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Sample records for age-associated cognitive decline

  1. Enhanced defense against mitochondrial hydrogen peroxide attenuates age-associated cognition decline.

    PubMed

    Chen, Liuji; Na, Ren; Ran, Qitao

    2014-11-01

    Increased mitochondrial hydrogen peroxide (H2O2) is associated with Alzheimer's disease and brain aging. Peroxiredoxin 3 (Prdx3) is the key mitochondrial antioxidant defense enzyme in detoxifying H2O2. To investigate the importance of mitochondrial H2O2 in age-associated cognitive decline, we compared cognition between aged (17-19 months) APP transgenic mice and APP/Prdx3 double transgenic mice (dTG) and between old (24 months) wild-type mice and Prdx3 transgenic mice (TG). Compared with aged APP mice, aged dTG mice showed improved cognition that was correlated with reduced brain amyloid beta levels and decreased amyloid beta production. Old TG mice also showed significantly increased cognitive ability compared with old wild-type mice. Both aged dTG mice and old TG mice had reduced mitochondrial oxidative stress and increased mitochondrial function. Moreover, CREB signaling, a signaling pathway important for cognition was enhanced in both aged dTG mice and old TG mice. Thus, our results indicate that mitochondrial H2O2 is a key culprit of age-associated cognitive impairment, and that a reduction of mitochondrial H2O2 could improve cognition by maintaining mitochondrial health and enhancing CREB signaling.

  2. Age-associated Cognitive Decline: Insights into Molecular Switches and Recovery Avenues

    PubMed Central

    Konar, Arpita; Singh, Padmanabh; Thakur, Mahendra K.

    2016-01-01

    Age-associated cognitive decline is an inevitable phenomenon that predisposes individuals for neurological and psychiatric disorders eventually affecting the quality of life. Scientists have endeavored to identify the key molecular switches that drive cognitive decline with advancing age. These newly identified molecules are then targeted as recovery of cognitive aging and related disorders. Cognitive decline during aging is multi-factorial and amongst several factors influencing this trajectory, gene expression changes are pivotal. Identifying these genes would elucidate the neurobiological underpinnings as well as offer clues that make certain individuals resilient to withstand the inevitable age-related deteriorations. Our laboratory has focused on this aspect and investigated a wide spectrum of genes involved in crucial brain functions that attribute to senescence induced cognitive deficits. We have recently identified master switches in the epigenome regulating gene expression alteration during brain aging. Interestingly, these factors when manipulated by chemical or genetic strategies successfully reverse the age-related cognitive impairments. In the present article, we review findings from our laboratory and others combined with supporting literary evidences on molecular switches of brain aging and their potential as recovery targets. PMID:27114845

  3. [Diabetes mellitus and cognitive decline].

    PubMed

    Iglseder, Bernhard

    2011-11-01

    From large epidemiological studies, it has been demonstrated that diabetes mellitus is a risk factor for cognitive decline: Compared to healthy controls, patients with diabetes perform worse on cognitive tests, they experience a pronounced cognitive decline over time and have a higher incidence of dementia. Mechanisms contributing to cognitive decline include vascular damage, negative consequences of hypo- and hyperglycemia, and various dysfunctions in insulin action, summarized as insulin resistance. Possible targets for prevention and treatment of cognitive decline have attracted scientific attention.

  4. Aging-associated formaldehyde-induced norepinephrine deficiency contributes to age-related memory decline.

    PubMed

    Mei, Yufei; Jiang, Chun; Wan, You; Lv, Jihui; Jia, Jianping; Wang, Xiaomin; Yang, Xu; Tong, Zhiqian

    2015-08-01

    A norepinephrine (NE) deficiency has been observed in aged rats and in patients with Alzheimer's disease and is thought to cause cognitive disorder. Which endogenous factor induces NE depletion, however, is largely unknown. In this study, we investigated the effects of aging-associated formaldehyde (FA) on the inactivation of NE in vitro and in vivo, and on memory behaviors in rodents. The results showed that age-related DNA demethylation led to hippocampal FA accumulation, and when this occurred, the hippocampal NE content was reduced in healthy male rats of different ages. Furthermore, biochemical analysis revealed that FA rapidly inactivated NE in vitro and that an intrahippocampal injection of FA markedly reduced hippocampal NE levels in healthy adult rats. Unexpectedly, an injection of FA (at a pathological level) or 6-hydroxydopamine (6-OHDA, a NE depletor) can mimic age-related NE deficiency, long-term potentiation (LTP) impairments, and spatial memory deficits in healthy adult rats. Conversely, an injection of NE reversed age-related deficits in both LTP and memory in aged rats. In agreement with the above results, the senescence-accelerated prone 8 (SAMP8) mice also exhibited a severe deficit in LTP and memory associated with a more severe NE deficiency and FA accumulation, when compared with the age-matched, senescence-resistant 1 (SAMR1) mice. Injection of resveratrol (a natural FA scavenger) or NE into SAMP8 mice reversed FA accumulation and NE deficiency and restored the magnitude of LTP and memory. Collectively, these findings suggest that accumulated FA is a critical endogenous factor for aging-associated NE depletion and cognitive decline.

  5. Inhibition of CaMKK2 Reverses Age-Associated Decline in Bone Mass

    PubMed Central

    Pritchard, Zachary J.; Cary, Rachel L.; Yang, Chang; Novack, Deborah V.; Voor, Michael J.; Sankar, Uma

    2016-01-01

    Decline in bone formation is a major contributing factor to the loss of bone mass associated with aging. We previously showed that the genetic ablation of the tissue-restricted and multifunctional Ca2+/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) stimulates trabecular bone mass accrual, mainly by promoting anabolic pathways and inhibiting catabolic pathways of bone remodeling. In this study, we investigated whether inhibition of this kinase using its selective cell-permeable inhibitor STO-609 will stimulate bone formation in 32 week old male WT mice and reverse age-associated of decline in bone volume and strength. Tri-weekly intraperitoneal injections of saline or STO-609 (10 μM) were performed for six weeks followed by metabolic labeling with calcein and alizarin red. New bone formation was assessed by dynamic histomorphometry whereas micro-computed tomography was employed to measure trabecular bone volume, microarchitecture and femoral mid-shaft geometry. Cortical and trabecular bone biomechanical properties were assessed using three-point bending and punch compression methods respectively. Our results reveal that as they progress from 12 to 32 weeks of age, WT mice sustain a significant decline in trabecular bone volume, microarchitecture and strength as well as cortical bone strength. However, treatment of the 32 week old WT mice with STO-609 stimulated apposition of new bone and completely reversed the age-associated decrease in bone volume, quality, as well as trabecular and cortical bone strength. We also observed that regardless of age, male Camkk2−/− mice possessed significantly elevated trabecular bone volume, microarchitecture and compressive strength as well as cortical bone strength compared to age-matched WT mice, implying that the chronic loss of this kinase attenuates age-associated decline in bone mass. Further, whereas STO-609 treatment and/or the absence of CaMKK2 significantly enhanced the femoral midshaft geometry, the

  6. The influence of soy-derived phosphatidylserine on cognition in age-associated memory impairment.

    PubMed

    Jorissen, B L; Brouns, F; Van Boxtel, M P; Ponds, R W; Verhey, F R; Jolles, J; Riedel, W J

    2001-01-01

    Phosphatidylserine (PS) is a phospholipid widely sold as a nutritional supplement. PS has been claimed to enhance neuronal membrane function and hence cognitive function, especially in the elderly. We report the results of a clinical trial of soybean-derived PS (S-PS) in aging subjects with memory complaints. Subjects were 120 elderly (> 57 years) of both sexes who fulfilled the more stringent criteria for age-associated memory impairment (AAMI); some also fulfilled the criteria for age-associated cognitive decline. Subjects were allocated at random to one of the three treatment groups: placebo, 300mg S-PS daily, or 600mg S-PS daily. Assessments were carried out at baseline, after 6 and 12 weeks of treatment, and after a wash-out period of 3 weeks. Tests of learning and memory, choice reaction time, planning and attentional functions were administered at each assessment. Delayed recall and recognition of a previously learned word list comprised the primary outcome measures. No significant differences were found in any of the outcome variables between the treatment groups. There were also no significant interactions between treatment and 'severity of memory complaints'. In conclusion, a daily supplement of S-PS does not affect memory or other cognitive functions in older individuals with memory complaints. PMID:11842880

  7. 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.

  8. Dietary Factors and Cognitive Decline

    PubMed Central

    Smith, P.J.; Blumenthal, J.A.

    2015-01-01

    Cognitive decline is an increasingly important public health problem, with more than 100 million adults worldwide projected to develop dementia by 2050. Accordingly, there has been an increased interest in preventive strategies that diminish this risk. It has been recognized that lifestyle factors including dietary patterns, may be important in the prevention of cognitive decline and dementia in later life. Several dietary components have been examined, including antioxidants, fatty acids, and B vitamins. In addition, whole dietary eating plans, including the Mediterranean diet (MeDi), and the Dietary Approaches to Stop Hypertension (DASH) diet, with and without weight loss, have become areas of increasing interest. Although prospective epidemiological studies have observed that antioxidants, fatty acids, and B vitamins are associated with better cognitive functioning, randomized clinical trials have generally failed to confirm the value of any specific dietary component in improving neurocognition. Several randomized trials have examined the impact of changing ‘whole’ diets on cognitive outcomes. The MeDi and DASH diets offer promising preliminary results, but data are limited and more research in this area is needed. PMID:26900574

  9. Role of blood volume in the age-associated decline in peak oxygen uptake in humans.

    PubMed

    Ito, T; Takamata, A; Yaegashi, K; Itoh, T; Yoshida, T; Kawabata, T; Kimura, M; Morimoto, T

    2001-10-01

    It has been reported that maximal oxygen uptake (VO(2 max)) is linearly correlated with blood volume (BV) in young people and that there is a reduction in VO(2 max) with aging. To examine the involvement of BV in the reduction of VO(2 max), we used an incremental cycle ergometer protocol in a semi-recumbent position to determine the relationship between peak oxygen uptake (VO(2 peak)) and BV in older subjects (69.1 +/- 1.0 years; n = 22), then compared that relationship with that in young subjects (22.3 +/- 0.5 years; n = 31). In the present study, VO(2 peak) and BV were significantly lower in the older subjects, compared with those in the young subjects. A linear correlation was demonstrated between the VO(2 peak) and BV in both the older (r = 0.705; p < 0.001) and the young (r = 0.681; p < 0.001) subjects within the groups. However, an analysis of covariance with BV as a covariate revealed that VO(2 peak) at a given BV was smaller in the older subjects than in the young subjects (p < 0.001), i.e., graphically, the regression line determined for the older subjects showed a downward shift. The decreased peak heart rate as a result of aging (153 +/- 3 beats/min in the older vs. 189 +/- 2 beats/min in the young subjects) contributed partly to this downward shift. These results suggest that the BV is an important determinant factor for VO(2 peak), especially within an age group, and that the age-associated decline of VO(2 peak) is also, to a relatively larger degree, because of factors other than BV and heart rate.

  10. Perioperative Cognitive Decline in the Aging Population

    PubMed Central

    Terrando, Niccolò; Brzezinski, Marek; Degos, Vincent; Eriksson, Lars I.; Kramer, Joel H.; Leung, Jacqueline M.; Miller, Bruce L.; Seeley, William W.; Vacas, Susana; Weiner, Michael W.; Yaffe, Kristine; Young, William L.; Xie, Zhongcong; Maze, Mervyn

    2011-01-01

    Elderly patients who have an acute illness or who undergo surgery often experience cognitive decline. The pathophysiologic mechanisms that cause neurodegeneration resulting in cognitive decline, including protein deposition and neuroinflammation, also play a role in animal models of surgery-induced cognitive decline. With the aging of the population, surgical candidates of advanced age with underlying neurodegeneration are encountered more often, raising concerns that, in patients with this combination, cognitive function will precipitously decline postoperatively. This special article is based on a symposium that the University of California, San Francisco, convened to explore the contributions of surgery and anesthesia to the development of cognitive decline in the aged patient. A road map to further elucidate the mechanisms, diagnosis, risk factors, mitigation, and treatment of postoperative cognitive decline in the elderly is provided. PMID:21878601

  11. Toward an alternative representation for disentangling age-associated differences in general and specific cognitive abilities.

    PubMed

    Schmiedek, Florian; Li, Shu-Chen

    2004-03-01

    Much of cognitive aging research concerns whether age-associated differences in various cognitive performances can be accounted for by general explanatory constructs or whether several specific processes are involved. Structural equation models have been proposed to disentangle general and specific age-associated differences in cognitive performance. This article demonstrates that existing methods that employ stepwise procedures run the risk of biasing results toward general resource accounts. An alternative model representation (i.e., the nested factor model) is proposed that affords simultaneous estimation of general and specific effects and is applied to data from the Berlin Aging Study. Using the nested factor model allowed the authors to detect that specific group factors explained 25% of the age-associated variance in addition to the general factor.

  12. Atrial Fibrillation, Cognitive Decline And Dementia

    PubMed Central

    Alonso, Alvaro; Arenas de Larriva, Antonio P.

    2016-01-01

    Atrial fibrillation (AF) is a common cardiac arrhythmia. Growing evidence supports a role for AF as a risk factor for cognitive decline and dementia. In this review, we summarize epidemiologic observations linking AF with cognitive outcomes, describe potential mechanisms, and explore the impact of AF treatments on cognitive decline and dementia. Community-based, observational studies show a consistent higher rate of cognitive decline and risk of dementia in persons with AF. These associations are partly due to the increased risk of clinical stroke in AF, but other mechanisms, including incidence of silent cerebral infarcts, microbleeds, and cerebral hypoperfusion, are likely additional contributors. Adequate oral anticoagulation and improved management of the overall cardiovascular risk profile in persons with AF offer the promise of reducing the impact of AF on cognitive decline and dementia. PMID:27547248

  13. Periodontitis and Cognitive Decline in Alzheimer's Disease.

    PubMed

    Ide, Mark; Harris, Marina; Stevens, Annette; Sussams, Rebecca; Hopkins, Viv; Culliford, David; Fuller, James; Ibbett, Paul; Raybould, Rachel; Thomas, Rhodri; Puenter, Ursula; Teeling, Jessica; Perry, V Hugh; Holmes, Clive

    2016-01-01

    Periodontitis is common in the elderly and may become more common in Alzheimer's disease because of a reduced ability to take care of oral hygiene as the disease progresses. Elevated antibodies to periodontal bacteria are associated with an increased systemic pro-inflammatory state. Elsewhere raised serum pro-inflammatory cytokines have been associated with an increased rate of cognitive decline in Alzheimer's disease. We hypothesized that periodontitis would be associated with increased dementia severity and a more rapid cognitive decline in Alzheimer's disease. We aimed to determine if periodontitis in Alzheimer's disease is associated with both increased dementia severity and cognitive decline, and an increased systemic pro inflammatory state. In a six month observational cohort study 60 community dwelling participants with mild to moderate Alzheimer's Disease were cognitively assessed and a blood sample taken for systemic inflammatory markers. Dental health was assessed by a dental hygienist, blind to cognitive outcomes. All assessments were repeated at six months. The presence of periodontitis at baseline was not related to baseline cognitive state but was associated with a six fold increase in the rate of cognitive decline as assessed by the ADAS-cog over a six month follow up period. Periodontitis at baseline was associated with a relative increase in the pro-inflammatory state over the six month follow up period. Our data showed that periodontitis is associated with an increase in cognitive decline in Alzheimer's Disease, independent to baseline cognitive state, which may be mediated through effects on systemic inflammation. PMID:26963387

  14. Periodontitis and Cognitive Decline in Alzheimer's Disease.

    PubMed

    Ide, Mark; Harris, Marina; Stevens, Annette; Sussams, Rebecca; Hopkins, Viv; Culliford, David; Fuller, James; Ibbett, Paul; Raybould, Rachel; Thomas, Rhodri; Puenter, Ursula; Teeling, Jessica; Perry, V Hugh; Holmes, Clive

    2016-01-01

    Periodontitis is common in the elderly and may become more common in Alzheimer's disease because of a reduced ability to take care of oral hygiene as the disease progresses. Elevated antibodies to periodontal bacteria are associated with an increased systemic pro-inflammatory state. Elsewhere raised serum pro-inflammatory cytokines have been associated with an increased rate of cognitive decline in Alzheimer's disease. We hypothesized that periodontitis would be associated with increased dementia severity and a more rapid cognitive decline in Alzheimer's disease. We aimed to determine if periodontitis in Alzheimer's disease is associated with both increased dementia severity and cognitive decline, and an increased systemic pro inflammatory state. In a six month observational cohort study 60 community dwelling participants with mild to moderate Alzheimer's Disease were cognitively assessed and a blood sample taken for systemic inflammatory markers. Dental health was assessed by a dental hygienist, blind to cognitive outcomes. All assessments were repeated at six months. The presence of periodontitis at baseline was not related to baseline cognitive state but was associated with a six fold increase in the rate of cognitive decline as assessed by the ADAS-cog over a six month follow up period. Periodontitis at baseline was associated with a relative increase in the pro-inflammatory state over the six month follow up period. Our data showed that periodontitis is associated with an increase in cognitive decline in Alzheimer's Disease, independent to baseline cognitive state, which may be mediated through effects on systemic inflammation.

  15. Can exercise prevent cognitive decline?

    PubMed

    Behrman, Sophie; Ebmeier, Klaus P

    2014-01-01

    As the tolerability of pharmacological agents decreases with age, exercise may be particularly helpful as a possible treatment or stabiliser of mood and cognitive function in older age. Exercise has been most commonly evaluated for the treatment of depression. Exercise interventions designed primarily for treatment of physical conditions in the elderly do appear to confer psychological benefits as well, with reduction in depressive symptoms over the course of treatment. The effects of exercise on reducing depressive symptoms are not dissimilar to the effects of antidepressant drugs and cognitive behaviour therapy. Exercise may be a useful low-tech intervention for people with mild to moderate depression. In particular, exercise may be helpful in the elderly and in patients who have had insufficient response to, or are intolerant of, pharmacotherapy. Mastery of a new skill and positive feedback from others may increase feelings of self-esteem and improve mood. Exercise may distract participants from persistent negative thoughts. Exercise has been shown to improve executive function acutely in adults of all ages. It is possible that dance routines or other exercise regimens requiring some cognitive input may confer additional benefit to cognitive function. Exercise has a moderate effect on the ability of people with dementia to perform activities of daily living and may improve cognitive function. Midlife exercise may also have an impact on later cognitive function. PMID:24617099

  16. Role of forkhead box protein A3 in age-associated metabolic decline

    PubMed Central

    Ma, Xinran; Xu, Lingyan; Gavrilova, Oksana; Mueller, Elisabetta

    2014-01-01

    Aging is associated with increased adiposity and diminished thermogenesis, but the critical transcription factors influencing these metabolic changes late in life are poorly understood. We recently demonstrated that the winged helix factor forkhead box protein A3 (Foxa3) regulates the expansion of visceral adipose tissue in high-fat diet regimens; however, whether Foxa3 also contributes to the increase in adiposity and the decrease in brown fat activity observed during the normal aging process is currently unknown. Here we report that during aging, levels of Foxa3 are significantly and selectively up-regulated in brown and inguinal white fat depots, and that midage Foxa3-null mice have increased white fat browning and thermogenic capacity, decreased adipose tissue expansion, improved insulin sensitivity, and increased longevity. Foxa3 gain-of-function and loss-of-function studies in inguinal adipose depots demonstrated a cell-autonomous function for Foxa3 in white fat tissue browning. Furthermore, our analysis revealed that the mechanisms of Foxa3 modulation of brown fat gene programs involve the suppression of peroxisome proliferator activated receptor γ coactivtor 1 α (PGC1α) levels through interference with cAMP responsive element binding protein 1-mediated transcriptional regulation of the PGC1α promoter. Overall, our data demonstrate a role for Foxa3 in energy expenditure and in age-associated metabolic disorders. PMID:25225406

  17. Oxidative stress in the etiology of age-associated decline in glucose metabolism.

    PubMed

    Salmon, Adam B

    2012-01-01

    One of the most common pathologies in aging humans is the development of glucose metabolism dysfunction. The high incidence of metabolic dysfunction, in particular type 2 diabetes mellitus, is a significant health and economic burden on the aging population. However, the mechanisms that regulate this age-related physiological decline, and thus potential preventative treatments, remain elusive. Even after accounting for age-related changes in adiposity, lean mass, blood lipids, etc., aging is an independent factor for reduced glucose tolerance and increased insulin resistance. Oxidative stress has been shown to have significant detrimental impacts on the regulation of glucose homeostasis in vitro and in vivo. Furthermore, oxidative stress has been shown to be modulated by age and diet in several model systems. This review provides an overview of these data and addresses whether increases in oxidative stress with aging may be a primary determinant of age-related metabolic dysfunction.

  18. Age-associated decline in mitochondrial respiration and electron transport in Drosophila melanogaster

    PubMed Central

    2005-01-01

    The principal objective of the present study was to identify specific alterations in mitochondrial respiratory functions during the aging process. Respiration rates and the activities of electron transport chain complexes were measured at various ages in mitochondria isolated from thoraces of the fruit fly, Drosophila melanogaster, which consist primarily of flight muscles. The rates of state 3 respiration (ADP-stimulated), RCRs (respiratory control ratios) and uncoupled respiration rates decreased significantly as a function of age, using either NAD+- or FAD-linked substrates; however, there were no differences in state 4 respiration (ADP-depleted) rates. There was also a significant age-related decline in the activity of cytochrome c oxidase (complex IV), but not of the other mitochondrial oxidoreductases examined. Exposure of mitochondria isolated from young flies to low doses of KCN or NaAz (sodium azide), complex IV inhibitors, decreased cytochrome c oxidase activity and increased the production of H2O2. Collectively, these results support the hypothesis that impairment of mitochondrial respiration may be a causal factor in the aging process, and that such impairment may result from and contribute to increased H2O2 production in vivo. PMID:15853766

  19. Neural mechanisms of ageing and cognitive decline

    PubMed Central

    Bishop, Nicholas A.; Lu, Tao; Yankner, Bruce A.

    2010-01-01

    During the past century, treatments for the diseases of youth and middle age have helped raise life expectancy significantly. However, cognitive decline has emerged as one of the greatest health threats of old age, with nearly 50% of adults over the age of 85 afflicted with Alzheimer’s disease. Developing therapeutic interventions for such conditions demands a greater understanding of the processes underlying normal and pathological brain ageing. Recent advances in the biology of ageing in model organisms, together with molecular and systems-level studies of the brain, are beginning to shed light on these mechanisms and their potential roles in cognitive decline. PMID:20336135

  20. Polyphenols found in berry fruit improve age-associated changes in cognitive function and brain inflammation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Research has demonstrated, in both human and animals, that cognitive functioning decreases with age, to include deficits in processing speed, executive function, memory, and spatial learning. The cause of these functional declines is not entirely understood; however, neuronal losses and the associat...

  1. Developmental Origin of Oligodendrocyte Lineage Cells Determines Response to Demyelination and Susceptibility to Age-Associated Functional Decline

    PubMed Central

    Crawford, Abbe H.; Tripathi, Richa B.; Richardson, William D.; Franklin, Robin J.M.

