermates. In young GKI mice, dopamine transients are slower, independent of dopamine transporter (DAT), increasing the lifetime of extracellular dopamine. Slowing of dopamine transients is observed with age in littermates, suggesting premature ageing of dopamine synapses in GKI mice. Thus, GKI mice exhibit early, but declining, synaptic and behavioral phenotypes, making them amenable to investigation of early pathophysiological, and later parkinsonian-like, alterations. This model will prove valuable in efforts to develop neuroprotection for PD. PMID:28930069

Initial elevations in glutamate and dopamine neurotransmission decline with age, as does exploratory behavior, in LRRK2 G2019S knock-in mice.

PubMed

Volta, Mattia; Beccano-Kelly, Dayne A; Paschall, Sarah A; Cataldi, Stefano; MacIsaac, Sarah E; Kuhlmann, Naila; Kadgien, Chelsie A; Tatarnikov, Igor; Fox, Jesse; Khinda, Jaskaran; Mitchell, Emma; Bergeron, Sabrina; Melrose, Heather; Farrer, Matthew J; Milnerwood, Austen J

2017-09-20

LRRK2 mutations produce end-stage Parkinson's disease (PD) with reduced nigrostriatal dopamine, whereas, asymptomatic carriers have increased dopamine turnover and altered brain connectivity. LRRK2 pathophysiology remains unclear, but reduced dopamine and mitochondrial abnormalities occur in aged G2019S mutant knock-in (GKI) mice. Conversely, cultured GKI neurons exhibit increased synaptic transmission. We assessed behavior and synaptic glutamate and dopamine function across a range of ages. Young GKI mice exhibit more vertical exploration, elevated glutamate and dopamine transmission, and aberrant D2-receptor responses. These phenomena decline with age, but are stable in littermates. In young GKI mice, dopamine transients are slower, independent of dopamine transporter (DAT), increasing the lifetime of extracellular dopamine. Slowing of dopamine transients is observed with age in littermates, suggesting premature ageing of dopamine synapses in GKI mice. Thus, GKI mice exhibit early, but declining, synaptic and behavioral phenotypes, making them amenable to investigation of early pathophysiological, and later parkinsonian-like, alterations. This model will prove valuable in efforts to develop neuroprotection for PD.

Combined bronchodilators (tiotropium plus olodaterol) for patients with chronic obstructive pulmonary disease.

PubMed

Ramadan, Wijdan H; Kabbara, Wissam K; El Khoury, Ghada M; Al Assir, Sarah A

2015-01-01

Chronic obstructive pulmonary disease (COPD), a respiratory disease characterized by a progressive decline in lung function, is considered to be a leading cause of morbidity and mortality. Long-acting inhaled bronchodilators, such as long-acting β2 agonists (LABAs) or long-acting muscarinic antagonists (LAMAs), are the cornerstone of maintenance therapy for patients with moderate-to-very-severe COPD. For patients not sufficiently controlled on a single long-acting bronchodilator, a combination of different bronchodilators has shown a significant increase in lung function. Tiotropium, a once-daily dosing LAMA, demonstrated sustained improvements in lung function as well as improved health-related quality of life, reduced exacerbations, and increased survival without altering the rate of decline in the mean forced expiratory volume in 1 second (FEV1) with fairly tolerable side effects. Olodaterol is a once-daily dosing LABA that has proven to be effective in improving lung function, reducing rescue medication use, and improving dyspnea and health-related quality of life, as well as improving exercise endurance with an acceptable safety profile. The combination of olodaterol and tiotropium provided additional improvements in lung function greater than monotherapy with each drug alone. Several well-designed randomized trials confirmed that the synergistic effect of both drugs in combination was able to improve lung function and health-related quality of life without a significant increase in adverse effects. The objective of this paper is to review available evidence on the clinical efficacy and safety of tiotropium, olodaterol, and their combination in patients with COPD.

Exercise interventions in polypathological aging patients that coexist with diabetes mellitus: improving functional status and quality of life.

PubMed

Cadore, Eduardo Lusa; Izquierdo, Mikel

2015-06-01

In elderly populations, diabetes is associated with reduced muscle strength, poor muscle quality, and accelerated loss of muscle mass. In addition, diabetes mellitus increases risk for accelerated aging and for the development of frailty syndrome. This disease is also associated with a polypathological condition, and its complications progressively affect quality of life and survival. Exercise interventions, including resistance training, represent the cornerstones of diabetes management, especially in patients at severe functional decline. This review manuscript aimed to describe the beneficial effects of different exercise interventions on the functional capacity of elderly diabetics, including those at polypathological condition. The SciELO, Science Citation Index, MEDLINE, Scopus, SPORTDiscus, and ScienceDirect databases were searched from 1980 to 2015 for articles published from original scientific investigations. In addition to the beneficial effects of exercise interventions on glycemic control, and on the cardiovascular risk factors associated with diabetes, physical exercise is an effective intervention to improve muscle strength, power output, and aerobic power and functional capacity in elderly diabetic patients. Thus, a combination of resistance and endurance training is the most effective exercise intervention to promote overall physical fitness in these patients. In addition, in diabetic patients with frailty and severe functional decline, a multicomponent exercise program including strength and power training, balance exercises, and gait retraining may be an effective intervention to reduce falls and improve functional capacity and quality of life in these patients.

Employment status, social function decline and caregiver burden among stroke survivors. A South Indian study.

PubMed

Sreedharan, Sapna Erat; Unnikrishnan, J P; Amal, M G; Shibi, B S; Sarma, Sankara; Sylaja, P N

2013-09-15

Stroke leaves at least 60% of the survivors with moderate to severe disability limiting their employment status and social functioning leading to high levels of caregiver burden. We sought to study the employment status and level of change of social functioning of stroke survivors and their principal caregiver and correlate it with severity of stroke, functional disability, and anxiety and depression scores. One hundred and fifty stroke survivors and principal caregivers (3 months-2 years post-stroke) were recruited for the study. The employment status pre- and post-stroke was assessed. The social function of the patient and caregiver was analyzed using a 6 item social function scale developed for the study, encompassing culturally relevant questions. A 20 point scale adapted from Burden assessment schedule was used to assess the caregiver burden. Mean age of the study group was 54.37±12.072 (range 22-75 years), with 116 males and 34 females. Spouse was the principal caregiver for 142/150 patients (94.6%). In the stroke survivors, compared to the pre-stroke employment status of 62.7%, only 20.7% were employed post-stroke with half having change of job. But the employment status of caregiver was not reduced post-stroke (34.7% vs 33.3%). Employment loss in stroke survivors had a statistically significant association with severity of functional disability, male gender and presence of limb weakness (p values 0.037, 0.0001 and 0.043 respectively). There was an overall decline in social functions among the 6 parameters assessed in both the stroke survivors and caregivers. Of the caregiver burden, financial burden was more among female and older caregivers. The functional status and motor weakness of the stroke survivors did not tend to worsen the overall caregiver burden. Loss of occupation among stroke survivors is high. The decline in social function among stroke survivors and caregivers was significant. Even though functional disability contributed to employment loss and social function decline among stroke survivors, it did not have a significant impact on caregiver burden. © 2013 Elsevier B.V. All rights reserved

Successional dynamics and restoration implications of a montane coniferous forest in the central Appalachians, USA

Treesearch

Thomas M. Schuler; Rachel J. Collins

2002-01-01

Central Appalachian montane red spruce (Picea rubens Sarg.) communities have been greatly reduced in extent and functional quality over the past century. This community decline has put several plant and animal species, such as the endangered Virginia northern flying squirrel (Glaucomys sabrinus fuscus Shaw), at risk from habitat...

Reduced Specificity of Hippocampal and Posterior Ventrolateral Prefrontal Activity during Relational Retrieval in Normal Aging

ERIC Educational Resources Information Center

Giovanello, Kelly S.; Schacter, Daniel L.

2012-01-01

Neuroimaging studies of episodic memory in young adults demonstrate greater functional neural activity in ventrolateral pFC and hippocampus during retrieval of relational information as compared with item information. We tested the hypothesis that healthy older adults--individuals who exhibit behavioral declines in relational memory--would show…

Berry phenolics are associated with cognitive enhancement in blueberry- and strawberry-supplemented healthy older adults

USDA-ARS?s Scientific Manuscript database

The aging process often involves functional declines in cognition, leading to lower quality of life and increased need for care among older adults. Epidemiological evidence suggests that a diet rich in fruits and vegetables can reduce the risk of age-related cognitive impairment, in part due to the ...

The Effects of Sleep Deprivation on Item and Associative Recognition Memory

ERIC Educational Resources Information Center

Ratcliff, Roger; Van Dongen, Hans P. A.

2018-01-01

Sleep deprivation adversely affects the ability to perform cognitive tasks, but theories range from predicting an overall decline in cognitive functioning because of reduced stability in attentional networks to specific deficits in various cognitive domains or processes. We measured the effects of sleep deprivation on two memory tasks, item…

Telmisartan prevented cognitive decline partly due to PPAR-{gamma} activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mogi, Masaki; Li Jianmei; Tsukuda, Kana

Telmisartan is a unique angiotensin receptor blocker (ARB) and partial agonist of peroxisome proliferator-activated receptor (PPAR)-{gamma}. Here, we investigated the preventive effect of telmisartan on cognitive decline in Alzheimer disease. In ddY mice, intracerebroventricular injection of A{beta} 1-40 significantly attenuated their cognitive function evaluated by shuttle avoidance test. Pretreatment with a non-hypotensive dose of telmisartan significantly inhibited such cognitive decline. Interestingly, co-treatment with GW9662, a PPAR-{gamma} antagonist, partially inhibited this improvement of cognitive decline. Another ARB, losartan, which has less PPAR-{gamma} agonistic effect, also inhibited A{beta}-injection-induced cognitive decline; however the effect was smaller than that of telmisartan and was notmore » affected by GW9662. Immunohistochemical staining for A{beta} showed the reduced A{beta} deposition in telmisartan-treated mice. However, this reduction was not observed in mice co-administered GW9662. These findings suggest that ARB has a preventive effect on cognitive impairment in Alzheimer disease, and telmisartan, with PPAR-{gamma} activation, could exert a stronger effect.« less

An Evidence-Based Construction of the Models of Decline of Functioning. Part 1: Two Major Models of Decline of Functioning

ERIC Educational Resources Information Center

Okawa, Yayoi; Nakamura, Shigemi; Kudo, Minako; Ueda, Satoshi

2009-01-01

The purpose of this study is to confirm the working hypothesis on two major models of functioning decline and two corresponding models of rehabilitation program in an older population through detailed interviews with the persons who have functioning declines and on-the-spot observations of key activities on home visits. A total of 542…

Catechin treatment improves cerebrovascular flow-mediated dilation and learning abilities in atherosclerotic mice

PubMed Central

Drouin, Annick; Bolduc, Virginie; Thorin-Trescases, Nathalie; Bélanger, Élisabeth; Fernandes, Priscilla; Baraghis, Edward; Lesage, Frédéric; Gillis, Marc-Antoine; Villeneuve, Louis; Hamel, Edith; Ferland, Guylaine; Thorin, Eric

2013-01-01

Severe dyslipidemia and the associated oxidative stress could accelerate the age-related decline in cerebrovascular endothelial function and cerebral blood flow (CBF), leading to neuronal loss and impaired learning abilities. We hypothesized that a chronic treatment with the polyphenol catechin would prevent endothelial dysfunction, maintain CBF responses, and protect learning abilities in atherosclerotic (ATX) mice. We treated ATX (C57Bl/6-LDLR−/− hApoB+/+; 3 mo old) mice with catechin (30 mg·kg−1·day−1) for 3 mo, and C57Bl/6 [wild type (WT), 3 and 6 mo old] mice were used as controls. ACh- and flow-mediated dilations (FMD) were recorded in pressurized cerebral arteries. Basal CBF and increases in CBF induced by whisker stimulation were measured by optical coherence tomography and Doppler, respectively. Learning capacities were evaluated with the Morris water maze test. Compared with 6-mo-old WT mice, cerebral arteries from 6-mo-old ATX mice displayed a higher myogenic tone, lower responses to ACh and FMD, and were insensitive to NOS inhibition (P < 0.05), suggesting endothelial dysfunction. Basal and increases in CBF were lower in 6-mo-old ATX than WT mice (P < 0.05). A decline in the learning capabilities was also observed in ATX mice (P < 0.05). Catechin 1) reduced cerebral superoxide staining (P < 0.05) in ATX mice, 2) restored endothelial function by reducing myogenic tone, improving ACh- and FMD and restoring the sensitivity to nitric oxide synthase inhibition (P < 0.05), 3) increased the changes in CBF during stimulation but not basal CBF, and 4) prevented the decline in learning abilities (P < 0.05). In conclusion, catechin treatment of ATX mice prevents cerebrovascular dysfunctions and the associated decline in learning capacities. PMID:21186270

Diabetes and Cognitive Decline in Older Adults: The Ginkgo Evaluation of Memory Study.

PubMed

Palta, Priya; Carlson, Michelle C; Crum, Rosa M; Colantuoni, Elizabeth; Sharrett, A Richey; Yasar, Sevil; Nahin, Richard L; DeKosky, Steven T; Snitz, Beth; Lopez, Oscar; Williamson, Jeff D; Furberg, Curt D; Rapp, Stephen R; Golden, Sherita Hill

2017-12-12

Previous studies have shown that individuals with diabetes exhibit accelerated cognitive decline. However, methodological limitations have limited the quality of this evidence. Heterogeneity in study design, cognitive test administration, and methods of analysis of cognitive data have made it difficult to synthesize and translate findings to practice. We analyzed longitudinal data from the Ginkgo Evaluation of Memory Study to test our hypothesis that older adults with diabetes have greater test-specific and domain-specific cognitive declines compared to older adults without diabetes. Tests of memory, visuo-spatial construction, language, psychomotor speed, and executive function were administered. Test scores were standardized to z-scores and averaged to yield domain scores. Linear random effects models were used to compare baseline differences and changes over time in test and domain scores among individuals with and without diabetes. Among the 3,069 adults, aged 72-96 years, 9.3% reported diabetes. Over a median follow-up of 6.1 years, participants with diabetes exhibited greater baseline differences in a test of executive function (trail making test, Part B) and greater declines in a test of language (phonemic verbal fluency). For the composite cognitive domain scores, participants with diabetes exhibited lower baseline executive function and global cognition domain scores, but no significant differences in the rate of decline. Identifying cognitive domains most affected by diabetes can lead to targeted risk modification, possibly in the form of lifestyle interventions such as diet and physical activity, which we know to be beneficial for improving vascular risk factors, such as diabetes, and therefore may reduce the risk of executive dysfunction and possible dementia. © The Author 2017. 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.

Modeling Longitudinal Changes in Older Adults’ Memory for Spoken Discourse: Findings from the ACTIVE Cohort

PubMed Central

Payne, Brennan R.; Gross, Alden L.; Parisi, Jeanine M.; Sisco, Shannon M.; Stine-Morrow, Elizabeth A. L.; Marsiske, Michael; Rebok, George W.

2014-01-01

Episodic memory shows substantial declines with advancing age, but research on longitudinal trajectories of spoken discourse memory (SDM) in older adulthood is limited. Using parallel process latent growth curve models, we examined 10 years of longitudinal data from the no-contact control group (N = 698) of the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) randomized controlled trial in order to test (a) the degree to which SDM declines with advancing age, (b) predictors of these age-related declines, and (c) the within-person relationship between longitudinal changes in SDM and longitudinal changes in fluid reasoning and verbal ability over 10 years, independent of age. Individuals who were younger, White, had more years of formal education, were male, and had better global cognitive function and episodic memory performance at baseline demonstrated greater levels of SDM on average. However, only age at baseline uniquely predicted longitudinal changes in SDM, such that declines accelerated with greater age. Independent of age, within-person decline in reasoning ability over the 10-year study period was substantially correlated with decline in SDM (r = .87). An analogous association with SDM did not hold for verbal ability. The findings suggest that longitudinal declines in fluid cognition are associated with reduced spoken language comprehension. Unlike findings from memory for written prose, preserved verbal ability may not protect against developmental declines in memory for speech. PMID:24304364

Prospective Study on the Impact of Fear of Falling on Functional Decline among Community Dwelling Elderly Women

PubMed Central

Choi, Kyungwon; Jeon, Gyeong-Suk; Cho, Sung-il

2017-01-01

Fear of falling (FOF) is expected to have effects on functional decline in the elderly. In this study, we examined over 2 years the effect of change in FOF on functional decline in community dwelling elderly. We conducted a secondary analysis using data from elderly women, 70 years of age and older, who participated in the Korean Longitudinal Study of Aging (KLoSA). Participants were divided into four categories according to change in FOF between the 2010 and 2012 surveys. Multiple logistic regression analysis was conducted regarding the effects of changes in FOF on functional decline after controlling for variables as known risk factors for functional decline. Rates of functional decline were highest in the “consistently having FOF” group, whereas they were lowest in the “consistently no FOF” group in both 2010 and 2012. Characteristics independently associated with functional decline were change in FOF, depressive symptoms, low frequency of meeting friends, and fear-induced activity avoidance. Longer exposure to FOF was associated with an increased risk of functional decline. FOF is an important health problem that deserves attention in its own right. Public health approaches for elderly persons should address early detection, prevention, and intervention programs for FOF. PMID:28448461

Prefrontal atrophy, disrupted NREM slow waves, and impaired hippocampal-dependent memory in aging

PubMed Central

Mander, Bryce A.; Rao, Vikram; Lu, Brandon; Saletin, Jared M.; Lindquist, John R.; Ancoli-Israel, Sonia; Jagust, William; Walker, Matthew P.

2014-01-01

Aging has independently been associated with regional brain atrophy, reduced non-rapid eye movement (NREM) slow-wave activity (SWA), and impaired long-term retention of episodic memories. However, that the interaction of these factors represents a neuropatholgical pathway associated with cognitive decline in later life remains unknown. Here, we show that age-related medial prefrontal cortex (mPFC) grey-matter atrophy is associated with reduced NREM SWA activity in older adults, the extent to which statistically mediates the impairment of overnight sleep-dependent memory retention. Moreover, this memory impairment was further associated with persistent hippocampal activation and reduced task-related hippocampal-prefrontal cortex connectivity, potentially representing impoverished hippocampal-neocortical memory transformation. Together, these data support a model in which age-related mPFC atrophy diminishes SWA, the functional consequence of which is impaired long-term memory. Such findings suggest that sleep disruption in the elderly, mediated by structural brain changes, represent a novel contributing factor to age-related cognitive decline in later life. PMID:23354332

The ethological trap: functional and numerical responses of highly efficient invasive predators driving prey extinctions.

PubMed

Spencer, Ricky-John; Van Dyke, James U; Thompson, Michael B

2016-10-01

Ecological traps are threats to organisms, and exist in a range of biological systems. A subset of ecological trap theory is the "ethological trap," whereby behaviors canalized by past natural selection become traps when environments change rapidly. Invasive predators are major threats to imperiled species and their ability to exploit canalized behaviors of naive prey is particularly important for the establishment of the predator and the decline of the native prey. Our study uses ecological theory to demonstrate that invasive predator controls require shifts in management priorities. Total predation rate (i.e., total response) is the product of both the functional response and numerical response of predators to prey. Functional responses are the changes in the rate of prey consumption by individual predators, relative to prey abundance. Numerical responses are the aggregative rates of prey consumption by all predators relative to prey density, which change with predator density via reproduction or migration, in response to changes in prey density. Traditional invasive predator management methods focus on reducing predator populations, and thus manage for numerical responses. These management efforts fail to manage for functional responses, and may not eliminate impacts of highly efficient individual predators. We explore this problem by modeling the impacts of functional and numerical responses of invasive foxes depredating imperiled Australian turtle nests. Foxes exhibit exceptionally efficient functional responses. A single fox can destroy >95% of turtle nests in a nesting area, which eliminates juvenile recruitment. In this case, the ethological trap is the "Arribada" nesting strategy, an emergent behavior whereby most turtles in a population nest simultaneously in the same nesting grounds. Our models show that Arribada nesting events do not oversaturate foxes, and small numbers of foxes depredate all of the nests in a given Arribada. Widely scattering nests may reduce fox predation rates, but the long generation times of turtles combined with their rapid recent decline suggests that evolutionary responses in nesting strategy may be unlikely. Our study demonstrates that reducing populations of highly efficient invasive predators is insufficient for preserving native prey species. Instead, management must reduce individual predator efficiency, independent of reducing predator population size. © 2016 by the Ecological Society of America.

Sensory-Cognitive Interactions in Older Adults

PubMed Central

Humes, Larry E.; Young, Levi A.

2016-01-01

Objectives To review evidence regarding sensory and cognitive interactions in older adults published since 2009, the approximate date of the most recent reviews on this topic. Design Following an electronic database search of articles published in English since 2009 on measures of hearing and cognition or vision and cognition in older adults, a total of 437 articles were identified. Screening by title and abstract for appropriateness of topic and for articles presenting original research in peer-reviewed journals reduced the final number of articles reviewed to 34. These articles were qualitatively evaluated and synthesized with the existing knowledge base. Results Additional evidence has been obtained since 2009 associating declines in vision, hearing, or both with declines in cognition among older adults. The observed sensory-cognitive associations are generally stronger when more than one sensory domain is measured and when the sensory measures involve more than simple threshold sensitivity. Conclusions Evidence continues to accumulate supporting a link between decline in sensory function and cognitive decline in older adults. PMID:27355770

Sensory-Cognitive Interactions in Older Adults.

PubMed

Humes, Larry E; Young, Levi A

2016-01-01

The objective of this study was regarding sensory and cognitive interactions in older adults published since 2009, the approximate date of the most recent reviews on this topic. After an electronic database search of articles published in English since 2009 on measures of hearing and cognition or vision and cognition in older adults, a total of 437 articles were identified. Screening by title and abstract for appropriateness of topic and for articles presenting original research in peer-reviewed journals reduced the final number of articles reviewed to 34. These articles were qualitatively evaluated and synthesized with the existing knowledge base. Additional evidence has been obtained since 2009 associating declines in vision, hearing, or both with declines in cognition among older adults. The observed sensory-cognitive associations are generally stronger when more than one sensory domain is measured and when the sensory measures involve more than simple threshold sensitivity. Evidence continues to accumulate supporting a link between decline in sensory function and cognitive decline in older adults.

Long-term impact of childhood disadvantage on late-life functional decline among older Japanese: Results from the JAGES prospective cohort study.

PubMed

Murayama, Hiroshi; Fujiwara, Takeo; Tani, Yukako; Amemiya, Airi; Matsuyama, Yusuke; Nagamine, Yuiko; Kondo, Katsunori

2017-09-11

Increasing evidence suggests an impact of childhood disadvantage on late-life functional impairment in Western countries. However, the processes by which childhood disadvantage affects functional capacity are influenced by several factors unique to particular societies. We examined the impact of childhood disadvantage on functional decline among older Japanese, using a large-scale prospective cohort study. Data came from surveys conducted in 2010 and 2013 as part of the Japan Gerontological Evaluation Study (JAGES), a nationwide cohort study targeting community-dwelling people aged 65 years and over. Childhood disadvantage included subjective childhood socioeconomic status (SES), body height and educational level. The sample was stratified by age at baseline (65-69 y, 70-74 y, 75-79 y, and ≥ 80 y). A total of 11,601 respondents were analyzed. In the 65-69 y group, lower childhood SES was associated with functional decline, but this association was mediated by adult SES. In contrast, childhood SES was independently associated with functional decline in the older cohort. In the 75-79 y group, lower childhood SES was associated with functional decline. However, in the ≥ 80 y group, people with higher childhood SES were more likely to experience functional decline. Shorter height was associated with functional decline in the 70-74 y group. Higher education was related to functional decline in all age groups except the ≥ 80 y group. These findings suggest that childhood disadvantage affects functional decline, but its effect varies by age cohort. The mechanisms underlying the association between childhood disadvantage and functional decline may be influenced by social and historical context. © The Author 2017. 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.

Physical Activity Predicts Higher Physical Function in Older Adults: The Osteoarthritis Initiative.

PubMed

Batsis, John A; Germain, Cassandra M; Vásquez, Elizabeth; Zbehlik, Alicia J; Bartels, Stephen J

2016-01-01

Physical activity reduces mobility impairments in elders. We examined the association of physical activity on risk of subjective and objective physical function in adults with and at risk for osteoarthritis (OA). Adults aged ≥ 60 years from the longitudinal Osteoarthritis Initiative, a prospective observational study of knee OA, were classified by sex-specific quartiles of Physical Activity Score for the Elderly scores. Using linear mixed models, we assessed 6-year data on self-reported health, gait speed, Late-Life Function and Disability Index (LLFDI) and chair stand. Of 2252 subjects, mean age ranged from 66 to 70 years. Within each quartile, physical component (PCS) of the Short Form-12 and gait speed decreased from baseline to follow-up in both sexes (all P < .001), yet the overall changes across PASE quartiles between these 2 time points were no different (P = .40 and .69, males and females, respectively). Decline in PCS occurred in the younger age group, but rates of change between quartiles over time were no different in any outcomes in either sex. LLFDI scores declined in the 70+ age group. Adjusting for knee extensor strength reduced the strength of association. Higher physical activity is associated with maintained physical function and is mediated by muscle strength, highlighting the importance of encouraging physical activity in older adults with and at risk for OA.

Budesonide ameliorates lung function of the cigarette smoke-exposed rats through reducing matrix metalloproteinase-1 content

PubMed Central

Sun, Jiawei; Zhang, Ping; Zhang, Bin; Li, Kang; Li, Zhu; Li, Junhong; Zhang, Yongjian; Sun, Wuzhuang

2015-01-01

Objectives: This study was conducted to investigate an effect of inhaled budesonide on cigarette smoke-exposed lungs with a possible mechanism involved in the event. Methods: Rats were exposed to air (control) and cigarette smoke (smoking) in presence and absence of budesonide. Inflammatory cell count in bronchoalveolar lavage fluid (BALF), lung function testing, mean liner intercept (MLI) in lung tissue, mean alveolar number (MAN) and a ratio of bronchial wall thickness and external diameter (BWT/D) were determined in the grouped rats, respectively. Contents of matrix metalloproteinase (MMP)-1, MMP-2 and tissue inhibitor of metalloproteinase (TIMP)-2 productions in BALF were examined as well. Results: There were significant changes in the above assessments in the smoking rats as compared to those in the control rats (all P < 0.01 and 0.05). Budesonide inhalation significantly decreased the numbers of the BALF cells and partly reversed lung function decline in the challenged rats (P < 0.01 and 0.05). However, this corticosteroid did not influence pathological changes in fine structures of the tobacco smoke-exposed lungs. Treatment with budesonide resulted in an obvious decrease in the MMP-1 but not MMP-2 and TIMP-2 productions (P < 0.05). Conclusion: Inhaled budesonide mitigates the ongoing inflammatory process in the smoked lungs and ameliorates declining lung function through reducing MMP-1 content. PMID:26191209

Budesonide ameliorates lung function of the cigarette smoke-exposed rats through reducing matrix metalloproteinase-1 content.

PubMed

Sun, Jiawei; Zhang, Ping; Zhang, Bin; Li, Kang; Li, Zhu; Li, Junhong; Zhang, Yongjian; Sun, Wuzhuang

2015-01-01

This study was conducted to investigate an effect of inhaled budesonide on cigarette smoke-exposed lungs with a possible mechanism involved in the event. Rats were exposed to air (control) and cigarette smoke (smoking) in presence and absence of budesonide. Inflammatory cell count in bronchoalveolar lavage fluid (BALF), lung function testing, mean liner intercept (MLI) in lung tissue, mean alveolar number (MAN) and a ratio of bronchial wall thickness and external diameter (BWT/D) were determined in the grouped rats, respectively. Contents of matrix metalloproteinase (MMP)-1, MMP-2 and tissue inhibitor of metalloproteinase (TIMP)-2 productions in BALF were examined as well. There were significant changes in the above assessments in the smoking rats as compared to those in the control rats (all P<0.01 and 0.05). Budesonide inhalation significantly decreased the numbers of the BALF cells and partly reversed lung function decline in the challenged rats (P<0.01 and 0.05). However, this corticosteroid did not influence pathological changes in fine structures of the tobacco smoke-exposed lungs. Treatment with budesonide resulted in an obvious decrease in the MMP-1 but not MMP-2 and TIMP-2 productions (P<0.05). Inhaled budesonide mitigates the ongoing inflammatory process in the smoked lungs and ameliorates declining lung function through reducing MMP-1 content.

Reduced body size and cub recruitment in polar bears associated with sea ice decline.

PubMed

Rode, Karyn D; Amstrup, Steven C; Regehr, Eric V

2010-04-01

Rates of reproduction and survival are dependent upon adequate body size and condition of individuals. Declines in size and condition have provided early indicators of population decline in polar bears (Ursus maritimus) near the southern extreme of their range. We tested whether patterns in body size, condition, and cub recruitment of polar bears in the southern Beaufort Sea of Alaska were related to the availability of preferred sea ice habitats and whether these measures and habitat availability exhibited trends over time, between 1982 and 2006. The mean skull size and body length of all polar bears over three years of age declined over time, corresponding with long-term declines in the spatial and temporal availability of sea ice habitat. Body size of young, growing bears declined over time and was smaller after years when sea ice availability was reduced. Reduced litter mass and numbers of yearlings per female following years with lower availability of optimal sea ice habitat, suggest reduced reproductive output and juvenile survival. These results, based on analysis of a long-term data set, suggest that declining sea ice is associated with nutritional limitations that reduced body size and reproduction in this population.

Reduced body size and cub recruitment in polar bears associated with sea ice decline

USGS Publications Warehouse

Rode, Karyn D.; Amstrup, Steven C.; Regehr, Eric V.

2010-01-01

Rates of reproduction and survival are dependent upon adequate body size and condition of individuals. Declines in size and condition have provided early indicators of population decline in polar bears (Ursus maritimus) near the southern extreme of their range. We tested whether patterns in body size, condition, and cub recruitment of polar bears in the southern Beaufort Sea of Alaska were related to the availability of preferred sea ice habitats and whether these measures and habitat availability exhibited trends over time, between 1982 and 2006. The mean skull size and body length of all polar bears over three years of age declined over time, corresponding with long‐term declines in the spatial and temporal availability of sea ice habitat. Body size of young, growing bears declined over time and was smaller after years when sea ice availability was reduced. Reduced litter mass and numbers of yearlings per female following years with lower availability of optimal sea ice habitat, suggest reduced reproductive output and juvenile survival. These results, based on analysis of a long‐term data set, suggest that declining sea ice is associated with nutritional limitations that reduced body size and reproduction in this population.

Devastating decline of forest elephants in central Africa.

PubMed

Maisels, Fiona; Strindberg, Samantha; Blake, Stephen; Wittemyer, George; Hart, John; Williamson, Elizabeth A; Aba'a, Rostand; Abitsi, Gaspard; Ambahe, Ruffin D; Amsini, Fidèl; Bakabana, Parfait C; Hicks, Thurston Cleveland; Bayogo, Rosine E; Bechem, Martha; Beyers, Rene L; Bezangoye, Anicet N; Boundja, Patrick; Bout, Nicolas; Akou, Marc Ella; Bene, Lambert Bene; Fosso, Bernard; Greengrass, Elizabeth; Grossmann, Falk; Ikamba-Nkulu, Clement; Ilambu, Omari; Inogwabini, Bila-Isia; Iyenguet, Fortune; Kiminou, Franck; Kokangoye, Max; Kujirakwinja, Deo; Latour, Stephanie; Liengola, Innocent; Mackaya, Quevain; Madidi, Jacob; Madzoke, Bola; Makoumbou, Calixte; Malanda, Guy-Aimé; Malonga, Richard; Mbani, Olivier; Mbendzo, Valentin A; Ambassa, Edgar; Ekinde, Albert; Mihindou, Yves; Morgan, Bethan J; Motsaba, Prosper; Moukala, Gabin; Mounguengui, Anselme; Mowawa, Brice S; Ndzai, Christian; Nixon, Stuart; Nkumu, Pele; Nzolani, Fabian; Pintea, Lilian; Plumptre, Andrew; Rainey, Hugo; de Semboli, Bruno Bokoto; Serckx, Adeline; Stokes, Emma; Turkalo, Andrea; Vanleeuwe, Hilde; Vosper, Ashley; Warren, Ymke

2013-01-01

African forest elephants- taxonomically and functionally unique-are being poached at accelerating rates, but we lack range-wide information on the repercussions. Analysis of the largest survey dataset ever assembled for forest elephants (80 foot-surveys; covering 13,000 km; 91,600 person-days of fieldwork) revealed that population size declined by ca. 62% between 2002-2011, and the taxon lost 30% of its geographical range. The population is now less than 10% of its potential size, occupying less than 25% of its potential range. High human population density, hunting intensity, absence of law enforcement, poor governance, and proximity to expanding infrastructure are the strongest predictors of decline. To save the remaining African forest elephants, illegal poaching for ivory and encroachment into core elephant habitat must be stopped. In addition, the international demand for ivory, which fuels illegal trade, must be dramatically reduced.

Geriatric Assessment and Functional Decline in Older Patients with Lung Cancer.

PubMed

Decoster, L; Kenis, C; Schallier, D; Vansteenkiste, J; Nackaerts, K; Vanacker, L; Vandewalle, N; Flamaing, J; Lobelle, J P; Milisen, K; De Grève, J; Wildiers, H

2017-10-01

Older patients with lung cancer are a heterogeneous population making treatment decisions complex. This study aims to evaluate the value of geriatric assessment (GA) as well as the evolution of functional status (FS) in older patients with lung cancer, and to identify predictors associated with functional decline and overall survival (OS). At baseline, GA was performed in patients ≥70 years with newly diagnosed lung cancer. FS measured by activities of daily living (ADL) and instrumental activities of daily living (IADL) was reassessed at follow-up to define functional decline and OS was collected. Predictors for functional decline and OS were determined. Two hundred and forty-five patients were included in this study. At baseline, GA deficiencies were present in all domains and ADL and IADL were impaired in 51 and 63% of patients, respectively. At follow-up, functional decline in ADL was observed in 23% and in IADL in 45% of patients. In multivariable analysis, radiotherapy was predictive for ADL decline. No other predictors for ADL or IADL decline were identified. Stage and baseline performance status were predictive for OS. Older patients with lung cancer present with multiple deficiencies covering all geriatric domains. During treatment, functional decline is observed in almost half of the patients. None of the specific domains of the GA were predictive for functional decline or survival, probably because of the high impact of the aggressiveness of this tumor type leading to a poor prognosis.

Cumulative incidence of functional decline after minor injuries in previously independent older Canadian individuals in the emergency department.

PubMed

Sirois, Marie-Josée; Émond, Marcel; Ouellet, Marie-Christine; Perry, Jeffrey; Daoust, Raoul; Morin, Jacques; Dionne, Clermont; Camden, Stéphanie; Moore, Lynne; Allain-Boulé, Nadine

2013-10-01

To estimate the cumulative incidence of functional decline in independent older adults 3 and 6 months after a minor injury treated in the emergency department (ED) and to identify predictors of this functional decline. Prospective cohort study. Three Canadian teaching EDs. Individuals aged 65 and older who were independent in basic activities of daily living before their injury and were evaluated in the ED for minor injuries (N = 335). Functional decline was defined as a loss of 2 or more out of 28 points on the self-reported Older Americans Resources Services scale. Sociodemographic, mobility, and clinical risk factors for functional decline in non-ED studies were measured at the ED visit and 3 and 6 months after the injury. Generalized linear mixed models were used to explore differences in functional decline between groups determined according to the different factors. The cumulative incidence of decline was 14.9% (95% confidence interval (CI) = 7.6-29.1%) at 3 months and 17.3% (95% CI = 9.7-30.9%) at 6 months. Predictors of functional decline were occasional use of a walking aid (relative risk (RR)=2.4, 95% CI = 1.4-4.2), needing help in instrumental activities of daily living (IADLs) before the injury (RR = 3.1, 95% CI=1.7-5.5), taking five or more daily medications (RR = 1.8, 95% CI = 1.0-3.2), and the emergency physicians' assessment of functional decline (RR = 2.8, 95% CI = 1.5-5.3). Minor injuries in independent older adults treated in EDs are associated with a 15% cumulative incidence of functional decline 3 months after the injury that persisted 6 months later. Simple-to-measure factors such as occasional use of a walking aid, daily medication, need for help with IADLs, and physician assessment of decline may help identify independent older adults at risk of functional decline during their consultation. These results confirm the need to improve risk assessment and management of this population in EDs. © 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.

Epidemiological aspects of ageing.

PubMed Central

Khaw, K T

1997-01-01

A major societal challenge is to improve quality of life and prevent or reduce disability and dependency in an ageing population. Increasing age is associated with increasing risk of disability and loss of independence, due to functional impairments such as loss of mobility, hearing and vision; a major issue must be how far disability can be prevented. Ageing is associated with loss of bone tissue, reduction in muscle mass, reduced respiratory function, decline in cognitive function, rise in blood pressure and macular degeneration which predispose to disabling conditions such as osteoporosis, heart disease, dementia and blindness. However, there are considerable variations in different communities in terms of the rate of age-related decline. Large geographic and secular variations in the age-adjusted incidence of major chronic diseases such as stroke, hip fracture, coronary heart disease, cancer, visual loss from cataract, glaucoma and macular degeneration suggest strong environmental determinants in diet, physical activity and smoking habit. The evidence suggests that a substantial proportion of chronic disabling conditions associated with ageing are preventable, or at least postponable and not an inevitable accompaniment of growing old. Postponement or prevention of these conditions may not only increase longevity, but, more importantly, reduce the period of illnesses such that the majority of older persons may live high-quality lives, free of disability, until very shortly before death. We need to understand better the factors influencing the onset of age-related disability in the population, so that we have appropriate strategies to maintain optimal health in an ageing population. PMID:9460067

Epidemiological aspects of ageing.

PubMed

Khaw, K T

1997-12-29

A major societal challenge is to improve quality of life and prevent or reduce disability and dependency in an ageing population. Increasing age is associated with increasing risk of disability and loss of independence, due to functional impairments such as loss of mobility, hearing and vision; a major issue must be how far disability can be prevented. Ageing is associated with loss of bone tissue, reduction in muscle mass, reduced respiratory function, decline in cognitive function, rise in blood pressure and macular degeneration which predispose to disabling conditions such as osteoporosis, heart disease, dementia and blindness. However, there are considerable variations in different communities in terms of the rate of age-related decline. Large geographic and secular variations in the age-adjusted incidence of major chronic diseases such as stroke, hip fracture, coronary heart disease, cancer, visual loss from cataract, glaucoma and macular degeneration suggest strong environmental determinants in diet, physical activity and smoking habit. The evidence suggests that a substantial proportion of chronic disabling conditions associated with ageing are preventable, or at least postponable and not an inevitable accompaniment of growing old. Postponement or prevention of these conditions may not only increase longevity, but, more importantly, reduce the period of illnesses such that the majority of older persons may live high-quality lives, free of disability, until very shortly before death. We need to understand better the factors influencing the onset of age-related disability in the population, so that we have appropriate strategies to maintain optimal health in an ageing population.

Genetic Contributions to Age-Related Decline in Executive Function: A 10-Year Longitudinal Study of COMT and BDNF Polymorphisms

PubMed Central

Erickson, Kirk I.; Kim, Jennifer S.; Suever, Barbara L.; Voss, Michelle W.; Francis, B. Magnus; Kramer, Arthur F.

2008-01-01

Genetic variability in the dopaminergic and neurotrophic systems could contribute to age-related impairments in executive control and memory function. In this study we examined whether genetic polymorphisms for catechol-O-methyltransferase (COMT) and brain-derived neurotrophic factor (BDNF) were related to the trajectory of cognitive decline occurring over a 10-year period in older adults. A single nucleotide polymorphism in the COMT (Val158/108Met) gene affects the concentration of dopamine in the prefrontal cortex. In addition, a Val/Met substitution in the pro-domain for BDNF (Val66Met) affects the regulated secretion and trafficking of BDNF with Met carriers showing reduced secretion and poorer cognitive function. We found that impairments over the 10-year span on a task-switching paradigm did not vary as a function of the COMT polymorphism. However, for the BDNF polymorphism the Met carriers performed worse than Val homozygotes at the first testing session but only the Val homozygotes demonstrated a significant reduction in performance over the 10-year span. Our results argue that the COMT polymorphism does not affect the trajectory of age-related executive control decline, whereas the Val/Val polymorphism for BDNF may promote faster rates of cognitive decay in old age. These results are discussed in relation to the role of BDNF in senescence and the transforming impact of the Met allele on cognitive function in old age. PMID:18958211

Cerebroprotective effect of piracetam in patients undergoing coronary bypass burgery.

PubMed

Holinski, Sebastian; Claus, Benjamin; Alaaraj, Nour; Dohmen, Pascal Maria; Kirilova, Kremena; Neumann, Konrad; Uebelhack, Ralf; Konertz, Wolfgang

2008-11-01

Reduction of cognitive function is a possible side effect after cardiac surgery using cardiopulmonary bypass. We investigated the cerebroprotective effect of piracetam on cognitive performance in patients undergoing coronary artery bypass surgery under cardiopulmonary bypass. Patients scheduled for elective, primary and isolated coronary bypass surgery were randomised either to piracetam or placebo group. The study was performed in a double blind fashion. Patients received either 12 g piracetam or placebo at the beginning of the operation. Six neuropsychological subtests from the Syndrom Kurz Test and the Alzheimer's Disease Assessment Scale were performed preoperatively and on the third postoperative day. To assess the overall cognitive function and the degree of cognitive decline across all tests after surgery we combined the six test-scores by principal component analysis. A total number of 120 patients were enrolled into the study. Preoperative overall cognitive function were not significantly different between the groups. The postoperative combined score of the neuropsychological tests showed a deterioration of cognitive function in both groups (placebo-pre: -0.06+/-0.99 vs placebo-post: -1.38+/-1.11; p<0.0005 and piracetam-pre: 0.06+/-1.02 vs piracetam-post: -0.65+/-0.93; p<0.0005). However, the piracetam patients performed significantly better compared to the placebo patients after the operation and had a less decline of overall cognitive function (p<0.0005). Piracetam has a cerebroprotective effect in patients undergoing coronary artery bypass surgery with the use of cardiopulmonary bypass. It reduces an early postoperative substantial decline of neuropsychological abilities.

"No Time to Play": Perceptions toward Physical Activity in Youth with Cystic Fibrosis

ERIC Educational Resources Information Center

Moola, Fiona; Faulkner, Guy E. J.; Schneiderman, Jane E.

2012-01-01

Although physical activity may reduce lung function decline in youth with cystic fibrosis (CF), most patients are inactive. Little is known about why youth with CF are inactive or how to facilitate physical activity. This study explored perceptions toward physical activity in 14 youth with CF at a Canadian Hospital. Qualitative interviews were…

Long-term efficacy of a rural community-based integrated intervention for prevention and management of chronic obstructive pulmonary disease: a cluster randomized controlled trial in China's rural areas.

PubMed

Yuan, X; Tao, Y; Zhao, J P; Liu, X S; Xiong, W N; Xie, J G; Ni, W; Xu, Y J; Liu, H G

2015-11-01

This study aimed to assess the efficacy of a rural community-based integrated intervention for early prevention and management of chronic obstructive pulmonary disease (COPD) in China. This 18-year cluster-randomized controlled trial encompassing 15 villages included 1008 patients (454 men and 40 women in the intervention group [mean age, 54 ± 10 years]; 482 men and 32 women in the control group [mean age, 53 ± 10 years]) with confirmed COPD or at risk for COPD. Villages were randomly assigned to the intervention or the control group, and study participants residing within the villages received treatment accordingly. Intervention group patients took part in a program that included systematic health education, smoking cessation counseling, and education on management of COPD. Control group patients received usual care. The groups were compared after 18 years regarding the incidence of COPD, decline in lung function, and mortality of COPD. COPD incidence was lower in the intervention group than in the control group (10% vs 16%, <0.05). A decline in lung function was also significantly delayed in the intervention group compared to the control group of COPD and high-risk patients. The intervention group showed significant improvement in smoking cessation compared with the control group, and smokers in the intervention group had lower smoking indices than in the control group (350 vs 450, <0.05). The intervention group also had a significantly lower cumulative COPD-related death rate than the control group (37% vs 47%, <0.05). A rural community-based integrated intervention is effective in reducing the incidence of COPD among those at risk, delaying a decline in lung function in COPD patients and those at risk, and reducing mortality of COPD.

SGLT2-inhibitor and DPP-4 inhibitor improve brain function via attenuating mitochondrial dysfunction, insulin resistance, inflammation, and apoptosis in HFD-induced obese rats.

PubMed

Sa-Nguanmoo, Piangkwan; Tanajak, Pongpan; Kerdphoo, Sasiwan; Jaiwongkam, Thidarat; Pratchayasakul, Wasana; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2017-10-15

Dipeptidyl peptidase-4 inhibitor (vildagliptin) has been shown to exert beneficial effects on insulin sensitivity and neuroprotection in obese-insulin resistance. Recent studies demonstrated the neuroprotection of the sodium-glucose co-transporter 2 inhibitor (dapagliflozin) in diabetes. However, the comparative effects of both drugs and a combination of two drugs on metabolic dysfunction and brain dysfunction impaired by the obese-insulin resistance have never been investigated. Forty male Wistar rats were divided into two groups, and received either a normal-diet (ND, n=8) or a high-fat diet (HFD, n=32) for 16weeks. At week 13, the HFD-fed rats were divided into four subgroups (n=8/subgroup) to receive either a vehicle, vildagliptin (3mg/kg/day) dapagliflozin (1mg/kg/day) or combined drugs for four weeks. ND rats were given a vehicle for four weeks. Metabolic parameters and brain function were investigated. The results demonstrated that HFD rats developed obese-insulin resistance and cognitive decline. Dapagliflozin had greater efficacy on improved peripheral insulin sensitivity and reduced weight gain than vildagliptin. Single therapy resulted in equally improved brain mitochondrial function, insulin signaling, apoptosis and prevented cognitive decline. However, only dapagliflozin improved hippocampal synaptic plasticity. A combination of the drugs had greater efficacy in improving brain insulin sensitivity and reducing brain oxidative stress than the single drug therapy. These findings suggested that dapagliflozin and vildagliptin equally prevented cognitive decline in the obese-insulin resistance, possibly through some similar mechanisms. Dapagliflozin had greater efficacy than vildagliptin for preserving synaptic plasticity, thus combined drugs could be the best therapeutic approach for neuroprotection in the obese-insulin resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

Role of physical activity in reducing cognitive decline in older Mexican-American adults.

PubMed

Ottenbacher, Allison J; Snih, Soham Al; Bindawas, Saad M; Markides, Kyriakos S; Graham, James E; Samper-Ternent, Rafael; Raji, Mukaila; Ottenbacher, Kenneth J

2014-09-01

The effect of physical activity on cognitive function in older adults from minority and disadvantaged populations is not well understood. This study examined the longitudinal association between physical activity and cognition in older Mexican Americans. The study methodology included a prospective cohort with longitudinal analysis of data from the Hispanic Established Populations for the Epidemiologic Study of the Elderly. General linear mixed models were used to assess the associations and interactions between physical activity and cognitive function over 14 years. Community-based assessments were performed in participants' homes. Physical activity was recorded for 1,669 older Mexican Americans using the Physical Activity Scale for the Elderly. Cognition was measured using the Mini-Mental State Examination (MMSE) and separated into memory and nonmemory components. A statistically significant positive association was observed between levels of physical activity and cognitive function after adjusting for age, sex, marital status, education, and comorbid health conditions. There was a statistically significant difference in MMSE scores over time between participants in the third (β = 0.11, standard error (SE) = 0.05) and fourth (β = 0.10, SE = 0.2) quartiles of physical activity and those in the first. The protective effect of physical activity on cognitive decline was evident for the memory component of the MMSE but not the nonmemory component after adjusting for covariates. Greater physical activity at baseline was associated with less cognitive decline over 14 years in older Mexican Americans. The reduction in cognitive decline appeared to be related to the memory components of cognitive function. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

Executive and attentional functions in chronic pain: Does performance decrease with increasing task load?

PubMed Central

Oosterman, Joukje M; Derksen, Laura C; van Wijck, Albert JM; Kessels, Roy PC; Veldhuijzen, Dieuwke S

2012-01-01

BACKGROUND: Diminished executive function and attentional control has been reported in chronic pain patients. However, the precise pattern of impairment in these aspects of cognition in chronic pain remains unclear. Moreover, a decline in psychomotor speed could potentially influence executive and attentional control performance in pain patients. OBJECTIVE: To examine different aspects of executive and attentional control in chronic pain together with the confounding role of psychomotor slowing. METHODS: Neuropsychological tests of sustained attention, planning ability, inhibition and mental flexibility were administered to 34 participants with chronic pain and 32 control participants. RESULTS: Compared with the controls, participants with chronic pain took longer to complete tests of sustained attention and mental flexibility, but did not perform worse on inhibition or planning tasks. The decreased performance on the mental flexibility task likely reflects a reduction in psychomotor speed. The pattern of performance on the sustained attention task reveals a specific decline in attention, indicated by a disproportionate decline in performance with an increase in task duration and by increased fluctuations in attention during task performance. No additional effect was noted of pain intensity, pain duration, pain catastrophizing, depressive symptoms, reduced sleep because of the pain or opioid use. CONCLUSIONS: Executive and attention functions are not uniformly affected in chronic pain. At least part of the previously reported decline in executive function in this group may reflect psychomotor slowing. Overall, limited evidence was found that executive and attention performance is indeed lower in chronic pain. Therefore, it can be concluded that in chronic pain sustained attention performance is diminished while mental flexibility, planning and inhibition appear to be intact. PMID:22606680

Role of social support in cognitive function among elders.

PubMed

Zhu, Shuzhen; Hu, Jie; Efird, Jimmy T

2012-08-01

To examine cognitive function and its relationships to demographic characteristics and social support among elders in central China. Cognitive decline is prevalent among elders. Few studies have explored the relationship between social support and cognitive function among elders. A cross-sectional, descriptive correlational study. A quasi-random, point of reference sample of 120 elders residing in central China was recruited for study. Instruments used included a: Socio-demographic Questionnaire, the Multidimensional Scale on Perceived Social Support and the Mini-Mental State Examination. Hierarchical multiple regression was performed to examine the relationships among demographic variables, social support and cognitive function. Age, education and social support accounted for 45·2% of the variance in cognitive function. Family support was the strongest predictor of cognitive function. Elders who had higher educational levels and more family support had better cognitive function. Relevance to clinical practice.  Community healthcare providers should consolidate social support among elders in China and use family support interventions to reduce or delay cognitive decline, especially among those of increased age who are illiterate. Elders who had higher educational level and more family support had better cognitive function levels. Interventions that include family support are needed to improve cognitive function among elders in China. © 2012 Blackwell Publishing Ltd.

Functional decline in Huntington's disease.

PubMed

Feigin, A; Kieburtz, K; Bordwell, K; Como, P; Steinberg, K; Sotack, J; Zimmerman, C; Hickey, C; Orme, C; Shoulson, I

1995-03-01

We prospectively evaluated 129 patients with manifest Huntington's disease (HD) to determine the rate of illness progression and the clinical features that correlate with functional decline. A single examiner evaluated each patient using the HD Functional Capacity Scale. Standardized motor performance was also assessed in 94 of the patients (73%) using the HD Rating Scale. Total Functional Capacity declined at a rate of 0.63 +/- 0.75 U per year. As functional capacity worsened, chorea lessened, and dystonia intensified. There was no correlation between rate of functional decline and age at onset of HD, body weight, gender of affected parent, or history of neuroleptic use.

Food-Derived Antioxidant Polysaccharides and Their Pharmacological Potential in Neurodegenerative Diseases

PubMed Central

Li, Haifeng; Ding, Fei; Xiao, Lingyun; Shi, Ruona; Wang, Hongyu; Han, Wenjing

2017-01-01

Oxidative stress is known to impair architecture and function of cells, which may lead to various chronic diseases, and therefore therapeutic and nutritional interventions to reduce oxidative damages represent a viable strategy in the amelioration of oxidative stress-related disorders, including neurodegenerative diseases. Over the past decade, a variety of natural polysaccharides from functional and medicinal foods have attracted great interest due to their antioxidant functions such as scavenging free radicals and reducing oxidative damages. Interestingly, these antioxidant polysaccharides are also found to attenuate neuronal damages and alleviate cognitive and motor decline in a range of neurodegenerative models. It has recently been established that the neuroprotective mechanisms of polysaccharides are related to oxidative stress-related pathways, including mitochondrial function, antioxidant defense system and pathogenic protein aggregation. Here, we first summarize the current status of antioxidant function of food-derived polysaccharides and then attempt to appraise their anti-neurodegeneration activities. PMID:28753972

Further education improves cognitive reserve and triggers improvement in selective cognitive functions in older adults: The Tasmanian Healthy Brain Project.

PubMed

Thow, Megan E; Summers, Mathew J; Saunders, Nichole L; Summers, Jeffery J; Ritchie, Karen; Vickers, James C

2018-01-01

The strong link between early-life education and subsequent reduced risk of dementia suggests that education in later life could enhance cognitive function and may reduce age-related cognitive decline and protect against dementia. Episodic memory, working memory, executive function, and language processing performances were assessed annually over 4 years in 359 healthy older adults who attended university for a minimum of 12 months (intervention) and were compared against 100 healthy adult controls. Multiple group latent growth curve modeling revealed a significant improvement in language processing capacity over time in the intervention group. No changes were detected for episodic memory, working memory, or executive function. These results suggest that complex mental stimulation resulting from late-life further education results in improved crystallized knowledge but no changes to fluid cognitive functions.

The quality of life of patients developed delirium after coronary artery bypass grafting is determined by cognitive function after discharge: A cross-sectional study.

PubMed

Chen, Yuling; Ding, Shu; Tao, Xiangjun; Feng, Xinwei; Lu, Sai; Shen, Yuzhi; Wu, Ying; An, Xiangguang

2017-10-01

Postoperative delirium (POD) and declined cognitive function were common in patients (especially elderly patients) who underwent coronary artery bypass grafting (CABG), which may affect quality of life (QoL). The aim of this study was to determine the relationships among age, POD, declined cognitive function, and QoL in patients who underwent CABG. Consecutive patients who underwent first time elective CABG and assessed for POD using Confusion Assessment Method for intensive care unit for 5 postoperative days from November 2013 to March 2015 were recruited. A cross-sectional study was conducted during April 2015 to assess their cognitive function and QoL, using the Telephone Interview for Cognitive Status Scale and Medical Outcomes Study 36-Item Short Form Health Survey. The relationships among age, POD, declined cognitive function, and QoL were tested using path analysis. Declined cognitive function was associated with poorer QoL. POD was associated with declined cognitive function but was not associated with poorer QoL. Ageing was not associated with QoL but was associated with POD and declined cognitive function. The QoL of patients developed delirium after CABG is determined by cognitive function after discharge. Necessary strategies should be implemented to prevent POD and declined cognitive function, especially in elderly patients. © 2017 John Wiley & Sons Australia, Ltd.

Activation of Gαq Signaling Enhances Memory Consolidation and Slows Cognitive Decline.

PubMed

Arey, Rachel N; Stein, Geneva M; Kaletsky, Rachel; Kauffman, Amanda; Murphy, Coleen T

2018-05-02

Perhaps the most devastating decline with age is the loss of memory. Therefore, identifying mechanisms to restore memory function with age is critical. Using C. elegans associative learning and memory assays, we identified a gain-of-function G αq signaling pathway mutant that forms a long-term (cAMP response element binding protein [CREB]-dependent) memory following one conditioned stimulus-unconditioned stimulus (CS-US) pairing, which usually requires seven CS-US pairings. Increased CREB activity in AIM interneurons reduces the threshold for memory consolidation through transcription of a set of previously identified "long-term memory" genes. Enhanced G αq signaling in the AWC sensory neuron is both necessary and sufficient for improved memory and increased AIM CREB activity, and activation of G αq specifically in aged animals rescues the ability to form memory. Activation of G αq in AWC sensory neurons non-cell autonomously induces consolidation after one CS-US pairing, enabling both cognitive function maintenance with age and restoration of memory function in animals with impaired memory performance without decreased longevity. Copyright © 2018 Elsevier Inc. All rights reserved.

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

Longitudinal changes in speech recognition in older persons.

PubMed

Dubno, Judy R; Lee, Fu-Shing; Matthews, Lois J; Ahlstrom, Jayne B; Horwitz, Amy R; Mills, John H

2008-01-01

Recognition of isolated monosyllabic words in quiet and recognition of key words in low- and high-context sentences in babble were measured in a large sample of older persons enrolled in a longitudinal study of age-related hearing loss. Repeated measures were obtained yearly or every 2 to 3 years. To control for concurrent changes in pure-tone thresholds and speech levels, speech-recognition scores were adjusted using an importance-weighted speech-audibility metric (AI). Linear-regression slope estimated the rate of change in adjusted speech-recognition scores. Recognition of words in quiet declined significantly faster with age than predicted by declines in speech audibility. As subjects aged, observed scores deviated increasingly from AI-predicted scores, but this effect did not accelerate with age. Rate of decline in word recognition was significantly faster for females than males and for females with high serum progesterone levels, whereas noise history had no effect. Rate of decline did not accelerate with age but increased with degree of hearing loss, suggesting that with more severe injury to the auditory system, impairments to auditory function other than reduced audibility resulted in faster declines in word recognition as subjects aged. Recognition of key words in low- and high-context sentences in babble did not decline significantly with age.

Felt Obligation to Help Others as a Protective Factor Against Losses in Psychological Well-being Following Functional Decline in Middle and Later Life

PubMed Central

2009-01-01

This study examined felt obligation to help others in two domains (close others and society) as protective factors against losses in psychological well-being following functional decline. Lagged-dependent regression models were estimated using data from 849 respondents aged 35–74 years and without any functional limitations at baseline in the 1995–2005 National Survey of Midlife in the United States. Greater felt obligation to help close others protected against declining self-acceptance in the face of more severe functional decline, and greater felt obligation to help society protected against declining personal growth and self-acceptance. Greater felt obligation to help close others and society protected against increasing depressive symptoms at younger ages in adulthood. Findings suggest the importance for additional research on how aspects of altruism can promote psychological adaptation to declining functional health in middle and later life. PMID:19825942

Cardiovascular risk factors and dementia.

PubMed

Fillit, Howard; Nash, David T; Rundek, Tatjana; Zuckerman, Andrea

2008-06-01

Dementias, such as Alzheimer's disease (AD) and vascular dementia, are disorders of aging populations and represent a significant economic burden. Evidence is accumulating to suggest that cardiovascular disease (CVD) risk factors may be instrumental in the development of dementia. The goal of this review was to discuss the relationship between specific CVD risk factors and dementia and how current treatment strategies for dementia should focus on reducing CVD risks. We conducted a review of the literature for the simultaneous presence of 2 major topics, cardiovascular risk factors and dementia (eg, AD). Special emphasis was placed on clinical outcome studies examining the effects of treatments of pharmacologically modifiable CVD risk factors on dementia and cognitive impairment. Lifestyle risk factors for CVD, such as obesity, lack of exercise, smoking, and certain psychosocial factors, have been associated with an increased risk of cognitive decline and dementia. Some evidence suggests that effectively managing these factors may prevent cognitive decline/dementia. Randomized, placebo-controlled trials of antihypertensive medications have found that such therapy may reduce the risk of cognitive decline, and limited data suggest a benefit for patients with AD. Some small open-label and randomized clinical trials of statins have observed positive effects on cognitive function; larger studies of statins in patients with AD are ongoing. Although more research is needed, current evidence indicates an association between CVD risk factors--such as hypertension, dyslipidemia, and diabetes mellitus--and cognitive decline/dementia. From a clinical perspective, these data further support the rationale for physicians to provide effective management of CVD risk factors and for patients to be compliant with such recommendations to possibly prevent cognitive decline/dementia.

The Utility of the Remnant Kidney Volume/Body Surface Area Ratio and Tumor Diameter as Predictors of Postoperative Degree of Renal Functional Decline in Patients With Renal Cell Carcinoma Treated by Radical Nephrectomy.

PubMed

Sejima, Takehiro; Yamaguchi, Noriya; Iwamoto, Hideto; Masago, Toshihiko; Morizane, Shuichi; Ono, Koji; Koumi, Tsutomu; Honda, Masashi; Takenaka, Atsushi

2015-08-01

To characterize the preoperative factors affecting renal cell carcinoma patients as predictive of post-radical nephrectomy (RN) mild (M-decline) or severe (S-decline) renal functional decline and to elucidate the histopathologic features of the resected normal kidney cortex, as well as the occurrence of cardiovascular disease (CVD) in both M-decline and S-decline patients. M-decline and S-decline were categorized as a percentage of postoperative estimated glomerular filtration rate decline of <20 and of >40, respectively. The preoperative factors analyzed were patient demographics, comorbidities, and radiographic findings, including remnant kidney status and tumor size. The factors based on postoperative information analyzed were tumor and normal cortex pathology and CVD events. In 175 patient cohort, 21 and 32 cases were categorized as M-decline and S-decline, respectively. Absence of comorbidities, larger remnant kidney volume (RKV)/body surface area (BSA) ratio, and larger tumor diameter were significantly predictive of M-decline, whereas smaller tumor diameter was significantly predictive of S-decline. The global glomerulosclerosis extent in nephrectomized normal cortex of S-decline cases was significantly higher than in other types of cases. No CVD event was observed in M-decline cases. This is the first report to identify the RKV/BSA ratio as a promising predictor of post-RN degree of renal functional decline. Post-RN prevention of life-threatening outcomes according to preoperative and postoperative information, including the degree of post-RN renal functional decline and histopathology of the nephrectomized normal cortex, should be considerable in future urological tasks. Copyright © 2015 Elsevier Inc. All rights reserved.

Change in Sexual Functioning Over the Menopause Transition: Results from the Study of Women’s Health Across the Nation (SWAN)

PubMed Central

Avis, Nancy E.; Colvin, Alicia; Karlamangla, Arun S.; Crawford, Sybil; Hess, Rachel; Waetjen, L. Elaine; Brooks, Maria; Tepper, Ping G.; Greendale, Gail A.

2016-01-01

Objective To identify whether there is a decline in sexual functioning related to the menopause transition or to hysterectomy. Methods In a cohort of 1,390 women aged 42–52, with intact uterus and at least one ovary, not using hormone therapy, and pre- or early perimenopausal at baseline, we fit piecewise linear growth curves to 5,798 repeated measurements (7 visits spanning 14.5 years) of a sexual functioning score (range, 5–25) as a function of time relative to date of final menstrual period (FMP) or hysterectomy. Results Mean sexual functioning at baseline in women with a dateable FMP was 18.0 (standard deviation, 3.4). There was no change in sexual function until 20 months before the FMP. From 20 months before until one year after the FMP, sexual function decreased by 0.35 annually (95% CI:−0.44, −0.26) and continued to decline more than one year after the FMP, but at a slower rate (−0.13 annually, 95% CI:−0.17, −0.10). The decline was smaller in African-Americans and larger in Japanese compared to whites. Vaginal dryness, lubricant use, depressive symptoms, or anxiety did not explain decline in sexual function. Women who had a hysterectomy prior to the FMP did not show decline in sexual function prior to hysterectomy, but scores declined afterwards (0.21 annually, 95% CI:−0.28, −0.14). Conclusions Decline in sexual function became apparent 20 months prior to FMP and slowed one year after FMP through 5 years afterwards. A decline in sexual function was observed immediately after hysterectomy and persisted for the 5 years of observation. PMID:27801705

Ecological intensification to mitigate impacts of conventional intensive land use on pollinators and pollination.

PubMed

Kovács-Hostyánszki, Anikó; Espíndola, Anahí; Vanbergen, Adam J; Settele, Josef; Kremen, Claire; Dicks, Lynn V

2017-05-01

Worldwide, human appropriation of ecosystems is disrupting plant-pollinator communities and pollination function through habitat conversion and landscape homogenisation. Conversion to agriculture is destroying and degrading semi-natural ecosystems while conventional land-use intensification (e.g. industrial management of large-scale monocultures with high chemical inputs) homogenises landscape structure and quality. Together, these anthropogenic processes reduce the connectivity of populations and erode floral and nesting resources to undermine pollinator abundance and diversity, and ultimately pollination services. Ecological intensification of agriculture represents a strategic alternative to ameliorate these drivers of pollinator decline while supporting sustainable food production, by promoting biodiversity beneficial to agricultural production through management practices such as intercropping, crop rotations, farm-level diversification and reduced agrochemical use. We critically evaluate its potential to address and reverse the land use and management trends currently degrading pollinator communities and potentially causing widespread pollination deficits. We find that many of the practices that constitute ecological intensification can contribute to mitigating the drivers of pollinator decline. Our findings support ecological intensification as a solution to pollinator declines, and we discuss ways to promote it in agricultural policy and practice. © 2017 The Authors. Ecology Letters published by CNRS and John Wiley & Sons Ltd.

Symptomatic BK Virus Infection Is Associated with Kidney Function Decline and Poor Overall Survival in Allogeneic Hematopoietic Stem Cell Recipients

PubMed Central

Abudayyeh, Ala; Hamdi, Amir; Lin, Heather; Abdelrahim, Maen; Rondon, Gabriela; Andersson, Borje S; Afrough, Aimaz; Martinez, Charles S; Tarrand, Jeffrey J; Kontoyiannis, Dimitrios P.; Marin, David; Gaber, A. Osama; Salahudeen, Abdulla; Oran, Betul; Chemaly, Roy F.; Olson, Amanda; Jones, Roy; Popat, Uday; Champlin, Richard E; Shpall, Elizabeth J.; Winkelmayer, Wolfgang C.; Rezvani, Katayoun

2017-01-01

Nephropathy due to BK virus infection is an evolving challenge in patients undergoing hematopoietic stem cell transplantation. We hypothesized that BKV infection was a marker of Kidney Function Decline and a poor prognostic factor in HSCT recipients who experience this complication. In this retrospective study, we analyzed all patients who underwent their first allogeneic hematopoietic stem cell transplantation at our institution between 2004 and 2012. We evaluated the incidence of persistent kidney function decline, which was defined as a confirmed reduction in estimated glomerular filtration rate of at least 25% from baseline using the CKD-EPI equation. Cox proportional hazard regression was used to model the cause-specific hazard of kidney function decline and Fine and Gray’s method was used to account for the competing risks of death. Among 2477 recipients of a first allogeneic hematopoietic stem cell transplantation, BK viruria was detected in 25% (n=629) and kidney function decline in 944 (38.1%). On multivariate analysis, after adjusting for age, sex, acute graft-versus-host disease, chronic graft versus host disease, preparative conditioning regimen, and graft source, BK viruria remained a significant risk factor for kidney function decline (P <0.001). In addition, patients with BKV infection and kidney function decline experienced worse overall survival. Post-allogeneic hematopoietic stem cell transplantation, BKV infection was strongly and independently associated with subsequent kidney function decline and worse patient survival after HSCT. PMID:26608093

Cthrc1 lowers pulmonary collagen associated with bleomycin-induced fibrosis and protects lung function.