    2016-01-01

    Summary Oligodendrocyte progenitors (OPs) arise from distinct ventral and dorsal domains within the ventricular germinal zones of the embryonic CNS. The functional significance, if any, of these different populations is not known. Using dual-color reporter mice to distinguish ventrally and dorsally derived OPs, we show that, in response to focal demyelination of the young adult spinal cord or corpus callosum, dorsally derived OPs undergo enhanced proliferation, recruitment, and differentiation as compared with their ventral counterparts, making a proportionally larger contribution to remyelination. However, with increasing age (up to 13 months), the dorsally derived OPs become less able to differentiate into mature oligodendrocytes. Comparison of dorsally and ventrally derived OPs in culture revealed inherent differences in their migration and differentiation capacities. Therefore, the responsiveness of OPs to demyelination, their contribution to remyelination, and their susceptibility to age-associated functional decline are markedly dependent on their developmental site of origin in the developing neural tube. PMID:27149850

  2. Reversal of cognitive decline in Alzheimer's disease

    PubMed Central

    Bredesen, Dale E.; Amos, Edwin C.; Canick, Jonathan; Ackerley, Mary; Raji, Cyrus; Fiala, Milan; Ahdidan, Jamila

    2016-01-01

    Alzheimer's disease is one of the most significant healthcare problems nationally and globally. Recently, the first description of the reversal of cognitive decline in patients with early Alzheimer's disease or its precursors, MCI (mild cognitive impairment) and SCI (subjective cognitive impairment), was published [1]. The therapeutic approach used was programmatic and personalized rather than monotherapeutic and invariant, and was dubbed metabolic enhancement for neurodegeneration (MEND). Patients who had had to discontinue work were able to return to work, and those struggling at work were able to improve their performance. The patients, their spouses, and their co-workers all reported clear improvements. Here we report the results from quantitative MRI and neuropsychological testing in ten patients with cognitive decline, nine ApoE4+ (five homozygous and four heterozygous) and one ApoE4−, who were treated with the MEND protocol for 5-24 months. The magnitude of the improvement is unprecedented, providing additional objective evidence that this programmatic approach to cognitive decline is highly effective. These results have far-reaching implications for the treatment of Alzheimer's disease, MCI, and SCI; for personalized programs that may enhance pharmaceutical efficacy; and for personal identification of ApoE genotype. PMID:27294343

  3. Consequences of Age-Related Cognitive Declines

    PubMed Central

    Salthouse, Timothy

    2013-01-01

    Adult age differences in a variety of cognitive abilities are well documented, and many of those abilities have been found to be related to success in the workplace and in everyday life. However, increased age is seldom associated with lower levels of real-world functioning, and the reasons for this lab-life discrepancy are not well understood. This article briefly reviews research concerned with relations of age to cognition, relations of cognition to successful functioning outside the laboratory, and relations of age to measures of work performance and achievement. The final section discusses several possible explanations for why there are often little or no consequences of age-related cognitive declines in everyday functioning. PMID:21740223

  4. Cognitive Decline and the Default American Lifestyle

    PubMed Central

    2011-01-01

    Objectives. Upward trends in IQ, education, and mental work suggest that cognitive function among seniors should be rising strongly across cohorts. There is little sign of such improvement in recent decades, and some analyses find poorer function in the newer cohorts. This essay explores possible explanations of the anomaly. Methods. Major long-term trends that might increase cognitive impairment are reviewed, and their implications are considered. Results. Physical activity is declining, food is increasingly manufactured, body fat is increasing, diabetes and metabolic syndrome are on the rise, the number of prescription drugs per person is increasing, and the proportion of the population either old or obese is growing. Discussion. Technological and economic development may lower the cognitive function needed for survival. They also lower physical activity in daily life. Sedentary work, transportation, and leisure undermine the aerobic and metabolic fitness required for the brain to perform well. Some prescription drugs impair cognitive function, and others do so when taken for many years or in combination with others. The growing fraction of the population that is either old or obese may further lower physical activity norms and requirements and substitute medical intervention for health, accelerating a trend toward cognitive impairment. PMID:21743052

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

    PubMed Central

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

    2014-01-01

    The aging brain undergoes a range of changes varying from subtle structural and physiological changes causing only minor functional decline under healthy normal aging conditions, to severe cognitive or neurological impairment associated with extensive loss of neurons and circuits due to age-associated neurodegenerative disease conditions. Understanding how biological aging processes affect the brain and how they contribute to the onset and progress of age-associated neurodegenerative diseases is a core research goal in contemporary neuroscience. This review focuses on the idea that changes in intrinsic neuronal electrical excitability associated with (per)oxidation of membrane lipids and activation of phospholipase A2 (PLA2) enzymes are an important mechanism of learning and memory failure under normal aging conditions. Specifically, in the context of this special issue on the biology of cognitive aging we portray the opportunities offered by the identifiable neurons and behaviorally characterized neural circuits of the freshwater snail Lymnaea stagnalis in neuronal aging research and recapitulate recent insights indicating a key role of lipid peroxidation-induced PLA2 as instruments of aging, oxidative stress and inflammation in age-associated neuronal and memory impairment in this model system. The findings are discussed in view of accumulating evidence suggesting involvement of analogous mechanisms in the etiology of age-associated dysfunction and disease of the human and mammalian brain. PMID:25538730

  6. Decreased Default Mode Network connectivity correlates with age-associated structural and cognitive changes

    PubMed Central

    Vidal-Piñeiro, Didac; Valls-Pedret, Cinta; Fernández-Cabello, Sara; Arenaza-Urquijo, Eider M.; Sala-Llonch, Roser; Solana, Elisabeth; Bargalló, Núria; Junqué, Carme; Ros, Emilio; Bartrés-Faz, David

    2014-01-01

    Ageing entails cognitive and motor decline as well as brain changes such as loss of gray (GM) and white matter (WM) integrity, neurovascular and functional connectivity alterations. Regarding connectivity, reduced resting-state fMRI connectivity between anterior and posterior nodes of the Default Mode Network (DMN) relates to cognitive function and has been postulated to be a hallmark of ageing. However, the relationship between age-related connectivity changes and other neuroimaging-based measures in ageing is fragmentarily investigated. In a sample of 116 healthy elders we aimed to study the relationship between antero-posterior DMN connectivity and measures of WM integrity, GM integrity and cerebral blood flow (CBF), assessed with an arterial spin labeling sequence. First, we replicated previous findings demonstrating DMN connectivity decreases in ageing and an association between antero-posterior DMN connectivity and memory scores. The results showed that the functional connectivity between posterior midline structures and the medial prefrontal cortex was related to measures of WM and GM integrity but not to CBF. Gray and WM correlates of anterio-posterior DMN connectivity included, but were not limited to, DMN areas and cingulum bundle. These results resembled patterns of age-related vulnerability which was studied by comparing the correlates of antero-posterior DMN with age-effect maps. These age-effect maps were obtained after performing an independent analysis with a second sample including both young and old subjects. We argue that antero-posterior connectivity might be a sensitive measure of brain ageing over the brain. By using a comprehensive approach, the results provide valuable knowledge that may shed further light on DMN connectivity dysfunctions in ageing. PMID:25309433

  7. Decreased Default Mode Network connectivity correlates with age-associated structural and cognitive changes.

    PubMed

    Vidal-Piñeiro, Didac; Valls-Pedret, Cinta; Fernández-Cabello, Sara; Arenaza-Urquijo, Eider M; Sala-Llonch, Roser; Solana, Elisabeth; Bargalló, Núria; Junqué, Carme; Ros, Emilio; Bartrés-Faz, David

    2014-01-01

    Ageing entails cognitive and motor decline as well as brain changes such as loss of gray (GM) and white matter (WM) integrity, neurovascular and functional connectivity alterations. Regarding connectivity, reduced resting-state fMRI connectivity between anterior and posterior nodes of the Default Mode Network (DMN) relates to cognitive function and has been postulated to be a hallmark of ageing. However, the relationship between age-related connectivity changes and other neuroimaging-based measures in ageing is fragmentarily investigated. In a sample of 116 healthy elders we aimed to study the relationship between antero-posterior DMN connectivity and measures of WM integrity, GM integrity and cerebral blood flow (CBF), assessed with an arterial spin labeling sequence. First, we replicated previous findings demonstrating DMN connectivity decreases in ageing and an association between antero-posterior DMN connectivity and memory scores. The results showed that the functional connectivity between posterior midline structures and the medial prefrontal cortex was related to measures of WM and GM integrity but not to CBF. Gray and WM correlates of anterio-posterior DMN connectivity included, but were not limited to, DMN areas and cingulum bundle. These results resembled patterns of age-related vulnerability which was studied by comparing the correlates of antero-posterior DMN with age-effect maps. These age-effect maps were obtained after performing an independent analysis with a second sample including both young and old subjects. We argue that antero-posterior connectivity might be a sensitive measure of brain ageing over the brain. By using a comprehensive approach, the results provide valuable knowledge that may shed further light on DMN connectivity dysfunctions in ageing.

  8. Age associated declines in muscle mass, strength, power, and physical performance: impact on fear of falling and quality of life

    Technology Transfer Automated Retrieval System (TEKTRAN)

    SUMMARY: This 3 year longitudinal study among older adults showed that declining muscle mass, strength, power, and physical performance are independent contributing factors to increased fear of falling, while declines of muscle mass and physical performance contribute to deterioration of quality of ...

  9. VASCULAR RISK FACTORS AND COGNITIVE DECLINE IN A POPULATION SAMPLE

    PubMed Central

    Ganguli, Mary; Fu, Bo; Snitz, Beth E.; Unverzagt, Frederick W.; Loewenstein, David A.; Hughes, Tiffany F.; Chang, Chung-Chou H.

    2014-01-01

    We examined several vascular factors in relation to rates of decline in five cognitive domains in a population-based cohort. In an age-stratified random sample (N=1982) aged 65+ years, we assessed at baseline the cognitive domains of attention, executive function, memory, language, and visuospatial function, and also vascular, inflammatory, and metabolic indices. Random effects models generated slopes of cognitive decline over the next four years; linear models identified vascular factors associated with these slopes, adjusting for demographics, baseline cognition, and potential interactions. Several vascular risk factors (history of stroke, diabetes, central obesity, C-Reactive Protein), although associated with lower baseline cognitive performance, did not predict rate of subsequent decline. APOE*4 genotype was associated with accelerated decline in language, memory, and executive functions. Homocysteine elevation was associated with faster decline in executive function. Hypertension (history or systolic blood pressure >140 mm) was associated with slower decline in memory. Baseline alcohol consumption was associated with slower decline in attention, language, and memory. Different indices of vascular risk are associated with low performance and with rates of decline in different cognitive domains. Cardiovascular mechanisms explain at least some of the variance in cognitive decline. Selective survival may also play a role. PMID:24126216

  10. Dietary Approaches and Supplements in the Prevention of Cognitive Decline and Alzheimer's Disease.

    PubMed

    Dominguez, Ligia J; Barbagallo, Mario

    2016-01-01

    Age-associated cognitive decline and dementia are conditions in which there is deterioration in memory, thinking, and behavior, with profound effects on the ability to perform everyday activities and well-being. Even if dementia mainly affects older persons, it is not a normal part of aging. Alzheimer's disease accounts for 60-75% of dementia cases. The number of persons affected will increase in the next decades in parallel with aging of the world population. Hence, unless some approach is found to reduce age-related deterioration of cognitive functions, health care costs will continue to rise exponentially. There is a wealth of epidemiological evidence supporting a relationship between diet and Alzheimer's disease, and suggesting that the risk of cognitive decline may be reduced by dietary interventions. It has been proposed that adopting a healthy diet and lifestyle that improves cardiovascular function may help delaying the onset of Alzheimer's disease due to its potential association with vascular disease. Several nutrients, dietary components, supplements and dietary patterns have been reported in relation to their association with cognition and with the development of cognitive decline and Alzheimer's disease. The possible effect of diet on the prevention of dementia is of tremendous scientific and general interest, because hitherto there is no definitive evidence of any effective pharmacological treatment for dementia. The aim of this review is to evaluate the evidence for the effects of some dietary components, supplements, and dietary patterns as neuroprotective, with potential to delay cognitive decline and the onset of dementia.

  11. Late Life Leisure Activities and Risk of Cognitive Decline

    PubMed Central

    2013-01-01

    Background. Studies concerning the effect of different types of leisure activities on various cognitive domains are limited. This study tests the hypothesis that mental, physical, and social activities have a domain-specific protection against cognitive decline. Methods. A cohort of a geographically defined population in China was examined in 2003–2005 and followed for an average of 2.4 years. Leisure activities were assessed in 1,463 adults aged 65 years and older without cognitive or physical impairment at baseline, and their cognitive performances were tested at baseline and follow-up examinations. Results. High level of mental activity was related to less decline in global cognition (β = −.23, p < .01), language (β = −.11, p < .05), and executive function (β = −.13, p < .05) in ANCOVA models adjusting for age, gender, education, history of stroke, body mass index, Apolipoprotein E genotype, and baseline cognition. High level of physical activity was related to less decline in episodic memory (β = −.08, p < .05) and language (β = −.15, p < .01). High level of social activity was associated with less decline in global cognition (β = −.11, p < .05). Further, a dose-response pattern was observed: although participants who did not engage in any of the three activities experienced a significant global cognitive decline, those who engaged in any one of the activities maintained their cognition, and those who engaged in two or three activities improved their cognition. The same pattern was observed in men and in women. Conclusions. Leisure activities in old age may protect against cognitive decline for both women and men, and different types of activities seem to benefit different cognitive domains. PMID:22879456

  12. Berry fruit can improve age-associated neuronal and cognitive deficits: from the laboratory to the clinic

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Research has demonstrated, in both human and animals, that cognitive functioning decreases with age, to include deficits in processing speed, executive function, memory, and spatial learning. The cause of these functional declines is not entirely understood; however, neuronal losses and the associat...

  13. Decreased recall of primacy words predicts cognitive decline.

    PubMed

    Bruno, Davide; Reiss, Philip T; Petkova, Eva; Sidtis, John J; Pomara, Nunzio

    2013-03-01

    One of the cognitive changes associated with Alzheimer's disease is a diminution of the primacy effect, i.e., the tendency toward better recall of items studied early on a list compared with the rest. We examined whether learning and recall of primacy words predicted subsequent cognitive decline in 204 elderly subjects who were non-demented and cognitively intact when first examined. Our results show that poorer primacy performance in the Rey Auditory Verbal Learning Test delayed recall trials, but not in immediate recall trials, is an effective predictor of subsequent decline in general cognitive function. This pattern of performance can be interpreted as evidence that failure to consolidate primacy items is a marker of cognitive decline.

  14. Differential effects of blueberry polyphenols on age-associated neuroinflammation and cognition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long-term effects of oxidative stress and inflammatory insults are thought to contribute to the decrements in cognitive performance seen in aging and neurodegenerative diseases. In previous studies, we have shown the beneficial effects of various dark-colored berry fruits in reversing age-related de...

  15. TDP-43 Pathology, Cognitive Decline, and Dementia in Old Age

    PubMed Central

    Wilson, Robert S.; Yu, Lei; Trojanowski, John Q.; Chen, Er-Yun; Boyle, Patricia A.; Bennett, David A.; Schneider, Julie A.

    2013-01-01

    Importance Cognitive decline is a leading cause of disability and death in old age but its neurobiological bases are not well understood. Objective To test the hypothesis that transactive response DNA-binding protein 43 (TDP-43) is related to late life cognitive decline. Design Longitudinal clinical-pathologic cohort study. Setting More than 40 Catholic groups across the United States. Participants A total of 130 older Catholic nuns, priests, and monks underwent annual clinical evaluations, including detailed cognitive testing, for a mean of 10.1 years prior to death. On neuropathologic examination, we collected semiquantitative measures of TDP-43 pathology, density of neuronal neurofibrillary tangles, area occupied by amyloid-beta plaques, and the presence of alpha-synuclein Lewy bodies from multiple brain regions. Gross and microscopic cerebral infarcts and hippocampal sclerosis were also identified. Main Outcome Measure Annual rate of change in a previously established composite measure of global cognition during a mean of 10.1 years of annual observation before death. Results TDP-43 pathology ranging from sparse to severe was identified in 46% of participants and was associated with amyloid plaques, tangles, and hippocampal sclerosis but not neocortical Lewy bodies or cerebral infarcts. After controlling for amyloid plaques, tangles, and hippocampal sclerosis, TDP-43 pathology was associated with more rapid cognitive decline and accounted for nearly as much of the variability in rates of global cognitive decline as did tangles. TDP-43 pathology had a distinct cognitive profile that differed from other neuropathologic processes (related to decline in episodic and working memory but not in other cognitive domains), and it was elevated in those who developed dementia but not in those with mild cognitive impairment. Conclusion The results suggest that TDP-43 is an important brain pathology underlying cognitive decline and dementia in old age. PMID:24080705

  16. Nutritional management of older adults with cognitive decline and dementia.

    PubMed

    Ogawa, Sumito

    2014-04-01

    Age-related cognitive decline is a main predictor of disability among elderly people, and with the continued expansion of the aging population and the increase in life expectancy, the prevalence of mild cognitive impairment and dementia represented by Alzheimer's disease (AD), which is a multifactorial neurodegenerative disorder of older adults, have increased. Recent epidemiological and observational studies suggest a relationship exists between lifestyle factors, including nutrition and diet, and cognitive function in aging adults. It is also suggested that malnutrition and nutrient deficiencies are associated with cognitive decline in patients with dementia. There are a variety of nutritional factors, including nutritional status and dietary patterns, that might be associated with cognitive function, and specific micronutrients and dietary components have been suggested to have an association with cognitive function as well. Based on these findings and evidence, evaluation of nutritional state, as well as nutritional intervention, might be able to play a role in the management and prevention of dementia.

  17. Nutritional management of older adults with cognitive decline and dementia.

    PubMed

    Ogawa, Sumito

    2014-04-01

    Age-related cognitive decline is a main predictor of disability among elderly people, and with the continued expansion of the aging population and the increase in life expectancy, the prevalence of mild cognitive impairment and dementia represented by Alzheimer's disease (AD), which is a multifactorial neurodegenerative disorder of older adults, have increased. Recent epidemiological and observational studies suggest a relationship exists between lifestyle factors, including nutrition and diet, and cognitive function in aging adults. It is also suggested that malnutrition and nutrient deficiencies are associated with cognitive decline in patients with dementia. There are a variety of nutritional factors, including nutritional status and dietary patterns, that might be associated with cognitive function, and specific micronutrients and dietary components have been suggested to have an association with cognitive function as well. Based on these findings and evidence, evaluation of nutritional state, as well as nutritional intervention, might be able to play a role in the management and prevention of dementia. PMID:24650061

  18. Obesity and cognitive decline: role of inflammation and vascular changes

    PubMed Central

    Nguyen, Jason C. D.; Killcross, A. Simon; Jenkins, Trisha A.

    2014-01-01

    The incidence of obesity in middle age is increasing markedly, and in parallel the prevalence of metabolic disorders including cardiovascular disease and type II diabetes is also rising. Numerous studies have demonstrated that both obesity and metabolic disorders are associated with poorer cognitive performance, cognitive decline, and dementia. In this review we discuss the effects of obesity on cognitive performance, including both clinical and preclinical observations, and discuss some of the potential mechanisms involved, namely inflammation and vascular and metabolic alterations. PMID:25477778

  19. Active cognitive lifestyle associates with cognitive recovery and a reduced risk of cognitive decline.

    PubMed

    Marioni, Riccardo E; van den Hout, Ardo; Valenzuela, Michael J; Brayne, Carol; Matthews, Fiona E

    2012-01-01

    Education and lifestyle factors linked with complex mental activity are thought to affect the progression of cognitive decline. Collectively, these factors can be combined to create a cognitive reserve or cognitive lifestyle score. This study tested the association between cognitive lifestyle score and cognitive change in a population-based cohort of older persons from five sites across England and Wales. Data came from 13,004 participants of the Medical Research Council Cognitive Function and Ageing Study who were aged 65 years and over. Cognition was assessed at multiple waves over 16 years using the Mini-Mental State Examination. Subjects were grouped into four cognitive states (no impairment, slight impairment, moderate impairment, severe impairment) and cognitive lifestyle score was assessed as a composite measure of education, mid-life occupation, and current social engagement. A multi-state model was used to test the effect of cognitive lifestyle score on cognitive transitions. Hazard ratios for cognitive lifestyle score showed significant differences between those in the upper compared to the lower tertile with a more active cognitive lifestyle associating with: a decreased risk of moving from no to slight impairment (0.58, 95% CI (0.45, 0.74)); recovery from a slightly impaired state back to a non-impaired state (2.93 (1.35, 6.38)); but an increased mortality risk from a severely impaired state (1.28 (1.12, 1.45)). An active cognitive lifestyle is associated with a more favorable cognitive trajectory in older persons. Future studies would ideally incorporate neuroradiological and neuropathological data to determine if there is causal evidence for these associations. PMID:21971400

  20. [Cognitive decline in elderly individuals with type 2 diabetes mellitus].

    PubMed

    Sakurai, Takashi

    2013-11-01

    Cognitive decline in diabetes impairs the activity of daily living and shortens the healthy life expectancy. Once diabetes is accompanied by demented disorders, it becomes difficult to achieve good control of diabetes. Treatment for diabetes and demented disease should be provided concomitantly, because cognitive dysfunction worsens diabetic control and hyperglycemia worsens cognitive function vice versa, resulting in increased risks of acute metabolic failure. Compliance to medical treatment of diabetes is seriously impaired in the elderly with cognitive decline. Comprehensive approach with several medical specialists and care stuffs is thus needed. This manuscript briefly summaries the recent evidence for target of glycemic control and appropriate use of anti-diabetic medication in diabetic elderly with cognitive impairment.

  1. Clinical Report: Cognitive decline in a patient with Cardiofaciocutaneous syndrome.

    PubMed

    Cabrera, Sergio; Morel, Chantal; Tartaglia, Maria Carmela

    2016-05-01

    Cardiofaciocutaneous Syndrome (CFCS) is a rare genetic syndrome caused by mutations in one of four genes: BRAF, MAP2K1, MAP2K2, and KRAS. There is tremendous phenotypic heterogeneity in patients with CFCS and so confirmation of diagnosis requires genetic testing. Neurologic and/or cognitive symptoms are present in almost all CFCS individuals. Little is known about cognitive function in older patients with CFCS. In this report, we present the cognitive, neuropsychiatric, and imaging findings of a patient diagnosed with CFCS who after having remained stable developed progressive cognitive/behavioral and motor decline.

  2. Quantitative EEG and Cognitive Decline in Parkinson's Disease.

    PubMed

    Cozac, Vitalii V; Gschwandtner, Ute; Hatz, Florian; Hardmeier, Martin; Rüegg, Stephan; Fuhr, Peter

    2016-01-01

    Cognitive decline is common with the progression of Parkinson's disease (PD). Different candidate biomarkers are currently studied for the risk of dementia in PD. Several studies have shown that quantitative EEG (QEEG) is a promising predictor of PD-related cognitive decline. In this paper we briefly outline the basics of QEEG analysis and analyze the recent publications addressing the predictive value of QEEG in the context of cognitive decline in PD. The MEDLINE database was searched for relevant publications from January 01, 2005, to March 02, 2015. Twenty-four studies reported QEEG findings in various cognitive states in PD. Spectral and connectivity markers of QEEG could help to discriminate between PD patients with different level of cognitive decline. QEEG variables correlate with tools for cognitive assessment over time and are associated with significant hazard ratios to predict PD-related dementia. QEEG analysis shows high test-retest reliability and avoids learning effects associated with some neuropsychological testing; it is noninvasive and relatively easy to repeat.

  3. Infectious Burden and Cognitive Decline in the Northern Manhattan Study

    PubMed Central

    Wright, Clinton B.; Gardener, Hannah; Dong, Chuanhui; Yoshita, Mitsuhiro; DeCarli, Charles; Sacco, Ralph L.; Stern, Yaakov; Elkind, Mitchell S.V.

    2016-01-01

    Objectives To determine whether infectious burden (IB) is associated with worse performance and decline on a battery of neuropsychological tests. Design Prospective cohort study (Northern Manhattan Study (NOMAS)). Setting Community. Participants A subsample of 588 stroke-free NOMAS participants with IB and cognitive data (mean age 71±8, 62% female, 14% white, 16% black, 70% Hispanic) and 419 with repeat cognitive testing. Measurements Samples used for IB data were collected at baseline. Two waves of neurocognitive assessments occurred during follow-up. Participants underwent a neuropsychological battery and had repeated testing (mean time span 6±2 years). Using factor analysis–derived domain-specific Z scores for language, memory, executive function, and processing speed, associations between a quantitative stroke risk-weighted IB index (IBI), based on five common infections (Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, herpes simplex viruses 1 and 2), and cognitive performance and decline in each domain was examined. Results Adjusting for demographic characteristics, socioeconomic status, crystallized cognitive abilities, and vascular risk factors, the IBI was inversely associated with executive function at baseline (beta=−0.10, p=.01) but not with baseline language, memory, or processing speed performance in adjusted analyses. The IBI was associated with cognitive decline in the memory domain, adjusting for demographic and vascular risk factors (p=.02). Conclusion A quantitative measure of IB explained variability in baseline executive function performance and associated with decline in memory. Past exposure to common infections may contribute to vascular cognitive impairment and warrants further study. PMID:26289683

  4. Quantitative EEG and Cognitive Decline in Parkinson's Disease

    PubMed Central

    Cozac, Vitalii V.; Gschwandtner, Ute; Hatz, Florian; Hardmeier, Martin; Rüegg, Stephan

    2016-01-01

    Cognitive decline is common with the progression of Parkinson's disease (PD). Different candidate biomarkers are currently studied for the risk of dementia in PD. Several studies have shown that quantitative EEG (QEEG) is a promising predictor of PD-related cognitive decline. In this paper we briefly outline the basics of QEEG analysis and analyze the recent publications addressing the predictive value of QEEG in the context of cognitive decline in PD. The MEDLINE database was searched for relevant publications from January 01, 2005, to March 02, 2015. Twenty-four studies reported QEEG findings in various cognitive states in PD. Spectral and connectivity markers of QEEG could help to discriminate between PD patients with different level of cognitive decline. QEEG variables correlate with tools for cognitive assessment over time and are associated with significant hazard ratios to predict PD-related dementia. QEEG analysis shows high test-retest reliability and avoids learning effects associated with some neuropsychological testing; it is noninvasive and relatively easy to repeat. PMID:27148466

  5. Rapid cognitive decline: not always Creutzfeldt-Jakob disease.

    PubMed

    Randall, A; Ellis, R; Hywel, B; Davies, R R; Alusi, S H; Larner, A J

    2015-01-01

    A patient with rapidly progressive cognitive decline over an approximately four month period was suspected to have sporadic Creutzfeldt-Jakob disease. Features thought to support this diagnosis included psychiatric symptoms (anxiety and depression), visual hallucinations and a visual field defect. However, the finding of papilloedema broadened the differential diagnosis. Although standard brain imaging and electroencephalography had shown only non-specific abnormalities, subsequent cerebral angiography disclosed an intracranial dural arteriovenous fistula. Following embolisation, the patient made a good functional recovery. Intracranial dural arteriovenous fistula merits consideration in any patient with subacute cognitive decline, and should be included in the differential diagnosis of sporadic Creutzfeldt-Jakob disease. PMID:26517100

  6. Cognitive Decline in Older Persons Initiating Anticholinergic Medications

    PubMed Central

    Shah, Raj C.; Janos, Alicia L.; Kline, Julia E.; Yu, Lei; Leurgans, Sue E.; Wilson, Robert S.; Wei, Peter; Bennett, David A.; Heilman, Kenneth M.; Tsao, Jack W.

    2013-01-01

    Background This study examines the effect of initiating medications with anticholinergic activity on the cognitive functions of older persons. Methods Participants were 896 older community-dwelling, Catholic clergy without baseline dementia. Medication data was collected annually. The Anticholinergic Cognitive Burden Scale was utilized to identify use of a medication with probable or definite anticholinergic activity. Participants had at least two annual cognitive evaluations. Results Over a mean follow-up of 10 years, the annual rate of global cognitive function decline for never users, prevalent users, and incident users was −0.062 (SE = 0.005), −0.081(SE = 0.011), and −0.096 (SE = 0.007) z-score units/year, respectively. Compared to never users, incident users had a more rapid decline (difference = −0.034 z-score units/year, SE = 0.008, p<0.001) while prevalent users did not have a significantly more rapid decline (p = 0.1). Conclusions Older persons initiating a medication with anticholinergic activity have a steeper annual decline in cognitive functioning than those who are not taking these medications. PMID:23741303

  7. Neighborhood Integration and Connectivity Predict Cognitive Performance and Decline

    PubMed Central

    Watts, Amber; Ferdous, Farhana; Moore, Keith Diaz; Burns, Jeffrey M.