PubMed

Binks, Andrew P; Beyer, Megyn; Miller, Ryan; LeClair, Renee J

2017-03-01

Idiopathic pulmonary fibrosis (IPF) involves collagen deposition that results in a progressive decline in lung function. This process involves activation of Smad2/3 by transforming growth factor (TGF)- β and Wnt signaling pathways. Collagen Triple Helix Repeat-Containing-1 (Cthrc1) protein inhibits Smad2/3 activation. To test the hypothesis that Cthrc1 limits collagen deposition and the decline of lung function, Cthrc1 knockout (Cthrc1 -/- ) and wild-type mice (WT) received intratracheal injections of 2.5 U/kg bleomycin or saline. Lungs were harvested after 14 days and Bronchoalveolar lavage (BAL) TGF- β , IL1- β , hydroxyproline and lung compliance were assessed. TGF- β was significantly higher in Cthrc1 -/- compared to WT (53.45 ± 6.15 ng/mL vs. 34.48 ± 11.05) after saline injection. Bleomycin injection increased TGF- β in both Cthrc1 -/- (66.37 ± 8.54 ng/mL) and WT (63.64 ± 8.09 ng/mL). Hydroxyproline was significantly higher in Cthrc1 -/- compared to WT after bleomycin-injection (2.676 ± 0.527  μ g/mg vs. 1.889 ± 0.520, P  = 0.028). Immunohistochemistry of Cthrc1 -/- lung sections showed intracellular localization and activation of β -catenin Y654 in areas of tissue remodeling that was not evident in WT Lung compliance was significantly reduced by bleomycin in Cthrc1 -/- but there was no effect in WT animals. These data suggest Cthrc1 reduces fibrotic tissue formation in bleomycin-induced lung fibrosis and the effect is potent enough to limit the decline in lung function. We conclude that Cthrc1 plays a protective role, limiting collagen deposition and could form the basis of a novel therapy for pulmonary fibrosis. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Functional decline after incident wrist fractures—Study of Osteoporotic Fractures: prospective cohort study

PubMed Central

Song, Jing; Dunlop, Dorothy D; Fink, Howard A; Cauley, Jane A

2010-01-01

Objective To study the effect of an incident wrist fracture on functional status in women enrolled in the Study of Osteoporotic Fractures. Design Prospective cohort study. Setting Baltimore, Minneapolis, Portland, and the Monongahela valley in Pennsylvania, USA Participants 6107 women aged 65 years and older without previous wrist or hip fracture recruited from the community between September 1986 and October 1988. Main outcome measure Clinically important functional decline, defined as a functional deterioration of 5 points in five activities of daily living each scored from 0 to 3 (equivalent to one standard deviation decrease in functional ability). Results Over a mean follow-up of 7.6 years, 268 women had an incident wrist fracture and 41 (15%) of these developed clinically important functional decline. Compared with women without wrist fractures, those with incident wrist fractures had greater annual functional decline after adjustment for age, body mass index, and health status. Occurrence of a wrist fracture increased the odds of having a clinically important functional decline by 48% (odds ratio 1.48, 95% confidence interval 1.04 to 2.12), even after adjustment for age, body mass index, health status, baseline functional status, lifestyle factors, comorbidities, and neuromuscular function. Conclusions Wrist fractures contribute to clinically important functional decline in older women. PMID:20616099

Devastating Decline of Forest Elephants in Central Africa

PubMed Central

Blake, Stephen; Wittemyer, George; Hart, John; Williamson, Elizabeth A.; Aba’a, Rostand; Abitsi, Gaspard; Ambahe, Ruffin D.; Amsini, Fidèl; Bakabana, Parfait C.; Hicks, Thurston Cleveland; Bayogo, Rosine E.; Bechem, Martha; Beyers, Rene L.; Bezangoye, Anicet N.; Boundja, Patrick; Bout, Nicolas; Akou, Marc Ella; Bene, Lambert Bene; Fosso, Bernard; Greengrass, Elizabeth; Grossmann, Falk; Ikamba-Nkulu, Clement; Ilambu, Omari; Inogwabini, Bila-Isia; Iyenguet, Fortune; Kiminou, Franck; Kokangoye, Max; Kujirakwinja, Deo; Latour, Stephanie; Liengola, Innocent; Mackaya, Quevain; Madidi, Jacob; Madzoke, Bola; Makoumbou, Calixte; Malanda, Guy-Aimé; Malonga, Richard; Mbani, Olivier; Mbendzo, Valentin A.; Ambassa, Edgar; Ekinde, Albert; Mihindou, Yves; Morgan, Bethan J.; Motsaba, Prosper; Moukala, Gabin; Mounguengui, Anselme; Mowawa, Brice S.; Ndzai, Christian; Nixon, Stuart; Nkumu, Pele; Nzolani, Fabian; Pintea, Lilian; Plumptre, Andrew; Rainey, Hugo; de Semboli, Bruno Bokoto; Serckx, Adeline; Stokes, Emma; Turkalo, Andrea; Vanleeuwe, Hilde; Vosper, Ashley; Warren, Ymke

2013-01-01

African forest elephants– taxonomically and functionally unique–are being poached at accelerating rates, but we lack range-wide information on the repercussions. Analysis of the largest survey dataset ever assembled for forest elephants (80 foot-surveys; covering 13,000 km; 91,600 person-days of fieldwork) revealed that population size declined by ca. 62% between 2002–2011, and the taxon lost 30% of its geographical range. The population is now less than 10% of its potential size, occupying less than 25% of its potential range. High human population density, hunting intensity, absence of law enforcement, poor governance, and proximity to expanding infrastructure are the strongest predictors of decline. To save the remaining African forest elephants, illegal poaching for ivory and encroachment into core elephant habitat must be stopped. In addition, the international demand for ivory, which fuels illegal trade, must be dramatically reduced. PMID:23469289

Age-Associated Decline in Dendritic Cell Function and the Impact of Mediterranean Diet Intervention in Elderly Subjects.

PubMed

Clements, Sarah J; Maijo, Monica; Ivory, Kamal; Nicoletti, Claudio; Carding, Simon R

2017-01-01

Aging is accompanied by increased susceptibility to infection and age-associated chronic diseases. It is also associated with reduced vaccine responses, which is often attributed to immunosenescence and the functional decline of the immune system. Immunosenescence is characterized by a chronic, low-grade, inflammatory state termed inflammaging. Habitants of Mediterranean (MED) regions maintain good health into old age; often attributed to MED diets. Adoption of a MED-diet by elderly subjects, in Norfolk (UK), may improve immune responses of these individuals and in particular, dendritic cell (DC) function. A total of 120 elderly subjects (65-79 years old) recruited onto the Nu-AGE study, a multicenter European dietary study specifically addressing the needs of the elderly, across five countries, and were randomized to the control or MED-diet groups, for one year. Blood samples were taken pre- and post-intervention for DC analysis and were compared with each other, and to samples obtained from 45 young (18-40 years old) subjects. MED-diet compliance was assessed using high performance liquid chromatography-with tandem mass spectrometry analysis of urine samples. Immune cell and DC subset numbers and concentrations of secreted proteins were determined by flow cytometric analysis. As expected, reduced myeloid DC numbers were observed in blood samples from elderly subjects compared with young. The elevated secretion of the adipokine, resistin, after ex vivo stimulation of peripheral blood mononuclear cells from elderly subjects, was significantly reduced after MED-diet intervention. This study provides further evidence of numerical and functional effects of aging on DCs. The MED-diet showed potential to impact on the aging immune cells investigated and could provide an economical approach to address problems associated with our aging population.

Reduced Accuracy and Sensitivity in the Perception of Emotional Facial Expressions in Individuals with High Autism Spectrum Traits

ERIC Educational Resources Information Center

Poljac, Ervin; Poljac, Edita; Wagemans, Johan

2013-01-01

Autism spectrum disorder (ASD) is among other things characterized by specific impairments in emotion processing. It is not clear, however, to what extent the typical decline in affective functioning is related to the specific autistic traits. We employed "The Autism Spectrum-Quotient" (AQ) to quantify autistic traits in a group of 500…

The Sky Is Falling, but Popenoe's Analysis Won't Help Us Do Anything about It.

ERIC Educational Resources Information Center

Cowan, Philip A.

1993-01-01

Responds to previous article by Popenoe on American family decline from 1960 through 1990. Argues that it is possible to reject Popenoe's causal analysis but to accept his conclusion that there is much troubling in the American family. Considers what can be done to reduce prevalence of family distress and increase adaptive functioning of…

Concurrent change in dehydroepiandrosterone sulfate and functional performance in the oldest old: results from the Cardiovascular Health Study All Stars study.

PubMed

Sanders, J L; Cappola, A R; Arnold, A M; Boudreau, R M; Chaves, P H; Robbins, J; Cushman, M; Newman, A B

2010-09-01

The correlation between dehydroepiandrosterone sulfate (DHEAS) decline and age led to the hypothesis that DHEAS might be a marker of primary aging, though conflicting data from observational studies of mortality do not support this. We evaluated concurrent DHEAS and functional decline in a very old cohort to test if DHEAS change tracks with functional change during aging. DHEAS and functional performance (gait speed, grip strength, Modified Mini-Mental State Examination [3MSE] score, and digit symbol substitution test [DSST] score) were measured in 1996-1997 and 2005-2006 in 989 participants in the Cardiovascular Health Study All Stars study (mean age 85.2 years in 2005-2006, 63.5% women and 16.5% African American). We used multivariable linear regression to test the association of DHEAS decline with functional decline. After adjustment, each standard deviation decrease in DHEAS was associated with greater declines in gait speed (0.12 m/s, p = .01), grip strength (0.09 kg, p = .03), 3MSE score (0.13 points, p < .001), and DSST score (0.14 points, p = .001) in women only. Additional adjustment for baseline DHEAS attenuated the association with grip strength but did not alter other estimates appreciably, and baseline DHEAS was unassociated with functional decline. In this cohort of very old individuals, DHEAS decline tracked with declines in gait speed, 3MSE score, and DSST score, but not grip strength, in women independent of baseline DHEAS level. DHEAS decline might be a marker for age-associated performance decline, but its relevance is specific to women.

Interactions among plants, bacteria, and fungi reduce extracellular enzyme activities under long-term N fertilization.

PubMed

Carrara, Joseph E; Walter, Christopher A; Hawkins, Jennifer S; Peterjohn, William T; Averill, Colin; Brzostek, Edward R

2018-06-01

Atmospheric nitrogen (N) deposition has enhanced soil carbon (C) stocks in temperate forests. Most research has posited that these soil C gains are driven primarily by shifts in fungal community composition with elevated N leading to declines in lignin degrading Basidiomycetes. Recent research, however, suggests that plants and soil microbes are dynamically intertwined, whereby plants send C subsidies to rhizosphere microbes to enhance enzyme production and the mobilization of N. Thus, under elevated N, trees may reduce belowground C allocation leading to cascading impacts on the ability of microbes to degrade soil organic matter through a shift in microbial species and/or a change in plant-microbe interactions. The objective of this study was to determine the extent to which couplings among plant, fungal, and bacterial responses to N fertilization alter the activity of enzymes that are the primary agents of soil decomposition. We measured fungal and bacterial community composition, root-microbial interactions, and extracellular enzyme activity in the rhizosphere, bulk, and organic horizon of soils sampled from a long-term (>25 years), whole-watershed, N fertilization experiment at the Fernow Experimental Forest in West Virginia, USA. We observed significant declines in plant C investment to fine root biomass (24.7%), root morphology, and arbuscular mycorrhizal (AM) colonization (55.9%). Moreover, we found that declines in extracellular enzyme activity were significantly correlated with a shift in bacterial community composition, but not fungal community composition. This bacterial community shift was also correlated with reduced AM fungal colonization indicating that declines in plant investment belowground drive the response of bacterial community structure and function to N fertilization. Collectively, we find that enzyme activity responses to N fertilization are not solely driven by fungi, but instead reflect a whole ecosystem response, whereby declines in the strength of belowground C investment to gain N cascade through the soil environment. © 2018 John Wiley & Sons Ltd.

Reduced Myxobolus cerebralis actinospore production in a Colorado reservior may be linked to changes in Tubifex tubifex population structure

USGS Publications Warehouse

Nehring, R. Barry; Hancock, B.; Catanese, M.; Stinson, M.E.T.; Winkelman, Dana L.; Wood, J.; Epp, J.

2013-01-01

Elucidating the dynamics of a parasitic infection requiring two hosts in a natural ecosystem can be a daunting task. Myxobolus cerebralis (Mc), the myxozoan parasite that causes whirling disease in some salmonids, was detected in the Colorado River upstream of Windy Gap Reservoir (WGR) in 1988. Subsequently, whirling disease was implicated in the decline of wild Rainbow Trout Oncorhynchus mykiss in the river when WGR was identified as a point source of Mc triactinomyxons (TAMs). Between 1997 and 2004, numerous investigations began to elucidate the etiology of Mc in WGR. During this period, Mc TAM production in WGR declined more than 90%. Explanations for the decline have included differences in stream discharge between years, changes in the thermal regime of the lake, severe drought, changes in the fish population structure in WGR, and reductions in the prevalence and severity of Mc infection in salmonids in the Colorado and Fraser rivers upstream of WGR. All of these have been discredited as explanations for the reduced TAM production. In 2005, a new study was conducted to replicate the studies completed in 1998. In this paper, the results of a new real-time polymerase chain reaction assay utilized to quantify the mitochondrial 16S rDNA specific to each of four lineages of Tubifex tubifex in pooled samples of 50 oligochaetes are presented. These results suggest that compared with 1998, the densities of aquatic oligochaetes and T. tubifex have increased, TAM production has been greatly reduced, and the decline is congruent with the dominance of lineages I, V, and VI of T. tubifex—three lineages that are refractory or highly resistant to Mc infection—in the oligochaete population. While it is possible that the resistant lineages function as biofilters that deactivate Mc myxospores, the reason for the decline in TAM production in WGR remains an enigma.

Decline in cognitive function and risk of elder self-neglect: finding from the Chicago Health Aging Project.

PubMed

Dong, XinQi; Simon, Melissa A; Wilson, Robert S; Mendes de Leon, Carlos F; Rajan, K Bharat; Evans, Denis A

2010-12-01

To examine the longitudinal association between decline in cognitive function and risk of elder self-neglect in a community-dwelling population. Prospective population-based study. Geographically defined community in Chicago. Community-dwelling subjects reported to the social services agency from 1993 to 2005 for self-neglect who also participated in the Chicago Health Aging Project (CHAP). Of the 5,519 participants in CHAP, 1,017 were reported to social services agency for suspected elder self-neglect from 1993 to 2005. Social services agency identified reported elder self-neglect. The primary predictor was decline in cognitive function assessed using the Mini-Mental State Examination (MMSE), the Symbol Digit Modalities Test (Executive Function), and immediate and delayed recall of the East Boston Memory Test (Episodic Memory). An index of global cognitive function scores was derived by averaging z-scores of all tests. Outcome of interest was elder self-neglect. Logistic and linear regression models were used to assess these longitudinal associations. After adjusting for potential confounding factors, decline in global cognitive function, MMSE score, and episodic memory were not independently associated with greater risk of reported and confirmed elder self-neglect. Decline in executive function was associated with greater risk of reported and confirmed elder self-neglect. Decline in global cognitive function was associated with greater risk of greater self-neglect severity (parameter estimate=0.76, standard error=0.31, P=.01). Decline in executive function was associated with risk of reported and confirmed elder self-neglect. Decline in global cognitive function was associated with risk of greater self-neglect severity. © 2010, Copyright the Authors. Journal compilation © 2010, The American Geriatrics Society.

Artificial light at night as a new threat to pollination.

PubMed

Knop, Eva; Zoller, Leana; Ryser, Remo; Gerpe, Christopher; Hörler, Maurin; Fontaine, Colin

2017-08-10

Pollinators are declining worldwide and this has raised concerns for a parallel decline in the essential pollination service they provide to both crops and wild plants. Anthropogenic drivers linked to this decline include habitat changes, intensive agriculture, pesticides, invasive alien species, spread of pathogens and climate change. Recently, the rapid global increase in artificial light at night has been proposed to be a new threat to terrestrial ecosystems; the consequences of this increase for ecosystem function are mostly unknown. Here we show that artificial light at night disrupts nocturnal pollination networks and has negative consequences for plant reproductive success. In artificially illuminated plant-pollinator communities, nocturnal visits to plants were reduced by 62% compared to dark areas. Notably, this resulted in an overall 13% reduction in fruit set of a focal plant even though the plant also received numerous visits by diurnal pollinators. Furthermore, by merging diurnal and nocturnal pollination sub-networks, we show that the structure of these combined networks tends to facilitate the spread of the negative consequences of disrupted nocturnal pollination to daytime pollinator communities. Our findings demonstrate that artificial light at night is a threat to pollination and that the negative effects of artificial light at night on nocturnal pollination are predicted to propagate to the diurnal community, thereby aggravating the decline of the diurnal community. We provide perspectives on the functioning of plant-pollinator communities, showing that nocturnal pollinators are not redundant to diurnal communities and increasing our understanding of the human-induced decline in pollinators and their ecosystem service.

Clinical features and predictors for disease natural progression in adults with Pompe disease: a nationwide prospective observational study

PubMed Central

2012-01-01

Background Due partly to physicians’ unawareness, many adults with Pompe disease are diagnosed with great delay. Besides, it is not well known which factors influence the rate of disease progression, and thus disease outcome. We delineated the specific clinical features of Pompe disease in adults, and mapped out the distribution and severity of muscle weakness, and the sequence of involvement of the individual muscle groups. Furthermore, we defined the natural disease course and identified prognostic factors for disease progression. Methods We conducted a single-center, prospective, observational study. Muscle strength (manual muscle testing, and hand-held dynamometry), muscle function (quick motor function test), and pulmonary function (forced vital capacity in sitting and supine positions) were assessed every 3–6 months and analyzed using repeated-measures ANOVA. Results Between October 2004 and August 2009, 94 patients aged between 25 and 75 years were included in the study. Although skeletal muscle weakness was typically distributed in a limb-girdle pattern, many patients had unfamiliar features such as ptosis (23%), bulbar weakness (28%), and scapular winging (33%). During follow-up (average 1.6 years, range 0.5-4.2 years), skeletal muscle strength deteriorated significantly (mean declines of −1.3% point/year for manual muscle testing and of −2.6% points/year for hand-held dynamometry; both p<0.001). Longer disease duration (>15 years) and pulmonary involvement (forced vital capacity in sitting position <80%) at study entry predicted faster decline. On average, forced vital capacity in supine position deteriorated by 1.3% points per year (p=0.02). Decline in pulmonary function was consistent across subgroups. Ten percent of patients declined unexpectedly fast. Conclusions Recognizing patterns of common and less familiar characteristics in adults with Pompe disease facilitates timely diagnosis. Longer disease duration and reduced pulmonary function stand out as predictors of rapid disease progression, and aid in deciding whether to initiate enzyme replacement therapy, or when. PMID:23147228

Handgrip Strength Predicts Functional Decline at Discharge in Hospitalized Male Elderly: A Hospital Cohort Study

PubMed Central

García-Peña, Carmen; García-Fabela, Luis C.; Gutiérrez-Robledo, Luis M.; García-González, Jose J.; Arango-Lopera, Victoria E.; Pérez-Zepeda, Mario U.

2013-01-01

Functional decline after hospitalization is a common adverse outcome in elderly. An easy to use, reproducible and accurate tool to identify those at risk would aid focusing interventions in those at higher risk. Handgrip strength has been shown to predict adverse outcomes in other settings. The aim of this study was to determine if handgrip strength measured upon admission to an acute care facility would predict functional decline (either incident or worsening of preexisting) at discharge among older Mexican, stratified by gender. In addition, cutoff points as a function of specificity would be determined. A cohort study was conducted in two hospitals in Mexico City. The primary endpoint was functional decline on discharge, defined as a 30-point reduction in the Barthel Index score from that of the baseline score. Handgrip strength along with other variables was measured at initial assessment, including: instrumental activities of daily living, cognition, depressive symptoms, delirium, hospitalization length and quality of life. All analyses were stratified by gender. Logistic regression to test independent association between handgrip strength and functional decline was performed, along with estimation of handgrip strength test values (specificity, sensitivity, area under the curve, etc.). A total of 223 patients admitted to an acute care facility between 2007 and 2009 were recruited. A total of 55 patients (24.7%) had functional decline, 23.46% in male and 25.6% in women. Multivariate analysis showed that only males with low handgrip strength had an increased risk of functional decline at discharge (OR 0.88, 95% CI 0.79–0.98, p = 0.01), with a specificity of 91.3% and a cutoff point of 20.65 kg for handgrip strength. Females had not a significant association between handgrip strength and functional decline. Measurement of handgrip strength on admission to acute care facilities may identify male elderly patients at risk of having functional decline, and intervene consequently. PMID:23936113

Relations between Recent Past Leisure Activities with Risks of Dementia and Cognitive Functions after Stroke

PubMed Central

Wong, Adrian; Lau, Alexander Y. L.; Lo, Eugene; Tang, Michael; Wang, Zhaolu; Liu, Wenyan; Tanner, Nicole; Chau, Natalie; Law, Lorraine; Shi, Lin; Chu, Winnie C. W.; Yang, Jie; Xiong, Yun-yun; Lam, Bonnie Y. K.; Au, Lisa; Chan, Anne Y. Y.; Soo, Yannie; Leung, Thomas W. H.; Wong, Lawrence K. S.; Lam, Linda C. W.; Mok, Vincent C. T.

2016-01-01

Background Leisure activity participation has been shown to lower risks of cognitive decline in non-stroke populations. However, effects of leisure activities participation upon cognitive functions and risk of dementia after stroke are unclear. The purpose of this study is to examine the effects of recent past leisure activities participation upon cognitive functions and risk of incident dementia after stroke. Methods Hospital-based, retrospective cohort study. 88 of 1,013 patients with stroke or TIA having no prestroke dementia were diagnosed to have incident poststroke dementia (PSD) 3–6 months after stroke. Regular participation (≥3 times per week) in intellectual, recreational, social and physical activities over the year before the index stroke was retrospectively recorded at 3–6 months after stroke. Results Logistic regression analyses showed that regular participation in intellectual (RR 0.36, 95%CI 0.20–0.63) and stretching & toning physical exercise (0.37, 0.21–0.64) was significantly associated with a reduced risk of PSD after controlling for age, education, prestroke cognitive decline, stroke subtype, prior strokes and chronic brain changes including white matter changes, old infarcts and global atrophy. Results were similar in patients with past strokes in unadjusted models. Participation in increased number of activities in general (r = 0.41, p<0.01) and in intellectual (r = 0.40, p<0.01), recreational (r = 0.24, p<0.01), strenuous aerobic (r = 0.23, p<0.01) and mind-body (r = 0.10, p<0.01) activities was associated with higher poststroke Mini-mental State Examination scores in models adjusted for prestroke cognitive decline. Conclusions Regular participation in intellectual activities and stretching & toning exercise was associated with a significantly reduced short-term risk of PSD in patients with and without recurrent strokes. Participation in greater number of recent past leisure activities was associated with better poststroke cognitive performance. Findings of this retrospective cohort study call for studies of activity intervention for prevention of cognitive decline in individuals at elevated risk of stroke. PMID:27454124

Functional neuroimaging of normal aging: Declining brain, adapting brain.

PubMed

Sugiura, Motoaki

2016-09-01

Early functional neuroimaging research on normal aging brain has been dominated by the interest in cognitive decline. In this framework the age-related compensatory recruitment of prefrontal cortex, in terms of executive system or reduced lateralization, has been established. Further details on these compensatory mechanisms and the findings reflecting cognitive decline, however, remain the matter of intensive investigations. Studies in another framework where age-related neural alteration is considered adaptation to the environmental change are recently burgeoning and appear largely categorized into three domains. The age-related increase in activation of the sensorimotor network may reflect the alteration of the peripheral sensorimotor systems. The increased susceptibility of the network for the mental-state inference to the socioemotional significance may be explained by the age-related motivational shift due to the altered social perception. The age-related change in activation of the self-referential network may be relevant to the focused positive self-concept of elderly driven by a similar motivational shift. Across the domains, the concept of the self and internal model may provide the theoretical bases of this adaptation framework. These two frameworks complement each other to provide a comprehensive view of the normal aging brain. Copyright © 2016 Elsevier B.V. All rights reserved.

A robust neuromuscular system protects rat and human skeletal muscle from sarcopenia.

PubMed

Pannérec, Alice; Springer, Margherita; Migliavacca, Eugenia; Ireland, Alex; Piasecki, Mathew; Karaz, Sonia; Jacot, Guillaume; Métairon, Sylviane; Danenberg, Esther; Raymond, Frédéric; Descombes, Patrick; McPhee, Jamie S; Feige, Jerome N

2016-04-01

Declining muscle mass and function is one of the main drivers of loss of independence in the elderly. Sarcopenia is associated with numerous cellular and endocrine perturbations, and it remains challenging to identify those changes that play a causal role and could serve as targets for therapeutic intervention. In this study, we uncovered a remarkable differential susceptibility of certain muscles to age-related decline. Aging rats specifically lose muscle mass and function in the hindlimbs, but not in the forelimbs. By performing a comprehensive comparative analysis of these muscles, we demonstrate that regional susceptibility to sarcopenia is dependent on neuromuscular junction fragmentation, loss of motoneuron innervation, and reduced excitability. Remarkably, muscle loss in elderly humans also differs in vastus lateralis and tibialis anterior muscles in direct relation to neuromuscular dysfunction. By comparing gene expression in susceptible and non-susceptible muscles, we identified a specific transcriptomic signature of neuromuscular impairment. Importantly, differential molecular profiling of the associated peripheral nerves revealed fundamental changes in cholesterol biosynthetic pathways. Altogether our results provide compelling evidence that susceptibility to sarcopenia is tightly linked to neuromuscular decline in rats and humans, and identify dysregulation of sterol metabolism in the peripheral nervous system as an early event in this process.

[Functional decline and presence of symptoms in palliative care: Cause or consequence?

PubMed

Zamora-Mur, Alfredo; Nabal-Vicuña, María; Zamora-Catevilla, Aranzazu; García-Foncillas, Rafael; Calderero-Aragón, Verónica; Aubí-Catevilla, Óscar; Lostalé-Latorre, Fernando

Several publications have related functional decline to the appearance of symptoms, especially psychiatric or psychological ones, such as anxiety and depression. Moreover, an initial depressive disorder or prior to functional decline usually worsens it. It was decided to investigate the relationship between the presence of functional decline, measured by a decrease in the Barthel index (BI), and the presence of symptoms. A prospective analytical study conducted on patients referred to a Home Care Support Team (HCST). The study included 638 cases, of which 53.9% (N=344) were male, 56% (N=357) with cancer and 44% (N=281) geriatric. The mean age was 79.64 years+- 10.8. Significant differences (P<.001) were found in functional decline measured by mean decline in the BI between cancer (34.4) and non-cancer patients (12.12). Significant differences (P<.001) were also found in all recorded symptoms (pain, dyspnoea, anorexia, nausea, anxiety, depression, and insomnia), more frequently in cancer patients, except psychomotor agitation. A higher presence of symptoms was detected in patients with greater functional decline, with decreases in BI above 20 points. There were no differences in previous treatments, except in certain analgesics. Differences were found in the different treatments prescribed by HCST. The presence of functional decline and its level may be related to the appearance of symptoms, especially in cancer patients. Copyright © 2016 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

Declining incidence of low-trauma knee fractures in elderly women: nationwide statistics in Finland between 1970 and 2006.

PubMed

Kannus, P; Niemi, S; Parkkari, J; Sievänen, H; Palvanen, M

2009-01-01

The study assessed the recent secular trend in the incidence of low-trauma knee fractures among older Finns in the years 1970-2006. The clear rise in women's fracture incidence from early 1970s until the late 1990s was followed by a declining fracture rate. Exact reasons for the decline are unknown, but a cohort effect toward a healthier female population with improved functionality and reduced risk of injurious slips, trips and falls could partly explain the phenomenon. Although low-trauma fractures of elderly adults have been recognized as a major public health concern in modern societies with aging populations, fresh nationwide information on their secular trends is sparse. We determined the current trend in the number and incidence (per 100,000 persons) of low-trauma knee fractures among elderly people in Finland, an EU country with a well-defined white population of 5.3 million, by taking into account all persons 60 years of age or older who were admitted to our hospitals for primary treatment of such fractures from 1970 to 2006. The number and incidence of low-trauma knee fractures among 60-year-old or older Finnish women sharply rose between 1970 and 1997, from 218 (number) and 55 (incidence) in 1970 to 733 and 124 in 1997. However, thereafter both the number and incidence of fractures have continuously declined so that there were only 626 fractures in these women in 2006 (incidence 94). In the age-adjusted fracture incidence, the findings were similar. During 1970-1997, the age-adjusted incidence of low-trauma knee fractures in our elderly women clearly rose (from 60 to 118), but thereafter, this incidence declined to 85 in 2006. In men, the fracture incidence did not show consistent trend changes over time (30 in 1970 and 36 in 2006). The sharp rise in the incidence of low-trauma knee fractures in Finnish elderly women from early 1970s until late 1990s has been followed by a declining fracture rate. Exact reasons for this are unknown, but a cohort effect toward a healthier aging female population with improved functional ability and reduced risk of injurious slips, trips and falls cannot be excluded.

L-cysteine efflux in erythrocytes as a function of human age: correlation with reduced glutathione and total anti-oxidant potential.

PubMed

Kumar, Prabhanshu; Maurya, Pawan Kumar

2013-06-01

Thiol compounds such as cysteine (Cys) and reduced glutathione (GSH) play an important role in human aging and age-related diseases. In erythrocytes, GSH is synthesized by glutamic acid, cysteine, and glycine, but the rate of GSH synthesis is determined only by the availability of L-cysteine. Cysteine supplementation has been shown to ameliorate several parameters that are known to degenerate during human aging. We have studied L-cysteine efflux in vitro in human erythrocytes as a function of age by suspending cells in solution containing 10 mM L-cysteine for uptake; later cells were re-suspended in phosphate-buffered saline (PBS)-glucose to allow efflux. Change in the free sulfhydryl (-SH) concentration was then measured to calculate the rate of efflux. The GSH/oxidized glutathione (GSSG) ratio was taken as a control to study the oxidation/reduction state of the erythrocyte. The total anti-oxidant potential of plasma was measured in terms of ferric reducing ability of plasma (FRAP) values. We have shown a significant (p<0.0001) decline in the efflux of L-cysteine in erythrocytes during human aging, and the GSH/GSSG ratio decreases as a function of human age. The decline in L-cysteine efflux during aging correlates with the decrease in GSH and the FRAP value. This finding may help to explain the shift in the redox status and low GSH concentration that might determine the rate of L-cysteine efflux observed in erythrocytes and an important factor in the development of oxidative stress in erythrocytes during aging.

Successful physiological aging and episodic memory: a brain stimulation study.

PubMed

Manenti, Rosa; Cotelli, Maria; Miniussi, Carlo

2011-01-01

Functional neuroimaging studies have shown that younger adults tend to asymmetrically recruit specific regions of an hemisphere in an episodic memory task (Hemispheric Encoding Retrieval Asymmetry-HERA model). In older adults, this hemispheric asymmetry is generally reduced as suggested by the Hemispheric Asymmetry Reduction for OLDer Adults-HAROLD-model. Recent works suggest that while low-performing older adults do not show this reduced asymmetry, high-performing older adults counteract age-related neural decline through a plastic reorganization of cerebral networks that results in reduced functional asymmetry. However, the issue of whether high- and low-performing older adults show different degrees of asymmetry and the relevance of this process for counteracting aging have not been clarified. We used transcranial magnetic stimulation (TMS) to transiently interfere with the function of the dorsolateral prefrontal cortex (DLPFC) during encoding or retrieval of associated and non-associated word pairs. A group of healthy older adults was studied during encoding and retrieval of word pairs. The subjects were divided in two subgroups according to their experimental performance (i.e., high- and low-performing). TMS effects on retrieval differed according to the subject's subgroup. In particular, the predominance of left vs. right DLPFC effects during encoding, predicted by the HERA model, was observed only in low-performing older adults, while the asymmetry reduction predicted by the HAROLD model was selectively shown for the high-performing group. The present data confirm that older adults with higher memory performance show less prefrontal asymmetry as an efficient strategy to counteract age-related memory decline. Copyright © 2010 Elsevier B.V. All rights reserved.

[Cognitive impairment, nutritional status and clinical profile in chronic obstructive pulmonary disease].

PubMed

López Torres, Isabel; Torres-Sánchez, Irene; Martín Salvador, Adelina; Ortiz Rubio, Araceli; Rodríguez Alzueta, Elisabeth; Valenza, Marie Carmen

2014-11-01

Chronic obstructive pulmonary disease (COPD) is a progressive disease with a prevalence that increases with the aging of the subject. It presents a high prevalence of comorbidities, such as cognitive decline, which is gaining great clinical relevance in recent years. Factors such as pulmonary function, hypoxemia, hypercapnia or exacerbations contribute to the decline of cognitive functions. The nutritional status has been added to these factors as contributing to cognitive function decline when presenting in COPD. To evidence the relationship between cognitive decline, nutritional status and the clinical profile of patients admitted because of an acute exacerbation of COPD (AECOPD). 110 subjects hospitalized because of COPD, divided in two groups according to their nutritional status and assessment of cognitive decline at admittance, nutritional status and clinical profile. Significant differences between groups concerning nutritional status in anthropometric variables (sex and IMC), functional ability (Barthel index and Daily Life Activities Scale), quality of life (Euroqol- 5D y SGRQ), sleep quality (Pittsburgh), mood (HAD) and cognitive decline (MoCa attention, MoCa abstraction). (p<0.05). Cognitive function is affected in COPD patients with an altered nutritional status when compared to those with a normal nutritional status. The nutritional decline is a factor contributing to the impairment of cognitive functions in this kind of patients, particularly a decline in attention and abstraction ability. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Pivotal roles of Fezf2 in differentiation of cone OFF bipolar cells and functional maturation of cone ON bipolar cells in retina.

PubMed

Suzuki-Kerr, Haruna; Iwagawa, Toshiro; Sagara, Hiroshi; Mizota, Atsushi; Suzuki, Yutaka; Watanabe, Sumiko

2018-06-01

During development of the retina, common retinal progenitor cells give rise to six classes of neurons that subsequently further diversify into more than 55 subtypes of neuronal subtypes. Here, we have investigated the expression and function of Fezf2, Fez zinc finger family of protein, in the developing mouse retina. Expression of Fezf2 transcripts was strongly observed in the embryonic retinal progenitors at E14.5 and declined quickly in subsequent development of retina. Then, in postnatal stage at around day 8, Fezf2 was transiently expressed then declined again. Loss-of-function analysis using retinas from mice in which Fezf2 coding region was substituted with β-galactosidase showed that Fezf2 is expressed in a subset of cone OFF bipolar cells and required for their differentiation. Using electroretinogram, we found that Fezf2 knockout retina exhibited significantly reduced photopic b-wave, suggesting functional abnormality of cone ON bipolar cells. Furthermore, reduced expression of synaptic protein Trpm1 and structural alteration of ON bipolar cell invagination, both of which affected cone photoreceptor terminal synaptic activity, was identified by transmission electron microscopy and immunohistochemistry, respectively. Taken together, our results show that Fezf2 is indispensable in differentiation of bipolar precursors into cone OFF bipolar cells and in functional maturation of cone ON bipolar cells during development of mouse retina. These results contribute to our understanding of how diversity of neuronal subtypes and hence specificity of neuronal connections are established in the retina by intrinsic cues. Copyright © 2018 Elsevier Ltd. All rights reserved.

Skeletal Muscle Mitochondria and Aging: A Review

PubMed Central

Peterson, Courtney M.; Johannsen, Darcy L.; Ravussin, Eric

2012-01-01

Aging is characterized by a progressive loss of muscle mass and muscle strength. Declines in skeletal muscle mitochondria are thought to play a primary role in this process. Mitochondria are the major producers of reactive oxygen species, which damage DNA, proteins, and lipids if not rapidly quenched. Animal and human studies typically show that skeletal muscle mitochondria are altered with aging, including increased mutations in mitochondrial DNA, decreased activity of some mitochondrial enzymes, altered respiration with reduced maximal capacity at least in sedentary individuals, and reduced total mitochondrial content with increased morphological changes. However, there has been much controversy over measurements of mitochondrial energy production, which may largely be explained by differences in approach and by whether physical activity is controlled for. These changes may in turn alter mitochondrial dynamics, such as fusion and fission rates, and mitochondrially induced apoptosis, which may also lead to net muscle fiber loss and age-related sarcopenia. Fortunately, strategies such as exercise and caloric restriction that reduce oxidative damage also improve mitochondrial function. While these strategies may not completely prevent the primary effects of aging, they may help to attenuate the rate of decline. PMID:22888430

Maintaining ecosystem resilience: functional responses of tree cavity nesters to logging in temperate forests of the Americas.

PubMed

Ibarra, José Tomás; Martin, Michaela; Cockle, Kristina L; Martin, Kathy

2017-06-30

Logging often reduces taxonomic diversity in forest communities, but little is known about how this biodiversity loss affects the resilience of ecosystem functions. We examined how partial logging and clearcutting of temperate forests influenced functional diversity of birds that nest in tree cavities. We used point-counts in a before-after-control-impact design to examine the effects of logging on the value, range, and density of functional traits in bird communities in Canada (21 species) and Chile (16 species). Clearcutting, but not partial logging, reduced diversity in both systems. The effect was much more pronounced in Chile, where logging operations removed critical nesting resources (large decaying trees), than in Canada, where decaying aspen Populus tremuloides were retained on site. In Chile, logging was accompanied by declines in species richness, functional richness (amount of functional niche occupied by species), community-weighted body mass (average mass, weighted by species densities), and functional divergence (degree of maximization of divergence in occupied functional niche). In Canada, clearcutting did not affect species richness but nevertheless reduced functional richness and community-weighted body mass. Although some cavity-nesting birds can persist under intensive logging operations, their ecosystem functions may be severely compromised unless future nest trees can be retained on logged sites.

Association of pulse wave velocity and pulse pressure with decline in kidney function.

PubMed

Kim, Chang Seong; Kim, Ha Yeon; Kang, Yong Un; Choi, Joon Seok; Bae, Eun Hui; Ma, Seong Kwon; Kim, Soo Wan

2014-05-01

The association between arterial stiffness and decline in kidney function in patients with mild to moderate chronic kidney disease (CKD) is not well established. This study investigated whether pulse wave velocity (PWV) and pulse pressure (PP) are independently associated with glomerular filtration rate (GFR) and rapid decline in kidney function in early CKD. Carotid femoral PWV (cfPWV), brachial-ankle PWV (baPWV), and PP were measured in a cohort of 913 patients (mean age, 63±10 years; baseline estimated GFR, 84±18 mL/min/1.73 m(2) ). Estimated GFR was measured at baseline and at follow-up. The renal outcome examined was rapid decline in kidney function (estimated GFR loss, >3 mL/min/1.73 m(2) per year). The median follow-up duration was 3.2 years. Multivariable adjusted linear regression model indicated that arterial PWV (both cfPWV and baPWV) and PP increased as estimated GFR declined, but neither was associated with kidney function after adjustment for various covariates. Multivariable logistic regression analysis found that cfPWV and baPWV were not associated with rapid decline in kidney function (odds ratio [OR], 1.39, 95% confidence interval [CI], 0.41-4.65; OR, 2.51, 95% CI, 0.66-9.46, respectively), but PP was (OR, 1.22, 95% CI, 1.01-1.48; P=.045). Arterial stiffness assessed using cfPWV and baPWV was not correlated with lower estimated GFR and rapid decline in kidney function after adjustment for various confounders. Thus, PP is an independent risk factor for rapid decline in kidney function in populations with relatively preserved kidney function (estimated GFR ≥30 mL/min/1.73 m(2) ). ©2014 Wiley Periodicals, Inc.

Sleep-dependent memory consolidation in healthy aging and mild cognitive impairment.

PubMed

Pace-Schott, Edward F; Spencer, Rebecca M C

2015-01-01

Sleep quality and architecture as well as sleep's homeostatic and circadian controls change with healthy aging. Changes include reductions in slow-wave sleep's (SWS) percent and spectral power in the sleep electroencephalogram (EEG), number and amplitude of sleep spindles, rapid eye movement (REM) density and the amplitude of circadian rhythms, as well as a phase advance (moved earlier in time) of the brain's circadian clock. With mild cognitive impairment (MCI) there are further reductions of sleep quality, SWS, spindles, and percent REM, all of which further diminish, along with a profound disruption of circadian rhythmicity, with the conversion to Alzheimer's disease (AD). Sleep disorders may represent risk factors for dementias (e.g., REM Behavior Disorder presages Parkinson's disease) and sleep disorders are themselves extremely prevalent in neurodegenerative diseases. Working memory , formation of new episodic memories, and processing speed all decline with healthy aging whereas semantic, recognition, and emotional declarative memory are spared. In MCI, episodic and working memory further decline along with declines in semantic memory. In young adults, sleep-dependent memory consolidation (SDC) is widely observed for both declarative and procedural memory tasks. However, with healthy aging, although SDC for declarative memory is preserved, certain procedural tasks, such as motor-sequence learning, do not show SDC. In younger adults, fragmentation of sleep can reduce SDC, and a normative increase in sleep fragmentation may account for reduced SDC with healthy aging. Whereas sleep disorders such as insomnia, obstructive sleep apnea, and narcolepsy can impair SDC in the absence of neurodegenerative changes, the incidence of sleep disorders increases both with normal aging and, further, with neurodegenerative disease. Specific features of sleep architecture, such as sleep spindles and SWS are strongly linked to SDC. Diminution of these features with healthy aging and their further decline with MCI may account for concomitant declines in SDC. Notably these same sleep features further markedly decline, in concert with declining cognitive function, with the progression to AD. Therefore, progressive changes in sleep quality, architecture, and neural regulation may constitute a contributing factor to cognitive decline that is seen both with healthy aging and, to a much greater extent, with neurodegenerative disease.

Effects of brain-derived neurotrophic factor on dopaminergic function and motor behavior during aging

PubMed Central

Boger, Heather A.; Mannangatti, Padmanabhan; Samuvel, Devadoss J.; Saylor, Alicia J.; Bender, Tara S.; McGinty, Jacqueline F.; Fortress, Ashley M.; Zaman, Vandana; Huang, Peng; Middaugh, Lawrence D.; Randall, Patrick K.; Jayanthi, Lankupalle D.; Rohrer, Baerbel; Helke, Kristi L.; Granholm, Ann-Charlotte; Ramamoorthy, Sammanda

2010-01-01

Brain-derived neurotrophic factor (BDNF) is critical in synaptic plasticity and in the survival and function of midbrain dopamine neurons. In the present study, we assessed the effects of a partial genetic deletion of BDNF on motor function and dopamine (DA) neurotransmitter measures by comparing (Bdnf+/−) with wildtype mice (WT) at different ages. Bdnf+/ and WT mice had similar body weights until 12 months of age; however, at 21 months, Bdnf+/− mice were significantly heavier than WT mice. Horizontal and vertical motor activity was reduced for Bdnf+/− compared to WT mice; but was not influenced by Age. Performance on an accelerating rotarod declined with age for both genotypes and was exacerbated for Bdnf+/− mice. Body weight did not correlate with any of the three behavioral measures studied. DA neurotransmitter markers indicated no genotypic difference in striatal tyrosine hydroxylase (TH), dopamine transporter (DAT), or vesicular monoamine transporter 2 (VMAT2) immunoreactivity at any age. However, DA transport via DAT (starting at 12 months) and VMAT2 (starting at 3 months) as well as KCl-stimulated DA release were reduced in Bdnf+/− mice and declined with age suggesting an increasingly important role for BDNF in the release and uptake of DA with the aging process. These findings suggest that a BDNF expression deficit becomes more critical to dopaminergic dynamics and related behavioral activities with increasing age. PMID:20860702

Can functional equivalency between seagrasses and other coastal habitats offset loss of ecosystem health with reduced seagrass abundance?

NASA Astrophysics Data System (ADS)

Cebrian, J.; Anton, A.; Christiaen, B.; Gamble, R.; Stutes, J.

2016-02-01

Seagrasses provide important ecosystem services, such as habitat for fisheries, shoreline stabilization, pollution filtration, and carbon sequestration. Thus, seagrass loss may seriously compromise coastal ecosystem services worldwide. However, functional equivalency (or redundancy) between seagrasses and other components of coastal ecosystems, such as algae and marshes, can offset the loss of services under declining seagrass abundance. That is, if seagrasses are redundant with algae and marshes in their functionality, then ecosystem services may be preserved in changing coasts with declining seagrass but pervading algal and marsh communities. Here we present several instances of functional redundancy between seagrasses and other coastal components in the Northern Gulf of Mexico. We first examine how net ecosystem production, which sets a limit to carbon accumulation and export to neighbouring communities, changes with eutrophication-induced seagrass decline and concomitant increase in algal abundance. Results from comparative and manipulative field studies are congruent and show no change in net ecosystem production despite drastic shifts from seagrass to algal dominance. We further provide evidence that fringing marshes can counteract the reduction in habitat provision for structure-dependent fisheries due to seagrass loss. Using a large-scale field comparison we show that, as long as fringing marshes are preserved, the abundance and diversity of structure-dependent fisheries are maintained despite large seagrass loss. Functional redundancy for habitat provision also occurs between seagrasses and well-oxygenated macroagal stands, since canopy-dwelling faunal abundance remains unaltered if seagrasses are replaced by normoxic algal stands. In concert the results demonstrate substantial functional equivalency between seagrasses and other coastal components, and indicate seagrass loss does not necessarily result in depressed coastal ecosystem health and services.

Adiponectin is not associated with renal function decline in community-dwelling elderly adults.

PubMed

Kobayashi, Hiroki; Otsuka, Hiromasa; Yanai, Mitsuru; Haketa, Akira; Hara, Motohiko; Hishiki, Mikano; Abe, Masanori; Soma, Masayoshi

2018-05-01

Adiponectin secreted by adipocytes plays an important role in the regulation of glucose and fatty acid metabolism. Contrary to findings in patients with chronic kidney disease (CKD), no prospective data about the association of serum adiponectin with renal function decline in the general population have yet appeared. Our objective was to analyze the relationship of total and high molecular weight (HMW) adiponectin with renal function decline as measured by cystatin C in community-dwelling elderly adults without moderate or severe CKD.In a prospective observational analysis, a total of 216 healthy elderly volunteers with eGFRcys ≥60 mL/min/1.73 m underwent anthropometric and laboratory tests at baseline and at follow-up visits. A subgroup with serum samples collected 5 years apart was further analyzed.There were no differences in either total or HMW adiponectin level between subjects subsequently undergoing rapid renal function decline and subjects with normal physiologic renal function decline (P = .71, P = .81). On univariate linear regression, neither total nor HMW adiponectin were associated with annual renal function decline (β = -0.23; P = .71, β = -0.057; P = .90). Multivariate analysis did not show a significant contribution of either total or HMW adiponectin to annual renal function decline (β = -0.50; P = .46, β = 0.01; P = .98). In the logistic regression analysis, we did not observe any statistically significant association of serum adiponectin levels with rapid renal function decline or incidence of CKD.Contrary to findings in populations with CKD, neither total nor HMW adiponectin had a substantial association with renal function decline in an elderly population with eGFRcys ≥60 mL/min/1.73 m. Our results and conclusions should not be extrapolated to subjects with other characteristics.

Cognitive Impairment Precedes and Predicts Functional Impairment in Mild Alzheimer's Disease.

PubMed

Liu-Seifert, Hong; Siemers, Eric; Price, Karen; Han, Baoguang; Selzler, Katherine J; Henley, David; Sundell, Karen; Aisen, Paul; Cummings, Jeffrey; Raskin, Joel; Mohs, Richard

2015-01-01

The temporal relationship of cognitive deficit and functional impairment in Alzheimer's disease (AD) is not well characterized. Recent analyses suggest cognitive decline predicts subsequent functional decline throughout AD progression. To better understand the relationship between cognitive and functional decline in mild AD using autoregressive cross-lagged (ARCL) panel analyses in several clinical trials. Data included placebo patients with mild AD pooled from two multicenter, double-blind, Phase 3 solanezumab (EXPEDITION/2) or semagacestat (IDENTITY/2) studies, and from AD patients participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cognitive and functional outcomes were assessed using AD Assessment Scale-Cognitive subscale (ADAS-Cog), AD Cooperative Study-Activities of Daily Living instrumental subscale (ADCS-iADL), or Functional Activities Questionnaire (FAQ), respectively. ARCL panel analyses evaluated relationships between cognitive and functional impairment over time. In EXPEDITION, ARCL panel analyses demonstrated cognitive scores significantly predicted future functional impairment at 5 of 6 time points, while functional scores predicted subsequent cognitive scores in only 1 of 6 time points. Data from IDENTITY and ADNI programs yielded consistent results whereby cognition predicted subsequent function, but not vice-versa. Analyses from three databases indicated cognitive decline precedes and predicts subsequent functional decline in mild AD dementia, consistent with previously proposed hypotheses, and corroborate recent publications using similar methodologies. Cognitive impairment may be used as a predictor of future functional impairment in mild AD dementia and can be considered a critical target for prevention strategies to limit future functional decline in the dementia process.

Iohexol clearance is superior to creatinine-based renal function estimating equations in detecting short-term renal function decline in chronic heart failure.

PubMed

Cvan Trobec, Katja; Kerec Kos, Mojca; von Haehling, Stephan; Anker, Stefan D; Macdougall, Iain C; Ponikowski, Piotr; Lainscak, Mitja

2015-12-01

To compare the performance of iohexol plasma clearance and creatinine-based renal function estimating equations in monitoring longitudinal renal function changes in chronic heart failure (CHF) patients, and to assess the effects of body composition on the equation performance. Iohexol plasma clearance was measured in 43 CHF patients at baseline and after at least 6 months. Simultaneously, renal function was estimated with five creatinine-based equations (four- and six-variable Modification of Diet in Renal Disease, Cockcroft-Gault, Cockcroft-Gault adjusted for lean body mass, Chronic Kidney Disease Epidemiology Collaboration equation) and body composition was assessed using bioimpedance and dual-energy x-ray absorptiometry. Over a median follow-up of 7.5 months (range 6-17 months), iohexol clearance significantly declined (52.8 vs 44.4 mL/[min ×1.73 m2], P=0.001). This decline was significantly higher in patients receiving mineralocorticoid receptor antagonists at baseline (mean decline -22% of baseline value vs -3%, P=0.037). Mean serum creatinine concentration did not change significantly during follow-up and no creatinine-based renal function estimating equation was able to detect the significant longitudinal decline of renal function determined by iohexol clearance. After accounting for body composition, the accuracy of the equations improved, but not their ability to detect renal function decline. Renal function measured with iohexol plasma clearance showed relevant decline in CHF patients, particularly in those treated with mineralocorticoid receptor antagonists. None of the equations for renal function estimation was able to detect these changes. ClinicalTrials.gov registration number: NCT01829880.

Apolipoprotein E4 is associated with improved cognitive function in Amazonian forager-horticulturalists with a high parasite burden

PubMed Central

Trumble, Benjamin C.; Stieglitz, Jonathan; Blackwell, Aaron D.; Allayee, Hooman; Beheim, Bret; Finch, Caleb E.; Gurven, Michael; Kaplan, Hillard

2017-01-01

The apolipoprotein E4 (E4) allele is present worldwide, despite its associations with higher risk of cardiovascular morbidity, accelerated cognitive decline during aging, and Alzheimer’s disease (AD). The E4 allele is especially prevalent in some tropical regions with a high parasite burden. Equatorial populations also face a potential dual burden of high E4 prevalence combined with parasitic infections that can also reduce cognitive performance. We examined the interactions of E4, parasite burden, and cognitive performance in a traditional, nonindustrialized population of Amazonian forager-horticulturalists (N = 372) to test whether E4 protects against cognitive decline in environments with a heavy pathogen burden. Contrary to observations in industrial populations, older adult E4 carriers with high parasite burdens either maintained or showed slight improvements in cognitive performance, whereas non-E4 carriers with a high parasite burden showed reduced cognitive performance. Being an E4 carrier is the strongest risk factor to date of AD and cognitive decline in industrial populations; it is associated with greater cognitive performance in individuals facing a high parasite and pathogen load, suggesting advantages to the E4 allele under certain environmental conditions. The current mismatch between postindustrial hygienic lifestyles and active parasite-rich environs may be critical for understanding genetic risk for cognitive aging.—Trumble, B. C., Stieglitz, J., Blackwell, A. D., Allayee, H., Beheim, B., Finch, C. E., Gurven, M., Kaplan, H. Apolipoprotein E4 is associated with improved cognitive function in Amazonian forager-horticulturalists with a high parasite burden. PMID:28031319

Apolipoprotein E4 is associated with improved cognitive function in Amazonian forager-horticulturalists with a high parasite burden.

PubMed

Trumble, Benjamin C; Stieglitz, Jonathan; Blackwell, Aaron D; Allayee, Hooman; Beheim, Bret; Finch, Caleb E; Gurven, Michael; Kaplan, Hillard

2017-04-01

The apolipoprotein E4 (E4) allele is present worldwide, despite its associations with higher risk of cardiovascular morbidity, accelerated cognitive decline during aging, and Alzheimer 's disease (AD). The E4 allele is especially prevalent in some tropical regions with a high parasite burden. Equatorial populations also face a potential dual burden of high E4 prevalence combined with parasitic infections that can also reduce cognitive performance. We examined the interactions of E4, parasite burden, and cognitive performance in a traditional, nonindustrialized population of Amazonian forager-horticulturalists ( N = 372) to test whether E4 protects against cognitive decline in environments with a heavy pathogen burden. Contrary to observations in industrial populations, older adult E4 carriers with high parasite burdens either maintained or showed slight improvements in cognitive performance, whereas non-E4 carriers with a high parasite burden showed reduced cognitive performance. Being an E4 carrier is the strongest risk factor to date of AD and cognitive decline in industrial populations; it is associated with greater cognitive performance in individuals facing a high parasite and pathogen load, suggesting advantages to the E4 allele under certain environmental conditions. The current mismatch between postindustrial hygienic lifestyles and active parasite-rich environs may be critical for understanding genetic risk for cognitive aging.-Trumble, B. C., Stieglitz, J., Blackwell, A. D., Allayee, H., Beheim, B., Finch, C. E., Gurven, M., Kaplan, H. Apolipoprotein E4 is associated with improved cognitive function in Amazonian forager-horticulturalists with a high parasite burden. © FASEB.

Metabolic Syndrome and 16-year Cognitive Decline in Community-Dwelling Older Adults

PubMed Central

McEvoy, Linda K.; Laughlin, Gail A.; Barrett-Connor, Elizabeth; Bergstrom, Jaclyn; Kritz-Silverstein, Donna; Der-Martirosian, Claudia; von Mühlen, Denise

2012-01-01

PURPOSE To determine whether metabolic syndrome is associated with accelerated cognitive decline in community-dwelling older adults. METHODS Longitudinal study of 993 adults (mean 66.8 ± 8.7 years) from the Rancho Bernardo Study. Metabolic syndrome components, defined by 2001 NCEP-ATP III criteria, were measured in 1984–87. Cognitive function was first assessed in 1988–92. Cognitive assessments were repeated approximately every four years, for a maximum 16-year follow-up. Mixed-effects models examined longitudinal rate of cognitive decline by metabolic syndrome status, controlling for factors plausibly associated with cognitive function (diabetes, inflammation). RESULTS Metabolic syndrome was more common in men than women (14% vs. 9%, p=0.01). In women, metabolic syndrome was associated with greater executive function and long term memory decline. These associations did not differ by inflammatory biomarker levels. Diabetes did not alter the association of metabolic syndrome with long-term recall but modified the association with executive function: metabolic syndrome was associated with accelerated executive function decline in diabetic women only. Metabolic syndrome was not related to rate of decline on any cognitive measure in men. CONCLUSIONS Metabolic syndrome was a risk factor for accelerated cognitive decline, but only in women. Prevention of metabolic syndrome may aid in maintenance of cognitive function with age. PMID:22285865

Disease Progression in Mild Dementia due to Alzheimer Disease in an 18-Month Observational Study (GERAS): The Impact on Costs and Caregiver Outcomes.

PubMed

Jones, Roy W; Lebrec, Jeremie; Kahle-Wrobleski, Kristin; Dell'Agnello, Grazia; Bruno, Giuseppe; Vellas, Bruno; Argimon, Josep M; Dodel, Richard; Haro, Josep Maria; Wimo, Anders; Reed, Catherine

2017-01-01

We assessed whether cognitive and functional decline in community-dwelling patients with mild Alzheimer disease (AD) dementia were associated with increased societal costs and caregiver burden and time outcomes. Cognitive decline was defined as a ≥3-point reduction in the Mini-Mental State Examination and functional decline as a decrease in the ability to perform one or more basic items of the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) or ≥20% of instrumental ADL items. Total societal costs were estimated from resource use and caregiver hours using 2010 costs. Caregiver burden was assessed using the Zarit Burden Interview (ZBI); caregiver supervision and total hours were collected. Of 566 patients with mild AD enrolled in the GERAS study, 494 were suitable for the current analysis. Mean monthly total societal costs were greater for patients showing functional (+61%) or cognitive decline (+27%) compared with those without decline. In relation to a typical mean monthly cost of approximately EUR 1,400 at baseline, this translated into increases over 18 months to EUR 2,254 and 1,778 for patients with functional and cognitive decline, respectively. The number of patients requiring supervision doubled among patients showing functional or cognitive decline compared with those not showing decline, while caregiver total time increased by 70 and 33%, respectively and ZBI total score by 5.3 and 3.4 points, respectively. Cognitive and, more notably, functional decline were associated with increases in costs and caregiver outcomes in patients with mild AD dementia.

Sarcopenia during neoadjuvant therapy for oesophageal cancer: characterising the impact on muscle strength and physical performance.

PubMed

Guinan, Emer M; Doyle, S L; Bennett, A E; O'Neill, L; Gannon, J; Elliott, J A; O'Sullivan, J; Reynolds, J V; Hussey, J

2018-05-01

Preoperative chemo(radio)therapy for oesophageal cancer (OC) may have an attritional impact on body composition and functional status, impacting postoperative outcome. Physical decline with skeletal muscle loss has not been previously characterised in OC and may be amenable to physical rehabilitation. This study characterises skeletal muscle mass and physical performance from diagnosis to post-neoadjuvant therapy in patients undergoing preoperative chemo(radio)therapy for OC. Measures of body composition (axial computerised tomography), muscle strength (handgrip), functional capacity (walking distance), anthropometry (weight, height and waist circumference), physical activity, quality-of-life and nutritional status were captured prospectively. Sarcopenia status was defined as pre-sarcopenic (low muscle mass only), sarcopenic (low muscle mass and low muscle strength or function) or severely sarcopenic (low muscle mass and low muscle strength and low muscle function). Twenty-eight participants were studied at both time points (mean age 62.86 ± 8.18 years, n = 23 male). Lean body mass reduced by 4.9 (95% confidence interval 3.2 to 6.7) kg and mean grip strength reduced by 4.3 (2.5 to 6.1) kg from pre- to post-neoadjuvant therapy. Quality-of-life scores capturing gastrointestinal symptoms improved. Measures of anthropometry, walking distance, physical activity and nutritional status did not change. There was an increase in sarcopenic status from diagnosis (pre-sarcopenic n = 2) to post-treatment (pre-sarcopenic n = 5, severely sarcopenic n = 1). Despite maintenance of body weight, functional capacity and activity habits, participants experience declines in muscle mass and strength. Interventions involving exercise and/or nutritional support to build muscle mass and strength during preoperative therapy, even in patients who are functioning normally, are warranted.

Functional and structural adaptations of skeletal muscle to microgravity

NASA Technical Reports Server (NTRS)

Fitts, R. H.; Riley, D. R.; Widrick, J. J.

2001-01-01

Our purpose is to summarize the major effects of space travel on skeletal muscle with particular emphasis on factors that alter function. The primary deleterious changes are muscle atrophy and the associated decline in peak force and power. Studies on both rats and humans demonstrate a rapid loss of cell mass with microgravity. In rats, a reduction in muscle mass of up to 37% was observed within 1 week. For both species, the antigravity soleus muscle showed greater atrophy than the fast-twitch gastrocnemius. However, in the rat, the slow type I fibers atrophied more than the fast type II fibers, while in humans, the fast type II fibers were at least as susceptible to space-induced atrophy as the slow fiber type. Space flight also resulted in a significant decline in peak force. For example, the maximal voluntary contraction of the human plantar flexor muscles declined by 20-48% following 6 months in space, while a 21% decline in the peak force of the soleus type I fibers was observed after a 17-day shuttle flight. The reduced force can be attributed both to muscle atrophy and to a selective loss of contractile protein. The former was the primary cause because, when force was expressed per cross-sectional area (kNm(-2)), the human fast type II and slow type I fibers of the soleus showed no change and a 4% decrease in force, respectively. Microgravity has been shown to increase the shortening velocity of the plantar flexors. This increase can be attributed both to an elevated maximal shortening velocity (V(0)) of the individual slow and fast fibers and to an increased expression of fibers containing fast myosin. Although the cause of the former is unknown, it might result from the selective loss of the thin filament actin and an associated decline in the internal drag during cross-bridge cycling. Despite the increase in fiber V(0), peak power of the slow type I fiber was reduced following space flight. The decreased power was a direct result of the reduced force caused by the fiber atrophy. In addition to fiber atrophy and the loss of force and power, weightlessness reduces the ability of the slow soleus to oxidize fats and increases the utilization of muscle glycogen, at least in rats. This substrate change leads to an increased rate of fatigue. Finally, with return to the 1g environment of earth, rat studies have shown an increased occurrence of eccentric contraction-induced fiber damage. The damage occurs with re-loading and not in-flight, but the etiology has not been established.

Cognitive function trajectories and their determinants in older people: 8 years of follow-up in the English Longitudinal Study of Ageing.

PubMed

Zaninotto, Paola; Batty, G David; Allerhand, Michael; Deary, Ian J

2018-04-24

Maintaining cognitive function is an important aspect of healthy ageing. In this study, we examined age trajectories of cognitive decline in a large nationally representative sample of older people in England. We explored the factors that influence such decline and whether these differed by gender. Latent growth curve modelling was used to explore age-specific changes, and influences on them, in an 8-year period in memory, executive function, processing speed and global cognitive function among 10 626 participants in the English Longitudinal Study of Ageing. We run gender-specific models with the following exposures: age, education, wealth, childhood socioeconomic status, cardiovascular disease, diabetes, physical function, body mass index, physical activity, alcohol, smoking, depression and dementia. After adjustment, women had significantly less decline than men in memory (0.011, SE 0.006), executive function (0.012, SE 0.006) and global cognitive function (0.016, SE 0.004). Increasing age and dementia predicted faster rates of decline in all cognitive function domains. Depression and alcohol consumption predicted decline in some cognitive function domains in men only. Poor physical function, physical inactivity and smoking were associated with faster rates of decline in specific cognitive domains in both men and women. For example, relative to study members who were physically active, the sedentary experienced greater declines in memory (women -0.018, SE 0.009) and global cognitive function (men -0.015, SE 0.007 and women -0.016, SE 0.007). The potential determinants of cognitive decline identified in this study, in particular modifiable risk factors, should be tested in the context of randomised controlled trials. © 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.

Young APOE[subscript 4] Targeted Replacement Mice Exhibit Poor Spatial Learning and Memory, with Reduced Dendritic Spine Density in the Medial Entorhinal Cortex

ERIC Educational Resources Information Center

Rodriguez, Gustavo A.; Burns, Mark P.; Weeber, Edwin J.; Rebeck, G. William

2013-01-01

The apolipoprotein E4 ("APOE-[epsilon]4") allele is the strongest genetic risk factor for developing late-onset Alzheimer's disease, and may predispose individuals to Alzheimer's-related cognitive decline by affecting normal brain function early in life. To investigate the impact of human APOE alleles on cognitive performance in mice, we trained…

Consumption of alcoholic beverages and cognitive decline at middle age: the Doetinchem Cohort Study.

PubMed

Nooyens, Astrid C J; Bueno-de-Mesquita, H Bas; van Gelder, Boukje M; van Boxtel, Martin P J; Verschuren, W M Monique

2014-02-01

Accelerated cognitive decline increases the risk of dementia. Slowing down the rate of cognitive decline leads to the preservation of cognitive functioning in the elderly, who can live independently for a longer time. Alcohol consumption may influence the rate of cognitive decline. The aim of the present study was to evaluate the associations between the total consumption of alcoholic beverages and different types of alcoholic beverages and cognitive decline at middle age. In 2613 men and women of the Doetinchem Cohort Study, aged 43-70 years at baseline (1995-2002), cognitive function (global cognitive function and the domains memory, speed and flexibility) was assessed twice, with a 5-year time interval. In linear regression analyses, the consumption of different types of alcoholic beverages was analysed in relation to cognitive decline, adjusting for confounders. We observed that, in women, the total consumption of alcoholic beverages was inversely associated with the decline in global cognitive function over a 5-year period (P for trend = 0·02), while no association was observed in men. Regarding the consumption of different types of alcoholic beverages in men and women together, red wine consumption was inversely associated with the decline in global cognitive function (P for trend < 0·01) as well as memory (P for trend < 0·01) and flexibility (P for trend = 0·03). Smallest declines were observed at a consumption of about 1·5 glasses of red wine per d. No other types of alcoholic beverages were associated with cognitive decline. In conclusion, only (moderate) red wine consumption was consistently associated with less strong cognitive decline. Therefore, it is most likely that non-alcoholic substances in red wine are responsible for any cognition-preserving effects.

Effects of Sex and Education on Cognitive Change Over a 27-Year Period in Older Adults: The Rancho Bernardo Study.

PubMed

Reas, Emilie T; Laughlin, Gail A; Bergstrom, Jaclyn; Kritz-Silverstein, Donna; Barrett-Connor, Elizabeth; McEvoy, Linda K

2017-08-01

This study investigated how cognitive function changes with age and whether rates of decline vary by sex or education in a large, homogenous longitudinal cohort characterized by high participation rates, long duration of follow-up, and minimal loss to follow-up. Between 1988 and 2016, 2,225 community-dwelling participants of the Rancho Bernardo Study, aged 31 to 99 years at their initial cognitive assessment, completed neuropsychological testing approximately every 4 years, over a maximum 27-year follow-up. Linear mixed effects regression models defined sex-specific cognitive trajectories, adjusting for education and retest effects. Significant decline across all cognitive domains began around age 65 years and accelerated after age 80 years. Patterns of decline were generally similar between sexes, although men declined more rapidly than women on the global function test. Higher education was associated with slower decline on the tests of executive and global functions. After excluding 517 participants with evidence of cognitive impairment, accelerating decline with age remained for all tests, and women declined more rapidly than men on the executive function test. Accelerating decline with advancing age occurs across multiple cognitive domains in community-dwelling older adults, with few differences in rates of decline between men and women. Higher education may provide some protection against executive and global function decline with age. These findings better characterize normal cognitive aging, a critical prerequisite for identifying individuals at risk for cognitive impairment, and lay the groundwork for future studies of health and behavioral factors that affect age-related decline in this cohort. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Menopause Is Associated with Accelerated Lung Function Decline.

PubMed

Triebner, Kai; Matulonga, Bobette; Johannessen, Ane; Suske, Sandra; Benediktsdóttir, Bryndís; Demoly, Pascal; Dharmage, Shyamali C; Franklin, Karl A; Garcia-Aymerich, Judith; Gullón Blanco, José Antonio; Heinrich, Joachim; Holm, Mathias; Jarvis, Debbie; Jõgi, Rain; Lindberg, Eva; Moratalla Rovira, Jesús Martínez; Muniozguren Agirre, Nerea; Pin, Isabelle; Probst-Hensch, Nicole; Puggini, Luca; Raherison, Chantal; Sánchez-Ramos, José Luis; Schlünssen, Vivi; Sunyer, Jordi; Svanes, Cecilie; Hustad, Steinar; Leynaert, Bénédicte; Gómez Real, Francisco

2017-04-15

Menopause is associated with changes in sex hormones, which affect immunity, inflammation, and osteoporosis and may impair lung function. Lung function decline has not previously been investigated in relation to menopause. To study whether lung function decline, assessed by FVC and FEV 1 , is accelerated in women who undergo menopause. The population-based longitudinal European Community Respiratory Health Survey provided serum samples, spirometry, and questionnaire data about respiratory and reproductive health from three study waves (n = 1,438). We measured follicle-stimulating hormone and luteinizing hormone and added information on menstrual patterns to determine menopausal status using latent class analysis. Associations with lung function decline were investigated using linear mixed effects models, adjusting for age, height, weight, pack-years, current smoking, age at completed full-time education, spirometer, and including study center as random effect. Menopausal status was associated with accelerated lung function decline. The adjusted mean FVC decline was increased by -10.2 ml/yr (95% confidence interval [CI], -13.1 to -7.2) in transitional women and -12.5 ml/yr (95% CI, -16.2 to -8.9) in post-menopausal women, compared with women menstruating regularly. The adjusted mean FEV 1 decline increased by -3.8 ml/yr (95% CI, -6.3 to -2.9) in transitional women and -5.2 ml/yr (95% CI, -8.3 to -2.0) in post-menopausal women. Lung function declined more rapidly among transitional and post-menopausal women, in particular for FVC, beyond the expected age change. Clinicians should be aware that respiratory health often deteriorates during reproductive aging.

Caloric restriction preserves memory and reduces anxiety of aging mice with early enhancement of neurovascular functions.

PubMed

Parikh, Ishita; Guo, Janet; Chuang, Kai-Hsiang; Zhong, Yu; Rempe, Ralf G; Hoffman, Jared D; Armstrong, Rachel; Bauer, Björn; Hartz, Anika M S; Lin, Ai-Ling

2016-11-08

Neurovascular integrity plays an important role in protecting cognitive and mental health in aging. Lifestyle interventions that sustain neurovascular integrity may thus be critical on preserving brain functions in aging and reducing the risk for age-related neurodegenerative disorders. Here we show that caloric restriction (CR) had an early effect on neurovascular enhancements, and played a critical role in preserving vascular, cognitive and mental health in aging. In particular, we found that CR significantly enhanced cerebral blood flow (CBF) and blood-brain barrier function in young mice at 5-6 months of age. The neurovascular enhancements were associated with reduced mammalian target of rapamycin expression, elevated endothelial nitric oxide synthase signaling, and increased ketone bodies utilization. With age, CR decelerated the rate of decline in CBF. The preserved CBF in hippocampus and frontal cortex were highly correlated with preserved memory and learning, and reduced anxiety, of the aging mice treated with CR (18-20 months of age). Our results suggest that dietary intervention started in the early stage (e.g., young adults) may benefit cognitive and mental reserve in aging. Understanding nutritional effects on neurovascular functions may have profound implications in human brain aging and age-related neurodegenerative disorders.

Idiopathic Pulmonary Fibrosis: Gender-Age-Physiology Index Stage for Predicting Future Lung Function Decline.

PubMed

Salisbury, Margaret L; Xia, Meng; Zhou, Yueren; Murray, Susan; Tayob, Nabihah; Brown, Kevin K; Wells, Athol U; Schmidt, Shelley L; Martinez, Fernando J; Flaherty, Kevin R

2016-02-01

Idiopathic pulmonary fibrosis is a progressive lung disease with variable course. The Gender-Age-Physiology (GAP) Index and staging system uses clinical variables to stage mortality risk. It is unknown whether clinical staging predicts future decline in pulmonary function. We assessed whether the GAP stage predicts future pulmonary function decline and whether interval pulmonary function change predicts mortality after accounting for stage. Patients with idiopathic pulmonary fibrosis (N = 657) were identified retrospectively at three tertiary referral centers, and baseline GAP stages were assessed. Mixed models were used to describe average trajectories of FVC and diffusing capacity of the lung for carbon monoxide (Dlco). Multivariable Cox proportional hazards models were used to assess whether declines in pulmonary function ≥ 10% in 6 months predict mortality after accounting for GAP stage. Over a 2-year period, GAP stage was not associated with differences in yearly lung function decline. After accounting for stage, a 10% decrease in FVC or Dlco over 6 months independently predicted death or transplantation (FVC hazard ratio, 1.37; Dlco hazard ratio, 1.30; both, P ≤ .03). Patients with GAP stage 2 with declining pulmonary function experienced a survival profile similar to patients with GAP stage 3, with 1-year event-free survival of 59.3% (95% CI, 49.4-67.8) vs 56.9% (95% CI, 42.2-69.1). Baseline GAP stage predicted death or lung transplantation but not the rate of future pulmonary function decline. After accounting for GAP stage, a decline of ≥ 10% over 6 months independently predicted death or lung transplantation. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Physical function and independence 1 year after myocardial infarction: observations from the Translational Research Investigating Underlying disparities in recovery from acute Myocardial infarction: Patients' Health status registry.

PubMed

Dodson, John A; Arnold, Suzanne V; Reid, Kimberly J; Gill, Thomas M; Rich, Michael W; Masoudi, Frederick A; Spertus, John A; Krumholz, Harlan M; Alexander, Karen P

2012-05-01

Acute myocardial infarction (AMI) may contribute to health status declines including "independence loss" and "physical function decline." Despite the importance of these outcomes for prognosis and quality of life, their incidence and predictors have not been well described. We studied 2,002 patients with AMI enrolled across 24 sites in the TRIUMPH registry who completed assessments of independence and physical function at the time of AMI and 1 year later. Independence was evaluated by the EuroQol-5D (mobility, self-care, and usual activities), and physical function was assessed with the Short Form-12 physical component score. Declines in ≥1 level on EuroQol-5D and >5 points in PCS were considered clinically significant changes. Hierarchical, multivariable, modified Poisson regression models accounting for within-site variability were used to identify predictors of independence loss and physical function decline. One-year post AMI, 43.0% of patients experienced health status declines: 12.8% independence loss alone, 15.2% physical function decline alone, and 15.0% both. After adjustment, variables that predicted independence loss included female sex, nonwhite race, unmarried status, uninsured status, end-stage renal disease, and depression. Variables that predicted physical function decline were uninsured status, lack of cardiac rehabilitation referral, and absence of pre-AMI angina. Age was not predictive of either outcome after adjustment. >40% of patients experience independence loss or physical function decline 1 year after AMI. These changes are distinct but can occur simultaneously. Although some risk factors are not modifiable, others suggest potential targets for strategies to preserve patients' health status. Copyright © 2012 Mosby, Inc. All rights reserved.

Increasing Body Mass Index Predicts Rapid Decline in Renal Function: A 5 Year Retrospective Study.

PubMed

Ma, Xiaojing; Zhang, Chengyin; Su, Hong; Gong, Xiaojie; Kong, Xianglei

2018-05-02

While obesity is a recognized risk factor for chronic kidney disease, it remains unclear whether change in body mass index (ΔBMI ) is independently associated with decline in renal function (evaluated by the change in estimated glomerular filtration rate, ΔeGFR) over time. Accordingly, to help clarify this we conducted a retrospective study to measure the association of ΔBMI with decline in renal function in Chinese adult population. A total of 4007 adults (aged 45.3±13.7 years, 68.6% male) without chronic kidney disease at baseline were enrolled between 2008 and 2013. Logistic regression models were applied to explore the relationships between baseline BMI and ΔBMI, and rapid decline in renal function (defined as the lowest quartile of ΔeGFR ). During 5 years of follow-up, the ΔBMI and ΔeGFR were 0.47±1.6 (kg/m 2 ) and -3.0±8.8 (ml/min/1.73 m 2 ), respectively. After adjusted for potential confounders, ΔBMI (per 1 kg/m 2 increase) was independently associated with the rapid decline in renal function [with a fully adjusted OR of 1.12 (95% CI, 1.05 to 1.20). By contrast, the baseline BMI was not associated with rapid decline in renal function [OR=1.05 (95% CI, 0.98 to 1.13)]. The results were robust among 2948 hypertension-free and diabetes-free participants, the adjusted ORs of ΔBMI and baseline BMI were 1.14 (95% CI, 1.05 to 1.23) and 1.0 (95% CI, 0.96 to 1.04) for rapid decline in renal function, respectively. The study revealed that increasing ΔBMI predicts rapid decline in renal function. © Georg Thieme Verlag KG Stuttgart · New York.

Arterial stiffness and decline of renal function in a primary care population.

PubMed

van Varik, Bernard J; Vossen, Liv M; Rennenberg, Roger J; Stoffers, Henri E; Kessels, Alfons G; de Leeuw, Peter W; Kroon, Abraham A

2017-01-01

Arterial stiffness is an important pathophysiological factor linking cardiovascular disease and kidney disease. Controversy exists as to whether arterial stiffness causes renal function decline, or kidney dysfunction leads to stiffening or whether the association is mutual. We aimed to investigate the longitudinal association between arterial stiffness and annual rate of renal function decline. We prospectively investigated in a primary care population whether carotid-femoral pulse wave velocity (PWV) was associated with estimated glomerular filtration rate (eGFR) and annual decline in eGFR in participants aged ⩾40 years without overt kidney disease. Baseline data on PWV and eGFR were available for 587 participants; follow-up measurements with a mean duration of 5.6 years were available for 222 patients. PWV, female gender and mean arterial pressure were independently associated with eGFR at baseline, although age confounded this association. More importantly, baseline PWV, age and eGFR were independent predictors of renal function decline. Stratification for age showed that the effect of PWV on rate of eGFR decline was amplified with advancing age. On the other hand, baseline eGFR did not determine annual change in PWV, suggesting a unidirectional association between arterial stiffness and eGFR. Arterial stiffness amplifies age-related renal function decline, suggesting that arterial stiffness plays a causal role in the development of renal damage, at least at later stages of age-related renal function decline, possibly through impaired renal autoregulation and increased arterial blood pressure pulsatility.

[Functional deterioration of basic daily living activities after an emergency service consultation].

PubMed

Gutiérrez Rodríguez, J; Varela Suárez, C; Alonso Alvarez, M; Solano Jaurrieta, J J

2000-05-01

To determine the incidence of functional decline of elderly patients discharged from an emergency department and to analized functional impairment as a risk of readmission. A prospective cohort aged 75 or older were followed up after discharge from an emergency department between 01-02-95 and 01-04-95. The study protocol included sociodemografics, clinicals, functionals and mentalsoutcomes. We studied the incidence of functional decline in basic activities of daily living, with Barthel Index, and association with the risk of readmission. The sample was composed by 125 elders (mean aged 81.9 +/- 4.6 years and 60.8% were women). The incidence of functional decline in basic activities of daily living at the visit to emergency department was 20.8% and one moth after discharge was 18.4%. Both activities with more functional impairment were bathing, dressing and movility activities. Functional decline was associated with the risk of readmission at emergency department (Odds Ratio = 4.1 [1.4-11.8]) 20% of patients who are discharged of emergency department present a new functional impairment in basics activities of daily living. Functional decline is associated with the risk of readmission one moth after discharged.

Regular use of nonsteroidal anti-inflammatory drugs and cognitive function in aging women.

PubMed

Kang, Jae Hee; Grodstein, Francine

2003-05-27

To examine the relationship of nonsteroidal anti-inflammatory drug (NSAID) use and cognitive decline in young-old women. The authors prospectively studied 16,128 Nurses' Health Study participants, aged 70 to 81 years at baseline, who provided information on NSAID use and potential confounders in biennial questionnaires from 1976 through 1998. From 1995 through 2001, we administered, by telephone, six tests of cognitive function, including the Telephone Interview of Cognitive Status (TICS). Second interviews were begun 2 years later and completed on 13,255 women to date. The authors used multiple logistic regression to estimate relative risks (RR) of low baseline scores (defined as the bottom 10%) and substantial decline (worst 10%). Compared to never users, the RR was 0.75 (95% CI 0.59, 0.96) for a low baseline TICS score with current aspirin use of 15+ years duration, and 0.79 (95% CI 0.62, 1.02) for current use of NSAID (primarily ibuprofen) lasting 8+ years. Results for aspirin users were weaker on other tests, but long-term ibuprofen users had a RR of 0.75 (95% CI 0.56, 1.00) for a low baseline global score (combination of all six tests). The RR for substantial global cognitive decline was 0.93 (95% CI 0.68, 1.26) with long-term aspirin use, and 0.77 (95% CI 0.57, 1.05) with long-term ibuprofen use. In these young-old women, current, long-term NSAID users, especially of nonaspirin agents, showed reduced odds of low cognitive function and possibly lower rates of substantial cognitive decline over 2 years. Continued follow-up will help determine if associations differ at older ages.

Molecular profiling of aged neural progenitors identifies Dbx2 as a candidate regulator of age-associated neurogenic decline.

PubMed

Lupo, Giuseppe; Nisi, Paola S; Esteve, Pilar; Paul, Yu-Lee; Novo, Clara Lopes; Sidders, Ben; Khan, Muhammad A; Biagioni, Stefano; Liu, Hai-Kun; Bovolenta, Paola; Cacci, Emanuele; Rugg-Gunn, Peter J

2018-06-01

Adult neurogenesis declines with aging due to the depletion and functional impairment of neural stem/progenitor cells (NSPCs). An improved understanding of the underlying mechanisms that drive age-associated neurogenic deficiency could lead to the development of strategies to alleviate cognitive impairment and facilitate neuroregeneration. An essential step towards this aim is to investigate the molecular changes that occur in NSPC aging on a genomewide scale. In this study, we compare the transcriptional, histone methylation and DNA methylation signatures of NSPCs derived from the subventricular zone (SVZ) of young adult (3 months old) and aged (18 months old) mice. Surprisingly, the transcriptional and epigenomic profiles of SVZ-derived NSPCs are largely unchanged in aged cells. Despite the global similarities, we detect robust age-dependent changes at several hundred genes and regulatory elements, thereby identifying putative regulators of neurogenic decline. Within this list, the homeobox gene Dbx2 is upregulated in vitro and in vivo, and its promoter region has altered histone and DNA methylation levels, in aged NSPCs. Using functional in vitro assays, we show that elevated Dbx2 expression in young adult NSPCs promotes age-related phenotypes, including the reduced proliferation of NSPC cultures and the altered transcript levels of age-associated regulators of NSPC proliferation and differentiation. Depleting Dbx2 in aged NSPCs caused the reverse gene expression changes. Taken together, these results provide new insights into the molecular programmes that are affected during mouse NSPC aging, and uncover a new functional role for Dbx2 in promoting age-related neurogenic decline. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Physical activity and motor decline in older persons.

PubMed

Buchman, A S; Boyle, P A; Wilson, R S; Bienias, Julia L; Bennett, D A

2007-03-01

We tested the hypothesis that physical activity modifies the course of age-related motor decline. More than 850 older participants of the Rush Memory and Aging Project underwent baseline assessment of physical activity and annual motor testing for up to 8 years. Nine strength measures and nine motor performance measures were summarized into composite measures of motor function. In generalized estimating equation models, global motor function declined during follow-up (estimate, -0.072; SE, 0.008; P < 0.001). Each additional hour of physical activity at baseline was associated with about a 5% decrease in the rate of global motor function decline (estimate, 0.004; SE, 0.001; P = 0.007). Secondary analyses suggested that the association of physical activity with motor decline was mostly due to the effect of physical activity on the rate of motor performance decline. Thus, higher levels of physical activity are associated with a slower rate of motor decline in older persons.

Comparison of serum concentrations of symmetric dimethylarginine and creatinine as kidney function biomarkers in healthy geriatric cats fed reduced protein foods enriched with fish oil, L-carnitine, and medium-chain triglycerides.

PubMed

Hall, J A; Yerramilli, M; Obare, E; Yerramilli, M; Yu, S; Jewell, D E

2014-12-01

The purpose of this study was to determine whether feeding cats reduced protein and phosphorus foods with added fish oil, L-carnitine, and medium-chain triglycerides (MCT) altered serum biomarkers of renal function. Thirty-two healthy cats, mean age 14.0 (8.3-19.6) years, were fed control food or one of two experimental foods for 6 months. All foods had similar concentrations of moisture, protein, and fat (approximately 8.0%, 26.5%, and 20.0%, respectively). Both experimental foods contained added fish oil (1.5%) and L-carnitine (500 mg/kg). Experimental-food 2 also contained increased MCT (10.5% from coconut oil), 1.5% added corn oil, and reduced animal fat. Glomerular filtration rate (GFR), serum biochemistries, renal function biomarkers including serum creatinine (sCr) and symmetrical dimethylarginine (SDMA), and plasma metabolomic profiles were measured at baseline, and at 1.5, 3, and 6 months. Body composition was determined by dual-energy X-ray absorptiometry. Although both experimental foods altered plasma fatty acids, carnitine and related metabolites, and lysophospholipid concentrations, there were no changes in renal function biomarkers. There was, however, a benefit in using SDMA versus sCr to assess renal function in older cats with less total lean mass. Compared with cats <12 years, those >15 years had lower total lean mass (P < 0.01), lower GFR (P = 0.04), and lower sCr concentrations (P < 0.01). However, SDMA concentrations (P < 0.01) were higher in older cats. This study shows that in cats, serum SDMA concentration is more highly correlated with GFR than sCr concentration, and, unlike sCr, which declines with age because of muscle wasting, SDMA increases as GFR declines with age. Copyright © 2014 Elsevier Ltd. All rights reserved.

T-cell receptor excision circles (TREC) in CD4+ and CD8+ T-cell subpopulations in atopic dermatitis and psoriasis show major differences in the emission of recent thymic emigrants.

PubMed

Just, Helle L; Deleuran, Mette; Vestergaard, Christian; Deleuran, Bent; Thestrup-Pedersen, Kristian

2008-01-01

We used T-cell receptor excision circles (TREC) to evaluate thymic function in adult patients with atopic dermatitis and psoriasis. We observed that men, but not women, with atopic dermatitis had a significantly faster decline in TREC content with increasing age compared with healthy men. In contrast, both men and women with psoriasis had significantly reduced TREC levels, which were, on average, only 30% of that of healthy persons. In atopic dermatitis the levels of TREC declined with increasing levels of IgE, disease intensity and extent of eczema. Furthermore, patients with atopic dermatitis showed signs of altered thymus function, as they had a significantly greater variation in TREC content measured over time than healthy controls, especially within the CD8+ T-cell subpopulation. Because both atopic dermatitis and psoriasis patients have an increased number of T-cells, this indicates that atopic dermatitis patients can have compensatory emissions of thymic emigrants, whereas psoriatic patients do not, thus supporting different thymic function in these two diseases.

Treatment effects in multiple cognitive domains in Alzheimer’s disease: a two-year cohort study

PubMed Central

2014-01-01

Introduction Despite widespread use of second-generation cholinesterase inhibitors for the symptomatic treatment of Alzheimer’s disease (AD), little is known about the long term effects of cholinergic treatment on global cognitive function and potential specific effects in different cognitive domains. The objectives of this study were to determine the association between cholinergic treatment and global cognitive function over one and two years in a cohort of patients with mild or moderate AD and identify potential differences in domain-specific cognitive outcomes within this cohort. Methods A cohort of patients meeting the revised National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for mild or moderate AD, including patients both on treatment with a cholinesterase inhibitor and untreated controls (treated = 65, untreated = 65), were recruited from the Cognitive Neurology Clinic at Sunnybrook Health Sciences Centre, as part of the Sunnybrook Dementia Study. Patients were followed for one to two years and underwent standardized neuropsychological assessments to evaluate global and domain-specific cognitive function. Associations between cholinesterase inhibitor use and global and domain-specific cognitive outcome measures at one and two years of follow-up were estimated using mixed model linear regression, adjusting for age, education, and baseline mini mental state examination (MMSE). Results At one year, treated patients showed significantly less decline in global cognitive function, and treatment and time effects across tests of executive and visuospatial function. At two years, there was a significant trend towards less decline in global cognition for treated patients. Moreover, treated patients showed significant treatment and time effects across tests of executive functioning, memory, and visuospatial function. Conclusions The present study offers two important contributions to knowledge of the effectiveness of cholinesterase inhibitor treatment in patients with mild-moderate AD: 1) that second-generation cholinesterase inhibitors demonstrate long-term effectiveness for reducing global cognitive decline over one to two years of follow-up, and 2) that decline in function for cognitive domains, including executive function, memory, and visuospatial skill that are primarily mediated by frontal networks and by the cholinergic system, rather than memory, may be slowed by treatment targeting the cholinergic system. PMID:25484926

Vitamin D deficiency is associated with functional decline and falls in frail elderly women despite supplementation.

PubMed

Kotlarczyk, M P; Perera, S; Ferchak, M A; Nace, D A; Resnick, N M; Greenspan, S L

2017-04-01

We examined the impact of daily supplementation on vitamin D deficiency, function, and falls in female long-term care residents. Initial vitamin D deficiency was associated with greater functional decline and increased fall risk despite guideline-recommended supplementation, highlighting the importance of preventing vitamin D deficiency in frail elderly. Institute of Medicine (IOM) guidelines recommend 800 IU vitamin D daily for older adults and maintaining serum 25-hydroxyvitamin D [25(OH) D] above 20 ng/ml for optimal skeletal health. The adequacy of IOM guidelines for sustaining function and reducing falls in frail elderly is unknown. Female long-term care residents aged ≥65 enrolled in an osteoporosis clinical trial were included in this analysis (n = 137). Participants were classified based on baseline 25(OH) D levels as deficient (<20 ng/ml, n = 26), insufficient (20-30 ng/ml, n = 40), or sufficient (>30 ng/ml, n = 71). Deficient women were provided initial vitamin D repletion (50,000 IU D 3 weekly for 8 weeks). All were supplemented with 800 IU vitamin D 3 daily for 24 months. Annual functional assessments included Activities of Daily Living (ADLs), Instrumental ADL (IADL), physical performance test (PPT), gait speed, cognition (SPMSQ), and mental health (PHQ-9). We used linear mixed models for analysis of functional measures and logistic regression for falls. Daily supplementation maintained 25(OH) D levels above 20 ng/ml in 95% of participants. All groups demonstrated functional decline. Women initially deficient had a greater decline in physical function at 12 (IADL -2.0 ± 0.4, PPT -3.1 ± 0.7, both p < 0.01) and 24 months (IADL -2.5 ± 0.6, ADL -2.5 ± 0.6, both p < 0.01), a larger increase in cognitive deficits at 12 months (1.7 ± 0.4: p = 0.01) and more fallers (88.5%, p = 0.04) compared to those sufficient at baseline, despite supplementation to sufficient levels. IOM guidelines may not be adequate for frail elderly. Further study of optimal 25(OH) D levels for maintaining function and preventing falls is needed.

Iohexol clearance is superior to creatinine-based renal function estimating equations in detecting short-term renal function decline in chronic heart failure

PubMed Central

Cvan Trobec, Katja; Kerec Kos, Mojca; von Haehling, Stephan; Anker, Stefan D.; Macdougall, Iain C.; Ponikowski, Piotr; Lainscak, Mitja

2015-01-01

Aim To compare the performance of iohexol plasma clearance and creatinine-based renal function estimating equations in monitoring longitudinal renal function changes in chronic heart failure (CHF) patients, and to assess the effects of body composition on the equation performance. Methods Iohexol plasma clearance was measured in 43 CHF patients at baseline and after at least 6 months. Simultaneously, renal function was estimated with five creatinine-based equations (four- and six-variable Modification of Diet in Renal Disease, Cockcroft-Gault, Cockcroft-Gault adjusted for lean body mass, Chronic Kidney Disease Epidemiology Collaboration equation) and body composition was assessed using bioimpedance and dual-energy x-ray absorptiometry. Results Over a median follow-up of 7.5 months (range 6-17 months), iohexol clearance significantly declined (52.8 vs 44.4 mL/[min ×1.73 m2], P = 0.001). This decline was significantly higher in patients receiving mineralocorticoid receptor antagonists at baseline (mean decline -22% of baseline value vs -3%, P = 0.037). Mean serum creatinine concentration did not change significantly during follow-up and no creatinine-based renal function estimating equation was able to detect the significant longitudinal decline of renal function determined by iohexol clearance. After accounting for body composition, the accuracy of the equations improved, but not their ability to detect renal function decline. Conclusions Renal function measured with iohexol plasma clearance showed relevant decline in CHF patients, particularly in those treated with mineralocorticoid receptor antagonists. None of the equations for renal function estimation was able to detect these changes. ClinicalTrials.gov registration number NCT01829880 PMID:26718759

Association of serum albumin levels with kidney function decline and incident chronic kidney disease in elders.

PubMed

Lang, Joshua; Katz, Ronit; Ix, Joachim H; Gutierrez, Orlando M; Peralta, Carmen A; Parikh, Chirag R; Satterfield, Suzanne; Petrovic, Snezana; Devarajan, Prasad; Bennett, Michael; Fried, Linda F; Cummings, Steven R; Sarnak, Mark J; Shlipak, Michael G

2018-06-01

Previous studies in HIV-infected individuals have demonstrated serum albumin to be strongly associated with kidney function decline, independent of urine albumin and inflammatory markers. Lower serum albumin concentrations may be an under-appreciated risk factor for kidney function decline in elders. We performed a cohort analysis in the Health Aging and Body Composition Study, a cohort of well-functioning, bi-racial, community-dwelling elders between the age of 70 and 79 years. We examined the associations of serum albumin concentration with longitudinal kidney function decline by estimated glomerular filtration rate (eGFR). Outcomes included linear eGFR decline, rapid kidney function decline defined as >30% decrease in eGFR, defined as a final eGFR <60 mL/min/1.73 m2 in those with an eGFR >60 mL/min/1.73 m2 at baseline. Cystatin C-based eGFR was calculated at baseline, Year 3 and Year 10. Mean age was 74 years, and mean eGFR was 73 mL/min/1.73 m2 at baseline. The mean rate of eGFR change was 1.81 mL/min/1.73 m2 per year. After multivariate adjustment, lower serum albumin concentrations were strongly and independently associated with kidney function decline (-0.11 mL/min/1.73 m2 per year for each standard deviation decrease serum albumin; -0.01 to - 0.20) with no attenuation after adjustment for urine albumin and inflammatory markers (-0.12, -0.03 to - 0.22). When divided into quartiles, serum albumin levels ≤3.80 g/dL were associated with increased odds of rapid kidney function decline (odds ratio 1.59; 1.12-2.26) and increased risk of incident chronic kidney disease (incident rate ratio 1.29; 1.03-1.62) relative to levels >4.21g/dL. Urine albumin to creatinine ratio (ACR) was also significantly and independently associated with kidney function decline (-0.08 mL/min/1.73 m2 per year for urine ACR >30 mg/g; -0.82 to - 0.13). Lower serum albumin levels are strongly and independently associated with kidney function decline in elders, independent of clinical risk factors, urine albumin and measured inflammatory markers.

Declining lymphoid progenitor fitness promotes aging-associated leukemogenesis.

PubMed

Henry, Curtis J; Marusyk, Andriy; Zaberezhnyy, Vadym; Adane, Biniam; DeGregori, James

2010-12-14

Aging is associated with the functional decline of cells, tissues, and organs. At the same time, age is the single most important prognostic factor in the development of most human cancers, including chronic myelogenous and acute lymphoblastic leukemias initiated by Bcr-Abl oncogenic translocations. Prevailing paradigms attribute the association between aging and cancers to the accumulation of oncogenic mutations over time, because the accrual of oncogenic events is thought to be the rate-limiting step in initiation and progression of cancers. Conversely, aging-associated functional decline caused by both cell-autonomous and non-cell-autonomous mechanisms is likely to reduce the fitness of stem and progenitor cell populations. This reduction in fitness should be conducive for increased selection of oncogenic mutations that can at least partially alleviate fitness defects, thereby promoting the initiation of cancers. We tested this hypothesis using mouse hematopoietic models. Our studies indicate that the dramatic decline in the fitness of aged B-lymphopoiesis coincides with altered receptor-associated kinase signaling. We further show that Bcr-Abl provides a much greater competitive advantage to old B-lymphoid progenitors compared with young progenitors, coinciding with restored kinase signaling pathways, and that this enhanced competitive advantage translates into increased promotion of Bcr-Abl-driven leukemias. Moreover, impairing IL-7-mediated signaling is sufficient to promote selection for Bcr-Abl-expressing B progenitors. These studies support an unappreciated causative link between aging and cancer: increased selection of oncogenic mutations as a result of age-dependent alterations of the fitness landscape.

Fertility and sexual life of men after their forties and in older age.

PubMed

Schill, W B

2001-03-01

Owing to the demographic development, the aging male will require more consideration in future. In contrast to a rapid decline of estradiol during menopause in women, the process of aging in the male is retarded and subject to high individual variations. Impairment of spermatogenesis is observed as a continuous process occurring over decades. However, only about 50 % of men in their eighties show complete loss of fertility. In principle, spermatogenesis may be retained well into senescence. Of importance for the individual health condition is the fact that the number of Leydig cells declines with advancing age. Thus, altered sex hormone concentrations in aging men result from both functional disturbances and a gradual reduction in Leydig cells. Furthermore, an impaired feed-back mechanism of the pituitary-gonadal axis occurs, with disappearance of the circadian testosterone (T) rhythm. LH and FSH levels are increased, and a reduced bioavailability of sex hormones is observed. Lower total testosterone concentrations in men over 60 years are accompanied by clinical signs of reduced virility, such as decreased muscle mass and strength as well as reduced sexual hair growth and libido. An age-related decline in androgen secretion and plasma testosterone levels therefore suggests the use of androgen supplementation. However, there is a lack of risk-benefit long-term studies. Increased research in the male is mandatory to meet the requirements of the aging population. This should include the availability of precise epidemiological data about the frequency of partial androgen deficiency in aging males (PADAM).

Disease Progression in Mild Dementia due to Alzheimer Disease in an 18-Month Observational Study (GERAS): The Impact on Costs and Caregiver Outcomes

PubMed Central

Jones, Roy W.; Lebrec, Jeremie; Kahle-Wrobleski, Kristin; Dell'Agnello, Grazia; Bruno, Giuseppe; Vellas, Bruno; Argimon, Josep M.; Dodel, Richard; Haro, Josep Maria; Wimo, Anders; Reed, Catherine

2017-01-01

Background/Aims We assessed whether cognitive and functional decline in community-dwelling patients with mild Alzheimer disease (AD) dementia were associated with increased societal costs and caregiver burden and time outcomes. Methods Cognitive decline was defined as a ≥3-point reduction in the Mini-Mental State Examination and functional decline as a decrease in the ability to perform one or more basic items of the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) or ≥20% of instrumental ADL items. Total societal costs were estimated from resource use and caregiver hours using 2010 costs. Caregiver burden was assessed using the Zarit Burden Interview (ZBI); caregiver supervision and total hours were collected. Results Of 566 patients with mild AD enrolled in the GERAS study, 494 were suitable for the current analysis. Mean monthly total societal costs were greater for patients showing functional (+61%) or cognitive decline (+27%) compared with those without decline. In relation to a typical mean monthly cost of approximately EUR 1,400 at baseline, this translated into increases over 18 months to EUR 2,254 and 1,778 for patients with functional and cognitive decline, respectively. The number of patients requiring supervision doubled among patients showing functional or cognitive decline compared with those not showing decline, while caregiver total time increased by 70 and 33%, respectively and ZBI total score by 5.3 and 3.4 points, respectively. Conclusion Cognitive and, more notably, functional decline were associated with increases in costs and caregiver outcomes in patients with mild AD dementia. PMID:28611822

The impact of prostate cancer diagnosis and treatment decision-making on health-related quality of life before treatment onset.

PubMed

Cuypers, Maarten; Lamers, Romy E D; Cornel, Erik B; van de Poll-Franse, Lonneke V; de Vries, Marieke; Kil, Paul J M

2018-04-01

The objective of this study is to test if patients' health-related quality of life (HRQoL) declines after prostate biopsy to detect Pca, and after subsequent treatment decision-making in case Pca is confirmed, and to test whether personality state and traits are associated with these potential changes in HRQoL. Patients who were scheduled for prostate biopsy to detect Pca (N = 377) filled out a baseline questionnaire about HRQoL (EORTC QLQ-C30 and PR25), "big five" personality traits (BFI-10), optimism (LOT-r), and self-efficacy (Decision Self-efficacy Scale) (t0). Patients with confirmed Pca (N = 126) filled out a follow-up questionnaire on HRQoL within 2 weeks after treatment was chosen but had not yet started (t1). HRQoL declined between t0 and t1, reflected in impaired role and cognitive functioning, and elevated fatigue, constipation, and prostate-specific symptoms. Sexual activity and functioning improved. Baseline HRQoL scores were unrelated to the selection of a particular treatment, but for patients who chose a curative treatment, post-decision HRQoL showed a greater decline compared to patients who chose active surveillance. Optimism was associated with HRQoL at baseline; decisional self-efficacy was positively associated with HRQoL at follow-up. No associations between HRQoL and the "big five" personality traits were found. Patients who have undergone prostate biopsy and treatment decision-making for Pca experience a decline in HRQoL. Choosing treatment with a curative intent was associated with greater decline in HRQoL. Interventions aimed at optimism and decision self-efficacy could be helpful to reduce HRQoL impairment around the time of prostate biopsy and treatment decision-making.

Urbanization and kidney function decline in low and middle income countries.

PubMed

Jagannathan, Ram; Patzer, Rachel E

2017-08-29

Urbanization is expected to increase in low and middle-income countries (LMICs), and might contribute to the increased disease burden. The association between urbanization and CKD is incompletely understood among LMICs. Recently, Inoue et al., explored the association of urbanization on renal function from the China Health and Nutrition Survey. The study found that individuals living in an urban environment had a higher odds of reduced renal function independent of behavioral and cardiometabolic measures, and this effect increased in a dose dependent manner. In this commentary, we discuss the results of these findings and explain the need for more surveillance studies among LMICs.

Androgens and menopause.

PubMed

Shulman, L P

2009-12-01

The cessation of ovarian sex steroidigenesis, either as result as surgical extirpation, certain medical therapies or the gradual cessation of ovarian function, leads to menopause with all its associated physiological, physical and lifestyle changes. The changing hormonal milieu of menopause is most commonly associated with declining levels of estrogens. However, ovarian senescence also results in declining levels of androgens. Indeed, it is the loss of physiological levels of estrogens and androgens that result in the varied signs and symptoms of menopause including vasomotor symptoms, bone mineral density loss, reduced interest in sex, alterations in mood and energy and hair loss, among others. This paper will provide a review of the role of androgens in the menopause and assess the potential of androgen therapies in the management of the menopause.

Self-rated health is associated with subsequent functional decline among older adults in Japan.

PubMed

Hirosaki, Mayumi; Okumiya, Kiyohito; Wada, Taizo; Ishine, Masayuki; Sakamoto, Ryota; Ishimoto, Yasuko; Kasahara, Yoriko; Kimura, Yumi; Fukutomi, Eriko; Chen, Wen Ling; Nakatsuka, Masahiro; Fujisawa, Michiko; Otsuka, Kuniaki; Matsubayashi, Kozo

2017-09-01

Previous studies have reported that self-rated health (SRH) predicts subsequent mortality. However, less is known about the association between SRH and functional ability. The aim of this study was to examine whether SRH predicts decline in basic activities of daily living (ADL), even after adjustment for depression, among community-dwelling older adults in Japan. A three-year prospective cohort study was conducted among 654 residents aged 65 years and older without disability in performing basic ADL at baseline. SRH was assessed using a visual analogue scale (range; 0-100), and dichotomized into low and high groups. Information on functional ability, sociodemographic factors, depressive symptoms, and medical conditions were obtained using a self-administered questionnaire. Logistic regression analysis was used to examine the association between baseline SRH and functional decline three years later. One hundred and eight (16.5%) participants reported a decline in basic ADL at the three-year follow-up. Multiple logistic regression analysis showed that the low SRH group had a higher risk for functional decline compared to the high SRH group, even after controlling for potential confounding factors (odds ratio (OR) = 2.4; 95% confidence interval (CI) = 1.3-4.4). Furthermore, a 10-point difference in SRH score was associated with subsequent functional decline (OR = 1.37; 95% CI = 1.16-1.61). SRH was an independent predictor of functional decline. SRH could be a simple assessment tool for predicting the loss or maintenance of functional ability in community-dwelling older adults. Positive self-evaluation might be useful to maintain an active lifestyle and stay healthy.

The effect on physical performance of a functional assessment and immediate rehabilitation of acutely admitted elderly patients with reduced functional performance: the design of a randomised clinical trial

PubMed Central

Bruun, Inge Hansen; Nørgaard, Birgitte; Maribo, Thomas; Schiøttz-Christensen, Berit; Mogensen, Christian Backer

2014-01-01

Introduction Illness and hospitalisation, even of short duration, pose separate risks for permanently reduced functional performance in elderly medical patients. Functional assessment in the acute pathway will ensure early detection of declining performance and form the basis for mobilisation during hospitalisation and subsequent rehabilitation. For optimal results rehabilitation should begin immediately after discharge.The aim of this study is to investigate the effect of a systematic functional assessment in the emergency department (ED) of elderly medical patients with reduced functional performance when combined with immediate postdischarge rehabilitation. Method and analysis The study is a two-way factorial randomised clinical trial. Participants will be recruited among patients admitted to the ED who are above 65 years of age with reduced functional performance. Patients will be randomly assigned to one of four groups: (1) functional assessment and immediate rehabilitation; (2) functional assessment and rehabilitation as usual; (3) assessment as usual and immediate rehabilitation; (4) assessment and rehabilitation as usual. Primary outcome 30 s chair-stand test administered at admission and 3 weeks after discharge. Ethics and dissemination The study has been approved by the Regional Scientific Ethical Committees of Southern Denmark in February 2014. The study findings will be published in peer-reviewed journals and presented at national and international conferences. Trial registration number: ClinicalTrials.gov Identifier: NCT02062541. PMID:24939812

Association between Soluble Klotho and Change in Kidney Function: The Health Aging and Body Composition Study.

PubMed

Drew, David A; Katz, Ronit; Kritchevsky, Stephen; Ix, Joachim; Shlipak, Michael; Gutiérrez, Orlando M; Newman, Anne; Hoofnagle, Andy; Fried, Linda; Semba, Richard D; Sarnak, Mark

2017-06-01

CKD appears to be a condition of soluble klotho deficiency. Despite known associations between low soluble klotho levels and conditions that promote kidney damage, such as oxidative stress and fibrosis, little information exists regarding the longitudinal association between soluble klotho levels and change in kidney function. We assayed serum soluble α -klotho in 2496 participants within the Health Aging and Body Composition study, a cohort of older adults. The associations between soluble klotho levels and decline in kidney function (relative decline: eGFR decline ≥30%; absolute decline: eGFR decline >3 ml/min per year) and incident CKD (incident eGFR <60 ml/min per 1.73 m 2 and >1 ml/min per year decline) were evaluated. We adjusted models for demographics, baseline eGFR, urine albumin-to-creatinine ratio, comorbidity, and measures of mineral metabolism. Among participants, the mean (SD) age was 75 (3) years, 52% were women, and 38% were black. Median (25th, 75th percentiles) klotho level was 630 (477, 817) pg/ml. In fully adjusted models, each two-fold higher level of klotho associated with lower odds of decline in kidney function (odds ratio, 0.78 [95% confidence interval, 0.66 to 0.93] for 30% decline in eGFR, and 0.85 [95% confidence interval, 0.73 to 0.98] for >3 ml/min per year decline in eGFR), but not of incident CKD (incident rate ratio, 0.90 [95% confidence interval, 0.78 to 1.04]). Overall, a higher soluble klotho level independently associated with a lower risk of decline in kidney function. Future studies should attempt to replicate these results in other cohorts and evaluate the underlying mechanism. Copyright © 2017 by the American Society of Nephrology.

Decline of kidney function during the pre-dialysis period in chronic kidney disease patients: a systematic review and meta-analysis.

PubMed

Janmaat, Cynthia J; van Diepen, Merel; van Hagen, Cheyenne Ce; Rotmans, Joris I; Dekker, Friedo W; Dekkers, Olaf M

2018-01-01

Substantial heterogeneity exists in reported kidney function decline in pre-dialysis chronic kidney disease (CKD). By design, kidney function decline can be studied in CKD 3-5 cohorts or dialysis-based studies. In the latter, patients are selected based on the fact that they initiated dialysis, possibly leading to an overestimation of the true underlying kidney function decline in the pre-dialysis period. We performed a systematic review and meta-analysis to compare the kidney function decline during pre-dialysis in CKD stage 3-5 patients, in these two different study types. We searched PubMed, EMBASE, Web of Science and Cochrane to identify eligible studies reporting an estimated glomerular filtration rate (eGFR) decline (mL/min/1.73 m 2 ) in adult pre-dialysis CKD patients. Random-effects meta-analysis was performed to obtain weighted mean annual eGFR decline. We included 60 studies (43 CKD 3-5 cohorts and 17 dialysis-based studies). The meta-analysis yielded a weighted annual mean (95% CI) eGFR decline during pre-dialysis of 2.4 (95% CI: 2.2, 2.6) mL/min/1.73 m 2 in CKD 3-5 cohorts compared to 8.5 (95% CI: 6.8, 10.1) in dialysis-based studies (difference 6.0 [95% CI: 4.8, 7.2]). To conclude, dialysis-based studies report faster mean annual eGFR decline during pre-dialysis than CKD 3-5 cohorts. Thus, eGFR decline data from CKD 3-5 cohorts should be used to guide clinical decision making in CKD patients and for power calculations in randomized controlled trials with CKD progression during pre-dialysis as the outcome.

Abrupt Decline in Kidney Function Before Initiating Hemodialysis and All-Cause Mortality: The Chronic Renal Insufficiency Cohort (CRIC) Study.

PubMed

Hsu, Raymond K; Chai, Boyang; Roy, Jason A; Anderson, Amanda H; Bansal, Nisha; Feldman, Harold I; Go, Alan S; He, Jiang; Horwitz, Edward J; Kusek, John W; Lash, James P; Ojo, Akinlolu; Sondheimer, James H; Townsend, Raymond R; Zhan, Min; Hsu, Chi-Yuan

2016-08-01

It is not clear whether the pattern of kidney function decline in patients with chronic kidney disease (CKD) may relate to outcomes after reaching end-stage renal disease (ESRD). We hypothesize that an abrupt decline in kidney function prior to ESRD predicts early death after initiating maintenance hemodialysis therapy. Prospective cohort study. The Chronic Renal Insufficiency Cohort (CRIC) Study enrolled men and women with mild to moderate CKD. For this study, we studied 661 individuals who developed chronic kidney failure that required hemodialysis therapy initiation. The primary predictor was the presence of an abrupt decline in kidney function prior to ESRD. We incorporated annual estimated glomerular filtration rates (eGFRs) into a mixed-effects model to estimate patient-specific eGFRs at 3 months prior to initiation of hemodialysis therapy. Abrupt decline was defined as having an extrapolated eGFR≥30mL/min/1.73m(2) at that time point. All-cause mortality within 1 year after initiating hemodialysis therapy. Multivariable Cox proportional hazards. Among 661 patients with CKD initiating hemodialysis therapy, 56 (8.5%) had an abrupt predialysis decline in kidney function and 69 died within 1 year after initiating hemodialysis therapy. After adjustment for demographics, cardiovascular disease, diabetes, and cancer, abrupt decline in kidney function was associated with a 3-fold higher risk for death within the first year of ESRD (adjusted HR, 3.09; 95% CI, 1.65-5.76). Relatively small number of outcomes; infrequent (yearly) eGFR determinations; lack of more granular clinical data. Abrupt decline in kidney function prior to ESRD occurred in a significant minority of incident hemodialysis patients and predicted early death in ESRD. Copyright © 2016 National Kidney Foundation, Inc. All rights reserved.

Obesity and Functioning Among Individuals with Chronic Obstructive Pulmonary Disease (COPD).

PubMed

Katz, Patricia; Iribarren, Carlos; Sanchez, Gabriela; Blanc, Paul D

2016-06-01

In COPD, body composition studies have focused primarily on low BMI. We examined obesity (BMI ≥ 30 kg/m(2)) as a risk factor for poor function and longitudinal functional decline. Data from a longitudinal cohort of adults with COPD (n = 1096) and an age- and sex-matched comparison group collected in two in-person visits ∼49 months apart were analyzed. Two measures of functioning were examined: six-minute walk distance (6MWD) and Short Physical Performance Battery (SPPB). Multivariate regression analyses examined relationships of obesity with functioning. Secondary analyses stratified by GOLD classification (GOLD-0/1, GOLD-2, GOLD-3/4). Obesity (53% of COPD cohort) was associated cross-sectionally with 6MWD and SPPB in COPD, and only with 6MWD in the comparison group. Obesity predicted significant functional decline in 6MWD for individuals with COPD (odds ratio (OR) for decline [95% CI] 1.8 [1.1, 2.9]), but not the comparison group. Secondary analyses revealed that the risk of decline was significant only in those with more severe COPD (GOLD 3/4, OR = 2.3 [1.0, 5.4]). Obesity was highly prevalent and was associated with poor function concurrently and with subsequent decline in 6MWD in COPD. Obesity in COPD should be considered a risk not only for more co-morbidities and greater health care use, but also for functional decline.

Effects of almond consumption on the post-lunch dip and long-term cognitive function in energy-restricted overweight and obese adults.

PubMed

Dhillon, Jaapna; Tan, Sze-Yen; Mattes, Richard D

2017-02-01

The post-lunch dip in cognition is a well-established phenomenon of decreased alertness, memory and vigilance after lunch consumption. Lunch composition reportedly influences the post-lunch dip. Moreover, dieting is associated with cognitive function impairments. The negative effects of dieting have been reversed with nut-supplemented diets. The aims of this study were to (1) evaluate the acute effect of an almond-enriched high-fat lunch or high-carbohydrate lunch on the post-lunch decline in cognitive function, and (2) evaluate the effects of chronic almond consumption as part of an energy-restricted diet on the memory and attention domains of cognitive function. In total, eighty-six overweight and obese adults were randomised to consume either an almond-enriched diet (AED) or a nut-free control diet (NFD) over a 12-week weight loss intervention. Participants were also randomised to receive either an almond-enriched high-fat lunch (A-HFL) (>55 % energy from fat, almonds contributing 70-75 % energy) or a high-carbohydrate lunch (HCL) (>85 % energy from carbohydrates) at the beginning and end of the weight loss intervention. Memory and attention performance indices decreased after lunch consumption (P<0·001). The A-HFL group ameliorated the decline in memory scores by 57·7 % compared with the HCL group (P=0·004). Both lunch groups had similar declines in attention. Moreover, memory and attention performance indices increased after the 12-week intervention period (P<0·05) with no difference between the AED and NFD groups. In conclusion, almond consumption at a midday meal can reduce the post-lunch dip in memory. However, long-term almond consumption may not further improve cognitive function outcomes in a weight loss intervention.

The Contribution of Generative Leisure Activities to Cognitive Function among Sri Lankan Elderly

PubMed Central

Maselko, Joanna; Sebranek, Matthew; Mun, Mirna Hodzic; Perera, Bilesha; Ahs, Jill; Østbye, Truls

2014-01-01

OBJECTIVES Although a substantive body of research has shown a protective association between leisure activities and cognitive function, consistent evidence is lacking about which specific types of activities should be promoted. The objective of this analysis was to examine the unique contribution of generative leisure activities, defined as activities motivated by “a concern for others and a need to contribute something to the next generation” (Erikson). DESIGN Cross-sectional survey. SETTING Peri-urban and rural area in southern Sri Lanka. PARTICIPANTS Community dwelling adults aged 60+ (n=252). MEASUREMENTS Main predictors were leisure activities grouped into generative, social, or solitary. Main outcome was cognitive function assessed with Montreal Cognitive Assessment (MoCA) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). RESULTS We found that more frequent engagement in generative leisure activities was associated with higher levels of cognitive function, independent of the impact of other social and solitary leisure activities. In a fully adjusted model combining all three leisure activities, generative activities independently predicted cognitive function as measured with the MoCA (β =0.47 (0.11 to 0.83) and the IQCODE (β = -0.81 (-1.54 to -0.09)). In this combined model, solitary activities were also independently associated with slower cognitive decline with the MoCA (β =0.40 (0.16, 0.64), but not with IQCODE (β =-0.38 (-0.88, 0.12)); the association with social activities did not reach statistical significance with either measure. These associations did not differ meaningfully by gender. CONCLUSION Generative leisure activities are a promising area for the development of interventions aimed at reducing cognitive decline among the elderly. PMID:25139145

Association Between Years of Competition and Shoulder Function in Collegiate Swimmers.

PubMed

Dischler, Jack D; Baumer, Timothy G; Finkelstein, Evan; Siegal, Daniel S; Bey, Michael J

Shoulder injuries are common among competitive swimmers, and the progression of shoulder pathology is not well understood. The objective of this study was to assess the extent to which years of competitive swim training were associated with physical properties of the supraspinatus muscle and tendon, shoulder strength, and self-reported assessments of shoulder pain and function. Increasing years of competition will be associated with declining physical properties of the supraspinatus muscle/tendon and declining self-reported assessments of pain and function. Descriptive epidemiology study. Level 4. After institutional approval, 18 collegiate female swimmers enrolled in the study. For each swimmer, supraspinatus tendon thickness was measured; tendinosis was assessed using ultrasound imaging, supraspinatus muscle shear wave velocity was assessed using shear wave elastography, isometric shoulder strength was measured using a Biodex system, and self-reported assessments of pain/function were assessed using the Western Ontario Rotator Cuff (WORC) score. All subjects were tested before the start of the collegiate swim season. Linear regression was used to assess the association between years of competition and the outcome measures. Years of participation was positively associated with tendon thickness ( P = 0.01) and negatively associated with shear wave velocity ( P = 0.04) and WORC score ( P < 0.01). Shoulder strength was not associated with years of participation ( P > 0.39). Long-term competitive swim training is associated with declining measures of supraspinatus muscle/tendon properties and self-reported measures of pain and function. Although specific injury mechanisms are still not fully understood, these findings lend additional insight into the development of rotator cuff pathology in swimmers. Lengthy swimming careers may lead to a chronic condition of reduced mechanical properties in the supraspinatus muscle and tendon, thereby increasing the likelihood of rotator cuff pathology.

Cerebroprotective effect of piracetam in patients undergoing open heart surgery.

PubMed

Holinski, Sebastian; Claus, Benjamin; Alaaraj, Nour; Dohmen, Pascal Maria; Neumann, Konrad; Uebelhack, Ralf; Konertz, Wolfgang

2011-01-01

Reduction of cognitive function is a possible side effect after the use of cardiopulmonary bypass (CPB) during cardiac surgery. Since it has been proven that piracetam is cerebroprotective in patients undergoing coronary bypass surgery, we investigated the effects of piracetam on the cognitive performance of patients undergoing open heart surgery. Patients scheduled for elective open heart surgery were randomized to the piracetam or placebo group in a double-blind study. Patients received 12 g of piracetam or placebo at the beginning of the operation. Six neuropsychological subtests from the Syndrom Kurz Test and the Alzheimer's Disease Assessment Scale were performed preoperatively and on day 3, postoperatively. To assess the overall cognitive function and the degree of cognitive decline across all tests after the surgery, we combined the six test-scores by principal component analysis. A total of 88 patients with a mean age of 67 years were enrolled into the study. The mean duration of CPB was 110 minutes. Preoperative clinical parameters and overall cognitive functions were not significantly different between the groups. The postoperative combined score of the neuropsychological tests showed deterioration of cognitive function in both groups (piracetam: preoperative 0.19 ± 0.97 vs. postoperative -0.97 ± 1.38, p <0.0005 and placebo: preoperative -0.14 ± 0.98 vs. postoperative -1.35 ± 1.23, p <0.0005). Patients taking piracetam did not perform better than those taking placebo, and both groups had the same decline of overall cognitive function (p = 0.955). Piracetam had no cerebroprotective effect in patients undergoing open heart surgery. Unlike the patients who underwent coronary surgery, piracetam did not reduce the early postoperative decline of neuropsychological abilities in heart valve patients.

Molecular and biological hallmarks of ageing.

PubMed

Aunan, J R; Watson, M M; Hagland, H R; Søreide, K

2016-01-01

Ageing is the inevitable time-dependent decline in physiological organ function that eventually leads to death. Age is a major risk factor for many of the most common medical conditions, such as cardiovascular disease, cancer, diabetes and Alzheimer's disease. This study reviews currently known hallmarks of ageing and their clinical implications. A literature search of PubMed/MEDLINE was conducted covering the last decade. Average life expectancy has increased dramatically over the past century and is estimated to increase even further. Maximum longevity, however, appears unchanged, suggesting a universal limitation to the human organism. Understanding the underlying molecular processes of ageing and health decline may suggest interventions that, if used at an early age, can prevent, delay, alleviate or even reverse age-related diseases. Hallmarks of ageing can be grouped into three main categories. The primary hallmarks cause damage to cellular functions: genomic instability, telomere attrition, epigenetic alterations and loss of proteostasis. These are followed by antagonistic responses to such damage: deregulated nutrient sensing, altered mitochondrial function and cellular senescence. Finally, integrative hallmarks are possible culprits of the clinical phenotype (stem cell exhaustion and altered intercellular communication), which ultimately contribute to the clinical effects of ageing as seen in physiological loss of reserve, organ decline and reduced function. The sum of these molecular hallmarks produces the clinical picture of the elderly surgical patient: frailty, sarcopenia, anaemia, poor nutrition and a blunted immune response system. Improved understanding of the ageing processes may give rise to new biomarkers of risk or prognosis, novel treatment targets and translational approaches across disciplines that may improve outcomes. © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

Cognitive changes in people with temporal lobe epilepsy over a 13-year period.

PubMed

Mameniškienė, Rūta; Rimšienė, Justė; Puronaitė, Roma

2016-10-01

The aims of our study were to evaluate cognitive decline in people with temporal lobe epilepsy over a period of 13years and to determine what clinical and treatment characteristics may have been associated with these. Thirty-three individuals with temporal lobe epilepsy underwent the same neuropsychological assessment of verbal and nonverbal memory, attention, and executive functions using the same cognitive test battery as one used 13years ago. Long-term verbal and nonverbal memory was tested four weeks later. Results were compared with those carried out 13years earlier. There was no significant change in verbal and verbal-logical memory tests; however, nonverbal memory worsened significantly. Long-term verbal memory declined for 21.9% of participants, long-term verbal-logical memory for 34.4%, and long-term nonverbal memory for 56.3%. Worsening of working verbal and verbal-logical memory was associated with longer epilepsy duration and lower levels of patients' education; worsening of verbal delayed recall and long-term verbal-logical memory was associated with higher seizure frequency. Decline in long-term nonverbal memory had significant association with a longer duration of epilepsy. The worsening of reaction and attention inversely correlated with the symptoms of depression. Over a 13-year period, cognitive functions did not change significantly. Good seizure control and reduced symptoms of depression in this sample of people with temporal lobe epilepsy were associated with better cognitive functioning. The predictors of change of cognitive functions could be complex and require further study. Copyright © 2016 Elsevier Inc. All rights reserved.

Renal function decline predicted by left atrial expansion index in non-diabetic cohort with preserved systolic heart function.

PubMed

Hsiao, Shih-Hung; Chiou, Kuan-Rau

2017-05-01

Since natriuretic peptide and troponin are associated with renal prognosis and left atrial (LA) parameters are indicators of subclinical cardiovascular abnormalities, this study investigated whether LA expansion index can predict renal decline. This study analysed 733 (69% male) non-diabetic patients with sinus rhythm, preserved systolic function, and estimated glomerular filtration rate (eGFR) higher than 60 mL/min/1.73 m2. In all patients, echocardiograms were performed and LA expansion index was calculated. Renal function was evaluated annually. The endpoint was a downhill trend in renal function with a final eGFR of <60 mL/min/1.73 m2. Rapid renal decline was defined as an annual decline in eGFR >3 mL/min/1.73 m2. The median follow-up time was 5.2 years, and 57 patients (7.8%) had renal function declines (19 had rapid renal declines, and 38 had incidental renal dysfunction). Events were associated with left ventricular mass index, LA expansion index, and heart failure during the follow-up period. The hazard ratio was 1.426 (95% confidence interval, 1.276-1.671; P < 0.0001) per 10% decrease in LA expansion index and was independently associated with an increased event rate. Compared with the highest quartile for the LA expansion index, the lowest quartile had a 9.7-fold risk of renal function decline in the unadjusted model and a 6.9-fold risk after adjusting for left ventricular mass index and heart failure during the follow-up period. Left atrial expansion index is a useful early indicator of renal function decline and may enable the possibility of early intervention to prevent renal function from worsening. NCT01171040. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

The Influence of Executive Functioning on Facial and Subjective Pain Responses in Older Adults

PubMed Central

2016-01-01

Cognitive decline is known to reduce reliability of subjective pain reports. Although facial expressions of pain are generally considered to be less affected by this decline, empirical support for this assumption is sparse. The present study therefore examined how cognitive functioning relates to facial expressions of pain and whether cognition acts as a moderator between nociceptive intensity and facial reactivity. Facial and subjective responses of 51 elderly participants to mechanical stimulation at three intensities levels (50 kPa, 200 kPa, and 400 kPa) were assessed. Moreover, participants completed a neuropsychological examination of executive functioning (planning, cognitive inhibition, and working memory), episodic memory, and psychomotor speed. The results showed that executive functioning has a unique relationship with facial reactivity at low pain intensity levels (200 kPa). Moreover, cognitive inhibition (but not other executive functions) moderated the effect of pressure intensity on facial pain expressions, suggesting that the relationship between pressure intensity and facial reactivity was less pronounced in participants with high levels of cognitive inhibition. A similar interaction effect was found for cognitive inhibition and subjective pain report. Consequently, caution is needed when interpreting facial (as well as subjective) pain responses in individuals with a high level of cognitive inhibition. PMID:27274618

Eicosapentaenoic acid but not docosahexaenoic acid restores skeletal muscle mitochondrial oxidative capacity in old mice

PubMed Central

Johnson, Matthew L; Lalia, Antigoni Z; Dasari, Surendra; Pallauf, Maximilian; Fitch, Mark; Hellerstein, Marc K; Lanza, Ian R

2015-01-01

Mitochondrial dysfunction is often observed in aging skeletal muscle and is implicated in age-related declines in physical function. Early evidence suggests that dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) improve mitochondrial function. Here, we show that 10 weeks of dietary eicosapentaenoic acid (EPA) supplementation partially attenuated the age-related decline in mitochondrial function in mice, but this effect was not observed with docosahexaenoic acid (DHA). The improvement in mitochondrial function with EPA occurred in the absence of any changes in mitochondrial abundance or biogenesis, which was evaluated from RNA sequencing, large-scale proteomics, and direct measurements of muscle mitochondrial protein synthesis rates. We find that EPA improves muscle protein quality, specifically by decreasing mitochondrial protein carbamylation, a post-translational modification that is driven by inflammation. These results demonstrate that EPA attenuated the age-related loss of mitochondrial function and improved mitochondrial protein quality through a mechanism that is likely linked with anti-inflammatory properties of n-3 PUFAs. Furthermore, we demonstrate that EPA and DHA exert some common biological effects (anticoagulation, anti-inflammatory, reduced FXR/RXR activation), but also exhibit many distinct biological effects, a finding that underscores the importance of evaluating the therapeutic potential of individual n-3 PUFAs. PMID:26010060

Hierarchy and Speed of Loss in Physical Functioning: A Comparison Across Older U.S. and English Men and Women.

PubMed

Bendayan, Rebecca; Cooper, Rachel; Wloch, Elizabeth G; Hofer, Scott M; Piccinin, Andrea M; Muniz-Terrera, Graciela

2017-08-01

We aimed to identify the hierarchy of rates of decline in 16 physical functioning measures in U.S. and English samples, using a systematic and integrative coordinated data analysis approach. The U.S. sample consisted of 13,612 Health and Retirement Study participants, and the English sample consisted of 5,301 English Longitudinal Study of Ageing participants. Functional loss was ascertained using self-reported difficulties performing 6 activities of daily living and 10 mobility tasks. The variables were standardized, rates of decline were computed, and mean rates of decline were ranked. Mann-Whitney U tests were performed to compare rates of decline between studies. In both studies, the rates of decline followed a similar pattern; difficulty with eating was the activity that showed the slowest decline and climbing several flights of stairs and stooping, kneeling, or crouching the fastest declines. There were statistical differences in the speed of decline in all 16 measures between countries. American women had steeper declines in 10 of the measures than English women. Similar differences were found between American and English men. Reporting difficulties climbing several flights of stairs without resting, and stooping, kneeling, or crouching are the first indicators of functional loss reported in both populations. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America.

Surgery-Independent Language Function Decline in Patients Undergoing Awake Craniotomy.

PubMed

Gonen, Tal; Sela, Gal; Yanakee, Ranin; Ram, Zvi; Grossman, Rachel

2017-03-01

Despite selection process before awake-craniotomy, some patients experience an unexpected decline in language functions in the operating room (OR), compared with their baseline evaluation, which may impair their functional monitoring. To investigate this phenomenon we prospectively compared language function the day before surgery and on entrance to the OR. Data were collected prospectively from consecutive patients undergoing awake-craniotomy with intraoperative cortical mapping for resection of gliomas affecting language areas. Language functions of 79 patients were evaluated and compared 1-2 days before surgery and after entering the OR. Changes in functional linguistic performance were analyzed with respect to demographic, clinical, and pathologic characteristics. There was a significant decline in language function, beyond sedation effect, after entering the OR, (from median/interquartile range: 0.94/0.72-0.98 to median/interquartile range: 0.86/0.51-0.94; Z = -7.19, P < 0.001). Univariate analyses revealed that this decline was related to age, preoperative Karnofsky Performance Scale, tumor location, tumor pathology, and preexisting language deficits. Multivariate stepwise regression identified tumor pathology and the presence of preoperative language deficit as significant independent predictors for this functional decline. Patients undergoing awake-craniotomy may experience a substantial decline in language functioning after entering the OR. Tumor grade and the presence of preoperative language deficits were significant risk factors for this phenomenon, suggesting a possible relation between cognitive reserve, psychobehavioral coping abilities and histologic features of a tumor involving language areas. Capturing and identifying this unique population of patients who are prone to experience such language decline may improve our ability in the future to select patients eligible for awake-craniotomy. Copyright © 2016 Elsevier Inc. All rights reserved.

Alcohol affects brain functional connectivity and its coupling with behavior: greater effects in male heavy drinkers.

PubMed

Shokri-Kojori, E; Tomasi, D; Wiers, C E; Wang, G-J; Volkow, N D

2017-08-01

Acute and chronic alcohol exposure significantly affect behavior but the underlying neurobiological mechanisms are still poorly understood. Here, we used functional connectivity density (FCD) mapping to study alcohol-related changes in resting brain activity and their association with behavior. Heavy drinkers (HD, N=16, 16 males) and normal controls (NM, N=24, 14 males) were tested after placebo and after acute alcohol administration. Group comparisons showed that NM had higher FCD in visual and prefrontal cortices, default mode network regions and thalamus, while HD had higher FCD in cerebellum. Acute alcohol significantly increased FCD within the thalamus, impaired cognitive and motor functions, and affected self-reports of mood/drug effects in both groups. Partial least squares regression showed that alcohol-induced changes in mood/drug effects were associated with changes in thalamic FCD in both groups. Disruptions in motor function were associated with increases in cerebellar FCD in NM and thalamus FCD in HD. Alcohol-induced declines in cognitive performance were associated with connectivity increases in visual cortex and thalamus in NM, but in HD, increases in precuneus FCD were associated with improved cognitive performance. Acute alcohol reduced 'neurocognitive coupling', the association between behavioral performance and FCD (indexing brain activity), an effect that was accentuated in HD compared with NM. Findings suggest that reduced cortical connectivity in HD contribute to decline in cognitive abilities associated with heavy alcohol consumption, whereas increased cerebellar connectivity in HD may have compensatory effects on behavioral performance. The results reveal how drinking history alters the association between brain FCD and individual differences in behavioral performance.

"The Future Is Ours Too": A Training Process to Enable the Learning Perception and Increase Self-Efficacy in the Use of Tablets in the Elderly

ERIC Educational Resources Information Center

Gatti, Fabiana M.; Brivio, Eleonora; Galimberti, Carlo

2017-01-01

The generational digital divide can be understood as a response to the physical and psychosocial decline of older people. Recently, there has been interest in reducing the generational digital divide because of societal costs, and several studies state that tablets seem to help the elderly due to usability and functions that easily fulfill the…

Fibroblast Growth Factor 23: A Biomarker of Kidney Function Decline.

PubMed

Drew, David A; Katz, Ronit; Kritchevsky, Stephen; Ix, Joachim H; Shlipak, Michael G; Newman, Anne B; Hoofnagle, Andy; Fried, Linda; Sarnak, Mark J; Gutierrez, Orlando M

2018-01-01

Fibroblast growth factor 23 (FGF-23) is a hormone that regulates phosphorus levels and vitamin D metabolism. Previous studies have shown FGF-23 to be a risk factor for incident end-stage renal disease; however, there are less data on the association of FGF-23 with earlier kidney-related outcomes. Serum FGF-23 was assayed using an intact ELISA assay in 2,496 participants of the Healthy Aging and Body Composition Study, a cohort of well-functioning older adults. Kidney function was estimated by assaying cystatin C at baseline and years 3 and 10. The associations between FGF-23 and decline in kidney function (defined by estimated glomerular filtration rate (eGFR) decline ≥30% or ≥3 mL/min/year) and incident chronic kidney disease (CKD; incident eGFR <60 mL/min/1.73 m2 and ≥1 mL/min/year decline) were evaluated. Models were adjusted for demographics, baseline eGFR, urine albumin/creatinine ratio, comorbidity, and serum calcium, phosphorus, 25(OH) vitamin D and parathyroid hormone. The mean (SD) age was 75 (3) years, with 52% female and 38% black. There were 405 persons with 30% decline, 702 with >3 mL/min/year decline, and 536 with incident CKD. In fully adjusted continuous models, doubling of FGF-23 concentrations was not associated with kidney function decline (OR [95% CI] = 0.98 [0.82-1.19] for ≥30% decline and OR 1.17 [95% CI 1.00-1.37] for ≥3 mL/min/year decline), or incident CKD (incident rate ratio [IRR] 1.05 [95% CI 0.91-1.22]). In adjusted quartile analysis, the highest quartile of FGF-23 was significantly associated with incident CKD (IRR 1.27 [95% CI 1.02-1.58] for highest vs. lowest quartile). Higher FGF-23 concentrations were not consistently associated with decline in kidney function or incident CKD in community-dwelling older adults. © 2018 S. Karger AG, Basel.

Self-Assessed Hearing Handicap in Older Adults With Poorer-Than-Predicted Speech Recognition in Noise.

PubMed

Eckert, Mark A; Matthews, Lois J; Dubno, Judy R

2017-01-01

Even older adults with relatively mild hearing loss report hearing handicap, suggesting that hearing handicap is not completely explained by reduced speech audibility. We examined the extent to which self-assessed ratings of hearing handicap using the Hearing Handicap Inventory for the Elderly (HHIE; Ventry & Weinstein, 1982) were significantly associated with measures of speech recognition in noise that controlled for differences in speech audibility. One hundred sixty-two middle-aged and older adults had HHIE total scores that were significantly associated with audibility-adjusted measures of speech recognition for low-context but not high-context sentences. These findings were driven by HHIE items involving negative feelings related to communication difficulties that also captured variance in subjective ratings of effort and frustration that predicted speech recognition. The average pure-tone threshold accounted for some of the variance in the association between the HHIE and audibility-adjusted speech recognition, suggesting an effect of central and peripheral auditory system decline related to elevated thresholds. The accumulation of difficult listening experiences appears to produce a self-assessment of hearing handicap resulting from (a) reduced audibility of stimuli, (b) declines in the central and peripheral auditory system function, and (c) additional individual variation in central nervous system function.

Self-Assessed Hearing Handicap in Older Adults With Poorer-Than-Predicted Speech Recognition in Noise

PubMed Central

Matthews, Lois J.; Dubno, Judy R.

2017-01-01

Purpose Even older adults with relatively mild hearing loss report hearing handicap, suggesting that hearing handicap is not completely explained by reduced speech audibility. Method We examined the extent to which self-assessed ratings of hearing handicap using the Hearing Handicap Inventory for the Elderly (HHIE; Ventry & Weinstein, 1982) were significantly associated with measures of speech recognition in noise that controlled for differences in speech audibility. Results One hundred sixty-two middle-aged and older adults had HHIE total scores that were significantly associated with audibility-adjusted measures of speech recognition for low-context but not high-context sentences. These findings were driven by HHIE items involving negative feelings related to communication difficulties that also captured variance in subjective ratings of effort and frustration that predicted speech recognition. The average pure-tone threshold accounted for some of the variance in the association between the HHIE and audibility-adjusted speech recognition, suggesting an effect of central and peripheral auditory system decline related to elevated thresholds. Conclusion The accumulation of difficult listening experiences appears to produce a self-assessment of hearing handicap resulting from (a) reduced audibility of stimuli, (b) declines in the central and peripheral auditory system function, and (c) additional individual variation in central nervous system function. PMID:28060993

A 6-year Longitudinal Study of Self-harm and Suicidal Behaviors among Chinese Adolescents in Hong Kong.

PubMed

Law, Ben M F; Shek, Daniel T L

2016-02-01

To examine the trajectories of self-harm and suicidal behaviors among Chinese adolescents in Hong Kong and to investigate the related predictors, including gender, family nonintactness, economic disadvantage, positive youth development, and family functioning. We used quantitative data from a large sample of adolescent participants. Participants initially joined this study when they were in grade 7 (wave 1), and they were followed from grade 8 (wave 2) to grade 12 (wave 6). The participants consisted of 2023 grade 12 students from 28 secondary schools in Hong Kong. A multistage cluster random sampling method was adopted. Self-harm and suicidal behaviors. The trajectories of self-harm and suicidal behaviors in general declined from grade 7 to grade 12. Regarding the effect of gender, whereas adolescent girls showed a higher prevalence for self-harm and suicidal behaviors at baseline and other waves, adolescent boys showed a pronounced decline in self-harm rates. Adolescents from nonintact families were more likely to self-harm or engage in suicidal behaviors at wave 6. Economic disadvantage at wave 4 predicted higher suicidal behavior among adolescents but not self-harm at wave 6. Regarding positive youth development, several protective factors that include cognitive-behavioral competencies, prosocial attributes, general positive youth development qualities, and positive identity could help reduce self-harm and suicidal behaviors at different time points. Regarding the role of family functioning, more family conflicts predicted higher suicidality in adolescence (self-harm and suicidal behaviors), and family communication affected self-harming behaviors at wave 6. The trajectories of self-harm and suicidal behaviors decline from early to late adolescence among Chinese adolescents. Positive youth development and constructive family functioning are critical to help reduce suicidal behaviors. Regarding increased risk, more attention should be paid to adolescent girls and adolescents from nonintact and economic disadvantaged families. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Categorizing natural history trajectories of ambulatory function measured by the 6-minute walk distance in patients with Duchenne muscular dystrophy.