    2015-01-01

    Objective Neighborhood characteristics may be important for promoting walking, but little research has focused on older adults, especially those with cognitive impairment. We evaluated the role of neighborhood characteristics on cognitive function and decline over a 2-year period adjusting for measures of walking. Method In a study of 64 older adults with and without mild Alzheimer's disease (AD), we evaluated neighborhood integration and connectivity using geographical information systems data and space syntax analysis. In multiple regression analyses, we used these characteristics to predict 2-year declines in factor analytically derived cognitive scores (attention, verbal memory, mental status) adjusting for age, sex, education, and self-reported walking. Results Neighborhood integration and connectivity predicted cognitive performance at baseline, and changes in cognitive performance over 2 years. The relationships between neighborhood characteristics and cognitive performance were not fully explained by self-reported walking. Discussion Clearer definitions of specific neighborhood characteristics associated with walkability are needed to better understand the mechanisms by which neighborhoods may impact cognitive outcomes. These results have implications for measuring neighborhood characteristics, design and maintenance of living spaces, and interventions to increase walking among older adults. We offer suggestions for future research measuring neighborhood characteristics and cognitive function. PMID:26504889

  8. Hearing loss and cognitive decline in older adults.

    PubMed

    Lin, Frank R; Yaffe, Kristine; Xia, Jin; Xue, Qian-Li; Harris, Tamara B; Purchase-Helzner, Elizabeth; Satterfield, Suzanne; Ayonayon, Hilsa N; Ferrucci, Luigi; Simonsick, Eleanor M

    2013-02-25

    BACKGROUND Whether hearing loss is independently associated with accelerated cognitive decline in older adults is unknown. METHODS We studied 1984 older adults (mean age, 77.4 years) enrolled in the Health ABC Study, a prospective observational study begun in 1997-1998. Our baseline cohort consisted of participants without prevalent cognitive impairment (Modified Mini-Mental State Examination [3MS] score, ≥80) who underwent audiometric testing in year 5. Participants were followed up for 6 years. Hearing was defined at baseline using a pure-tone average of thresholds at 0.5 to 4 kHz in the better-hearing ear. Cognitive testing was performed in years 5, 8, 10, and 11 and consisted of the 3MS (measuring global function) and the Digit Symbol Substitution test (measuring executive function). Incident cognitive impairment was defined as a 3MS score of less than 80 or a decline in 3MS score of more than 5 points from baseline. Mixed-effects regression and Cox proportional hazards regression models were adjusted for demographic and cardiovascular risk factors. RESULTS In total, 1162 individuals with baseline hearing loss (pure-tone average >25 dB) had annual rates of decline in 3MS and Digit Symbol Substitution test scores that were 41% and 32% greater, respectively, than those among individuals with normal hearing. On the 3MS, the annual score changes were -0.65 (95% CI, -0.73 to -0.56) vs -0.46 (95% CI, -0.55 to -0.36) points per year (P = .004). On the Digit Symbol Substitution test, the annual score changes were -0.83 (95% CI, -0.94 to -0.73) vs -0.63 (95% CI, -0.75 to -0.51) points per year (P = .02). Compared to those with normal hearing, individuals with hearing loss at baseline had a 24% (hazard ratio, 1.24; 95% CI, 1.05-1.48) increased risk for incident cognitive impairment. Rates of cognitive decline and the risk for incident cognitive impairment were linearly associated with the severity of an individual's baseline hearing loss. CONCLUSIONS Hearing loss is

  9. Both Financial and Cognitive Decline Predict Clinical Progression in MCI.

    PubMed

    Gerstenecker, Adam; Triebel, Kristen L; Martin, Roy; Snyder, Scott; Marson, Daniel C

    2016-01-01

    We investigated the roles of financial/functional and cognitive abilities in predicting clinical progression in patients with mild cognitive impairment (MCI). In a longitudinal sample of 51 patients with consensus conference diagnosed MCI likely due to Alzheimer disease (AD), two-year change scores were calculated for a performance measure of functional ability, cognitive variables, and 3 outcome measures used to track progression in neurological disorders. We examined patterns of financial and cognitive decline across the 2-year study period, and used these data and the 3 outcome variables to construct discrete predictor models of clinical progression in MCI. We found that both financial skills and cognitive abilities declined over the 2-year study period, were significantly associated with clinical progression, and contributed unique variance to all 3 predictor models. The resulting models accounted for 40% to 75% of variance in clinical progression across outcome variables. Taken together, our results indicate that changes in both cognitive abilities and higher order functional skills appear integral to understanding clinical progression in MCI likely due to AD. Specifically, declines in financial skills contribute unique variance to measures commonly used to track progression in neurological disorders associated with aging, and thus represent an important functional marker of clinical progression in prodromal AD.

  10. Epigenetic alterations in the suprachiasmatic nucleus and hippocampus contribute to age-related cognitive decline

    PubMed Central

    Deibel, Scott H.; Zelinski, Erin L.; Keeley, Robin J.; Kovalchuk, Olga; McDonald, Robert J.

    2015-01-01

    Circadian rhythm dysfunction and cognitive decline, specifically memory loss, frequently accompany natural aging. Circadian rhythms and memory are intertwined, as circadian rhythms influence memory formation and recall in young and old rodents. Although, the precise relationship between circadian rhythms and memory is still largely unknown, it is hypothesized that circadian rhythm disruption, which occurs during aging, contributes to age-associated cognitive decline, specifically memory loss. While there are a variety of mechanisms that could mediate this effect, changes in the epigenome that occur during aging has been proposed as a potential candidate. Interestingly, epigenetic mechanisms, such as DNA methylation and sirtuin1 (SIRT1) are necessary for both circadian rhythms and memory. During aging, similar alterations of epigenetic mechanisms occur in the suprachiasmatic nucleus (SCN) and hippocampus, which are necessary for circadian rhythm generation and memory, respectively. Recently, circadian rhythms have been linked to epigenetic function in the hippocampus, as some of these epigenetic mechanisms oscillate in the hippocampus and are disrupted by clock gene deletion. The current paper will review how circadian rhythms and memory change with age, and will suggest how epigenetic changes in these processes might contribute to age-related cognitive decline. PMID:26252151

  11. Epigenetic alterations in the suprachiasmatic nucleus and hippocampus contribute to age-related cognitive decline.

    PubMed

    Deibel, Scott H; Zelinski, Erin L; Keeley, Robin J; Kovalchuk, Olga; McDonald, Robert J

    2015-09-15

    Circadian rhythm dysfunction and cognitive decline, specifically memory loss, frequently accompany natural aging. Circadian rhythms and memory are intertwined, as circadian rhythms influence memory formation and recall in young and old rodents. Although, the precise relationship between circadian rhythms and memory is still largely unknown, it is hypothesized that circadian rhythm disruption, which occurs during aging, contributes to age-associated cognitive decline, specifically memory loss. While there are a variety of mechanisms that could mediate this effect, changes in the epigenome that occur during aging has been proposed as a potential candidate. Interestingly, epigenetic mechanisms, such as DNA methylation and sirtuin1 (SIRT1) are necessary for both circadian rhythms and memory. During aging, similar alterations of epigenetic mechanisms occur in the suprachiasmatic nucleus (SCN) and hippocampus, which are necessary for circadian rhythm generation and memory, respectively. Recently, circadian rhythms have been linked to epigenetic function in the hippocampus, as some of these epigenetic mechanisms oscillate in the hippocampus and are disrupted by clock gene deletion. The current paper will review how circadian rhythms and memory change with age, and will suggest how epigenetic changes in these processes might contribute to age-related cognitive decline. PMID:26252151

  12. Crowdsourced estimation of cognitive decline and resilience in Alzheimer's disease.

    PubMed

    Allen, Genevera I; Amoroso, Nicola; Anghel, Catalina; Balagurusamy, Venkat; Bare, Christopher J; Beaton, Derek; Bellotti, Roberto; Bennett, David A; Boehme, Kevin L; Boutros, Paul C; Caberlotto, Laura; Caloian, Cristian; Campbell, Frederick; Chaibub Neto, Elias; Chang, Yu-Chuan; Chen, Beibei; Chen, Chien-Yu; Chien, Ting-Ying; Clark, Tim; Das, Sudeshna; Davatzikos, Christos; Deng, Jieyao; Dillenberger, Donna; Dobson, Richard J B; Dong, Qilin; Doshi, Jimit; Duma, Denise; Errico, Rosangela; Erus, Guray; Everett, Evan; Fardo, David W; Friend, Stephen H; Fröhlich, Holger; Gan, Jessica; St George-Hyslop, Peter; Ghosh, Satrajit S; Glaab, Enrico; Green, Robert C; Guan, Yuanfang; Hong, Ming-Yi; Huang, Chao; Hwang, Jinseub; Ibrahim, Joseph; Inglese, Paolo; Iyappan, Anandhi; Jiang, Qijia; Katsumata, Yuriko; Kauwe, John S K; Klein, Arno; Kong, Dehan; Krause, Roland; Lalonde, Emilie; Lauria, Mario; Lee, Eunjee; Lin, Xihui; Liu, Zhandong; Livingstone, Julie; Logsdon, Benjamin A; Lovestone, Simon; Ma, Tsung-Wei; Malhotra, Ashutosh; Mangravite, Lara M; Maxwell, Taylor J; Merrill, Emily; Nagorski, John; Namasivayam, Aishwarya; Narayan, Manjari; Naz, Mufassra; Newhouse, Stephen J; Norman, Thea C; Nurtdinov, Ramil N; Oyang, Yen-Jen; Pawitan, Yudi; Peng, Shengwen; Peters, Mette A; Piccolo, Stephen R; Praveen, Paurush; Priami, Corrado; Sabelnykova, Veronica Y; Senger, Philipp; Shen, Xia; Simmons, Andrew; Sotiras, Aristeidis; Stolovitzky, Gustavo; Tangaro, Sabina; Tateo, Andrea; Tung, Yi-An; Tustison, Nicholas J; Varol, Erdem; Vradenburg, George; Weiner, Michael W; Xiao, Guanghua; Xie, Lei; Xie, Yang; Xu, Jia; Yang, Hojin; Zhan, Xiaowei; Zhou, Yunyun; Zhu, Fan; Zhu, Hongtu; Zhu, Shanfeng

    2016-06-01

    Identifying accurate biomarkers of cognitive decline is essential for advancing early diagnosis and prevention therapies in Alzheimer's disease. The Alzheimer's disease DREAM Challenge was designed as a computational crowdsourced project to benchmark the current state-of-the-art in predicting cognitive outcomes in Alzheimer's disease based on high dimensional, publicly available genetic and structural imaging data. This meta-analysis failed to identify a meaningful predictor developed from either data modality, suggesting that alternate approaches should be considered for prediction of cognitive performance.

  13. Crowdsourced estimation of cognitive decline and resilience in Alzheimer's disease.

    PubMed

    Allen, Genevera I; Amoroso, Nicola; Anghel, Catalina; Balagurusamy, Venkat; Bare, Christopher J; Beaton, Derek; Bellotti, Roberto; Bennett, David A; Boehme, Kevin L; Boutros, Paul C; Caberlotto, Laura; Caloian, Cristian; Campbell, Frederick; Chaibub Neto, Elias; Chang, Yu-Chuan; Chen, Beibei; Chen, Chien-Yu; Chien, Ting-Ying; Clark, Tim; Das, Sudeshna; Davatzikos, Christos; Deng, Jieyao; Dillenberger, Donna; Dobson, Richard J B; Dong, Qilin; Doshi, Jimit; Duma, Denise; Errico, Rosangela; Erus, Guray; Everett, Evan; Fardo, David W; Friend, Stephen H; Fröhlich, Holger; Gan, Jessica; St George-Hyslop, Peter; Ghosh, Satrajit S; Glaab, Enrico; Green, Robert C; Guan, Yuanfang; Hong, Ming-Yi; Huang, Chao; Hwang, Jinseub; Ibrahim, Joseph; Inglese, Paolo; Iyappan, Anandhi; Jiang, Qijia; Katsumata, Yuriko; Kauwe, John S K; Klein, Arno; Kong, Dehan; Krause, Roland; Lalonde, Emilie; Lauria, Mario; Lee, Eunjee; Lin, Xihui; Liu, Zhandong; Livingstone, Julie; Logsdon, Benjamin A; Lovestone, Simon; Ma, Tsung-Wei; Malhotra, Ashutosh; Mangravite, Lara M; Maxwell, Taylor J; Merrill, Emily; Nagorski, John; Namasivayam, Aishwarya; Narayan, Manjari; Naz, Mufassra; Newhouse, Stephen J; Norman, Thea C; Nurtdinov, Ramil N; Oyang, Yen-Jen; Pawitan, Yudi; Peng, Shengwen; Peters, Mette A; Piccolo, Stephen R; Praveen, Paurush; Priami, Corrado; Sabelnykova, Veronica Y; Senger, Philipp; Shen, Xia; Simmons, Andrew; Sotiras, Aristeidis; Stolovitzky, Gustavo; Tangaro, Sabina; Tateo, Andrea; Tung, Yi-An; Tustison, Nicholas J; Varol, Erdem; Vradenburg, George; Weiner, Michael W; Xiao, Guanghua; Xie, Lei; Xie, Yang; Xu, Jia; Yang, Hojin; Zhan, Xiaowei; Zhou, Yunyun; Zhu, Fan; Zhu, Hongtu; Zhu, Shanfeng

    2016-06-01

    Identifying accurate biomarkers of cognitive decline is essential for advancing early diagnosis and prevention therapies in Alzheimer's disease. The Alzheimer's disease DREAM Challenge was designed as a computational crowdsourced project to benchmark the current state-of-the-art in predicting cognitive outcomes in Alzheimer's disease based on high dimensional, publicly available genetic and structural imaging data. This meta-analysis failed to identify a meaningful predictor developed from either data modality, suggesting that alternate approaches should be considered for prediction of cognitive performance. PMID:27079753

  14. Age-associated declines in muscle mass, strength, power, and physical performance: impact on fear of falling and quality of life

    PubMed Central

    Trombetti, A.; Reid, K. F.; Hars, M.; Herrmann, F. R.; Pasha, E.; Phillips, E. M.; Fielding, R. A.

    2016-01-01

    Summary This 3-year longitudinal study among older adults showed that declining muscle mass, strength, power, and physical performance are independent contributing factors to increased fear of falling, while declines of muscle mass and physical performance contribute to deterioration of quality of life. Our findings reinforce the importance of preserving muscle health with advancing age. Introduction The age-associated loss of skeletal muscle quantity and function are critical determinants of independent physical functioning in later life. Longitudinal studies investigating how decrements in muscle components of sarcopenia impact fear of falling (FoF) and quality of life (QoL) in older adults are lacking. Methods Twenty-six healthy older subjects (age, 74.1±3.7; Short Physical Performance Battery (SPPB) score ≥10) and 22 mobility-limited older subjects (age, 77.2±4.4; SPPB score ≥9) underwent evaluations of lower extremity muscle size and composition by computed tomography, strength and power, and physical performance at baseline and after 3-year follow-up. The Falls Efficacy Scale (FES) and Short Form-36 questionnaire (SF-36) were also administered at both timepoints to assess FoF and QoL, respectively. Results At 3-year follow-up, muscle cross-sectional area (CSA) (p<0.013) and power decreased (p<0.001), while intermuscular fat infiltration increased (p<0.001). These decrements were accompanied with a longer time to complete 400 m by 22±46 s (p<0.002). Using linear mixed-effects regression models, declines of muscle CSA, strength and power, and SPPB score were associated with increased FES score (p<0.05 for each model). Reduced physical component summary score of SF-36 over follow-up was independently associated with decreased SPPB score (p<0.020), muscle CSA (p<0.046), and increased 400 m walk time (p<0.003). Conclusions In older adults with and without mobility limitations, declining muscle mass, strength, power, and physical performance contribute

  15. Monounsaturated, trans & saturated fatty acids and cognitive decline in women

    PubMed Central

    Naqvi, Asghar Z.; Harty, Brian; Mukamal, Kenneth J.; Stoddard, Anne M.; Vitolins, Mara; Dunn, Julie E.

    2011-01-01

    Objectives Prospectively assess effects of select dietary fats on cognitive decline Design Prospective observational; 3-year follow-up Setting Subjects recruited at Northwestern University who participated in Women's Health Initiative Observational Study or control group of Diet Modification arm. Participants 482 women ≥ 60 years Measurements We averaged dietary intake from a validated food frequency questionnaire (FFQ) administered twice (mean=2.7 years apart) before baseline cognitive assessment (mean=2.9 years after 2nd FFQ). Testing of memory, vision, executive function, language, and attention was performed at 2 time points, 3 years apart. We created a global Z-score for both time points by averaging all Z-scores for each participant and defined global cognitive change as the difference between follow-up and baseline Z-scores. Results Median intakes of saturated fats (SFA), trans-fats, (TFA), dietary cholesterol (DC) and monounsaturated fats (MUFA) were 18.53 g/d, 3.45 g/d, 0.201 g/d and 19.39 g/d, respectively. There were no associations between degree of cognitive decline and intakes of SFA (p=0.69), TFA (p=0.54) or DC (p=0.64) after adjusting for baseline cognition, total energy, age, education, reading ability, Apolipoprotein E (ε4) allele, BMI, estrogen and beta-blocker use, and intake of caffeine and other fatty acids. In contrast, compared with participants in the lowest quartile, MUFA intake was associated with lower cognitive decline in fully adjusted linear regression models, with decline of 0.21 + 0.05 SE in the lowest versus 0.05 + 0.05 SE in the highest quartiles (p=0.02). This effect of MUFA intake was primarily in the visual and memory domains (p=0.03 for both). Conclusion Higher intakes of SFA, TFA and DC in these women were not associated with cognitive decline, while MUFA intake was associated with less cognitive decline. PMID:21568955

  16. Dietary patterns, cognitive decline, and dementia: a systematic review.

    PubMed

    van de Rest, Ondine; Berendsen, Agnes Am; Haveman-Nies, Annemien; de Groot, Lisette Cpgm

    2015-03-01

    Nutrition is an important modifiable risk factor that plays a role in the strategy to prevent or delay the onset of dementia. Research on nutritional effects has until now mainly focused on the role of individual nutrients and bioactive components. However, the evidence for combined effects, such as multinutrient approaches, or a healthy dietary pattern, such as the Mediterranean diet, is growing. These approaches incorporate the complexity of the diet and possible interaction and synergy between nutrients. Over the past few years, dietary patterns have increasingly been investigated to better understand the link between diet, cognitive decline, and dementia. In this systematic review we provide an overview of the literature on human studies up to May 2014 that examined the role of dietary patterns (derived both a priori as well as a posteriori) in relation to cognitive decline or dementia. The results suggest that better adherence to a Mediterranean diet is associated with less cognitive decline, dementia, or Alzheimer disease, as shown by 4 of 6 cross-sectional studies, 6 of 12 longitudinal studies, 1 trial, and 3 meta-analyses. Other healthy dietary patterns, derived both a priori (e.g., Healthy Diet Indicator, Healthy Eating Index, and Program National Nutrition Santé guideline score) and a posteriori (e.g., factor analysis, cluster analysis, and reduced rank regression), were shown to be associated with reduced cognitive decline and/or a reduced risk of dementia as shown by all 6 cross-sectional studies and 6 of 8 longitudinal studies. More conclusive evidence is needed to reach more targeted and detailed guidelines to prevent or postpone cognitive decline.

  17. Dietary Patterns, Cognitive Decline, and Dementia: A Systematic Review12

    PubMed Central

    van de Rest, Ondine; Berendsen, Agnes AM; Haveman-Nies, Annemien; de Groot, Lisette CPGM

    2015-01-01

    Nutrition is an important modifiable risk factor that plays a role in the strategy to prevent or delay the onset of dementia. Research on nutritional effects has until now mainly focused on the role of individual nutrients and bioactive components. However, the evidence for combined effects, such as multinutrient approaches, or a healthy dietary pattern, such as the Mediterranean diet, is growing. These approaches incorporate the complexity of the diet and possible interaction and synergy between nutrients. Over the past few years, dietary patterns have increasingly been investigated to better understand the link between diet, cognitive decline, and dementia. In this systematic review we provide an overview of the literature on human studies up to May 2014 that examined the role of dietary patterns (derived both a priori as well as a posteriori) in relation to cognitive decline or dementia. The results suggest that better adherence to a Mediterranean diet is associated with less cognitive decline, dementia, or Alzheimer disease, as shown by 4 of 6 cross-sectional studies, 6 of 12 longitudinal studies, 1 trial, and 3 meta-analyses. Other healthy dietary patterns, derived both a priori (e.g., Healthy Diet Indicator, Healthy Eating Index, and Program National Nutrition Santé guideline score) and a posteriori (e.g., factor analysis, cluster analysis, and reduced rank regression), were shown to be associated with reduced cognitive decline and/or a reduced risk of dementia as shown by all 6 cross-sectional studies and 6 of 8 longitudinal studies. More conclusive evidence is needed to reach more targeted and detailed guidelines to prevent or postpone cognitive decline. PMID:25770254

  18. Cognitive Declines Precede and Predict Functional Declines in Aging and Alzheimer’s Disease

    PubMed Central

    Zahodne, Laura B.; Manly, Jennifer J.; MacKay-Brandt, Anna; Stern, Yaakov

    2013-01-01

    Objective To investigate the temporal ordering of cognitive and functional declines separately in older adults with or without Alzheimer’s disease (AD). Design and Setting A community-based longitudinal study of aging and dementia in Northern Manhattan (Washington Heights/Hamilton Heights Inwood Columbia Aging Project) and a multicenter, clinic-based longitudinal study of prevalent AD at Columbia University Medical Center, Johns Hopkins School of Medicine, Massachusetts General Hospital, and the Hôpital de la Salpêtrière in Paris, France (the Predictors Study). Participants 3,443 initially non-demented older adults (612 with eventual incident dementia) and 517 patients with AD. Main Outcome Measures Cognitive measures included the modified Mini-Mental State Exam and composite scores of memory and language derived from a standardized neuropsychological battery. Function was measured with the Blessed Dementia Rating Scale, completed by the participant (in the sample of non-demented older adults) or an informant (in the sample of prevalent AD patients). Data were analyzed with autoregressive cross-lagged panel analysis. Results Cognitive scores more consistently predicted subsequent functional abilities than vice versa in non-demented older adults, participants with eventual incident dementia, and patients with prevalent AD. Conclusions Cognitive declines appear to precede and cause functional declines prior to and following dementia diagnosis. Standardized neuropsychological tests are valid predictors of later functional changes in both non-demented and demented older adults. PMID:24023894

  19. Can education rescue genetic liability for cognitive decline?

    PubMed

    Cook, C Justin; Fletcher, Jason M

    2015-02-01

    Although there is a vast literature linking education and later health outcomes, the mechanisms underlying these associations are relatively unknown. In the spirit of some medical literature that leverages developmental abnormalities to understand mechanisms of normative functioning, we explore the ability of higher educational attainments to "rescue" biological/genetic liabilities in brain function through inheritance of a variant of the APOE gene shown to lead to cognitive decline, dementia, and Alzheimer's disease in old age. Deploying a between-sibling design that allows quasi-experimental variation in genotype and educational attainment within a standard gene-environment interaction framework, we show evidence that the genetic effects of the "risky" APOE variant on old-age cognitive decline are absent in individuals who complete college (vs. high school graduates). Auxiliary analyses suggest that the likely mechanisms of education are most consistent through changing brain processes (i.e., "how we think") and potentially building cognitive reserves, rather than alleviating old age cognitive decline through the channels of higher socioeconomic status and resources over the life course.

  20. Veterans have less age-related cognitive decline.

    PubMed

    McLay, R N; Lyketsos, C G

    2000-08-01

    Military service involves exposure to a number of stresses, both psychological and physical. On the other hand, military personnel generally maintain excellent fitness, and veterans have increased access to education and health care. The overall effect on age-related cognitive decline, whether for good or ill, of having served in the armed forces has not been investigated previously. In this study, we examined a diverse population of 208 veterans and 1,216 civilians followed as part of the Epidemiologic Catchment Area Study in 1981, 1982, and 1993 to 1996. We examined change in Mini-Mental State Examination (MMSE) score after a median of 11.5 years. Veterans were found to have significantly less decrease in MMSE scores at follow-up even after sex, race, and education were taken into account. These results suggest an overall positive effect of military service on the rate of age-related cognitive decline. PMID:10957857

  1. Nutrition, the brain and cognitive decline: insights from epigenetics.

    PubMed

    Dauncey, M J

    2014-11-01

    Nutrition affects the brain throughout life, with profound implications for cognitive decline and dementia. These effects are mediated by changes in expression of multiple genes, and responses to nutrition are in turn affected by individual genetic variability. An important layer of regulation is provided by the epigenome: nutrition is one of the many epigenetic regulators that modify gene expression without changes in DNA sequence. Epigenetic mechanisms are central to brain development, structure and function, and include DNA methylation, histone modifications and non-protein-coding RNAs. They enable cell-specific and age-related gene expression. Although epigenetic events can be highly stable, they can also be reversible, highlighting a critical role for nutrition in prevention and treatment of disease. Moreover, they suggest key mechanisms by which nutrition is involved in the pathogenesis of age-related cognitive decline: many nutrients, foods and diets have both immediate and long-term effects on the epigenome, including energy status, that is, energy intake, physical activity, energy metabolism and related changes in body composition, and micronutrients involved in DNA methylation, for example, folate, vitamins B6 and B12, choline, methionine. Optimal brain function results from highly complex interactions between numerous genetic and environmental factors, including food intake, physical activity, age and stress. Future studies linking nutrition with advances in neuroscience, genomics and epigenomics should provide novel approaches to the prevention of cognitive decline, and treatment of dementia and Alzheimer's disease.

  2. Metal chaperones prevent zinc-mediated cognitive decline.

    PubMed

    Adlard, Paul A; Parncutt, Jacqui; Lal, Varsha; James, Simon; Hare, Dominic; Doble, Philip; Finkelstein, David I; Bush, Ashley I

    2015-09-01

    Zinc transporter-3 (ZnT3) protein is responsible for loading zinc into presynaptic vesicles and consequently controls the availability of zinc at the glutamatergic synapse. ZnT3 has been shown to decline with age and in Alzheimer's disease (AD) and is crucially involved in learning and memory. In this study, we utilised whole animal behavioural analyses in the ZnT3 KO mouse line, together with electrophysiological analysis of long-term potentiation in brain slices from ZnT3 KO mice, to show that metal chaperones (clioquinol, 30 mg/kg/day for 6weeks) can prevent the age-dependent cognitive phenotype that characterises these animals. This likely occurs as a result of a homeostatic restoration of synaptic protein expression, as clioquinol significantly restored levels of various pre- and postsynaptic proteins that are critical for normal cognition, including PSD-95; AMPAR and NMDAR2b. We hypothesised that this clioquinol-mediated restoration of synaptic health resulted from a selective increase in synaptic zinc content within the hippocampus. While we demonstrated a small regional increase in hippocampal zinc content using synchrotron x-ray fluorescence microscopy, further sub-region analyses are required to determine whether this effect is seen in other regions of the hippocampal formation that are more closely linked to the synaptic plasticity effects observed in this study. These data support our recent report on the use of a different metal chaperone (PBT2) to prevent normal age-related cognitive decline and demonstrate that metal chaperones are efficacious in preventing the zinc-mediated cognitive decline that characterises ageing and disease.

  3. Relationship between regional atrophy rates and cognitive decline in mild cognitive impairment.

    PubMed

    McDonald, Carrie R; Gharapetian, Lusineh; McEvoy, Linda K; Fennema-Notestine, Christine; Hagler, Donald J; Holland, Dominic; Dale, Anders M

    2012-02-01

    We investigated the relationship between regional atrophy rates and 2-year cognitive decline in a large cohort of patients with mild cognitive impairment (MCI; n = 103) and healthy controls (n = 90). Longitudinal magnetic resonance image (MRI) scans were analyzed using high-throughput image analysis procedures. Atrophy rates were derived by calculating percent cortical volume loss between baseline and 24 month scans. Stepwise regressions were performed to investigate the contribution of atrophy rates to language, memory, and executive functioning decline, controlling for age, gender, baseline performances, and disease progression. In MCI, left temporal lobe atrophy rates were associated with naming decline, whereas bilateral temporal, left frontal, and left anterior cingulate atrophy rates were associated with semantic fluency decline. Left entorhinal atrophy rate was associated with memory decline and bilateral frontal atrophy rates were associated with executive function decline. These data provide evidence that regional atrophy rates in MCI contribute to domain-specific cognitive decline, which appears to be partially independent of disease progression. MRI measures of regional atrophy can provide valuable information for understanding the neural basis of cognitive impairment in MCI.