PubMed

Mercuri, Eugenio; Signorovitch, James Edward; Swallow, Elyse; Song, Jinlin; Ward, Susan J

2016-09-01

High variability in patients' changes in 6 minute walk distance (6MWD) over time has complicated clinical trials of treatment efficacy in Duchenne muscular dystrophy (DMD). We assessed whether boys with DMD could be grouped into classes that shared similar ambulatory function trajectories as measured by 6MWD. Ambulatory boys aged 5 years or older with genetically confirmed DMD who were enrolled in a natural history study at 11 care centers throughout Italy were included. For each boy, standardized assessments of 6MWD were available at annual intervals spanning 3 years. Trajectories of 6MWD vs. age and trajectories of 6MWD vs. time from enrollment were examined using latent class analysis. A total of 96 boys were included. At enrollment, the mean age was 8.3 years (mean 6MWD: 374 meters). After accounting for age, baseline 6MWD, and steroid use, four latent trajectory classes were identified as explaining 3-year 6MWD outcomes significantly better than a single average trajectory. Patient trajectories of 6MWD change from enrollment were categorized as having fast decline (n = 25), moderate decline (n = 19), stable function (n = 37), and improving function (n = 15) during the 3-year follow-up. After accounting for trajectory classes, the standard deviation of variation in 6MWD was reduced by approximately 40%. The natural history of ambulatory function in DMD may be composed of distinct trajectory classes. The extent to which trajectories are associated with novel and established prognostic factors warrants further study. Reducing unexplained variation in patient outcomes could help to further improve DMD clinical trial design and analysis. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Use and Adoption of an Assisted Cognition System to Support Therapies for People with Dementia.

PubMed

Navarro, René F; Rodríguez, Marcela D; Favela, Jesús

2016-01-01

The cognitive deficits in persons with dementia (PwD) can produce significant functional impairment from early stages. Although memory decline is most prominent, impairments in attention, orientation, language, reasoning, and executive functioning are also common. Dementia is also characterized by changes in personality and behavioral functioning that can be very challenging for caregivers and patients. This paper presents results on the use and adoption of an assisted cognition system to support occupational therapy to address psychological and behavioral symptoms of dementia. During 16 weeks, we conducted an in situ evaluation with two caregiver-PwD dyads to assess the adoption and effectiveness of the system to ameliorate challenging behaviors and reducing caregiver burden. Evaluation results indicate that intervention personalization and a touch-based interface encouraged the adoption of the system, helping reduce challenging behaviors in PwD and caregiver burden.

A systematic review of the role of vitamin insufficiencies and supplementation in COPD.

PubMed

Tsiligianni, Ioanna G; van der Molen, Thys

2010-12-06

Pulmonary inflammation, oxidants-antioxidants imbalance, as well as innate and adaptive immunity have been proposed as playing a key role in the development of COPD. The role of vitamins, as assessed either by food frequency questionnaires or measured in serum levels, have been reported to improve pulmonary function, reduce exacerbations and improve symptoms. Vitamin supplements have therefore been proposed to be a potentially useful additive to COPD therapy. A systematic literature review was performed on the association of vitamins and COPD. The role of vitamin supplements in COPD was then evaluated. The results of this review showed that various vitamins (vitamin C, D, E, A, beta and alpha carotene) are associated with improvement in features of COPD such as symptoms, exacerbations and pulmonary function. High vitamin intake would probably reduce the annual decline of FEV1. There were no studies that showed benefit from vitamin supplementation in improved symptoms, decreased hospitalization or pulmonary function.

Bacopa monnieri as an Antioxidant Therapy to Reduce Oxidative Stress in the Aging Brain

PubMed Central

Simpson, Tamara; Pase, Matthew; Stough, Con

2015-01-01

The detrimental effect of neuronal cell death due to oxidative stress and mitochondrial dysfunction has been implicated in age-related cognitive decline and neurodegenerative disorders such as Alzheimer's disease. The Indian herb Bacopa monnieri is a dietary antioxidant, with animal and in vitro studies indicating several modes of action that may protect the brain against oxidative damage. In parallel, several studies using the CDRI08 extract have shown that extracts of Bacopa monnieri improve cognitive function in humans. The biological mechanisms of this cognitive enhancement are unknown. In this review we discuss the animal studies and in vivo evidence for Bacopa monnieri as a potential therapeutic antioxidant to reduce oxidative stress and improve cognitive function. We suggest that future studies incorporate neuroimaging particularly magnetic resonance spectroscopy into their randomized controlled trials to better understand whether changes in antioxidant status in vivo cause improvements in cognitive function. PMID:26413126

Assessment and management of respiratory function in patients with Duchenne muscular dystrophy: current and emerging options

PubMed Central

LoMauro, Antonella; D’Angelo, Maria Grazia; Aliverti, Andrea

2015-01-01

Duchenne muscular dystrophy (DMD) is an X-linked myopathy resulting in progressive weakness and wasting of all the striated muscles including the respiratory muscles. The consequences are loss of ambulation before teen ages, cardiac involvement and breathing difficulties, the main cause of death. A cure for DMD is not currently available. In the last decades the survival of patients with DMD has improved because the natural history of the disease can be changed thanks to a more comprehensive therapeutic approach. This comprises interventions targeted to the manifestations and complications of the disease, particularly in the respiratory care. These include: 1) pharmacological intervention, namely corticosteroids and idebenone that significantly reduce the decline of spirometric parameters; 2) rehabilitative intervention, namely lung volume recruitment techniques that help prevent atelectasis and slows the rate of decline of pulmonary function; 3) scoliosis treatment, namely steroid therapy that is used to reduce muscle inflammation/degeneration and prolong ambulation in order to delay the onset of scoliosis, being an additional contribution to the restrictive lung pattern; 4) cough assisted devices that improve airway clearance thus reducing the risk of pulmonary infections; and 5) non-invasive mechanical ventilation that is essential to treat nocturnal hypoventilation, sleep disordered breathing, and ultimately respiratory failure. Without any intervention death occurs within the first 2 decades, however, thanks to this multidisciplinary therapeutic approach life expectancy of a newborn with DMD nowadays can be significantly prolonged up to his fourth decade. This review is aimed at providing state-of-the-art methods and techniques for the assessment and management of respiratory function in DMD patients. PMID:26451113

Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology.

PubMed

Insel, Philip S; Mattsson, Niklas; Mackin, R Scott; Schöll, Michael; Nosheny, Rachel L; Tosun, Duygu; Donohue, Michael C; Aisen, Paul S; Jagust, William J; Weiner, Michael W

2016-05-17

To estimate points along the spectrum of β-amyloid pathology at which rates of change of several measures of neuronal injury and cognitive decline begin to accelerate. In 460 patients with mild cognitive impairment (MCI), we estimated the points at which rates of florbetapir PET, fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to baseline CSF Aβ42. Points of initial acceleration in rates of decline were estimated using mixed-effects regression. Rates of neuronal injury and cognitive and even functional decline accelerate substantially before the conventional threshold for amyloid positivity, with rates of florbetapir PET and FDG PET accelerating early. Temporal lobe atrophy rates also accelerate prior to the threshold, but not before the acceleration of cognitive and functional decline. A considerable proportion of patients with MCI would not meet inclusion criteria for a trial using the current threshold for amyloid positivity, even though on average, they are experiencing cognitive/functional decline associated with prethreshold levels of CSF Aβ42. Future trials in early Alzheimer disease might consider revising the criteria regarding β-amyloid thresholds to include the range of amyloid associated with the first signs of accelerating rates of decline. © 2016 American Academy of Neurology.

Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology

PubMed Central

Mattsson, Niklas; Mackin, R. Scott; Schöll, Michael; Nosheny, Rachel L.; Tosun, Duygu; Donohue, Michael C.; Aisen, Paul S.; Jagust, William J.; Weiner, Michael W.

2016-01-01

Objective: To estimate points along the spectrum of β-amyloid pathology at which rates of change of several measures of neuronal injury and cognitive decline begin to accelerate. Methods: In 460 patients with mild cognitive impairment (MCI), we estimated the points at which rates of florbetapir PET, fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to baseline CSF Aβ42. Points of initial acceleration in rates of decline were estimated using mixed-effects regression. Results: Rates of neuronal injury and cognitive and even functional decline accelerate substantially before the conventional threshold for amyloid positivity, with rates of florbetapir PET and FDG PET accelerating early. Temporal lobe atrophy rates also accelerate prior to the threshold, but not before the acceleration of cognitive and functional decline. Conclusions: A considerable proportion of patients with MCI would not meet inclusion criteria for a trial using the current threshold for amyloid positivity, even though on average, they are experiencing cognitive/functional decline associated with prethreshold levels of CSF Aβ42. Future trials in early Alzheimer disease might consider revising the criteria regarding β-amyloid thresholds to include the range of amyloid associated with the first signs of accelerating rates of decline. PMID:27164667

Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Insel, Philip S.; Mattsson, Niklas; Mackin, R. Scott

Objective: Our objective is to estimate points along the spectrum of β-amyloid pathology at which rates of change of several measures of neuronal injury and cognitive decline begin to accelerate. Methods: In 460 patients with mild cognitive impairment (MCI), we estimated the points at which rates of florbetapir PET, fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to baseline CSF Aβ 42. Points of initial acceleration in rates of decline were estimated using mixed-effects regression. Results: Rates of neuronal injury and cognitive and even functional decline accelerate substantially before the conventional threshold for amyloidmore » positivity, with rates of florbetapir PET and FDG PET accelerating early. Temporal lobe atrophy rates also accelerate prior to the threshold, but not before the acceleration of cognitive and functional decline. Conclusions: A considerable proportion of patients with MCI would not meet inclusion criteria for a trial using the current threshold for amyloid positivity, even though on average, they are experiencing cognitive/functional decline associated with prethreshold levels of CSF Aβ 42. Lastly, future trials in early Alzheimer disease might consider revising the criteria regarding β-amyloid thresholds to include the range of amyloid associated with the first signs of accelerating rates of decline.« less

Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology

DOE PAGES

Insel, Philip S.; Mattsson, Niklas; Mackin, R. Scott; ...

2016-04-15

Objective: Our objective is to estimate points along the spectrum of β-amyloid pathology at which rates of change of several measures of neuronal injury and cognitive decline begin to accelerate. Methods: In 460 patients with mild cognitive impairment (MCI), we estimated the points at which rates of florbetapir PET, fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to baseline CSF Aβ 42. Points of initial acceleration in rates of decline were estimated using mixed-effects regression. Results: Rates of neuronal injury and cognitive and even functional decline accelerate substantially before the conventional threshold for amyloidmore » positivity, with rates of florbetapir PET and FDG PET accelerating early. Temporal lobe atrophy rates also accelerate prior to the threshold, but not before the acceleration of cognitive and functional decline. Conclusions: A considerable proportion of patients with MCI would not meet inclusion criteria for a trial using the current threshold for amyloid positivity, even though on average, they are experiencing cognitive/functional decline associated with prethreshold levels of CSF Aβ 42. Lastly, future trials in early Alzheimer disease might consider revising the criteria regarding β-amyloid thresholds to include the range of amyloid associated with the first signs of accelerating rates of decline.« less

Effect of spaceflight on the isotonic contractile properties of single skeletal muscle fibers in the rhesus monkey

NASA Technical Reports Server (NTRS)

Fitts, R. H.; Romatowski, J. G.; Blaser, C.; De La Cruz, L.; Gettelman, G. J.; Widrick, J. J.

2000-01-01

Experiments from both Cosmos and Space Shuttle missions have shown weightlessness to result in a rapid decline in the mass and force of rat hindlimb extensor muscles. Additionally, despite an increased maximal shortening velocity, peak power was reduced in rat soleus muscle post-flight. In humans, declines in voluntary peak isometric ankle extensor torque ranging from 15-40% have been reported following long- and short-term spaceflight and prolonged bed rest. Complete understanding of the cellular events responsible for the fiber atrophy and the decline in force, as well as the development of effective countermeasures, will require detailed knowledge of how the physiological and biochemical processes of muscle function are altered by spaceflight. The specific purpose of this investigation was to determine the extent to which the isotonic contractile properties of the slow- and fast-twitch fiber types of the soleus and gastrocnemius muscles of rhesus monkeys (Macaca mulatta) were altered by a 14-day spaceflight.

Behavioral deficits during early stages of aging in Caenorhabditis elegans result from locomotory deficits possibly linked to muscle frailty.

PubMed Central

Glenn, Charles F.; Chow, David K.; Gami, Minaxi S.; Iser, Wendy B.; Hanselman, Keaton B.; Wolkow, Catherine A.; David, Lawrence; Goldberg, Ilya G.; Cooke, Carol A.

2005-01-01

Many behavioral responses require the coordination of sensory inputs with motor outputs. Aging is associated with progressive declines in both motor function and muscle structure. However, the consequences of age-related motor deficits upon behavior have not been clearly defined. Here, we examined the effects of aging on behavior in the nematode, Caenorhabditis elegans. As animals aged, mild locomotory deficits appeared that were sufficient to impair behavioral responses to sensory cues. In contrast, sensory ability appeared well-maintained during aging. Age-related behavioral declines were delayed in animals with mutations in the daf-2/insulin-like pathway governing longevity. A decline in muscle tissue integrity was correlated with the onset of age-related behavioral deficits, although significant muscle deterioration did not. Treatment with a muscarinic agonist significantly improved locomotory behavior in aged animals, indicating that improved neuromuscular signaling may be one strategy for reducing the severity of age-related behavioral impairments. PMID:15699524

The Tölz Temporal Topography Study: mapping the visual field across the life span. Part II: cognitive factors shaping visual field maps.

PubMed

Poggel, Dorothe A; Treutwein, Bernhard; Calmanti, Claudia; Strasburger, Hans

2012-08-01

Part I described the topography of visual performance over the life span. Performance decline was explained only partly by deterioration of the optical apparatus. Part II therefore examines the influence of higher visual and cognitive functions. Visual field maps for 95 healthy observers of static perimetry, double-pulse resolution (DPR), reaction times, and contrast thresholds, were correlated with measures of visual attention (alertness, divided attention, spatial cueing), visual search, and the size of the attention focus. Correlations with the attentional variables were substantial, particularly for variables of temporal processing. DPR thresholds depended on the size of the attention focus. The extraction of cognitive variables from the correlations between topographical variables and participant age substantially reduced those correlations. There is a systematic top-down influence on the aging of visual functions, particularly of temporal variables, that largely explains performance decline and the change of the topography over the life span.

Neuroprotective Actions of Dietary Choline

PubMed Central

Blusztajn, Jan Krzysztof; Slack, Barbara E.; Mellott, Tiffany J.

2017-01-01

Choline is an essential nutrient for humans. It is a precursor of membrane phospholipids (e.g., phosphatidylcholine (PC)), the neurotransmitter acetylcholine, and via betaine, the methyl group donor S-adenosylmethionine. High choline intake during gestation and early postnatal development in rat and mouse models improves cognitive function in adulthood, prevents age-related memory decline, and protects the brain from the neuropathological changes associated with Alzheimer’s disease (AD), and neurological damage associated with epilepsy, fetal alcohol syndrome, and inherited conditions such as Down and Rett syndromes. These effects of choline are correlated with modifications in histone and DNA methylation in brain, and with alterations in the expression of genes that encode proteins important for learning and memory processing, suggesting a possible epigenomic mechanism of action. Dietary choline intake in the adult may also influence cognitive function via an effect on PC containing eicosapentaenoic and docosahexaenoic acids; polyunsaturated species of PC whose levels are reduced in brains from AD patients, and is associated with higher memory performance, and resistance to cognitive decline. PMID:28788094

Neuroprotective Actions of Dietary Choline.

PubMed

Blusztajn, Jan Krzysztof; Slack, Barbara E; Mellott, Tiffany J

2017-07-28

Choline is an essential nutrient for humans. It is a precursor of membrane phospholipids (e.g., phosphatidylcholine (PC)), the neurotransmitter acetylcholine, and via betaine, the methyl group donor S -adenosylmethionine. High choline intake during gestation and early postnatal development in rat and mouse models improves cognitive function in adulthood, prevents age-related memory decline, and protects the brain from the neuropathological changes associated with Alzheimer's disease (AD), and neurological damage associated with epilepsy, fetal alcohol syndrome, and inherited conditions such as Down and Rett syndromes. These effects of choline are correlated with modifications in histone and DNA methylation in brain, and with alterations in the expression of genes that encode proteins important for learning and memory processing, suggesting a possible epigenomic mechanism of action. Dietary choline intake in the adult may also influence cognitive function via an effect on PC containing eicosapentaenoic and docosahexaenoic acids; polyunsaturated species of PC whose levels are reduced in brains from AD patients, and is associated with higher memory performance, and resistance to cognitive decline.

Citicoline Affects Appetite and Cortico-Limbic Responses to Images of High Calorie Foods

PubMed Central

Killgore, William D. S.; Ross, Amy J.; Kamiya, Toshi; Kawada, Yoko; Renshaw, Perry F.; Yurgelun-Todd, Deborah A.

2011-01-01

Cytidine-5’-diphosphocholine (citicoline) has a variety of cognitive enhancing, neuroprotective, and neuroregenerative properties. In cocaine-addicted individuals, citicoline has been shown to increase brain dopamine levels and reduce cravings. The effects of this compound on appetite, food cravings, and brain responses to food are unknown. We compared the effects of treatment with citicoline (500 mg/day versus 2000 mg/day) for six weeks on changes in appetite ratings, weight, and cortico-limbic responses to images of high calorie foods using functional magnetic resonance imaging (fMRI). After six weeks, there was no significant change in weight status, although significant declines in appetite ratings were observed for the 2000 mg/day group. The higher dose group also showed significant increases in functional brain responses to food stimuli within the amygdala, insula, and lateral orbitofrontal cortex. Increased activation in these regions correlated with declines in appetite ratings. These preliminary findings suggest a potential usefulness of citicoline in modulating appetite, but further research is warranted. PMID:19260039

Altered ovarian function affects skeletal homeostasis independent of the action of follicle-stimulating hormone.

PubMed

Gao, Jianjun; Tiwari-Pandey, Rashmi; Samadfam, Rana; Yang, Yinzhi; Miao, Dengshun; Karaplis, Andrew C; Sairam, M Ram; Goltzman, David

2007-06-01

Osteoporosis is a leading public health problem. Although a major cause in women is thought to be a decline in estrogen, it has recently been proposed that FSH or follitropin is required for osteoporotic bone loss. We examined the FSH receptor null mouse (FORKO mouse) to determine whether altered ovarian function could induce bone loss independent of FSH action. By 3 months of age, FORKO mice developed age-dependent declines in bone mineral density and trabecular bone volume of the lumbar spine and femur, which could be partly reversed by ovarian transplantation. Bilateral ovariectomy reduced elevated circulating testosterone levels in FORKO mice and decreased bone mass to levels indistinguishable from those in ovariectomized wild-type controls. Androgen receptor blockade and especially aromatase inhibition each produced bone volume reductions in the FORKO mouse. The results indicate that ovarian secretory products, notably estrogen, and peripheral conversion of ovarian androgen to estrogen can alter bone homeostasis independent of any bone resorptive action of FSH.

Cortical activation during power grip task with pneumatic pressure gauge: an fMRI study

NASA Astrophysics Data System (ADS)

Mohamad, M.; Mardan, N. H.; Ismail, S. S.

2017-05-01

Aging is associated with a decline in cognitive and motor function. But, the relationships with motor performance are less well understood. In this study, functional magnetic resonance imaging (fMRI) was used to assess cortical activation in older adults. This study employed power grip task that utilised block paradigm consisted of alternate 30s rest and active. A visual cue was used to pace the hand grip movement that clenched a cylindrical rubber bulb connected with pressure pneumatic gauge that measure the pressure (Psi). The objective of this study is determined the brain areas activated during motor task and the correlation between percentage signal change of each motor area (BA 4 and 6) and hand grip pressure. Result showed there was a significant difference in mean percentage signal change in BA 4 and BA 6 in both hemispheres and negative correlation obtained in BA 4 and BA 6. These results indicate that a reduced ability in the motor networks contribute to age-related decline in motor performance.

Fall and Fracture Risk in Sarcopenia and Dynapenia With and Without Obesity: the Role of Lifestyle Interventions.

PubMed

Scott, David; Daly, Robin M; Sanders, Kerrie M; Ebeling, Peter R

2015-08-01

Due to their differing etiologies and consequences, it has been proposed that the term "sarcopenia" should revert to its original definition of age-related muscle mass declines, with a separate term, "dynapenia", describing muscle strength and function declines. There is increasing interest in the interactions of sarcopenia and dynapenia with obesity. Despite an apparent protective effect of obesity on fracture, increased adiposity may compromise bone health, and the presence of sarcopenia and/or dynapenia ("sarcopenic obesity" and "dynapenic obesity") may exacerbate the risk of falls and fracture in obese older adults. Weight loss interventions are likely to be beneficial for older adults with sarcopenic and dynapenic obesity but may result in further reductions in muscle and bone health. The addition of exercise including progressive resistance training and nutritional strategies, including protein and vitamin D supplementation, may optimise body composition and muscle function outcomes thereby reducing falls and fracture risk in this population.

Stem cells and aging from a quasi-immortal point of view.

PubMed

Boehm, Anna-Marei; Rosenstiel, Philip; Bosch, Thomas C G

2013-11-01

Understanding aging and how it affects an organism's lifespan is a fundamental problem in biology. A hallmark of aging is stem cell senescence, the decline of functionality, and number of somatic stem cells, resulting in an impaired regenerative capacity and reduced tissue function. In addition, aging is characterized by profound remodeling of the immune system and a quantitative decline of adequate immune responses, a phenomenon referred to as immune-senescence. Yet, what is causing stem cell and immune-senescence? This review discusses experimental studies of potentially immortal Hydra which have made contributions to answering this question. Hydra transcription factor FoxO has been shown to modulate both stem cell proliferation and innate immunity, lending strong support to a role of FoxO as critical rate-of-aging regulator from Hydra to human. Constructing a model of how FoxO responds to diverse environmental factors provides a framework for how stem cell factors might contribute to aging. © 2013 WILEY Periodicals, Inc.

Climate change and amphibians

USGS Publications Warehouse

Corn, P.S.

2005-01-01

Amphibian life histories are exceedingly sensitive to temperature and precipitation, and there is good evidence that recent climate change has already resulted in a shift to breeding earlier in the year for some species. There are also suggestions that the recent increase in the occurrence of El Niño events has caused declines of anurans in Central America and is linked to elevated mortality of amphibian embryos in the northwestern United States. However, evidence linking amphibian declines in Central America to climate relies solely on correlations, and the mechanisms underlying the declines are not understood. Connections between embryo mortality and declines in abundance have not been demonstrated. Analyses of existing data have generally failed to find a link between climate and amphibian declines. It is likely, however, that future climate change will cause further declines of some amphibian species. Reduced soil moisture could reduce prey species and eliminate habitat. Reduced snowfall and increased summer evaporation could have dramatic effects on the duration or occurrence of seasonal wetlands, which are primary habitat for many species of amphibians. Climate change may be a relatively minor cause of current amphibian declines, but it may be the biggest future challenge to the persistence of many species

Renal function following xenon anesthesia for partial nephrectomy-An explorative analysis of a randomized controlled study.

PubMed

Stevanovic, Ana; Schaefer, Patrick; Coburn, Mark; Rossaint, Rolf; Stoppe, Christian; Boor, Peter; Pfister, David; Heidenreich, Axel; Christ, Hildegard; Hellmich, Martin; Fahlenkamp, Astrid V

2017-01-01

Perioperative preservation of renal function has a significant impact on morbidity and mortality in kidney surgery. Nephroprotective effects of the anesthetic xenon on ischemia-reperfusion injury were found in several experimental studies. We aimed to explore whether xenon anesthesia can reduce renal damage in humans undergoing partial nephrectomy and to gather pilot data of possible nephroprotection in these patients. A prospective randomized, single-blinded, controlled study. Single-center, University Hospital of Aachen, Germany between July 2013-October 2015. Forty-six patients with regular renal function undergoing partial nephrectomy. Patients were randomly assigned to receive xenon- (n = 23) or isoflurane (n = 23) anesthesia. Primary outcome was the maximum postoperative glomerular filtration rate (GFR) decline within seven days after surgery. Secondary outcomes included intraoperative and tumor-related data, assessment of further kidney injury markers, adverse events and optional determination of renal function after 3-6 months. Unexpected radical nephrectomy was performed in 5 patients, thus they were excluded from the per-protocol analysis, but included in the intention-to-treat analysis. The maximum postoperative GFR decline was attenuated by 45% in the xenon-group (10.9 ml min-1 1.73 cm-2 versus 19.7 ml min-1 1.73 cm-2 in the isoflurane group), but without significance (P = 0.084). Occurrence of adverse events was reduced (P = 0.003) in the xenon group. Renal function was similar among the groups after 3-6 months. Xenon anesthesia was feasible and safe in patients undergoing partial nephrectomy with regard to postoperative renal function. We found no significant effect on early renal function but less adverse events in the xenon group. Larger randomized controlled studies in more heterogeneous collectives are required, to confirm or refute the possible clinical benefit on renal function by xenon. ClinicalTrials.gov NCT01839084 and EudraCT 2012-005698-30.

Local loss and spatial homogenization of plant diversity reduce ecosystem multifunctionality.

PubMed

Hautier, Yann; Isbell, Forest; Borer, Elizabeth T; Seabloom, Eric W; Harpole, W Stanley; Lind, Eric M; MacDougall, Andrew S; Stevens, Carly J; Adler, Peter B; Alberti, Juan; Bakker, Jonathan D; Brudvig, Lars A; Buckley, Yvonne M; Cadotte, Marc; Caldeira, Maria C; Chaneton, Enrique J; Chu, Chengjin; Daleo, Pedro; Dickman, Christopher R; Dwyer, John M; Eskelinen, Anu; Fay, Philip A; Firn, Jennifer; Hagenah, Nicole; Hillebrand, Helmut; Iribarne, Oscar; Kirkman, Kevin P; Knops, Johannes M H; La Pierre, Kimberly J; McCulley, Rebecca L; Morgan, John W; Pärtel, Meelis; Pascual, Jesus; Price, Jodi N; Prober, Suzanne M; Risch, Anita C; Sankaran, Mahesh; Schuetz, Martin; Standish, Rachel J; Virtanen, Risto; Wardle, Glenda M; Yahdjian, Laura; Hector, Andy

2018-01-01

Biodiversity is declining in many local communities while also becoming increasingly homogenized across space. Experiments show that local plant species loss reduces ecosystem functioning and services, but the role of spatial homogenization of community composition and the potential interaction between diversity at different scales in maintaining ecosystem functioning remains unclear, especially when many functions are considered (ecosystem multifunctionality). We present an analysis of eight ecosystem functions measured in 65 grasslands worldwide. We find that more diverse grasslands-those with both species-rich local communities (α-diversity) and large compositional differences among localities (β-diversity)-had higher levels of multifunctionality. Moreover, α- and β-diversity synergistically affected multifunctionality, with higher levels of diversity at one scale amplifying the contribution to ecological functions at the other scale. The identity of species influencing ecosystem functioning differed among functions and across local communities, explaining why more diverse grasslands maintained greater functionality when more functions and localities were considered. These results were robust to variation in environmental drivers. Our findings reveal that plant diversity, at both local and landscape scales, contributes to the maintenance of multiple ecosystem services provided by grasslands. Preserving ecosystem functioning therefore requires conservation of biodiversity both within and among ecological communities.

Change in motor function and adverse health outcomes in older African-Americans.

PubMed

Buchman, Aron S; Wilson, Robert S; Leurgans, Sue E; Bennett, David A; Barnes, Lisa L

2015-10-01

We tested whether declining motor function accelerates with age in older African-Americans. Eleven motor performances were assessed annually in 513 older African-Americans. During follow-up of 5 years, linear mixed-effect models showed that motor function declined by about 0.03 units/year (Estimate, -0.026, p<0.001); about 4% more rapidly for each additional year of age at baseline. A proportional hazard model showed that both baseline motor function level and its rate of change were independent predictors of death and incident disability (all p's<0.001). These models showed that the additional annual amount of motor decline in 85 year old persons at baseline versus 65 year old persons was associated with a 1.5-fold higher rate of death and a 3-fold higher rate of developing Katz disability. The rate of declining motor function accelerates with increasing age and its rate of decline predicts adverse health outcomes in older African-Americans. Copyright © 2015 Elsevier Inc. All rights reserved.

Change in Motor Function and Adverse Health Outcomes in Older African Americas

PubMed Central

Buchman, Aron S.; Wilson, Robert S.; Leurgans, Sue E.; Bennett, David A.; Barnes, Lisa L.

2015-01-01

Objective We tested whether declining motor function accelerates with age in older African Americans. Methods Eleven motor performances were assessed annually in 513 older African Americans. Results During follow-up of 5 years, linear mixed-effect models showed that motor function declined by about 0.03 units/yr (Estimate, −0.026, p<0.001); about 4% more rapidly for each additional year of age at baseline. A proportional hazard model showed that both baseline motor function level and its rate of change were independent predictors of death and incident disability (all p’s <0.001). These models showed that the additional annual amount of motor decline in 85 year old persons at baseline versus 65 year old persons was associated with a 1.5-fold higher rate of death and a 3-fold higher rate of developing Katz disability. Conclusions The rate of declining motor function accelerates with increasing age and its rate of decline predicts adverse health outcomes in older African Americans. PMID:26209439

The impact of socioeconomic inequalities and lack of health insurance on physical functioning among middle-aged and older adults in the United States.

PubMed

Kim, Jinhyun; Richardson, Virginia

2012-01-01

Socioeconomic inequalities and lack of private health insurance have been viewed as significant contributors to health disparities in the United States. However, few studies have examined their impact on physical functioning over time, especially in later life. The current study investigated the impact of socioeconomic inequalities and lack of private health insurance on individuals' growth trajectories in physical functioning, as measured by activities of daily living. Data from the Health and Retirement Study (1994-2006) were used for this study, 6519 black and white adults who provided in-depth information about health, socioeconomic, financial and health insurance information were analysed. Latent growth curve modelling was used to estimate the initial level of physical functioning and its rate of change over time. Results showed that higher level of income and assets and having private health insurance significantly predicted better physical functioning. In particular, decline in physical functioning was slower among those who had private health insurance. Interestingly, changes in economic status, such as decreases in income and assets, had a greater impact on women's physical functioning than on men's. Black adults did not suffer more rapid declines in physical functioning than white adults after controlling for socioeconomic status. The current longitudinal study suggested that anti-poverty and health insurance policies should be enhanced to reduce the negative impact of socioeconomic inequalities on physical functioning throughout an individual's life course. © 2011 Blackwell Publishing Ltd.

Transgenic expression of Bcl-2 modulates energy metabolism, prevents cytosolic acidification during ischemia, and reduces ischemia/reperfusion injury.

PubMed

Imahashi, Kenichi; Schneider, Michael D; Steenbergen, Charles; Murphy, Elizabeth

2004-10-01

The antiapoptotic protein Bcl-2 is targeted to the mitochondria, but it is uncertain whether Bcl-2 affects only myocyte survival after ischemia, or whether it also affects metabolic functions of mitochondria during ischemia. Hearts from mice overexpressing human Bcl-2 and from their wild-type littermates (WT) were subjected to 24 minutes of global ischemia followed by reperfusion. During ischemia, the decrease in pH(i) and the initial rate of decline in ATP were significantly reduced in Bcl-2 hearts compared with WT hearts (P<0.05). The reduced acidification during ischemia was dependent on the activity of mitochondrial F1F0-ATPase. In the presence of oligomycin (Oligo), an F1F0-ATPase inhibitor, the decrease in pH(i) was attenuated in WT hearts, but in Bcl-2 hearts, Oligo had no additional effect on pH(i) during ischemia. Likewise, addition of Oligo to WT hearts slowed the rate of decline in ATP during ischemia to a level similar to that observed in Bcl-2 hearts, but addition of Oligo had no significant effect on the rate of decline in ATP in Bcl-2 hearts during ischemia. These data are consistent with Bcl-2-mediated inhibition of consumption of glycolytic ATP. Furthermore, mitochondria from Bcl-2 hearts have a reduced rate of consumption of ATP on uncoupler addition. This could be accomplished by limiting ATP entry into the mitochondria through the voltage-dependent anion channel, and/or the adenine nucleotide transporter, or by direct inhibition of the F1F0-ATPase. Immunoprecipitation showed greater interaction between Bcl-2 and voltage-dependent anion channel during ischemia. These data indicate that Bcl-2 modulation of metabolism contributes to cardioprotection.

The Functional Transitions Model: Maximizing Ability in the Context of Progressive Disability Associated with Alzheimer's Disease

ERIC Educational Resources Information Center

Slaughter, Susan; Bankes, Jane

2007-01-01

The Functional Transitions Model (FTM) integrates the theoretical notions of progressive functional decline associated with Alzheimer's disease (AD), excess disability, and transitions occurring intermittently along the trajectory of functional decline. Application of the Functional Transitions Model to clinical practice encompasses the paradox of…

Mindfulness and meditation: treating cognitive impairment and reducing stress in dementia.

PubMed

Russell-Williams, Jesse; Jaroudi, Wafa; Perich, Tania; Hoscheidt, Siobhan; El Haj, Mohamad; Moustafa, Ahmed A

2018-02-21

This study investigates the relationship between mindfulness, meditation, cognition and stress in people with Alzheimer's disease (AD), dementia, mild cognitive impairment and subjective cognitive decline. Accordingly, we explore how the use of meditation as a behavioural intervention can reduce stress and enhance cognition, which in turn ameliorates some dementia symptoms. A narrative review of the literature was conducted with any studies using meditation as an intervention for dementia or dementia-related memory conditions meeting inclusion criteria. Studies where moving meditation was the main intervention were excluded due to the possible confounding of exercise. Ten papers were identified and reviewed. There was a broad use of measures across all studies, with cognitive assessment, quality of life and perceived stress being the most common. Three studies used functional magnetic resonance imaging to measure functional changes to brain regions during meditation. The interventions fell into the following three categories: mindfulness, most commonly mindfulness-based stress reduction (six studies); Kirtan Kriya meditation (three studies); and mindfulness-based Alzheimer's stimulation (one study). Three of these studies were randomised controlled trials. All studies reported significant findings or trends towards significance in a broad range of measures, including a reduction of cognitive decline, reduction in perceived stress, increase in quality of life, as well as increases in functional connectivity, percent volume brain change and cerebral blood flow in areas of the cortex. Limitations and directions for future studies on meditation-based treatment for AD and stress management are suggested.

Study of computerized spirometric parameters of traffic police personnel of Saurashtra region, Gujarat, India.

PubMed

Makwana, Amit H; Solanki, Jayesh D; Gokhale, Pradnya A; Mehta, Hemant B; Shah, Chinmay J; Gadhavi, Bhakti P

2015-01-01

Air pollution due to road traffic is a serious health hazard and air quality crisis in cities is mainly due to vehicular emission. Thus the persons who are continuously exposed are at an increased risk. The study was carried out to evaluate the extent of impairment in lung function in traffic police personnel compared to matched unexposed control group. A cross-sectional study was conducted to measure the spirometric parameters of 100 traffic police personnel, aged 20-55 years, working in Saurashtra region, as compared to matched control group, consisting of 100 unexposed males. Measurement of lung volumes and capacities was done with SPIROEXCEL. The statistical analysis was carried out with Graph pad instat 3. Traffic police personnel had significantly declined forced vital capacity (FVC), forced expiratory volume in one second (FEV 1), slow vital capacity (SVC) and maximum voluntary ventilation (MVV) when compared with predictive normal values, which is probably due to exposure to vehicular exhaust. Comparison of test values between groups showed significantly reduced FVC, MVV and increased FEV1/FVC ratio and insignificantly declined FEV1 and SVC in cases as compared to controls. Traffic personnel with longer duration of exposure showed significantly reduced lung functions than those with shorter duration. Smokers showed lower test values as compared to non-smokers with significance only in unexposed group. The effect of pollution by vehicular exhausts may be responsible for these pulmonary function impairments and traffic police personnel should be offered personal protective or preventive measures.

The neurological basis of occupation.

PubMed

Gutman, Sharon A; Schindler, Victoria P

2007-01-01

The purpose of the present paper was to survey the literature about the neurological basis of human activity and its relationship to occupation and health. Activities related to neurological function were organized into three categories: those that activate the brain's reward system; those that promote the relaxation response; and those that preserve cognitive function into old age. The results from the literature review correlating neurological evidence and activities showed that purposeful and meaningful activities could counter the effects of stress-related diseases and reduce the risk for dementia. Specifically, it was found that music, drawing, meditation, reading, arts and crafts, and home repairs, for example, can stimulate the neurogical system and enhance health and well-being, Prospective research studies are needed to examine the effects of purposeful activities on reducing stress and slowing the rate of cognitive decline.

Simulated effects of pumping irrigation wells on ground-water levels in western Saginaw County, Michigan

USGS Publications Warehouse

Hoard, Christopher J.; Westjohn, David B.

2001-01-01

Success of agriculture in many areas of Michigan relies on withdrawal of large quantities of ground water for irrigation. In some areas of the State, water-level declines associated with large ground-water withdrawals may adversely affect nearby residential wells. Residential wells in several areas of Saginaw County, in Michigan's east-central Lower Peninsula, recently went dry shortly after irrigation of crop lands commenced; many of these wells also went dry during last year's agricultural cycle (summer 2000). In September 2000, residential wells that had been dry returned to function after cessation of pumping from large-capacity irrigation wells. To evaluate possible effects of groundwater withdrawals from irrigation wells on residential wells, the U.S. Geological Survey used hydrogeologic data including aquifer tests, water-level records, geologic logs, and numerical models to determine whether water-level declines and the withdrawal of ground water for agricultural irrigation are related. Numerical simulations based on representative irrigation well pumping volumes and a 3-month irrigation period indicate water-level declines that range from 5.3 to 20 feet, 2.8 to 12 feet and 1.7 to 6.9 feet at distances of about 0.5, 1.5 and 3 miles from irrigation wells, respectively. Residential wells that are equipped with shallow jet pumps and that are within 0.5 miles of irrigation wells would likely experience reduced yield or loss of yield during peak periods of irrigation. The actual 1 extent that irrigation pumping cause reduced function of residential wells, however, cannot be fully predicted on the basis of the data analyzed because many _other factors may be adversely affecting the yield of residential wells.

Vulnerable elders survey and socioeconomic status predict functional decline and death among older women with newly diagnosed nonmetastatic breast cancer.

PubMed

Owusu, Cynthia; Margevicius, Seunghee; Schluchter, Mark; Koroukian, Siran M; Schmitz, Kathryn H; Berger, Nathan A

2016-08-15

The purpose of this study was to determine the ability of the Vulnerable Elders Survey (VES-13) to predict the composite outcome of functional decline and death within 12 months of breast cancer treatment among women 65 years old or older with newly diagnosed stage I to III breast cancer. Two hundred and six participants were recruited from ambulatory oncology clinics at an academic center between April 2008 and April 2013. Participants competed the VES-13 at baseline just before neoadjuvant/adjuvant treatment. The primary outcome, functional decline/death, was defined as either a decrease of at least 1 point on the Activities of Daily Living scale and/or the Instrumental Activities of Daily Living scale or death between baseline and 12 months (yes or no). One hundred and eighty four participants (89%) completed 12 months of follow-up. Twenty-two percent functionally declined (n = 34) or died (n = 7). Univariately, with increasing VES-13 scores, the estimated risk of functional decline/death rose from 23% for participants with a VES-13 score of 3 to 76% for participants with a VES-13 score of 10. In multivariate logistic regression analysis, VES-13 scores (adjusted odds ratio, 1.37; 95% confidence interval, 1.18-1.57) and having a high school education or less (adjusted odds ratio, 2.47; 95% confidence interval, 1.08-5.65) were independent predictors of functional decline/death (area under the receiver operator curve, 0.79). Among older women with newly diagnosed nonmetastatic breast cancer, approximately 1 in 5 functionally declined and/or died within 12 months of breast cancer treatment initiation. Women with high school education or less were disproportionately affected. The VES-13 is a useful instrument for the early identification of those at risk for functional decline and/or death. Cancer 2016;122:2579-86. © 2016 American Cancer Society. © 2016 American Cancer Society.

Age-related variance in decisions under ambiguity is explained by changes in reasoning, executive functions, and decision-making under risk.

PubMed

Schiebener, Johannes; Brand, Matthias

2017-06-01

Previous literature has explained older individuals' disadvantageous decision-making under ambiguity in the Iowa Gambling Task (IGT) by reduced emotional warning signals preceding decisions. We argue that age-related reductions in IGT performance may also be explained by reductions in certain cognitive abilities (reasoning, executive functions). In 210 participants (18-86 years), we found that the age-related variance on IGT performance occurred only in the last 60 trials. The effect was mediated by cognitive abilities and their relation with decision-making performance under risk with explicit rules (Game of Dice Task). Thus, reductions in cognitive functions in older age may be associated with both a reduced ability to gain explicit insight into the rules of the ambiguous decision situation and with failure to choose the less risky options consequently after the rules have been understood explicitly. Previous literature may have underestimated the relevance of cognitive functions for age-related decline in decision-making performance under ambiguity.

Vitamin D deficiency is associated with functional decline and falls in frail elderly women despite supplementation

PubMed Central

Kotlarczyk, Mary P.; Perera, Subashan; Ferchak, Mary Anne; Nace, David A.; Resnick, Neil M.; Greenspan, Susan L.

2018-01-01

Purpose Institute of Medicine (IOM) guidelines recommend 800 IU vitamin D daily for older adults and maintaining serum 25-hydroxyvitamin D [25(OH)D] above 20 ng/ml for optimal skeletal health. The adequacy of IOM guidelines for sustaining function and reducing falls in frail elderly is unknown. Methods Female long-term care residents age ≥ 65 enrolled in an osteoporosis clinical trial were included in this analysis (n=137). Participants were classified based on baseline 25(OH)D levels as deficient (<20 ng/ml, n=26), insufficient (20–30 ng/ml, n=40), or sufficient (>30 ng/ml, n=71). Deficient women were provided initial vitamin D repletion (50,000 IU D3 weekly for 8 weeks). All were supplemented with 800 IU vitamin D3 daily for 24 months. Annual functional assessments included Activities of Daily Living (ADL), Instrumental ADL (IADL), Physical Performance Test (PPT), gait speed, cognition (SPMSQ), and mental health (PHQ-9). We used linear mixed models for analysis of functional measures and logistic regression for falls. Results Daily supplementation maintained 25(OH)D levels above 20 ng/ml in 95% of participants. All groups demonstrated functional decline. Women initially deficient had a greater decline in physical function at 12 (IADL: −2.0±0.4, PPT: −3.1±0.7, both p<0.01) and 24 months (IADL: −2.5±0.6, ADL: −2.5±0.6, both p<0.01), a larger increase in cognitive deficits at 12 months (1.7±0.4: p=0.01), and more fallers (88.5%, p=0.04) compared to those sufficient at baseline, despite supplementation to sufficient levels. Conclusions IOM guidelines may not be adequate for frail elderly. Further study of optimal 25(OH)D levels for maintaining function and preventing falls is needed. PMID:27975302

Trajectories of age-related cognitive decline and potential associated factors of cognitive function in senior citizens of Beijing.

PubMed

Li, He; Lv, Chenlong; Zhang, Ting; Chen, Kewei; Chen, Chuansheng; Gai, Guozhong; Hu, Liangping; Wang, Yongyan; Zhang, Zhanjun

2014-01-01

With a longer life expectancy and an increased prevalence of neurodegenerative diseases, investigations on trajectories of cognitive aging have become exciting and promising. This study aimed to estimate the patterns of age-related cognitive decline and the potential associated factors of cognitive function in community-dwelling residents of Beijing, China. In this study, 1248 older adults aged 52-88 years [including 175 mild cognitive impairment (MCI) subjects] completed a battery of neuropsychological scales. The personal information, including demographic information, medical history, eating habits, lifestyle regularity and leisure activities, was also collected. All cognitive function exhibited an agerelated decline in normal volunteers. Piece-wise linear fitting results suggested that performance on the Auditory Verbal Learning Test remained stable until 58 years of age and continued to decline thereafter. The decline in processing speed and executive function began during the early 50's. Scores on visual-spatial and language tests declined after 66 years of age. The decline stage of the general mental status ranged from 63 to 70 years of age. However, the MCI group did not exhibit an obvious age-related decline in most cognitive tests. Multivariate linear regression analyses indicated that education, gender, leisure activities, diabetes and eating habits were associated with cognitive abilities. These results indicated various trajectories of age-related decline across multiple cognitive domains. We also found different patterns of agerelated cognitive decline between MCI and normal elderly. These findings could help improve the guidance of cognitive intervention program and have implications for public policy issues.

[Fertility change in Mexico and the politics of population].

PubMed

Zavala De Cosio, M E

1993-01-01

This introduction to a detailed study of fertility change in Mexico assesses the available fertility data and describes the sources used, traces the beginning and course of the demographic transition in Mexico, and describes the work. Mexico's demographic transition began around 1930 with the acceleration of mortality decline. The considerable time lag between the mortality decline and the beginning of the fertility decline resulted in a period of very rapid growth. Between 1955 and 1975, the growth rate exceeded 3% annually. The start of the fertility decline dated to about 1970, the time of a major reform of population policy and creation of institutions to reduce growth. But the fertility decline was not solely the result of population programs. An incipient fertility decline could be observed in the metropolitan and more educated population sectors beginning in the early 1960s. The onset of the mortality decline in the 1930s resulted from the sustained social and economic progress made possible after the conclusion of the Mexican Revolution. Between 1930 and 1980, the adult illiteracy rate declined from 61.2% to 17%, while life expectancy increased from 33 years to 63.2 years. In Mexico as in other Latin American countries, the mortality decline, which disturbed the traditional balance between high mortality and high fertility, was the force setting off the demographic transition and the necessary precursor to fertility decline. The first of two main sections of the book focuses on examination of fertility variations in Mexico since around 1900 using cross-sectional and longitudinal methods of analysis. The second part describes the origins, history, and institutions involved in Mexico's population policies and the demographic programs and their principal results. The influence of population policies in demographic change is assessed, especially in the case of fertility changes induced by family planning programs. Both the first and second parts sought to place Mexican fertility trends in the context of the demographic transition and to observe the functioning and effects of demographic programs.

Lung function decline rates according to GOLD group in patients with chronic obstructive pulmonary disease

PubMed Central

Kim, Joohae; Yoon, Ho Il; Oh, Yeon-Mok; Lim, Seong Yong; Lee, Ji-Hyun; Kim, Tae-Hyung; Lee, Sang Yeub; Lee, Jin Hwa; Lee, Sang-Do; Lee, Chang-Hoon

2015-01-01

Background Since the Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups A–D were introduced, the lung function changes according to group have been evaluated rarely. Objective We investigated the rate of decline in annual lung function in patients categorized according to the 2014 GOLD guidelines. Methods Patients with COPD included in the Korean Obstructive Lung Disease (KOLD) prospective study, who underwent yearly postbronchodilator spirometry at least three times, were included. The main outcome was the annual decline in postbronchodilator forced expiratory volume in 1 second (FEV1), which was analyzed by random-slope and random-intercept mixed linear regression. Results A total 175 participants were included. No significant postbronchodilator FEV1 decline was observed between the groups (−34.4±7.9 [group A]; −26.2±9.4 [group B]; −22.7±16.0 [group C]; and −24.0±8.7 mL/year [group D]) (P=0.79). The group with less symptoms (−32.3±7.2 vs −25.0±6.5 mL/year) (P=0.44) and the low risk group (−31.0±6.1 vs −23.6±7.7 mL/year) (P=0.44) at baseline showed a more rapid decline in the postbronchodilator FEV1, but the trends were not statistically significant. However, GOLD stages classified by FEV1 were significantly related to the annual lung function decline. Conclusion There was no significant difference in lung function decline rates according to the GOLD groups. Prior classification using postbronchodilator FEV1 predicts decline in lung function better than does the new classification. PMID:26379432

Increased lung function decline in blue-collar workers exposed to welding fumes.

PubMed

Thaon, Isabelle; Demange, Valérie; Herin, Fabrice; Touranchet, Annie; Paris, Christophe

2012-07-01

There is no consensus at the present time about the effect of welding on lung function decline. This study compared lung function decline between blue-collar workers exposed and not exposed to welding fumes in a French longitudinal cohort of 21,238 subjects aged 37 to 52 years at inclusion. Medical data, occupation, sector of activity, and spirometry were recorded twice by occupational physicians in 1990 and 1995. A job-exposure matrix was used to identify 503 male blue-collar workers exposed to welding fumes and 709 control subjects and to define the weekly duration of exposure to welding fumes. Baseline lung function parameters were higher in workers exposed to welding fumes than in control subjects. After a 5-year follow-up, welding-fume exposure was associated with a nonsignificant decline in FVC (P = .06) and FEV(1) (P = .07) after adjustment for age, pack-years, BMI, and baseline value of the parameter. A significant accelerated decline in FEV(1) (P = .046) was also observed in never smokers exposed to welding fumes. An “exposure-response” relationship was observed between FEV(1) decline and weekly duration of exposure to welding fumes in nonsmokers but not in smokers. Blue-collar workers exposed to welding fumes showed accelerated decline in lung function, which, in nonsmokers, was related to weekly duration of exposure.

The effects of ageing on respiratory muscle function and performance in older adults.

PubMed

Watsford, Mark L; Murphy, Aron J; Pine, Matthew J

2007-02-01

The reduced physiological capacity evident with ageing may affect the ability to perform many tasks, potentially affecting quality of life. Previous research has clearly demonstrated the reduced capacity of the respiratory system with ageing and described the effect that habitual physical activity has upon this decline. This research aimed to examine the influence of age on respiratory muscle (RM) function and the relationship between RM function and physical performance within the Australian population. Seventy-two healthy older adults (50-79 years) were divided into males (n=36) and females (n=36) and examined for pulmonary function, RM strength, inspiratory muscle endurance (IME) and 1.6 km walking performance. There were no significant age by gender effects for any variables; however, ageing was significantly related to reduced RM function and walking capacity within each gender. Furthermore, regression analysis showed that the RM strength could be predicted from age. Partial correlations controlling for age indicated that expiratory muscle strength was significantly related to walking performance in males (p=0.04), whilst IME contributed significantly to walking performance in all participants. These within-gender effects and relationships indicate that RM strength is an important physiological variable to maintain in the older population, as it may be related to functional ability.

Exercise improves mitochondrial and redox-regulated stress responses in the elderly: better late than never!

PubMed

Cobley, James N; Moult, Peter R; Burniston, Jatin G; Morton, James P; Close, Graeme L

2015-04-01

Ageing is associated with several physiological declines to both the cardiovascular (e.g. reduced aerobic capacity) and musculoskeletal system (muscle function and mass). Ageing may also impair the adaptive response of skeletal muscle mitochondria and redox-regulated stress responses to an acute exercise bout, at least in mice and rodents. This is a functionally important phenomenon, since (1) aberrant mitochondrial and redox homeostasis are implicated in the pathophysiology of musculoskeletal ageing and (2) the response to repeated exercise bouts promotes exercise adaptations and some of these adaptations (e.g. improved aerobic capacity and exercise-induced mitochondrial remodelling) offset age-related physiological decline. Exercise-induced mitochondrial remodelling is mediated by upstream signalling events that converge on downstream transcriptional co-factors and factors that orchestrate a co-ordinated nuclear and mitochondrial transcriptional response associated with mitochondrial remodelling. Recent translational human investigations have demonstrated similar exercise-induced mitochondrial signalling responses in older compared with younger skeletal muscle, regardless of training status. This is consistent with data indicating normative mitochondrial remodelling responses to long-term exercise training in the elderly. Thus, human ageing is not accompanied by diminished mitochondrial plasticity to acute and chronic exercise stimuli, at least for the signalling pathways measured to date. Exercise-induced increases in reactive oxygen and nitrogen species promote an acute redox-regulated stress response that manifests as increased heat shock protein and antioxidant enzyme content. In accordance with previous reports in rodents and mice, it appears that sedentary ageing is associated with a severely attenuated exercise-induced redox stress response that might be related to an absent redox signal. In this regard, regular exercise training affords some protection but does not completely override age-related defects. Despite some failed redox-regulated stress responses, it seems mitochondrial responses to exercise training are intact in skeletal muscle with age and this might underpin the protective effect of exercise training on age-related musculoskeletal decline. Whilst further investigation is required, recent data suggest that it is never too late to begin exercise training and that lifelong training provides protection against several age-related declines at both the molecular (e.g. reduced mitochondrial function) and whole-body level (e.g. aerobic capacity).

Reduced hippocampal activation during episodic encoding in middle-aged individuals at genetic risk of Alzheimer's Disease: a cross-sectional study

PubMed Central

Trivedi, Mehul A; Schmitz, Taylor W; Ries, Michele L; Torgerson, Britta M; Sager, Mark A; Hermann, Bruce P; Asthana, Sanjay; Johnson, Sterling C

2006-01-01

Background The presence of the apolipoprotein E (APOE) ε4 allele is a major risk factor for the development of Alzheimer's disease (AD), and has been associated with metabolic brain changes several years before the onset of typical AD symptoms. Functional MRI (fMRI) is a brain imaging technique that has been used to demonstrate hippocampal activation during measurement of episodic encoding, but the effect of the ε4 allele on hippocampal activation has not been firmly established. Methods The present study examined the effects of APOE genotype on brain activation patterns in the medial temporal lobe (MTL) during an episodic encoding task using a well-characterized novel item versus familiar item contrast in cognitively normal, middle-aged (mean = 54 years) individuals who had at least one parent with AD. Results We found that ε3/4 heterozygotes displayed reduced activation in the hippocampus and MTL compared to ε3/3 homozygotes. There were no significant differences between the groups in age, education or neuropsychological functioning, suggesting that the altered brain activation seen in ε3/4 heterozygotes was not associated with impaired cognitive function. We also found that participants' ability to encode information on a neuropsychological measure of learning was associated with greater activation in the anterior MTL in the ε3/3 homozygotes, but not in the ε3/4 heterozygotes. Conclusion Together with previous studies reporting reduced glucose metabolism and AD-related neuropathology, this study provides convergent validity for the idea that the MTL exhibits functional decline associated with the APOE ε4 allele. Importantly, these changes were detected in the absence of meaningful neuropsychological differences between the groups. A focus of ongoing work in this laboratory is to determine if these findings are predictive of subsequent cognitive decline. PMID:16412236

Fitness, but not physical activity, is related to functional integrity of brain networks associated with aging.

PubMed

Voss, Michelle W; Weng, Timothy B; Burzynska, Agnieszka Z; Wong, Chelsea N; Cooke, Gillian E; Clark, Rachel; Fanning, Jason; Awick, Elizabeth; Gothe, Neha P; Olson, Erin A; McAuley, Edward; Kramer, Arthur F

2016-05-01

Greater physical activity and cardiorespiratory fitness are associated with reduced age-related cognitive decline and lower risk for dementia. However, significant gaps remain in the understanding of how physical activity and fitness protect the brain from adverse effects of brain aging. The primary goal of the current study was to empirically evaluate the independent relationships between physical activity and fitness with functional brain health among healthy older adults, as measured by the functional connectivity of cognitively and clinically relevant resting state networks. To build context for fitness and physical activity associations in older adults, we first demonstrate that young adults have greater within-network functional connectivity across a broad range of cortical association networks. Based on these results and previous research, we predicted that individual differences in fitness and physical activity would be most strongly associated with functional integrity of the networks most sensitive to aging. Consistent with this prediction, and extending on previous research, we showed that cardiorespiratory fitness has a positive relationship with functional connectivity of several cortical networks associated with age-related decline, and effects were strongest in the default mode network (DMN). Furthermore, our results suggest that the positive association of fitness with brain function can occur independent of habitual physical activity. Overall, our findings provide further support that cardiorespiratory fitness is an important factor in moderating the adverse effects of aging on cognitively and clinically relevant functional brain networks. Copyright © 2015 Elsevier Inc. All rights reserved.

Fitness, but not physical activity, is related to functional integrity of brain networks associated with aging

PubMed Central

Voss, Michelle W.; Weng, Timothy B.; Burzynska, Agnieszka Z.; Wong, Chelsea N.; Cooke, Gillian E.; Clark, Rachel; Fanning, Jason; Awick, Elizabeth; Gothe, Neha P.; Olson, Erin A.; McAuley, Edward; Kramer, Arthur F.

2015-01-01

Greater physical activity and cardiorespiratory fitness are associated with reduced age-related cognitive decline and lower risk for dementia. However, significant gaps remain in the understanding of how physical activity and fitness protect the brain from adverse effects of brain aging. The primary goal of the current study was to empirically evaluate the independent relationships between physical activity and fitness with functional brain health among healthy older adults, as measured by the functional connectivity of cognitively and clinically relevant resting state networks. To build context for fitness and physical activity associations in older adults, we first demonstrate that young adults have greater within-network functional connectivity across a broad range of cortical association networks. Based on these results and previous research, we predicted that individual differences in fitness and physical activity would be most strongly associated with functional integrity of the networks most sensitive to aging. Consistent with this prediction, and extending on previous research, we showed that cardiorespiratory fitness has a positive relationship with functional connectivity of several cortical networks associated with age-related decline, and effects were strongest in the Default Mode Network (DMN). Furthermore, our results suggest that the positive association of fitness with brain function can occur independent of habitual physical activity. Overall, our findings provide further support that cardiorespiratory fitness is an important factor in moderating the adverse effects of aging on cognitively and clinically relevant functional brain networks. PMID:26493108

Decline in word-finding: The objective cognitive finding most relevant to patients after mesial temporal lobe epilepsy surgery.

PubMed

Pauli, Carla; de Oliveira Thais, Maria Emilia Rodrigues; Guarnieri, Ricardo; Schwarzbold, Marcelo Liborio; Diaz, Alexandre Paim; Ben, Juliana; Linhares, Marcelo Neves; Markowitsch, Hans Joachim; Wolf, Peter; Wiebe, Samuel; Lin, Katia; Walz, Roger

2017-10-01

The purpose of this study was to investigate the following: i) the objective impairment in neuropsychological tests that were associated with the subjective perception of cognitive function decline in Brazilian patients who underwent mesial temporal lobe epilepsy (MTLE) surgery and ii) the predictive variables for those impaired objective neuropsychological tests. Forty-eight adults with MTLE (27 right HS and 23 male) were divided according to their perception of changes (Decline or No-decline) of cognitive function domain of the QOLIE-31 questionnaire applied before and 1year after the ATL. The mean (SD) of changes in the raw score difference of the neuropsychological tests before and after the ATL was compared between Decline and No-decline groups. Receiver Operating Characteristic curves, sensitivity, specificity, and predictive values were used to assess the optimum cutoff points of neuropsychological test score changes to predict patient-reported subjective cognitive decline. Six (12.5%) patients reported a perception of cognitive function decline after ATL. Among the 25 cognitive tests analyzed, only changes in the Boston Naming Test (BNT) were associated with subjective cognitive decline reported by patients. A reduction of ≥8 points in the raw score of BNT after surgery had 91% of sensitivity and 45% specificity for predicting subjective perception of cognitive function decline by the patient. Left side surgery and age older than 40years were more associated with an important BNT reduction with overall accuracy of 91.7%, 95% predictive ability for no impairment, and 75% for impairment of cognitive function. Impairment in word-finding seems to be the objective cognitive finding most relevant to Brazilian patients after mesial temporal lobe epilepsy surgery. Similar to American patients, the side of surgery and age are good predictors for no decline in the BNT, but shows a lower accuracy to predict its decline. If replicated in other populations, the results may have wider implications for the surgical management of patients with drug-resistant MTLE. Copyright © 2017 Elsevier Inc. All rights reserved.

The impact of menopause on functional status in women with rheumatoid arthritis.

PubMed

Mollard, Elizabeth; Pedro, Sofia; Chakravarty, Eliza; Clowse, Megan; Schumacher, Rebecca; Michaud, Kaleb

2018-05-01

The aim of this study was to investigate the association of menopause with functional status outcomes in women with RA. Participants were women in a US-wide observational cohort who developed RA before menopause. The HAQ measured functional status. We controlled for confounding variables and used univariate and multivariable generalized estimating equation methods with the sandwich estimator of variance. Best models were selected using the quasi-likelihood under the independence model criterion. A sensitivity analysis was performed using linear mixed effects regression models. A total of 8189 women were eligible. Of these, 2005 (24.5%) were pre-menopausal, 611 (7.5%) transitioned through menopause during the study, and 5573 (68.1%) were post-menopausal. Within each respective group, the mean (s.d.) ages were 39.7 (7.8), 50.7 (3.4) and 62.3 (9.3) years. Our results showed that women who were pre-menopausal had less functional decline as measured by the HAQ compared with women who were post-menopausal; these results were robust and strong even after adjustment for other significant factors. The ever-use of hormonal replacement therapy, ever having a pregnancy, and longer length of reproductive life were associated with less functional decline. After menopause, the trajectory of functional decline worsened and accelerated in women with RA. The results suggest that menopausal status is associated with functional decline in women with RA. Furthermore, menopause is associated with a worsening progression of functional decline. These data indicate that menopause has a significant impact on the level and rate of functional decline in women with RA.

Healthy eating and reduced risk of cognitive decline

PubMed Central

Dehghan, Mahshid; O'Donnell, Martin; Anderson, Craig; Teo, Koon; Gao, Peggy; Sleight, Peter; Dagenais, Gilles; Probstfield, Jeffrey L.; Mente, Andrew; Yusuf, Salim

2015-01-01

Objective: We sought to determine the association of dietary factors and risk of cognitive decline in a population at high risk of cardiovascular disease. Methods: Baseline dietary intake and measures of the Mini-Mental State Examination were recorded in 27,860 men and women who were enrolled in 2 international parallel trials of the ONTARGET (Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial) and TRANSCEND (Telmisartan Randomised Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease) studies. We measured diet quality using the modified Alternative Healthy Eating Index. Cox proportional hazards regression was used to determine the association between diet quality and risk of ≥3-point decline in Mini-Mental State Examination score, and reported as hazard ratio with 95% confidence intervals with adjustment for covariates. Results: During 56 months of follow-up, 4,699 cases of cognitive decline occurred. We observed lower risk of cognitive decline among those in the healthiest dietary quintile of modified Alternative Healthy Eating Index compared with lowest quintile (hazard ratio 0.76, 95% confidence interval 0.66–0.86, Q5 vs Q1). Lower risk of cognitive decline was consistent regardless of baseline cognitive level. Conclusion: We found that higher diet quality was associated with a reduced risk of cognitive decline. Improved diet quality represents an important potential target for reducing the global burden of cognitive decline. PMID:25948720

Caloric restriction preserves memory and reduces anxiety of aging mice with early enhancement of neurovascular functions

PubMed Central

Parikh, Ishita; Guo, Janet; Chuang, Kai-Hsiang; Zhong, Yu; Rempe, Ralf G.; Hoffman, Jared D.; Armstrong, Rachel; Bauer, Björn; Hartz, Anika M.S.; Lin, Ai-Ling

2016-01-01

Neurovascular integrity plays an important role in protecting cognitive and mental health in aging. Lifestyle interventions that sustain neurovascular integrity may thus be critical on preserving brain functions in aging and reducing the risk for age-related neurodegenerative disorders. Here we show that caloric restriction (CR) had an early effect on neurovascular enhancements, and played a critical role in preserving vascular, cognitive and mental health in aging. In particular, we found that CR significantly enhanced cerebral blood flow (CBF) and blood-brain barrier function in young mice at 5-6 months of age. The neurovascular enhancements were associated with reduced mammalian target of rapamycin expression, elevated endothelial nitric oxide synthase signaling, and increased ketone bodies utilization. With age, CR decelerated the rate of decline in CBF. The preserved CBF in hippocampus and frontal cortex were highly correlated with preserved memory and learning, and reduced anxiety, of the aging mice treated with CR (18-20 months of age). Our results suggest that dietary intervention started in the early stage (e.g., young adults) may benefit cognitive and mental reserve in aging. Understanding nutritional effects on neurovascular functions may have profound implications in human brain aging and age-related neurodegenerative disorders. PMID:27829242

Niche Contractions in Declining Species: Mechanisms and Consequences.

PubMed

Scheele, Ben C; Foster, Claire N; Banks, Sam C; Lindenmayer, David B

2017-05-01

A fundamental aim of conservation biology is to understand how species respond to threatening processes, with much research effort focused on identifying threats and quantifying spatial and temporal patterns of species decline. Here, we argue that threats often reduce the realized niche breadth of declining species because environmental, biotic, and evolutionary processes reduce or amplify threats, or because a species' capacity to tolerate threats varies across niche space. Our 'niche reduction hypothesis' provides a new lens for understanding why species decline in some locations and not others. This perspective can improve management of declining species by identifying where to focus resources and which interventions are most likely to be effective in a given environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oxidative stress, aging, and central nervous system disease in the canine model of human brain aging.

PubMed

Head, Elizabeth; Rofina, Jaime; Zicker, Steven

2008-01-01

Decline in cognitive functions that accompany aging in dogs may have a biologic basis, and many of the disorders associated with aging in dogs may be mitigated through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of laboratory and clinical studies, antioxidants may be one class of nutraceutical that provides benefits to aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which may lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes may lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs.

Speed accuracy trade-off under response deadlines

PubMed Central

Karşılar, Hakan; Simen, Patrick; Papadakis, Samantha; Balcı, Fuat

2014-01-01

Perceptual decision making has been successfully modeled as a process of evidence accumulation up to a threshold. In order to maximize the rewards earned for correct responses in tasks with response deadlines, participants should collapse decision thresholds dynamically during each trial so that a decision is reached before the deadline. This strategy ensures on-time responding, though at the cost of reduced accuracy, since slower decisions are based on lower thresholds and less net evidence later in a trial (compared to a constant threshold). Frazier and Yu (2008) showed that the normative rate of threshold reduction depends on deadline delays and on participants' uncertainty about these delays. Participants should start collapsing decision thresholds earlier when making decisions under shorter deadlines (for a given level of timing uncertainty) or when timing uncertainty is higher (for a given deadline). We tested these predictions using human participants in a random dot motion discrimination task. Each participant was tested in free-response, short deadline (800 ms), and long deadline conditions (1000 ms). Contrary to optimal-performance predictions, the resulting empirical function relating accuracy to response time (RT) in deadline conditions did not decline to chance level near the deadline; nor did the slight decline we typically observed relate to measures of endogenous timing uncertainty. Further, although this function did decline slightly with increasing RT, the decline was explainable by the best-fitting parameterization of Ratcliff's diffusion model (Ratcliff, 1978), whose parameters are constant within trials. Our findings suggest that at the very least, typical decision durations are too short for participants to adapt decision parameters within trials. PMID:25177265

Longitudinal associations between physical and cognitive performance among community-dwelling older adults.

PubMed

Tolea, Magdalena I; Morris, John C; Galvin, James E

2015-01-01

To assess the directionality of the association between physical and cognitive decline in later life, we compared patterns of decline in performance across groups defined by baseline presence of cognitive and/or physical impairment [none (n = 217); physical only (n = 169); cognitive only (n = 158), or both (n = 220)] in a large sample of participants in a cognitive aging study at the Knight Alzheimer's Disease Research Center at Washington University in St. Louis who were followed for up to 8 years (3,079 observations). Rates of decline reached 20% for physical performance and varied across cognitive tests (global, memory, speed, executive function, and visuospatial skills). We found that physical decline was better predicted by baseline cognitive impairment (slope = -1.22, p<0.001), with baseline physical impairment not contributing to further decline in physical performance (slope = -0.25, p = 0.294). In turn, baseline physical impairment was only marginally associated with rate of cognitive decline across various cognitive domains. The cognitive-functional association is likely to operate in the direction of cognitive impairment to physical decline although physical impairment may also play a role in cognitive decline/dementia. Interventions to prevent further functional decline and development of disability and complete dependence may benefit if targeted to individuals with cognitive impairment who are at increased risk.

Lung function decline over 25 years of follow-up among black and white adults in the ARIC study cohort.

PubMed

Mirabelli, Maria C; Preisser, John S; Loehr, Laura R; Agarwal, Sunil K; Barr, R Graham; Couper, David J; Hankinson, John L; Hyun, Noorie; Folsom, Aaron R; London, Stephanie J

2016-04-01

Interpretation of longitudinal information about lung function decline from middle to older age has been limited by loss to follow-up that may be correlated with baseline lung function or the rate of decline. We conducted these analyses to estimate age-related decline in lung function across groups of race, sex, and smoking status while accounting for dropout from the Atherosclerosis Risk in Communities Study. We analyzed data from 13,896 black and white participants, aged 45-64 years at the 1987-1989 baseline clinical examination. Using spirometry data collected at baseline and two follow-up visits, we estimated annual population-averaged mean changes in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) by race, sex, and smoking status using inverse-probability-weighted independence estimating equations conditioning-on-being-alive. Estimated rates of FEV1 decline estimated using inverse-probability-weighted independence estimating equations conditioning on being alive were higher among white than black participants at age 45 years (e.g., male never smokers: black: -29.5 ml/year; white: -51.9 ml/year), but higher among black than white participants by age 75 (black: -51.2 ml/year; white: -26). Observed differences by race were more pronounced among men than among women. By smoking status, FEV1 declines were larger among current than former or never smokers at age 45 across all categories of race and sex. By age 60, FEV1 decline was larger among former and never than current smokers. Estimated annual declines generated using unweighted generalized estimating equations were smaller for current smokers at younger ages in all four groups of race and sex compared with results from weighted analyses that accounted for attrition. Using methods accounting for dropout from an approximately 25-year health study, estimated rates of lung function decline varied by age, race, sex, and smoking status, with largest declines observed among current smokers at younger ages. Published by Elsevier Ltd.

The MMSE orientation for time domain is a strong predictor of subsequent cognitive decline in the elderly.

PubMed

Guerrero-Berroa, Elizabeth; Luo, Xiaodong; Schmeidler, James; Rapp, Michael A; Dahlman, Karen; Grossman, Hillel T; Haroutunian, Vahram; Beeri, Michal Schnaider

2009-12-01

The mini-mental state exam (MMSE) has been used to address questions such as determination of appropriate cutoff scores for differentiation of individuals with intact cognitive function from patients with dementia and rate of cognitive decline. However, little is known about the relationship of performance in specific cognitive domains to subsequent overall decline. To examine the specific and/or combined contribution of four MMSE domains (orientation for time, orientation for place, delayed recall, and attention) to prediction of overall cognitive decline on the MMSE. Linear mixed models were applied to 505 elderly nursing home residents (mean age = 85, > 12 years education = 27%; 79% F, mean follow-up = 3.20 years) to examine the relationship between baseline scores of these domains and total MMSE scores over time. Orientation for time was the only domain significantly associated with MMSE decline over time. Combination of poor delayed recall with either attention or orientation for place was associated with significantly increased decline on the MMSE. The MMSE orientation for time predicts overall decline on MMSE scores over time. A good functioning domain added to good functioning delayed recall was associated with slower rate of decline. Copyright (c) 2009 John Wiley & Sons, Ltd.

Exploring 2.5-Year Trajectories of Functional Decline in Older Adults by Applying a Growth Mixture Model and Frequency of Outings as a Predictor: A 2010-2013 JAGES Longitudinal Study.

PubMed

Saito, Junko; Kondo, Naoki; Saito, Masashige; Takagi, Daisuke; Tani, Yukako; Haseda, Maho; Tabuchi, Takahiro; Kondo, Katsunori

2018-06-23

We explored the distinct trajectories of functional decline among older adults in Japan, and evaluated whether the frequency of outings, an important indicator of social activity, predicts the identified trajectories. We analyzed data on 2,364 adults aged 65 years or older from the Japan Aichi Gerontological Evaluation Study. Participants were initially independent and later developed functional disability during a 31-month follow-up period. We used the level of long-term care needs certified in the public health insurance system as a proxy of functional ability and linked the fully tracked data of changes in the care levels to the baseline data. A low frequency of outings was defined as leaving one's home less than once per week at baseline. We applied a growth mixture model to identify trajectories in functional decline by sex and then examined the association between the frequency of outings and the identified trajectories using multinomial logistic regression analysis. Three distinct trajectories were identified: "slowly declining" (64.3% of men and 79.7% of women), "persistently disabled" (4.5% and 3.7%, respectively), and "rapidly declining" (31.3% and 16.6%, respectively). Men with fewer outings had 2.14 times greater odds (95% confidence interval, 1.03-4.41) of being persistently disabled. The association between outing frequency and functional decline trajectory was less clear statistically among women. While the majority of older adults showed a slow functional decline, some showed persistent moderate disability. Providing more opportunities to go out or assistance in that regard may be important for preventing persistent disability, and such needs might be greater among men.

Longer time spent in bed attempting to sleep is associated with rapid renal function decline: the Dongfeng-Tongji cohort study.

PubMed

Li, Yizhun; Yang, Liangle; Wang, Hao; Jiang, Haijing; Qiu, Gaokun; Liu, Yiyi; Xiao, Yang; Yang, Handong; Wu, Tangchun; Zhang, Xiaomin

2018-03-01

Prospective evidence on the relation between time in bed and renal dysfunction remains limited. We aimed to investigate the association of time spent in bed attempting to sleep (TSBS) with renal function decline in a middle-aged and elderly Chinese population. About 16,733 eligible participants with a mean age of 62.3 years at baseline were included. Rapid renal function decline was defined as (baseline eGFR - revisit eGFR)/years of follow-up ≥5 mL/min per 1.73 m 2 /year. A total of 1738 study participants experienced rapid renal function decline after a median 4.6-year follow-up. Logistic regression models were used for multivariate analyses. The adjusted odds ratio (OR) of rapid renal function decline was 1.18 (95% CI: 1.02, 1.37) for TSBS ≥9 h/night compared with TSBS 7 to <8 h/night. This association remained significant (OR = 1.19, 95% CI: 1.03, 1.38) after further adjustment for sleep quality, midday napping and usage of sleeping pills. Particularly, the association appeared to be prominent in individuals with diabetes. Longer TSBS (≥9 h) was independently associated with an increased risk of rapid renal function decline. Our findings emphasized the importance to have optimal TSBS. Key messages Our study firstly investigated the association between time spent in bed attempting to sleep (TSBS) and renal dysfunction in Chinese adults. Compared with individuals TSBS 7 to <8 h, individuals with TSBS ≥9 h had 19% increased risk for rapid renal function decline after adjustment for multivariate confounders. The association appeared to be prominent in individuals with diabetes.

Aging and Hearing Health: The Life-course Approach.

PubMed

Davis, Adrian; McMahon, Catherine M; Pichora-Fuller, Kathleen M; Russ, Shirley; Lin, Frank; Olusanya, Bolajoko O; Chadha, Shelly; Tremblay, Kelly L

2016-04-01

Sensory abilities decline with age. More than 5% of the world's population, approximately 360 million people, have disabling hearing loss. In adults, disabling hearing loss is defined by thresholds greater than 40 dBHL in the better hearing ear.Hearing disability is an important issue in geriatric medicine because it is associated with numerous health issues, including accelerated cognitive decline, depression, increased risk of dementia, poorer balance, falls, hospitalizations, and early mortality. There are also social implications, such as reduced communication function, social isolation, loss of autonomy, impaired driving ability, and financial decline. Furthermore, the onset of hearing loss is gradual and subtle, first affecting the detection of high-pitched sounds and with difficulty understanding speech in noisy but not in quiet environments. Consequently, delays in recognizing and seeking help for hearing difficulties are common. Age-related hearing loss has no known cure, and technologies (hearing aids, cochlear implants, and assistive devices) improve thresholds but do not restore hearing to normal. Therefore, health care for persons with hearing loss and people within their communication circles requires education and counseling (e.g., increasing knowledge, changing attitudes, and reducing stigma), behavior change (e.g., adapting communication strategies), and environmental modifications (e.g., reducing noise). In this article, we consider the causes, consequences, and magnitude of hearing loss from a life-course perspective. We examine the concept of "hearing health," how to achieve it, and implications for policy and practice. © The Author 2016. 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.

Disproportionate Declines in Ground-Foraging Insectivorous Birds after Mistletoe Removal

PubMed Central

Watson, David M.

2015-01-01

Insectivorous birds have been recognized as disproportionately sensitive to land-use intensification and habitat loss, with those species feeding primarily on the ground exhibiting some of the most dramatic declines. Altered litter inputs and availability of epigeic arthropods have been suggested to underlie reduced abundances and shrinking distributions but direct evidence is lacking. I used a patch-scale removal experiment in southern Australia to evaluate whether ground-feeding insectivores are especially vulnerable to altered litter-fall. Building on work demonstrating the importance of mistletoe litter to nutrient dynamics, litter was reduced by removing mistletoe (Loranthaceae) from one set of eucalypt woodlands, responses of birds three years after mistletoe removal compared with otherwise similar control woodlands containing mistletoe. Despite not feeding on mistletoes directly, insectivores exhibited the greatest response to mistletoe removal. Among woodland residents, ground-foraging insectivores showed the most dramatic response; treatment woodlands losing an average of 37.4% of their pre-treatment species richness. Once these 19 species of ground-foraging insectivores were excluded, remaining woodland species showed no significant effect of mistletoe removal. This response reflects greater initial losses in treatment woodlands during the study (which coincided with a severe drought) and double the number of species returning to control woodlands (where mistletoe numbers and litter were not manipulated) post-drought. These findings support the productivity-based explanation of declining insectivores, suggesting diminished litter-fall reduced habitat quality for these birds via decreased availability of their preferred prey. In addition to altered prey availability, interactions between litter-fall and epigeic arthropods exemplify the importance of below-ground / above-ground linkages driving ecosystem function. PMID:26640895

Fractures as an independent predictor of functional decline in older people: a population-based study with an 8-year follow-up.

PubMed

Piirtola, Maarit; Löppönen, Minna; Vahlberg, Tero; Isoaho, Raimo; Kivelä, Sirkka-Liisa; Räihä, Ismo

2012-01-01

Fractures among older people are common, but there is scant evidence about the impact of fractures on functional decline in an unselected older population. The objective of this study was to analyze the impact of lower and upper body fractures on functional performance among older adults during an 8-year follow-up. A population-based cohort of 616 Finnish persons aged 65 and over was followed for up to 8 years, and the association between fractures and the risk of short-term (0-2 years) and long-term (up to 8 years) functional decline was analyzed. Fractures were categorized according their functional influence on mobility and activities of daily living (ADL) into lower and upper body fractures. Multivariate cumulative logistic regression model was used in the analyses. During the 8-year follow-up, 112 (18%) persons sustained at least one fracture. In the multivariate analyses, lower body fractures predicted both short-term and long-term decline in mobility [cumulative odds ratio (COR) 4.7, 95% confidence interval (95% CI) 1.9-11.7 and COR 2.6, 95% CI 1.1-6.2, respectively] and in ADL performance (COR 3.1, 95% CI 1.3-7.6 and COR 4.7, 95% CI 2.0-11.4, respectively). Upper body fractures predicted decline in ADL performance during the long-term follow-up (COR 2.5, 95% CI 1.3-4.8). Pre-fracture functional decline and inactivity in leisure time physical exercise were independently associated with the risk of decline in extensive activities. Fractures have an independent influence on the development of functional decline in older persons regardless of the pre-fracture health. Prevention of falls and fractures and improvement of treatment, rehabilitation and follow-up process after fractures are needed. Copyright © 2011 S. Karger AG, Basel.

Liraglutide prevents cognitive decline in a rat model of streptozotocin-induced diabetes independently from its peripheral metabolic effects.

PubMed

Palleria, Caterina; Leo, Antonio; Andreozzi, Francesco; Citraro, Rita; Iannone, Michelangelo; Spiga, Rosangela; Sesti, Giorgio; Constanti, Andrew; De Sarro, Giovambattista; Arturi, Franco; Russo, Emilio

2017-03-15

Diabetes has been identified as a risk factor for cognitive dysfunctions. Glucagone like peptide 1 (GLP-1) receptor agonists have neuroprotective effects in preclinical animal models. We evaluated the effects of GLP-1 receptor agonist, liraglutide (LIR), on cognitive decline associated with diabetes. Furthermore, we studied LIR effects against hippocampal neurodegeneration induced by streptozotocin (STZ), a well-validated animal model of diabetes and neurodegeneration associated with cognitive decline. Diabetes and/or cognitive decline were induced in Wistar rats by intraperitoneal or intracerebroventricular injection of STZ and then rats were treated with LIR (300μg/kg daily subcutaneously) for 6 weeks. Rats underwent behavioral tests: Morris water maze, passive avoidance, forced swimming (FST), open field, elevated plus maze, rotarod tests. Furthermore, LIR effects on hippocampal neurodegeneration and mTOR pathway (AKT, AMPK, ERK and p70S6K) were assessed. LIR improved learning and memory only in STZ-treated animals. Anxiolytic effects were observed in all LIR-treated groups but pro-depressant effects in CTRL rats were observed. At a cellular/molecular level, intracerebroventricular STZ induced hippocampal neurodegeneration accompanied by decreased phosphorylation of AMPK, AKT, ERK and p70S6K. LIR reduced hippocampal neuronal death and prevented the decreased phosphorylation of AKT and p70S6K; AMPK was hyper-phosphorylated in comparison to CTRL group, while LIR had no effects on ERK. LIR reduced animal endurance in the rotarod test and this effect might be also linked to a reduction in locomotor activity during only the last two minutes of the FST. LIR had protective effects on cognitive functions in addition to its effects on blood glucose levels. LIR effects in the brain also comprised anxiolytic and pro-depressant actions (although influenced by reduced endurance). Finally, LIR protected from diabetes-dependent hippocampal neurodegeneration likely through an effect on mTOR pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

Fishing out marine parasites? Impacts of fishing on rates of parasitism in the ocean.

PubMed

Wood, Chelsea L; Lafferty, Kevin D; Micheli, Fiorenza

2010-06-01

Among anthropogenic effects on the ocean, fishing is one of the most pervasive and extends deepest into the past. Because fishing reduces the density of fish (reducing transmission efficiency of directly transmitted parasites), selectively removes large fish (which tend to carry more parasites than small fish), and reduces food web complexity (reducing transmission efficiency of trophically transmitted parasites), the removal of fish from the world's oceans over the course of hundreds of years may be driving a longterm, global decline in fish parasites. There has been growing recognition in recent years that parasites are a critical part of biodiversity and that their loss could substantially alter ecosystem function. Such a loss may be among the last major ecological effects of industrial fishing to be recognized by scientists.

Fishing out marine parasites? Impacts of fishing on rates of parasitism in the ocean

USGS Publications Warehouse

Wood, Chelsea L.; Lafferty, Kevin D.; Micheli, Fiorenza

2010-01-01

Among anthropogenic effects on the ocean, fishing is one of the most pervasive and extends deepest into the past. Because fishing reduces the density of fish (reducing transmission efficiency of directly transmitted parasites), selectively removes large fish (which tend to carry more parasites than small fish), and reduces food web complexity (reducing transmission efficiency of trophically transmitted parasites), the removal of fish from the world’s oceans over the course of hundreds of years may be driving a long-term, global decline in fish parasites. There has been growing recognition in recent years that parasites are a critical part of biodiversity and that their loss could substantially alter ecosystem function. Such a loss may be among the last major ecological effects of industrial fishing to be recognized by scientists.

Cognitive Aging Research: What Does It Say about Cognition? Aging?

ERIC Educational Resources Information Center

Glucksberg, Sam

Cognitive aging research needs to clarify whether or not there are functional or ability declines with aging and, if so, to understand and mediate these declines. Recent research which has demonstrated declines in cognitive functioning with age has involved episodic memory and rehearsal-independent forms of such memory. It is not known how much of…

Loneliness and Cognitive Function in Older Adults: Findings From the Chinese Longitudinal Healthy Longevity Survey

PubMed Central

Chen, Shu-Lin; Tu, Xin; Conwell, Yeates

2017-01-01

Objectives: To examine the relationship between loneliness and cognitive function and to explore the mediating role of physical health on the loneliness–cognition relationship in Chinese older adults (OAs). Method: Data came from a nationally representative sample of 14,199 Chinese OAs (aged 65+) from 2002, 2005, 2008, and 2011 waves of the Chinese Longitudinal Healthy Longevity Survey. A latent variable cross-lagged panel model combined with mediation analysis was used to determine the relationship between loneliness and cognitive function and the mediating effect of increase in the number of chronic conditions (ΔNCCs) on the ascertained loneliness–cognition relationship. Results: Severe loneliness at prior assessment points was significantly associated with poorer cognitive function at subsequent assessments, and vice versa. The ΔNCCs partially mediated this prospective reciprocal relationships, accounting for 2.58% of the total effect of loneliness on cognition and 4.44% of the total effect of cognition on loneliness, respectively. Discussion: Loneliness may predict subsequent cognitive decline, and vice versa. This loneliness–cognition relationship is partially explained by their impact on physical health. Multidisciplinary interventions aimed at reducing loneliness and cognitive decline per se and their associated risk factors as well as improving chronic illness management would be beneficial for emotional well-being and cognitive health in OAs. PMID:27013536

Neuronal CCL2 is upregulated during hepatic encephalopathy and contributes to microglia activation and neurological decline

PubMed Central

2014-01-01

Background Acute liver failure leads to systemic complications with one of the most dangerous being a decline in neurological function, termed hepatic encephalopathy. Neurological dysfunction is exacerbated by an increase of toxic metabolites in the brain that lead to neuroinflammation. Following various liver diseases, hepatic and circulating chemokines, such as chemokine ligand 2 (CCL2), are elevated, though their effects on the brain following acute liver injury and subsequent hepatic encephalopathy are unknown. CCL2 is known to activate microglia in other neuropathies, leading to a proinflammatory response. However, the effects of CCL2 on microglia activation and the pathogenesis of hepatic encephalopathy following acute liver injury remain to be determined. Methods Hepatic encephalopathy was induced in mice via injection of azoxymethane (AOM) in the presence or absence of INCB 3284 dimesylate (INCB), a chemokine receptor 2 inhibitor, or C 021 dihydrochloride (C021), a chemokine receptor 4 inhibitor. Mice were monitored for neurological decline and time to coma (loss of all reflexes) was recorded. Tissue was collected at coma and used for real-time PCR, immunoblots, ELISA, or immunostaining analyses to assess the activation of microglia and consequences on pro-inflammatory cytokine expression. Results Following AOM administration, microglia activation was significantly increased in AOM-treated mice compared to controls. Concentrations of CCL2 in the liver, serum, and cortex were significantly elevated in AOM-treated mice compared to controls. Systemic administration of INCB or C021 reduced liver damage as assessed by serum liver enzyme biochemistry. Administration of INCB or C021 significantly improved the neurological outcomes of AOM-treated mice, reduced microglia activation, reduced phosphorylation of ERK1/2, and alleviated AOM-induced cytokine upregulation. Conclusions These findings suggest that CCL2 is elevated systemically following acute liver injury and that CCL2 is involved in both the microglia activation and neurological decline associated with hepatic encephalopathy. Methods used to modulate CCL2 levels and/or reduce CCR2/CCR4 activity may be potential therapeutic targets for the management of hepatic encephalopathy due to acute liver injury. PMID:25012628

Neuronal CCL2 is upregulated during hepatic encephalopathy and contributes to microglia activation and neurological decline.

PubMed

McMillin, Matthew; Frampton, Gabriel; Thompson, Michelle; Galindo, Cheryl; Standeford, Holly; Whittington, Eric; Alpini, Gianfranco; DeMorrow, Sharon

2014-07-10

Acute liver failure leads to systemic complications with one of the most dangerous being a decline in neurological function, termed hepatic encephalopathy. Neurological dysfunction is exacerbated by an increase of toxic metabolites in the brain that lead to neuroinflammation. Following various liver diseases, hepatic and circulating chemokines, such as chemokine ligand 2 (CCL2), are elevated, though their effects on the brain following acute liver injury and subsequent hepatic encephalopathy are unknown. CCL2 is known to activate microglia in other neuropathies, leading to a proinflammatory response. However, the effects of CCL2 on microglia activation and the pathogenesis of hepatic encephalopathy following acute liver injury remain to be determined. Hepatic encephalopathy was induced in mice via injection of azoxymethane (AOM) in the presence or absence of INCB 3284 dimesylate (INCB), a chemokine receptor 2 inhibitor, or C 021 dihydrochloride (C021), a chemokine receptor 4 inhibitor. Mice were monitored for neurological decline and time to coma (loss of all reflexes) was recorded. Tissue was collected at coma and used for real-time PCR, immunoblots, ELISA, or immunostaining analyses to assess the activation of microglia and consequences on pro-inflammatory cytokine expression. Following AOM administration, microglia activation was significantly increased in AOM-treated mice compared to controls. Concentrations of CCL2 in the liver, serum, and cortex were significantly elevated in AOM-treated mice compared to controls. Systemic administration of INCB or C021 reduced liver damage as assessed by serum liver enzyme biochemistry. Administration of INCB or C021 significantly improved the neurological outcomes of AOM-treated mice, reduced microglia activation, reduced phosphorylation of ERK1/2, and alleviated AOM-induced cytokine upregulation. These findings suggest that CCL2 is elevated systemically following acute liver injury and that CCL2 is involved in both the microglia activation and neurological decline associated with hepatic encephalopathy. Methods used to modulate CCL2 levels and/or reduce CCR2/CCR4 activity may be potential therapeutic targets for the management of hepatic encephalopathy due to acute liver injury.

Reduced sperm counts in guppies (Poecilia reticulata) following exposure to low levels of tributyltin and bisphenol A.

PubMed Central

Haubruge, E; Petit, F; Gage, M J

2000-01-01

There is increasing evidence that normal male reproductive function can be disrupted by exposure to pollutants in the environment that can exogenously mimic, antagonize or block sex-hormone function. One possible consequence of exposure to these xenobiotics is disruption to spermatogenesis, but results thus far provide only indirect and inconsistent evidence. In this study we exposed adult male guppies (Poeciliidae: Teleostei) to environmentally relevant levels of the common xenobiotics tributyltin (11.2-22.3 ngl-1) and bisphenol A (274-549 micrograms l-1) in experimental aquaria. After 21 days of exposure, we found significant declines (by 40-75%) in total sperm counts for male fishes exposed to tributyltin and bisphenol A compared with controls. This short-term decline in sperm count is unlikely to be the result of endocrine-mediated alteration of the germ line, and we found no change in testis size or sperm lengths between treatments. However, Sertoli cells, which facilitate the transport of maturing sperm into the testicular deferent duct (where they are stored prior to ejaculation), are directly sensitive to xenobiotic action and it is therefore possible that spermatogenesis was inhibited through in vivo interference with normal Sertoli-cell function. PMID:11413652

Non-invasive brain stimulation of the aging brain: State of the art and future perspectives.

PubMed

Tatti, Elisa; Rossi, Simone; Innocenti, Iglis; Rossi, Alessandro; Santarnecchi, Emiliano

2016-08-01

Favored by increased life expectancy and reduced birth rate, worldwide demography is rapidly shifting to older ages. The golden age of aging is not only an achievement but also a big challenge because of the load of the elderly on social and medical health care systems. Moreover, the impact of age-related decline of attention, memory, reasoning and executive functions on self-sufficiency emphasizes the need of interventions to maintain cognitive abilities at a useful degree in old age. Recently, neuroscientific research explored the chance to apply Non-Invasive Brain Stimulation (NiBS) techniques (as transcranial electrical and magnetic stimulation) to healthy aging population to preserve or enhance physiologically-declining cognitive functions. The present review will update and address the current state of the art on NiBS in healthy aging. Feasibility of NiBS techniques will be discussed in light of recent neuroimaging (either structural or functional) and neurophysiological models proposed to explain neural substrates of the physiologically aging brain. Further, the chance to design multidisciplinary interventions to maximize the efficacy of NiBS techniques will be introduced as a necessary future direction. Copyright © 2016 Elsevier B.V. All rights reserved.

Reduced sperm counts in guppies (Poecilia reticulata) following exposure to low levels of tributyltin and bisphenol A.

PubMed

Haubruge, E; Petit, F; Gage, M J

2000-11-22

There is increasing evidence that normal male reproductive function can be disrupted by exposure to pollutants in the environment that can exogenously mimic, antagonize or block sex-hormone function. One possible consequence of exposure to these xenobiotics is disruption to spermatogenesis, but results thus far provide only indirect and inconsistent evidence. In this study we exposed adult male guppies (Poeciliidae: Teleostei) to environmentally relevant levels of the common xenobiotics tributyltin (11.2-22.3 ngl-1) and bisphenol A (274-549 micrograms l-1) in experimental aquaria. After 21 days of exposure, we found significant declines (by 40-75%) in total sperm counts for male fishes exposed to tributyltin and bisphenol A compared with controls. This short-term decline in sperm count is unlikely to be the result of endocrine-mediated alteration of the germ line, and we found no change in testis size or sperm lengths between treatments. However, Sertoli cells, which facilitate the transport of maturing sperm into the testicular deferent duct (where they are stored prior to ejaculation), are directly sensitive to xenobiotic action and it is therefore possible that spermatogenesis was inhibited through in vivo interference with normal Sertoli-cell function.

Health benefits of hard martial arts in adults: a systematic review.

PubMed

Origua Rios, Sandra; Marks, Jennifer; Estevan, Isaac; Barnett, Lisa M

2018-07-01

Participation in organized sports is promoted as a means of increasing physical activity levels and reducing chronic disease risk in adults. Hard martial arts practice (i.e. using body contact techniques), has gained in popularity over time. This review explores the evidence for health benefits of "hard" martial arts practice within the adult population. A systematic electronic database search was conducted, and quality assessments applied the Effective Public Health Practice Project tool. Twenty-eight studies met the inclusion criteria, examining balance, cognitive function, muscular skeletal status, psychological, cardiovascular fitness, and metabolic effects. The majority of studies reported positive effects resulting from hard martial arts practice, showing some improvement and maintenance of balance, cognitive function and psychological health. Benefits may be obtained regardless of the age of practice commencement. However, quality of the evidence is affected by methodological weaknesses across the studies. "Hard" martial arts seem to have potential to improve balance and cognitive functions that decline with age, which can lead to poorer health outcomes among the elderly (e.g. cognitive decline, falls and fractures). Benefits should be further investigated with improved intervention studies, representative samples and longer follow-up periods in order to establish associations with morbidity and mortality in the long term.

The assessment of macular electrophysiology and macular morphology in patients with vitiligo.

PubMed

Aydin, Rukiye; Ozsutcu, Mustafa; Erdur, Sevil Karaman; Dikkaya, Funda; Balevi, Ali; Ozbek, Merve; Senturk, Fevzi

2018-02-01

We aimed to analyze the electrophysiologic function and morphology of macula in vitiligo patients. Seventeen patients with vitiligo and 11 healthy subjects were studied. All participants underwent multifocal electroretinography (mfERG) and spectral domain optical coherence tomography (SD-OCT) evaluations. The mfERG (P1 mfERG responses central and peripheral) and retinal layer segmentation parameters (nine ETDRS subfields) were compared in vitiligo and control groups. The mean P1 response amplitudes were significantly decreased in central and peripheral rings of the fovea in patients with vitiligo compared with controls (p = 0.002 and p = 0.006, respectively). There was a tendency toward a prolonged mean implicit time for both central and peripheral in patients with vitiligo compared to controls, however, with no statistical significance (p = 0.453 and p = 0.05, respectively). There was no statistically significant difference in all retinal layers thickness between two groups. In patients with vitiligo, while photoreceptor segment preserved in SD-OCT, mfERG reduced showing potential decline in central retinal function. This study showed a potential decline in central retinal function in patients with vitiligo even if they have normal fundus appearance and SD-OCT findings.

The level of cognitive function and recognition of emotions in older adults

PubMed Central

Singh-Manoux, Archana; Batty, G. David; Ebmeier, Klaus P.; Jokela, Markus; Harmer, Catherine J.; Kivimäki, Mika

2017-01-01

Background The association between cognitive decline and the ability to recognise emotions in interpersonal communication is not well understood. We aimed to investigate the association between cognitive function and the ability to recognise emotions in other people’s facial expressions across the full continuum of cognitive capacity. Methods Cross-sectional analysis of 4039 participants (3016 men, 1023 women aged 59 to 82 years) in the Whitehall II study. Cognitive function was assessed using a 30-item Mini-Mental State Examination (MMSE), further classified into 8 groups: 30, 29, 28, 27, 26, 25, 24, and <24 (possible dementia) MMSE points. The Facial Expression Recognition Task (FERT) was used to examine recognition of anger, fear, disgust, sadness, and happiness. Results The multivariable adjusted difference in the percentage of accurate recognition between the highest and lowest MMSE group was 14.9 (95%CI, 11.1–18.7) for anger, 15.5 (11.9–19.2) for fear, 18.5 (15.2–21.8) for disgust, 11.6 (7.3–16.0) for sadness, and 6.3 (3.1–9.4) for happiness. However, recognition of several emotions was reduced already after 1 to 2-point reduction in MMSE and with further points down in MMSE, the recognition worsened at an accelerated rate. Conclusions The ability to recognize emotion in facial expressions is affected at an early stage of cognitive impairment and might decline at an accelerated rate with the deterioration of cognitive function. Accurate recognition of happiness seems to be less affected by a severe decline in cognitive performance than recognition of negatively valued emotions. PMID:28977015

Urinary peptidomics in a rodent model of diabetic nephropathy highlights epidermal growth factor as a biomarker for renal deterioration in patients with type 2 diabetes.

PubMed

Betz, Boris B; Jenks, Sara J; Cronshaw, Andrew D; Lamont, Douglas J; Cairns, Carolynn; Manning, Jonathan R; Goddard, Jane; Webb, David J; Mullins, John J; Hughes, Jeremy; McLachlan, Stela; Strachan, Mark W J; Price, Jackie F; Conway, Bryan R

2016-05-01

Many diabetic patients suffer from declining renal function without developing albuminuria. To identify alternative biomarkers for diabetic nephropathy (DN) we performed urinary peptidomic analysis in a rodent model in which hyperglycemia and hypertension synergize to promote renal pathologic changes consistent with human DN. We identified 297 increased and 15 decreased peptides in the urine of rats with DN compared with controls, including peptides derived from proteins associated with DN and novel candidate biomarkers. We confirmed by ELISA that one of the parent proteins, urinary epidermal growth factor (uEGF), was more than 2-fold reduced in rats with DN in comparison with controls. To assess the clinical utility of uEGF we examined renal outcomes in 642 participants from the Edinburgh Type 2 Diabetes Study who were normoalbuminuric and had preserved renal function at baseline. After adjustment for established renal risk factors, a lower uEGF to creatinine ratio was associated with new-onset estimated glomerular filtration rate less than 60 ml/min per 1.73m(2) (odds ratio 0.48; 95% confidence interval, 0.26-0.90), rapid (over 5% per annum) decline in renal function (odds ratio 0.44; 95% confidence interval, 0.27-0.72) or the composite of both outcomes (odds ratio 0.38; 95% confidence interval, 0.24-0.62). Thus, the utility of a low uEGF to creatinine ratio as a biomarker of progressive decline in renal function in normoalbuminuric patients should be assessed in additional populations. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Effects and biological limitations of +Gz acceleration on the autonomic functions-related circulation in rats.

PubMed

Nishida, Yasuhiro; Maruyama, Satoshi; Shouji, Ichiro; Kemuriyama, Takehito; Tashiro, Akimasa; Ohta, Hiroyuki; Hagisawa, Kohsue; Hiruma, Megumi; Yokoe, Hidetake

2016-11-01

The effects of gravitational loading (G load) on humans have been studied ever since the early 20th century. After the dangers of G load in the vertical head-to-leg direction (+Gz load) became evident, many animal experiments were performed between 1920 and 1945 in an effort to identify the origins of high G-force-induced loss of consciousness (G-LOC), which led to development of the anti-G suit. The establishment of norms and training for G-LOC prevention resulted in a gradual decline in reports of animal experiments on G load, a decline that steepened with the establishment of anti-G techniques in humans, such as special breathing methods and skeletal muscle contraction, called an anti-G straining maneuver, which are voluntary physiological functions. Because the issue involves humans during flight, the effects on humans themselves are clearly of great importance, but ethical considerations largely preclude any research on the human body that probes to any depth the endogenous physiological states and functions. The decline in reports on animal experiments may therefore signify a general decline in research into the changes seen in the various involuntary, autonomic functions. The declining number of related reports on investigations of physiological autonomic systems other than the circulatory system seems to bear this out. In this review, we therefore describe our findings on the effects of G load on the autonomic nervous system, cardiac function, cerebral blood flow, tissue oxygen level, and other physiological autonomic functions as measured in animal experiments, including denervation or pharmacological blocking, in an effort to present the limits and the mechanisms of G-load response extending physiologically. We demonstrate previously unrecognized risks due to G load, and also describe fundamental research aimed at countering these effects and development of a scientific training measure devised for actively enhancing +Gz tolerance in involuntary, autonomic system functions. The research described here is rough and incomplete, but it is offered as a beginning, in the hope that researchers may find it of reference and carry the effort toward completion. The advances described here include (1) a finding that cerebral arterial perfusion pressure decreases to nearly zero under +5.0 Gz loads, (2) indications that G load may cause myocardial microinjuries, (3) detection of differences between cerebral regions in tissue-oxygen level under +3.0 Gz load, (4) discovery that hypotension is deeper under decreasing +Gz loads than increasing +Gz loads with use of an anti-G system, due in part to suppression of baroreceptor reflex, and (5) revelations and efforts investigating new measures to reduce cerebral hypotension, namely the "teeth-clenching pressor response" and preconditioning with slight but repeated G loads.

Interplay between financial assets and social relations on decline in physical function and mortality among older people.

PubMed

Jørgensen, Terese Sara Høj; Lund, Rikke; Siersma, Volkert Dirk; Nilsson, Charlotte Juul

2018-06-01

It is well established that socioeconomic position (SEP) and social relations impact physical function and mortality in old age. Due to differential vulnerability, few social relations may lead to greater decline in physical function and mortality among older people with low compared to high SEP. The aim was to investigate whether older people with few social relations experience greater decline in physical function and mortality when also subject to low financial assets? The study population included 4060 older people aged 75 or 80 years at baseline in 1998-1999. Social relations at baseline and physical function at baseline and after 1.5, 3.0 and 4.5 years were obtained from questionnaires. Financial assets at baseline and mortality during 10 years of follow-up were obtained from registers. Analyses of the associations between financial assets combined with social relations and decline in physical function and mortality, respectively, were conducted. Among males, but not females, low financial assets and few social relations were associated with the greatest decline in physical function. Yet, interaction only reached significance between financial assets and visits. Among males and females, low financial assets and few social relations were associated with the highest mortality. Interactions only reached significance between financial assets and visits for females and social activity for males. In conclusion, few social relations implied greater decline in physical function among older males and higher mortality among older males and females with low financial assets; however, the study only supports the presence of differential vulnerability for visits and social activity.

Molecular Mechanisms Responsible for Increased Vulnerability of the Ageing Oocyte to Oxidative Damage

PubMed Central

Redgrove, Kate A.; McLaughlin, Eileen A.

2017-01-01

In their midthirties, women experience a decline in fertility, coupled to a pronounced increase in the risk of aneuploidy, miscarriage, and birth defects. Although the aetiology of such pathologies are complex, a causative relationship between the age-related decline in oocyte quality and oxidative stress (OS) is now well established. What remains less certain are the molecular mechanisms governing the increased vulnerability of the aged oocyte to oxidative damage. In this review, we explore the reduced capacity of the ageing oocyte to mitigate macromolecular damage arising from oxidative insults and highlight the dramatic consequences for oocyte quality and female fertility. Indeed, while oocytes are typically endowed with a comprehensive suite of molecular mechanisms to moderate oxidative damage and thus ensure the fidelity of the germline, there is increasing recognition that the efficacy of such protective mechanisms undergoes an age-related decline. For instance, impaired reactive oxygen species metabolism, decreased DNA repair, reduced sensitivity of the spindle assembly checkpoint, and decreased capacity for protein repair and degradation collectively render the aged oocyte acutely vulnerable to OS and limits their capacity to recover from exposure to such insults. We also highlight the inadequacies of our current armoury of assisted reproductive technologies to combat age-related female infertility, emphasising the need for further research into mechanisms underpinning the functional deterioration of the ageing oocyte. PMID:29312475

The effects of sleep deprivation on item and associative recognition memory.

PubMed

Ratcliff, Roger; Van Dongen, Hans P A

2018-02-01

Sleep deprivation adversely affects the ability to perform cognitive tasks, but theories range from predicting an overall decline in cognitive functioning because of reduced stability in attentional networks to specific deficits in various cognitive domains or processes. We measured the effects of sleep deprivation on two memory tasks, item recognition ("was this word in the list studied") and associative recognition ("were these two words studied in the same pair"). These tasks test memory for information encoded a few minutes earlier and so do not address effects of sleep deprivation on working memory or consolidation after sleep. A diffusion model was used to decompose accuracy and response time distributions to produce parameter estimates of components of cognitive processing. The model assumes that over time, noisy evidence from the task stimulus is accumulated to one of two decision criteria, and parameters governing this process are extracted and interpreted in terms of distinct cognitive processes. Results showed that sleep deprivation reduces drift rate (evidence used in the decision process), with little effect on the other components of the decision process. These results contrast with the effects of aging, which show little decline in item recognition but large declines in associative recognition. The results suggest that sleep deprivation degrades the quality of information stored in memory and that this may occur through degraded attentional processes. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Spaceflight effects on single skeletal muscle fiber function in the rhesus monkey.

PubMed

Fitts, R H; Desplanches, D; Romatowski, J G; Widrick, J J

2000-11-01

The purpose of this investigation was to understand how 14 days of weightlessness alters the cellular properties of individual slow- and fast-twitch muscle fibers in the rhesus monkey. The diameter of the soleus (Sol) type I, medial gastrocnemius (MG) type I, and MG type II fibers from the vivarium controls averaged 60 +/- 1, 46 +/- 2, and 59 +/- 2 microm, respectively. Both a control 1-G capsule sit (CS) and spaceflight (SF) significantly reduced the Sol type I fiber diameter (20 and 13%, respectively) and peak force, with the latter declining from 0.48 +/- 0.01 to 0.31 +/- 0.02 (CS group) and 0.32 +/- 0.01 mN (SF group). When the peak force was expressed as kiloNewtons per square meter (kN/m(2)), only the SF group showed a significant decline. This group also showed a significant 15% drop in peak fiber stiffness that suggests that fewer cross bridges were contracting in parallel. In the MG, SF but not CS depressed the type I fiber diameter and force. Additionally, SF significantly depressed absolute (mN) and relative (kN/m(2)) force in the fast-twitch MG fibers by 30% and 28%, respectively. The Ca(2+) sensitivity of the type I fiber (Sol and MG) was significantly reduced by growth but unaltered by SF. Flight had no significant effect on the mean maximal fiber shortening velocity in any fiber type or muscle. The post-SF Sol type I fibers showed a reduced peak power and, at peak power, an elevated velocity and decreased force. In conclusion, CS and SF caused atrophy and a reduced force and power in the Sol type I fiber. However, only SF elicited atrophy and reduced force (mN) in the MG type I fiber and a decline in relative force (kN/m(2)) in the Sol type I and MG type II fibers.

Spaceflight effects on single skeletal muscle fiber function in the rhesus monkey

NASA Technical Reports Server (NTRS)

Fitts, R. H.; Desplanches, D.; Romatowski, J. G.; Widrick, J. J.

2000-01-01

The purpose of this investigation was to understand how 14 days of weightlessness alters the cellular properties of individual slow- and fast-twitch muscle fibers in the rhesus monkey. The diameter of the soleus (Sol) type I, medial gastrocnemius (MG) type I, and MG type II fibers from the vivarium controls averaged 60 +/- 1, 46 +/- 2, and 59 +/- 2 microm, respectively. Both a control 1-G capsule sit (CS) and spaceflight (SF) significantly reduced the Sol type I fiber diameter (20 and 13%, respectively) and peak force, with the latter declining from 0.48 +/- 0.01 to 0.31 +/- 0.02 (CS group) and 0.32 +/- 0.01 mN (SF group). When the peak force was expressed as kiloNewtons per square meter (kN/m(2)), only the SF group showed a significant decline. This group also showed a significant 15% drop in peak fiber stiffness that suggests that fewer cross bridges were contracting in parallel. In the MG, SF but not CS depressed the type I fiber diameter and force. Additionally, SF significantly depressed absolute (mN) and relative (kN/m(2)) force in the fast-twitch MG fibers by 30% and 28%, respectively. The Ca(2+) sensitivity of the type I fiber (Sol and MG) was significantly reduced by growth but unaltered by SF. Flight had no significant effect on the mean maximal fiber shortening velocity in any fiber type or muscle. The post-SF Sol type I fibers showed a reduced peak power and, at peak power, an elevated velocity and decreased force. In conclusion, CS and SF caused atrophy and a reduced force and power in the Sol type I fiber. However, only SF elicited atrophy and reduced force (mN) in the MG type I fiber and a decline in relative force (kN/m(2)) in the Sol type I and MG type II fibers.

Environmental enrichment strengthens corticocortical interactions and reduces amyloid-β oligomers in aged mice

PubMed Central

Mainardi, Marco; Di Garbo, Angelo; Caleo, Matteo; Berardi, Nicoletta; Sale, Alessandro; Maffei, Lamberto

2013-01-01

Brain aging is characterized by global changes which are thought to underlie age-related cognitive decline. These include variations in brain activity and the progressive increase in the concentration of soluble amyloid-β (Aβ) oligomers, directly impairing synaptic function and plasticity even in the absence of any neurodegenerative disorder. Considering the high social impact of the decline in brain performance associated to aging, there is an urgent need to better understand how it can be prevented or contrasted. Lifestyle components, such as social interaction, motor exercise and cognitive activity, are thought to modulate brain physiology and its susceptibility to age-related pathologies. However, the precise functional and molecular factors that respond to environmental stimuli and might mediate their protective action again pathological aging still need to be clearly identified. To address this issue, we exploited environmental enrichment (EE), a reliable model for studying the effect of experience on the brain based on the enhancement of cognitive, social and motor experience, in aged wild-type mice. We analyzed the functional consequences of EE on aged brain physiology by performing in vivo local field potential (LFP) recordings with chronic implants. In addition, we also investigated changes induced by EE on molecular markers of neural plasticity and on the levels of soluble Aβ oligomers. We report that EE induced profound changes in the activity of the primary visual and auditory cortices and in their functional interaction. At the molecular level, EE enhanced plasticity by an upward shift of the cortical excitation/inhibition balance. In addition, EE reduced brain Aβ oligomers and increased synthesis of the Aβ-degrading enzyme neprilysin. Our findings strengthen the potential of EE procedures as a non-invasive paradigm for counteracting brain aging processes. PMID:24478697

Environmental enrichment strengthens corticocortical interactions and reduces amyloid-β oligomers in aged mice.

PubMed

Mainardi, Marco; Di Garbo, Angelo; Caleo, Matteo; Berardi, Nicoletta; Sale, Alessandro; Maffei, Lamberto

2014-01-01

Brain aging is characterized by global changes which are thought to underlie age-related cognitive decline. These include variations in brain activity and the progressive increase in the concentration of soluble amyloid-β (Aβ) oligomers, directly impairing synaptic function and plasticity even in the absence of any neurodegenerative disorder. Considering the high social impact of the decline in brain performance associated to aging, there is an urgent need to better understand how it can be prevented or contrasted. Lifestyle components, such as social interaction, motor exercise and cognitive activity, are thought to modulate brain physiology and its susceptibility to age-related pathologies. However, the precise functional and molecular factors that respond to environmental stimuli and might mediate their protective action again pathological aging still need to be clearly identified. To address this issue, we exploited environmental enrichment (EE), a reliable model for studying the effect of experience on the brain based on the enhancement of cognitive, social and motor experience, in aged wild-type mice. We analyzed the functional consequences of EE on aged brain physiology by performing in vivo local field potential (LFP) recordings with chronic implants. In addition, we also investigated changes induced by EE on molecular markers of neural plasticity and on the levels of soluble Aβ oligomers. We report that EE induced profound changes in the activity of the primary visual and auditory cortices and in their functional interaction. At the molecular level, EE enhanced plasticity by an upward shift of the cortical excitation/inhibition balance. In addition, EE reduced brain Aβ oligomers and increased synthesis of the Aβ-degrading enzyme neprilysin. Our findings strengthen the potential of EE procedures as a non-invasive paradigm for counteracting brain aging processes.

Preservation of cognitive and functional ability as markers of longevity.

PubMed

Schupf, Nicole; Costa, Rosann; Tang, Ming-Xin; Andrews, Howard; Tycko, Benjamin; Lee, Joseph H; Mayeux, Richard

2004-10-01

Longevity is a complex biological process for which the phenotypes have not been established. Preservation of cognitive and physical function may be important and preservation of these functions is, in part, inherited. We investigated the relation between rate of change in cognitive and functional abilities in probands and risk of death in their siblings. Probands were classified as showing no decline, slow, medium, or rapid rate of decline, based on the slope of change in cognitive and physical/functional factors over three or more assessments. Siblings of probands who did not decline on measures of memory, visuospatial/cognitive function or ADL skills were approximately half as likely to die as siblings of probands who had the most rapid decline. The reduction in risk of death in siblings of probands who did not decline in was primarily observed among siblings of probands who were older than 75 years, suggesting that genetic influences on life span may be greater at older ages. There was no association between probands' rate of change in language, IADL skills, upper or lower extremity mobility and risk of death in siblings. The results of the present study identify phenotypes associated with preserved cognitive and functional abilities which may serve as markers for longevity.

The Potential Utility of Eye Movements in the Detection and Characterization of Everyday Functional Difficulties in Mild Cognitive Impairment.

PubMed

Seligman, Sarah C; Giovannetti, Tania

2015-06-01

Mild cognitive impairment (MCI) refers to the intermediate period between the typical cognitive decline of normal aging and more severe decline associated with dementia, and it is associated with greater risk for progression to dementia. Research has suggested that functional abilities are compromised in MCI, but the degree of impairment and underlying mechanisms remain poorly understood. The development of sensitive measures to assess subtle functional decline poses a major challenge for characterizing functional limitations in MCI. Eye-tracking methodology has been used to describe visual processes in everyday, naturalistic action among healthy older adults as well as several case studies of severely impaired individuals, and it has successfully differentiated healthy older adults from those with MCI on specific visual tasks. These studies highlight the promise of eye-tracking technology as a method to characterize subtle functional decline in MCI. However, to date no studies have examined visual behaviors during completion of naturalistic tasks in MCI. This review describes the current understanding of functional ability in MCI, summarizes findings of eye-tracking studies in healthy individuals, severe impairment, and MCI, and presents future research directions to aid with early identification and prevention of functional decline in disorders of aging.

Eicosapentaenoic acid but not docosahexaenoic acid restores skeletal muscle mitochondrial oxidative capacity in old mice.

PubMed

Johnson, Matthew L; Lalia, Antigoni Z; Dasari, Surendra; Pallauf, Maximilian; Fitch, Mark; Hellerstein, Marc K; Lanza, Ian R

2015-10-01

Mitochondrial dysfunction is often observed in aging skeletal muscle and is implicated in age-related declines in physical function. Early evidence suggests that dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) improve mitochondrial function. Here, we show that 10 weeks of dietary eicosapentaenoic acid (EPA) supplementation partially attenuated the age-related decline in mitochondrial function in mice, but this effect was not observed with docosahexaenoic acid (DHA). The improvement in mitochondrial function with EPA occurred in the absence of any changes in mitochondrial abundance or biogenesis, which was evaluated from RNA sequencing, large-scale proteomics, and direct measurements of muscle mitochondrial protein synthesis rates. We find that EPA improves muscle protein quality, specifically by decreasing mitochondrial protein carbamylation, a post-translational modification that is driven by inflammation. These results demonstrate that EPA attenuated the age-related loss of mitochondrial function and improved mitochondrial protein quality through a mechanism that is likely linked with anti-inflammatory properties of n-3 PUFAs. Furthermore, we demonstrate that EPA and DHA exert some common biological effects (anticoagulation, anti-inflammatory, reduced FXR/RXR activation), but also exhibit many distinct biological effects, a finding that underscores the importance of evaluating the therapeutic potential of individual n-3 PUFAs. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Two Days' Sleep Debt Causes Mood Decline During Resting State Via Diminished Amygdala-Prefrontal Connectivity.

PubMed

Motomura, Yuki; Katsunuma, Ruri; Yoshimura, Michitaka; Mishima, Kazuo

2017-10-01

Sleep debt (SD) has been suggested to evoke emotional instability by diminishing the suppression of the amygdala by the medial prefrontal cortex (MPFC). Here, we investigated how short-term SD affects resting-state functional connectivity between the amygdala and MPFC, self-reported mood, and sleep parameters. Eighteen healthy adult men aged 29 ± 8.24 years participated in a 2-day sleep control session (SC; time in bed [TIB], 9 hours) and 2-day SD session (TIB, 3 hours). On day 2 of each session, resting-state functional magnetic resonance imaging was performed, followed immediately by measuring self-reported mood on the State-Trait Anxiety Inventory-State subscale (STAI-S). STAI-S score was significantly increased, and functional connectivity between the amygdala and MPFC was significantly decreased in SD compared with SC. Significant correlations were observed between reduced rapid eye movement (REM) sleep and reduced left amygdala-MPFC functional connectivity (FCL_amg-MPFC) and between reduced FCL_amg-MPFC and increased STAI-S score in SD compared with SC. These findings suggest that reduced MPFC functional connectivity of amygdala activity is involved in mood deterioration under SD, and that REM sleep reduction is involved in functional changes in the corresponding brain regions. Having adequate REM sleep may be important for mental health maintenance. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Cleaning at Home and at Work in Relation to Lung Function Decline and Airway Obstruction.

PubMed

Svanes, Øistein; Bertelsen, Randi J; Lygre, Stein H L; Carsin, Anne E; Antó, Josep M; Forsberg, Bertil; García-García, José M; Gullón, José A; Heinrich, Joachim; Holm, Mathias; Kogevinas, Manolis; Urrutia, Isabel; Leynaert, Bénédicte; Moratalla, Jesús M; Le Moual, Nicole; Lytras, Theodore; Norbäck, Dan; Nowak, Dennis; Olivieri, Mario; Pin, Isabelle; Probst-Hensch, Nicole; Schlünssen, Vivi; Sigsgaard, Torben; Skorge, Trude D; Villani, Simona; Jarvis, Debbie; Zock, Jan P; Svanes, Cecilie

2018-05-01

Cleaning tasks may imply exposure to chemical agents with potential harmful effects to the respiratory system, and increased risk of asthma and respiratory symptoms among professional cleaners and in persons cleaning at home has been reported. Long-term consequences of cleaning agents on respiratory health are, however, not well described. This study aimed to investigate long-term effects of occupational cleaning and cleaning at home on lung function decline and airway obstruction. The European Community Respiratory Health Survey (ECRHS) investigated a multicenter population-based cohort at three time points over 20 years. A total of 6,235 participants with at least one lung function measurement from 22 study centers, who in ECRHS II responded to questionnaire modules concerning cleaning activities between ECRHS I and ECRHS II, were included. The data were analyzed with mixed linear models adjusting for potential confounders. As compared with women not engaged in cleaning (ΔFEV 1  = -18.5 ml/yr), FEV 1 declined more rapidly in women responsible for cleaning at home (-22.1; P = 0.01) and occupational cleaners (-22.4; P = 0.03). The same was found for decline in FVC (ΔFVC = -8.8 ml/yr; -13.1, P = 0.02; and -15.9, P = 0.002; respectively). Both cleaning sprays and other cleaning agents were associated with accelerated FEV 1 decline (-22.0, P = 0.04; and -22.9, P = 0.004; respectively). Cleaning was not significantly associated with lung function decline in men or with FEV 1 /FVC decline or airway obstruction. Women cleaning at home or working as occupational cleaners had accelerated decline in lung function, suggesting that exposures related to cleaning activities may constitute a risk to long-term respiratory health.

Self-esteem and symptoms of depression in children with seizures: relationships with neuropsychological functioning and family variables over time.

PubMed

Austin, Joan K; Perkins, Susan M; Johnson, Cynthia S; Fastenau, Philip S; Byars, Anna W; deGrauw, Ton J; Dunn, David W

2010-10-01

To test over time the relationships of neuropsychological functioning to mental health in children following a first recognized seizure and, of primary importance, to determine if the strength of these relationships differs based on risk and protective factors. In a larger prospective study, 135 children with a first seizure (ages 8-14 years) and 73 healthy sibling controls completed neuropsychological testing at baseline and 36 months. Structured telephone interviews were used to obtain data from children on mental health and family environment; major caregiving parents provided data on demographic and family variables. Data analyses included correlation coefficients and linear regression models. Children with seizures showed an overall trend for improvement in mental health. More children with seizures than siblings had declines in processing speed. Declines in neuropsychological functioning were correlated with worse mental health. With regard to risk and protective factors, higher parent education protected against decline in self-esteem related to decline in processing speed. Better family functioning and greater parental support protected against decline in self-esteem related to decrease in verbal memory and learning. Older child age protected against increase in depressive symptoms related to decline in processing speed. Seizure onset had a negative impact on mental health in children with declines in cognitive functioning except for older children and those with more family resources. Children should be assessed for declines in processing speed and, if found, those subgroups of children with less educated or more anxious parents and those in less supportive families should be targeted for interventions. Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.

Adherence to a Mediterranean-Style Diet and Effects on Cognition in Adults: A Qualitative Evaluation and Systematic Review of Longitudinal and Prospective Trials.

PubMed

Hardman, Roy J; Kennedy, Greg; Macpherson, Helen; Scholey, Andrew B; Pipingas, Andrew

2016-01-01

The Mediterranean-style diet (MedDiet) involves substantial intake of fruits, vegetables, and fish, and a lower consumption of dairy, red meat, and sugars. Over the past 15 years, much empirical evidence supports the suggestion that a MedDiet may be beneficial with respect to reducing the incidence of cardiovascular disease, cancer, metabolic syndrome, and dementia. A number of cross-sectional studies that have examined the impact of MedDiet on cognition have yielded largely positive results. The objective of this review is to evaluate longitudinal and prospective trials to gain an understanding of how a MedDiet may impact cognitive processes over time. The included studies were aimed at improving cognition or minimizing of cognitive decline. Studies reviewed included assessments of dietary status using either a food frequency questionnaire or a food diary assessment. Eighteen articles meeting our inclusion criteria were subjected to systematic review. These revealed that higher adherence to a MedDiet is associated with slower rates of cognitive decline, reduced conversion to Alzheimer's disease, and improvements in cognitive function. The specific cognitive domains that were found to benefit with improved Mediterranean Diet Score were memory (delayed recognition, long-term, and working memory), executive function, and visual constructs. The current review has also considered a number of methodological issues in making recommendations for future research. The utilization of a dietary pattern, such as the MedDiet, will be essential as part of the armamentarium to maintain quality of life and reduce the potential social and economic burden of dementia.

Adherence to a Mediterranean-Style Diet and Effects on Cognition in Adults: A Qualitative Evaluation and Systematic Review of Longitudinal and Prospective Trials

PubMed Central

Hardman, Roy J.; Kennedy, Greg; Macpherson, Helen; Scholey, Andrew B.; Pipingas, Andrew

2016-01-01

The Mediterranean-style diet (MedDiet) involves substantial intake of fruits, vegetables, and fish, and a lower consumption of dairy, red meat, and sugars. Over the past 15 years, much empirical evidence supports the suggestion that a MedDiet may be beneficial with respect to reducing the incidence of cardiovascular disease, cancer, metabolic syndrome, and dementia. A number of cross-sectional studies that have examined the impact of MedDiet on cognition have yielded largely positive results. The objective of this review is to evaluate longitudinal and prospective trials to gain an understanding of how a MedDiet may impact cognitive processes over time. The included studies were aimed at improving cognition or minimizing of cognitive decline. Studies reviewed included assessments of dietary status using either a food frequency questionnaire or a food diary assessment. Eighteen articles meeting our inclusion criteria were subjected to systematic review. These revealed that higher adherence to a MedDiet is associated with slower rates of cognitive decline, reduced conversion to Alzheimer’s disease, and improvements in cognitive function. The specific cognitive domains that were found to benefit with improved Mediterranean Diet Score were memory (delayed recognition, long-term, and working memory), executive function, and visual constructs. The current review has also considered a number of methodological issues in making recommendations for future research. The utilization of a dietary pattern, such as the MedDiet, will be essential as part of the armamentarium to maintain quality of life and reduce the potential social and economic burden of dementia. PMID:27500135

Reduced temporal processing in older, normal-hearing listeners evident from electrophysiological responses to shifts in interaural time difference.

PubMed

Ozmeral, Erol J; Eddins, David A; Eddins, Ann C

2016-12-01

Previous electrophysiological studies of interaural time difference (ITD) processing have demonstrated that ITDs are represented by a nontopographic population rate code. Rather than narrow tuning to ITDs, neural channels have broad tuning to ITDs in either the left or right auditory hemifield, and the relative activity between the channels determines the perceived lateralization of the sound. With advancing age, spatial perception weakens and poor temporal processing contributes to declining spatial acuity. At present, it is unclear whether age-related temporal processing deficits are due to poor inhibitory controls in the auditory system or degraded neural synchrony at the periphery. Cortical processing of spatial cues based on a hemifield code are susceptible to potential age-related physiological changes. We consider two distinct predictions of age-related changes to ITD sensitivity: declines in inhibitory mechanisms would lead to increased excitation and medial shifts to rate-azimuth functions, whereas a general reduction in neural synchrony would lead to reduced excitation and shallower slopes in the rate-azimuth function. The current study tested these possibilities by measuring an evoked response to ITD shifts in a narrow-band noise. Results were more in line with the latter outcome, both from measured latencies and amplitudes of the global field potentials and source-localized waveforms in the left and right auditory cortices. The measured responses for older listeners also tended to have reduced asymmetric distribution of activity in response to ITD shifts, which is consistent with other sensory and cognitive processing models of aging. Copyright © 2016 the American Physiological Society.

Contrasting olfaction, vision, and audition as predictors of cognitive change and impairment in non-demented older adults.

PubMed

MacDonald, Stuart W S; Keller, Connor J C; Brewster, Paul W H; Dixon, Roger A

2018-05-01

This study examines the relative utility of a particular class of noninvasive functional biomarkers-sensory functions-for detecting those at risk of cognitive decline and impairment. Three central research objectives were examined including whether (a) olfactory function, vision, and audition exhibited significant longitudinal declines in nondemented older adults; (b) multiwave change for these sensory function indicators predicted risk of mild cognitive impairment (MCI); and (c) change within persons for each sensory measure shared dynamic time-varying associations with within-person change in cognitive functioning. A longitudinal sample (n = 408) from the Victoria Longitudinal Study was assembled. Three cognitive status subgroups were identified: not impaired cognitively, single-assessment MCI, and multiple-assessment MCI. We tested independent predictive associations, contrasting change in sensory function as predictors of cognitive decline and impairment, utilizing both linear mixed models and logistic regression analysis. Olfaction and, to a lesser extent, vision were identified as the most robust predictors of cognitive status and decline; audition showed little predictive influence. These findings underscore the potential utility of deficits in olfactory function, in particular, as an early marker of age- and pathology-related cognitive decline. Functional biomarkers may represent potential candidates for use in the early stages of a multistep screening approach for detecting those at risk of cognitive impairment, as well as for targeted intervention. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

A multi-ingredient dietary supplement abolishes large-scale brain cell loss, improves sensory function, and prevents neuronal atrophy in aging mice.

PubMed

Lemon, J A; Aksenov, V; Samigullina, R; Aksenov, S; Rodgers, W H; Rollo, C D; Boreham, D R

2016-06-01

Transgenic growth hormone mice (TGM) are a recognized model of accelerated aging with characteristics including chronic oxidative stress, reduced longevity, mitochondrial dysfunction, insulin resistance, muscle wasting, and elevated inflammatory processes. Growth hormone/IGF-1 activate the Target of Rapamycin known to promote aging. TGM particularly express severe cognitive decline. We previously reported that a multi-ingredient dietary supplement (MDS) designed to offset five mechanisms associated with aging extended longevity, ameliorated cognitive deterioration and significantly reduced age-related physical deterioration in both normal mice and TGM. Here we report that TGM lose more than 50% of cells in midbrain regions, including the cerebellum and olfactory bulb. This is comparable to severe Alzheimer's disease and likely explains their striking age-related cognitive impairment. We also demonstrate that the MDS completely abrogates this severe brain cell loss, reverses cognitive decline and augments sensory and motor function in aged mice. Additionally, histological examination of retinal structure revealed markers consistent with higher numbers of photoreceptor cells in aging and supplemented mice. We know of no other treatment with such efficacy, highlighting the potential for prevention or amelioration of human neuropathologies that are similarly associated with oxidative stress, inflammation and cellular dysfunction. Environ. Mol. Mutagen. 57:382-404, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Water relations in cutover peatlands

NASA Astrophysics Data System (ADS)

Price, Jonathan S.; Ketcheson, Scott J.

Sphagnum mosses, the dominant peat-forming plant in many northern peatlands, generally do not regenerate spontaneously in mined peatlands because water transfer between the cutover peat and incipient moss diaspores cannot overcome the capillary barrier effect between the two hydraulically distinct layers. Artificial drainage networks established throughout peatlands, coupled with the removal of the acrotelm during the peat extraction process, drastically alter the natural system function through the exposure of more decomposed catotelm peat and increased compression, oxidation, and shrinkage, subsequently decreasing average pore diameter and enhancing this capillary barrier effect. Water table (WT) fluctuations, constrained within the reduced specific yield of the altered catotelm, exhibit increased variability and rapid decline. The increased effective stress caused by a declining WT can result in seasonal surface subsidence of 8 to 10 cm, thereby reducing saturated hydraulic conductivity by three orders of magnitude. Restoration efforts aim to alter the disturbed hydrological regime, creating conditions more favorable for the recolonization of Sphagnum mosses and the ultimate reestablishment of an upper acrotelm layer. Due to the large areal coverage and high organic carbon content, the response of peatlands to disturbances caused by resource extraction, and their return to functioning ecosystems, must be thoroughly addressed. This paper integrates both published and unpublished work to facilitate an overview of our understanding of the hydrological impact of peat cutting and its implications for restoration.

Vestibular dysfunction in the adult CBA/CaJ mouse after lead and cadmium treatment

PubMed Central

Klimpel, Katarina E. M.; Lee, Min Young; King, W. Michael; Raphael, Yehoash; Schacht, Jochen; Neitzel, Richard L.

2017-01-01

OBJECTIVES The vestibular system allows the perception of position and motion and its dysfunction presents as motion impairment, vertigo and balance abnormalities, leading to debilitating psychological discomfort and difficulty performing daily tasks. Although declines and deficits in vestibular function have been noted in rats exposed to lead (Pb) and in humans exposed to Pb and cadmium (Cd), no studies have directly examined the pathological and pathophysiological effects upon the vestibular apparatus of the inner ear. METHODS Eighteen young adult mice were exposed through their drinking water (3 mM Pb, 300 μM Cd, or a control treatment) for 10 weeks. Before and after treatment, they underwent a vestibular assessment, consisting of a rotarod performance test and a novel head stability test to measure the vestibulocolic reflex. At the conclusion of the study, the utricles were analyzed immunohistologically for condition of hair cells and nerve fibers. RESULTS Increased levels of Pb exposure correlated with decreased head stability in space; no significant decline in performance on rotarod test was found. No damage to the hair cells or the nerve fibers of the utricle was observed in histology. CONCLUSIONS The young adult CBA/CaJ mouse is able to tolerate occupationally-relevant Pb and Cd exposure well, but the correlation between Pb exposure and reduced head stability suggests that Pb exposure causes a decline in vestibular function. PMID:27257108

Probability of treatment following acute decline in lung function in children with cystic fibrosis is related to baseline pulmonary function.

PubMed

Morgan, Wayne J; Wagener, Jeffrey S; Yegin, Ashley; Pasta, David J; Millar, Stefanie J; Konstan, Michael W

2013-10-01

To determine whether the association between high forced expiratory volume in 1 second (FEV1) and increased rate of decline in FEV1 in children with cystic fibrosis could be due to less frequent intervention after acute declines (sudden decline events) in FEV1. Patients with cystic fibrosis aged 6-17 years enrolled in the Epidemiologic Study of Cystic Fibrosis were assessed for a sudden decline event, defined as a 10% relative decline in FEV1% predicted from an average of 3 consecutive stable baseline spirometries. The likelihood of therapeutic intervention within 14 days before and 56 days after this event was then related to their baseline FEV1% predicted age-specific decile using a logistic regression adjusting for age group (6-12 years, 13-17 years) and presence of Pseudomonas aeruginosa on respiratory culture. A total of 10 888 patients had at least 1 sudden decline event in FEV1. Patients in the highest FEV1 decile were significantly less likely than those in the lowest decile to receive intravenous antibiotics (OR, 0.14; 95% CI, 0.11-0.18; P < .001) or be hospitalized (OR, 0.18; 95% CI, 0.14-0.23; P < .001) following decline. Children and adolescents with high baseline lung function are less likely to receive a therapeutic intervention following an acute decline in FEV1, which may explain their greater rate of FEV1 decline. Copyright © 2013 Mosby, Inc. All rights reserved.

Effects of Biocompatible versus Standard Fluid on Peritoneal Dialysis Outcomes

PubMed Central

Brown, Fiona G.; Clarke, Margaret; Boudville, Neil; Elias, Tony J.; Foo, Marjorie W.Y.; Jones, Bernard; Kulkarni, Hemant; Langham, Robyn; Ranganathan, Dwarakanathan; Schollum, John; Suranyi, Michael; Tan, Seng H.; Voss, David

2012-01-01

The clinical benefits of using “biocompatible” neutral pH solutions containing low levels of glucose degradation products for peritoneal dialysis compared with standard solutions are uncertain. In this multicenter, open-label, parallel-group, randomized controlled trial, we randomly assigned 185 incident adult peritoneal dialysis patients with residual renal function to use either biocompatible or conventional solution for 2 years. The primary outcome measure was slope of renal function decline. Secondary outcome measures comprised time to anuria, fluid volume status, peritonitis-free survival, technique survival, patient survival, and adverse events. We did not detect a statistically significant difference in the rate of decline of renal function between the two groups as measured by the slopes of GFR: −0.22 and −0.28 ml/min per 1.73 m2 per month (P=0.17) in the first year in the biocompatible and conventional groups, respectively, and, −0.09 and −0.10 ml/min per 1.73 m2 per month (P=0.9) in the second year. The biocompatible group exhibited significantly longer times to anuria (P=0.009) and to the first peritonitis episode (P=0.01). This group also had fewer patients develop peritonitis (30% versus 49%) and had lower rates of peritonitis (0.30 versus 0.49 episodes per year, P=0.01). In conclusion, this trial does not support a role for biocompatible fluid in slowing the rate of GFR decline, but it does suggest that biocompatible fluid may delay the onset of anuria and reduce the incidence of peritonitis compared with conventional fluid in peritoneal dialysis. PMID:22440906

PubMed Central

Forli, F.; Guglielmi, V.; De Corso, E.; Paludetti, G.; Berrettini, S.; Fetoni, A.R.

2016-01-01

SUMMARY Age-related hearing loss (ARHL) has a multifactorial pathogenesis and it is an inevitable hearing impairment associated with reduction of communicative skills related to ageing. Increasing evidence has linked ARHL to more rapid progression of cognitive decline and incidental dementia. Many aspects of daily living of elderly people have been associated to hearing abilities, showing that hearing loss (HL) affects the quality of life, social relationships, motor skills, psychological aspects and function and morphology in specific brain areas. Epidemiological and clinical studies confirm the assumption of a relationship between these conditions. However, the mechanisms are still unclear and are reviewed herein. Long-term hearing deprivation of auditory inputs can impact cognitive performance by decreasing the quality of communication leading to social isolation and depression and facilitate dementia. On the contrary, the limited cognitive skills may reduce the cognitive resources available for auditory perception, increasing the effects of HL. In addition, hearing loss and cognitive decline may reflect a 'common cause' on the auditory pathway and brain. In fact, some pathogenetic factors are recongised in common microvascular disease factors such as diabetes, atherosclerosis and hypertension. Interdisciplinary efforts to investigate and address HL in the context of brain and cognitive ageing are needed. Surprisingly, few studies have been adressed on the effectiveness of hearing aids in changing the natural history of cognitive decline. Effective interventions with hearing aids or cochlear implant may improve social and emotional function, communication, cognitive function and positively impact quality of life. The aim of this review is to overview new insights on this challenging topic and provide new ideas for future research. PMID:27214827

Are informal carers and community care workers effective in managing malnutrition in the older adult community? A systematic review of current evidence.