  4. Mobile technologies in the early detection of cognitive decline.

    PubMed

    Allard, Michèle; Husky, Mathilde; Catheline, Gwénaëlle; Pelletier, Amandine; Dilharreguy, Bixente; Amieva, Hélène; Pérès, Karine; Foubert-Samier, Alexandra; Dartigues, Jean-François; Swendsen, Joel

    2014-01-01

    The identification of biological and pathophysiological processes implicated in different forms of dementia is itself dependent on reliable descriptions of cognitive performance and capacities. However, traditional instruments are often unable to detect subtle declines in cognitive functions due to natural variation at the time of testing. Mobile technologies permit the repeated assessment of cognitive functions and may thereby provide more reliable descriptions of early cognitive difficulties that are inaccessible to clinic or hospital-based instruments. This assessment strategy is also able to characterize in real-time the dynamic associations between cognitive performance and specific daily life behaviors or activities. In a cohort of elderly rural residents, 60 individuals were administered neuropsychological and neuroimaging exams as well as a one-week period of electronic ambulatory monitoring of behavior, semantic memory performance, and daily life experiences. Whereas imaging markers were unrelated to traditional neuropsychological test scores, they were significantly associated with mobile assessments of semantic memory performance. Moreover, certain daily life activities such as reading or completing crossword puzzles were associated with increases in semantic memory performance over the subsequent hours of the same day. The revolution in mobile technologies provides unprecedented opportunities to overcome the barriers of time and context that characterize traditional hospital and clinical-based assessments. The combination of both novel and traditional methods should provide the best opportunity for identifying the earliest risk factors and biomarkers for Alzheimer's disease and other forms of dementia.

  5. Patterns of Cognitive Decline Prior to Dementia in Persons with Mild Cognitive Impairment

    PubMed Central

    Cloutier, Simon; Chertkow, Howard; Kergoat, Marie-Jeanne; Gauthier, Serge; Belleville, Sylvie

    2015-01-01

    Abstract Only a limited number of studies have investigated the decline of discrete cognitive domains as individuals progress from mild cognitive impairment (MCI) to dementia. Thus, the goal of this longitudinal study was to evaluate the cognitive changes underway during the years preceding a diagnosis of probable Alzheimer’s disease (AD), and to compare these changes to those found in MCI participants who do not progress to dementia. Participants were compared as a function of whether they later converted to AD (n = 47) or not (n = 74). Cognitive change was assessed prior to the conversion year, using that year as a starting point. A combination of polynomial regression analyses and mixed ANOVAs assessed 1) the trajectory of cognitive decline for each domain and 2) the differences between non-progressors and those who had converted to AD. The different cognitive domains demonstrated very different patterns of decline in the group of MCI progressors. A quadratic function, i.e., many years of stable performance followed by a rapid decline just prior to diagnosis, was observed for delayed recall, working memory, and spatial memory. In contrast, a gradual linear decline was observed for immediate recall, executive function, and visuo-spatial abilities. Finally, language in progressors was impaired on all time periods relative to non-progressors, but there was no further change between the first assessments and conversion to AD. Individuals with MCI who progress to AD show abnormal cognition at least two years prior to their dementia diagnosis. The pattern of symptom change observed appears to depend upon the cognitive domain and thus, clinical studies should not assume similar rate of decline across domains. In contrast and, apart from verbal memory, the non-progressors present a performance similar to that of healthy older adults. PMID:26401770

  6. Relationship between Frailty and Cognitive Decline in Older Mexican Americans

    PubMed Central

    Samper-Ternent, Rafael; Snih, Soham Al; Raji, Mukaila A.; Markides, Kyriakos S.; Ottenbacher, Kenneth J.

    2009-01-01

    Objective Examine the association between frailty status and change in cognitive function over time in older Mexican Americans. Design Data used are from the Hispanic Established Population for the Epidemiological Study of the Elderly (H-EPESE) Setting Five Southwestern states: Texas, New Mexico, Colorado, Arizona, and California. Participants 1,370 non-institutionalized Mexican American men and women aged 65 and older with a Mini Mental State Examination (MMSE) ≥ 21 at baseline (1995−1996). Measurements Frailty defined as three or more of the following components: 1) unintentional weight-loss of > 10-lbs, 2) weakness (lowest 20% in grip-strength), 3) self-reported exhaustion, 4) slow walking speed (lowest 20% 16ft walk-time in seconds), and 5) low physical activity level (lowest 20% Physical Activity Scale for the Elderly (PASE) score). Socio-demographic factors, MMSE, medical conditions (stroke, heart-attack, diabetes, arthritis, cancer and hypertension), depressive symptoms and visual-impairment were obtained. Results Of the 1370 subjects, 684 (49.9%) were not-frail, 626 (45.7%) were pre-frail (1 − 2 components) and 60 (4.4%) were frail (≥3 components) in 1995/96. Using general linear mixed models, we found that frail subjects had greater cognitive decline over 10-years compared with non-frail subjects (Estimate = −0.67, SE = 0.13; p< .0001). This association remained statistically significant after controlling for potential confounding factors. Conclusion Frail status in older Mexican Americans with MMSE ≥ 21 at baseline is an independent predictor of MMSE score decline over a 10-year period. Future research is needed to establish pathophysiological components that can clarify the relationship between frailty and cognitive decline. PMID:18811611

  7. Enriched childhood experiences moderate age-related motor and cognitive decline.

    PubMed

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

    2013-01-01

    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.

  8. 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

  9. [Preventive strategy for cognitive decline in elderly with diabetes mellitus].

    PubMed

    Sakurai, Takashi

    2014-04-01

    Diabetes increases the risk of cognitive decline including vascular dementia and Alzheimer's disease. Preventive strategy for cognitive impairment is thus needed in elderly with diabetes. To avoid brain injury in diabetic elderly patients, management of hypoglycemia, hyperglycemia, fluctuation of blood glucose, insulin resistance, and cerebral vessel disease is crucial. Recent clinical trials show hyperglycemia should be controlled with HbA1c of 7.2-7.4% for prevention of newly onset of dementia in the elderly. In contrast, little is known for target glucose levels in diabetic elderly combined with demented disease. Careful insight of hypoglycemia seems more important in the elderly. Now, a variety of pharmacological agents for treatment of diabetes is available and it seems clear that a comprehensive approach will be required in order to achieve healthy brain function.

  10. Reversal of cognitive decline: a novel therapeutic program.

    PubMed

    Bredesen, Dale E

    2014-09-01

    This report describes a novel, comprehensive, and personalized therapeutic program that is based on the underlying pathogenesis of Alzheimer's disease, and which involves multiple modalities designed to achieve metabolic enhancement for neurodegeneration (MEND). The first 10 patients who have utilized this program include patients with memory loss associated with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI). Nine of the 10 displayed subjective or objective improvement in cognition beginning within 3-6 months, with the one failure being a patient with very late stage AD. Six of the patients had had to discontinue working or were struggling with their jobs at the time of presentation, and all were able to return to work or continue working with improved performance. Improvements have been sustained, and at this time the longest patient follow-up is two and one-half years from initial treatment, with sustained and marked improvement. These results suggest that a larger, more extensive trial of this therapeutic program is warranted. The results also suggest that, at least early in the course, cognitive decline may be driven in large part by metabolic processes. Furthermore, given the failure of monotherapeutics in AD to date, the results raise the possibility that such a therapeutic system may be useful as a platform on which drugs that would fail as monotherapeutics may succeed as key components of a therapeutic system. PMID:25324467

  11. Reversal of cognitive decline: A novel therapeutic program

    PubMed Central

    Bredesen, Dale E.

    2014-01-01

    This report describes a novel, comprehensive, and personalized therapeutic program that is based on the underlying pathogenesis of Alzheimer's disease, and which involves multiple modalities designed to achieve metabolic enhancement for neurodegeneration (MEND). The first 10 patients who have utilized this program include patients with memory loss associated with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI). Nine of the 10 displayed subjective or objective improvement in cognition beginning within 3-6 months, with the one failure being a patient with very late stage AD. Six of the patients had had to discontinue working or were struggling with their jobs at the time of presentation, and all were able to return to work or continue working with improved performance. Improvements have been sustained, and at this time the longest patient follow-up is two and one-half years from initial treatment, with sustained and marked improvement. These results suggest that a larger, more extensive trial of this therapeutic program is warranted. The results also suggest that, at least early in the course, cognitive decline may be driven in large part by metabolic processes. Furthermore, given the failure of monotherapeutics in AD to date, the results raise the possibility that such a therapeutic system may be useful as a platform on which drugs that would fail as monotherapeutics may succeed as key components of a therapeutic system. PMID:25324467

  12. Basal Forebrain Cholinergic Circuits and Signaling in Cognition and Cognitive Decline.

    PubMed

    Ballinger, Elizabeth C; Ananth, Mala; Talmage, David A; Role, Lorna W

    2016-09-21

    Recent work continues to place cholinergic circuits at center stage for normal executive and mnemonic functioning and provides compelling evidence that the loss of cholinergic signaling and cognitive decline are inextricably linked. This Review focuses on the last few years of studies on the mechanisms by which cholinergic signaling contributes to circuit activity related to cognition. We attempt to identify areas of controversy, as well as consensus, on what is and is not yet known about how cholinergic signaling in the CNS contributes to normal cognitive processes. In addition, we delineate the findings from recent work on the extent to which dysfunction of cholinergic circuits contributes to cognitive decline associated with neurodegenerative disorders.

  13. Basal Forebrain Cholinergic Circuits and Signaling in Cognition and Cognitive Decline.

    PubMed

    Ballinger, Elizabeth C; Ananth, Mala; Talmage, David A; Role, Lorna W

    2016-09-21

    Recent work continues to place cholinergic circuits at center stage for normal executive and mnemonic functioning and provides compelling evidence that the loss of cholinergic signaling and cognitive decline are inextricably linked. This Review focuses on the last few years of studies on the mechanisms by which cholinergic signaling contributes to circuit activity related to cognition. We attempt to identify areas of controversy, as well as consensus, on what is and is not yet known about how cholinergic signaling in the CNS contributes to normal cognitive processes. In addition, we delineate the findings from recent work on the extent to which dysfunction of cholinergic circuits contributes to cognitive decline associated with neurodegenerative disorders. PMID:27657448

  14. The Cognitive Decline of Marshal Philippe Pétain.

    PubMed

    Jennekens, Frans G I

    2015-01-01

    In 1940, at the age of 84, Marshal Pétain was appointed the head of state and government of France. His health was excellent but he tired easily. He felt unable to learn and his memory was weak. During a crisis situation in 1942, he did not lead, plan and decide and he was replaced as head of government. From 1943 on, he was increasingly apathetic. In 1945/1946 he had difficulty finding words after a short conversation. A parliamentary committee concluded in 1947 that he was senile. His mental condition worsened in the years thereafter. In retrospect, it is clear that the final responsibility for the policies of the French government in the Second World War had rested on a man who was going through a predementia process of cognitive decline. PMID:26107612

  15. Cognitive aging: a common decline of episodic recollection and spatial memory in rats.

    PubMed

    Robitsek, R Jonathan; Fortin, Norbert J; Koh, Ming Teng; Gallagher, Michela; Eichenbaum, Howard

    2008-09-01

    In humans, recognition memory declines with aging, and this impairment is characterized by a selective loss in recollection of previously studied items contrasted with relative sparing of familiarity for items in the study list. Rodent models of cognitive aging have focused on water maze learning and have demonstrated an age-associated loss in spatial, but not cued memory. The current study examined odor recognition memory in young and aged rats and compared performance in recognition with that in water maze learning. In the recognition task, young rats used both recollection and familiarity. In contrast, the aged rats showed a selective loss of recollection and relative sparing of familiarity, similar to the effects of hippocampal damage. Furthermore, performance on the recall component, but not the familiarity component, of recognition was correlated with spatial memory and recollection was poorer in aged rats that were also impaired in spatial memory. These results extend the pattern of impairment in recollection and relative sparing of familiarity observed in human cognitive aging to rats, and suggest a common age-related impairment in both spatial learning and the recollective component of nonspatial recognition memory.

  16. Clinical predictors of cognitive decline in patients with mild cognitive impairment: the Chongqing aging study.

    PubMed

    Li, Ling; Wang, Yanjiang; Yan, Jiachuan; Chen, Yang; Zhou, Rui; Yi, Xu; Shi, Qianqian; Zhou, Huadong

    2012-07-01

    Mild cognitive impairment (MCI) is considered as the early stage of dementia which currently has no effective treatments. Reducing progression of cognitive decline at the MCI stage could be an important strategy for preventing conversion to dementia. The goal of this work was to screen for clinical predictors indicating the prognosis of MCI comprehensively; therefore, we assumed vascular risk factors (VRFs), carotid stenosis, and white matter changes (WMC) to be independent predictors. A total of 257 patients with MCI underwent collection of VRF information, neuropsychological evaluation, computed tomography angiography (CTA) to investigate carotid stenosis, and magnetic resonance imaging (MRI) to identify severity of WMC. After a 3-year follow-up period, the neuropsychological evaluation, CTA, and MRI were repeated to assess the progression of cognitive decline, carotid stenosis, and WMC. The conversion rate from MCI to dementia was 11.65% per year, and the conversion rate from MCI to Alzheimer's disease was 7.05% per year in our cohort. Cognitive decline (in terms of changes in Mini Mental State Examination scores) was associated with diabetes mellitus (p = 0.004), baseline WMC severity (p < 0.001), baseline carotid stenosis (p < 0.001), and WMC severity change (p < 0.001). Besides, diabetes, baseline WMC severity, baseline moderate-to-severe carotid stenosis, and carotid stenosis change during follow-up were predictors of conversion from MCI to dementia. Given the potential clinical predictors, our findings could imply that controlling blood glucose, removing carotid stenosis, and improving cerebral perfusion could be effective measures to delay cognitive decline in patients with MCI and prevent conversion from MCI to dementia. PMID:22186849

  17. Automated Semantic Indices Related to Cognitive Function and Rate of Cognitive Decline

    PubMed Central

    Pakhomov, Serguei V.S.; Hemmy, Laura S.; Lim, Kelvin O.

    2012-01-01

    The objective of our study is to introduce a fully automated, computational linguistic technique to quantify semantic relations between words generated on a standard semantic verbal fluency test and to determine its cognitive and clinical correlates. Cognitive differences between patients with Alzheimer’s disease and mild cognitive impairment are evident in their performance on the semantic verbal fluency test. In addition to the semantic verbal fluency test score, several other performance characteristics sensitive to disease status and predictive of future cognitive decline have been defined in terms of words generated from semantically related categories (clustering) and shifting between categories (switching). However, the traditional assessment of clustering and switching has been performed manually in a qualitative fashion resulting in subjective scoring with limited reproducibility and scalability. Our approach uses word definitions and hierarchical relations between the words in WordNet®, a large electronic lexical database, to quantify the degree of semantic similarity and relatedness between words. We investigated the novel semantic fluency indices of mean cumulative similarity and relatedness between all pairs of words regardless of their order, and mean sequential similarity and relatedness between pairs of adjacent words in a sample of patients with clinically diagnosed probable (n=55) or possible (n=27) Alzheimer’s disease or mild cognitive impairment (n=31). The semantic fluency indices differed significantly between the diagnostic groups, and were strongly associated with neuropsychological tests of executive function, as well as the rate of global cognitive decline. Our results suggest that word meanings and relations between words shared across individuals and computationally modeled via WordNet and large text corpora provide the necessary context to account for the variability in language-based behavior and relate it to cognitive dysfunction

  18. Comparing three methods of computerised cognitive training for older adults with subclinical cognitive decline.

    PubMed

    Gooding, Amanda L; Choi, Jimmy; Fiszdon, Joanna M; Wilkins, Kirsten; Kirwin, Paul D; van Dyck, Christopher H; Devanand, Davangere; Bell, Morris D; Rivera Mindt, Monica

    2016-10-01

    Cognitive rehabilitation for mild cognitive impairment (MCI) and early Alzheimer's disease is readily available to the geriatric population. Initial evidence suggests that techniques incorporating motivational strategies to enhance treatment engagement may provide more benefit than computerised training alone. Seventy four adults with subclinical cognitive decline were randomly assigned to computerised cognitive training (CCT), Cognitive Vitality Training (CVT), or an Active Control Group (ACG), and underwent neuropsychological evaluations at baseline and four-month follow-up. Significant differences were found in changes in performance on the Modified Mini Mental State Examination (mMMSE) and measures of verbal learning and memory across treatment groups. Experimental groups showed greater preservation of functioning on the mMMSE than the ACG group, the CVT group performed better than the ACG group on one measure of verbal learning and both measures of verbal memory, and the CCT group performed better than the ACG group on one measure of verbal learning and one measure of verbal memory. There were no significant group differences between the CVT and CCT groups on measures of verbal learning or memory. It was concluded that computerised cognitive training may offer the most benefit when incorporated into a therapeutic milieu rather than administered alone, although both appear superior to more generic forms of cognitive stimulation.

  19. 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.

  20. Vitamin E (E) supplementation reverses the age associated decline in phosphorylation of the adaptor protein LAT in CD4+ T cells of old mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    T cell proliferation and interleukin (IL-2) production declines with age. Engagement of the T cell receptor (TCR) by antigen (Ag), known as the immune synapse (IS), in coordination with phosphorylation of key signaling proteins, leads to increased IL-2 synthesis and T cell proliferation. Defects in ...

  1. Relationship between metabolic and vascular conditions and cognitive decline among older Mexican Americans

    PubMed Central

    Downer, Brian; Raji, Mukaila A.; Markides, Kyriakos S.

    2015-01-01

    Objective Metabolic and vascular conditions have been independently associated with dementia and cognitive decline among older adults, but research on the combined effects that these conditions have on cognitive decline, especially among older Mexican Americans, is lacking. The purpose of this study was to examine the relationship between metabolic and vascular conditions and cognitive decline among older Mexican Americans. Methods The final sample included 2767 participants of the Hispanic Established Populations for the Epidemiologic Study of the Elderly. Linear mixed-effects regression was used to model cognitive decline across six examinations (1993–2007) according to the number (zero, one, two, and three to four) of metabolic and vascular conditions (hypertension, diabetes, stroke, and heart attack). Results Of the 2767 participants included in the final sample, 777 had zero conditions, 1314 had one condition, 553 had two conditions, and 123 had three to four conditions. Participants with two or three to four conditions had significantly greater cognitive decline compared with participants with zero or one condition. Stroke had the largest effect size on cognitive decline based on the proportion of variance that stroke accounted for in the linear mixed-effects model. Conclusion Mexican American older adults with multiple metabolic and vascular conditions exhibit greater cognitive decline than those with zero or one condition. Public health interventions designed to reduce the prevalence of chronic metabolic and vascular conditions, in particular stroke, may limit the severity of cognitive decline among older Mexican Americans. PMID:26032435

  2. Impaired Sleep Predicts Cognitive Decline in Old People: Findings from the Prospective KORA Age Study

    PubMed Central

    Johar, Hamimatunnisa; Kawan, Rasmila; Emeny, Rebecca Thwing; Ladwig, Karl-Heinz

    2016-01-01

    Study Objectives: To investigate the association between sleep-related characteristics and cognitive change over 3 years of follow up in an aged population. Methods: Sleep characteristics and covariates were assessed at baseline in a standardized interview and clinical examination of the population-based KORA Age Study (n = 740, mean age = 75 years). Cognitive score (determined by telephone interview for cognitive status, TICS-m) was recorded at baseline and 3 years later. Results: At baseline, 82.83% (n = 613) of participants had normal cognitive status, 13.51% (n = 100) were classified with mild cognitive impairment (MCI), and 3.64% (n = 27) with probable dementia. The effect of three distinct patterns of poor sleep (difficulties initiating [DIS] or maintaining sleep [DMS], daytime sleepiness [DS] or sleep duration) were considered on a change in cognitive score with adjustments for potential confounders in generalized linear regression models. Cognitive decline was more pronounced in individuals with DMS compared to those with no DMS (β = 1.33, 95% CI = 0.41–2.24, P < 0.001). However, the predictive power of DMS was only significant in individuals with normal cognition and not impaired subjects at baseline. Prolonged sleep duration increased the risk for cognitive decline in cognitively impaired elderly (β = 1.86, 95% CI = 0.15–3.57, P = 0.03). Other sleep characteristics (DIS and DS) were not significantly associated with cognitive decline. Conclusions: DMS and long sleep duration were associated with cognitive decline in normal and cognitively impaired elderly, respectively. The identification of impaired sleep quality may offer intervention strategies to deter cognitive decline in the elderly with normal cognitive function. Citation: Johar H, Kawan R, Emeny RT, Ladwig KH. Impaired sleep predicts cognitive decline in old people: findings from the prospective KORA age study. SLEEP 2016;39(1):217–226. PMID:26414903

  3. The potential effects of meditation on age-related cognitive decline: a systematic review.

    PubMed

    Gard, Tim; Hölzel, Britta K; Lazar, Sara W

    2014-01-01

    With a rapidly aging society it becomes increasingly important to counter normal age-related decline in cognitive functioning. Growing evidence suggests that cognitive training programs may have the potential to counteract this decline. On the basis of a growing body of research that shows that meditation has positive effects on cognition in younger and middle-aged adults, meditation may be able to offset normal age-related cognitive decline or even enhance cognitive function in older adults. In this paper, we review studies investigating the effects of meditation on age-related cognitive decline. We searched the Web of Science (1900 to present), PsycINFO (1597 to present), MEDLINE (1950 to present), and CABI (1910 to present) to identify original studies investigating the effects of meditation on cognition and cognitive decline in the context of aging. Twelve studies were included in the review, six of which were randomized controlled trials. Studies involved a wide variety of meditation techniques and reported preliminary positive effects on attention, memory, executive function, processing speed, and general cognition. However, most studies had a high risk of bias and small sample sizes. Reported dropout rates were low and compliance rates high. We conclude that meditation interventions for older adults are feasible, and preliminary evidence suggests that meditation can offset age-related cognitive decline.

  4. The potential effects of meditation on age-related cognitive decline: a systematic review

    PubMed Central

    Gard, Tim; Hölzel, Britta K.; Lazar, Sara W.

    2014-01-01

    With a rapidly aging society it becomes increasingly important to counter normal age-related decline in cognitive functioning. Growing evidence suggests that cognitive training programs may have the potential to counteract this decline. On the basis of a growing body of research that shows that meditation has positive effects on cognition in younger and middle-aged adults, meditation may be able to offset normal age-related cognitive decline or even enhance cognitive function in older adults. In this paper, we review studies investigating the effects of meditation on age-related cognitive decline. We searched the Web of Science (1900 to present), PsycINFO (1597 to present), MEDLINE (1950 to present), and CABI (1910 to present) to identify original studies investigating the effects of meditation on cognition and cognitive decline in the context of aging. Twelve studies were included in the review, six of which were randomized controlled trials. Studies involved a wide variety of meditation techniques and reported preliminary positive effects on attention, memory, executive function, processing speed, and general cognition. However, most studies had a high risk of bias and small sample sizes. Reported dropout rates were low and compliance rates high. We conclude that meditation interventions for older adults are feasible, and preliminary evidence suggests that meditation can offset age-related cognitive decline. PMID:24571182

  5. Dysregulation of the Bmi-1/p16(Ink⁴a) pathway provokes an aging-associated decline of submandibular gland function.

    PubMed

    Yamakoshi, Kimi; Katano, Satoshi; Iida, Mayu; Kimura, Hiromi; Okuma, Atsushi; Ikemoto-Uezumi, Madoka; Ohtani, Naoko; Hara, Eiji; Maruyama, Mitsuo

    2015-08-01

    Bmi-1 prevents stem cell aging, at least partly, by blocking expression of the cyclin-dependent kinase inhibitor p16(Ink4a) . Therefore, dysregulation of the Bmi-1/p16(Ink4a) pathway is considered key to the loss of tissue homeostasis and development of associated degenerative diseases during aging. However, because Bmi-1 knockout (KO) mice die within 20 weeks after birth, it is difficult to determine exactly where and when dysregulation of the Bmi-1/p16(Ink4a) pathway occurs during aging in vivo. Using real-time in vivo imaging of p16(Ink4a) expression in Bmi-1-KO mice, we uncovered a novel function of the Bmi-1/p16(Ink4a) pathway in controlling homeostasis of the submandibular glands (SMGs), which secrete saliva into the oral cavity. This pathway is dysregulated during aging in vivo, leading to induction of p16(Ink4a) expression and subsequent declined SMG function. These findings will advance our understanding of the molecular mechanisms underlying the aging-related decline of SMG function and associated salivary gland hypofunction, which is particularly problematic among the elderly.

  6. Disentangling the effects of age and APOE on neuropathology and late life cognitive decline.

    PubMed

    Yu, Lei; Boyle, Patricia A; Leurgans, Sue; Schneider, Julie A; Bennett, David A

    2014-04-01

    Age and APOE are the most robust risk factors for dementia and cognitive decline, but the underlying neurobiology remains unclear. We examined the extent to which the hallmark pathologies of Alzheimer's disease, Lewy body disease, and cerebrovascular diseases account for the association of age and APOE with decline in episodic memory versus nonepisodic cognitive abilities. Up to 20 waves of longitudinal cognitive data were collected from 858 autopsied participants in 2 ongoing clinical-pathologic cohort studies of aging. Neuropathologic examinations quantified measures of beta amyloid (Aβ) plaque, mesial temporal and neocortical neurofibrillary tangles, macro- and microinfarcts, and neocortical Lewy bodies. Random coefficient models estimated person-specific slopes of decline in episodic memory and nonepisodic cognition. Path analysis examined the relation of age, APOE, and the 6 pathologic indices to the slopes of cognitive decline. The effect of age on decline in episodic memory was mediated by Aβ, mesial temporal and neocortical tau tangles, and macroscopic infarcts; age on decline in nonepisodic cognition was mediated by Aβ, neocortical tangles, and macroscopic infarcts. The effect of APOE on decline in episodic memory was mediated by Aβ, mesial temporal and neocortical tangles, and neocortical Lewy bodies; APOE on nonepisodic cognition was mediated by Aβ, neocortical tangles, and neocortical Lewy bodies. There were no direct effects of age and APOE on decline after accounting for these pathologic pathways.