PubMed

Marshall, S; Bauer, J; Capra, S; Isenring, E

2013-01-01

Enhancing the effectiveness of the community and aged care workforce to prevent malnutrition and functional decline is important in reducing hospital and aged care facility demand. To investigate the impact of nutrition-related interventions delivered to or by informal carers and non-clinical community care workers on malnutrition-related health outcomes of community-dwelling older adults (≥65 years). Intervention studies were searched for using six electronic databases for English-language publications from January 1980 to 30 May 2012. Nine studies were eligible for inclusion. The strength and quality of the evidence was moderate (six studies with level II intervention evidence, five with positive quality). Types of interventions used were highly varied. The majority of interventions were delivered to informal carers (6 studies), with three of these studies also involving older adult care recipients. Five interventions were targeted at identifying, preventing and/or treating malnutrition specifically (two positive quality, three neutral quality, n=2368). As a result of these interventions, nutritional status improved or stabilized (two positive quality, two neutral quality, n=2333). No study reported an improvement in functional status but two successfully prevented further decline in their participants (two neutral quality, n=1097). Interventions targeted at identifying, preventing and/or treating malnutrition were able to improve or prevent decline in nutritional and functional status, without increasing informal carer burden. The findings of this review support the involvement of non-clinical community care workers and informal carers as part of the nutritional care team for community-dwelling older adults.

Enteric hyperoxaluria in chronic pancreatitis.

PubMed

Demoulin, Nathalie; Issa, Zaina; Crott, Ralph; Morelle, Johann; Danse, Etienne; Wallemacq, Pierre; Jadoul, Michel; Deprez, Pierre H

2017-05-01

Chronic pancreatitis may lead to steatorrhea, enteric hyperoxaluria, and kidney damage. However, the prevalence and determinants of hyperoxaluria in chronic pancreatitis patients as well as its association with renal function decline have not been investigated.We performed an observational study. Urine oxalate to creatinine ratio was assessed on 2 independent random urine samples in consecutive adult patients with chronic pancreatitis followed at the outpatient clinic from March 1 to October 31, 2012. Baseline characteristics and annual estimated glomerular filtration rate (eGFR) change during follow-up were compared between patients with hyper- and normo-oxaluria.A total of 48 patients with chronic pancreatitis were included. The etiology of the disease was toxic (52%), idiopathic (27%), obstructive (11%), autoimmune (6%), or genetic (4%). Hyperoxaluria (defined as urine oxalate to creatinine ratio >32 mg/g) was found in 23% of patients. Multivariate regression analysis identified clinical steatorrhea, high fecal acid steatocrit, and pancreatic atrophy as independent predictors of hyperoxaluria. Taken together, a combination of clinical steatorrhea, steatocrit level >31%, and pancreatic atrophy was associated with a positive predictive value of 100% for hyperoxaluria. On the contrary, none of the patients with a fecal elastase-1 level >100 μg/g had hyperoxaluria. Longitudinal evolution of eGFR was available in 71% of the patients, with a mean follow-up of 904 days. After adjustment for established determinants of renal function decline (gender, diabetes, bicarbonate level, baseline eGFR, and proteinuria), a urine oxalate to creatinine ratio >32 mg/g was associated with a higher risk of eGFR decline.Hyperoxaluria is highly prevalent in patients with chronic pancreatitis and associated with faster decline in renal function. A high urine oxalate to creatinine ratio in patients with chronic pancreatitis is best predicted by clinical steatorrhea, a high acid steatocrit, and pancreatic atrophy. Further studies will need to investigate the mechanisms of renal damage in chronic pancreatitis and the potential benefits of therapies reducing oxaluria.

The Association between a Mediterranean-Style Diet and Kidney Function in the Northern Manhattan Study Cohort

PubMed Central

Moon, Yeseon P.; Scarmeas, Nikolaos; Gu, Yian; Gardener, Hannah; Cheung, Ken; Wright, Clinton B.; Sacco, Ralph L.; Nickolas, Thomas L.; Elkind, Mitchell S.V.

2014-01-01

Background and objectives Various dietary strategies have been investigated to slow kidney function decline. However, it is unknown whether a Mediterranean diet, which has been associated with improved cardiovascular risk, is associated with change in kidney function. Design, setting, participants, & measurements This study used the Northern Manhattan Study, a prospective, multiethnic, observational cohort of participants who were stroke free at baseline. Data were collected between 1993 and 2008. Serum creatinine measurements were taken a mean 6.9 years apart. A baseline dietary questionnaire was extrapolated into a previously used 9-point scoring system (MeDi). The primary outcome was incident eGFR<60 ml/min per 1.73 m2using the Modification of Diet in Renal Disease formula. A secondary outcome was the upper quartile of annualized eGFR decline (≥2.5 ml/min per 1.73 m2 per year). Conditional logistic regression models adjusted for demographics and baseline vascular risk factors. Results Mean baseline age was 64 years, with 59% women and 65% Hispanics (N=900); mean baseline eGFR was 83.1 ml/min per 1.73 m2. Incident eGFR<60 ml/min per 1.73 m2 developed in 14% . In adjusted models, every 1-point increase in the MeDi score, indicating increasing adherence to a Mediterranean diet, was associated with decreased odds of incident eGFR<60 ml/min per 1.73 m2 (odds ratio, 0.83; 95% confidence interval, 0.71 to 0.96) and decreased odds of being in the upper quartile of eGFR decline (odds ratio, 0.88; 95% confidence interval, 0.79 to 0.98). Conclusions A Mediterranean diet was associated with a reduced incidence of eGFR<60 ml/min per 1.73 m2 and upper quartile of eGFR decline in a multiethnic cohort. PMID:25359387

The association between a Mediterranean-style diet and kidney function in the Northern Manhattan Study cohort.

PubMed

Khatri, Minesh; Moon, Yeseon P; Scarmeas, Nikolaos; Gu, Yian; Gardener, Hannah; Cheung, Ken; Wright, Clinton B; Sacco, Ralph L; Nickolas, Thomas L; Elkind, Mitchell S V

2014-11-07

Various dietary strategies have been investigated to slow kidney function decline. However, it is unknown whether a Mediterranean diet, which has been associated with improved cardiovascular risk, is associated with change in kidney function. This study used the Northern Manhattan Study, a prospective, multiethnic, observational cohort of participants who were stroke free at baseline. Data were collected between 1993 and 2008. Serum creatinine measurements were taken a mean 6.9 years apart. A baseline dietary questionnaire was extrapolated into a previously used 9-point scoring system (MeDi). The primary outcome was incident eGFR<60 ml/min per 1.73 m(2)using the Modification of Diet in Renal Disease formula. A secondary outcome was the upper quartile of annualized eGFR decline (≥ 2.5 ml/min per 1.73 m(2) per year). Conditional logistic regression models adjusted for demographics and baseline vascular risk factors. Mean baseline age was 64 years, with 59% women and 65% Hispanics (N=900); mean baseline eGFR was 83.1 ml/min per 1.73 m(2). Incident eGFR<60 ml/min per 1.73 m(2) developed in 14% . In adjusted models, every 1-point increase in the MeDi score, indicating increasing adherence to a Mediterranean diet, was associated with decreased odds of incident eGFR<60 ml/min per 1.73 m(2) (odds ratio, 0.83; 95% confidence interval, 0.71 to 0.96) and decreased odds of being in the upper quartile of eGFR decline (odds ratio, 0.88; 95% confidence interval, 0.79 to 0.98). A Mediterranean diet was associated with a reduced incidence of eGFR<60 ml/min per 1.73 m(2) and upper quartile of eGFR decline in a multiethnic cohort. Copyright © 2014 by the American Society of Nephrology.

A waitlist control-group study of cognitive, mood, and quality of life outcome after posteroventral pallidotomy in Parkinson disease.

PubMed

Carr, Jason A R; Honey, Christopher R; Sinden, Marci; Phillips, Anthony G; Martzke, Jeffrey S

2003-07-01

The aim of this study was to examine neuropsychological outcome from unilateral posteroventral pallidotomy (PVP) in Parkinson disease while controlling for confounding factors such as test practice and disease progression. Participants underwent baseline and 2-month follow-up assessments of cognition, quality of life, mood, and motor functioning. The surgery group (22 patients) underwent PVP (15 left, seven right) after baseline assessment. The waitlist group (14 patients) underwent PVP after follow up. At follow up, the left PVP group exhibited a decline on verbal measures of learning, fluency, working memory, and speeded color naming. The incidence of significant decline on these measures after left PVP ranged from 50 to 86%. The right PVP group did not exhibit a significant cognitive decline, but fluency did decline in 71% of patients who underwent right PVP. Participants who underwent PVP reported better bodily pain and social functioning at follow up than participants in the waitlist group. Improved bodily pain was evident for 62% of the surgery group, and social functioning improved for 19%. Surgery did not alter reported physical functioning or mood. Dyskinesia improved after surgery, but there were no improvements in "on-state" manual dexterity or handwriting. Most patients who underwent left PVP exhibited declines in learning, fluency, working memory, and speeded color naming. Accounting for retesting effects altered the magnitude of these declines by up to one quarter of a standard deviation, but did not increase the breadth of postsurgical neuropsychological decline beyond that typically reported in the literature. It was found that PVP improved dyskinesia, bodily pain, and social functioning, but did not lead to improvement on other objective and self-reported measures of motor functioning.

Development and validation of a prediction model for functional decline in older medical inpatients.

PubMed

Takada, Toshihiko; Fukuma, Shingo; Yamamoto, Yosuke; Tsugihashi, Yukio; Nagano, Hiroyuki; Hayashi, Michio; Miyashita, Jun; Azuma, Teruhisa; Fukuhara, Shunichi

2018-05-17

To prevent functional decline in older inpatients, identification of high-risk patients is crucial. The aim of this study was to develop and validate a prediction model to assess the risk of functional decline in older medical inpatients. In this retrospective cohort study, patients ≥65 years admitted acutely to medical wards were included. The healthcare database of 246 acute care hospitals (n = 229,913) was used for derivation, and two acute care hospitals (n = 1767 and 5443, respectively) were used for validation. Data were collected using a national administrative claims and discharge database. Functional decline was defined as a decline of the Katz score at discharge compared with on admission. About 6% of patients in the derivation cohort and 9% and 2% in each validation cohort developed functional decline. A model with 7 items, age, body mass index, living in a nursing home, ambulance use, need for assistance in walking, dementia, and bedsore, was developed. On internal validation, it demonstrated a c-statistic of 0.77 (95% confidence interval (CI) = 0.767-0.771) and good fit on the calibration plot. On external validation, the c-statistics were 0.79 (95% CI = 0.77-0.81) and 0.75 (95% CI = 0.73-0.77) for each cohort, respectively. Calibration plots showed good fit in one cohort and overestimation in the other one. A prediction model for functional decline in older medical inpatients was derived and validated. It is expected that use of the model would lead to early identification of high-risk patients and introducing early intervention. Copyright © 2018 Elsevier B.V. All rights reserved.

Advances in human reproductive ecology.

PubMed

Ellison, P T

1994-01-01

Human reproductive ecology pertains to reproduction biology and changes due to environmental influences. The research literature relies on clinical, epidemiological, and demographic analysis. The emphasis is on normal, nonpathological states and a broad range of ecological conditions. This review focused on the importance of age and energetic stress from ecological conditions rather than dieting or self-directed exercise in changing female fecundity. The literature on male reproductive ecology is still small but growing. J.W. Wood provided a comprehensive overview of the field. Natural fertility, as defined by Henry, is the lack of parity-specific fertility limitation. There is evidence that fertility can vary widely in natural fertility populations. There are consistent age patterns among different natural fertility populations. Doring found that there was higher frequency of anovulatory and luteal insufficiency in cycles during perimenarche and perimenopausal periods. Infertility studies have shown declines in pregnancy rates in women over the age of 30 years. Ovum donation evaluations have found both uterine age and ovarian and oocyte age to be related to the probability of a successful pregnancy. Basal follicle stimulating hormone and the endometrial thickness are important predictors of ovarian capacity and related to age and declining fecundity. Much of the literature on fecundity is derived from women with impaired reproductive physiology. In Lipson and Ellison's study of healthy women, average follicular and average luteal estradiol values declined with increasing subject age. Low follicular levels were correlated with smaller follicular size, low oocyte fertilizability, reduced endometrial thickness, and low pregnancy rates. Comparisons across populations have shown that populations experience declines in luteal function with age, but levels of luteal functions varied widely. Chronic conditions which slow growth and delay reproductive maturation may impact on lower ovarian function throughout adult life. There is a range of ovarian function along a continuum due to energetic stress. Evidence from the Lese in Zaire, the Tamang of Nepal, and Polish farm women outside Crakow suggest that workload affects ovarian function. Luteal function and ovulatory frequency is lower when women are losing weight. Among the Tamang losing weight between seasons there was evidence of lower ovarian function during the monsoon season. Polish farm women who work very hard in summer had lower ovarian function. The effect of lactation on amenorrhea appears to be due to the energetic stress on the mother in the intensity and duration of suckling. Women in poorer nutritional status may require more intense suckling. Seasonality of energy balance may be related to seasonality of female fecundity and conceptions.

A profile of four patterns of vulnerability to functional decline in older general medicine patients in Victoria, Australia: a cross sectional survey.

PubMed

Beddoes-Ley, Lenore; Khaw, Damien; Duke, Maxine; Botti, Mari

2016-08-05

There are limited published data reporting Australian hospitalized elders' vulnerability to functional decline to guide best practice interventions. The objectives of this study were to describe the prevalence of vulnerability to functional decline and explore profiles of vulnerability related to the performance of physical activity in a representative group of elders in a single centre in Victoria, Australia. A cross-sectional survey of patients aged ≥ 70 years (Mean age 82.4, SD 7 years) admitted to a general medical ward of an Australian tertiary-referral metropolitan public hospital from March 2010 to March 2011 (n = 526). Patients were screened using the Vulnerable Elders Survey (VES-13). Distinct typologies of physical difficulties were identified using latent class analysis. Most elders scored ≥3/10 on the VES-13 and were rated vulnerable to functional decline (n = 480, 89.5 %). Four distinct classes of physical difficulty were identified: 1) Elders with higher physical functioning (n = 114, 21.7 %); 2) Ambulant elders with diminished strength (n = 24, 4.6 %); 3) Elders with impaired mobility, strength and ability to stoop (n = 267, 50.8 %) and 4) Elders with extensive physical impairment (n = 121, 23 %) Vulnerable elders were distributed through all classes. Older general medicine patients in Victoria, Australia, are highly vulnerable to functional decline. We identified four distinct patterns of physical difficulties associated with vulnerability to functional decline that can inform health service planning, delivery and education.

[Functional impairment associated with cognitive impairment in hospitalised elderly].

PubMed

Ocampo-Chaparro, José Mauricio; Mosquera-Jiménez, José Ignacio; Davis, Annabelle S; Reyes-Ortiz, Carlos A

The aim of this study was to analyse the effect of cognitive impairment on functional decline in hospitalised patients aged ≥60 years. Measurements at admission included demographic data, Charlson's comorbidity index, and cognitive impairment (according to education level). Data were also collected on hospital length of stay, depression, and delirium developed during hospitalisation. The outcome, Barthel Index (BI), was measured at admission, discharge, and 1-month post-discharge. Patients with BI≤75 at admission (n=54) or with a missing BI value were excluded (n=1). Multivariate logistic regression analyses were conducted to explore predictive factors with functional decline (BI≤75) from admission to discharge, and 1-month later. Of the 133 patients included, 24.8% and 19.6% had a BI≤75 at discharge and at 1-month, respectively. Compared with men, women had more than double risk for functional decline at discharge and 1-month (P<.05). Compared with those without delirium and without cognitive impairment, those with delirium and cognitive impairment had an increased risk for functional decline (BI≤75) at discharge (OR 5.15, 95% CI; 1.94-13.67), and at 1-month (OR 6.26, 95% CI; 2.30-17.03). Similarly, those with comorbidity (≥2) had increased functional decline at discharge (OR 2.36, 95% CI; 1.14-4.87), and at 1-month after discharge (OR 2.71, 95% CI; 1.25-5.89). Delirium during hospitalisation, together with cognitive impairment on admission, was a strong predictor of functional decline. Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

Effect of Early Referral to Specialist in Dementia on Institutionalization and Functional Decline: Findings from a Population-Based Study.

PubMed

Pimouguet, Clément; Le-Goff, Mélanie; Rizzuto, Debora; Berr, Claudine; Leffondré, Karen; Pérès, Karine; Dartigues, Jean FranÇois; Helmer, Catherine

2016-01-01

Although early diagnosis has been hypothesized to benefit both patients and caregivers, until now studies evaluating the effect of early dementia diagnosis are lacking. To investigate the influence of early specialist referral for dementia on the risk of institutionalization and functional decline in Activity of Daily Living (ADL). Incident dementia cases were screened in a prospective population-based cohort, the Three-City Study, and initial specialist consultation for cognitive complaint was assessed at dementia diagnosis. Proportional hazard regression and illness-death models were used to test the association between specialist referral and, respectively, institutionalization and functional decline. Only one third of the incident individuals with dementia had consulted a specialist for cognitive problems early (36%). After adjustment on potential confounders (including cognitive and functional decline) and competing risk of death, participants who had consulted a specialist early in the disease course presented a higher rate of being institutionalized than those who did not (Hazard Ratio = 2.00, 95% Confidence Interval (CI): 1.09- 3.64). But early specialist referral was not associated with further functional decline (HR = 1.09, 95% CI: 0.71- 1.67). Early specialist referral in dementia is associated with increased risk of institutionalization but not with functional decline in ADL. These findings suggest that early care referral in dementia may be a marker of concern for patients and/or caregivers; subsequent medical and social care could be suboptimal or inappropriate to allow patients to stay longer at home.

Smoking and nonsmoking asthma: differences in clinical outcome and pathogenesis.

PubMed

Fattahi, Fatemeh; Hylkema, Machteld N; Melgert, Barbro N; Timens, Wim; Postma, Dirkje S; ten Hacken, Nick H T

2011-02-01

Cigarette smoking in asthma is frequently present and is associated with worsening of symptoms, accelerated lung-function decline, a higher frequency of hospital admissions, a higher degree of asthma severity, poorer asthma control and reduced responsiveness to corticosteroids. Furthermore, it is associated with reduced numbers of eosinophils and higher numbers of mast cells in the submucosa of the airway wall. Airway remodeling is increased as evidenced by increased epithelial thickness and goblet cell hyperplasia in smoking asthmatics. The pathogenesis responsible for smoking-induced changes in airway inflammation and remodeling in asthma is complex and largely unknown. The underlying mechanism of reduced corticosteroid responsiveness is also unknown. This article discusses differences between smoking and nonsmoking asthmatics regarding the clinical expression of asthma, lung function, response to corticosteroids, airway inflammation and remodeling processes. Possible pathogenetic mechanisms that may explain the links between cigarette smoking and changes in the clinical expression of asthma will be discussed, as well as the beneficial effects of smoking cessation.

Effect of retirement on cognitive function: the Whitehall II cohort study.

PubMed

Xue, Baowen; Cadar, Dorina; Fleischmann, Maria; Stansfeld, Stephen; Carr, Ewan; Kivimäki, Mika; McMunn, Anne; Head, Jenny

2017-12-26

According to the 'use it or lose it' hypothesis, a lack of mentally challenging activities might exacerbate the loss of cognitive function. On this basis, retirement has been suggested to increase the risk of cognitive decline, but evidence from studies with long follow-up is lacking. We tested this hypothesis in a cohort of 3433 civil servants who participated in the Whitehall II Study, including repeated measurements of cognitive functioning up to 14 years before and 14 years after retirement. Piecewise models, centred at the year of retirement, were used to compare trajectories of verbal memory, abstract reasoning, phonemic verbal fluency, and semantic verbal fluency before and after retirement. We found that all domains of cognition declined over time. Declines in verbal memory were 38% faster after retirement compared to before, after taking account of age-related decline. In analyses stratified by employment grade, higher employment grade was protective against verbal memory decline while people were still working, but this 'protective effect' was lost when individuals retired, resulting in a similar rate of decline post-retirement across employment grades. We did not find a significant impact of retirement on the other cognitive domains. In conclusion, these findings are consistent with the hypothesis that retirement accelerates the decline in verbal memory function. This study points to the benefits of cognitively stimulating activities associated with employment that could benefit older people's memory.

Physical Exercise As Stabilizer For Alzheimer'S Disease Cognitive Decline: Current Status.

PubMed

Machado, Sergio; Filho, Alberto Souza de Sá; Wilbert, Matheus; Barbieri, Gabriela; Almeida, Victor; Gurgel, Alexandre; Rosa, Charles V; Lins, Victor; Paixão, Alexandre; Santana, Kamila; Ramos, Gabriel; Neto, Geraldo Maranhão; Paes, Flá; Rocha, Nuno; Murillo-Rodriguez, Eric

2017-01-01

Mental health decline is one of the main responsible factors for augments in health care costs, and diagnosis of Alzheimer's disease (AD). Some studies stated physical exercise is useful for reduction in cognitive decline and AD. Moreover, a recent review argued that evidence are scarce due to few studies published and lack of configuration information of exercise protocol, such as intensity and duration of exercise, number of sessions and other relevant data, to allow appropriate assessment. Here, we discussed the possible confounders or factors responsible for these differences and possible neurophysiological mechanisms. Most studies revealed a possible positive association between physical exercise and cognitive assessments. There are inconsistencies in studies design responsible for varying use of cognitive assessments and different assessments of fitness. However, these studies do not fail to provide evidence about the benefits of exercise, but fail to make it possible because of the lack of dose-response information in AD patients. Physical exercise of moderate intensity should be considered as standard recommendation to reduce cognitive decline, probably due to the improvement in neurodegenerative mechanisms, and the increase in neuroplastic and neuroprotective neurotrophic factors. Therefore, it is suggested that physical exercise is an important neuroprotective modulator, bringing significant control of the disease and amplifying brain functions.

Sources of Disconnection in Neurocognitive Aging: Cerebral White Matter Integrity, Resting-state Functional Connectivity, and White Matter Hyperintensity Volume

PubMed Central

Madden, David J.; Parks, Emily L.; Tallman, Catherine W.; Boylan, Maria A.; Hoagey, David A.; Cocjin, Sally B.; Packard, Lauren E.; Johnson, Micah A.; Chou, Ying-hui; Potter, Guy G.; Chen, Nan-kuei; Siciliano, Rachel E.; Monge, Zachary A.; Honig, Jesse A.; Diaz, Michele T.

2017-01-01

Age-related decline in fluid cognition can be characterized as a disconnection among specific brain structures, leading to a decline in functional efficiency. The potential sources of disconnection, however, are unclear. We investigated imaging measures of cerebral white matter integrity, resting-state functional connectivity, and white matter hyperintensity (WMH) volume as mediators of the relation between age and fluid cognition, in 145 healthy, community-dwelling adults 19–79 years of age. At a general level of analysis, with a single composite measure of fluid cognition and single measures of each of the three imaging modalities, age exhibited an independent influence on the cognitive and imaging measures, and the imaging variables did not mediate the age-cognition relation. At a more specific level of analysis, resting-state functional connectivity of sensorimotor networks was a significant mediator of the age-related decline in executive function. These findings suggest that different levels of analysis lead to different models of neurocognitive disconnection, and that resting-state functional connectivity, in particular, may contribute to age-related decline in executive function. PMID:28389085

Hypertension and vascular dementia in the elderly: the potential role of anti-hypertensive agents.

PubMed

Coca, Antonio

2013-09-01

Vascular dementia (VaD) - a severe form of vascular cognitive impairment - and cognitive decline are associated with hypertension and therefore it seems logical to consider that reducing BP with anti-hypertensive therapy may protect against the development/onset of cognitive function impairment or dementia. This narrative, non-systematic review discusses the available evidence on the potential correlation between the use of anti-hypertensive agents and the risk of VaD and cognitive decline. MEDLINE was searched for inclusion of relevant studies. No limitations in time were considered. A consensus on the potential effects of anti-hypertensive treatment in the reduction of VaD and associated cognitive decline has not been reached. A protective effect of anti-hypertensive agents has been observed in a number of studies although it is still unclear whether different classes of anti-hypertensive agents have a different effect on the development of VaD. The protective effect of anti-hypertensive agents appears to depend on the specific drug used - positive effects have been observed with calcium channel blockers (CCBs), such as lercanidipine and nitrendipine, the combination perindopril-indapamide and telmisartan.

Fish consumption, intake of fats and cognitive decline at middle and older age: the Doetinchem Cohort Study.

PubMed

Nooyens, Astrid C J; van Gelder, Boukje M; Bueno-de-Mesquita, H Bas; van Boxtel, Martin P J; Verschuren, W M Monique

2018-06-01

To get insight in the impact of fish and fat intake in the prevention of accelerated cognitive decline with ageing, we tested associations between fish and different fat intakes and 5-year change in cognitive functions. In 2612 men and women of the Doetinchem Cohort Study, aged 43-70 years at baseline, dietary intake (including fish consumption) and cognitive function were assessed at baseline and at 5-year follow-up. Average fish consumption (frequency) and intakes (as energy percentages) of total fat, saturated, mono unsaturated, and polyunsaturated fatty acids (PUFA), linoleic, docosahexaenoic, eicosapentaenoic, and a-linolenic acid (ALA), and cholesterol were averaged over baseline and follow-up. Intakes were studied in relation to 5-year change in global cognitive function, memory, information processing speed, and cognitive flexibility, using ANCOVA and multivariate linear regression analyses. No consistent association between (fatty) fish consumption and cognitive decline was observed. Higher cholesterol intake was associated with faster cognitive decline (p < 0.05). Higher n-3 PUFA (especially ALA) intake was associated with slower decline in global cognitive function and memory (p < 0.01). Intakes of other fatty acids were not associated with cognitive decline. Higher cholesterol intake was detrimental, while higher ALA intake was beneficial for maintaining cognitive function with ageing, already at middle age.

Caloric restriction impedes age-related decline of mitochondrial function and neuronal activity

PubMed Central

Lin, Ai-Ling; Coman, Daniel; Jiang, Lihong; Rothman, Douglas L; Hyder, Fahmeed

2014-01-01

Caloric restriction (CR) prolongs lifespan and retards many detrimental effects of aging, but its effect on brain mitochondrial function and neuronal activity—especially in healthy aging—remains unexplored. Here we measured rates of neuronal glucose oxidation and glutamate–glutamine neurotransmitter cycling in young control, old control (i.e., healthy aging), and old CR rats using in vivo nuclear magnetic resonance spectroscopy. We found that, compared with the young control, neuronal energy production and neurotransmission rates were significantly reduced in healthy aging, but were preserved in old CR rats. The results suggest that CR mitigated the age-related deceleration of brain physiology. PMID:24984898

Exercise Promotes Healthy Aging of Skeletal Muscle

PubMed Central

Cartee, Gregory D.; Hepple, Russell T.; Bamman, Marcas M.; Zierath, Juleen R.

2016-01-01

Primary aging is the progressive and inevitable process of bodily deterioration during adulthood. In skeletal muscle, primary aging causes defective mitochondrial energetics, and reduced muscle mass. Secondary aging refers to additional deleterious structural and functional age-related changes caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes “healthy aging” by inducing modifications in skeletal muscle. PMID:27304505

Indication for Dialysis Initiation and Mortality in Patients With Chronic Kidney Failure: A Retrospective Cohort Study

PubMed Central

Rivara, Matthew B.; Chen, Chang Huei; Nair, Anupama; Cobb, Denise; Himmelfarb, Jonathan; Mehrotra, Rajnish

2016-01-01

Background Initiation of maintenance dialysis for patients with chronic kidney failure is a period of high risk for adverse patient outcomes. Whether indications for dialysis initiation are associated with mortality among this population is unknown. Study Design Retrospective cohort study. Setting & Participants 461 patients who initiated dialysis (hemodialysis, 437; peritoneal dialysis, 24) from January 1st, 2004 through December 31st, 2012 and were treated in facilities operated by a single dialysis organization. Follow-up for the primary outcome was through December 31st, 2013. Predictor Clinically documented primary indication for dialysis initiation, as categorized into four groups: laboratory evidence of kidney function decline (reference category), uremic symptoms, volume overload or hypertension, and other/unknown. Outcomes All-cause mortality Results Over a median follow-up of 2.4 years, 183 (40%) patients died. Crude mortality rates were 10.0 (95% CI, 6.8–14.7), 12.7 (95% CI, 10.2–15.7), 21.7 (95% CI, 16.4–28.6), and 12.2 (95% CI, 6.8–14.7) per 100 patient-years among patients initiating dialysis primarily for laboratory evidence of kidney function decline, uremic symptoms, volume overload or hypertension, and other/unknown reason, respectively. Following adjustment for demographic variables, coexisting illnesses, and estimated glomerular filtration rate, initiation of dialysis for uremic symptoms, volume overload or hypertension, or for other/unknown reasons were associated with 1.12 (95% CI, 0.72–1.77), 1.71 (95% CI, 1.03–2.84), and 1.28 (95% CI, 0.73–2.26) times higher risk, respectively, for subsequent mortality compared to initiation for laboratory evidence of kidney function decline. Limitations Possibility of residual confounding by unmeasured variables; reliance on clinical documentation to ascertain exposure Conclusions Patients initiating dialysis due to volume overload may have increased risk for mortality compared to patients initiating dialysis due to laboratory evidence of kidney function decline. Further studies are needed to identify and test interventions that might reduce this risk. PMID:27637132

Multigenerational effects of inbreeding in Cucurbita pepo ssp. texana (Cucurbitaceae).

PubMed

Hayes, C Nelson; Winsor, James A; Stephenson, Andrew G

2005-02-01

The shape of the fitness function relating the decline in fitness with coefficient of inbreeding (f) can provide evidence concerning the genetic basis of inbreeding depression, but few studies have examined inbreeding depression across a range of f using noncultivated species. Futhermore, studies have rarely examined the effects of inbreeding depression in the maternal parent on offspring fitness. To estimate the shape of the fitness function, we examined the relationship between f and fitness across a range off from 0.000 to 0.875 for components of both male and female fitness in Cucurbita pepo ssp. texana. Each measure of female fitness declined with f, including pistillate flower number, fruit number, seed number per fruit, seed mass per fruit, and percentage seed germination. Several aspects of male fitness also declined with f, including staminate flower number, pollen number per flower, and the number of days of flowering, although cumulative inbreeding depression was less severe for male (0.34) than for female function (0.39). Fitness tended to decline linearly with f between f = 0.00 and f = 0.75 for most traits and across cumulative lifetime fitness (mean = 0.66), suggesting that individual genes causing inbreeding depression are additive and the result of many alleles of small effect. However, most traits also showed a small reduction in inbreeding depression between f = 0.75 and f = 0.875, and evidence of purging or diminishing epistasis was found for in vitro pollen-tube growth rate. To examine inbreeding depression as a maternal effect, we performed outcross pollinations on f = 0.0 and f = 0.5 mothers and found that depression due to maternal inbreeding was 0.07, compared to 0.10 for offspring produced through one generation of selfing. In at least some families, maternal inbreeding reduced fruit number, seed number and mass, staminate flower number, pollen diameter, and pollen-tube growth rate. Collectively these results suggest that, while the fitness function appears to be largely linear for most traits, maternal effects may compound the effects of inbreeding depression in multigenerational studies, though this may be partially offset by purging or diminishing epistasis.

Indication of Cognitive Change and Associated Risk Factor after Thoracic Surgery in the Elderly: A Pilot Study.

PubMed

Kulason, Kay; Nouchi, Rui; Hoshikawa, Yasushi; Noda, Masafumi; Okada, Yoshinori; Kawashima, Ryuta

2017-01-01

Background: This pilot study investigated the effects of partial pulmonary lobectomy lung surgery on cognitive functions of elderly Japanese patients. It is recognized that elderly patients undergoing surgery have increased risk of Postoperative Cognitive Decline (POCD), a condition in which learning, memory, and processing speed is greatly reduced after surgery. Since elderly patients are more likely to exhibit symptoms of POCD, the incidence is increasing as the population receiving surgery is aging. Methods: Cognitive function was measured for all subjects ( n = 12) before and after surgery using three different cognitive tests: Mini-Mental Status Exam-Japanese (MMSE-J), Frontal Assessment Battery (FAB), and a computerized Cogstate Brief Battery (CBB). Changes in these measures indicate changes in cognitive function. In addition, the 12-item General Health Questionnaire (GHQ-12), the Geriatric Depression Scale (GDS), and the 5-item Quality of Life questionnaire (QOL-5) were administered at each time point to measure mental and emotional state. Changes in outcome measures were analyzed via Wilcoxon signed-rank test. Exploratory correlation analysis was conducted using Spearman's rho. Results: Data show a decline in detection (DET; p = 0.045) and identification (IDN; p = 0.038). Spearman's correlation coefficient show a significant correlation between postoperative DET scores and postoperative IDN scores (ρ = 0.78, p = 0.005), a significant correlation between change in IDN and baseline GHQ-12 scores (ρ = -0.595, p = 0.027), and a significant correlation between change in one-back (OBK) scores and duration of anesthesia (ρ = -0.72, p = 0.012). Discussion: This was the first report to examine cognitive decline after major thoracic surgery in Japanese patients. Previous studies have evidenced that POCD is a common phenomenon after surgery, and that age is a major risk factor. The CCB measured significant change in two cognitive domains: attention and psycomotor function. This study clarified that decline in cognition is detectable in certain measures after thoracic surgery in the elderly Japanese patient population. Additionally, longer anesthetic exposure may negatively impact attention and working memory, and preoperative mental wellbeing is a possible predictor of POCD. These preliminary results have important implications and support the need for future studies.

The association of periodontal disease with kidney function decline: a longitudinal retrospective analysis of the MrOS dental study.

PubMed

Grubbs, Vanessa; Vittinghoff, Eric; Taylor, George; Kritz-Silverstein, Donna; Powe, Neil; Bibbins-Domingo, Kirsten; Ishani, Areef; Cummings, Steven R

2016-03-01

Identifying modifiable risk factors for chronic kidney disease (CKD) is essential for reducing its burden. Periodontal disease is common, modifiable and has been implicated as a novel potential CKD risk factor, but evidence of its association with kidney function decline over time is limited. In a longitudinal retrospective cohort of 761 elderly men with preserved kidney function [estimated glomerular filtration rate > 60 mL/min/1.73 m(2) using a calibrated creatinine and cystatin C (eGFRcr-cys) equation] at baseline, we performed multivariable Poisson's regression to examine the association of severe periodontal disease with incident CKD, defined as incident eGFRcr-cys <60 mL/min/1.73 m(2) and rapid (>5% annualized) eGFRcr-cys decline. Severe periodontal disease was defined in two ways: (i) ≥5 mm proximal attachment loss in 30% of teeth examined (European Workshop in Periodontology Group C, European Workshop); and (ii) 2+ interproximal sites with attachment loss ≥6 mm and 1+ interproximal sites with probing depth ≥5 mm (Centers for Disease Control/American Academy of Periodontology, CDC/AAP). At baseline, the mean age was 73.4 (SD 4.8) years, the median eGFRcr-cys was 82.4 mL/min/1.73 m(2), and 35.5 and 25.4% of participants had severe periodontal disease by European Workshop and CDC/AAP criteria, respectively. After a mean follow-up of 4.9 years (SD 0.3), 56 (7.4%) participants had incident CKD. Severe periodontal disease was associated with a 2-fold greater rate of incident CKD [incidence rate ratio (IRR) 2.01 (1.21-3.44), P = 0.007] after adjusting for confounders compared with not severe periodontal disease by European Workshop criteria but did not reach statistical significance by CDC/AAP criteria [IRR 1.10 (0.63-1.91), P = 0.9]. Severe periodontal disease may be associated with incident clinically significant kidney function decline among a cohort of elderly men. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Childhood predictors of lung function trajectories and future COPD risk: a prospective cohort study from the first to the sixth decade of life.

PubMed

Bui, Dinh S; Lodge, Caroline J; Burgess, John A; Lowe, Adrian J; Perret, Jennifer; Bui, Minh Q; Bowatte, Gayan; Gurrin, Lyle; Johns, David P; Thompson, Bruce R; Hamilton, Garun S; Frith, Peter A; James, Alan L; Thomas, Paul S; Jarvis, Deborah; Svanes, Cecilie; Russell, Melissa; Morrison, Stephen C; Feather, Iain; Allen, Katrina J; Wood-Baker, Richard; Hopper, John; Giles, Graham G; Abramson, Michael J; Walters, Eugene H; Matheson, Melanie C; Dharmage, Shyamali C

2018-04-05

Lifetime lung function is related to quality of life and longevity. Over the lifespan, individuals follow different lung function trajectories. Identification of these trajectories, their determinants, and outcomes is important, but no study has done this beyond the fourth decade. We used six waves of the Tasmanian Longitudinal Health Study (TAHS) to model lung function trajectories measured at 7, 13, 18, 45, 50, and 53 years. We analysed pre-bronchodilator FEV 1 z-scores at the six timepoints using group-based trajectory modelling to identify distinct subgroups of individuals whose measurements followed a similar pattern over time. We related the trajectories identified to childhood factors and risk of chronic obstructive pulmonary disease (COPD) using logistic regression, and estimated population-attributable fractions of COPD. Of the 8583 participants in the original cohort, 2438 had at least two waves of lung function data at age 7 years and 53 years and comprised the study population. We identified six trajectories: early below average, accelerated decline (97 [4%] participants); persistently low (136 [6%] participants); early low, accelerated growth, normal decline (196 [8%] participants); persistently high (293 [12%] participants); below average (772 [32%] participants); and average (944 [39%] participants). The three trajectories early below average, accelerated decline; persistently low; and below average had increased risk of COPD at age 53 years compared with the average group (early below average, accelerated decline: odds ratio 35·0, 95% CI 19·5-64·0; persistently low: 9·5, 4·5-20·6; and below average: 3·7, 1·9-6·9). Early-life predictors of the three trajectories included childhood asthma, bronchitis, pneumonia, allergic rhinitis, eczema, parental asthma, and maternal smoking. Personal smoking and active adult asthma increased the impact of maternal smoking and childhood asthma, respectively, on the early below average, accelerated decline trajectory. We identified six potential FEV 1 trajectories, two of which were novel. Three trajectories contributed 75% of COPD burden and were associated with modifiable early-life exposures whose impact was aggravated by adult factors. We postulate that reducing maternal smoking, encouraging immunisation, and avoiding personal smoking, especially in those with smoking parents or low childhood lung function, might minimise COPD risk. Clinicians and patients with asthma should be made aware of the potential long-term implications of non-optimal asthma control for lung function trajectory throughout life, and the role and benefit of optimal asthma control on improving lung function should be investigated in future intervention trials. National Health and Medical Research Council of Australia; European Union's Horizon 2020; The University of Melbourne; Clifford Craig Medical Research Trust of Tasmania; The Victorian, Queensland & Tasmanian Asthma Foundations; The Royal Hobart Hospital; Helen MacPherson Smith Trust; and GlaxoSmithKline. Copyright © 2018 Elsevier Ltd. All rights reserved.

Associations of interleukin-1 gene cluster polymorphisms with C-reactive protein concentration and lung function decline in smoking-induced chronic obstructive pulmonary disease

PubMed Central

Wang, Yu; Shumansky, Karey; Sin, Don D; Man, SF Paul; Akhabir, Loubna; Connett, John E; Anthonisen, Nicholas R; Paré, Peter D; Sandford, Andrew J; He, Jian-Qing

2015-01-01

Objective: We reported association of haplotypes formed by IL-1b (IL1B)-511C/T (rs16944) and a variable number of tandem repeats (rs2234663) in intron 3 of IL-1 receptor antagonist (IL1RN) with rate of lung function decline in smoking-induced COPD. The aim of current study was to further investigate this association. Methods: We genotyped an additional 19 polymorphisms in IL1 cluster (including IL1A, IL1B and IL1RN) in non-Hispanic whites who had the fastest (n = 268) and the slowest (n = 292) decline of FEV1% predicted in the same study. We also analyzed the association of all 21 polymorphisms with serum CRP levels. Results: None of 21 polymorphisms showed significant association with rate of decline of lung function or CRP levels after adjusting for multiple comparisons. Before adjusting for multiple comparisons, only IL1RN_19327 (rs315949) showed significant association with lung function decline (P = 0.03, additive model). The frequencies of genotypes containing the IL1RN_19327A allele were 71.9% and 62.2%, respectively in the fast and slow decline groups (P = 0.02, odds ratio = 1.6, 95% confidence interval = 1.1-2.3); the IL1B_5200 (rs1143633) and rs2234663 in IL1RN were associated with serum CRP levels (P=0.04 and 0.03, respectively). Conclusions: No single marker was significantly associated with either rate of lung function decline or serum CRP levels. PMID:26722511

A systematic review of the role of vitamin insufficiencies and supplementation in COPD

PubMed Central

2010-01-01

Background Pulmonary inflammation, oxidants-antioxidants imbalance, as well as innate and adaptive immunity have been proposed as playing a key role in the development of COPD. The role of vitamins, as assessed either by food frequency questionnaires or measured in serum levels, have been reported to improve pulmonary function, reduce exacerbations and improve symptoms. Vitamin supplements have therefore been proposed to be a potentially useful additive to COPD therapy. Methods A systematic literature review was performed on the association of vitamins and COPD. The role of vitamin supplements in COPD was then evaluated. Conclusions The results of this review showed that various vitamins (vitamin C, D, E, A, beta and alpha carotene) are associated with improvement in features of COPD such as symptoms, exacerbations and pulmonary function. High vitamin intake would probably reduce the annual decline of FEV1. There were no studies that showed benefit from vitamin supplementation in improved symptoms, decreased hospitalization or pulmonary function. PMID:21134250

Age-Related Decline in Primary CD8+ T Cell Responses Is Associated with the Development of Senescence in Virtual Memory CD8+ T Cells.

PubMed

Quinn, Kylie M; Fox, Annette; Harland, Kim L; Russ, Brendan E; Li, Jasmine; Nguyen, Thi H O; Loh, Liyen; Olshanksy, Moshe; Naeem, Haroon; Tsyganov, Kirill; Wiede, Florian; Webster, Rosela; Blyth, Chantelle; Sng, Xavier Y X; Tiganis, Tony; Powell, David; Doherty, Peter C; Turner, Stephen J; Kedzierska, Katherine; La Gruta, Nicole L

2018-06-19

Age-associated decreases in primary CD8 + T cell responses occur, in part, due to direct effects on naive CD8 + T cells to reduce intrinsic functionality, but the precise nature of this defect remains undefined. Aging also causes accumulation of antigen-naive but semi-differentiated "virtual memory" (T VM ) cells, but their contribution to age-related functional decline is unclear. Here, we show that T VM cells are poorly proliferative in aged mice and humans, despite being highly proliferative in young individuals, while conventional naive T cells (T N cells) retain proliferative capacity in both aged mice and humans. Adoptive transfer experiments in mice illustrated that naive CD8 T cells can acquire a proliferative defect imposed by the aged environment but age-related proliferative dysfunction could not be rescued by a young environment. Molecular analyses demonstrate that aged T VM cells exhibit a profile consistent with senescence, marking an observation of senescence in an antigenically naive T cell population. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

The relationship of self-rated function and self-rated health to concurrent functional ability, functional decline, and mortality: findings from the Nun Study.

PubMed

Greiner, P A; Snowdon, D A; Greiner, L H

1996-09-01

We investigated the relationship of self-rated function (i.e., the ability to take care of oneself) and self-rated health to concurrent functional ability, functional decline, and mortality in participants in the Nun Study, a longitudinal study of aging and Alzheimer's disease. A total of 629 of the 678 study participants self-rated their function and health and completed an initial functional assessment in 1991-93. Survivors completed a second assessment in 1993-94. Overall, self-rated function had a stronger relationship to functional ability at the first assessment and to functional decline between the first and second assessments than did self-rated health. Self-rated function also had a stronger relationship to mortality than did self-rated health. Self-rated function may be a better marker of global function than is self-rated health and may be a useful addition to clinical assessment and scientific investigation of the relationships among function, health, and disease.

Surveying predictors of late-life longitudinal change in daily activity energy expenditure.

PubMed

Valiani, Vincenzo; Sourdet, Sandrine; Schoeller, Dale A; Mackey, Dawn C; Bauer, Douglas C; Glynn, Nancy W; Yamada, Yosuke; Harris, Tamara B; Manini, Todd M

2017-01-01

Total daily energy expenditure (TEE) is composed of resting metabolic rate (RMR), post-prandial thermogenesis and activity energy expenditure (AEE). Higher AEE is strongly associated with lower mortality and physical limitations among older adults, but factors that predict changes in AEE in septu and octogenarians are not clearly understood. To identify factors associated with late-life longitudinal change in AEE. Energy expenditure was re-assessed in 83 participants (average age at baseline, 74.4±3.2 years)-an average of 7.5±0.54 years since the baseline measure. RMR was measured using indirect calorimetry and the thermic effect of meals was estimated at 10% of TEE. AEE was calculated as: TEE(0.9)-RMR. Participants were categorized into two groups according to the estimated day-to-day precision of the doubly-labeled water technique. Those who were within 10% or increased relative to their initial AEE measurement were categorized as having preserved AEE. Participants who declined greater than 10% of their initial measurement were categorized as having reduced AEE. A variety of socio-demographic, functional and mental factors, body composition, community and personal behaviors, blood measurements and health conditions were evaluated between groups at baseline and changes during follow-up. Daily AEE declined 106.61±293.25 kcal, which equated to a 14.63±40.57 kcal/d decrease per year. Fifty-nine percent (n = 49) preserved their AEE and 41% (n = 34) declined. Those who demonstrated a decline in AEE were older, had lower walking speed at baseline and showed a higher lean mass loss during follow up. Otherwise, groups were similar for socio-demographic characteristics, body composition, mental and physical function, health conditions and community and personal behaviors at baseline and change in these factors during follow-up. This study demonstrates that AEE declines through the 8th decade of life and is associated with age, lower walking speed at baseline and lean mass loss. Additionally, there are a significant number of individuals who appear to be resilient to these declines despite having health events that are expected to have a negative impact on their physical activity.

Aging-related limit of exercise efficacy on motor decline

PubMed Central

Arnold, Jennifer C.; Cantu, Mark A.; Kasanga, Ella A.; Nejtek, Vicki A.; Papa, Evan V.; Bugnariu, Nicoleta; Salvatore, Michael F.

2017-01-01

Identifying lifestyle strategies and allied neurobiological mechanisms that reduce aging-related motor impairment is imperative, given the accelerating number of retirees and increased life expectancy. A physically active lifestyle prior to old age can reduce risk of debilitating motor decline. However, if exercise is initiated after motor decline has begun in the lifespan, it is unknown if aging itself may impose a limit on exercise efficacy to decelerate further aging-related motor decline. In Brown-Norway/Fischer 344 F1 hybrid (BNF) rats, locomotor activity begins to decrease in middle age (12–18 months). One mechanism of aging-related motor decline may be decreased expression of GDNF family receptor, GFRα-1, which is decreased in substantia nigra (SN) between 12 and 30 months old. Moderate exercise, beginning at 18 months old, increases nigral GFRα-1 and tyrosine hydroxylase (TH) expression within 2 months. In aged rats, replenishing aging-related loss of GFRα-1 in SN increases TH in SN alone and locomotor activity. A moderate exercise regimen was initiated in sedentary male BNF rats in a longitudinal study to evaluate if exercise could attenuate aging-related motor decline when initiated at two different ages in the latter half of the lifespan (18 or 24 months old). Motor decline was reversed in the 18-, but not 24-month-old, cohort. However, exercise efficacy in the 18-month-old group was reduced as the rats reached 27 months old. GFRα-1 expression was not increased in either cohort. These studies suggest exercise can decelerate motor decline when begun in the latter half of the lifespan, but its efficacy may be limited by age of initiation. Decreased plasticity of GFRα-1 expression following exercise may limit its efficacy to reverse motor decline. PMID:29176896

Aging-related limit of exercise efficacy on motor decline.

PubMed

Arnold, Jennifer C; Cantu, Mark A; Kasanga, Ella A; Nejtek, Vicki A; Papa, Evan V; Bugnariu, Nicoleta; Salvatore, Michael F

2017-01-01

Identifying lifestyle strategies and allied neurobiological mechanisms that reduce aging-related motor impairment is imperative, given the accelerating number of retirees and increased life expectancy. A physically active lifestyle prior to old age can reduce risk of debilitating motor decline. However, if exercise is initiated after motor decline has begun in the lifespan, it is unknown if aging itself may impose a limit on exercise efficacy to decelerate further aging-related motor decline. In Brown-Norway/Fischer 344 F1 hybrid (BNF) rats, locomotor activity begins to decrease in middle age (12-18 months). One mechanism of aging-related motor decline may be decreased expression of GDNF family receptor, GFRα-1, which is decreased in substantia nigra (SN) between 12 and 30 months old. Moderate exercise, beginning at 18 months old, increases nigral GFRα-1 and tyrosine hydroxylase (TH) expression within 2 months. In aged rats, replenishing aging-related loss of GFRα-1 in SN increases TH in SN alone and locomotor activity. A moderate exercise regimen was initiated in sedentary male BNF rats in a longitudinal study to evaluate if exercise could attenuate aging-related motor decline when initiated at two different ages in the latter half of the lifespan (18 or 24 months old). Motor decline was reversed in the 18-, but not 24-month-old, cohort. However, exercise efficacy in the 18-month-old group was reduced as the rats reached 27 months old. GFRα-1 expression was not increased in either cohort. These studies suggest exercise can decelerate motor decline when begun in the latter half of the lifespan, but its efficacy may be limited by age of initiation. Decreased plasticity of GFRα-1 expression following exercise may limit its efficacy to reverse motor decline.

Contrasting responses of functional diversity to major losses in taxonomic diversity.

PubMed

Edie, Stewart M; Jablonski, David; Valentine, James W

2018-01-23

Taxonomic diversity of benthic marine invertebrate shelf species declines at present by nearly an order of magnitude from the tropics to the poles in each hemisphere along the latitudinal diversity gradient (LDG), most steeply along the western Pacific where shallow-sea diversity is at its tropical maximum. In the Bivalvia, a model system for macroevolution and macroecology, this taxonomic trend is accompanied by a decline in the number of functional groups and an increase in the evenness of taxa distributed among those groups, with maximum functional evenness (FE) in polar waters of both hemispheres. In contrast, analyses of this model system across the two era-defining events of the Phanerozoic, the Permian-Triassic and Cretaceous-Paleogene mass extinctions, show only minor declines in functional richness despite high extinction intensities, resulting in a rise in FE owing to the persistence of functional groups. We hypothesize that the spatial decline of taxonomic diversity and increase in FE along the present-day LDG primarily reflect diversity-dependent factors, whereas retention of almost all functional groups through the two mass extinctions suggests the operation of diversity-independent factors. Comparative analyses of different aspects of biodiversity thus reveal strongly contrasting biological consequences of similarly severe declines in taxonomic diversity and can help predict the consequences for functional diversity among different drivers of past, present, and future biodiversity loss.

The nurse's load: early-life exposure to brood-rearing affects behavior and lifespan in honey bees (Apis mellifera).

PubMed

Amdam, Gro V; Rueppell, Olav; Fondrk, M Kim; Page, Robert E; Nelson, C Mindy

2009-01-01

Long-lived honey bees (Apis mellifera) develop in fall. This pattern may be explained by reduced nurse loads. When the amount of brood in colonies declines as a function of adverse foraging conditions, adult bees build up surplus nutrient stores that include vitellogenin, a behavioral affector protein that also can increase lifespan. Although the seasonal reduction in exposure to nursing tasks predictably results in vitellogenin accumulation, the assumption that long-lived adults thereby develop is confounded by a concomitant decline in foraging effort. Foraging activity reduces lifespan, and is influenced by colony resource consumption, brood pheromones, availability of nectar and pollen, and weather. Here, we perform the first controlled experiment where the nursing environment of pre-foraging sister bees was set to vary, while their foraging environment later was set to be the same. We measure vitellogenin, age at foraging onset and lifespan. We establish that reduced brood-rearing increases vitellogenin levels, and delays foraging onset and death. Longevity is largely explained by the effect of nursing on the onset of foraging behavior, but is also influenced by the level of brood-rearing independent of behavioral change. Our findings are consistent with the roles of vitellogenin in regulation of honey bee behavior and lifespan.

Microbial communities biostimulated by ethanol during uranium (VI) bioremediation in contaminated sediment as shown by stable isotope probing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leigh, Mary Beth; Wu, Wei -Min; Cardenas, Erick

Stable isotope probing (SIP) was used to identify microbes stimulated by ethanol addition in microcosms containing two sediments collected from the bioremediation test zone at the US Department of Energy Oak Ridge site, TN, USA. One sample was highly bioreduced with ethanol while another was less reduced. Microcosms with the respective sediments were amended with 13C labeled ethanol and incubated for 7 days for SIP. Ethanol was rapidly converted to acetate within 24 h accompanied with the reduction of nitrate and sulfate. The accumulation of acetate persisted beyond the 7 d period. Aqueous U did not decline in the microcosmmore » with the reduced sediment due to desorption of U but continuously declined in the less reduced sample. Microbial growth and concomitant 13C-DNA production was detected when ethanol was exhausted and abundant acetate had accumulated in both microcosms. This coincided with U(VI) reduction in the less reduced sample. 13C originating from ethanol was ultimately utilized for growth, either directly or indirectly, by the dominant microbial community members within 7 days of incubation. The microbial community was comprised predominantly of known denitrifiers, sulfate-reducing bacteria and iron (III) reducing bacteria including Desulfovibrio, Sphingomonas, Ferribacterium, Rhodanobacter, Geothrix, Thiobacillus and others, including the known U(VI)-reducing bacteria Acidovorax, Anaeromyxobacter, Desulfovibrio, Geobacter and Desulfosporosinus. As a result, the findings suggest that ethanol biostimulates the U(VI)-reducing microbial community by first serving as an electron donor for nitrate, sulfate, iron (III) and U(VI) reduction, and acetate which then functions as electron donor for U(VI) reduction and carbon source for microbial growth.« less

Effects of home-based diet and exercise on functional outcomes among older, overweight long-term cancer survivors: RENEW: a randomized controlled trial.

PubMed

Morey, Miriam C; Snyder, Denise C; Sloane, Richard; Cohen, Harvey Jay; Peterson, Bercedis; Hartman, Terryl J; Miller, Paige; Mitchell, Diane C; Demark-Wahnefried, Wendy

2009-05-13

Five-year survival rates for early stage colorectal, breast, and prostate cancer currently exceed 90% and are increasing. Cancer survivors are at greater risk for second malignancies, other comorbidities, and accelerated functional decline. Lifestyle interventions may provide benefit, but it is unknown whether long-term cancer survivors can modify their lifestyle behaviors sufficiently to improve functional status. To determine whether a telephone counseling and mailed print material-based diet and exercise intervention is effective in reorienting functional decline in older, overweight cancer survivors. Randomized controlled trial of 641 overweight (body mass index > or = 25 and < 40), long-term (> or = 5 years) survivors (aged 65-91 years) of colorectal, breast, and prostate cancer, who were randomly assigned to an intervention group (n = 319) or delayed intervention (control) group (n = 322) in Canada, the United Kingdom, and 21 US states. Individuals were recruited for the Reach out to Enhance Wellness (RENEW) trial from July 1, 2005, through May 17, 2007. A 12-month, home-based tailored program of telephone counseling and mailed materials promoting exercise, improved diet quality, and modest weight loss. The control group was wait-listed for 12 months. Change in self-reported physical function on the Short-Form 36 physical function subscale (score range, 0-100; a high score indicates better functioning) from baseline to 12 months was the primary end point. Secondary outcomes included changes in function on the basic and advanced lower extremity function subscales of the Late Life Function and Disability Index (score range, 0-100), physical activity, body mass index, and overall health-related quality of life. The mean baseline Short-Form 36 physical function score was 75.7. At the 12-month follow-up, the mean function scores declined less rapidly in the intervention group (-2.15; 95% confidence interval [CI], -0.36 to -3.93) compared with the control group (-4.84; 95% CI, -3.04 to -6.63) (P = .03). The mean baseline basic lower extremity function score was 78.2. The mean changes in basic lower extremity function were 0.34 (95% CI, -0.84 to 1.52) in the intervention group compared with -1.89 (95% CI, -0.70 to -3.09) in the control group (P = .005). Physical activity, dietary behaviors, and overall quality of life increased significantly in the intervention group compared with the control group, and weight loss also was greater (2.06 kg [95% CI, 1.69 to 2.43 kg] vs 0.92 kg [95% CI, 0.51 to 1.33 kg], respectively; P < .001). Among older, long-term survivors of colorectal, breast, and prostate cancer, a diet and exercise intervention reduced the rate of self-reported functional decline compared with no intervention. clinicaltrials.gov Identifier: NCT00303875.

Adaptor Protein-1 Complex Affects the Endocytic Trafficking and Function of Peptidylglycine α-Amidating Monooxygenase, a Luminal Cuproenzyme*

PubMed Central

Bonnemaison, Mathilde L.; Bäck, Nils; Duffy, Megan E.; Ralle, Martina; Mains, Richard E.; Eipper, Betty A.

2015-01-01

The adaptor protein-1 complex (AP-1), which transports cargo between the trans-Golgi network and endosomes, plays a role in the trafficking of Atp7a, a copper-transporting P-type ATPase, and peptidylglycine α-amidating monooxygenase (PAM), a copper-dependent membrane enzyme. Lack of any of the four AP-1 subunits impairs function, and patients with MEDNIK syndrome, a rare genetic disorder caused by lack of expression of the σ1A subunit, exhibit clinical and biochemical signs of impaired copper homeostasis. To explore the role of AP-1 in copper homeostasis in neuroendocrine cells, we used corticotrope tumor cells in which AP-1 function was diminished by reducing expression of its μ1A subunit. Copper levels were unchanged when AP-1 function was impaired, but cellular levels of Atp7a declined slightly. The ability of PAM to function was assessed by monitoring 18-kDa fragment-NH2 production from proopiomelanocortin. Reduced AP-1 function made 18-kDa fragment amidation more sensitive to inhibition by bathocuproine disulfonate, a cell-impermeant Cu(I) chelator. The endocytic trafficking of PAM was altered, and PAM-1 accumulated on the cell surface when AP-1 levels were reduced. Reduced AP-1 function increased the Atp7a presence in early/recycling endosomes but did not alter the ability of copper to stimulate its appearance on the plasma membrane. Co-immunoprecipitation of a small fraction of PAM and Atp7a supports the suggestion that copper can be transferred directly from Atp7a to PAM, a process that can occur only when both proteins are present in the same subcellular compartment. Altered luminal cuproenzyme function may contribute to deficits observed when the AP-1 function is compromised. PMID:26170456

Measuring Frailty Can Help Emergency Departments Identify Independent Seniors at Risk of Functional Decline After Minor Injuries.

PubMed

Sirois, Marie-Josée; Griffith, Lauren; Perry, Jeffrey; Daoust, Raoul; Veillette, Nathalie; Lee, Jacques; Pelletier, Mathieu; Wilding, Laura; Émond, Marcel

2017-01-01

This study aims to (i) describe frailty in the subgroup of independent community-dwelling seniors consulting emergency departments (EDs) for minor injuries, (ii) examine the association between frailty and functional decline 3 months postinjury, (iii) ascertain the predictive accuracy of frailty measures and emergency physicians' for functional decline. Prospective cohort in 2011-2013 among 1,072 seniors aged 65 years or older, independent in basic daily activities, evaluated in Canadian EDs for minor injuries.Frailty was assessed at EDs using the Canadian Study of Health and Aging-Clinical Frailty scale (CSHA-CFS) and the Study of Osteoporotic Fracture frailty index (SOF). Functional decline was defined as a loss ≥2/28 on the Older American Resources Services scale 3 months postinjury. Generalized mixed models were used to explore differences in functional decline across frailty levels. Areas under the receiver operating characteristic curve were used to ascertain the predictive accuracy of frailty measures and emergency physicians' clinical judgment. The SOF and CSHA-CFS were available in 342 and 1,058 participants, respectively. The SOF identified 55.6%, 32.7%, 11.7% patients as robust, prefrail, and frail. These CSHA-CFS (n = 1,058) proportions were 51.9%, 38.3%, and 9.9%. The 3-month incidence of functional decline was 12.1% (10.0%-14.6%). The Areas under the receiver operating characteristic curves of the CSHA-CFS and the emergency physicians' were similar (0.548-0.777), while the SOF was somewhat higher (0.704-0.859). Measuring frailty in community-dwelling seniors with minor injuries in EDs may enhance current risk screening for functional decline. However, before implementation in usual care, feasibility issues such as inter-rater reliability and acceptability of frailty tools in the EDs have to be addressed. © The Author 2015. 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.

Measuring Frailty Can Help Emergency Departments Identify Independent Seniors at Risk of Functional Decline After Minor Injuries

PubMed Central

Griffith, Lauren; Perry, Jeffrey; Daoust, Raoul; Veillette, Nathalie; Lee, Jacques; Pelletier, Mathieu; Wilding, Laura; Émond, Marcel

2017-01-01

Background. This study aims to (i) describe frailty in the subgroup of independent community-dwelling seniors consulting emergency departments (EDs) for minor injuries, (ii) examine the association between frailty and functional decline 3 months postinjury, (iii) ascertain the predictive accuracy of frailty measures and emergency physicians’ for functional decline. Method. Prospective cohort in 2011–2013 among 1,072 seniors aged 65 years or older, independent in basic daily activities, evaluated in Canadian EDs for minor injuries. Frailty was assessed at EDs using the Canadian Study of Health and Aging-Clinical Frailty scale (CSHA-CFS) and the Study of Osteoporotic Fracture frailty index (SOF). Functional decline was defined as a loss ≥2/28 on the Older American Resources Services scale 3 months postinjury. Generalized mixed models were used to explore differences in functional decline across frailty levels. Areas under the receiver operating characteristic curve were used to ascertain the predictive accuracy of frailty measures and emergency physicians’ clinical judgment. Results. The SOF and CSHA-CFS were available in 342 and 1,058 participants, respectively. The SOF identified 55.6%, 32.7%, 11.7% patients as robust, prefrail, and frail. These CSHA-CFS (n = 1,058) proportions were 51.9%, 38.3%, and 9.9%. The 3-month incidence of functional decline was 12.1% (10.0%−14.6%). The Areas under the receiver operating characteristic curves of the CSHA-CFS and the emergency physicians’ were similar (0.548–0.777), while the SOF was somewhat higher (0.704–0.859). Conclusion. Measuring frailty in community-dwelling seniors with minor injuries in EDs may enhance current risk screening for functional decline. However, before implementation in usual care, feasibility issues such as inter-rater reliability and acceptability of frailty tools in the EDs have to be addressed. PMID:26400735

Arterial wave reflections and kidney function decline among persons with preserved estimated glomerular filtration rate: the Multi-Ethnic Study of Atherosclerosis.

PubMed

Hsu, Jeffrey J; Katz, Ronit; Chirinos, Julio A; Jacobs, David R; Duprez, Daniel A; Peralta, Carmen A

2016-05-01

Differences in arterial wave reflections have been associated with increased risk for heart failure and mortality. Whether these measures are also associated with kidney function decline is not well established. Reflection magnitude (RM, defined as the ratio of the backward wave [Pb] to that of the forward wave [Pf]), augmentation index (AIx), and pulse pressure amplification (PPA) were derived from radial tonometry measures among 5232 participants free of cardiovascular disease who were enrolled in the Multiethnic Study of Atherosclerosis. Kidney function was estimated by creatinine and cystatin C measurements, as well as albumin-to-creatinine ratio. We evaluated the associations of Pb, Pf, RM, AIx, and PPA with annualized estimated glomerular filtration rate (eGFR) change and rapid kidney function decline over 5 years, using generalized linear mixed models and logistic regression, respectively. Of the study participants, 48% were male, mean age was 62 years, mean eGFR and median albumin-to-creatinine ratio at baseline were 84 mL/min/1.73 m(2) and 5.3 mg/g, respectively. In demographically adjusted models, both Pb and Pf had similarly strong associations with kidney function decline; compared to those in the lowest tertiles, the persons in the highest tertiles of Pb and Pf had a 1.01 and 0.99 mL/min/1.73 m(2)/year faster eGFR decline, respectively (P < .05). However, these associations were attenuated after adjustment for systolic blood pressure. We found no significant associations between RM, AIx, or PPA and kidney function decline. In conclusion, the reflected and forward wave components were similarly associated with kidney function decline, and these associations were explained by differences in systolic blood pressure. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Clinical implications of the reduced activity of the GH-IGF-I axis in older men.

PubMed

Ceda, G P; Dall'Aglio, E; Maggio, M; Lauretani, F; Bandinelli, S; Falzoi, C; Grimaldi, W; Ceresini, G; Corradi, F; Ferrucci, L; Valenti, G; Hoffman, A R

2005-01-01

During the last decade, a significant body of evidence has accumulated, indicating that IGF-I might play a role in several pathological conditions commonly seen during aging, such as atherosclerosis and cardiovascular disease (CVD), cognitive decline, dementia, sarcopenia and frailty. A vascular protective role for IGF-I has been suggested because of its ability to stimulate nitric oxide production from endothelial and vascular smooth muscle cells. In cross sectional studies, low IGF-I levels have been associated with unfavorable CVD risk factors profile, such as atherosclerosis, abnormal lipoprotein levels and hypertension, while in prospective studies, lower IGF-I levels predict future development of ischemic heart disease. The fall in IGF-I levels with aging correlates with cognitive decline and it has been suggested that IGF-I plays a role in the development of dementia. IGF-I is highly expressed within the brain and is essential for normal brain development. IGF-I has anti-apoptotic and neuroprotective effects and promotes projection neuron growth, dendritic arborization and synaptogenesis. Collectively, these data are consistent with a causal link between the age-related decline in GH and IGF-I levels and cognitive deficits in older persons. Finally, there is evidence of a relationship between declining GH and IGF-I levels and age-related changes in body composition and physical function. However, few studies have documented a precise role of IGF-I in the development of sarcopenia, frailty and poor mobility. We have recently documented that serum IGF-I is significantly associated with measures of muscle strength and physical performance in men and to a lesser extent in women. In conclusion, IGF-I is a pleiotropic hormone that in older persons may positively affect the cardiovascular system, the central nervous system and physical function.

Local bumble bee decline linked to recovery of honey bees, drought effects on floral resources.

PubMed

Thomson, Diane M

2016-10-01

Time series of abundances are critical for understanding how abiotic factors and species interactions affect population dynamics, but are rarely linked with experiments and also scarce for bee pollinators. This gap is important given concerns about declines in some bee species. I monitored honey bee (Apis mellifera) and bumble bee (Bombus spp.) foragers in coastal California from 1999, when feral A. mellifera populations were low due to Varroa destructor, until 2014. Apis mellifera increased substantially, except between 2006 and 2011, coinciding with declines in managed populations. Increases in A. mellifera strongly correlated with declines in Bombus and reduced diet overlap between them, suggesting resource competition consistent with past experimental results. Lower Bombus numbers also correlated with diminished floral resources. Declines in floral abundances were associated with drought and reduced spring rainfall. These results illustrate how competition with an introduced species may interact with climate to drive local decline of native pollinators. © 2016 John Wiley & Sons Ltd/CNRS.

The control of translational accuracy is a determinant of healthy ageing in yeast

PubMed Central

Leadsham, Jane E.; Sauvadet, Aimie; Tarrant, Daniel; Adam, Ilectra S.; Saromi, Kofo; Laun, Peter; Rinnerthaler, Mark; Breitenbach-Koller, Hannelore; Breitenbach, Michael; Tuite, Mick F.; Gourlay, Campbell W.