  7. Walking ability to predict future cognitive decline in old adults: A scoping review.

    PubMed

    Kikkert, Lisette H J; Vuillerme, Nicolas; van Campen, Jos P; Hortobágyi, Tibor; Lamoth, Claudine J

    2016-05-01

    Early identification of individuals at risk for cognitive decline may facilitate the selection of those who benefit most from interventions. Current models predicting cognitive decline include neuropsychological and/or biological markers. Additional markers based on walking ability might improve accuracy and specificity of these models because motor and cognitive functions share neuroanatomical structures and psychological processes. We reviewed the relationship between walking ability at one point of (mid) life and cognitive decline at follow-up. A systematic literature search identified 20 longitudinal studies. The average follow-up time was 4.5 years. Gait speed quantified walking ability in most studies (n=18). Additional gait measures (n=4) were step frequency, variability and step-length. Despite methodological weaknesses, results revealed that gait slowing (0.68-1.1 m/sec) preceded cognitive decline and the presence of dementia syndromes (maximal odds and hazard ratios of 10.4 and 11.1, respectively). The results indicate that measures of walking ability could serve as additional markers to predict cognitive decline. However, gait speed alone might lack specificity. We recommend gait analysis, including dynamic gait parameters, in clinical evaluations of patients with suspected cognitive decline. Future studies should focus on examining the specificity and accuracy of various gait characteristics to predict future cognitive decline. PMID:26861693

  8. A Simulation Platform for Quantifying Survival Bias: An Application to Research on Determinants of Cognitive Decline.

    PubMed

    Mayeda, Elizabeth Rose; Tchetgen Tchetgen, Eric J; Power, Melinda C; Weuve, Jennifer; Jacqmin-Gadda, Hélène; Marden, Jessica R; Vittinghoff, Eric; Keiding, Niels; Glymour, M Maria

    2016-09-01

    Bias due to selective mortality is a potential concern in many studies and is especially relevant in cognitive aging research because cognitive impairment strongly predicts subsequent mortality. Biased estimation of the effect of an exposure on rate of cognitive decline can occur when mortality is a common effect of exposure and an unmeasured determinant of cognitive decline and in similar settings. This potential is often represented as collider-stratification bias in directed acyclic graphs, but it is difficult to anticipate the magnitude of bias. In this paper, we present a flexible simulation platform with which to quantify the expected bias in longitudinal studies of determinants of cognitive decline. We evaluated potential survival bias in naive analyses under several selective survival scenarios, assuming that exposure had no effect on cognitive decline for anyone in the population. Compared with the situation with no collider bias, the magnitude of bias was higher when exposure and an unmeasured determinant of cognitive decline interacted on the hazard ratio scale to influence mortality or when both exposure and rate of cognitive decline influenced mortality. Bias was, as expected, larger in high-mortality situations. This simulation platform provides a flexible tool for evaluating biases in studies with high mortality, as is common in cognitive aging research. PMID:27578690

  9. Bereavement and behavioral changes as risk factors for cognitive decline in adults with Down syndrome

    PubMed Central

    Fonseca, Luciana Mascarenhas; de Oliveira, Melaine Cristina; de Figueiredo Ferreira Guilhoto, Laura Maria; Cavalheiro, Esper Abrao; Bottino, Cássio MC

    2014-01-01

    Background Cognitive decline and Alzheimer’s disease often affect older adults with Down syndrome (DS) much earlier than those in the general population. There is also growing evidence of the effects of negative life events on the mental health and behavior of individuals with intellectual disability. However, to our knowledge, this is the first study investigating objective cognitive decline following bereavement in aging individuals with DS. Objective The objective of this study was to determine whether cognitive decline correlates with bereavement following the recent loss of a caregiver or with behavioral changes in a sample of adult individuals with DS who do not meet the criteria for dementia or depression, using the longitudinal assessment of the Cambridge Cognitive Examination (CAMCOG), together with the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Methods We evaluated 18 subjects at baseline and over a follow-up period of 14–22 months, attempting to determine whether cognitive decline correlates with bereavement following the recent loss of the main caregiver or with behavioral changes (as assessed with the Neuropsychiatric Inventory). Results The mean rate of change in CAMCOG was −1.83 (standard deviation 4.51). Behavioral changes had a significant direct influence on cognitive decline. When bereavement was accompanied by behavioral changes, the probability of cognitive decline was 87% (odds ratio 3.82). Conclusion The occurrence of behavioral changes attributed to bereavement following the loss of the primary caregiver significantly increases the probability of cognitive decline in individuals with DS. Longitudinal comparison of the CAMCOG and use of the IQCODE appear to enrich the analysis of cognitive decline in individuals with DS. Further studies involving larger samples are needed in order to corroborate and expand upon our findings, which can have implications for the clinical management of older adults with DS. PMID

  10. Diet and cognitive decline at middle age: the role of antioxidants.

    PubMed

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

    2015-05-14

    To assess the relationship between dietary intake of antioxidants (vitamin C, vitamin E, β-carotene, lutein, flavonoids and lignans) and cognitive decline at middle age, analyses were performed on data from the population based Doetinchem Cohort Study. Habitual diet and cognitive function were assessed twice with a 5-year interval in 2613 persons aged 43-70 year at baseline (1995-2002). Diet was assessed with a validated 178-item semi-quantitative FFQ. Cognitive function was assessed with a neuropsychological test battery, consisting of the 15 Words Learning Test, the Stroop Test, the Word Fluency test, and the Letter Digit Substitution Test. Scores on global cognitive function, memory, processing speed, and cognitive flexibility were calculated. In regression analyses, quintiles of antioxidant intake were associated with change in cognitive domain scores. Results showed that higher lignan intake was linearly associated with less decline in global cognitive function (P= 0.01), memory (P< 0.01) and processing speed (P= 0.04), with about two times less declines in the highest v. the lowest quintile. In the lowest quintile of vitamin E intake, decline in memory was twice as fast as in all higher quintiles (P< 0.01). Global cognitive decline in the highest lutein intake group was greater than in the lowest intake group (P< 0.05). Higher flavonoid intake was associated with greater decline in cognitive flexibility (P for trend = 0.04). Intakes of other antioxidants were not associated with cognitive decline. We conclude that within the range of a habitual dietary intake, higher intake of lignans is associated with less cognitive decline at middle age.

  11. Therapeutic approaches to age-associated neurocognitive disorders

    PubMed Central

    O'Hara, Ruth; Derouesné, Christian; Fountoulakis, Konstantinos N.; Yesavage, Jerome A.

    2001-01-01

    The United Nations projects that the number of individuals with dementia in developed countries alone will be approximately 36,7 million by the year 2050. International recognition of the significant emotional and economic burden of Alzheimer's disease has been matched by a dramatic increase in the development of pharmacological and nonpharmacological approaches to this illness in the past decade. Changing demographics have underscored the necessity to develop similar approaches for the remediation of the cognitive impairment associated with more benign syndromes, such as mild cognitive impairment (MCI) and age-associated cognitive decline (AACD). The present article aims to provide an overview of the most current therapeutic approaches to age-associated neurocognitive disorders. Additionally, it discusses the conceptual and methodological issues that surround the design, implementation, and interpretation of such approaches. PMID:22033831

  12. Changes in physical activity and cognitive decline in older adults living in the community.

    PubMed

    Lee, Yunhwan; Kim, Jinhee; Han, Eun Sook; Chae, Songi; Ryu, Mikyung; Ahn, Kwang Ho; Park, Eun Ju

    2015-01-01

    Accumulating evidence suggests that physical activity may be beneficial in preserving cognition in late life. This study examined the association between baseline and changes in physical activity and cognitive decline in community-dwelling older people. Data were from the Korean Longitudinal Study of Aging, with 2605 aged 65 years and older subjects interviewed in 2006 and followed up for 2 years. Cognitive decline was defined by calculating the Reliable Change Index using the Mini-Mental State Examination. Physical activity levels were categorized as sedentary, low, or high. Changes in physical activity were classified as inactive, decreaser, increaser, or active. Logistic regression analysis of baseline and changes in physical activity with cognitive decline was performed. Compared with the sedentary group at baseline, both the low and high activity groups were less likely to experience cognitive decline. The active (odds ratio [OR] = 0.40, 95 % confidence interval [CI] 0.23-0.68) and increaser (OR = 0.45, 95 % CI 0.27-0.74) group, compared with the inactive counterpart, demonstrated a significantly lower likelihood of cognitive decline. Older adults who remained active or increased activity over time had a reduced risk of cognitive decline. Engagement in physical activity in late life may have cognitive health benefits.

  13. Roles of Arterial Stiffness and Blood Pressure in Hypertension-Associated Cognitive Decline in Healthy Adults.

    PubMed

    Hajjar, Ihab; Goldstein, Felicia C; Martin, Greg S; Quyyumi, Arshed A

    2016-01-01

    Although there is strong evidence that hypertension leads to cognitive decline, especially in the executive domain, the relationship between blood pressure and cognition has been conflicted. Hypertension is characterized by blood pressure elevation and increased arterial stiffness. We aimed at investigating whether arterial stiffness would be superior to blood pressure in predicting cognitive decline and explaining the hypertension-executive decline association. A randomly selected asymptomatic population (n=591, age=49.2 years, 70% women, 27% black, and education=18 years) underwent annual vascular and cognitive assessments. Cognition was assessed using computerized versions commonly used cognitive tests, and principal component analysis was used for deriving cognitive scores for executive function, memory, and working memory. Arterial stiffness was measured by carotid-femoral pulse wave velocity (PWV). Higher PWV, but not blood pressure, was associated with a steeper decline in executive (P=0.0002), memory (P=0.05), and working memory (P=0.02) scores after adjusting for demographics, education, and baseline cognitive performance. This remained true after adjusting for hypertension. Hypertension was associated with greater decline in executive score (P=0.0029) and those with combined hypertension and elevated PWV (>7 m/s) had the greatest decline in executive score (P value hypertension×PWV=0.02). PWV explained the association between hypertension and executive function (P value for hypertension=0.0029 versus 0.24 when adjusting for PWV). In healthy adults, increased arterial stiffness is superior to blood pressure in predicting cognitive decline in all domains and in explaining the hypertension-executive function association. Arterial stiffness, especially in hypertension, may be a target in the prevention of cognitive decline.

  14. The emerging role of dietary fructose in obesity and cognitive decline.

    PubMed

    Lakhan, Shaheen E; Kirchgessner, Annette

    2013-08-08

    The incidence of obesity has increased dramatically over the past several years, and in parallel, so has the prevalence of type 2 diabetes (T2D). Numerous studies have demonstrated that both obesity and T2D are associated with lower cognitive performance, cognitive decline, and dementia. Intake of dietary fructose has also increased. In fact, high-fructose corn syrup (HFCS) accounts for as much as 40% of caloric sweeteners used in the United States. Given the increase in the incidence of Alzheimer's disease (AD), characterized by an age-related decline in memory and cognitive functioning, in this report we review the effects of obesity on cognitive performance and the impact of high fructose intake in promoting cognitive decline. The paper then considers the effects of omega-3 fatty acids (FAs), which have been linked to promising results in cognitive function including ameliorating the impact of a high-fructose diet.

  15. The emerging role of dietary fructose in obesity and cognitive decline.

    PubMed

    Lakhan, Shaheen E; Kirchgessner, Annette

    2013-01-01

    The incidence of obesity has increased dramatically over the past several years, and in parallel, so has the prevalence of type 2 diabetes (T2D). Numerous studies have demonstrated that both obesity and T2D are associated with lower cognitive performance, cognitive decline, and dementia. Intake of dietary fructose has also increased. In fact, high-fructose corn syrup (HFCS) accounts for as much as 40% of caloric sweeteners used in the United States. Given the increase in the incidence of Alzheimer's disease (AD), characterized by an age-related decline in memory and cognitive functioning, in this report we review the effects of obesity on cognitive performance and the impact of high fructose intake in promoting cognitive decline. The paper then considers the effects of omega-3 fatty acids (FAs), which have been linked to promising results in cognitive function including ameliorating the impact of a high-fructose diet. PMID:23924506

  16. Neuroanatomical Substrates of Age-Related Cognitive Decline

    ERIC Educational Resources Information Center

    Salthouse, Timothy A.

    2011-01-01

    There are many reports of relations between age and cognitive variables and of relations between age and variables representing different aspects of brain structure and a few reports of relations between brain structure variables and cognitive variables. These findings have sometimes led to inferences that the age-related brain changes cause the…

  17. Foreign language training as cognitive therapy for age-related cognitive decline: a hypothesis for future research.

    PubMed

    Antoniou, Mark; Gunasekera, Geshri M; Wong, Patrick C M

    2013-12-01

    Over the next fifty years, the number of older adults is set to reach record levels. Protecting older adults from the age-related effects of cognitive decline is one of the greatest challenges of the next few decades as it places increasing pressure on families, health systems, and economies on a global scale. The disease-state of age-related cognitive decline-Alzheimer's disease and other dementias-hijacks our consciousness and intellectual autonomy. However, there is evidence that cognitively stimulating activities protect against the adverse effects of cognitive decline. Similarly, bilingualism is also considered to be a safeguard. We propose that foreign language learning programs aimed at older populations are an optimal solution for building cognitive reserve because language learning engages an extensive brain network that is known to overlap with the regions negatively affected by the aging process. It is recommended that future research should test this potentially fruitful hypothesis. PMID:24051310

  18. Cognitive reserve moderates decline in information processing speed in multiple sclerosis patients.

    PubMed

    Benedict, Ralph H B; Morrow, Sarah A; Weinstock Guttman, Bianca; Cookfair, Diane; Schretlen, David J

    2010-09-01

    Cognitive reserve is widely recognized as a moderator of cognitive decline in patients with senile dementias such as Alzheimer's disease. The same effect may occur in multiple sclerosis (MS), an immunologic disorder affecting the central nervous system. While MS is traditionally considered an inflammatory, white matter disease, degeneration of gray matter is increasingly recognized as the primary contributor to progressive cognitive decline. Our aim was to determine if individual differences in estimated cognitive reserve protect against the progression of cognitive dysfunction in MS. Ninety-one patients assessed twice roughly 5 years apart were identified retrospectively. Cognitive testing emphasized mental processing speed. Cognitive reserve was estimated by years of education and by performance on the North American Adult Reading Test (NAART). After controlling for baseline characteristics, both years of education (p = .013) and NAART scores (p = .049) significantly improved regression models predicting cognitive decline. Symbol Digit Modalities Test (SDMT) performance showed no significant change in patients with > 14 years of education, whereas it declined significantly in patients with ≤ 14 years of education. We conclude that greater cognitive reserve as indexed by either higher premorbid intelligence or more years of education protects against the progression of cognitive dysfunction in MS.

  19. Cognitive Decline and Oral Health in Middle-aged Adults in the ARIC Study

    PubMed Central

    Naorungroj, S.; Slade, G.D.; Beck, J.D.; Mosley, T.H.; Gottesman, R.F.; Alonso, A.; Heiss, G.

    2013-01-01

    Even before dementia becomes apparent, cognitive decline may contribute to deterioration in oral health. This cohort study of middle-aged adults evaluated associations of six-year change in cognitive function with oral health behaviors and conditions in the Atherosclerosis Risk in Communities (ARIC) study. Cognitive function was measured at study visits in 1990-1992 and 1996-1998 with three tests: (a) Delayed Word Recall (DWR), (b) Digit Symbol Substitution (DSS), and (c) Word Fluency (WF). Cognitive decline scores were computed as ‘studentized’ residuals of 1996-1998 scores regressed against 1990-1992 scores. In 1996-1998, 10,050 participants answered dental screening questions, and 5,878 of 8,782 dentate participants received a comprehensive oral examination. Multiple regression models used cognitive change to predict oral health behaviors and conditions with adjustment for covariates. In the fully adjusted models, greater decline in all three measures of cognitive function was associated with increased odds of complete tooth loss. Greater decline in DSS and WF scores was associated with infrequent toothbrushing. Decline in WF scores was also associated with higher plaque levels. In these middle-aged adults, six-year cognitive decline was modestly associated with less frequent toothbrushing, plaque deposit, and greater odds of edentulism, but not with other oral behaviors or diseases. PMID:23872988

  20. Cognitive decline and oral health in middle-aged adults in the ARIC study.

    PubMed

    Naorungroj, S; Slade, G D; Beck, J D; Mosley, T H; Gottesman, R F; Alonso, A; Heiss, G

    2013-09-01

    Even before dementia becomes apparent, cognitive decline may contribute to deterioration in oral health. This cohort study of middle-aged adults evaluated associations of six-year change in cognitive function with oral health behaviors and conditions in the Atherosclerosis Risk in Communities (ARIC) study. Cognitive function was measured at study visits in 1990-1992 and 1996-1998 with three tests: (a) Delayed Word Recall (DWR), (b) Digit Symbol Substitution (DSS), and (c) Word Fluency (WF). Cognitive decline scores were computed as 'studentized' residuals of 1996-1998 scores regressed against 1990-1992 scores. In 1996-1998, 10,050 participants answered dental screening questions, and 5,878 of 8,782 dentate participants received a comprehensive oral examination. Multiple regression models used cognitive change to predict oral health behaviors and conditions with adjustment for covariates. In the fully adjusted models, greater decline in all three measures of cognitive function was associated with increased odds of complete tooth loss. Greater decline in DSS and WF scores was associated with infrequent toothbrushing. Decline in WF scores was also associated with higher plaque levels. In these middle-aged adults, six-year cognitive decline was modestly associated with less frequent toothbrushing, plaque deposit, and greater odds of edentulism, but not with other oral behaviors or diseases. PMID:23872988

  1. Structural Neuroimaging Markers of Cognitive Decline in Parkinson's Disease.

    PubMed

    Hanganu, Alexandru; Monchi, Oury

    2016-01-01

    Cognitive impairment in patients with Parkinson's disease is a major challenge since it has been established that 25 to 40% of patients will develop cognitive impairment early in the disease. Furthermore, it has been reported that up to 80% of Parkinsonian patients will eventually develop dementia. Thus, it is important to improve the diagnosing procedures in order to detect cognitive impairment at early stages of development and to delay as much as possible the developing of dementia. One major challenge is that patients with mild cognitive impairment exhibit measurable cognitive deficits according to recently established criteria, yet those deficits are not severe enough to interfere with daily living, hence being avoided by patients, and might be overseen by clinicians. Recent advances in neuroimaging brain analysis allowed the establishment of several anatomical markers that have the potential to be considered for early detection of cognitive impairment in Parkinsonian patients. This review aims to outline the neuroimaging possibilities in diagnosing cognitive impairment in patients with Parkinson's disease and to take into consideration the near-future possibilities of their implementation into clinical practice.

  2. Structural Neuroimaging Markers of Cognitive Decline in Parkinson's Disease

    PubMed Central

    Hanganu, Alexandru; Monchi, Oury

    2016-01-01

    Cognitive impairment in patients with Parkinson's disease is a major challenge since it has been established that 25 to 40% of patients will develop cognitive impairment early in the disease. Furthermore, it has been reported that up to 80% of Parkinsonian patients will eventually develop dementia. Thus, it is important to improve the diagnosing procedures in order to detect cognitive impairment at early stages of development and to delay as much as possible the developing of dementia. One major challenge is that patients with mild cognitive impairment exhibit measurable cognitive deficits according to recently established criteria, yet those deficits are not severe enough to interfere with daily living, hence being avoided by patients, and might be overseen by clinicians. Recent advances in neuroimaging brain analysis allowed the establishment of several anatomical markers that have the potential to be considered for early detection of cognitive impairment in Parkinsonian patients. This review aims to outline the neuroimaging possibilities in diagnosing cognitive impairment in patients with Parkinson's disease and to take into consideration the near-future possibilities of their implementation into clinical practice. PMID:27190672

  3. Obstructive Sleep Apnea and 15-Year Cognitive Decline: The Atherosclerosis Risk in Communities (ARIC) Study

    PubMed Central

    Lutsey, Pamela L.; Bengtson, Lindsay G.S.; Punjabi, Naresh M.; Shahar, Eyal; Mosley, Thomas H.; Gottesman, Rebecca F.; Wruck, Lisa M.; MacLehose, Richard F.; Alonso, Alvaro

    2016-01-01

    Study Objectives: Prospective data evaluating abnormal sleep quality and quantity with cognitive decline are limited because most studies used subjective data and/or had short follow-up. We hypothesized that, over 15 y of follow-up, participants with objectively measured obstructive sleep apnea (OSA) and other indices of poor sleep quantity and quality would experience greater decline in cognitive functioning than participants with normal sleep patterns. Methods: ARIC participants (n = 966; mean age 61 y, 55% women) with in-home polysomnography (1996–1998) and repeated cognitive testing were followed for 15 y. Three cognitive tests (Delayed Word Recall, Word Fluency, and Digit Symbol Substitution) were administered at two time points (1996–1998 and 2011–2013). Ten additional cognitive tests were administered at the 2011–2013 neurocognitive examination. OSA was modeled using established clinical OSA severity categories. Multivariable linear regression was used to explore associations of OSA and other sleep indices with change in cognitive tests between the two assessments. Results: A median of 14.9 y (max: 17.3) passed between the two cognitive assessments. OSA category and additional indices of sleep (other measures of hypoxemia and disordered breathing, sleep fragmentation, sleep duration) were not associated with change in any cognitive test. Analyses of OSA severity categories and 10 cognitive tests administered only in 2011–2013 also showed little evidence of an association. Conclusions: Overall, abnormal sleep quality and quantity at midlife was not related to cognitive decline and later-life cognition. The effect of adverse sleep quality and quantity on cognitive decline among the elderly remains to be determined. Citation: Lutsey PL, Bengtson LG, Punjabi NM, Shahar E, Mosley TH, Gottesman RF, Wruck LM, MacLehose RF, Alonso A. Obstructive sleep apnea and 15-year cognitive decline: the Atherosclerosis Risk in Communities (ARIC) study. SLEEP 2016

  4. Pattern and Rate of Cognitive Decline in Cerebral Small Vessel Disease: A Prospective Study

    PubMed Central

    Lawrence, Andrew J.; Brookes, Rebecca L.; Zeestraten, Eva A.; Barrick, Thomas R.; Morris, Robin G.; Markus, Hugh S.

    2015-01-01

    Objectives Cognitive impairment, predominantly affecting processing speed and executive function, is an important consequence of cerebral small vessel disease (SVD). To date, few longitudinal studies of cognition in SVD have been conducted. We determined the pattern and rate of cognitive decline in SVD and used the results to determine sample size calculations for clinical trials of interventions reducing cognitive decline. Methods 121 patients with MRI confirmed lacunar stroke and leukoaraiosis were enrolled into the prospective St George’s Cognition And Neuroimaging in Stroke (SCANS) study. Patients attended one baseline and three annual cognitive assessments providing 36 month follow-up data. Neuropsychological assessment comprised a battery of tests assessing working memory, long-term (episodic) memory, processing speed and executive function. We calculated annualized change in cognition for the 98 patients who completed at least two time-points. Results Task performance was heterogeneous, but significant cognitive decline was found for the executive function index (p<0.007). Working memory and processing speed decreased numerically, but not significantly. The executive function composite score would require the smallest samples sizes for a treatment trial with an aim of halting decline, but this would still require over 2,000 patients per arm to detect a 30% difference with power of 0.8 over a three year follow-up. Conclusions The pattern of cognitive decline seen in SVD over three years is consistent with the pattern of impairments at baseline. Rates of decline were slow and sample sizes would need to be large for clinical trials aimed at halting decline beyond initial diagnosis using cognitive scores as an outcome measure. This emphasizes the importance of more sensitive surrogate markers in this disease. PMID:26273828

  5. Computerized and virtual reality cognitive training for individuals at high risk of cognitive decline: systematic review of the literature.

    PubMed

    Coyle, Hannah; Traynor, Victoria; Solowij, Nadia

    2015-04-01

    The aim of this study was to assess the efficacy of cognitive training, specifically computerized cognitive training (CCT) and virtual reality cognitive training (VRCT), programs for individuals living with mild cognitive impairment (MCI) or dementia and therefore at high risk of cognitive decline. After searching a range of academic databases (CINHAL, PSYCinfo, and Web of Science), the studies evaluated (N = 16) were categorized as CCT (N = 10), VRCT (N = 3), and multimodal interventions (N = 3). Effect sizes were calculated, but a meta-analysis was not possible because of the large variability of study design and outcome measures adopted. The cognitive domains of attention, executive function, and memory (visual and verbal) showed the most consistent improvements. The positive effects on psychological outcomes (N = 6) were significant reductions on depressive symptoms (N = 3) and anxiety (N = 2) and improved perceived use of memory strategy (N = 1). Assessments of activities of daily living demonstrated no significant improvements (N = 8). Follow-up studies (N = 5) demonstrated long-term improvements in cognitive and psychological outcomes (N = 3), and the intervention groups showed a plateau effect of cognitive functioning compared with the cognitive decline experienced by control groups (N = 2). CCT and VRCT were moderately effective in long-term improvement of cognition for those at high risk of cognitive decline. Total intervention time did not mediate efficacy. Future research needs to improve study design by including larger samples, longitudinal designs, and a greater range of outcome measures, including functional and quality of life measures, to assess the wider effect of cognitive training on individuals at high risk of cognitive decline.

  6. Cerebral amyloidosis associated with cognitive decline in autosomal dominant Alzheimer disease

    PubMed Central

    Wang, Fen; Gordon, Brian A.; Ryman, Davis C.; Ma, Shengmei; Xiong, Chengjie; Hassenstab, Jason; Goate, Alison; Fagan, Anne M.; Cairns, Nigel J.; Marcus, Daniel S.; McDade, Eric; Ringman, John M.; Graff-Radford, Neill R.; Ghetti, Bernardino; Farlow, Martin R.; Sperling, Reisa; Salloway, Steve; Schofield, Peter R.; Masters, Colin L.; Martins, Ralph N.; Rossor, Martin N.; Jucker, Mathias; Danek, Adrian; Förster, Stefan; Lane, Christopher A.S.; Morris, John C.; Bateman, Randall J.

    2015-01-01

    Objective: To investigate the associations of cerebral amyloidosis with concurrent cognitive performance and with longitudinal cognitive decline in asymptomatic and symptomatic stages of autosomal dominant Alzheimer disease (ADAD). Methods: Two hundred sixty-three participants enrolled in the Dominantly Inherited Alzheimer Network observational study underwent neuropsychological evaluation as well as PET scans with Pittsburgh compound B. One hundred twenty-one participants completed at least 1 follow-up neuropsychological evaluation. Four composite cognitive measures representing global cognition, episodic memory, language, and working memory were generated using z scores from a battery of 13 standard neuropsychological tests. General linear mixed-effects models were used to investigate the relationship between baseline cerebral amyloidosis and baseline cognitive performance and whether baseline cerebral amyloidosis predicts cognitive change over time (mean follow-up 2.32 years ± 0.92, range 0.89–4.19) after controlling for estimated years from expected symptom onset, APOE ε4 allelic status, and education. Results: In asymptomatic mutation carriers, amyloid burden was not associated with baseline cognitive functioning but was significantly predictive of longitudinal decline in episodic memory. In symptomatic mutation carriers, cerebral amyloidosis was correlated with worse baseline performance in multiple cognitive composites and predicted greater decline over time in global cognition, working memory, and Mini-Mental State Examination. Conclusions: Cerebral amyloidosis predicts longitudinal episodic memory decline in presymptomatic ADAD and multidomain cognitive decline in symptomatic ADAD. These findings imply that amyloidosis in the brain is an indicator of early cognitive decline and provides a useful outcome measure for early assessment and prevention treatment trials. PMID:26245925

  7. [Vascular factors and progression of cognitive decline in elderly people].

    PubMed

    Bidzan, Leszek; Bidzan, Mariola

    2005-01-01

    The aim of the study was to assess the impact of vascular factors on the rate of progression of cognitive impairment. The study included 291 subjects without dementia. Cognitive function were assessed with the Alzheimer Disease Assessment Scale--cognitive subscale (ADAS--cog) which were conducted at baseline and at the end of the study. Statistical analysis included 215 persons. During the observation AD developed in 19 subjects and 11 vascular and mix dementia (according to DSM-IIIR and DSM-IV criteria). Subjects were categorized by the baseline Modified Hachinski Ischemic Score as having vascular factors 0-1 point (n = 140) or vascular factors > 1 point (n = 75). Statistical analyses were based on the patients' Modified Hachinski Ischemic Score dichotomization. The results show that vascular factors were risk factors for Alzheimer type dementia but the study does not prove the impact of vascular factors on progression of cognitive impairment. PMID:16358597

  8. Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline.

    PubMed

    Cho, Kyung-Ok; Lybrand, Zane R; Ito, Naoki; Brulet, Rebecca; Tafacory, Farrah; Zhang, Ling; Good, Levi; Ure, Kerstin; Kernie, Steven G; Birnbaum, Shari G; Scharfman, Helen E; Eisch, Amelia J; Hsieh, Jenny

    2015-03-26

    Acute seizures after a severe brain insult can often lead to epilepsy and cognitive impairment. Aberrant hippocampal neurogenesis follows the insult but the role of adult-generated neurons in the development of chronic seizures or associated cognitive deficits remains to be determined. Here we show that the ablation of adult neurogenesis before pilocarpine-induced acute seizures in mice leads to a reduction in chronic seizure frequency. We also show that ablation of neurogenesis normalizes epilepsy-associated cognitive deficits. Remarkably, the effect of ablating adult neurogenesis before acute seizures is long lasting as it suppresses chronic seizure frequency for nearly 1 year. These findings establish a key role of neurogenesis in chronic seizure development and associated memory impairment and suggest that targeting aberrant hippocampal neurogenesis may reduce recurrent seizures and restore cognitive function following a pro-epileptic brain insult.

  9. Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline.

    PubMed

    Cho, Kyung-Ok; Lybrand, Zane R; Ito, Naoki; Brulet, Rebecca; Tafacory, Farrah; Zhang, Ling; Good, Levi; Ure, Kerstin; Kernie, Steven G; Birnbaum, Shari G; Scharfman, Helen E; Eisch, Amelia J; Hsieh, Jenny

    2015-01-01

    Acute seizures after a severe brain insult can often lead to epilepsy and cognitive impairment. Aberrant hippocampal neurogenesis follows the insult but the role of adult-generated neurons in the development of chronic seizures or associated cognitive deficits remains to be determined. Here we show that the ablation of adult neurogenesis before pilocarpine-induced acute seizures in mice leads to a reduction in chronic seizure frequency. We also show that ablation of neurogenesis normalizes epilepsy-associated cognitive deficits. Remarkably, the effect of ablating adult neurogenesis before acute seizures is long lasting as it suppresses chronic seizure frequency for nearly 1 year. These findings establish a key role of neurogenesis in chronic seizure development and associated memory impairment and suggest that targeting aberrant hippocampal neurogenesis may reduce recurrent seizures and restore cognitive function following a pro-epileptic brain insult. PMID:25808087

  10. Fructose in obesity and cognitive decline: is it the fructose or the excess energy?

    PubMed

    Chiavaroli, Laura; Ha, Vanessa; de Souza, Russell J; Kendall, Cyril Wc; Sievenpiper, John L

    2014-03-25

    We read with interest the review by Lakhan and Kirchgessner, proposing that high fructose intake promotes obesity, metabolic syndrome, diabetes, and cognitive decline. Their focus on the role of fructose seems premature due to confounding from energy and the heavy reliance on low quality evidence from animal models. There is a lack of high quality evidence directly assessing the role of fructose in cognitive decline. Although one cannot exclude the possibility of a link, it remains an unconfirmed hypothesis.

  11. 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. PMID:27178844

  12. 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

  13. Effect of plasma lipids and APOE genotype on cognitive decline.

    PubMed

    Yasuno, Fumihiko; Asada, Takashi

    2013-03-01

    A central tenet of brain aging is that "what is good for the heart is good for the brain." We examined the combined effect of plasma lipids and APOE genotype on cognitive function in elderly individuals. Plasma concentrations of high-density lipoprotein (HDL), low-density lipoprotein, triglyceride, total cholesterol, and apolipoprotein E (apoE) were evaluated in 622 community-dwelling individuals aged 65 years and older. We investigated the associations between plasma lipids and cognitive function in APOE4 carrier (E4+) and APOE4 noncarrier (E4-) groups using 3-year longitudinal data. At baseline and 3 years later, cognitive scores were correlated with plasma apoE levels in both E4- and E4+, and HDL level in E4-. Our findings suggest that an interaction between apoE and HDL is facilitated by APOE4, and is possibly linked with an enhancement of neuroplasticity and with resultant protective effects on cognitive function in later life. Preservation of higher plasma apoE and HDL from early life is proposed as a possible strategy for maintaining cognitive function in later life, especially for APOE4-positive individuals.

  14. Biological mechanisms of physical activity in preventing cognitive decline.

    PubMed

    Lista, I; Sorrentino, G

    2010-05-01

    In order to guarantee better conditions for competition, the nervous system has developed not only mechanisms controlling muscle effectors, but also retrograde systems that, starting from peripheral structures, may influence brain functions. Under such perspective, physical activity could play an important role in influencing cognitive brain functions including learning and memory. The results of epidemiological studies (cross-sectional, prospective and retrospective) support a positive relationship between cognition and physical activities. Recent meta-analysis confirmed a significant effect of exercise on cognitive functions. However, the biological mechanisms that underlie such beneficial effects are still to be completely elucidated. They include supramolecular mechanisms (e.g. neurogenesis, synaptogenesis, and angiogenesis) which, in turn, are controlled by molecular mechanisms, such as BDNF, IGF-1, hormone and second messengers.

  15. The role of B-vitamins in preventing and treating cognitive impairment and decline

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many epidemiologic studies have considered the question of whether markers of B-vitamin status are associated with cognitive function and cognitive decline. This avenue of research was sparked by the homocysteine (Hcy) theory of cardiovascular disease (CVD), which was extended to Alzheimer’s disease...

  16. C-reactive protein and genetic variants and cognitive decline in old age: The PROSPER Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plasma concentrations of C-reactive protein (CRP), a marker of chronic inflammation, have been associated with cognitive impairment in old age. However, it is unknown whether CRP is causally linked to cognitive decline. Within the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) tri...

  17. Prevention of Age-Related Cognitive Decline: Which Strategies, When, and for Whom?

    PubMed

    Shatenstein, Bryna; Barberger-Gateau, Pascale; Mecocci, Patrizia

    2015-01-01

    Brain aging is characterized by the progressive and gradual accumulation of detrimental changes in structure and function, which increase risk of age-related cognitive decline and dementia. This devastating chronic condition generates a huge social and economic burden and accounts for 11.2% of years of disability. The increase in lifespan has contributed to the increase in dementia prevalence; however, there is currently no curative treatment for most causes of dementias. This paper reviews evidence-based strategies to build, enhance, and preserve cognition over the lifespan by examining approaches that work best, proposing when in the life course they should be implemented, and in which population group(s). Recent work shows a tendency to decreased age-specific prevalence and incidence of cognitive problems and dementia among people born later in the first half of the 20th century, citing higher educational levels, improvements in lifestyle, and better handling of vascular risk factors. This implies that we can target modifiable environmental, lifestyle, and health risk factors to modify the trajectory of cognitive decline before the onset of irreversible dementia. Because building cognitive reserve and prevention of cognitive decline are of critical importance, interventions are needed at every stage of the life course to foster cognitive stimulation, and enable healthy eating habits and physical activity throughout the lifespan. Preventive interventions to decrease and delay cognitive decline and its consequences in old age will also require collaboration and action on the part of policy-makers at the political and social level.

  18. Nutraceutical properties of Mediterranean diet and cognitive decline: possible underlying mechanisms.

    PubMed

    Frisardi, Vincenza; Panza, Francesco; Seripa, Davide; Imbimbo, Bruno P; Vendemiale, Gianluigi; Pilotto, Alberto; Solfrizzi, Vincenzo

    2010-01-01

    Recent prospective studies provided evidence that higher adherence to a Mediterranean-type diet could be associated with slower cognitive decline, reduced risk of progression from mild cognitive impairment to Alzheimer's disease (AD), reduced risk of AD, and decreased mortality in AD patients. Furthermore, the Mediterranean diet (MeDi) combines several foods, micro- and macronutrients already separately proposed as potential protective factors against dementia and predementia syndromes. At present, epidemiological evidence suggests a possible association between fish consumption, monounsaturated fatty acids, and polyunsaturated fatty acids (PUFA) (particularly, n-3 PUFA), and reduced risk of cognitive decline and dementia. Light to moderate alcohol use may be associated with a reduced risk of incident dementia and AD, while for vascular dementia, cognitive decline, and predementia syndromes, the current evidence is only suggestive of a protective effect. Finally, the limited epidemiological evidence available on fruit and vegetable consumption and cognition generally support a protective role of these macronutrients against cognitive decline, dementia, and AD. We reviewed evidence on the possible mechanisms underlying the suggested protective role of MeDi against age-related changes in cognitive function, predementia syndromes, and dementia, examining the possible role of macronutrients and food nutrients of the MeDi and their nutraceutical properties in modulating the risk of cognitive decline. Although vascular variables are likely to be in the causal pathway between MeDi and dementia syndromes and should be considered as possible mediators, other nonvascular biological mechanisms (i.e., metabolic, oxidative, and inflammatory) may be invoked to explain the complex epidemiological association between MeDi and cognitive decline.

  19. Relation of neuropathology with cognitive decline among older persons without dementia

    PubMed Central

    Boyle, Patricia A.; Yu, Lei; Wilson, Robert S.; Schneider, Julie A.; Bennett, David A.

    2013-01-01

    Objective: Although it is now widely accepted that dementia has a long preclinical phase during which neuropathology accumulates and cognition declines, little is known about the relation of neuropathology with the longitudinal rate of change in cognition among older persons without dementia. We quantified the burden of the neuropathologies of the three most common causes of dementia [i.e., Alzheimer’s disease (AD), cerebrovascular disease (CVD), and Lewy body disease (LBD)] and examined their relation with cognitive decline in a large cohort of persons without dementia proximate to death. Methods: A total of 467 deceased participants without dementia from two longitudinal clinical-pathologic studies, Rush Memory and Aging Project and Religious Orders Study, completed a mean of 7 annual evaluations including 17 cognitive tests. Neuropathologic examinations provided quantitative measures of AD (i.e., amyloid load, tangle density), CVD (i.e., macroscopic infarcts, microinfarcts), and neocortical Lewy bodies. Random coefficient models were used to examine the relation of the neuropathologies with rates of global cognitive decline as well as decline in four specific cognitive systems. Results: At autopsy, 82% of persons without dementia had amyloid, 100% had tangles, 29% had macroscopic infarcts, 25% had microinfarcts, and 6% had neocortical Lewy bodies. Global cognition declined a mean of 0.034 unit per year (SE = 0.003, p < 0.001). In separate analyses, amyloid, tangles (p-values <0.001) and neocortical Lewy bodies (p = 0.015) were associated with an increased rate of global cognitive decline; macroscopic infarcts and microinfarcts were not. Further, when analyzed simultaneously, amyloid, tangles, and neocortical Lewy bodies remained associated with global cognitive decline (p-values <0.024). Finally, measures of AD were associated with decline in three of four systems, including episodic memory (i.e., tangles), semantic memory (i.e., amyloid and tangles), and

  20. Foreign language training as cognitive therapy for age-related cognitive decline: A hypothesis for future research

    PubMed Central

    Antoniou, Mark; Gunasekera, Geshri; Wong, Patrick C. M.

    2014-01-01

    Over the next fifty years, the number of older adults is set to reach record levels. Protecting older adults from the age-related effects of cognitive decline is one of the greatest challenges of the next few decades as it places increasing pressure on families, health systems, and economies on a global scale. The disease-state of age-related cognitive decline—Alzheimer's disease and other dementias—hijacks our consciousness and intellectual autonomy. However, there is evidence that cognitively stimulating activities protect against the adverse effects of cognitive decline. Similarly, bilingualism is also considered to be a safeguard. We propose that foreign language learning programs aimed at older populations are an optimal solution for building cognitive reserve because language learning engages an extensive brain network that is known to overlap with the regions negatively affected by the aging process. It is recommended that future research should test this potentially fruitful hypothesis. PMID:24051310

  1. Literature review on the role of dietary protein and amino acids in cognitive functioning and cognitive decline.

    PubMed

    van de Rest, Ondine; van der Zwaluw, Nikita L; de Groot, Lisette C P G M

    2013-11-01

    As the population of elderly people is growing rapidly, the number of individuals with dementia and cognitive impairment is also increasing. One of the preventive measures against cognitive decline is diet and different dietary factors have already been investigated. This review provides an overview of studies on dietary protein and cognitive functioning and cognitive decline. Also studies on the individual amino acids that are related to brain function, tryptophan and tyrosine, are discussed. Overall, the role of dietary protein intake on cognitive functioning as well as cognitive decline has hardly been studied; we found eight observational studies and three intervention studies. More studies investigated the role of tryptophan (14 studies) and tyrosine (nine studies) in relation to cognitive functioning, but all these studies were performed in young adult populations and mostly under special conditions. Research in elderly populations, in particular, is warranted. Also more research is needed to come to definitive conclusions and specific recommendations regarding protein intake or intake of specific amino acids for maintaining optimal cognitive functioning.

  2. Ascorbic Acid and the Brain: Rationale for the Use against Cognitive Decline

    PubMed Central

    Harrison, Fiona E.; Bowman, Gene L.; Polidori, Maria Cristina

    2014-01-01

    This review is focused upon the role of ascorbic acid (AA, vitamin C) in the promotion of healthy brain aging. Particular attention is attributed to the biochemistry and neuronal metabolism interface, transport across tissues, animal models that are useful for this area of research, and the human studies that implicate AA in the continuum between normal cognitive aging and age-related cognitive decline up to Alzheimer’s disease. Vascular risk factors and comorbidity relationships with cognitive decline and AA are discussed to facilitate strategies for advancing AA research in the area of brain health and neurodegeneration. PMID:24763117

  3. A systematic review of cognitive decline in dementia with Lewy bodies versus Alzheimer’s disease

    PubMed Central

    2014-01-01

    Introduction The aim of this review was to investigate whether there is a faster cognitive decline in dementia with Lewy bodies (DLB) than in Alzheimer’s disease (AD) over time. Methods PsycINFO and Medline were searched from 1946 to February 2013. A quality rating from 1 to 15 (best) was applied to the included studies. A quantitative meta-analysis was done on studies with mini mental state examination (MMSE) as the outcome measure. Results A total of 18 studies were included. Of these, six (36%) reported significant differences in the rate of cognitive decline. Three studies reported a faster cognitive decline on MMSE in patients with mixed DLB and AD compared to pure forms, whereas two studies reported a faster decline on delayed recall and recognition in AD and one in DLB on verbal fluency. Mean quality scores for studies that did or did not differ were not significantly different. Six studies reported MMSE scores and were included in the meta-analysis, which showed no significant difference in annual decline on MMSE between DLB (mean 3.4) and AD (mean 3.3). Conclusions Our findings do not support the hypothesis of a faster rate of cognitive decline in DLB compared to AD. Future studies should apply recent diagnostic criteria, as well as extensive diagnostic evaluation and ideally autopsy diagnosis. Studies with large enough samples, detailed cognitive tests, at least two years follow up and multivariate statistical analysis are also needed. PMID:25478024

  4. Cognitive decline is associated with risk aversion and temporal discounting in older adults without dementia.

    PubMed

    James, Bryan D; Boyle, Patricia A; Yu, Lei; Han, S Duke; Bennett, David A

    2015-01-01

    Risk aversion and temporal discounting are preferences that are strongly linked to sub-optimal financial and health decision making ability. Prior studies have shown they differ by age and cognitive ability, but it remains unclear whether differences are due to age-related cognitive decline or lower cognitive abilities over the life span. We tested the hypothesis that cognitive decline is associated with higher risk aversion and temporal discounting in 455 older persons without dementia from the Memory and Aging Project, a longitudinal cohort study of aging in Chicago. All underwent repeated annual cognitive evaluations using a detailed battery including 19 tests. Risk aversion was measured using standard behavioral economics questions: participants were asked to choose between a certain monetary payment versus a gamble in which they could gain more or nothing; potential gamble gains varied across questions. Temporal discounting: participants were asked to choose between an immediate, smaller payment and a delayed, larger one; two sets of questions addressed small and large stakes based on payment amount. Regression analyses were used to examine whether prior rate of cognitive decline predicted level of risk aversion and temporal discounting, controlling for age, sex, and education. Over an average of 5.5 (SD=2.9) years, cognition declined at an average of 0.016 units per year (SD=0.03). More rapid cognitive decline predicted higher levels of risk aversion (p=0.002) and temporal discounting (small stakes: p=0.01, high stakes: p=0.006). Further, associations between cognitive decline and risk aversion (p=0.015) and large stakes temporal discounting (p=0.026) persisted in analyses restricted to persons without any cognitive impairment (i.e., no dementia or mild cognitive impairment); the association of cognitive decline and small stakes temporal discounting was no longer statistically significant (p=0.078). These findings are consistent with the hypothesis that

  5. Cognitive Decline Is Associated with Risk Aversion and Temporal Discounting in Older Adults without Dementia

    PubMed Central

    James, Bryan D.; Boyle, Patricia A.; Yu, Lei; Han, S. Duke; Bennett, David A.

    2015-01-01

    Risk aversion and temporal discounting are preferences that are strongly linked to sub-optimal financial and health decision making ability. Prior studies have shown they differ by age and cognitive ability, but it remains unclear whether differences are due to age-related cognitive decline or lower cognitive abilities over the life span. We tested the hypothesis that cognitive decline is associated with higher risk aversion and temporal discounting in 455 older persons without dementia from the Memory and Aging Project, a longitudinal cohort study of aging in Chicago. All underwent repeated annual cognitive evaluations using a detailed battery including 19 tests. Risk aversion was measured using standard behavioral economics questions: participants were asked to choose between a certain monetary payment versus a gamble in which they could gain more or nothing; potential gamble gains varied across questions. Temporal discounting: participants were asked to choose between an immediate, smaller payment and a delayed, larger one; two sets of questions addressed small and large stakes based on payment amount. Regression analyses were used to examine whether prior rate of cognitive decline predicted level of risk aversion and temporal discounting, controlling for age, sex, and education. Over an average of 5.5 (SD=2.9) years, cognition declined at an average of 0.016 units per year (SD=0.03). More rapid cognitive decline predicted higher levels of risk aversion (p=0.002) and temporal discounting (small stakes: p=0.01, high stakes: p=0.006). Further, associations between cognitive decline and risk aversion (p=0.015) and large stakes temporal discounting (p=0.026) persisted in analyses restricted to persons without any cognitive impairment (i.e., no dementia or mild cognitive impairment); the association of cognitive decline and small stakes temporal discounting was no longer statistically significant (p=0.078). These findings are consistent with the hypothesis that

  6. Male cognitive performance declines in the absence of sexual selection

    PubMed Central

    Hollis, Brian; Kawecki, Tadeusz J.

    2014-01-01

    Sexual selection is responsible for the evolution of male ornaments and armaments, but its role in the evolution of cognition—the ability to process, retain and use information—is largely unexplored. Because successful courtship is likely to involve processing information in complex, competitive sexual environments, we hypothesized that sexual selection contributes to the evolution and maintenance of cognitive abilities in males. To test this, we removed mate choice and mate competition from experimental populations of Drosophila melanogaster by enforcing monogamy for over 100 generations. Males evolved under monogamy became less proficient than polygamous control males at relatively complex cognitive tasks. When faced with one receptive and several unreceptive females, polygamous males quickly focused on receptive females, whereas monogamous males continued to direct substantial courtship effort towards unreceptive females. As a result, monogamous males were less successful in this complex setting, despite being as quick to mate as their polygamous counterparts with only one receptive female. This diminished ability to use past information was not limited to the courtship context: monogamous males (but not females) also showed reduced aversive olfactory learning ability. Our results provide direct experimental evidence that the intensity of sexual selection is an important factor in the evolution of male cognitive ability. PMID:24573848

  7. Caffeine and cognitive decline in elderly women at high vascular risk

    PubMed Central

    Vercambre, Marie-Noël; Berr, Claudine; Ritchie, Karen; Kang, Jae H.

    2013-01-01

    Background Persons with vascular disorders are at higher risk of cognitive decline. Objective To determine whether caffeine may be associated with cognitive decline reduction in elderly at high vascular risk. Methods We included 2475 women aged 65+ years in the Women’s Antioxidant Cardiovascular Study, a randomized trial of antioxidants and B vitamins for cardiovascular disease secondary prevention. We ascertained regular caffeine intake at baseline (1995–1996) using a validated 116 item-food frequency questionnaire. From 1998–2000 to 2005–2006, we administered four telephone cognitive assessments at two-year intervals evaluating global cognition, verbal memory and category fluency. The primary outcome was the change in global cognitive score, which was the average of the z-scores of all tests. We used generalized linear models for repeated measures that were adjusted for various sociodemographic, health and lifestyle factors to evaluate the difference in cognitive decline rates across quintiles of caffeine intake. Results We observed significantly slower rates of cognitive decline with increasing caffeine intake (p-trend=0.02). The rate difference between the highest and lowest quintiles of usual caffeine intake (> 371 versus < 30 mg/day) was equivalent to that observed between those who were 7 years apart in age (p=0.006). Consumption of caffeinated coffee was significantly related to slower cognitive decline (p-trend=0.05), but not other caffeinated products (e.g., decaf, tea, cola, chocolate). We conducted interaction analyses and observed stronger associations in women assigned to vitamin B supplementation (p-interaction = 0.02). Conclusions Caffeine intake was related to moderately better cognitive maintenance over 5 years in older women with vascular disorders. PMID:23422357

  8. Random change point model for joint modeling of cognitive decline and dementia.

    PubMed

    Jacqmin-Gadda, Hélène; Commenges, Daniel; Dartigues, Jean-François

    2006-03-01

    We propose a joint model for cognitive decline and risk of dementia to describe the pre-diagnosis phase of dementia. We aim to estimate the time when the cognitive evolution of subjects in the pre-dementia phase becomes distinguishable from normal evolution and to study whether the shape of cognitive decline depends on educational level. The model combines a piecewise polynomial mixed model with a random change point for the evolution of the cognitive test and a log-normal model depending on the random change point for the time to dementia. Parameters are estimated by maximum likelihood using a Newton-Raphson-like algorithm. The expected cognitive evolution given age to dementia is then derived and the marginal distribution of dementia is estimated to check the log-normal assumption.

  9. Longitudinal cognitive decline in the AIBL cohort: The role of APOE ε4 status.

    PubMed

    Albrecht, Matthew A; Szoeke, Cassandra; Maruff, Paul; Savage, Greg; Lautenschlager, Nicola T; Ellis, Kathryn A; Taddei, Kevin; Martins, Ralph; Masters, Colin L; Ames, David; Foster, Jonathan K

    2015-08-01

    The ε4 polymorphism of the APOE gene confers a substantially increased risk of developing Alzheimer's disease. However, the influence of the ε4 allele on age-related cognitive functioning is more contentious. Previously, we demonstrated relatively little evidence for a role of the ε4 allele on baseline cognitive performance in older adults in the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing (Foster et al., 2013). We here investigated whether the APOE ε4 allele influenced cognitive status over time when the AIBL cohort was studied longitudinally over a 3-year period. The AIBL neuropsychological test battery was administered at baseline, after 18 months and again after 36 months. Participants comprised 764 Healthy Controls and 131 Mild Cognitively Impaired individuals enrolled in the AIBL Study of Ageing. We compared individuals within each group with and without an ε4 allele. Healthy Controls with an ε4 allele manifested a modest acceleration in cognitive decline over 36 months on measures of verbal episodic memory. By contrast, Mild Cognitively Impaired individuals with an ε4 allele showed increased cognitive decline across a range of cognitive tasks, putatively reflecting early cognitive signs of Alzheimer's disease. Given the long prodromal period that has been noted in late onset Alzheimer's disease, we suggest that these findings are consistent with a prodromal account rather than a phenotypic account of ε4-related cognitive ageing. PMID:26102189

  10. Clinical and radiological determinants of prestroke cognitive decline in a stroke cohort

    PubMed Central

    Pohjasvaara, T; Mantyla, R; Aronen, H; Leskela, M; Salonen, O; Kaste, M; Erkinjuntti, T

    1999-01-01

    OBJECTIVES—Stroke seems to be related to dementia more often than previously assumed and vascular factors are also related to Alzheimer's disease. The pathophysiology of poststroke dementia includes ischaemic changes in the brain, a combination of degenerative and vascular changes, and changes only related to Alzheimer's disease. Some cognitive decline recognised after a stroke may be due to pre-existing cognitive decline. The aim of this study was to determine the clinical and radiological determinants of prestroke cognitive decline.
METHODS—The study group comprised 337 of 486 consecutive patients aged 55 to 85 years who 3 months after ischaemic stroke completed a comprehensive neuropsychological test battery; structured medical, neurological, and mental status examination; interview of a knowledgeable informant containing structured questions on abnormality in the cognitive functions; assessment of social functions before the index stroke; and MRI.
RESULTS—Frequency of prestroke cognitive decline including that of dementia was 9.2% (31/337). The patients with prestroke cognitive decline were older, more often had less than 6 years of education, and had history of previous stroke. Vascular risk factors did not differ significantly between these two groups. White matter changes (p=0.004), cortical entorhinal, hippocampal, and medial temporal atrophy (p<0.001), cortical frontal atrophy (p=0.008); and any central atrophy (p<0.01), but not the frequencies or volumes of old, silent, or all infarcts on MRI differentiated those with and without prestroke cognitive decline. The correlates of prestroke cognitive decline in logistic regression analysis were medial temporal cortical atrophy (odds ratio (OR) 7.5, 95% confidence interval (95%CI) 3.2-18.2), history of previous ischaemic stroke (OR 4.4, 95% CI 1.8-10.6), and education (OR 0.9, 95% CI 0.8-0.9).
CONCLUSIONS—History of previous stroke, but not volumes or frequencies was found to correlate with

  11. Alzheimer's disease pattern of brain atrophy predicts cognitive decline in Parkinson's disease.

    PubMed

    Weintraub, Daniel; Dietz, Nicole; Duda, John E; Wolk, David A; Doshi, Jimit; Xie, Sharon X; Davatzikos, Christos; Clark, Christopher M; Siderowf, Andrew

    2012-01-01

    Research suggests overlap in brain regions undergoing neurodegeneration in Parkinson's and Alzheimer's disease. To assess the clinical significance of this, we applied a validated Alzheimer's disease-spatial pattern of brain atrophy to patients with Parkinson's disease with a range of cognitive abilities to determine its association with cognitive performance and decline. At baseline, 84 subjects received structural magnetic resonance imaging brain scans and completed the Dementia Rating Scale-2, and new robust and expanded Dementia Rating Scale-2 norms were applied to cognitively classify participants. Fifty-nine non-demented subjects were assessed annually with the Dementia Rating Scale-2 for two additional years. Magnetic resonance imaging scans were quantified using both a region of interest approach and voxel-based morphometry analysis, and a method for quantifying the presence of an Alzheimer's disease spatial pattern of brain atrophy was applied to each scan. In multivariate models, higher Alzheimer's disease pattern of atrophy score was associated with worse global cognitive performance (β = -0.31, P = 0.007), including in non-demented patients (β = -0.28, P = 0.05). In linear mixed model analyses, higher baseline Alzheimer's disease pattern of atrophy score predicted long-term global cognitive decline in non-demented patients [F(1, 110) = 9.72, P = 0.002], remarkably even in those with normal cognition at baseline [F(1, 80) = 4.71, P = 0.03]. In contrast, in cross-sectional and longitudinal analyses there was no association between region of interest brain volumes and cognitive performance in patients with Parkinson's disease with normal cognition. These findings support involvement of the hippocampus and parietal-temporal cortex with cognitive impairment and long-term decline in Parkinson's disease. In addition, an Alzheimer's disease pattern of brain atrophy may be a preclinical biomarker of cognitive decline in

  12. The Hippocampal Neuroproteome with Aging and Cognitive Decline: Past Progress and Future Directions

    PubMed Central

    VanGuilder, Heather D.; Freeman, Willard M.