2017-01-01

Life requires the maintenance of molecular function in the face of stochastic processes that tend to adversely affect macromolecular integrity. This is particularly relevant during ageing, as many cellular functions decline with age, including growth, mitochondrial function and energy metabolism. Protein synthesis must deliver functional proteins at all times, implying that the effects of protein synthesis errors like amino acid misincorporation and stop-codon read-through must be minimized during ageing. Here we show that loss of translational accuracy accelerates the loss of viability in stationary phase yeast. Since reduced translational accuracy also reduces the folding competence of at least some proteins, we hypothesize that negative interactions between translational errors and age-related protein damage together overwhelm the cellular chaperone network. We further show that multiple cellular signalling networks control basal error rates in yeast cells, including a ROS signal controlled by mitochondrial activity, and the Ras pathway. Together, our findings indicate that signalling pathways regulating growth, protein homeostasis and energy metabolism may jointly safeguard accurate protein synthesis during healthy ageing. PMID:28100667

The control of translational accuracy is a determinant of healthy ageing in yeast.

PubMed

von der Haar, Tobias; Leadsham, Jane E; Sauvadet, Aimie; Tarrant, Daniel; Adam, Ilectra S; Saromi, Kofo; Laun, Peter; Rinnerthaler, Mark; Breitenbach-Koller, Hannelore; Breitenbach, Michael; Tuite, Mick F; Gourlay, Campbell W

2017-01-01

Life requires the maintenance of molecular function in the face of stochastic processes that tend to adversely affect macromolecular integrity. This is particularly relevant during ageing, as many cellular functions decline with age, including growth, mitochondrial function and energy metabolism. Protein synthesis must deliver functional proteins at all times, implying that the effects of protein synthesis errors like amino acid misincorporation and stop-codon read-through must be minimized during ageing. Here we show that loss of translational accuracy accelerates the loss of viability in stationary phase yeast. Since reduced translational accuracy also reduces the folding competence of at least some proteins, we hypothesize that negative interactions between translational errors and age-related protein damage together overwhelm the cellular chaperone network. We further show that multiple cellular signalling networks control basal error rates in yeast cells, including a ROS signal controlled by mitochondrial activity, and the Ras pathway. Together, our findings indicate that signalling pathways regulating growth, protein homeostasis and energy metabolism may jointly safeguard accurate protein synthesis during healthy ageing. © 2017 The Authors.

Aging and Visual Attention

PubMed Central

Madden, David J.

2007-01-01

Older adults are often slower and less accurate than are younger adults in performing visual-search tasks, suggesting an age-related decline in attentional functioning. Age-related decline in attention, however, is not entirely pervasive. Visual search that is based on the observer’s expectations (i.e., top-down attention) is relatively preserved as a function of adult age. Neuroimaging research suggests that age-related decline occurs in the structure and function of brain regions mediating the visual sensory input, whereas activation of regions in the frontal and parietal lobes is often greater for older adults than for younger adults. This increased activation may represent an age-related increase in the role of top-down attention during visual tasks. To obtain a more complete account of age-related decline and preservation of visual attention, current research is beginning to explore the relation of neuroimaging measures of brain structure and function to behavioral measures of visual attention. PMID:18080001

Contrasting Olfaction, Vision, and Audition as Predictors of Cognitive Change and Impairment in Non-Demented Older Adults

PubMed Central

MacDonald, Stuart W.S.; Keller, Connor J.C.; Brewster, Paul W.H.; Dixon, Roger A.

2017-01-01

Objective This study examines the relative utility of a particular class of non-invasive functional biomarkers -- sensory functions -- for detecting those at risk of cognitive decline and impairment. Three central research objectives were examined including whether: (1) olfactory function, vision, and audition exhibited significant longitudinal declines in non-demented older adults, (2) multi-wave change for these sensory function indicators predicted risk of mild cognitive impairment, and (3) change within persons for each sensory measure shared dynamic time-varying associations with within-person change in cognitive functioning. Method A longitudinal sample (n=408) from the Victoria Longitudinal Study was assembled. Three cognitive status subgroups were identified: not impaired cognitively (NIC), single assessment mild cognitive impairment (SA-MCI), and multiple assessment mild cognitive impairment (MA-MCI). Results We tested independent predictive associations, contrasting change in sensory function as predictors of cognitive decline and impairment, utilizing both linear mixed models and logistic regression analysis. Olfaction and, to a lesser extent, vision were identified as the most robust predictors of cognitive status and decline; audition showed little predictive influence. Conclusions These findings underscore the potential utility of deficits in olfactory function, in particular, as an early marker of age- and pathology-related cognitive decline. Functional biomarkers may represent potential candidates for use in the early stages of a multi-step screening approach for detecting those at risk of cognitive impairment, as well as for targeted intervention. PMID:29809033

Review of the Persistence of Herpes Zoster Vaccine Efficacy in Clinical Trials.

PubMed

Cook, Stephen J; Flaherty, Dennis K

2015-11-01

The live attenuated herpes zoster vaccine(*) was approved for the prevention of shingles in 2006. Initial Phase III clinical trials proved vaccine efficacy persisted during the study duration; however, assessment of long-term efficacy required additional studies. This article reviews efficacy data for the zoster vaccine that have been published since 2004. It focuses on studies assessing declining vaccine efficacy. MEDLINE, EMBASE, CENTRAL, and CINAHL databases were searched for zoster vaccine efficacy trials. Randomized controlled trials published from 2004 to 2015 were included in the review. Six studies were included in the review. The zoster vaccine reduced the risk of herpes zoster by 51.3% to 72.4% in 2 Phase III trials. Primary and other analyses showed the vaccine was effective at reducing the burden of illness (61.1%), postherpetic neuralgia (66.5%), disease interference on functional status (66.2%), and disease impact on health-related quality of life (55%) compared with placebo. Surveillance studies showed a decrease in vaccine efficacy for reducing the incidence of herpes zoster during follow-up years 3.3 to 7.8 (39.6% relative reduction) and 4.7 to 11.6 (21.1% relative reduction). Initial zoster vaccine efficacy is significant, but declines in post-vaccination years 3 to 11. This raises the question about the need for possible revaccination with the zoster vaccine. Clinicians should consider the declining efficacy when administering the zoster vaccine to patients. Future studies will need to address the impact of the varicella vaccine on the incidence of shingles and whether this impacts the efficacy of the zoster vaccine. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

President Hails Continued Decline in Default Rate on Student Loans.

ERIC Educational Resources Information Center

Burd, Stephen

1997-01-01

President Bill Clinton used the declining default rate on college student loans as a basis for proposing tax breaks for college costs. Reduced defaults have saved taxpayer money and helped reduce the federal deficit. Over 150 colleges and universities, including 25 private institutions, risk losing eligibility for federal grant and loan programs…

Hyperfiltration and effect of nitric oxide inhibition on renal and endothelial function in humans with uncomplicated type 1 diabetes mellitus

PubMed Central

Reich, Heather N.; Jiang, Shan; Har, Ronnie; Nasrallah, Rania; Hébert, Richard L.; Lai, Vesta; Scholey, James W.; Sochett, Etienne B.

2012-01-01

Studies of experimental diabetes mellitus (DM) suggest that increased nitric oxide (NO) bioactivity contributes to renal hyperfiltration. However, the role of NO in mediating hyperfiltration has not been fully elucidated in humans. Our aim was to examine the effect of NO synthase inhibition on renal and peripheral vascular function in normotensive subjects with uncomplicated type 1 DM. Renal function and brachial artery flow-mediated vasodilatation (FMD) were measured before and after an intravenous infusion of the NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NMMA) in 21 healthy control and 37 type 1 DM patients. Measurements in DM participants were made under clamped euglycemic conditions. The effect of l-NMMA on circulating and urinary NO metabolites (NOx) and cGMP and on urinary prostanoids was also determined. Baseline characteristics were similar in the two groups. For analysis, the DM patients were divided into those with hyperfiltration (DM-H, n = 18) and normal glomerular filtration rate (GFR) levels (DM-N, n = 19). Baseline urine NOx and cGMP were highest in DM-H. l-NMMA led to a decline in GFR in DM-H (152 ± 16 to 140 ± 11 ml·min−1·1.73 m−2) but not DM-N or healthy control participants. The decline in effective renal plasma flow in response to l-NMMA (806 ± 112 to 539 ± 80 ml·min−1·1.73 m−2) in DM-H was also exaggerated compared with the other groups (repeated measures ANOVA, P < 0.05), along with declines in urinary NOx metabolites and cGMP. Baseline FMD was lowest in DM-H compared with the other groups and did not change in response to l-NMMA. l-NMMA reduced FMD and plasma markers of NO bioactivity in the healthy control and DM-N groups. In patients with uncomplicated type 1 DM, renal hyperfiltration is associated with increased NO bioactivity in the kidney and reduced NO bioactivity in the systemic circulation, suggesting a paradoxical state of high renal and low systemic vascular NO bioactivity. PMID:22855276

Attenuated anticorrelation between the default and dorsal attention networks with aging: evidence from task and rest.

PubMed

Spreng, R Nathan; Stevens, W Dale; Viviano, Joseph D; Schacter, Daniel L

2016-09-01

Anticorrelation between the default and dorsal attention networks is a central feature of human functional brain organization. Hallmarks of aging include impaired default network modulation and declining medial temporal lobe (MTL) function. However, it remains unclear if this anticorrelation is preserved into older adulthood during task performance, or how this is related to the intrinsic architecture of the brain. We hypothesized that older adults would show reduced within- and increased between-network functional connectivity (FC) across the default and dorsal attention networks. To test this hypothesis, we examined the effects of aging on task-related and intrinsic FC using functional magnetic resonance imaging during an autobiographical planning task known to engage the default network and during rest, respectively, with young (n = 72) and older (n = 79) participants. The task-related FC analysis revealed reduced anticorrelation with aging. At rest, there was a robust double dissociation, with older adults showing a pattern of reduced within-network FC, but increased between-network FC, across both networks, relative to young adults. Moreover, older adults showed reduced intrinsic resting-state FC of the MTL with both networks suggesting a fractionation of the MTL memory system in healthy aging. These findings demonstrate age-related dedifferentiation among these competitive large-scale networks during both task and rest, consistent with the idea that age-related changes are associated with a breakdown in the intrinsic functional architecture within and among large-scale brain networks. Copyright © 2016 Elsevier Inc. All rights reserved.

Terminal decline and practice effects in older adults without dementia: the MoVIES project.

PubMed

Dodge, Hiroko H; Wang, Chia-Ning; Chang, Chung-Chou H; Ganguli, Mary

2011-08-23

To track cognitive change over time in dementia-free older adults and to examine terminal cognitive decline. A total of 1,230 subjects who remained free from dementia over 14 years of follow-up were included in a population-based epidemiologic cohort study. First, we compared survivors and decedents on their trajectories of 5 cognitive functions (learning, memory, language, psychomotor speed, executive functions), dissociating practice effects which can mask clinically significant decline from age-associated cognitive decline. We used longitudinal mixed-effects models with penalized linear spline. Second, limiting the sample to 613 subjects who died during follow-up, we identified the inflection points at which the rate of cognitive decline accelerated, in relation to time of death, controlling for practice effects. We used mixed-effects model with a change point. Age-associated cognitive trajectories were similar between decedents and survivors without dementia. However, substantial differences were observed between the trajectories of practice effects of survivors and decedents, resembling those usually observed between normal and mildly cognitively impaired elderly. Executive and language functions showed the earliest terminal declines, more than 9 years prior to death, independent of practice effects. Terminal cognitive decline in older adults without dementia may reflect presymptomatic disease which does not cross the clinical threshold during life. Alternatively, cognitive decline attributed to normal aging may itself represent underlying neurodegenerative or vascular pathology. Although we cannot conclude definitively from this study, the separation of practice effects from age-associated decline could help identify preclinical dementia.

Effects of Hurricane Katrina on nursing facility resident mortality, hospitalization, and functional decline.

PubMed

Dosa, David; Feng, Zhanlian; Hyer, Kathy; Brown, Lisa M; Thomas, Kali; Mor, Vincent

2010-09-01

The study was designed to examine the 30- and 90-day mortality and hospitalization rates among nursing facility (NF) residents in the affected areas of Louisiana and Mississippi following Hurricane Katrina and to assess the rate of significant posthurricane functional decline. A secondary data analysis was conducted using Medicare claims merged with NF resident data from the Minimum Data Set. Thirty- and 90-day mortality and hospitalization rates for long-stay (>90 days) residents residing in 141 at-risk NFs during Hurricane Katrina were compared to rates for residents residing at the same facilities during the same time period in prior nonhurricane years (2003 and 2004). Functional decline was assessed as a 4+ drop in function using a 28-point Minimum Data Set Activities of Daily Living Scale. There were statistically significant differences (all P < .0001) in mortality, hospitalization, and functional decline among residents exposed to Hurricane Katrina. At 30 days, the mortality rate was 3.88% among the exposed cohort compared with 2.10% and 2.28% for residents in 2003 and 2004, respectively. The 90-day mortality rate was 9.27% compared with 6.71% and 6.31%, respectively. These mortality differences translated into an additional 148 deaths at 30 days and 230 deaths at 90 days. The 30-day hospitalization rate was 9.87% compared with 7.21% and 7.53%, respectively. The 90-day hospitalization rate was 20.39% compared with 18.61% and 17.82%, respectively. Finally, the rate of significant functional decline among survivors was 6.77% compared with 5.81% in 2003 and 5.10% in 2004. NF residents experienced a significant increase in mortality, hospitalization, and functional decline during Hurricane Katrina.

NFE2L2 pathway polymorphisms and lung function decline in chronic obstructive pulmonary disease

PubMed Central

Malhotra, Deepti; Boezen, H. Marike; Siedlinski, Mateusz; Postma, Dirkje S.; Wong, Vivien; Akhabir, Loubna; He, Jian-Qing; Connett, John E.; Anthonisen, Nicholas R.; Paré, Peter D.; Biswal, Shyam

2012-01-01

An oxidant-antioxidant imbalance in the lung contributes to the development of chronic obstructive pulmonary disease (COPD) that is caused by a complex interaction of genetic and environmental risk factors. Nuclear erythroid 2-related factor 2 (NFE2L2 or NRF2) is a critical molecule in the lung's defense mechanism against oxidants. We investigated whether polymorphisms in the NFE2L2 pathway affected the rate of decline of lung function in smokers from the Lung Health Study (LHS)(n = 547) and in a replication set, the Vlagtwedde-Vlaardingen cohort (n = 533). We selected polymorphisms in NFE2L2 in genes that positively or negatively regulate NFE2L2 transcriptional activity and in genes that are regulated by NFE2L2. Polymorphisms in 11 genes were significantly associated with rate of lung function decline in the LHS. One of these polymorphisms, rs11085735 in the KEAP1 gene, was previously shown to be associated with the level of lung function in the Vlagtwedde-Vlaardingen cohort but not with decline of lung function. Of the 23 associated polymorphisms in the LHS, only rs634534 in the FOSL1 gene showed a significant association in the Vlagtwedde-Vlaardingen cohort with rate of lung function decline, but the direction of the association was not consistent with that in the LHS. In summary, despite finding several nominally significant polymorphisms in the LHS, none of these associations were replicated in the Vlagtwedde-Vlaardingen cohort, indicating lack of effect of polymorphisms in the NFE2L2 pathway on the rate of decline of lung function. PMID:22693272

NFE2L2 pathway polymorphisms and lung function decline in chronic obstructive pulmonary disease.

PubMed

Sandford, Andrew J; Malhotra, Deepti; Boezen, H Marike; Siedlinski, Mateusz; Postma, Dirkje S; Wong, Vivien; Akhabir, Loubna; He, Jian-Qing; Connett, John E; Anthonisen, Nicholas R; Paré, Peter D; Biswal, Shyam

2012-08-01

An oxidant-antioxidant imbalance in the lung contributes to the development of chronic obstructive pulmonary disease (COPD) that is caused by a complex interaction of genetic and environmental risk factors. Nuclear erythroid 2-related factor 2 (NFE2L2 or NRF2) is a critical molecule in the lung's defense mechanism against oxidants. We investigated whether polymorphisms in the NFE2L2 pathway affected the rate of decline of lung function in smokers from the Lung Health Study (LHS)(n = 547) and in a replication set, the Vlagtwedde-Vlaardingen cohort (n = 533). We selected polymorphisms in NFE2L2 in genes that positively or negatively regulate NFE2L2 transcriptional activity and in genes that are regulated by NFE2L2. Polymorphisms in 11 genes were significantly associated with rate of lung function decline in the LHS. One of these polymorphisms, rs11085735 in the KEAP1 gene, was previously shown to be associated with the level of lung function in the Vlagtwedde-Vlaardingen cohort but not with decline of lung function. Of the 23 associated polymorphisms in the LHS, only rs634534 in the FOSL1 gene showed a significant association in the Vlagtwedde-Vlaardingen cohort with rate of lung function decline, but the direction of the association was not consistent with that in the LHS. In summary, despite finding several nominally significant polymorphisms in the LHS, none of these associations were replicated in the Vlagtwedde-Vlaardingen cohort, indicating lack of effect of polymorphisms in the NFE2L2 pathway on the rate of decline of lung function.

Evaluating Functional Decline in Patients with Multiple Sclerosis

ERIC Educational Resources Information Center

Rosenblum, Sara; Weiss, Patrice L.

2010-01-01

Multiple Sclerosis (MS) is a disease with a wide-ranging impact on functional status. The aim of the study was to examine the added value of simultaneously evaluating fatigue, personal ADL and handwriting performance as indicators for functional decline among patients with MS. Participants were 50 outpatients with MS and 26 matched healthy…

Can psychosocial work conditions protect against age-related cognitive decline? Results from a systematic review

PubMed Central

Nexø, Mette Andersen; Meng, Annette; Borg, Vilhelm

2016-01-01

According to the use it or lose it hypothesis, intellectually stimulating activities postpone age-related cognitive decline. A previous systematic review concluded that a high level of mental work demands and job control protected against cognitive decline. However, it did not distinguish between outcomes that were measured as cognitive function at one point in time or as cognitive decline. Our study aimed to systematically review which psychosocial working conditions were prospectively associated with high levels of cognitive function and/or changes in cognitive function over time. Articles were identified by a systematic literature search (MEDLINE, Web of Science (WOS), PsycNET, Occupational Safety and Health (OSH)). We included only studies with longitudinal designs examining the impact of psychosocial work conditions on outcomes defined as cognitive function or changes in cognitive function. Two independent reviewers compared title-abstract screenings, full-text screenings and quality assessment ratings. Eleven studies were included in the final synthesis and showed that high levels of mental work demands, occupational complexity or job control at one point in time were prospectively associated with higher levels of cognitive function in midlife or late life. However, the evidence to clarify whether these psychosocial factors also affected cognitive decline was insufficient, conflicting or weak. It remains speculative whether job control, job demands or occupational complexity can protect against cognitive decline. Future studies using methodological advancements can reveal whether workers gain more cognitive reserve in midlife and late life than the available evidence currently suggests. The public health implications of a previous review should thereby be redefined accordingly. PMID:27178844

Reassessment of Loblolly Pine Decline on the Oakmulgee Ranger District, Talladega National Forest, Alabama

Treesearch

Nolan J. Hess; William J. Otroana; John P. Jones; Arthur J. Goddard; Charles H. Walkinshaw

1999-01-01

Loblolly pine (Pinus taeda L.) decline has been a management concern on the Oakmulgee Ranger District since the 1960's. The symptoms include sparse crowns, reduced radial growth, deterioration of fine roots, decline, and mortality of loblolly pine by age 50.

Comparison of Acute Health Effects From Exposures to Diesel and Biodiesel Fuel Emissions

PubMed Central

Mehus, Aaron A.; Reed, Rustin J.; Lee, Vivien S. T.; Littau, Sally R.; Hu, Chengcheng; Lutz, Eric A.

2015-01-01

Objective: To investigate the comparative acute health effects associated with exposures to diesel and 75% biodiesel/25% diesel (B75) blend fuel emissions. Methods: We analyzed multiple health endpoints in 48 healthy adults before and after exposures to diesel and B75 emissions in an underground mine setting—lung function, lung and systemic inflammation, novel biomarkers of exposure, and oxidative stress were assessed. Results: B75 reduced respirable diesel particulate matter by 20%. Lung function declined significantly more after exposure to diesel emissions. Lung inflammatory cells along with sputum and plasma inflammatory mediators increased significantly to similar levels with both exposures. Urinary 8-hydroxydeoxyguanosine, a marker of oxidative stress, was not significantly changed after either exposure. Conclusions: Use of B75 lowered respirable diesel particulate matter exposure and some associated acute health effects, although lung and systemic inflammation were not reduced compared with diesel use. PMID:26147538

ACE Over Expression in Myelomonocytic Cells: Effect on a Mouse Model of Alzheimer's Disease

PubMed Central

Koronyo-Hamaoui, Maya; Shah, Kandarp; Koronyo, Yosef; Bernstein, Ellen; Giani, Jorge F.; Janjulia, Tea; Black, Keith L.; Shi, Peng D.; Gonzalez-Villalobos, Romer A.; Fuchs, Sebastien; Shen, Xiao Z.; Bernstein, Kenneth E.

2014-01-01

While it is well known that angiotensin converting enzyme (ACE) plays an important role in blood pressure control, ACE also has effects on renal function, hematopoiesis, reproduction, and aspects of the immune response. ACE 10/10 mice over express ACE in myelomonocytic cells. Macrophages from these mice have an increased polarization towards a pro-inflammatory phenotype that results in a very effective immune response to challenge by tumors or bacterial infection. In a mouse model of Alzheimer's disease (AD), the ACE 10/10 phenotype provides significant protection against AD pathology, including reduced inflammation, reduced burden of the neurotoxic amyloid-β protein and preserved cognitive function. Taken together, these studies show that increased myelomonocytic ACE expression in mice alters the immune response to better defend against many different types of pathologic insult, including the cognitive decline observed in an animal model of AD. PMID:24792094

Comparison of Acute Health Effects From Exposures to Diesel and Biodiesel Fuel Emissions.

PubMed

Mehus, Aaron A; Reed, Rustin J; Lee, Vivien S T; Littau, Sally R; Hu, Chengcheng; Lutz, Eric A; Burgess, Jefferey L

2015-07-01

To investigate the comparative acute health effects associated with exposures to diesel and 75% biodiesel/25% diesel (B75) blend fuel emissions. We analyzed multiple health endpoints in 48 healthy adults before and after exposures to diesel and B75 emissions in an underground mine setting-lung function, lung and systemic inflammation, novel biomarkers of exposure, and oxidative stress were assessed. B75 reduced respirable diesel particulate matter by 20%. Lung function declined significantly more after exposure to diesel emissions. Lung inflammatory cells along with sputum and plasma inflammatory mediators increased significantly to similar levels with both exposures. Urinary 8-hydroxydeoxyguanosine, a marker of oxidative stress, was not significantly changed after either exposure. Use of B75 lowered respirable diesel particulate matter exposure and some associated acute health effects, although lung and systemic inflammation were not reduced compared with diesel use.

Activating Developmental Reserve Capacity Via Cognitive Training or Non-invasive Brain Stimulation: Potentials for Promoting Fronto-Parietal and Hippocampal-Striatal Network Functions in Old Age

PubMed Central

Passow, Susanne; Thurm, Franka; Li, Shu-Chen

2017-01-01

Existing neurocomputational and empirical data link deficient neuromodulation of the fronto-parietal and hippocampal-striatal circuitries with aging-related increase in processing noise and declines in various cognitive functions. Specifically, the theory of aging neuronal gain control postulates that aging-related suboptimal neuromodulation may attenuate neuronal gain control, which yields computational consequences on reducing the signal-to-noise-ratio of synaptic signal transmission and hampering information processing within and between cortical networks. Intervention methods such as cognitive training and non-invasive brain stimulation, e.g., transcranial direct current stimulation (tDCS), have been considered as means to buffer cognitive functions or delay cognitive decline in old age. However, to date the reported effect sizes of immediate training gains and maintenance effects of a variety of cognitive trainings are small to moderate at best; moreover, training-related transfer effects to non-trained but closely related (i.e., near-transfer) or other (i.e., far-transfer) cognitive functions are inconsistent or lacking. Similarly, although applying different tDCS protocols to reduce aging-related cognitive impairments by inducing temporary changes in cortical excitability seem somewhat promising, evidence of effects on short- and long-term plasticity is still equivocal. In this article, we will review and critically discuss existing findings of cognitive training- and stimulation-related behavioral and neural plasticity effects in the context of cognitive aging, focusing specifically on working memory and episodic memory functions, which are subserved by the fronto-parietal and hippocampal-striatal networks, respectively. Furthermore, in line with the theory of aging neuronal gain control we will highlight that developing age-specific brain stimulation protocols and the concurrent applications of tDCS during cognitive training may potentially facilitate short- and long-term cognitive and brain plasticity in old age. PMID:28280465

Kidney function and cognitive decline in an oldest-old Chinese population.

PubMed

Bai, Kunhao; Pan, Yujing; Lu, Fanghong; Zhao, Yingxin; Wang, Jinwei; Zhang, Luxia

2017-01-01

Early-stage chronic kidney disease has been suggested to be correlated with cognitive decline, but the association has rarely been explored in the oldest old. This prospective study included 284 Chinese participants aged 80 years or older with serum creatinine levels <150 µmol/L. The median follow-up time was 3.3 years, and 247 (87.0%) participants provided valid data at their last visit. Kidney function was evaluated by measuring the estimated glomerular filtration rate (eGFR) at baseline, and cognitive function was evaluated using the Mini-Mental State Examination (MMSE) at both baseline and annual visits. A reliable decrease in the MMSE score over the follow-up period was observed based on a Reliable Change Index of 1.645 (equivalent to a 90% confidence interval [CI]), which was used to define cognitive decline. Poisson regression models were built to analyze the association between baseline kidney function and cognitive decline. A total of 18 (7.3%) cases of incident cognitive decline were observed during the follow-up period. After adjusting for potential confounders, the relative risk of developing cognitive decline was 4.03 (95% CI 1.09-13.81) among participants with an eGFR of 30-59 mL/min/1.73 m 2 compared to participants with an eGFR of ≥60 mL/min/1.73 m 2 . Early-stage chronic kidney disease was correlated with cognitive decline in an oldest-old Chinese population.

A randomised controlled intervention trial evaluating the efficacy of a Mediterranean dietary pattern on cognitive function and psychological wellbeing in healthy older adults: the MedLey study.

PubMed

Knight, Alissa; Bryan, Janet; Wilson, Carlene; Hodgson, Jonathan; Murphy, Karen

2015-04-28

The incidence of age-related cognitive decline is rising considerably around the world. There is evidence from a number of recent cross-sectional and prospective studies indicating positive associations between the Mediterranean dietary pattern (MedDiet) and improved cognitive outcomes among the elderly including, reduced age-related cognitive decline and enhanced age-related cognitive performance. However, to date no study has validated these associations in healthy older adult populations (≥65 years and above) with randomised evidence. The main aim of the present study is to provide justified evidence regarding the efficacy of a MedDiet approach to safely reduce the onset of cognitive decline, and promote optimal cognitive performance among healthy older adults using rigorous, randomised intervention methodology. MedLey is a 6-month, randomised controlled 2-cohort parallel group intervention trial, with initial assessment at baseline and repeated every three months. A sample of 166 healthy Australian men and women aged 65 years and above, with normal cognitive function and proficient in English language were recruited from metropolitan Adelaide, South Australia for the study. Participants randomly allocated to the experimental group are required to maintain an intervention dietary pattern based from the traditional Cretan MedDiet (i.e. vegetables, fruits, olive oil, legumes, fish, whole grain cereals, nuts and seeds and low consumption of processed foods, dairy products, red meat and vegetable oils) for six months, while those participants allocated to the control group are asked to maintain their customary lifestyle and diet. The primary outcome of interest is the quantitative difference in age-related cognitive performance, as measured by latent variables (cognitive constructs) sensitive to normal ageing and diet (i.e. speed of processing, memory, attention, executive functions, visual spatial and visuomotor ability). Secondary outcomes include change in biomarkers of inflammation, oxidative stress, lipid metabolism, glucose, insulin, blood flow velocity, and psychological well-being factors (i.e. stress, sleep, anxiety, depression). To our knowledge this will be one of the first randomised clinical trials worldwide to provide evidence for the cause-effect relationship between the MedDiet and age-related cognitive function in a healthy older adult population (≥65 years and over). Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12613000602729.

Genetic Ancestry-Smoking Interactions and Lung Function in African Americans: A Cohort Study

PubMed Central

Colangelo, Laura A.; Williams, L. Keoki; Sen, Saunak; Kritchevsky, Stephen B.; Meibohm, Bernd; Galanter, Joshua; Hu, Donglei; Gignoux, Christopher R.; Liu, Yongmei; Harris, Tamara B.; Ziv, Elad; Zmuda, Joseph; Garcia, Melissa; Leak, Tennille S.; Foreman, Marilyn G.; Smith, Lewis J.; Fornage, Myriam; Liu, Kiang; Burchard, Esteban G.

2012-01-01

Background Smoking tobacco reduces lung function. African Americans have both lower lung function and decreased metabolism of tobacco smoke compared to European Americans. African ancestry is also associated with lower pulmonary function in African Americans. We aimed to determine whether African ancestry modifies the association between smoking and lung function and its rate of decline in African Americans. Methodology/Principal Findings We evaluated a prospective ongoing cohort of 1,281 African Americans participating in the Health, Aging, and Body Composition (Health ABC) Study initiated in 1997. We also examined an ongoing prospective cohort initiated in 1985 of 1,223 African Americans in the Coronary Artery Disease in Young Adults (CARDIA) Study. Pulmonary function and tobacco smoking exposure were measured at baseline and repeatedly over the follow-up period. Individual genetic ancestry proportions were estimated using ancestry informative markers selected to distinguish European and West African ancestry. African Americans with a high proportion of African ancestry had lower baseline forced expiratory volume in one second (FEV1) per pack-year of smoking (−5.7 ml FEV1/ smoking pack-year) compared with smokers with lower African ancestry (−4.6 ml in FEV1/ smoking pack-year) (interaction P value  = 0.17). Longitudinal analyses revealed a suggestive interaction between smoking, and African ancestry on the rate of FEV1 decline in Health ABC and independently replicated in CARDIA. Conclusions/Significance African American individuals with a high proportion of African ancestry are at greater risk for losing lung function while smoking. PMID:22737244

Targeting functional fitness, hearing and health-related quality of life in older adults with hearing loss: Walk, Talk 'n' Listen, study protocol for a pilot randomized controlled trial.

PubMed

Lambert, Justin; Ghadry-Tavi, Rouzbeh; Knuff, Kate; Jutras, Marc; Siever, Jodi; Mick, Paul; Roque, Carolyn; Jones, Gareth; Little, Jonathan; Miller, Harry; Van Bergen, Colin; Kurtz, Donna; Murphy, Mary Ann; Jones, Charlotte Ann

2017-01-28

Hearing loss (HL) is a disability associated with poorer health-related quality of life including an increased risk for loneliness, isolation, functional fitness declines, falls, hospitalization and premature mortality. The purpose of this pilot trial is to determine the feasibility and acceptability of a novel intervention to reduce loneliness, improve functional fitness, social connectedness, hearing and health-related quality of life in older adults with HL. This 10-week, single-blind, pilot randomized control trial (RCT) will include a convenience sample of ambulatory adults aged 65 years or older with self-reported HL. Following baseline assessments, participants will be randomized to either intervention (exercise, health education, socialization and group auditory rehabilitation (GAR)) or control (GAR only) groups. The intervention group will attend a local YMCA twice a week and the control group once a week. Intervention sessions will include 45 min of strengthening, balance and resistance exercises, 30 min of group walking at a self-selected pace and 60 min of interactive health education or GAR. The control group will attend 60-min GAR sessions. GAR sessions will include education about hearing, hearing technologies, enhancing communication skills, and psychosocial support. Pre-post trial data collection and measures will include: functional fitness (gait speed, 30-s Sit to Stand Test), hearing and health-related quality of life, loneliness, depression, social participation and social support. At trial end, feasibility (recruitment, randomization, retention, acceptability) and GAR will be evaluated. Despite evidence suggesting that HL is associated with declines in functional fitness, there are no studies aimed at addressing functional fitness declines associated with the disability of HL. This pilot trial will provide knowledge about the physical, mental and social impacts on health related to HL as a disability. This will inform the feasibility of a larger RCT and preliminary evidence about the initial effects of a novel, community-based, holistic intervention addressing both the negative psychosocial and functional physical effects of HL among older adults. ClinicalTrials.gov, NCT02662192 . Registered on 14 January 2016.

Simvastatin mitigates functional and structural impairment of lung and right ventricle in a rat model of cigarette smoke-induced COPD.

PubMed

Wang, Yajie; Jiang, Xue; Zhang, Lihai; Wang, Lihong; Li, Zhu; Sun, Wuzhuang

2014-01-01

This study is conducted to investigate an effect of simvastatin on cigarette smoke-induced COPD. Rats were exposed to air (control) and cigarette smoke (smoking) in presence and absence of simvastatin. Heart and lung tissues were harvested for histopathologic and morphometric analysis. Body weight of rat, mean liner intercept (MLI), mean alveolar number (MAN), lung function test, mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI) and 5-HTT level in serum and BALF were examined in experimental rats, respectively. Application of simvastatin mitigated peribronchiolar inflammation and pulmonary bullae formed in the smoke-exposed lungs with weight gain as compared to the smoking rats (P < 0.05). Simvastatin-treated rats showed slight but significant decreases in MLI and MAN with a partial reversal of lung function decline (all P < 0.05). Treatment with simvastatin resulted in a significant decrease not only in mPAP and RVHI but also in a 5-HTT level in serum and BALF (P < 0.01 or 0.05) with a good correlation between the 5-HTT level and mPAP or RVHI (r = 0.693 and 0.479; 0.675 and 0.508). Simvastatin partly reverses lung function decline and attenuates structural impairments of lung and right ventricle possibly through reducing 5-HTT content in the model of COPD.

Simvastatin mitigates functional and structural impairment of lung and right ventricle in a rat model of cigarette smoke-induced COPD

PubMed Central

Wang, Yajie; Jiang, Xue; Zhang, Lihai; Wang, Lihong; Li, Zhu; Sun, Wuzhuang

2014-01-01

Objectives: This study is conducted to investigate an effect of simvastatin on cigarette smoke-induced COPD. Methods: Rats were exposed to air (control) and cigarette smoke (smoking) in presence and absence of simvastatin. Heart and lung tissues were harvested for histopathologic and morphometric analysis. Body weight of rat, mean liner intercept (MLI), mean alveolar number (MAN), lung function test, mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI) and 5-HTT level in serum and BALF were examined in experimental rats, respectively. Results: Application of simvastatin mitigated peribronchiolar inflammation and pulmonary bullae formed in the smoke-exposed lungs with weight gain as compared to the smoking rats (P < 0.05). Simvastatin-treated rats showed slight but significant decreases in MLI and MAN with a partial reversal of lung function decline (all P < 0.05). Treatment with simvastatin resulted in a significant decrease not only in mPAP and RVHI but also in a 5-HTT level in serum and BALF (P < 0.01 or 0.05) with a good correlation between the 5-HTT level and mPAP or RVHI (r = 0.693 and 0.479; 0.675 and 0.508). Conclusion: Simvastatin partly reverses lung function decline and attenuates structural impairments of lung and right ventricle possibly through reducing 5-HTT content in the model of COPD. PMID:25674219

Association of incidental emphysema with annual lung function decline and future development of airflow limitation

PubMed Central

Koo, Hyeon-Kyoung; Jin, Kwang Nam; Kim, Deog Kyeom; Chung, Hee Soon; Lee, Chang-Hoon

2016-01-01

Objectives Emphysema is one of the prognostic factors for rapid lung function decline in patients with COPD, but the impact of incidentally detected emphysema on population without spirometric abnormalities has not been evaluated. This study aimed to determine whether emphysema detected upon computed tomography (CT) screening would accelerate the rate of lung function decline and influence the possibility of future development of airflow limitation in a population without spirometric abnormalities. Materials and methods Subjects who participated in a routine screening for health checkup and follow-up pulmonary function tests for at least 3 years between 2004 and 2010 were retrospectively enrolled. The percentage of low-attenuation area below −950 Hounsfield units (%LAA−950) was calculated automatically. A calculated value of %LAA−950 that exceeded 10% was defined as emphysema. Adjusted annual lung function decline was analyzed using random-slope, random-intercept mixed linear regression models. Results A total of 628 healthy subjects within the normal range of spriometric values were included. Multivariable analysis showed that the emphysema group exhibited a faster decline in forced vital capacity (−33.9 versus −18.8 mL/year; P=0.02). Emphysema was not associated with the development of airflow limitation during follow-up. Conclusion Incidental emphysema quantified using CT scan was significantly associated with a more rapid decline in forced vital capacity in the population with normative spirometric values. However, an association between emphysema and future development of airflow limitation was not observed. PMID:26893550

Caloric Restriction in Older Adults-Differential Effects of Weight Loss and Reduced Weight on Brain Structure and Function.

PubMed

Prehn, Kristin; Jumpertz von Schwartzenberg, Reiner; Mai, Knut; Zeitz, Ulrike; Witte, A Veronica; Hampel, Dierk; Szela, Anna-Maria; Fabian, Sonja; Grittner, Ulrike; Spranger, Joachim; Flöel, Agnes

2017-03-01

Dietary modifications such as caloric restriction (CR) have been suggested as a means to improve memory and prevent age-related decline. However, it is unclear whether those effects remain stable over time or are related specifically to negative energy balance during the weight loss phase of CR. Using a randomized interventional design, we investigated changes in recognition memory and neural correlates in postmenopausal obese women (n = 19): 1) after intense weight loss in the course of a 12-week low-caloric diet (reduced body weight and negative energy balance) and 2) after having sustained the reduced weight over 4 more weeks (reduced body weight, but energy balance equilibrium). Participants were contrasted to a control group (n = 18) instructed not to change dietary habits. In the CR group, we found improved recognition memory, paralleled by increased gray matter volume in inferior frontal gyrus and hippocampus, and augmented hippocampal resting-state functional connectivity to parietal areas. Moreover, effects were specific for transient negative energy balance and could not be detected after subsequent weight maintenance. Our data demonstrate for the first time in humans that beneficial effects of CR on brain structure and function are due to weight loss rather than an overall reduced weight. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Time to cash in on positive interactions for coral restoration

PubMed Central

Silliman, Brian R.

2017-01-01

Coral reefs are among the most biodiverse and productive ecosystems on Earth, and provide critical ecosystem services such as protein provisioning, coastal protection, and tourism revenue. Despite these benefits, coral reefs have been declining precipitously across the globe due to human impacts and climate change. Recent efforts to combat these declines are increasingly turning to restoration to help reseed corals and speed-up recovery processes. Coastal restoration theory and practice has historically favored transplanting designs that reduce potentially harmful negative species interactions, such as competition between transplants. However, recent research in salt marsh ecosystems has shown that shifting this theory to strategically incorporate positive interactions significantly enhances restoration yield with little additional cost or investment. Although some coral restoration efforts plant corals in protected areas in order to benefit from the facilitative effects of herbivores that reduce competitive macroalgae, little systematic effort has been made in coral restoration to identify the entire suite of positive interactions that could promote population enhancement efforts. Here, we highlight key positive species interactions that managers and restoration practitioners should utilize to facilitate the restoration of corals, including (i) trophic facilitation, (ii) mutualisms, (iii) long-distance facilitation, (iv) positive density-dependence, (v) positive legacy effects, and (vi) synergisms between biodiversity and ecosystem function. As live coral cover continues to decline and resources are limited to restore coral populations, innovative solutions that increase efficiency of restoration efforts will be critical to conserving and maintaining healthy coral reef ecosystems and the human communities that rely on them. PMID:28652942

The benefits associated with volunteering among seniors: a critical review and recommendations for future research.

PubMed

Anderson, Nicole D; Damianakis, Thecla; Kröger, Edeltraut; Wagner, Laura M; Dawson, Deirdre R; Binns, Malcolm A; Bernstein, Syrelle; Caspi, Eilon; Cook, Suzanne L

2014-11-01

There is an urgent need to identify lifestyle activities that reduce functional decline and dementia associated with population aging. The goals of this article are to review critically the evidence on the benefits associated with formal volunteering among older adults, propose a theoretical model of how volunteering may reduce functional limitations and dementia risk, and offer recommendations for future research. Database searches identified 113 papers on volunteering benefits in older adults, of which 73 were included. Data from descriptive, cross-sectional, and prospective cohort studies, along with 1 randomized controlled trial, most consistently reveal that volunteering is associated with reduced symptoms of depression, better self-reported health, fewer functional limitations, and lower mortality. The extant evidence provides the basis for a model proposing that volunteering increases social, physical, and cognitive activity (to varying degrees depending on characteristics of the volunteer placement) which, through biological and psychological mechanisms, leads to improved functioning; we further propose that these volunteering-related functional improvements should be associated with reduced dementia risk. Recommendations for future research are that studies (a) include more objective measures of psychosocial, physical, and cognitive functioning; (b) integrate qualitative and quantitative methods in prospective study designs; (c) explore further individual differences in the benefits associated with volunteering; (d) include occupational analyses of volunteers' specific jobs in order to identify their social, physical, and cognitive complexity; (e) investigate the independent versus interactive health benefits associated with volunteering relative to engagement in other forms of activity; and (f) examine the relationship between volunteering and dementia risk. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Central obesity, leptin and cognitive decline: the Sacramento Area Latino Study on Aging.

PubMed

Zeki Al Hazzouri, Adina; Haan, Mary N; Whitmer, Rachel A; Yaffe, Kristine; Neuhaus, John

2012-01-01

Central obesity is a risk factor for cognitive decline. Leptin is secreted by adipose tissue and has been associated with better cognitive function. Aging Mexican Americans have higher levels of obesity than non-Hispanic Whites, but no investigations examined the relationship between leptin and cognitive decline among them or the role of central obesity in this association. We analyzed 1,480 dementia-free older Mexican Americans who were followed over 10 years. Cognitive function was assessed every 12-15 months with the Modified Mini Mental State Exam (3MSE) and the Spanish and English Verbal Learning Test (SEVLT). For females with a small waist circumference (≤35 inches), an interquartile range difference in leptin was associated with 35% less 3MSE errors and 22% less decline in the SEVLT score over 10 years. For males with a small waist circumference (≤40 inches), an interquartile range difference in leptin was associated with 44% less 3MSE errors and 30% less decline in the SEVLT score over 10 years. There was no association between leptin and cognitive decline among females or males with a large waist circumference. Leptin interacts with central obesity in shaping cognitive decline. Our findings provide valuable information about the effects of metabolic risk factors on cognitive function. Copyright © 2012 S. Karger AG, Basel.

Earliest functional declines in Huntington disease

PubMed Central

Beglinger, Leigh J.; O'Rourke, Justin J.F.; Wang, Chiachi; Langbehn, Douglas R.; Duff, Kevin; Paulsen, Jane S.

2013-01-01

We examined the gold standard for Huntington disease (HD) functional assessment, the Unified Huntington's Disease Rating Scale (UHDRS), in a group of at-risk participants not yet diagnosed but who later phenoconverted to manifest HD. We also sought to determine which skill domains first weaken and the clinical correlates of declines. Using the UHDRS Total Functional Capacity (TFC) and Functional Assessment Scale (FAS), we examined participants from Huntington Study Group clinics who were not diagnosed at their baseline visit but were diagnosed at a later visit (N = 265). Occupational decline was the most common with 65.1% (TFC) and 55.6% (FAS) reporting some loss of ability to engage in their typical work. Inability to manage finances independently (TFC 49.2%, FAS 35.1%) and drive safely (FAS 33.5%) were also found. Functional decline was significantly predicted by motor, cognitive, and depressive symptoms. The UHDRS captured early functional losses in individuals with HD prior to formal diagnosis, however, fruitful areas for expanded assessment of early functional changes are performance at work, ability to manage finances, and driving. These are also important areas for clinical monitoring and treatment planning as up to 65% experienced loss in at least one area prior to diagnosis. PMID:20471695

Serum Calcitriol Concentrations and Kidney Function Decline, Heart Failure, and Mortality in Elderly Community-Living Adults: The Health, Aging, and Body Composition Study.

PubMed

Selamet, Umut; Katz, Ronit; Ginsberg, Charles; Rifkin, Dena E; Fried, Linda F; Kritchevsky, Stephen B; Hoofnagle, Andrew N; Bibbins-Domingo, Kirsten; Drew, David; Harris, Tamara; Newman, Anne; Gutiérrez, Orlando M; Sarnak, Mark J; Shlipak, Michael G; Ix, Joachim H

2018-06-06

Lower 25-hydroxyvitamin D concentrations have been associated with risk for kidney function decline, heart failure, and mortality. However, 25-hydroxyvitamin D requires conversion to its active metabolite, calcitriol, for most biological effects. The associations of calcitriol concentrations with clinical events have not been well explored. Case-cohort study. Well-functioning community-living older adults aged 70 to 79 years at inception who participated in the Health, Aging, and Body Composition (Health ABC) Study. Serum calcitriol measured using positive ion electrospray ionization-tandem mass spectrometry. Major kidney function decline (≥30% decline in estimated glomerular filtration rate from baseline), incident heart failure (HF), and all-cause mortality during 10 years of follow-up. Baseline calcitriol concentrations were measured in a random subcohort of 479 participants and also in cases with major kidney function decline [n=397]) and incident HF (n=207) during 10 years of follow-up. Associations of serum calcitriol concentrations with these end points were evaluated using weighted Cox regression to account for the case-cohort design, while associations with mortality were assessed in the subcohort alone using unweighted Cox regression. During 8.6 years of mean follow-up, 212 (44%) subcohort participants died. In fully adjusted models, each 1-standard deviation lower calcitriol concentration was associated with 30% higher risk for major kidney function decline (95% CI, 1.03-1.65; P=0.03). Calcitriol was not significantly associated with incident HF (HR, 1.16; 95% CI, 0.94-1.47) or mortality (HR, 1.01; 95% CI, 0.81-1.26). We observed no significant interactions between calcitriol concentrations and chronic kidney disease status, baseline intact parathyroid or fibroblast factor 23 concentrations. Observational study design, calcitriol measurements at a single time point, selective study population of older adults only of white or black race. Lower calcitriol concentrations are independently associated with kidney function decline in community-living older adults. Future studies will be needed to clarify whether these associations reflect lower calcitriol concentrations resulting from abnormal kidney tubule dysfunction or direct mechanisms relating lower calcitriol concentrations to more rapid loss of kidney function. Published by Elsevier Inc.

Physical fitness is predictive for a decline in daily functioning in older adults with intellectual disabilities: results of the HA-ID study.

PubMed

Oppewal, Alyt; Hilgenkamp, Thessa I M; van Wijck, Ruud; Schoufour, Josje D; Evenhuis, Heleen M

2014-10-01

A high incidence of limitations in daily functioning is seen in older adults with intellectual disabilities (ID), along with poor physical fitness levels. The aim of this study was to assess the predictive value of physical fitness for daily functioning after 3 years, in 602 older adults with borderline to profound ID (≥ 50 years). At baseline, physical fitness levels and daily functioning (operationalized as basic activities of daily living [ADL] and mobility) were assessed. After 3 years, the measurements of daily functioning were repeated. At follow-up, 12.6% of the participants were completely independent in ADL and 48.5% had no mobility limitations. More than half of the participants (54.8%) declined in their ability to perform ADL and 37.5% declined in their mobility. Manual dexterity, visual reaction time, balance, comfortable and fast gait speed, muscular endurance, and cardiorespiratory fitness were significant predictors for a decline in ADL. For a decline in mobility, manual dexterity, balance, comfortable and fast walking speed, grip strength, muscular endurance, and cardiorespiratory fitness were all significant predictors. This proves the predictive validity of these physical fitness tests for daily functioning and stresses the importance of using physical fitness tests and implementing physical fitness enhancing programs in the care for older adults with ID. Copyright © 2014 Elsevier Ltd. All rights reserved.

Peritumoral Artery Scoring System: a Novel Scoring System to Predict Renal Function Outcome after Laparoscopic Partial Nephrectomy.

PubMed

Zhang, Ruiyun; Wu, Guangyu; Huang, Jiwei; Shi, Oumin; Kong, Wen; Chen, Yonghui; Xu, Jianrong; Xue, Wei; Zhang, Jin; Huang, Yiran

2017-06-06

The present study aimed to assess the impact of peritumoral artery characteristics on renal function outcome prediction using a novel Peritumoral Artery Scoring System based on computed tomography arteriography. Peritumoral artery characteristics and renal function were evaluated in 220 patients who underwent laparoscopic partial nephrectomy and then validate in 51 patients with split and total glomerular filtration rate (GFR). In particular, peritumoral artery classification and diameter were measured to assign arteries into low, moderate, and high Peritumoral Artery Scoring System risk categories. Univariable and multivariable logistic regression analyses were then used to determine risk factors for major renal functional decline. The Peritumoral Artery Scoring System and four other nephrometry systems were compared using receiver operating characteristic curve analysis. The Peritumoral Artery Scoring System was significantly superior to the other systems for predicting postoperative renal function decline (p < 0.001). In receiver operating characteristic analysis, our category system was a superior independent predictor of estimated glomerular filtration rate (eGFR) decline (area-under-the-curve = 0.865, p < 0.001) and total GFR decline (area-under-the-curve = 0.796, p < 0.001), and split GFR decline (area-under-the-curve = 0.841, p < 0.001). Peritumoral artery characteristics were independent predictors of renal function outcome after laparoscopic partial nephrectomy.

Aging and Intermittent Fasting Impact on Transcriptional Regulation and Physiological Responses of Adult Drosophila Neuronal and Muscle Tissues

PubMed Central

Zhang, Sharon; Ratliff, Eric P.; Molina, Brandon; El-Mecharrafie, Nadja; Mastroianni, Jessica; Kotzebue, Roxanne W.; Achal, Madhulika; Mauntz, Ruth E.; Gonzalez, Arysa; Barekat, Ayeh; Bray, William A.; Macias, Andrew M.; Daugherty, Daniel; Harris, Greg L.; Edwards, Robert A.; Finley, Kim D.

2018-01-01

The progressive decline of the nervous system, including protein aggregate formation, reflects the subtle dysregulation of multiple functional pathways. Our previous work has shown intermittent fasting (IF) enhances longevity, maintains adult behaviors and reduces aggregates, in part, by promoting autophagic function in the aging Drosophila brain. To clarify the impact that IF-treatment has upon aging, we used high throughput RNA-sequencing technology to examine the changing transcriptome in adult Drosophila tissues. Principle component analysis (PCA) and other analyses showed ~1200 age-related transcriptional differences in head and muscle tissues, with few genes having matching expression patterns. Pathway components showing age-dependent expression differences were involved with stress response, metabolic, neural and chromatin remodeling functions. Middle-aged tissues also showed a significant increase in transcriptional drift-variance (TD), which in the CNS included multiple proteolytic pathway components. Overall, IF-treatment had a demonstrably positive impact on aged transcriptomes, partly ameliorating both fold and variance changes. Consistent with these findings, aged IF-treated flies displayed more youthful metabolic, behavioral and basal proteolytic profiles that closely correlated with transcriptional alterations to key components. These results indicate that even modest dietary changes can have therapeutic consequences, slowing the progressive decline of multiple cellular systems, including proteostasis in the aging nervous system. PMID:29642630

Aging and Intermittent Fasting Impact on Transcriptional Regulation and Physiological Responses of Adult Drosophila Neuronal and Muscle Tissues.

PubMed

Zhang, Sharon; Ratliff, Eric P; Molina, Brandon; El-Mecharrafie, Nadja; Mastroianni, Jessica; Kotzebue, Roxanne W; Achal, Madhulika; Mauntz, Ruth E; Gonzalez, Arysa; Barekat, Ayeh; Bray, William A; Macias, Andrew M; Daugherty, Daniel; Harris, Greg L; Edwards, Robert A; Finley, Kim D

2018-04-10

The progressive decline of the nervous system, including protein aggregate formation, reflects the subtle dysregulation of multiple functional pathways. Our previous work has shown intermittent fasting (IF) enhances longevity, maintains adult behaviors and reduces aggregates, in part, by promoting autophagic function in the aging Drosophila brain. To clarify the impact that IF-treatment has upon aging, we used high throughput RNA-sequencing technology to examine the changing transcriptome in adult Drosophila tissues. Principle component analysis (PCA) and other analyses showed ~1200 age-related transcriptional differences in head and muscle tissues, with few genes having matching expression patterns. Pathway components showing age-dependent expression differences were involved with stress response, metabolic, neural and chromatin remodeling functions. Middle-aged tissues also showed a significant increase in transcriptional drift-variance (TD), which in the CNS included multiple proteolytic pathway components. Overall, IF-treatment had a demonstrably positive impact on aged transcriptomes, partly ameliorating both fold and variance changes. Consistent with these findings, aged IF-treated flies displayed more youthful metabolic, behavioral and basal proteolytic profiles that closely correlated with transcriptional alterations to key components. These results indicate that even modest dietary changes can have therapeutic consequences, slowing the progressive decline of multiple cellular systems, including proteostasis in the aging nervous system.

The Association between the Mediterranean Dietary Pattern and Cognitive Health: A Systematic Review

PubMed Central

Wright, Olivia R. L.

2017-01-01

The ageing population is accompanied by increased rates of cognitive decline and dementia. Not only does cognitive decline have a profound impact on an individual’s health and quality of life, but also on that of their caregivers. The Mediterranean diet (MD) has been known to aid in reducing the risk of cardiovascular diseases, cancer and diabetes. It has been recently linked to better cognitive function in the elderly population. The purpose of this review was to compile evidence based data that examined the effect of adherence to the MD on cognitive function and the risk of developing dementia or Alzheimer’s disease. This review followed PRISMA guidelines and was conducted using four databases and resulted in 31 articles of interest. Cross-sectional studies and cohort studies in the non-Mediterranean region showed mixed results. However, cohort studies in the Mediterranean region and randomized controlled trials showed more cohesive outcomes of the beneficial effect of the MD on cognitive function. Although more standardized and in-depth studies are needed to strengthen the existing body of evidence, results from this review indicate that the Mediterranean diet could play a major role in cognitive health and risk of Alzheimer’s disease and dementia. PMID:28657600

Mitochondrial bioenergetics decay in aging: beneficial effect of melatonin.

PubMed

Paradies, Giuseppe; Paradies, Valeria; Ruggiero, Francesca M; Petrosillo, Giuseppe

2017-11-01

Aging is a biological process characterized by progressive decline in physiological functions, increased oxidative stress, reduced capacity to respond to stresses, and increased risk of contracting age-associated disorders. Mitochondria are referred to as the powerhouse of the cell through their role in the oxidative phosphorylation to generate ATP. These organelles contribute to the aging process, mainly through impairment of electron transport chain activity, opening of the mitochondrial permeability transition pore and increased oxidative stress. These events lead to damage to proteins, lipids and mitochondrial DNA. Cardiolipin, a phospholipid of the inner mitochondrial membrane, plays a pivotal role in several mitochondrial bioenergetic processes as well as in mitochondrial-dependent steps of apoptosis and in mitochondrial membrane stability and dynamics. Cardiolipin alterations are associated with mitochondrial bienergetics decline in multiple tissues in a variety of physiopathological conditions, as well as in the aging process. Melatonin, the major product of the pineal gland, is considered an effective protector of mitochondrial bioenergetic function. Melatonin preserves mitochondrial function by preventing cardiolipin oxidation and this may explain, at least in part, the protective role of this compound in mitochondrial physiopathology and aging. Here, mechanisms through which melatonin exerts its protective role against mitochondrial dysfunction associated with aging and age-associated disorders are discussed.

Corpus callosum atrophy as a predictor of age-related cognitive and motor impairment: a 3-year follow-up of the LADIS study cohort.

PubMed

Ryberg, C; Rostrup, E; Paulson, O B; Barkhof, F; Scheltens, P; van Straaten, E C W; van der Flier, W M; Fazekas, F; Schmidt, R; Ferro, J M; Baezner, H; Erkinjuntti, T; Jokinen, H; Wahlund, L-O; Poggesi, A; Pantoni, L; Inzitari, D; Waldemar, G

2011-08-15

The aim of this 3-year follow-up study was to investigate whether corpus callosum (CC) atrophy may predict future motor and cognitive impairment in an elderly population. On baseline MRI from 563 subjects with age-related white matter changes (ARWMC) from the Leukoaraiosis And DISability (LADIS) study, the CC was segmented and subdivided into five anterior-posterior regions (CC1-CC5). Associations between the CC areas and decline in motor performance and cognitive functions over a 3-year period were analyzed. CC atrophy at baseline was significantly associated with impaired cognitive performance (p<0.01 for CC1, p<0.05 for CC5), motor function (p<0.05 for CC2 and CC5), and walking speed (p<0.01 for CC2 and CC5, p<0.05 for CC3 and total CC), and with development of dementia at 3 years (p<0.05 for CC1) after correction for appropriate confounders (ARWMC volume, atrophy, age, gender and handedness). In conclusion, CC atrophy, an indicator of reduced functional connectivity between cortical areas, seems to contribute, independently of ARWMC load, to future cognitive and motor decline in the elderly. Copyright © 2011 Elsevier B.V. All rights reserved.

The impact of retirement on age related cognitive decline - a systematic review.

PubMed

Meng, Annette; Nexø, Mette Andersen; Borg, Vilhelm

2017-07-21

Knowledge on factors affecting the rate of cognitive decline and how to maintain cognitive functioning in old age becomes increasingly relevant. The purpose of the current study was to systematically review the evidence for the impact of retirement on cognitive functioning and on age related cognitive decline. We conducted a systematic literature review, following the principles of the PRISMA statement, of longitudinal studies on the association between retirement and cognition. Only seven studies fulfilled the inclusion criteria. We found weak evidence that retirement accelerates the rate of cognitive decline in crystallised abilities, but only for individuals retiring from jobs high in complexity with people. The evidence of the impact of retirement on the rate of decline in fluid cognitive abilities is conflicting. The review revealed a major knowledge gap in regards to the impact of retirement on cognitive decline. More knowledge on the association between retirement and age related cognitive decline as well as knowledge on the mechanisms behind these associations is needed.

Gait Rather Than Cognition Predicts Decline in Specific Cognitive Domains in Early Parkinson's Disease.

PubMed

Morris, Rosie; Lord, Sue; Lawson, Rachael A; Coleman, Shirley; Galna, Brook; Duncan, Gordon W; Khoo, Tien K; Yarnall, Alison J; Burn, David J; Rochester, Lynn

2017-11-09

Dementia is significant in Parkinson's disease (PD) with personal and socioeconomic impact. Early identification of risk is of upmost importance to optimize management. Gait precedes and predicts cognitive decline and dementia in older adults. We aimed to evaluate gait characteristics as predictors of cognitive decline in newly diagnosed PD. One hundred and nineteen participants recruited at diagnosis were assessed at baseline, 18 and 36 months. Baseline gait was characterized by variables that mapped to five domains: pace, rhythm, variability, asymmetry, and postural control. Cognitive assessment included attention, fluctuating attention, executive function, visual memory, and visuospatial function. Mixed-effects models tested independent gait predictors of cognitive decline. Gait characteristics of pace, variability, and postural control predicted decline in fluctuating attention and visual memory, whereas baseline neuropsychological assessment performance did not predict decline. This provides novel evidence for gait as a clinical biomarker for PD cognitive decline in early disease. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America.

Longitudinal cognitive biomarkers predicting symptom onset in presymptomatic frontotemporal dementia.

PubMed

Jiskoot, Lize C; Panman, Jessica L; van Asseldonk, Lauren; Franzen, Sanne; Meeter, Lieke H H; Donker Kaat, Laura; van der Ende, Emma L; Dopper, Elise G P; Timman, Reinier; van Minkelen, Rick; van Swieten, John C; van den Berg, Esther; Papma, Janne M

2018-06-01

We performed 4-year follow-up neuropsychological assessment to investigate cognitive decline and the prognostic abilities from presymptomatic to symptomatic familial frontotemporal dementia (FTD). Presymptomatic MAPT (n = 15) and GRN mutation carriers (n = 31), and healthy controls (n = 39) underwent neuropsychological assessment every 2 years. Eight mutation carriers (5 MAPT, 3 GRN) became symptomatic. We investigated cognitive decline with multilevel regression modeling; the prognostic performance was assessed with ROC analyses and stepwise logistic regression. MAPT converters declined on language, attention, executive function, social cognition, and memory, and GRN converters declined on attention and executive function (p < 0.05). Cognitive decline in ScreeLing phonology (p = 0.046) and letter fluency (p = 0.046) were predictive for conversion to non-fluent variant PPA, and decline on categorical fluency (p = 0.025) for an underlying MAPT mutation. Using longitudinal neuropsychological assessment, we detected a mutation-specific pattern of cognitive decline, potentially suggesting prognostic value of neuropsychological trajectories in conversion to symptomatic FTD.

Associations of Sugar and Artificially Sweetened Soda with Albuminuria and Kidney Function Decline in Women

PubMed Central

Curhan, Gary C.

2011-01-01

Summary Background and objectives Sugar-sweetened soda is reported to be associated with increased risk for diabetes and albuminuria, but there are currently limited data on how sugar or artificially sweetened soda may be related to kidney function decline. Design, setting, participants, & measurements This study identified 3318 women participating in the Nurses' Health Study with data on soda intake and albuminuria; of these, 3256 also had data on estimated GFR (eGFR) change between 1989 and 2000. Cumulative average beverage intake was derived from the 1984, 1986, 1990, 1994, and 1998 food frequency questionnaires. Serving categories included <1/mo (referent), 1 to 4/mo, 2 to 6/wk, 1 to 1.9/d, and ≥2/d. Microalbuminuria (MA) was considered a urinary albumin-to-creatinine ratio of 25 to 355 μg/mg. For kidney function change, the primary outcome was a ≥30% decline in eGFR over 11 years; rapid eGFR decline defined as ≥3 ml/min per 1.73 m2 per year was also examined. Results Consumption of ≥2 servings per day of artificially sweetened (diet) soda was independently associated with eGFR decline ≥30% (OR 2.02, 95% CI 1.36 to 3.01) and ≥3 ml/min per 1.73 m2 per year (OR 2.20, 95% CI 1.36 to 3.55). No increased risk for eGFR decline was observed for <2 servings per day of diet soda. No associations were noted between diet soda and MA or sugar soda and MA or eGFR decline. Conclusions Consumption of ≥2 servings per day of artificially sweetened soda is associated with a 2-fold increased odds for kidney function decline in women. PMID:20884773

Associations of sugar and artificially sweetened soda with albuminuria and kidney function decline in women.

PubMed

Lin, Julie; Curhan, Gary C

2011-01-01

Sugar-sweetened soda is reported to be associated with increased risk for diabetes and albuminuria, but there are currently limited data on how sugar or artificially sweetened soda may be related to kidney function decline. This study identified 3318 women participating in the Nurses' Health Study with data on soda intake and albuminuria; of these, 3256 also had data on estimated GFR (eGFR) change between 1989 and 2000. Cumulative average beverage intake was derived from the 1984, 1986, 1990, 1994, and 1998 food frequency questionnaires. Serving categories included <1/mo (referent), 1 to 4/mo, 2 to 6/wk, 1 to 1.9/d, and ≥ 2/d. Microalbuminuria (MA) was considered a urinary albumin-to-creatinine ratio of 25 to 355 μg/mg. For kidney function change, the primary outcome was a ≥ 30% decline in eGFR over 11 years; rapid eGFR decline defined as ≥ 3 ml/min per 1.73 m(2) per year was also examined. Consumption of ≥ 2 servings per day of artificially sweetened (diet) soda was independently associated with eGFR decline ≥ 30% (OR 2.02, 95% CI 1.36 to 3.01) and ≥ 3 ml/min per 1.73 m(2) per year (OR 2.20, 95% CI 1.36 to 3.55). No increased risk for eGFR decline was observed for <2 servings per day of diet soda. No associations were noted between diet soda and MA or sugar soda and MA or eGFR decline. Consumption of ≥ 2 servings per day of artificially sweetened soda is associated with a 2-fold increased odds for kidney function decline in women.

Effects of polymorphic variations in tumor necrosis factor alpha and occupational exposure to grain dust on longitudinal decline in pulmonary function.

PubMed

Pahwa, Punam; Nakagawa, Kazuko; Koehncke, Niels; McDuffie, Helen H

2009-01-01

Longitudinal declines in pulmonary function are associated with individuals experiencing occupational exposure to organic dusts in combination with lifestyle factors such as cigarette smoking and with genetic factors, and interactions between these factors. To investigate the relationship between polymorphism of genes encoding Tumor Necrosis Factor Alpha (TNF-alpha) and longitudinal lung function decline in grain workers exposed to grain dust. Male grain handlers who participated in the Saskatchewan Grain Workers Surveillance Program from 2002 through 2005 provided demographic, occupational, lifestyle, and respiratory symptoms information as well as pulmonary function measurements and DNA for genotyping. Marginal models using the generalized estimating equations approach were fitted by using a SAS PROC GENMOD to predict the annual decline in Forced Expired Volume in one second (FEV(1)) and Forced Vital Capacity (FVC). Smoking intensity contributed to the decline in FEV(1.)Among *1/*1 homozygotes and *1/*2 heterozygotes, grain workers with <10 years in the grain industry had significantly lower FEV(1)declines compared to those of the other two exposure groups (>10 and < or =20 years, and >20 years in the grain industry). The annual declines in FEV(1)for grain workers who were either *1/*1 homozygote or *1/*2 heterozygote and had been in the grain industry for <10 years were lower by comparison to those of grain workers who were *2/*2 genotype and had been in the industry for <10 years. This research demonstrates that years in the grain industry is an effect modifier between TNF-alpha 308 genotype and longitudinal decline in FEV(1)in male subjects exposed to grain dust.

Caloric restriction: Impact upon pituitary function and reproduction

PubMed Central

Martin, Bronwen; Golden, Erin; Carlson, Olga D.; Egan, Josephine M.; Mattson, Mark P.; Maudsley, Stuart

2008-01-01

Reduced energy intake, or caloric restriction (CR), is known to extend life span and to retard age-related health decline in a number of different species, including worms, flies, fish, mice and rats. CR has been shown to reduce oxidative stress, improve insulin sensitivity, and alter neuroendocrine responses and central nervous system (CNS) function in animals. CR has particularly profound and complex actions upon reproductive health. At the reductionist level the most crucial physiological function of any organism is its capacity to reproduce. For a successful species to thrive, the balance between available energy (food) and the energy expenditure required for reproduction must be tightly linked. An ability to coordinate energy balance and fecundity involves complex interactions of hormones from both the periphery and the CNS and primarily centers upon the master endocrine gland, the anterior pituitary. In this review article we review the effects of CR on pituitary gonadotrope function and on the male and female reproductive axes. A better understanding of how dietary energy intake affects reproductive axis function and endocrine pulsatility could provide novel strategies for the prevention and management of reproductive dysfunction and its associated comorbidities. PMID:18329344

Endothelium-dependent control of cerebrovascular functions through age: exercise for healthy cerebrovascular aging.

PubMed

Bolduc, Virginie; Thorin-Trescases, Nathalie; Thorin, Eric

2013-09-01

Cognitive performances are tightly associated with the maximal aerobic exercise capacity, both of which decline with age. The benefits on mental health of regular exercise, which slows the age-dependent decline in maximal aerobic exercise capacity, have been established for centuries. In addition, the maintenance of an optimal cerebrovascular endothelial function through regular exercise, part of a healthy lifestyle, emerges as one of the key and primary elements of successful brain aging. Physical exercise requires the activation of specific brain areas that trigger a local increase in cerebral blood flow to match neuronal metabolic needs. In this review, we propose three ways by which exercise could maintain the cerebrovascular endothelial function, a premise to a healthy cerebrovascular function and an optimal regulation of cerebral blood flow. First, exercise increases blood flow locally and increases shear stress temporarily, a known stimulus for endothelial cell maintenance of Akt-dependent expression of endothelial nitric oxide synthase, nitric oxide generation, and the expression of antioxidant defenses. Second, the rise in circulating catecholamines during exercise not only facilitates adequate blood and nutrient delivery by stimulating heart function and mobilizing energy supplies but also enhances endothelial repair mechanisms and angiogenesis. Third, in the long term, regular exercise sustains a low resting heart rate that reduces the mechanical stress imposed to the endothelium of cerebral arteries by the cardiac cycle. Any chronic variation from a healthy environment will perturb metabolism and thus hasten endothelial damage, favoring hypoperfusion and neuronal stress.

CHERISH (collaboration for hospitalised elders reducing the impact of stays in hospital): protocol for a multi-site improvement program to reduce geriatric syndromes in older inpatients.