    2011-01-01

    Although steady progress on understanding brain aging has been made over recent decades through standard anatomical, immunohistochemical, and biochemical techniques, the biological basis of non-neurodegenerative cognitive decline with aging remains to be determined. This is due in part to technical limitations of traditional approaches, in which only a small fraction of neurobiologically relevant proteins, mRNAs or metabolites can be assessed at a time. With the development and refinement of proteomic technologies that enable simultaneous quantitative assessment of hundreds to thousands of proteins, neuroproteomic studies of brain aging and cognitive decline are becoming more widespread. This review focuses on the contributions of neuroproteomic investigations to advances in our understanding of age-related deficits of hippocampus-dependent spatial learning and memory. Accumulating neuroproteomic data demonstrate that hippocampal aging involves common themes of dysregulated metabolism, increased oxidative stress, altered protein processing, and decreased synaptic function. Additionally, growing evidence suggests that cognitive decline does not represent a “more aged” phenotype, but rather is associated with specific neuroproteomic changes that occur in addition to age-related alterations. Understanding if and how age-related changes in the hippocampal neuroproteome contribute to cognitive decline and elucidating the pathways and processes that lead to cognitive decline are critical objectives that remain to be achieved. Progress in the field and challenges that remain to be addressed with regard to animal models, behavioral testing, and proteomic reporting are also discussed. PMID:21647399

  13. Recognition of Famous Names Predicts Episodic Memory Decline in Cognitively Intact Elders

    PubMed Central

    Seidenberg, Michael; Kay, Christina; Woodard, John L.; Nielson, Kristy A.; Smith, J. Carson; Kandah, Cassandra; Guidotti Breting, Leslie M.; Novitski, Julia; Lancaster, Melissa; Matthews, Monica; Hantke, Nathan; Butts, Alissa; Rao, Stephen M.

    2013-01-01

    Objective: Semantic memory impairment is common in both Mild Cognitive Impairment (MCI) and early Alzheimer’s disease (AD), and the ability to recognize familiar people is particularly vulnerable. A time-limited temporal gradient (TG) in which well known people from decades earlier are better recalled than those learned recently is also reported in both AD and MCI. In this study, we hypothesized that the TG pattern on a famous name recognition task (FNRT) administered to cognitively intact elders would predict future episodic memory decline, and would also show a significant correlation with hippocampal volume. Methods: 78 healthy elders (ages 65-90) with normal cognition and episodic memory at baseline were administered a FNRT. Follow-up episodic memory testing 18 months later produced two groups: Declining (≥ 1 SD reduction in episodic memory) and Stable (< 1 SD). Results: The Declining group (N=27) recognized fewer recent famous names than the Stable group (N=51), while recognition for remote names was comparable. Baseline MRI volumes for both the left and right hippocampus was significantly smaller in the Declining group than the Stable group. Smaller baseline hippocampal volume was also significantly correlated with poorer performance for recent, but not remote famous names. Logistic regression analyses indicated that baseline TG performance was a significant predictor of group status (Declining versus Stable) independent of chronological age and APOE ε4 inheritance. Conclusions: Famous name recognition may serve as an early pre-clinical cognitive marker of episodic memory decline in older individuals. PMID:23688215

  14. Demographic and clinical characteristics related to cognitive decline in Alzheimer disease in China

    PubMed Central

    Peng, Dantao; Shi, Zhihong; Xu, Jun; Shen, Lu; Xiao, Shifu; Zhang, Nan; Li, Yi; Jiao, Jinsong; Wang, Yan-Jiang; Liu, Shuai; Zhang, Meilin; Wang, Meng; Liu, Shuling; Zhou, Yuying; Zhang, Xiao; Gu, Xiao-hua; Yang, Ce-ce; Wang, Yu; Jiao, Bin; Tang, Beisha; Wang, Jinhuan; Yu, Tao; Ji, Yong

    2016-01-01

    Abstract Alzheimer disease (AD) is the most frequent cause of dementia. AD diagnosis, progression, and treatment have not been analyzed nationwide in China. The primary aim of this study was to analyze demographic and clinical characteristics related to cognitive decline in AD patients treated at outpatient clinics in China. We performed a retrospective study of 1993 AD patients at 10 cognitive centers across 8 cities in China from March 2011 to October 2014. Of these, 891 patients were followed for more than 1 year. The mean age at diagnosis was 72.0 ± 10.0 years (range 38–96 years), and the mean age at onset of AD was 69.8 ± 9.5 years. Most patients (65.1%) had moderate to severe symptoms at the time of diagnosis, and mean Mini-Mental State Examination at diagnosis was 15.7 ± 7.7. AD patients showed significant cognitive decline at 12 months after diagnosis. Having more than 9 years of formal education was an independent risk factor related to rapid cognitive decline [odds ratio (OR) = 1.80; 95% confidence interval (95% CI): 1.11–2.91]. Early-onset AD patients experienced more rapid cognitive decline than late-onset patients (OR = 1.83; 95% CI: 1.09–3.06). Most AD patients in China had moderate to severe symptoms at the time of diagnosis and experienced significant cognitive decline within 1 year. Rapid cognitive decline in AD was related to having a higher educational level and younger age of onset. PMID:27367978

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

    SciTech Connect

    Mogi, Masaki; Li Jianmei; Tsukuda, Kana; Iwanami, Jun; Min, Li-Juan; Sakata, Akiko; Fujita, Teppei; Iwai, Masaru; Horiuchi, Masatsugu

    2008-10-24

    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 not 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.

  16. Chocolate Consumption is Associated with a Lower Risk of Cognitive Decline.

    PubMed

    Moreira, Afonso; Diógenes, Maria José; de Mendonça, Alexandre; Lunet, Nuno; Barros, Henrique

    2016-05-01

    Cocoa-related products like chocolate have taken an important place in our food habits and culture. In this work, we aim to examine the relationship between chocolate consumption and cognitive decline in an elderly cognitively healthy population. In the present longitudinal prospective study, a cohort of 531 participants aged 65 and over with normal Mini-Mental State Examination (MMSE; median 28) was selected. The median follow-up was 48 months. Dietary habits were evaluated at baseline. The MMSE was used to assess global cognitive function at baseline and at follow-up. Cognitive decline was defined by a decrease ≥ 2 points in the MMSE score between evaluations. Relative risk (RR) and 95% confidence interval (95% CI) estimates were adjusted for age, education, smoking, alcohol drinking, body mass index, hypertension, and diabetes. Chocolate intake was associated with a lower risk of cognitive decline (RR = 0.59, 95% CI 0.38-0.92). This protective effect was observed only among subjects with an average daily consumption of caffeine lower than 75 mg (69% of the participants; RR = 0.50, 95% CI 0.31-0.82). To our knowledge, this is the first prospective cohort study to show an inverse association between regular long-term chocolate consumption and cognitive decline in humans. PMID:27163823

  17. Trajectories of cognitive decline by driving mobility: evidence from the Health and Retirement Study

    PubMed Central

    Choi, Moon; Lohman, Matthew C.; Mezuk, Briana

    2014-01-01

    Objective The recent emphasis of the importance of “aging in place” has highlighted the role of transportation in health promotion over the life course. Driving cessation in later life is associated with numerous poor health outcomes including limitations in social and physical functioning and increased risk of mortality. However, little is known about the relationship between driving cessation and change in cognitive functioning in late life. This study examined the association between driving mobility and trajectories of cognitive functioning among older adults. Methods Using data from six waves [1998–2008] of the Health and Retirement Study, trajectories of cognitive functioning were estimated over a 10-year period using longitudinal mixed effects models [N = 9,135]. Cognitive function was assessed with a modified version of the Telephone Interview for Cognitive Status. Driving status and health characteristics were assessed by self-report. Results Older adults who did not drive (former and never drivers) at baseline had lower average cognitive scores compared with active drivers. Former drivers had accelerated cognitive decline over the subsequent 10 years compared with active drivers (β= −0.35, 95% Confidence Interval [CI] = −0.43 to −0.26) even after controlling for baseline cognitive functioning and health status. The transition to non-driving was associated with a faster cognitive decline among those who were driving at baseline (β = −0.31, 95% CI = −0.40 to −0.22). Conclusions Older adults without driving mobility had poorer cognitive functioning at baseline and experienced accelerated cognitive decline relative to active drivers over follow-up. PMID:24022894

  18. Greater cognitive decline with aging among elders with high serum concentrations of organochlorine pesticides.

    PubMed

    Kim, Se-A; Lee, Yu-Mi; Lee, Ho-Won; Jacobs, David R; Lee, Duk-Hee

    2015-01-01

    Although cognitive decline is very common in elders, age-related cognitive decline substantially differs among elders and the determinants of the differences in age-related cognitive decline are unclear. We investigated our hypothesis that the association between age and cognition was stronger in those with higher serum concentrations of organochlorine (OC) pesticides, common persistent and strongly lipophilic neurotoxic chemicals. Participants were 644 elders aged 60-85, participating in the National Health and Nutrition Examination Survey 1999-2002. Six OC pesticides (p,p'-dichlorodiphenyltrichloroethane (DDT), p,p'-dichlorodipenyldichloroethylene (DDE), β-hexachlorocyclohexane, trans-nonachlor, oxychlordane, and heptachlor epoxide) were evaluated. "Lower cognitive function" was defined as having a low Digit-Symbol Substitution Test (DSST) score (<25th percentile of DSST score, cutpoint 28 symbols substituted). Higher levels of β-hexachlorocyclohexane, trans-nonachlor, oxychlordane, and heptachlor epoxide modified the associations between age and lower cognitive function (Pinteraction<0.01, 0.03, <0.01, and 0.02, respectively). Elders in the 3rd tertile of these chemicals demonstrated a greater risk of lower cognitive function with aging, compared to those in the combined 1st and 2nd tertiles. Among those with highest OC pesticides (3rd tertile), the odds ratio for the risk of lower cognitive function was about 6 to 11 for the highest quintile of age (80-85 years) vs. the first quintile of age (60-63 years), while the association between age and lower cognitive function became flatter in those with lower OC pesticides (combined 1st and 2nd tertiles). Both DDT and DDE showed no interaction, with lower DSST scores for higher age irrespective of serum concentrations of DDT or DDE. Even though DSST score measures only one aspect of cognition, several OC pesticides modified aging-related prevalence of low cognitive score, a finding which should be evaluated in

  19. Age-related decline in cognitive control: the role of fluid intelligence and processing speed

    PubMed Central

    2014-01-01

    Background Research on cognitive control suggests an age-related decline in proactive control abilities whereas reactive control seems to remain intact. However, the reason of the differential age effect on cognitive control efficiency is still unclear. This study investigated the potential influence of fluid intelligence and processing speed on the selective age-related decline in proactive control. Eighty young and 80 healthy older adults were included in this study. The participants were submitted to a working memory recognition paradigm, assessing proactive and reactive cognitive control by manipulating the interference level across items. Results Repeated measures ANOVAs and hierarchical linear regressions indicated that the ability to appropriately use cognitive control processes during aging seems to be at least partially affected by the amount of available cognitive resources (assessed by fluid intelligence and processing speed abilities). Conclusions This study highlights the potential role of cognitive resources on the selective age-related decline in proactive control, suggesting the importance of a more exhaustive approach considering the confounding variables during cognitive control assessment. PMID:24401034

  20. Association Between Long-Term Cognitive Decline in Vietnam Veterans With TBI and Caregiver Attachment Style

    PubMed Central

    Guevara, Andrea Brioschi; Demonet, Jean-François; Polejaeva, Elena; Knutson, Kristine M.; Wassermann, Eric M.; Krueger, Frank; Grafman, Jordan

    2015-01-01

    Objective To examine whether a caregiver's attachment style is associated with patient cognitive trajectory after traumatic brain injury (TBI). Setting National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. Participants Forty Vietnam War veterans with TBI and their caregivers. Main Outcome Measure Cognitive performance, measured by the Armed Forces Qualification Test percentile score, completed at 2 time points: preinjury and 40 years postinjury. Design On the basis of caregivers’ attachment style (secure, fearful, preoccupied, dismissing), participants with TBI were grouped into a high or low group. To examine the association between cognitive trajectory of participants with TBI and caregivers’ attachment style, we ran four 2 × 2 analysis of covariance on cognitive performances. Results After controlling for other factors, cognitive decline was more pronounced in participants with TBI with a high fearful caregiver than among those with a low fearful caregiver. Other attachment styles were not associated with decline. Conclusion and Implication Caregiver fearful attachment style is associated with a significant decline in cognitive status after TBI. We interpret this result in the context of the neural plasticity and cognitive reserve literatures. Finally, we discuss its impact on patient demand for healthcare services and potential interventions. PMID:24695269

  1. Association Between Serum 25(OH) Vitamin D and the Risk of Cognitive Decline in Older Women

    PubMed Central

    Paudel, Misti; Taylor, Brent C.; Ishani, Areef; Rossom, Rebecca; Yaffe, Kristine; Blackwell, Terri; Lui, Li-Yung; Hochberg, Marc; Ensrud, Kristine E.

    2012-01-01

    Background: Results of prospective studies examining the association between 25 hydroxyvitamin D (25[OH]D) levels and cognitive decline have been inconsistent. We tested the hypothesis that lower 25(OH)D levels are associated with a greater likelihood of cognitive impairment and risk of cognitive decline. Methods: The study is a cross-sectional and longitudinal analysis of a prospective cohort of 6,257 community-dwelling elderly women followed for 4 years. Global cognitive function was measured by the Modified Mini-Mental State Examination and executive function was measured by Trail Making Test Part B (Trails B). Cognitive impairment at baseline was defined as a score >1.5 SD below the sample mean; cognitive decline was defined as decline from baseline to follow-up >1 SD from mean change in score. Results: Women with very low vitamin D levels had an increased odds of global cognitive impairment at baseline: odds ratio (95% confidence interval), 1.60 (1.05–2.42) for women with 25(OH)D <10 ng/mL (25 nmol/L) compared with those with 25(OH)D levels ≥30 ng/mL (75 nmol/L). Compared with women with baseline 25(OH)D level ≥30 ng/mL (75 nmol/L), women with lower levels had an increased risk of global cognitive decline: odds ratio (95% confidence interval), 1.58(1.12–2.22) for women with levels <10 ng/mL (25 nmol/L), and 1.31 (1.04–1.64) for those with levels 10–19.9 ng/mL (25–49 nmol/L). Levels of 25(OH)D were not associated with executive cognitive function. Conclusions: Low 25(OH)D levels among older women were associated with a higher odds of global cognitive impairment and a higher risk of global cognitive decline. PMID:22454371

  2. Cognitive Decline in Patients With Dementia as a Function of Depression

    PubMed Central

    Rapp, Michael A.; Schnaider-Beeri, Michal; Wysocki, Michael; Guerrero-Berroa, Elizabeth; Grossman, Hillel T.; Heinz, Andreas; Haroutunian, Vahram

    2011-01-01

    Objective There is evidence that major depression increases the risk for dementia, but there is conflicting evidence as to whether depression may accelerate cognitive decline in dementia. The authors tested the hypothesis that decline in cognitive function over time is more pronounced in patients with dementia with comorbid depression, when compared with patients with dementia without depression history. Design Prospective, longitudinal cohort study of aging. Setting Nursing home. Participants Three hundred thirteen elderly nursing home residents (mean age at baseline: 86.99 years, standard deviation = 6.7; 83.1% women). At baseline, 192 residents were diagnosed with dementia, and another 27 developed dementia during follow-up. Thirty residents suffered from major depression at any point during the study, and 48 residents had a history of depression. Measurements The authors measured cognitive decline using change in Mini-Mental State Examination (MMSE) scores over up to 36 months. The authors calculated multilevel regression models to estimate the effects of age, gender, education, dementia status, depression, depression history, and an interaction between dementia and depression, on change in MMSE scores over time. Results Beyond the effects of age, gender, and education, residents showed steeper cognitive decline in the presence of dementia (β = 13.69, standard error = 1.38) and depression (β = −4.16, SE = 1.2), which was further accelerated by the presence of both depression and dementia (β = −2.72, SE = 0.65). Conclusions In dementia, the presence of depression corresponds to accelerated cognitive decline beyond gender and level of education, suggesting a unique influence of depression on the rate of cognitive decline in dementia. PMID:20808140

  3. Military risk factors for cognitive decline, dementia and Alzheimer's disease.

    PubMed

    Veitch, Dallas P; Friedl, Karl E; Weiner, Michael W

    2013-11-01

    Delayed neurological health consequences of environmental exposures during military service have been generally underappreciated. The rapidly expanding understanding of Alzheimer's disease (AD) pathogenesis now makes it possible to quantitate some of the likely long-term health risks associated with military service. Military risk factors for AD include both factors elevated in military personnel such as tobacco use, traumatic brain injury (TBI), depression, and post-traumatic stress disorder (PTSD) and other nonspecific risk factors for AD including, vascular risk factors such as obesity and obesity-related diseases (e.g., metabolic syndrome), education and physical fitness. The degree of combat exposure, Vietnam era Agent Orange exposure and Gulf War Illness may also influence risk for AD. Using available data on the association of AD and specific exposures and risk factors, the authors have conservatively estimated 423,000 new cases of AD in veterans by 2020, including 140,000 excess cases associated with specific military exposures. The cost associated with these excess cases is approximately $5.8 billion to $7.8 billion. Mitigation of the potential impact of military exposures on the cognitive function of veterans and management of modifiable risk factors through specifically designed programs will be instrumental in minimizing the impact of AD in veterans in the future decades. PMID:23906002

  4. Traditional used Plants against Cognitive Decline and Alzheimer Disease

    PubMed Central

    Eckert, Gunter Peter

    2010-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized clinically by progressive memory deficits, impaired cognitive function, and altered and inappropriate behavior. Aging represents the most important risk factor for AD and the global trend in the phenomenon of population aging has dramatic consequences for public health, healthcare financing, and delivery systems in the word and, especially in developing countries. Mounting evidence obtained in in vitro and in vivo studies, suggests that various traditionally used plants in Asia, India, and Europe significantly affect key metabolic alterations culminating in AD-typical neurodegeneration. The present article aims to bring the reader up-to-date on the most recent studies and advances describing the direct and indirect activities of traditional used plants and its constituents possibly relieving features of AD. A variety of traditional used plants and its extracts exerted activities on AD related drug targets including AChE activity, antioxidative activity, modulation of Aβ-producing secretase activities, Aβ-degradation, heavy metal chelating, induction of neurotrophic factors, and cell death mechanisms. Although pre-clinical investigations identified promising drug candidates for AD, clinical evidences are still pending. PMID:21833177

  5. Declined Neural Efficiency in Cognitively Stable Human Immunodeficiency Virus Patients

    PubMed Central

    Ernst, Thomas; Yakupov, Renat; Nakama, Helenna; Crocket, Grace; Cole, Michael; Watters, Michael; Ricardo-Dukelow, Mary Lynn; Chang, Linda

    2009-01-01

    Objective To determine whether brain activation changes in clinically and neurocognitively normal human immunodeficiency virus (HIV)–infected and in HIV-seronegative control (SN) participants over a 1-year period. Methods Functional magnetic resonance imaging (fMRI) was performed in 32 SN and 31 HIV patients (all with stable combination antiretroviral treatment) at baseline and after 1 year. Each participant performed a set of visual attention tasks with increasing attentional load (from tracking two, three, or four balls). All HIV and SN participants had normal neuropsychological function at both examinations. Results Over 1 year, HIV patients showed no change in their neurocognitive status or in task performance during fMRI. However, HIV patients showed significant 1-year increases in fMRI signals in the prefrontal and posterior parietal cortices for the more difficult tasks, whereas SN control participants showed only decreases in brain activation in these regions. This resulted in significant interactions between HIV status and time of study in left insula, left parietal, left temporal, and several frontal regions (left and right middle frontal gyrus, and anterior cingulate). Interpretation Because fMRI task performance remained unchanged in both groups, the HIV patients appeared to maintain performance by increasing usage of the attention network, whereas the control participants reduced usage of the attention network after 1 year. These findings suggest improved efficiency or a practice effect in the SN participants but declined efficiency of the neural substrate in HIV patients, possibly because of ongoing brain injury associated with the HIV infection, despite their apparent stable clinical course. PMID:19334060

  6. Vascular and amyloid pathologies are independent predictors of cognitive decline in normal elderly

    PubMed Central

    Lesnick, Timothy G.; Przybelski, Scott A.; Knopman, David S.; Preboske, Greg M.; Kantarci, Kejal; Raman, Mekala R.; Machulda, Mary M.; Mielke, Michelle M.; Lowe, Val J.; Senjem, Matthew L.; Gunter, Jeffrey L.; Rocca, Walter A.; Roberts, Rosebud O.; Petersen, Ronald C.; Jack, Clifford R.

    2015-01-01

    Our primary objective was to investigate a biomarker driven model for the interrelationships between vascular disease pathology, amyloid pathology, and longitudinal cognitive decline in cognitively normal elderly subjects between 70 and 90 years of age. Our secondary objective was to investigate the beneficial effect of cognitive reserve on these interrelationships. We used brain amyloid-β load measured using Pittsburgh compound B positron emission tomography as a marker for amyloid pathology. White matter hyperintensities and brain infarcts were measured using fluid-attenuated inversion recovery magnetic resonance imaging as a marker for vascular pathology. We studied 393 cognitively normal elderly participants in the population-based Mayo Clinic Study of Aging who had a baseline 3 T fluid-attenuated inversion recovery magnetic resonance imaging assessment, Pittsburgh compound B positron emission tomography scan, baseline cognitive assessment, lifestyle measures, and at least one additional clinical follow-up. We classified subjects as being on the amyloid pathway if they had a global cortical amyloid-β load of ≥1.5 standard uptake value ratio and those on the vascular pathway if they had a brain infarct and/or white matter hyperintensities load ≥1.11% of total intracranial volume (which corresponds to the top 25% of white matter hyperintensities in an independent non-demented sample). We used a global cognitive z-score as a measure of cognition. We found no evidence that the presence or absence of vascular pathology influenced the presence or absence of amyloid pathology and vice versa, suggesting that the two processes seem to be independent. Baseline cognitive performance was lower in older individuals, in males, those with lower education/occupation, and those on the amyloid pathway. The rate of cognitive decline was higher in older individuals (P < 0.001) and those with amyloid (P = 0.0003) or vascular (P = 0.0037) pathologies. In those subjects with

  7. A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease.

    PubMed

    Jessen, Frank; Amariglio, Rebecca E; van Boxtel, Martin; Breteler, Monique; Ceccaldi, Mathieu; Chételat, Gaël; Dubois, Bruno; Dufouil, Carole; Ellis, Kathryn A; van der Flier, Wiesje M; Glodzik, Lidia; van Harten, Argonde C; de Leon, Mony J; McHugh, Pauline; Mielke, Michelle M; Molinuevo, Jose Luis; Mosconi, Lisa; Osorio, Ricardo S; Perrotin, Audrey; Petersen, Ronald C; Rabin, Laura A; Rami, Lorena; Reisberg, Barry; Rentz, Dorene M; Sachdev, Perminder S; de la Sayette, Vincent; Saykin, Andrew J; Scheltens, Philip; Shulman, Melanie B; Slavin, Melissa J; Sperling, Reisa A; Stewart, Robert; Uspenskaya, Olga; Vellas, Bruno; Visser, Pieter Jelle; Wagner, Michael

    2014-11-01

    There is increasing evidence that subjective cognitive decline (SCD) in individuals with unimpaired performance on cognitive tests may represent the first symptomatic manifestation of Alzheimer's disease (AD). The research on SCD in early AD, however, is limited by the absence of common standards. The working group of the Subjective Cognitive Decline Initiative (SCD-I) addressed this deficiency by reaching consensus on terminology and on a conceptual framework for research on SCD in AD. In this publication, research criteria for SCD in pre-mild cognitive impairment (MCI) are presented. In addition, a list of core features proposed for reporting in SCD studies is provided, which will enable comparability of research across different settings. Finally, a set of features is presented, which in accordance with current knowledge, increases the likelihood of the presence of preclinical AD in individuals with SCD. This list is referred to as SCD plus.

  8. Critical levels of brain atrophy associated with homocysteine and cognitive decline.

    PubMed

    de Jager, Celeste A

    2014-09-01

    Few B-vitamin trials to lower homocysteine (Hcy) have reported evidence of beneficial effects on cognition in older adults with cognitive impairment or Alzheimer's disease. This article reviews the role of Hcy in cognitive decline. It also considers some reasons why meta-analyses have failed to find effects of B-vitamin treatment. Findings from the successful VITACOG trial are examined from a new perspective of critical levels of Hcy and brain atrophy that may impact on the efficacy of B-vitamin treatment. It appears that there is a critical level of brain shrinkage, possibly mediated by elevated Hcy, which when reached, results in cognitive decline, especially in episodic memory performance. Supplements, food sources, and effects of folic acid fortification are discussed in relation to B12 deficiency.