PubMed

Mudge, Alison M; Banks, Merrilyn D; Barnett, Adrian G; Blackberry, Irene; Graves, Nicholas; Green, Theresa; Harvey, Gillian; Hubbard, Ruth E; Inouye, Sharon K; Kurrle, Sue; Lim, Kwang; McRae, Prue; Peel, Nancye M; Suna, Jessica; Young, Adrienne M

2017-01-09

Older inpatients are at risk of hospital-associated geriatric syndromes including delirium, functional decline, incontinence, falls and pressure injuries. These contribute to longer hospital stays, loss of independence, and death. Effective interventions to reduce geriatric syndromes remain poorly implemented due to their complexity, and require an organised approach to change care practices and systems. Eat Walk Engage is a complex multi-component intervention with structured implementation, which has shown reduced geriatric syndromes and length of stay in pilot studies at one hospital. This study will test effectiveness of implementing Eat Walk Engage using a multi-site cluster randomised trial to inform transferability of this intervention. A hybrid study design will evaluate the effectiveness and implementation strategy of Eat Walk Engage in a real-world setting. A multisite cluster randomised study will be conducted in 8 medical and surgical wards in 4 hospitals, with one ward in each site randomised to implement Eat Walk Engage (intervention) and one to continue usual care (control). Intervention wards will be supported to develop and implement locally tailored strategies to enhance early mobility, nutrition, and meaningful activities. Resources will include a trained, mentored facilitator, audit support, a trained healthcare assistant, and support by an expert facilitator team using the i-PARIHS implementation framework. Patient outcomes and process measures before and after intervention will be compared between intervention and control wards. Primary outcomes are any hospital-associated geriatric syndrome (delirium, functional decline, falls, pressure injuries, new incontinence) and length of stay. Secondary outcomes include discharge destination; 30-day mortality, function and quality of life; 6 month readmissions; and cost-effectiveness. Process measures including patient interviews, activity mapping and mealtime audits will inform interventions in each site and measure improvement progress. Factors influencing the trajectory of implementation success will be monitored on implementation wards. Using a hybrid design and guided by an explicit implementation framework, the CHERISH study will establish the effectiveness, cost-effectiveness and transferability of a successful pilot program for improving care of older inpatients, and identify features that support successful implementation. ACTRN12615000879561 registered prospectively 21/8/2015.

Functional Independence in Late-Life: Maintaining Physical Functioning in Older Adulthood Predicts Daily Life Function after Age 80

PubMed Central

Leng, Xiaoyan; La Monte, Michael J.; Tindle, Hilary A.; Cochrane, Barbara B.; Shumaker, Sally A.

2016-01-01

Abstract Background. We examined physical functioning (PF) trajectories (maintaining, slowly declining, and rapidly declining) spanning 15 years in older women aged 65–80 and protective factors that predicted better current levels and less decline in functional independence outcomes after age 80. Methods. Women’s Health Initiative extension participants who met criteria (enrolled in either the clinical trial or observational study cohort, >80 years at the data release cutoff, PF survey data from initial enrollment to age 80, and functional independence survey data after age 80) were included in these analyses (mean [ SD ] age = 84.0 [1.4] years; N = 10,478). PF was measured with the SF-36 (mean = 4.9 occasions). Functional independence was measured by self-reported level of dependence in basic and instrumental activities of daily living (ADLs and IADLs) (mean = 3.4 and 3.3 occasions). Results. Maintaining consistent PF in older adulthood extends functional independence in ADL and IADL in late-life. Protective factors shared by ADL and IADL include maintaining PF over time, self-reported excellent or very good health, no history of hip fracture after age 55, and no history of cardiovascular disease. Better IADL function is uniquely predicted by a body mass index less than 25 and no depression. Less ADL and IADL decline is predicted by better self-reported health, and less IADL decline is uniquely predicted by having no history of hip fracture after age 55. Conclusions. Maintaining or improving PF and preventing injury and disease in older adulthood (ages 65–80) has far-reaching implications for improving late-life (after age 80) functional independence. PMID:26858328

Functional Independence in Late-Life: Maintaining Physical Functioning in Older Adulthood Predicts Daily Life Function after Age 80.

PubMed

Vaughan, Leslie; Leng, Xiaoyan; La Monte, Michael J; Tindle, Hilary A; Cochrane, Barbara B; Shumaker, Sally A

2016-03-01

We examined physical functioning (PF) trajectories (maintaining, slowly declining, and rapidly declining) spanning 15 years in older women aged 65-80 and protective factors that predicted better current levels and less decline in functional independence outcomes after age 80. Women's Health Initiative extension participants who met criteria (enrolled in either the clinical trial or observational study cohort, >80 years at the data release cutoff, PF survey data from initial enrollment to age 80, and functional independence survey data after age 80) were included in these analyses (mean [SD] age = 84.0 [1.4] years; N = 10,478). PF was measured with the SF-36 (mean = 4.9 occasions). Functional independence was measured by self-reported level of dependence in basic and instrumental activities of daily living (ADLs and IADLs) (mean = 3.4 and 3.3 occasions). Maintaining consistent PF in older adulthood extends functional independence in ADL and IADL in late-life. Protective factors shared by ADL and IADL include maintaining PF over time, self-reported excellent or very good health, no history of hip fracture after age 55, and no history of cardiovascular disease. Better IADL function is uniquely predicted by a body mass index less than 25 and no depression. Less ADL and IADL decline is predicted by better self-reported health, and less IADL decline is uniquely predicted by having no history of hip fracture after age 55. Maintaining or improving PF and preventing injury and disease in older adulthood (ages 65-80) has far-reaching implications for improving late-life (after age 80) functional independence. © The Author 2016. 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.

Function of obestatin in the digestive system.

PubMed

Xing, Yue-Xian; Yang, Liu; Kuang, Hong-Yu; Gao, Xin-Yuan; Liu, Hao-Ling

2017-02-01

Physical health has a direct relationship with digestive function. Any abnormalities in the link may cause malnutrition, endocrine disorders, and the decline of organ functions. Obestatin, a biologically active peptide, is encoded by the ghrelin gene. Most studies suggest that obestatin is a pleiotropic peptide, which acts by suppressing the motility of the gastrointestinal tract, regulating the secretion of insulin, reducing inflammation and apoptosis, and promoting proliferation. These characteristics suggest that obestatin may represent an efficient way to prevent the occurrence and development of some digestive diseases. However, the functions of obestatin are not clear, and even appear to be contradictory. The aim of this review was to discuss the close relationship between obestatin and the digestive system, and to provide a unique perspective for the future development of obestatin relative to digestive diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Sleep restoration is associated with reduced plasma C-reactive protein and depression symptoms in military personnel with sleep disturbance after deployment.

PubMed

Heinzelmann, Morgan; Lee, Hyunhwa; Rak, Hannah; Livingston, Whitney; Barr, Taura; Baxter, Tristin; Scattergood-Keepper, Lindsay; Mysliwiec, Vincent; Gill, Jessica

2014-12-01

Deployed military personnel are vulnerable to chronic sleep disturbance, which is highly comorbid with post-traumatic stress disorder (PTSD) and depression, as well as declines in health-related quality of life (HRQOL). Inflammation is associated with HRQOL declines and sleep-related comorbidities; however, the impact of sleep changes on comorbid symptoms and inflammation in this population is unknown. In this observational study, we examined the relationship between reported sleep changes and concentrations of inflammatory biomarkers, interleukin 6 (IL-6), and C-reactive protein (CRP) in peripheral blood. The sample was dichotomized into two groups: (1) decrease in Pittsburgh Sleep Quality Index (PSQI; restorative sleep) and (2) no change or increase in PSQI (no change). Mixed between-within subjects analysis of variance tests were used to determine group differences on changes of inflammation and comorbid symptoms. In our sample of 66 recently deployed military personnel with insomnia, 34 participants reported restorative sleep whereas 32 reported no sleep changes. The two groups did not differ in demographic or clinical characteristics, with the exception of PTSD diagnosis at baseline. The restorative sleep group had significant reductions in CRP concentrations and depression symptoms, as well as reduced fatigue and improvements in emotional well-being, social functioning, and physical functioning at follow-up. Military personnel who report sleep restoration after deployment have reduced CRP concentrations, decreased severity of depression, and improved HRQOL. These findings suggest that treatment for sleep disturbances may be associated with improvements in mental and physical health, thereby supporting continued study in this line of research. Copyright © 2014 Elsevier B.V. All rights reserved.

Depression and the Onset of Dementia in Adults with Mental Retardation.

ERIC Educational Resources Information Center

Burt, Diana Byrd; And Others

1992-01-01

Comparison of 61 adults with Down's syndrome and 43 adults with mental retardation resulting from other causes found that 8 Down's syndrome adults had both depression and declines in functioning, whereas no adults in the other group showed functional declines. Greater severity of depression was related to poor functioning in adults with Down's…

Drosophila Clock Is Required in Brain Pacemaker Neurons to Prevent Premature Locomotor Aging Independently of Its Circadian Function

PubMed Central

Issa, Abdul-Raouf; Seugnet, Laurent; Klarsfeld, André

2017-01-01

Circadian clocks control many self-sustained rhythms in physiology and behavior with approximately 24-hour periodicity. In many organisms, oxidative stress and aging negatively impact the circadian system and sleep. Conversely, loss of the clock decreases resistance to oxidative stress, and may reduce lifespan and speed up brain aging and neurodegeneration. Here we examined the effects of clock disruptions on locomotor aging and longevity in Drosophila. We found that lifespan was similarly reduced in three arrhythmic mutants (ClkAR, cyc0 and tim0) and in wild-type flies under constant light, which stops the clock. In contrast, ClkAR mutants showed significantly faster age-related locomotor deficits (as monitored by startle-induced climbing) than cyc0 and tim0, or than control flies under constant light. Reactive oxygen species accumulated more with age in ClkAR mutant brains, but this did not appear to contribute to the accelerated locomotor decline of the mutant. Clk, but not Cyc, inactivation by RNA interference in the pigment-dispersing factor (PDF)-expressing central pacemaker neurons led to similar loss of climbing performance as ClkAR. Conversely, restoring Clk function in these cells was sufficient to rescue the ClkAR locomotor phenotype, independently of behavioral rhythmicity. Accelerated locomotor decline of the ClkAR mutant required expression of the PDF receptor and correlated to an apparent loss of dopaminergic neurons in the posterior protocerebral lateral 1 (PPL1) clusters. This neuronal loss was rescued when the ClkAR mutation was placed in an apoptosis-deficient background. Impairing dopamine synthesis in a single pair of PPL1 neurons that innervate the mushroom bodies accelerated locomotor decline in otherwise wild-type flies. Our results therefore reveal a novel circadian-independent requirement for Clk in brain circadian neurons to maintain a subset of dopaminergic cells and avoid premature locomotor aging in Drosophila. PMID:28072817

"Brain-muscle loop" in the fragility of older persons: from pathophysiology to new organizing models.

PubMed

Lauretani, Fulvio; Meschi, Tiziana; Ticinesi, Andrea; Maggio, Marcello

2017-12-01

The imperative action of the geriatric medicine is to prevent disability in older persons. Many epidemiological studies have been conducted in the last decades for improving knowledge of the aging process and their interactions with age-related diseases, especially for the identification of the relationship between sarcopenia and loss of mobility. Factors influencing muscle integrity can be classified into six main physiologic subsystems, but the central nervous system certainly plays a crucial role for maintaining muscle integrity in older persons. Recent data show that the reduced muscle strength and not muscle mass could be considered the core of the fragility in predicting changes of gait velocity and mobility and conferring a higher risk of mortality in older persons. Sarcopenia and cognitive decline could, therefore, produce slow gait velocity in older persons, with devastating effect and consequences. Perhaps the most notorious corollary is falling, which is often caused by an underlying gait problem. Injuries caused by accidental falls range from relatively innocent bruises to major fractures or head trauma. Another important consequence is reduced mobility, which leads to loss of independence. This immobility is often compounded by a fear of falling, which further immobilises patients and affects their quality of life and physical performance. When we search the association between brain pathology and muscle function in older persons, we amazingly find that established composite measure of physical frailty is associated with brain pathology. Sarcopenia, which produces muscle dysfunction, slow gait velocity and cognitive decline, could share a strong bidirectional relationship, and this suggests the coexistence of both cognitive and motor dysfunctions in older persons to characterize a new syndrome characterized by slow gait and cognitive complaints, the motoric-cognitive risk syndrome (MRC). In this review, we want to emphasize the relationship between memory complaints with muscle function integrating cognitive and physical evaluation, even with amyloid PET study, to identify older patients at high risk of cognitive and physical decline.

High Level of Chemokine CCL18 Is Associated With Pulmonary Function Deterioration, Lung Fibrosis Progression, and Reduced Survival in Systemic Sclerosis.

PubMed

Hoffmann-Vold, Anna-Maria; Tennøe, Anders Heiervang; Garen, Torhild; Midtvedt, Øyvind; Abraityte, Aurelija; Aaløkken, Trond Mogens; Lund, May Britt; Brunborg, Cathrine; Aukrust, Pål; Ueland, Thor; Molberg, Øyvind

2016-08-01

Markers for early identification of progressive interstitial lung disease (ILD) in systemic sclerosis (SSc) are in demand. Chemokine CCL18, which has been linked to pulmonary inflammation, is an interesting candidate, but data have not been consistent. We aimed to assess CCL18 levels in a large, prospective, unselected SSc cohort with longitudinal, paired data sets on pulmonary function and lung fibrosis. Sera from the Oslo University Hospital SSc cohort (n = 298) and healthy control subjects (n = 100) were analyzed for CCL18 by enzyme immunoassay. High CCL18 (>53 ng/mL) was defined using the mean value plus 2 SD in sera obtained from healthy control subjects as the cutoff. High serum CCL18 was identified in 35% (105 of 298). Annual decline in FVC differed significantly between high and low CCL18 subsets (13.3% and 4.7%; P = .016), as did the annual progression rate of lung fibrosis (0.9% [SD, 2.9] and 0.2% [SD, 1.9]). Highest rates of annual FVC decline > 10% (21%) and annual fibrosis progression (1.2%) were seen in patients with high CCL18 and early disease (< 3 years). In multivariate analyses, CCL18 was associated with annual FVC decline > 10% (OR, 1.1; 95% CI, 1.01-1.11) and FVC < 70% at follow-up (OR, 3.1; 95% CI, 1.08-8.83). Survival analyses showed that patients with high CCL18 had reduced 5- and 10-year cumulative survival compared with patients with low CCL18 (85% and 74%, compared with 97% and 89%, respectively; P = .001). The results from this prospective cohort reinforce the notion that high CCL18 may serve as a marker for early identification of progressive ILD in SSc. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Globalization and the price decline of illicit drugs.

PubMed

Costa Storti, Cláudia; De Grauwe, Paul

2009-01-01

This study aims at understanding the mechanisms underlying the dramatic decline of the retail prices of major drugs like cocaine and heroin during the past two decades. It also aims at analysing the implications of this decline for drug policies. We use a theoretical model to identify the possible causes of this price decline. This allows us to formulate the hypothesis that the major driving force behind the price decline is a reduction of the intermediation margin (the difference between the retail and producer prices). We also develop the hypothesis that globalization has been an important factor behind the decline of the intermediation margin. We then analyse the statistical information to test these hypotheses. We find that the decline in the retail prices of drugs is related to the strong decline in the intermediation margin in the drug business, and that globalization is the main driving force behind this phenomenon. Globalization has done so by increasing the efficiency of the distribution of drugs, by reducing the risk premium involved in dealing with drugs, and by increasing the degree of competition in the drug markets. We conclude that the cocaine and heroin price declines were due to a sharp fall in the intermediation margin, which was probably influenced by globalization. This phenomenon might have a strong impact on the effectiveness of drug policies, increasing the relative effectiveness of policies aiming at reducing the demand of drugs.

Decline in Physical Function and Risk for Elder Abuse Reported to Social Services in a Community-Dwelling Population of Older Adults

PubMed Central

Dong, XinQi; Simon, Melissa; Evans, Denis

2012-01-01

Objectives Elder abuse is an important public health and human rights issue and is associated with increased morbidity and mortality. This study aimed to examine the longitudinal association between decline in physical function and the risk for elder abuse. Design Prospective population-based study Setting Geographically defined community in Chicago. Participants Chicago Health and Aging Project (CHAP) is a population-based study (N=6,159), and we identified 143 CHAP participants who had elder abuse reported to social services agency from 1993–2010. Participants The primary independent variable was objectively assessed physical function using decline in physical performance testing (Tandem stand, measured walk and chair stand). Secondary independent variables were assessed using the decline in self-reported Katz, Nagi, and Rosow-Breslau scales. Outcomes were reported and confirmed elder abuse and specific subtypes of elder abuse (physical, psychological, caregiver neglect and financial exploitation). Logistic regression models were used to assess the association of decline in physical function measures and risk for elder abuse. Results After adjusting for potential confounders, every 1 point decline in physical performance testing (OR, 1.13(1.06–1.19)), Katz impairment (OR, 1.29(1.15–1.45)), Nagi impairment (OR, 1.30(1.13–1.49)) and Rosow Breslau impairment (OR, 1.42(1.15–1.74)) were associated with increased risk for elder abuse. Lowest tertiles of physical performance testing (OR, 4.92 (1.39–17.46), highest tertiles of Katz impairment (OR, 3.99 (2.18–7.31), Nagi impairment (OR, 2.37 (1.08–5.23), and Rosow Breslau impairment (2.85 (1.39–5.84) were associated with increased risk for elder abuse. Conclusion Decline in objectively assessed physical function and self-reported physical function are associated with increased risk for elder abuse. PMID:23002901

Changes in Function After a 6-Month Walking Intervention in Patients With Intermittent Claudication Who Are Obese or Nonobese.

PubMed

Addison, Odessa; Ryan, Alice S; Prior, Steven J; Katzel, Leslie I; Kundi, Rishi; Lal, Brajesh K; Gardner, Andrew W

Both obesity and peripheral artery disease (PAD) limit function and may work additively to reduce mobility. The purpose of this study was to compare the effects of a 6-month, center-based walking program on mobility function between adults who are weight-stable obese and nonobese with PAD. This is a secondary data analysis of 2 combined studies taken from previous work. Fifty-three adults with PAD and intermittent claudication participated in 6 months of treadmill training or standard of care. Patients were divided into 4 groups for analyses: exercise nonobese (Ex), exercise obese (ExO), standard-of-care nonobese (SC), and standard-of-care obese (SCO). Mobility was assessed by a standardized treadmill test to measure claudication onset time (COT) and peak walking time (PWT) as well as the distance walked during a 6-minute walk distance (6MWD) test. There was a significant (P < .001) interaction (intervention × obesity) effect on 6MWD, wherein both exercise groups improved (Ex = 7%, ExO = 16%; P < .02), the SC group did not change (0.9%; P > .05), and the SCO group tended to decline (-18%; P = .06). Both exercise intervention groups significantly improved COT (Ex = 92%, ExO = 102%; P < .01) and PWT (Ex = 54%, ExO = 103%; P < .001). There was no change (P > .05) in either standard-of-care group. Individuals who are obese and nonobese with PAD made similar improvements after a 6-month, center-based walking program. However, patients who are obese with PAD and do not exercise may be susceptible to greater declines in mobility. Exercise may be particularly important in patients who are obese with PAD to avoid declines in mobility.

Monitoring disease progression with plasma creatinine in amyotrophic lateral sclerosis clinical trials

PubMed Central

van Eijk, Ruben P A; Eijkemans, Marinus J C; Ferguson, Toby A; Nikolakopoulos, Stavros; Veldink, Jan H; van den Berg, Leonard H

2018-01-01

Objectives Plasma creatinine is a predictor of survival in amyotrophic lateral sclerosis (ALS). It remains, however, to be established whether it can monitor disease progression and serve as surrogate endpoint in clinical trials. Methods We used clinical trial data from three cohorts of clinical trial participants in the LITRA, EMPOWER and PROACT studies. Longitudinal associations between functional decline, muscle strength and survival with plasma creatinine were assessed. Results were translated to trial design in terms of sample size and power. Results A total of 13 564 measurements were obtained for 1241 patients. The variability between patients in rate of decline was lower in plasma creatinine than in ALS functional rating scale–Revised (ALSFRS-R; p<0.001). The average rate of decline was faster in the ALSFRS-R, with less between-patient variability at baseline (p<0.001). Plasma creatinine had strong longitudinal correlations with the ALSFRS-R (0.43 (0.39–0.46), p<0.001), muscle strength (0.55 (0.51–0.58), p<0.001) and overall mortality (HR 0.88 (0.86–0.91, p<0.001)). Using plasma creatinine as outcome could reduce the sample size in trials by 21.5% at 18 months. For trials up to 10 months, the ALSFRS-R required a lower sample size. Conclusions Plasma creatinine is an inexpensive and easily accessible biomarker that exhibits less variability between patients with ALS over time and is predictive for the patient’s functional status, muscle strength and mortality risk. Plasma creatinine may, therefore, increase the power to detect treatment effects and could be incorporated in future ALS clinical trials as potential surrogate outcome. PMID:29084868

The development of the modified blaylock tool for occupational therapy referral (MBTOTR): a preliminary evaluation of its utility in acute care.

PubMed

Tan, Emma Su Zan; Mackenzie, Lynette; Travasssaros, Katrina; Yeo, Megan

2016-08-01

Acute hospitals are facing more complex admissions with older people at increased risk of functional decline. This study aimed to create and trial the feasibility of a new screening tool designed to identify patients at risk of functional decline who need an occupational therapy referral within acute care. Ten screening tools were reviewed and the Modified Blaylock Tool for Occupational Therapy Referral (MBTOTR) was developed. The MBTOTR was applied in a retrospective chart review of 50 patients over the age of 65 years who were admitted to five acute wards. Data on patients identified at risk of functional decline were compared to patients who were referred to occupational therapy. Occupational therapy referrals were made by ward staff for 14 out of the 50 patients reviewed (32.5%). Only 14% (n = 7) of patients did not require a referral. The MBTOTR identified no irrelevant occupational therapy referrals. However, 66.5% of patients identified as needing an occupational therapy referral did not get one. The MBTOTR identified high risk acute patients requiring an occupational therapy referral who were not referred to occupational therapy. Use of the MBTOTR would facilitate early occupational therapy referrals for complex patients, and potentially better discharge outcomes. Implications for rehabilitation The MBTOTR can be used in acute care settings to facilitate relevant occupational therapy referrals. Without a screening tool, many older people who should have an occupational therapy assessment may not receive a referral for occupational therapy. Nursing and medical staff need to use this tool to identify older people in their care who may benefit from occupational therapy assessment and intervention. If occupational therapy referrals can be made early, this may contribute to reducing delays to discharge plans for complex patients.

Efficiency of electronically monitored amblyopia treatment between 5 and 16 years of age: new insight into declining susceptibility of the visual system.

PubMed

Fronius, Maria; Cirina, Licia; Ackermann, Hanns; Kohnen, Thomas; Diehl, Corinna M

2014-10-01

The notion of a limited, early period of plasticity of the visual system has been challenged by more recent research demonstrating functional enhancement even into adulthood. In amblyopia ("lazy eye") it is still unclear to what extent the reduced effect of treatment after early childhood is due to declining plasticity or lower compliance with prescribed patching. The aim of this study was to determine the dose-response relationship and treatment efficiency from acuity gain and electronically recorded patching dose rates, and to infer from these parameters on a facet of age dependence of functional plasticity related to occlusion for amblyopia. The Occlusion Dose Monitor was used to record occlusion in 27 participants with previously untreated strabismic and/or anisometropic amblyopia aged between 5.4 and 15.8 (mean 9.2) years during 4months of conventional treatment. Group data showed improvement of acuity throughout the age span, but significantly more in patients younger than 7years despite comparable patching dosages. Treatment efficiency declined with age, with the most pronounced effects before the age of 7years. Thus, electronic recording allowed this first quantitative insight into occlusion treatment spanning the age range from within to beyond the conventional age for patching. Though demonstrating improvement in over 7year old patients, it confirmed the importance of early detection and treatment of amblyopia. Treatment efficiency is presented as a tool extending insight into age-dependent functional plasticity of the visual system, and providing a basis for comparisons of effects of patching vs. emerging alternative treatment approaches for amblyopia. Copyright © 2014 Elsevier Ltd. All rights reserved.

Aging of vestibular function evaluated using correlational vestibular autorotation test

PubMed Central

Hsieh, Li-Chun; Lin, Hung-Ching; Lee, Guo-She

2014-01-01

Background Imbalance from degeneration of vestibular end organs is a common problem in the elderly. However, the decline of vestibular function with aging was revealed in few vestibular function tests such as vestibular autorotation test (VAT). In the current VAT, there are drawbacks of poor test–retest reliability, slippage of the sensor at high-speed rotations, and limited data about the effect of aging. We developed a correlational-VAT (cVAT) system that included a small, light sensor (less than 20 g) with wireless data transmission technique to evaluate the aging of vestibular function. Material and methods We enrolled 53 healthy participants aged between 25 and 75 years and divided them into five age groups. The test conditions were vertical and horizontal head autorotations of frequencies from 0 to 3 Hz with closed eyes or open eyes. The cross-correlation coefficient (CCC) between eye velocity and head velocity was obtained for the head autorotations between 1 Hz and 3 Hz. The mean of the CCCs was used to represent the vestibular function. Results Age was significantly and negatively correlated with the mean CCC for all test conditions, including horizontal or vertical autorotations with open eyes or closed eyes (P<0.05). The mean CCC with open eyes declined significantly at 55–65 years old and the mean CCC with closed eyes declined significantly at 65–75 years old. Conclusion Vestibular function evaluated using mean CCC revealed a decline with age, and the function of visual-vestibulo-ocular reflex declined 10 years earlier than the function of vestibulo-ocular reflex. PMID:25214774

Developmental changes in memorial comparisons: the effects of stimulus presentation mode.

PubMed

Wright, K P; Berch, D B

1992-06-01

First graders, fifth graders, and college students made comparative size judgments of either pictures (line drawings) or names (spoken words) of common objects by designating the "bigger" item in real life. Care was taken to equate the picture and word conditions on a number of critical parameters including method of item-pair presentation and activation of response-time intervals. All groups exhibited a symbolic distance effect. While judgments were faster with pictures than words, the magnitude of the difference did not change with age. Previous research suggesting a marked developmental decline in the magnitude of the "pictorial superiority effect" may have confounded reduced memory demands with stimulus presentation mode for young children. Finally, slopes of the symbolic distance functions were found to decrease with increasing grade level, at least from first to fifth grade. This is the first demonstration of an age-related decline in slopes for magnitude comparisons of concrete objects.

Nutraceuticals, aging, and cognitive dysfunction.

PubMed

Head, Elizabeth; Zicker, Steven C

2004-01-01

Decline in cognitive function that accompanies aging in dogs might have a biological basis, and many of the disorders associated with aging in canines might be preventable through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of laboratory and clinical studies, antioxidants might be one class of nutraceutical that benefits aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which can lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes might lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs; however, determining which compounds, combinations, dosage ranges, when to initiate intervention, and long-term effects constitute critical gaps in knowledge about this subject.

Functional neuroimaging and behavioral correlates of capacity decline in visual short-term memory after sleep deprivation.

PubMed

Chee, Michael W L; Chuah, Y M Lisa

2007-05-29

Sleep deprivation (SD) impairs short-term memory, but it is unclear whether this is because of reduced storage capacity or processes contributing to appropriate information encoding. We evaluated 30 individuals twice, once after a night of normal sleep and again after 24 h of SD. In each session, we evaluated visual memory capacity by presenting arrays of one to eight colored squares. Additionally, we measured cortical responses to varying visual array sizes without engaging memory. The magnitude of intraparietal sulcus activation and memory capacity after normal sleep were highly correlated. SD elicited a pattern of activation in both tasks, indicating that deficits in visual processing and visual attention accompany and could account for loss of short-term memory capacity. Additionally, a comparison between better and poorer performers showed that preservation of precuneus and temporoparietal junction deactivation with increasing memory load corresponds to less performance decline when one is sleep-deprived.

The Effects of Low Income Housing Tax Credit Developments on Neighborhoods.

PubMed

Baum-Snow, Nathaniel; Marion, Justin

2009-06-01

This paper evaluates the impacts of new housing developments funded with the Low Income Housing Tax Credit (LIHTC), the largest federal project based housing program in the U.S., on the neighborhoods in which they are built. A discontinuity in the formula determining the magnitude of tax credits as a function of neighborhood characteristics generates pseudo-random assignment in the number of low income housing units built in similar sets of census tracts. Tracts where projects are awarded 30 percent higher tax credits receive approximately six more low income housing units on a base of seven units per tract. These additional new low income developments cause homeowner turnover to rise, raise property values in declining areas and reduce incomes in gentrifying areas in neighborhoods near the 30th percentile of the income distribution. LIHTC units significantly crowd out nearby new rental construction in gentrifying areas but do not displace new construction in stable or declining areas.

Advanced statistical methods to study the effects of gastric tube and non-invasive ventilation on functional decline and survival in amyotrophic lateral sclerosis.

PubMed

Atassi, Nazem; Cudkowicz, Merit E; Schoenfeld, David A

2011-07-01

A few studies suggest that non-invasive ventilation (1) and gastric tube (G-tube) may have a positive impact on survival but the effect on functional decline is unclear. Confounding by indication may have produced biased estimates of the benefit seen in some of these retrospective studies. The objective of this study was to evaluate the effects of G-tube and NIV on survival and functional decline using advanced statistical models that adjust for confounding by indications. A database of 331 subjects enrolled in previous clinical trials in ALS was available for analysis. Marginal structural models (MSM) were used to compare the mortality hazards and ALSFRS-R slopes between treatment and non-treatment groups, after adjusting for confounding by indication. Results showed that the placement of a G-tube was associated with an additional 1.42 units/month decline in the ALSFRS-R slope (p < 0.0001) and increased mortality hazard of 0.28 (p = 0.02). The use of NIV had no significant effect on ALSFRS-R decline or mortality. In conclusion, marginal structural models can be used to adjust for confounding by indication in retrospective ALS studies. G-tube placement could be followed by a faster rate of functional decline and increased mortality. Our results may suffer from some of the limitations of retrospective analyses.

Influence of Cognitive Functioning on Age-Related Performance Declines in Visuospatial Sequence Learning.

PubMed

Krüger, Melanie; Hinder, Mark R; Puri, Rohan; Summers, Jeffery J

2017-01-01

Objectives: The aim of this study was to investigate how age-related performance differences in a visuospatial sequence learning task relate to age-related declines in cognitive functioning. Method: Cognitive functioning of 18 younger and 18 older participants was assessed using a standardized test battery. Participants then undertook a perceptual visuospatial sequence learning task. Various relationships between sequence learning and participants' cognitive functioning were examined through correlation and factor analysis. Results: Older participants exhibited significantly lower performance than their younger counterparts in the sequence learning task as well as in multiple cognitive functions. Factor analysis revealed two independent subsets of cognitive functions associated with performance in the sequence learning task, related to either the processing and storage of sequence information (first subset) or problem solving (second subset). Age-related declines were only found for the first subset of cognitive functions, which also explained a significant degree of the performance differences in the sequence learning task between age-groups. Discussion: The results suggest that age-related performance differences in perceptual visuospatial sequence learning can be explained by declines in the ability to process and store sequence information in older adults, while a set of cognitive functions related to problem solving mediates performance differences independent of age.

Nephrotic range proteinuria as a strong risk factor for rapid renal function decline during pre-dialysis phase in type 2 diabetic patients with severely impaired renal function.

PubMed

Kitai, Yuichiro; Doi, Yohei; Osaki, Keisuke; Sugioka, Sayaka; Koshikawa, Masao; Sugawara, Akira

2015-12-01

Proteinuria is an established risk factor for progression of renal disease, including diabetic nephropathy. The predictive power of proteinuria, especially nephrotic range proteinuria, for progressive renal deterioration has been well demonstrated in diabetic patients with normal to relatively preserved renal function. However, little is known about the relationship between severity of proteinuria and renal outcome in pre-dialysis diabetic patients with severely impaired renal function. 125 incident dialysis patients with type 2 diabetes were identified. This study was aimed at retrospectively evaluating the impact of nephrotic range proteinuria (urinary protein-creatinine ratio above 3.5 g/gCr) on renal function decline during the 3 months just prior to dialysis initiation. In total, 103 patients (82.4 %) had nephrotic range proteinuria. The median rate of decline in estimated glomerular filtration rate (eGFR) in this study population was 0.98 (interquartile range 0.51-1.46) ml/min/1.73 m(2) per month. Compared to patients without nephrotic range proteinuria, patients with nephrotic range proteinuria showed significantly faster renal function decline (0.46 [0.24-1.25] versus 1.07 [0.64-1.54] ml/min/1.73 m(2) per month; p = 0.007). After adjusting for gender, age, systolic blood pressure, serum albumin, calcium-phosphorus product, hemoglobin A1c, and use of an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker, patients with nephrotic range proteinuria showed a 3.89-fold (95 % CI 1.08-14.5) increased risk for rapid renal function decline defined as a decline in eGFR ≥0.5 ml/min/1.73 m(2) per month. Nephrotic range proteinuria is the predominant renal risk factor in type 2 diabetic patients with severely impaired renal function receiving pre-dialysis care.

Dietary Sodium/Potassium Intake Does Not Affect Cognitive Function or Brain Imaging Indices.

PubMed

Nowak, Kristen L; Fried, Linda; Jovanovich, Anna; Ix, Joachim; Yaffe, Kristine; You, Zhiying; Chonchol, Michel

2018-01-01

Dietary sodium may influence cognitive function through its effects on cerebrovascular function and cerebral blood flow. The aim of this study was to evaluate the association of dietary sodium intake with cognitive decline in community-dwelling older adults. We also evaluated the associations of dietary potassium and sodium:potassium intake with cognitive decline, and associations of these nutrients with micro- and macro-structural brain magnetic resonance imaging (MRI) indices. In all, 1,194 participants in the Health Aging and Body Composition study with measurements of dietary sodium intake (food frequency questionnaire [FFQ]) and change in the modified Mini Mental State Exam (3MS) were included. The age of participants was 74 ± 3 years with a mean dietary sodium intake of 2,677 ± 1,060 mg/day. During follow-up (6.9 ± 0.1 years), 340 (28%) had a clinically significant decline in 3MS score (≥1.5 SD of mean decline). After adjustment, dietary sodium intake was not associated with odds of cognitive decline (OR 0.96, 95% CI 0.50-1.84 per doubling of sodium). Similarly, potassium was not associated with cognitive decline; however, higher sodium:potassium intake was associated with increased odds of cognitive decline (OR 2.02 [95% CI 1.01-4.03] per unit increase). Neither sodium or potassium alone nor sodium:potassium were associated with micro- or macro-structural brain MRI indices. These results are limited by the use of FFQ. In community-dwelling older adults, higher sodium:potassium, but not sodium or potassium intake alone, was associated with decline in cognitive function, with no associations observed with micro- and macro-structural brain MRI indices. These findings do not support reduction dietary sodium/increased potassium intake to prevent cognitive decline with aging. © 2018 S. Karger AG, Basel.

Nutraceutical intervention reverses the negative effects of blood from aged rats on stem cells.

PubMed

Bickford, Paula C; Kaneko, Yuji; Grimmig, Bethany; Pappas, Colleen; Small, Brent; Sanberg, Cyndy D; Sanberg, Paul R; Tan, Jun; Douglas Shytle, R

2015-10-01

Aging is associated with a decline in function in many of the stem cell niches of the body. An emerging body of literature suggests that one of the reasons for this decline in function is due to cell non-autonomous influences on the niche from the body. For example, studies using the technique of parabiosis have demonstrated a negative influence of blood from aged mice on muscle satellite cells and neurogenesis in young mice. We examined if we could reverse this effect of aged serum on stem cell proliferation by treating aged rats with NT-020, a dietary supplement containing blueberry, green tea, vitamin D3, and carnosine that has been shown to increase neurogenesis in aged rats. Young and aged rats were administered either control NIH-31 diet or one supplemented with NT-020 for 28 days, and serum was collected upon euthanasia. The serum was used in cultures of both rat hippocampal neural progenitor cells (NPCs) and rat bone marrow-derived mesenchymal stem cells (MSCs). Serum from aged rats significantly reduced cell proliferation as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 5-bromo-2'-deoxyuridine (BrdU) assays in both NPCs and MSCs. Serum from aged rats treated with NT-020 was not different from serum from young rats. Therefore, NT-020 rescued the effect of serum from aged rats to reduce stem cell proliferation.

Moderating effects of coping styles on anxiety and depressive symptoms caused by psychological stress in Chinese patients with Type 2 diabetes.

PubMed

Zhang, C-X; Tse, L-A; Ye, X-Q; Lin, F-Y; Chen, Y-M; Chen, W-Q

2009-12-01

This study aimed to assess possible interactive effects of coping styles and psychological stress on depression and anxiety symptoms in Chinese patients with Type 2 diabetes. Three hundred and four patients with Type 2 diabetes underwent a face-to-face interview by trained research staff according to a standardized questionnaire including information on socio-demographic characteristics, psychological stress, coping styles and anxiety and depressive symptoms. The interactive effects of coping styles and psychological stress on depression and anxiety symptoms were assessed by hierarchical multiple regression analyses. There were significant associations of the four domains of psychological stress with anxiety and depressive symptoms, except for the relationship between 'reduced economic condition' and depressive symptoms. 'Negative coping style' significantly increased the level of both anxiety and depressive symptoms; whereas, 'active coping style' and 'avoidant coping style' decreased the risk of depressive symptoms. The interactions of 'negative coping style' with 'worrying about decline in body/physical function' and 'reduced economic condition' significantly increased the risk of anxiety and depressive symptoms, and the interaction of 'social/family crisis caused by the disease' with 'avoidance coping style' and 'worrying about decline in body/physical function' with 'active coping style' significantly decreased the risk of depressive symptoms. The results of this study suggest that certain coping styles might moderate the association of psychological stress with anxiety and depressive symptoms in Chinese patients with Type 2 diabetes.

Olfactory discrimination predicts cognitive decline among community-dwelling older adults

PubMed Central

Sohrabi, H R; Bates, K A; Weinborn, M G; Johnston, A N B; Bahramian, A; Taddei, K; Laws, S M; Rodrigues, M; Morici, M; Howard, M; Martins, G; Mackay-Sim, A; Gandy, S E; Martins, R N

2012-01-01

The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46–86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions using the Sniffin' Sticks battery indicated that, contrary to previous findings, olfactory discrimination, but not olfactory identification, significantly predicted subsequent cognitive decline (odds ratio=0.869; P<0.05; 95% confidence interval=0.764−0.988). The current study findings confirm previously reported associations between olfactory and cognitive functions, and indicate that impairment in olfactory discrimination can predict future cognitive decline. These findings further our current understanding of the association between cognition and olfaction, and support olfactory assessment in screening those at higher risk of dementia. PMID:22832962

Olfactory discrimination predicts cognitive decline among community-dwelling older adults.

PubMed

Sohrabi, H R; Bates, K A; Weinborn, M G; Johnston, A N B; Bahramian, A; Taddei, K; Laws, S M; Rodrigues, M; Morici, M; Howard, M; Martins, G; Mackay-Sim, A; Gandy, S E; Martins, R N

2012-05-22

The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46-86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions using the Sniffin' Sticks battery indicated that, contrary to previous findings, olfactory discrimination, but not olfactory identification, significantly predicted subsequent cognitive decline (odds ratio = 0.869; P<0.05; 95% confidence interval = 0.764-0.988). The current study findings confirm previously reported associations between olfactory and cognitive functions, and indicate that impairment in olfactory discrimination can predict future cognitive decline. These findings further our current understanding of the association between cognition and olfaction, and support olfactory assessment in screening those at higher risk of dementia.

NT-ProBNP and Troponin T and Risk of Rapid Kidney Function Decline and Incident CKD in Elderly Adults

PubMed Central

Katz, Ronit; Dalrymple, Lorien; de Boer, Ian; DeFilippi, Christopher; Kestenbaum, Bryan; Park, Meyeon; Sarnak, Mark; Seliger, Stephen; Shlipak, Michael

2015-01-01

Background and objectives Elevations in N-terminal pro–B-type natriuretic peptide and high-sensitivity troponin T are associated with poor cardiovascular outcomes. Whether elevations in these cardiac biomarkers are associated with decline in kidney function was evaluated. Design, setting, participants, & measurements N-terminal pro–B-type natriuretic peptide and troponin T were measured at baseline in 3752 participants free of heart failure in the Cardiovascular Health Study. eGFR was determined from the Chronic Kidney Disease Epidemiology Collaboration equation using serum cystatin C. Rapid decline in kidney function was defined as decline in serum cystatin C eGFR≥30%, and incident CKD was defined as the onset of serum cystatin C eGFR<60 among those without CKD at baseline (n=2786). Cox regression models were used to examine the associations of each biomarker with kidney function decline adjusting for demographics, baseline serum cystatin C eGFR, diabetes, and other CKD risk factors. Results In total, 503 participants had rapid decline in serum cystatin C eGFR over a mean follow-up time of 6.41 (1.81) years, and 685 participants developed incident CKD over a mean follow-up time of 6.41 (1.74) years. Participants in the highest quartile of N-terminal pro–B-type natriuretic peptide (>237 pg/ml) had an 67% higher risk of rapid decline and 38% higher adjusted risk of incident CKD compared with participants in the lowest quartile (adjusted hazard ratio for serum cystatin C eGFR rapid decline, 1.67; 95% confidence interval, 1.25 to 2.23; hazard ratio for incident CKD, 1.38; 95% confidence interval, 1.08 to 1.76). Participants in the highest category of troponin T (>10.58 pg/ml) had 80% greater risk of rapid decline compared with participants in the lowest category (adjusted hazard ratio, 1.80; 95% confidence interval, 1.35 to 2.40). The association of troponin T with incident CKD was not statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.92 to 1.50). Conclusions Elevated N-terminal pro–B-type natriuretic peptide and troponin T are associated with rapid decline of kidney function and incident CKD. Additional studies are needed to evaluate the mechanisms that may explain this association. PMID:25605700

Anti-inflammatory effects of physical activity in relationship to improved cognitive status in humans and mouse models of Alzheimer's disease.

PubMed

Stranahan, Alexis M; Martin, Bronwen; Maudsley, Stuart

2012-01-01

Physical activity has been correlated with a reduced incidence of cognitive decline and Alzheimer's disease in human populations. Although data from intervention-based randomized trials is scarce, there is some indication that exercise may confer protection against age-related deficits in cognitive function. Data from animal models suggests that exercise, in the form of voluntary wheel running, is associated with reduced amyloid deposition and enhanced clearance of amyloid beta, the major constituent of plaques in Alzheimer's disease. Treadmill exercise has also been shown to ameliorate the accumulation of phosphorylated tau, an essential component of neurofibrillary tangles in Alzheimer's models. A common therapeutic theme arising from studies of exercise-induced neuroprotection in human populations and in animal models involves reduced inflammation in the central nervous system. In this respect, physical activity may promote neuronal resilience by reducing inflammation.

Association between Functional Capacity Decline and Nutritional Status Based on the Nutrition Screening Initiative Checklist: A 2-Year Cohort Study of Japanese Community-Dwelling Elderly.

PubMed

Sugiura, Yumiko; Tanimoto, Yoshimi; Imbe, Ayumi; Inaba, Yuiko; Sakai, Satoshi; Shishikura, Kanako; Tanimoto, Keiji; Hanafusa, Toshiaki

2016-01-01

To assess whether nutritional status based on the Nutrition Screening Initiative Checklist is useful for predicting functional capacity decline in community-dwelling Japanese elderly. This two-year observational cohort study included 536 community-dwelling Japanese (65 years and older at baseline) who were independent in both activities and instrumental activities of daily living. Demographic attributes, chronic illness, lifestyle-related habits, nutritional status, functional capacity, and anthropometric measurements were assessed, with decline in functional capacity used as the outcome measure. Subjects were classified into three groups as follows based on the Nutrition Screening Initiative Checklist: low (59.5%), moderate (23.7%), and high (16.8%) nutritional risk. Significant differences were found between nutritional status and the following four baseline variables: age, hypertension, cerebrovascular diseases, and current smoking. However, no significant differences were evident between nutritional status and sex, body mass index, diabetes, drinking habit, or exercise habit. Logistic regression analysis adjusted for age, sex, body mass index, hypertension, cerebrovascular diseases and smoking habit showed that the high nutritional risk group was significantly associated with a decline in both activities of daily living (odds ratio: 4.96; 95% confidence interval (CI): 1.59-15.50) and instrumental activities of daily living (OR: 2.58; 95% CI: 1.31-5.06) compared with the low nutritional risk group. Poor nutritional status based on the Nutrition Screening Initiative Checklist was associated with a decline in functional capacity over a 2-year period in community-dwelling Japanese elderly. These results suggest that the Nutrition Screening Initiative Checklist is a suitable tool for predicting functional capacity decline in community-dwelling elderly.

Living actively in the face of impending death: constantly adjusting to bodily decline at the end-of-life.

PubMed

Morgan, Deidre D; Currow, David C; Denehy, Linda; Aranda, Sanchia A

2017-06-01

People with advanced cancer experience bodily change resulting in debilitating functional decline. Although inability to participate in everyday activities (occupation) contributes to profound suffering, limited research has examined the relationship between altered bodily experience (embodiment) and functional ability. The purpose of this study was to better understand the lived experience of functional decline for people with advanced cancer living at home. Indepth interviews were conducted with 10 community dwelling people with advanced cancer about their bodily experiences of functional decline. This study employed a pragmatic qualitative approach, informed by hermeneutic phenomenology. People described living with rapidly disintegrating bodies and how this affected their ability to participate in everyday activities. Analysis identified themes which were evaluated against conceptual frameworks of 'occupation' and 'embodiment'. People experienced a shifting sense of self. They had to continuously reinterpret changing bodies. Previously automatic movements became disjointed and effortful. Simple actions like standing or getting out of bed required increasing concentration. Relentless bodily breakdown disrupted peoples' relationship with time, hindering their ability, but not their desire, to participate in everyday activities. Contending with this deterioration is the work of adaptation to functional decline at the end-of-life. This study highlights the role active participation in everyday activities plays in mediating adjustment to functional decline. These findings challenge us to look beyond palliation of physical symptoms and psychospiritual care as ends in themselves. Symptom control and palliation should be viewed as mechanisms to optimise active participation in essential and valued activities. 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.

Can psychosocial work conditions protect against age-related cognitive decline? Results from a systematic review.

PubMed

Nexø, Mette Andersen; Meng, Annette; Borg, Vilhelm

2016-07-01

According to the use it or lose it hypothesis, intellectually stimulating activities postpone age-related cognitive decline. A previous systematic review concluded that a high level of mental work demands and job control protected against cognitive decline. However, it did not distinguish between outcomes that were measured as cognitive function at one point in time or as cognitive decline. Our study aimed to systematically review which psychosocial working conditions were prospectively associated with high levels of cognitive function and/or changes in cognitive function over time. Articles were identified by a systematic literature search (MEDLINE, Web of Science (WOS), PsycNET, Occupational Safety and Health (OSH)). We included only studies with longitudinal designs examining the impact of psychosocial work conditions on outcomes defined as cognitive function or changes in cognitive function. Two independent reviewers compared title-abstract screenings, full-text screenings and quality assessment ratings. Eleven studies were included in the final synthesis and showed that high levels of mental work demands, occupational complexity or job control at one point in time were prospectively associated with higher levels of cognitive function in midlife or late life. However, the evidence to clarify whether these psychosocial factors also affected cognitive decline was insufficient, conflicting or weak. It remains speculative whether job control, job demands or occupational complexity can protect against cognitive decline. Future studies using methodological advancements can reveal whether workers gain more cognitive reserve in midlife and late life than the available evidence currently suggests. The public health implications of a previous review should thereby be redefined accordingly. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Neurogranin as a predictor of memory and executive function decline in MCI patients.

PubMed

Headley, Alison; De Leon-Benedetti, Andres; Dong, Chuanhui; Levin, Bonnie; Loewenstein, David; Camargo, Christian; Rundek, Tatjana; Zetterberg, Henrik; Blennow, Kaj; Wright, Clinton B; Sun, Xiaoyan

2018-03-06

To determine whether high CSF levels of neurogranin (Ng) predict longitudinal decline in memory and executive function during early-stage Alzheimer disease (AD). Baseline levels of CSF Ng were studied in relation to cross-sectional and longitudinal cognitive performance over 8 years. Data were obtained from the Alzheimer's Disease Neuroimaging Initiative database, and participants with normal cognition (n = 111) and mild cognitive impairment (MCI) (n = 193) were included. High levels of CSF Ng were associated with poor baseline memory scores (β = -0.21, p < 0.0001). CSF Ng predicted both memory and executive function decline over time (β = -0.0313, p = 0.0068 and β = -0.0346, p = 0.0169, respectively) independently of age, sex, education, and APOE ε4 status. When the rate of decline by tertiles was examined, CSF Ng was a level-dependent predictor of memory function, whereby the group with highest levels of Ng showed the fastest rates of decline in both memory and executive function. When examined separately, elevated Ng was associated with cognitive decline in participants with MCI but not in those with normal cognition. The levels of CSF Ng were not associated with cognitive measures when tau and amyloid 42 (Aβ 42 ) were controlled for in these analyses. High CSF Ng associates with poor memory scores in participants with MCI cross-sectionally and with poor memory and executive function longitudinally. The association of Ng with cognitive measures disappears when tau and Aβ 42 are included in the statistical models. Our findings suggest that CSF Ng may serve as a biomarker of cognition. Synaptic dysfunction contributes to cognitive impairment in early-stage AD. © 2018 American Academy of Neurology.

The effect of modifiable healthy practices on higher-level functional capacity decline among Japanese community dwellers.

PubMed

Otsuka, Rei; Nishita, Yukiko; Tange, Chikako; Tomida, Makiko; Kato, Yuki; Nakamoto, Mariko; Ando, Fujiko; Shimokata, Hiroshi; Suzuki, Takao

2017-03-01

This study aimed to clarify the effects of the accumulation of 8 modifiable practices related to health, including smoking, alcohol drinking, physical activity, sleeping hours, body mass index, dietary diversity, ikigai (life worth living), and health checkup status, on higher-level functional capacity decline among Japanese community dwellers. Data were derived from the National Institute for Longevity Sciences - Longitudinal Study of Aging. Subjects comprised 1269 men and women aged 40 to 79 years at baseline (1997-2000) who participated in a follow-up postal survey (2013). Higher-level functional capacity was measured using the Tokyo Metropolitan Institute of Gerontology Index of Competence (total score and 3 subscales: instrumental self-maintenance, intellectual activity, and social role). The odds ratio (OR) and 95% confidence interval (CI) for a decline in higher-level functional capacity in the follow-up study according to the total number of healthy practices were analyzed using the lowest category as a reference. Multivariate adjusted ORs (95% CIs) for the total score of higher-level functional capacity, which declined according to the total number of healthy practices (0-4, 5-6, 7-8 groups) were 1.00 (reference), 0.63 (0.44-0.92), and 0.54 (0.31-0.94). For the score of social role decline, multivariate adjusted ORs (95% CIs) were 1.00 (reference), 0.62 (0.40-0.97), and 0.46 (0.23-0.90), respectively (P for trend = 0.04). Having more modifiable healthy practices, especially in social roles, may protect against a decline in higher-level functional capacity among middle-aged and elderly community dwellers in Japan.

Reciprocal Interaction of Dendrite Geometry and Nuclear Calcium-VEGFD Signaling Gates Memory Consolidation and Extinction.

PubMed

Hemstedt, Thekla J; Bengtson, C Peter; Ramírez, Omar; Oliveira, Ana M M; Bading, Hilmar

2017-07-19

Nuclear calcium is an important signaling end point in synaptic excitation-transcription coupling that is critical for long-term neuroadaptations. Here, we show that nuclear calcium acting via a target gene, VEGFD, is required for hippocampus-dependent fear memory consolidation and extinction in mice. Nuclear calcium-VEGFD signaling upholds the structural integrity and complexity of the dendritic arbor of CA1 neurons that renders those cells permissive for the efficient generation of synaptic input-evoked nuclear calcium transients driving the expression of plasticity-related genes. Therefore, the gating of memory functions rests on the reciprocally reinforcing maintenance of an intact dendrite geometry and a functional synapse-to-nucleus communication axis. In psychiatric and neurodegenerative disorders, therapeutic application of VEGFD may help to stabilize dendritic structures and network connectivity, which may prevent cognitive decline and could boost the efficacy of extinction-based exposure therapies. SIGNIFICANCE STATEMENT This study uncovers a reciprocal relationship between dendrite geometry, the ability to generate nuclear calcium transients in response to synaptic inputs, and the subsequent induction of expression of plasticity-related and dendritic structure-preserving genes. Insufficient nuclear calcium signaling in CA1 hippocampal neurons and, consequently, reduced expression of the nuclear calcium target gene VEGFD, a dendrite maintenance factor, leads to reduced-complexity basal dendrites of CA1 neurons, which severely compromises the animals' consolidation of both memory and extinction memory. The structure-protective function of VEGFD may prove beneficial in psychiatric disorders as well as neurodegenerative and aging-related conditions that are associated with loss of neuronal structures, dysfunctional excitation-transcription coupling, and cognitive decline. Copyright © 2017 the authors 0270-6474/17/376946-10$15.00/0.

Climate-driven diversity change in annual grasslands: Drought plus deluge does not equal normal.

PubMed

Harrison, Susan P; LaForgia, Marina L; Latimer, Andrew M

2018-04-01

Climate forecasts agree that increased variability and extremes will tend to reduce the availability of water in many terrestrial ecosystems. Increasingly severe droughts may be exacerbated both by warmer temperatures and by the relative unavailability of water that arrives in more sporadic and intense rainfall events. Using long-term data and an experimental water manipulation, we examined the resilience of a heterogeneous annual grassland community to a prolonged series of dry winters that led to a decline in plant species richness (2000-2014), followed by a near-record wet winter (2016-2017), a climatic sequence that broadly resembles the predicted future in its high variability. In our 80, 5-m 2 observational plots, species richness did not recover in response to the wet winter, and the positive relationship of richness to annual winter rainfall thus showed a significant weakening trend over the 18-year time period. In experiments on 100, 1-m 2 plots, wintertime water supplementation increased and drought shelters decreased the seedling survival and final individual biomass of native annual forbs, the main functional group contributing to the observed long-term decline in richness. Water supplementation also increased the total cover of native annual forbs, but only increased richness within nested subplots to which seeds were also added. We conclude that prolonged dry winters, by increasing seedling mortality and reducing growth of native forbs, may have diminished the seedbank and thus the recovery potential of diversity in this community. However, the wet winter and the watering treatment did cause recovery of the community mean values of a key functional trait (specific leaf area, an indicator of drought intolerance), suggesting that some aggregate community properties may be stabilized by functional redundancy among species. © 2017 John Wiley & Sons Ltd.

Societal and Family Lifetime Cost of Dementia: Implications for Policy.

PubMed

Jutkowitz, Eric; Kane, Robert L; Gaugler, Joseph E; MacLehose, Richard F; Dowd, Bryan; Kuntz, Karen M

2017-10-01

To estimate the cost of dementia and the extra cost of caring for someone with dementia over the cost of caring for someone without dementia. We developed an evidence-based mathematical model to simulate disease progression for newly diagnosed individuals with dementia. Data-driven trajectories of cognition, function, and behavioral and psychological symptoms were used to model disease progression and predict costs. Using modeling, we evaluated lifetime and annual costs of individuals with dementia, compared costs of those with and without clinical features of dementia, and evaluated the effect of reducing functional decline or behavioral and psychological symptoms by 10% for 12 months (implemented when Mini-Mental State Examination score ≤21). Mathematical model. Representative simulated U.S. incident dementia cases. Value of informal care, out-of-pocket expenditures, Medicaid expenditures, and Medicare expenditures. From time of diagnosis (mean age 83), discounted total lifetime cost of care for a person with dementia was $321,780 (2015 dollars). Families incurred 70% of the total cost burden ($225,140), Medicaid accounted for 14% ($44,090), and Medicare accounted for 16% ($52,540). Costs for a person with dementia over a lifetime were $184,500 greater (86% incurred by families) than for someone without dementia. Total annual cost peaked at $89,000, and net cost peaked at $72,400. Reducing functional decline or behavioral and psychological symptoms by 10% resulted in $3,880 and $680 lower lifetime costs than natural disease progression. Dementia substantially increases lifetime costs of care. Long-lasting, effective interventions are needed to support families because they incur the most dementia cost. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

The use of the indicator fluo-5N to measure sarcoplasmic reticulum calcium in single muscle fibres of the cane toad

PubMed Central

Kabbara, Akram A; Allen, David G

2001-01-01

Single fibres from the lumbrical muscles of the cane toad (Bufo marinus) were incubated in fluo-5N AM for 2 h at 35 °C in order to load the indicator into the sarcoplasmic reticulum. Fluo-5N is a low-affinity calcium indicator (KCa 90 μm). Successful sarcoplasmic reticulum (SR) loading was indicated by a fluorescence signal that declined during contraction. Confocal microscopy showed that the dye loaded principally in lines perpendicular to the long axis of the fibre that repeated each sarcomere. This is consistent with much of the dye residing in the SR. To establish the site of loading, fibres were exposed to 30 mm caffeine in the presence of 20 μm 2,5-di(tert-butyl)1,4-hydroquinone (TBQ, an SR pump inhibitor) which should release most Ca2+ from the SR; this procedure reduced the fluorescence to 46 ± 4 % of the control value. To determine how much indicator was in the myoplasm, fibres were exposed to 100 μg ml−1 saponin which permeabilizes the surface membrane; saponin treatment reduced the fluorescence to 51 ± 2 % of the control value. During maximally activated tetani (100 Hz stimulation rate, 22 °C) the component of signal from the SR declined by 33 ± 4 %. During relaxation the SR signal recovered in two phases with time constants of 0.38 ± 0.14 s and 10.1 ± 1.7 s. Partially activated tetani (30 Hz stimulation rate) showed a smaller SR signal. Application of the SR Ca2+ pump inhibitor TBQ slowed the rate of recovery of the SR signal. Muscle fatigue was produced by repeated short tetani until tension was reduced to 50 %. The SR signal during the periods between tetani declined steadily and the SR Ca2+ signal was eventually reduced to 71 ± 8 % of the control signal. This signal recovered in two phases when the muscle was rested. An initial phase had a time constant of 1.7 ± 0.2 s so that by 20 s of recovery the SR Ca2+ signal was 86 ± 7 % of control; the second phase was slower and by 5 min the SR Ca2+ signal was back to control values (98 ± 5 % control). In addition the magnitude of the SR signal decline associated with each tetanus (Δ[Ca2+]SR) declined monotonically throughout fatigue and returned to control after 5 min recovery. This approach can monitor the SR Ca2+ concentration in normally functioning muscle fibres with good time resolution. The method confirms other approaches that show that the free Ca2+ available for release in the SR declines during fatigue. This reduction in [Ca2+]SR will contribute to the failure of Ca2+ delivery to the myofilaments which is an important cause of muscle fatigue. PMID:11432994

The use of the indicator fluo-5N to measure sarcoplasmic reticulum calcium in single muscle fibres of the cane toad.

PubMed

Kabbara, A A; Allen, D G

2001-07-01

1. Single fibres from the lumbrical muscles of the cane toad (Bufo marinus) were incubated in fluo-5N AM for 2 h at 35 degrees C in order to load the indicator into the sarcoplasmic reticulum. Fluo-5N is a low-affinity calcium indicator (K(Ca) 90 microM). Successful sarcoplasmic reticulum (SR) loading was indicated by a fluorescence signal that declined during contraction. 2. Confocal microscopy showed that the dye loaded principally in lines perpendicular to the long axis of the fibre that repeated each sarcomere. This is consistent with much of the dye residing in the SR. 3. To establish the site of loading, fibres were exposed to 30 mM caffeine in the presence of 20 microM 2,5-di(tert-butyl)1,4-hydroquinone (TBQ, an SR pump inhibitor) which should release most Ca(2+) from the SR; this procedure reduced the fluorescence to 46 +/- 4 % of the control value. To determine how much indicator was in the myoplasm, fibres were exposed to 100 microg ml(-1) saponin which permeabilizes the surface membrane; saponin treatment reduced the fluorescence to 51 +/- 2 % of the control value. 4. During maximally activated tetani (100 Hz stimulation rate, 22 degrees C) the component of signal from the SR declined by 33 +/- 4 %. During relaxation the SR signal recovered in two phases with time constants of 0.38 +/- 0.14 s and 10.1 +/- 1.7 s. Partially activated tetani (30 Hz stimulation rate) showed a smaller SR signal. Application of the SR Ca(2+) pump inhibitor TBQ slowed the rate of recovery of the SR signal. 5. Muscle fatigue was produced by repeated short tetani until tension was reduced to 50 %. The SR signal during the periods between tetani declined steadily and the SR Ca(2+) signal was eventually reduced to 71 +/- 8 % of the control signal. This signal recovered in two phases when the muscle was rested. An initial phase had a time constant of 1.7 +/- 0.2 s so that by 20 s of recovery the SR Ca(2+) signal was 86 +/- 7 % of control; the second phase was slower and by 5 min the SR Ca(2+) signal was back to control values (98 +/- 5 % control). In addition the magnitude of the SR signal decline associated with each tetanus (Delta[Ca(2+)](SR)) declined monotonically throughout fatigue and returned to control after 5 min recovery. 6. This approach can monitor the SR Ca(2+) concentration in normally functioning muscle fibres with good time resolution. The method confirms other approaches that show that the free Ca(2+) available for release in the SR declines during fatigue. This reduction in [Ca(2+)](SR) will contribute to the failure of Ca(2+) delivery to the myofilaments which is an important cause of muscle fatigue.

Exercise Promotes Healthy Aging of Skeletal Muscle.

PubMed

Cartee, Gregory D; Hepple, Russell T; Bamman, Marcas M; Zierath, Juleen R

2016-06-14

Primary aging is the progressive and inevitable process of bodily deterioration during adulthood. In skeletal muscle, primary aging causes defective mitochondrial energetics and reduced muscle mass. Secondary aging refers to additional deleterious structural and functional age-related changes caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes "healthy aging" by inducing modifications in skeletal muscle. Copyright © 2016 Elsevier Inc. All rights reserved.

A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis.

PubMed

King, Talmadge E; Bradford, Williamson Z; Castro-Bernardini, Socorro; Fagan, Elizabeth A; Glaspole, Ian; Glassberg, Marilyn K; Gorina, Eduard; Hopkins, Peter M; Kardatzke, David; Lancaster, Lisa; Lederer, David J; Nathan, Steven D; Pereira, Carlos A; Sahn, Steven A; Sussman, Robert; Swigris, Jeffrey J; Noble, Paul W

2014-05-29

In two of three phase 3 trials, pirfenidone, an oral antifibrotic therapy, reduced disease progression, as measured by the decline in forced vital capacity (FVC) or vital capacity, in patients with idiopathic pulmonary fibrosis; in the third trial, this end point was not achieved. We sought to confirm the beneficial effect of pirfenidone on disease progression in such patients. In this phase 3 study, we randomly assigned 555 patients with idiopathic pulmonary fibrosis to receive either oral pirfenidone (2403 mg per day) or placebo for 52 weeks. The primary end point was the change in FVC or death at week 52. Secondary end points were the 6-minute walk distance, progression-free survival, dyspnea, and death from any cause or from idiopathic pulmonary fibrosis. In the pirfenidone group, as compared with the placebo group, there was a relative reduction of 47.9% in the proportion of patients who had an absolute decline of 10 percentage points or more in the percentage of the predicted FVC or who died; there was also a relative increase of 132.5% in the proportion of patients with no decline in FVC (P<0.001). Pirfenidone reduced the decline in the 6-minute walk distance (P=0.04) and improved progression-free survival (P<0.001). There was no significant between-group difference in dyspnea scores (P=0.16) or in rates of death from any cause (P=0.10) or from idiopathic pulmonary fibrosis (P=0.23). However, in a prespecified pooled analysis incorporating results from two previous phase 3 trials, the between-group difference favoring pirfenidone was significant for death from any cause (P=0.01) and from idiopathic pulmonary fibrosis (P=0.006). Gastrointestinal and skin-related adverse events were more common in the pirfenidone group than in the placebo group but rarely led to treatment discontinuation. Pirfenidone, as compared with placebo, reduced disease progression, as reflected by lung function, exercise tolerance, and progression-free survival, in patients with idiopathic pulmonary fibrosis. Treatment was associated with an acceptable side-effect profile and fewer deaths. (Funded by InterMune; ASCEND ClinicalTrials.gov number, NCT01366209.).

Mechanisms of Age-Related Decline in Memory Search across the Adult Life Span

ERIC Educational Resources Information Center

Hills, Thomas T.; Mata, Rui; Wilke, Andreas; Samanez-Larkin, Gregory R.

2013-01-01

Three alternative mechanisms for age-related decline in memory search have been proposed, which result from either reduced processing speed (global slowing hypothesis), overpersistence on categories (cluster-switching hypothesis), or the inability to maintain focus on local cues related to a decline in working memory (cue-maintenance hypothesis).…

The effects of hypertension on the cerebral circulation

PubMed Central

Pires, Paulo W.; Dams Ramos, Carla M.; Matin, Nusrat

2013-01-01

Maintenance of brain function depends on a constant blood supply. Deficits in cerebral blood flow are linked to cognitive decline, and they have detrimental effects on the outcome of ischemia. Hypertension causes alterations in cerebral artery structure and function that can impair blood flow, particularly during an ischemic insult or during periods of low arterial pressure. This review will focus on the historical discoveries, novel developments, and knowledge gaps in 1) hypertensive cerebral artery remodeling, 2) vascular function with emphasis on myogenic reactivity and endothelium-dependent dilation, and 3) blood-brain barrier function. Hypertensive artery remodeling results in reduction in the lumen diameter and an increase in the wall-to-lumen ratio in most cerebral arteries; this is linked to reduced blood flow postischemia and increased ischemic damage. Many factors that are increased in hypertension stimulate remodeling; these include the renin-angiotensin-aldosterone system and reactive oxygen species levels. Endothelial function, vital for endothelium-mediated dilation and regulation of myogenic reactivity, is impaired in hypertension. This is a consequence of alterations in vasodilator mechanisms involving nitric oxide, epoxyeicosatrienoic acids, and ion channels, including calcium-activated potassium channels and transient receptor potential vanilloid channel 4. Hypertension causes blood-brain barrier breakdown by mechanisms involving inflammation, oxidative stress, and vasoactive circulating molecules. This exposes neurons to cytotoxic molecules, leading to neuronal loss, cognitive decline, and impaired recovery from ischemia. As the population ages and the incidence of hypertension, stroke, and dementia increases, it is imperative that we gain a better understanding of the control of cerebral artery function in health and disease. PMID:23585139

Differential changes in functional disability and pain intensity over the course of psychological treatment for children with chronic pain

PubMed Central

Lynch-Jordan, Anne M.; Sil, Soumitri; Peugh, James; Cunningham, Natoshia; Kashikar-Zuck, Susmita; Goldschneider, Kenneth R.

2015-01-01

Patients presenting for treatment of chronic pain often believe that pain reduction must be achieved before returning to normal functioning. However, treatment programs for chronic pain typically take a rehabilitative approach, emphasizing decreasing pain-related disability first with the expectation that pain reduction will follow. This information is routinely provided to patients, yet no studies have systematically examined the actual trajectories of pain and disability in a clinical care setting. In this study of youth with chronic pain (N = 94, 8 to 18 years), it was hypothesized that 1) functional disability and pain would decrease over the course of psychological treatment for chronic pain and 2) functional disability would decrease more quickly than pain intensity. Participants received cognitive behavioral therapy (CBT) for pain management (M = 5.6 sessions) plus standard medical care. The Functional Disability Inventory and a Numeric Rating Scale of average pain intensity were completed by the child at every CBT session. Hierarchical linear modeling was conducted to examine the longitudinal trajectories of disability and pain. Standardized estimates of the slopes of change were obtained to test differences in rates of change between pain and disability. Results showed an overall significant decline in functional disability over time. Although pain scores reduced slightly from pretreatment to posttreatment, the longitudinal decline over treatment was not statistically significant. As expected, the rate of change of disability was significantly more rapid than pain. Evidence for variability in treatment response was noted, suggesting the need for additional research into individual trajectories of change in pediatric pain treatment. PMID:24954165