  9. Tooth loss, periodontal disease, and cognitive decline in the Atherosclerosis Risk in Communities (ARIC) study

    PubMed Central

    Naorungroj, S; Schoenbach, VJ; Wruck, L; Mosley, TH; Gottesman, RF; Alonso, A; Heiss, G; Beck, J; Slade, GD

    2014-01-01

    Objective The purpose of this prospective study was to investigate whether poor oral health predicted eight-year cognitive function change in predominantly late middle adults in the Atherosclerosis Risk in Communities (ARIC) study. Methods Participants included a subset of ARIC participants aged 52–75 years at 1996–1998 from two study sites: Forsyth County NC and Jackson MS. All subjects completed cognitive function assessments both in 1996–1998 and 2004–2006, and the same subjects received a dental examination at the initial visit. Cognitive assessment consisted of Delayed Word Recall (DWR), Digit Symbol Substitution (DSS), and Word Fluency (WF) tests. In the analysis, cognitive function for 911 dentally screened participants was evaluated, and 558 of 785 dentate participants received comprehensive oral examinations, including periodontal probing. Measures of oral health included dental status, number of teeth, and periodontal disease classified by the Biofilm-Gingival Interface (BGI) index. The generalized estimating equations (GEE) method was used to analyze repeated measures of cognitive scores with adjustment for socio-demographic characteristics and cardiovascular risk factors. Results Of 911 study participants, 13.8% were edentulous. About 13 % of dentally examined participants had periodontal pockets (≥4 mm) with severe bleeding. At the follow-up visit, DWR and WF scores were lower in edentulous compared to dentate people, whereas other oral health measures were not associated with cognitive function. Mean values declined over time for all three cognitive measures, although poor oral health conditions were not associated with greater degree of decline in cognitive function. Conclusions In these late-middle aged adults, complete tooth loss was significantly associated with lower cognitive performance. However, neither edentulism, number of teeth, nor periodontal disease predicted greater subsequent cognitive decline. PMID:25363061

  10. Fetuin-A, a New Vascular Biomarker of Cognitive Decline in Older Adults

    PubMed Central

    Laughlin, Gail A; McEvoy, Linda K.; Barrett-Connor, Elizabeth; Daniels, Lori B.; Ix, Joachim H.

    2014-01-01

    Objectives Fetuin-A is an abundant plasma protein known to predict vascular disease. Fetuin-A levels are lower in patients with Alzheimer’s disease in proportion to the severity of cognitive impairment, but their association with normal cognitive aging is unknown. We evaluated the association of serum fetuin-A levels with cognitive function in community-dwelling older adults. Design/Patients/Measurements A population-based study of 1382 older adults (median age 75) who had plasma fetuin-A levels and cognitive function evaluated in 1992–96; 855 had repeat cognitive function assessment a median of 4 years later. Results Adjusting for age, sex, education, and depression, higher levels of fetuin-A were associated with better baseline performance on the Mini-Mental Status Exam (MMSE) (P=0.012) and a tendency for better Trails Making B scores (P=0.066). In longitudinal analyses, the likelihood of a major decline (highest decile of change) in Trails B was 29% lower (P=0.010) for each SD higher baseline fetuin-A level; odds of major decline in MMSE was 42% lower (P=0.005) per SD higher fetuin-A for individuals with no known CVD, but were not related to fetuin-A in those with CVD (P=0.33). Fetuin-A was not related to Category Fluency performance. Results were independent of multiple vascular risk factors and comorbid conditions. Conclusions Higher plasma fetuin-A concentrations are associated with better performance on tests of global cognitive function and executive function and with less likelihood of major decline in these cognitive abilities over a 4-year period. Fetuin-A may serve as a biological link between vascular disease and normal age-related cognitive decline. PMID:24325554

  11. Perception and Cognition in the Ageing Brain: A Brief Review of the Short- and Long-Term Links between Perceptual and Cognitive Decline

    PubMed Central

    Roberts, Katherine L.; Allen, Harriet A.

    2016-01-01

    Ageing is associated with declines in both perception and cognition. We review evidence for an interaction between perceptual and cognitive decline in old age. Impoverished perceptual input can increase the cognitive difficulty of tasks, while changes to cognitive strategies can compensate, to some extent, for impaired perception. While there is strong evidence from cross-sectional studies for a link between sensory acuity and cognitive performance in old age, there is not yet compelling evidence from longitudinal studies to suggest that poor perception causes cognitive decline, nor to demonstrate that correcting sensory impairment can improve cognition in the longer term. Most studies have focused on relatively simple measures of sensory (visual and auditory) acuity, but more complex measures of suprathreshold perceptual processes, such as temporal processing, can show a stronger link with cognition. The reviewed evidence underlines the importance of fully accounting for perceptual deficits when investigating cognitive decline in old age. PMID:26973514

  12. Perception and Cognition in the Ageing Brain: A Brief Review of the Short- and Long-Term Links between Perceptual and Cognitive Decline.

    PubMed

    Roberts, Katherine L; Allen, Harriet A

    2016-01-01

    Ageing is associated with declines in both perception and cognition. We review evidence for an interaction between perceptual and cognitive decline in old age. Impoverished perceptual input can increase the cognitive difficulty of tasks, while changes to cognitive strategies can compensate, to some extent, for impaired perception. While there is strong evidence from cross-sectional studies for a link between sensory acuity and cognitive performance in old age, there is not yet compelling evidence from longitudinal studies to suggest that poor perception causes cognitive decline, nor to demonstrate that correcting sensory impairment can improve cognition in the longer term. Most studies have focused on relatively simple measures of sensory (visual and auditory) acuity, but more complex measures of suprathreshold perceptual processes, such as temporal processing, can show a stronger link with cognition. The reviewed evidence underlines the importance of fully accounting for perceptual deficits when investigating cognitive decline in old age.

  13. Postmortem MRI: a novel window into the neurobiology of late life cognitive decline.

    PubMed

    Dawe, Robert J; Yu, Lei; Leurgans, Sue E; Schneider, Julie A; Buchman, Aron S; Arfanakis, Konstantinos; Bennett, David A; Boyle, Patricia A

    2016-09-01

    This study tested the hypothesis that indices of brain tissue integrity derived from postmortem magnetic resonance imaging (MRI) are associated with late life decline in cognitive function and dementia, over and above contributions from common age-related neuropathologies. Cerebral hemispheres were obtained from 425 deceased older adults who had undergone 2 or more annual cognitive assessments, which included clinical diagnosis of dementia. Specimens underwent MRI to produce maps of transverse relaxation rate, R2. Voxelwise regression revealed brain regions where R2 was associated with cognitive decline. We then used random effects models to quantify the extent to which R2 accounted for variation in decline, after adjustment for demographics and neuropathologic indices of the 3 most common causes of dementia: Alzheimer's disease, cerebrovascular disease, and Lewy body disease. We additionally tested whether R2 was tied to greater likelihood of clinical diagnosis of Alzheimer's dementia using logistic regression models. During an average of 8.1 years, the mean rate of decline in global cognitive function was 0.13 unit per year (p < 0.0001). The tissue alteration most commonly related to decline was R2 slowing in white matter. Each unit decrease in R2 was associated with an additional 0.053-unit per year steepening of the rate of global cognitive decline (p < 0.001). Furthermore, R2 accounted for 8.4% of the variance in rate of global cognitive decline, above and beyond the 26.5% accounted for by demographics and neuropathologic indices, and 7.1%-11.2% of the variance of the decline rates in episodic, semantic, and working memory and perceptual speed. Alterations in R2 were also related to an increased odds of clinical diagnosis of Alzheimer's dementia (odds ratio = 2.000, 95% confidence interval 1.600, 2.604). Therefore, postmortem MRI indices of brain tissue integrity, particularly in white matter, are useful for elucidating the basis of late life cognitive

  14. What do parents have to do with my cognitive reserve? Life-course perspectives on twelve-year cognitive decline

    PubMed Central

    González, Hector M.; Tarraf, Wassim; Bowen, Mary E.; Johnson-Jennings, Michelle D.; Fisher, Gwenith G.

    2013-01-01

    Background/Aims To examine the cognitive reserve hypothesis by comparing the contribution of early childhood and life-course factors related to cognitive functioning in a nationally representative sample of older Americans. Methods We examined a prospective, nationally probability cohort study (Health and Retirement Study HRS; 1998-2010) of older adults (N=8,833) in the contiguous 48 United States. The main cognitive functioning outcome was a 35-point composite of memory (recall), mental status, and working memory tests. The main predictors were childhood socioeconomic position (SEP) and health, and individual-level adult achievement and health. Results Individual-level achievement indicators (i.e., education, income, and wealth) were positively and significantly associated with baseline cognitive function, while adult health was negatively associated with cognitive function. Controlling for individual-level adult achievement and other model covariates, childhood health presented a relatively small negative, but statistically significant association with initial cognitive function. Neither individual achievement nor childhood SEP was statistically linked to decline over time. Conclusions Cognitive reserve purportedly acquired through learning and mental stimulation across the life-course was associated with higher initial global cognitive functioning over the twelve-year period in this nationally representative study of older Americans. We found little supporting evidence that childhood economic conditions were negatively associated with cognitive function and change, particularly when individual-level achievement is considered. PMID:23860477

  15. 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.

  16. Automated Semantic Indices Related to Cognitive Function and Rate of Cognitive Decline

    ERIC Educational Resources Information Center

    Pakhomov, Serguei V. S.; Hemmy, Laura S.; Lim, Kelvin O.

    2012-01-01

    The objective of our study is to introduce a fully automated, computational linguistic technique to quantify semantic relations between words generated on a standard semantic verbal fluency test and to determine its cognitive and clinical correlates. Cognitive differences between patients with Alzheimer's disease and mild cognitive impairment are…

  17. Gene Behavior Interaction of Depressive Symptoms and the Apolipoprotein E ε4 Allele on Cognitive Decline

    PubMed Central

    Rajan, Kumar B.; Wilson, Robert S.; Skarupski, Kimberly A.; de Leon, Carlos Mendes; Evans, Denis A.

    2014-01-01

    Objective Depressive symptoms and the APOE ε4 allele are independent risk factors for cognitive decline. However, it is not clear whether the presence of both depressive symptoms and the APOE ε4 allele increases cognitive decline. Methods A prospective study of a population-based sample of 4,150 (70% African American and 63% women) participants, aged 65 years and older, who were interviewed at 3-year intervals. Depressive symptoms were measured using the 10-item version of the Center for Epidemiologic Studies Depression scale, with each item coded as presence or absence of a symptom. The APOE genotype was ascertained by DNA samples collected during follow-up. Cognitive function was assessed at the initial and follow-up interviews (average follow-up of 9.2 years), using a standardized global cognitive score. Results There were 1405 (34%) participants with one or more copies of the APOE ε4 allele. In participants with no depressive symptoms, cognitive function decreased by 0.0412-unit per year among those with no copies and 0.0704-unit per year among those with one or more copies of the APOE ε4 allele. For each additional symptom of depression, cognitive decline increased by 0.0021-unit per year among those with no copies and 0.0051-unit per year among those with one or more copies of the APOE ε4 allele. The three-way interaction of depressive symptoms, APOE ε4 allele, and time was significant (p=0.021). Conclusions The association of depressive symptoms on cognitive decline was increased among participants with one or more copies of the APOE ε4 allele compared to those without the allele. PMID:24434953

  18. APOE and BDNF polymorphisms moderate amyloid β-related cognitive decline in preclinical Alzheimer's disease

    PubMed Central

    Lim, Y Y; Villemagne, V L; Laws, S M; Pietrzak, R H; Snyder, P J; Ames, D; Ellis, K A; Harrington, K; Rembach, A; Martins, R N; Rowe, C C; Masters, C L; Maruff, P

    2015-01-01

    Accumulation of β-amyloid (Aβ) in the brain is associated with memory decline in healthy individuals as a prelude to Alzheimer's disease (AD). Genetic factors may moderate this decline. We examined the role of apolipoprotein E (ɛ4 carrier[ɛ4+], ɛ4 non-carrier[ɛ4−]) and brain-derived neurotrophic factor (BDNFVal/Val, BDNFMet) in the extent to which they moderate Aβ-related memory decline. Healthy adults (n=333, Mage=70 years) enrolled in the Australian Imaging, Biomarkers and Lifestyle study underwent Aβ neuroimaging. Neuropsychological assessments were conducted at baseline, 18-, 36- and 54-month follow-ups. Aβ positron emission tomography neuroimaging was used to classify participants as Aβ− or Aβ+. Relative to Aβ−ɛ4−, Aβ+ɛ4+ individuals showed significantly faster rates of cognitive decline over 54 months across all domains (d=0.40–1.22), while Aβ+ɛ4− individuals showed significantly faster decline only on verbal episodic memory (EM). There were no differences in rates of cognitive change between Aβ−ɛ4− and Aβ−ɛ4+ groups. Among Aβ+ individuals, ɛ4+/BDNFMet participants showed a significantly faster rate of decline on verbal and visual EM, and language over 54 months compared with ɛ4−/BDNFVal/Val participants (d=0.90–1.02). At least two genetic loci affect the rate of Aβ-related cognitive decline. Aβ+ɛ4+/BDNFMet individuals can expect to show clinically significant memory impairment after 3 years, whereas Aβ+ɛ4+/BDNFVal/Val individuals can expect a similar degree of impairment after 10 years. Little decline over 54 months was observed in the Aβ− and Aβ+ ɛ4− groups, irrespective of BDNF status. These data raise important prognostic issues in managing preclinical AD, and should be considered in designing secondary preventative clinical trials. PMID:25288138

  19. Fish Intake Is Associated with Slower Cognitive Decline in Chinese Older Adults123

    PubMed Central

    Qin, Bo; Plassman, Brenda L.; Edwards, Lloyd J.; Popkin, Barry M.; Adair, Linda S.; Mendez, Michelle A.

    2014-01-01

    Modifiable lifestyle changes, including dietary changes, could translate into a great reduction in the global burden of cognitive impairment and dementia. Few studies evaluated the benefits of fish intake for delaying cognitive decline, and no studies were conducted in a Chinese population, which may differ with respect to types, amounts, and correlates of fish consumption compared with Western populations. We hypothesized that higher consumption of fish would predict slower decline in cognitive function, independent of a wide range of potential confounders. This prospective cohort study comprised 1566 community-dwelling adults aged ≥55 y who completed a cognitive screening test at ≥2 waves of the China Health and Nutrition Survey in 1997, 2000, or 2004, with a mean follow-up of 5.3 y [age at entry (mean ± SD): 63 ± 6 y]. Diet was measured by 3-d 24-h recalls at baseline. Outcomes included repeated measures of global cognitive scores (baseline mean ± SD: 19 ± 6 points), composite cognitive Z-scores (standardized units), and standardized verbal memory scores (standardized units). Multivariable-adjusted linear mixed-effects models were used to evaluate the relation of fish intake with changes in cognitive scores. Age was found to significantly modify the association between fish consumption and cognitive change (P = 0.007). Among adults aged ≥65 y, compared with individuals who consumed <1 serving/wk (i.e., 100 g) fish, the mean annual rate of global cognitive decline was reduced by 0.35 point (95% CI: 0.13, 0.58) among those consuming ≥1 serving/wk, equivalent to the disparity associated with 1.6 y of age. Fish consumption was also associated with a slower decline in composite and verbal memory scores. No associations were observed among adults aged 55–64 y. Our findings suggest a potential role of fish consumption as a modifiable dietary factor to reduce the rate of cognitive decline in later life. PMID:25080536

  20. Can Exercise Ameliorate Aromatase Inhibitor-Induced Cognitive Decline in Breast Cancer Patients?

    PubMed

    Li, Cuicui; Zhou, Chenglin; Li, Rena

    2016-08-01

    Aromatase inhibitors (AIs) have been commonly used as an effective adjuvant therapy in treatment of breast cancer, especially for menopausal women with estrogen receptor-positive breast cancer. Due to the nature of aromatase, the key enzyme for endogenous estrogen synthesis, inhibitory of aromatase-induced side effects, such as cognitive impairment has been reported in both human and animal studies. While extensive evidence suggested that physical exercises can improve learning and memory activity and even prevent age-related cognitive decline, basic research revealed some common pathways between exercise and estrogen signaling that affected cognitive function. This review draws on clinical and basic studies to assess the potential impact of exercise in cognitive function from women treated with AIs for breast cancer and explore the potential mechanism and effects of exercise on estrogen-related cognition. PMID:26223800

  1. Electrophysiological entropy in younger adults, older controls and older cognitively declined adults.

    PubMed

    Hogan, Michael J; Kilmartin, Liam; Keane, Michael; Collins, Peter; Staff, Roger T; Kaiser, Jochen; Lai, Robert; Upton, Neil

    2012-03-22

    The current study examined electrophysiological entropy in younger adults, older adults, and older cognitively declined adults across four experimental conditions - eyes closed, eyes open, and during both encoding and recognition of words in a memory task. We hypothesised reduced entropy in older declined adults relative to both older controls and younger adults, with the largest group differences in entropy expected during the encoding and recognition phases of the experiment. We also hypothesised greater hemispheric asymmetry in younger adults compared with older controls and older declined adults. Results revealed significant increases in entropy from eyes closed to eyes open to task. Young adults showed higher entropy in the right relative to the left hemisphere in the temporal lobe and higher entropy in the left relative to the right hemisphere in the parietal lobe. Old cognitively declined adults showed no significant differences between right and left hemisphere entropy. There was a trend whereby older declined adults showed lower entropy than older controls in the frontal lobe, this difference being largest in the left hemisphere during the encoding phase of the experiment. Results indicate that measures of entropy are sensitive to information processing demands and that higher cognitive performance may not be a simple function of entropy level, but rather a combination of level and range, or differentiated range of entropy states across the brain.

  2. Effects of centrally acting ACE inhibitors on the rate of cognitive decline in dementia

    PubMed Central

    Gao, Yang; O'Caoimh, Rónán; Healy, Liam; Kerins, David M; Eustace, Joseph; Guyatt, Gordon; Sammon, David; Molloy, D William

    2013-01-01

    Objectives There is growing evidence that antihypertensive agents, particularly centrally acting ACE inhibitors (CACE-Is), which cross the blood–brain barrier, are associated with a reduced rate of cognitive decline. Given this, we compared the rates of cognitive decline in clinic patients with dementia receiving CACE-Is (CACE-I) with those not currently treated with CACE-Is (NoCACE-I), and with those who started CACE-Is, during their first 6 months of treatment (NewCACE-I). Design Observational case–control study. Setting 2 university hospital memory clinics. Participants 817 patients diagnosed with Alzheimer's disease, vascular or mixed dementia. Of these, 361 with valid cognitive scores were included for analysis, 85 CACE-I and 276 NoCACE-I. Measurements Patients were included if the baseline and end-point (standardised at 6 months apart) Standardised Mini-Mental State Examination (SMMSE) or Quick Mild Cognitive Impairment (Qmci) scores were available. Patients with comorbid depression or other dementia subtypes were excluded. The average 6-month rates of change in scores were compared between CACE-I, NoCACE-I and NewCACE-I patients. Results When the rate of decline was compared between groups, there was a significant difference in the median, 6-month rate of decline in Qmci scores between CACE-I (1.8 points) and NoCACE-I (2.1 points) patients (p=0.049), with similar, non-significant changes in SMMSE. Median SMMSE scores improved by 1.2 points in the first 6 months of CACE treatment (NewCACE-I), compared to a 0.8 point decline for the CACE-I (p=0.003) group and a 1 point decline for the NoCACE-I (p=0.001) group over the same period. Multivariate analysis, controlling for baseline characteristics, showed significant differences in the rates of decline, in SMMSE, between the three groups, p=0.002. Conclusions Cognitive scores may improve in the first 6 months after CACE-I treatment and use of CACE-Is is associated with a reduced rate of cognitive

  3. A review of new insights on the association between hearing loss and cognitive decline in ageing.

    PubMed

    Fortunato, S; Forli, F; Guglielmi, V; De Corso, E; Paludetti, G; Berrettini, S; Fetoni, A R

    2016-06-01

    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.

  4. A review of new insights on the association between hearing loss and cognitive decline in ageing.

    PubMed

    Fortunato, S; Forli, F; Guglielmi, V; De Corso, E; Paludetti, G; Berrettini, S; Fetoni, A R

    2016-06-01

    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

  5. Preventive effects of Chlorella on cognitive decline in age-dependent dementia model mice.

    PubMed

    Nakashima, Yuya; Ohsawa, Ikuroh; Konishi, Fumiko; Hasegawa, Takashi; Kumamoto, Shoichiro; Suzuki, Yoshihiko; Ohta, Shigeo

    2009-10-30

    Oxidative stress is one of the major causes of age-dependent memory loss and cognitive decline. Cytotoxic aldehydes are derived from lipid peroxides and their accumulation may be responsible for age-dependent neurodegeneration, including Alzheimer's disease. Since aldehyde dehydrogenases detoxify such aldehydes, we constructed transgenic mice with mitochondrial aldehyde dehydrogenase 2 (ALDH2) activity deficiency (DAL101 mice) as an age-dependent dementia model. This model animal is age-dependently progressed by persistent oxidative stress, and thus enables us to investigate foods that prevent dementia. Since Chlorella, a kind of alga, exhibits various anti-oxidative effects, we investigated whether Chlorella has the potential to prevent age-dependent cognitive impairment. We fed Chlorella to DAL101 mice and investigated its effects on oxidative stress and the progression of cognitive decline using the Morris water-maze and object recognition tests. The diet with Chlorella tended to reduce oxidative stress and significantly prevented the decline of cognitive ability, as shown by both methods. Moreover, consumption of Chlorella decreased the number of activated astrocytes in the DAL101 brain. These findings suggest that the prolonged consumption of Chlorella has the potential to prevent the progression of cognitive impairment.

  6. Use of the Internet as a prevention tool against cognitive decline in normal aging

    PubMed Central

    Klimova, Blanka

    2016-01-01

    Recent demographic trends indicate that older people appear to be one of the fastest growing population groups worldwide. In the year 2000, people older than 65 years represented 12.4% of the population. This number is expected to rise to 19% by 2030, particularly in developed countries. Therefore, there is sustained effort at both national and international levels to prolong the active life of these people as long as possible. Since the present older generation at the age of 55 years is already digitally literate, the use of technologies is one of the solutions. The purpose of this study is to discuss the role of the Internet in the prevention of cognitive decline in normal aging. The author examines clinical studies that exploit the use of the Internet, including online training programs, in the prevention of cognitive decline in healthy older individuals. The findings of the clinical studies indicate that the use of the Internet, especially online cognitive training programs, may have a positive effect on the improvement of cognitive functions in healthy older adults. Nevertheless, larger sample longitudinal randomized controlled clinical trials aimed at the prevention of cognitive decline among healthy older adults are needed. PMID:27672317

  7. Use of the Internet as a prevention tool against cognitive decline in normal aging

    PubMed Central

    Klimova, Blanka

    2016-01-01

    Recent demographic trends indicate that older people appear to be one of the fastest growing population groups worldwide. In the year 2000, people older than 65 years represented 12.4% of the population. This number is expected to rise to 19% by 2030, particularly in developed countries. Therefore, there is sustained effort at both national and international levels to prolong the active life of these people as long as possible. Since the present older generation at the age of 55 years is already digitally literate, the use of technologies is one of the solutions. The purpose of this study is to discuss the role of the Internet in the prevention of cognitive decline in normal aging. The author examines clinical studies that exploit the use of the Internet, including online training programs, in the prevention of cognitive decline in healthy older individuals. The findings of the clinical studies indicate that the use of the Internet, especially online cognitive training programs, may have a positive effect on the improvement of cognitive functions in healthy older adults. Nevertheless, larger sample longitudinal randomized controlled clinical trials aimed at the prevention of cognitive decline among healthy older adults are needed.

  8. Age of onset as a moderator of cognitive decline in pediatric-onset multiple sclerosis.

    PubMed

    Hosseini, Banafsheh; Flora, David B; Banwell, Brenda L; Till, Christine

    2014-09-01

    Cognitive impairment is often reported in pediatric-onset multiple sclerosis (MS). Using serial cognitive data from 35 individuals with pediatric-onset MS, this study examined how age at disease-onset and proxies of cognitive reserve may impact cognitive maturation over the course of childhood and adolescence. Neuropsychological evaluations were conducted at baseline and up to four more assessments. Of the 35 participants, 7 completed only one assessment, 5 completed two assessments, 13 completed three assessments, 10 completed four or more assessments. Growth curve modeling was used to assess longitudinal trajectories on the Trail Making Test-Part B (TMT-B) and the Symbol Digit Modalities (SDMT; oral version) and to examine how age at disease onset, baseline Full Scale IQ, and social status may moderate rate of change on these measures. Mean number of evaluations completed per patient was 2.8. Younger age at disease onset was associated with a greater likelihood of cognitive decline on both the TMT-B (p=.001) and SDMT (p=.005). Baseline IQ and parental social status did not moderate any of the cognitive trajectories. Findings suggest that younger age at disease-onset increases the vulnerability for disrupted performance on measures of information processing, visual scanning, perceptual/motor speed, and working memory. Proxies of cognitive reserve did not protect against the progression of decline on these measures. Young patients with MS should be advised to seek follow-up cognitive evaluation to assess cognitive maturation and to screen for the potential late emergence of cognitive deficits. (JINS, 2014, 20, 1-9).

  9. The 12 Years Preceding Mild Cognitive Impairment Due to Alzheimer’s Disease: The Temporal Emergence of Cognitive Decline

    PubMed Central

    Mistridis, Panagiota; Krumm, Sabine; Monsch, Andreas U.; Berres, Manfred; Taylor, Kirsten I.

    2015-01-01

    Abstract Background: The identification of the type and sequence of cognitive decline in preclinical mild cognitive impairment (MCI) prior to Alzheimer’s disease (AD) is crucial for understanding AD pathogenesis and implementing therapeutic interventions. Objective: To model the longitudinal courses of different neuropsychological functions in MCI due to AD. Methods: We investigated the prodromal phase of MCI over a 12-year period in 27 initially healthy participants with subsequent MCI preceding AD (NC-MCI) and 60 demographically matched healthy individuals (NC-NC). The longitudinal courses of cognitive performance (verbal and visual episodic memory, semantic memory, executive functioning, constructional praxis, psychomotor speed, language, and informant-based reports) were analyzed with linear mixed effects models. Results: The sequence with which different cognitive functions declined in the NC-MCI relative to the NC-NC group began with verbal memory and savings performance approximately eight years, and verbal episodic learning, visual memory, and semantic memory (animal fluency) circa four years prior to the MCI diagnosis. Executive functioning, psychomotor speed, and informant-based reports of the NC-MCI group declined approximately two years preceding the MCI diagnosis. Conclusions: Measurable neuropsychological deterioration occurs up to approximately eight years preceding MCI due to AD. PMID:26402083

  10. Can Training in a Real-Time Strategy Videogame Attenuate Cognitive Decline in Older Adults?

    PubMed Central

    Basak, Chandramallika; Boot, Walter R.; Voss, Michelle W.; Kramer, Arthur F.

    2014-01-01

    Declines in various cognitive abilities, particularly executive control functions, are observed in older adults. An important goal of cognitive training is to slow or reverse these age-related declines. However, opinion is divided in the literature regarding whether cognitive training can engender transfer to a variety of cognitive skills in older adults. Yet, recent research indicates that videogame training of young adults may engender broad transfer to skills of visual attention. In the current study, we used a real-time strategy videogame to attempt to train executive functions in older adults, such as working memory, task switching, short-term memory, inhibition, and reasoning. Older adults were either trained in a real-time strategy videogame for 23.5 hours (RON, n=20) or not (CONTROLS, n=20). A battery of cognitive tasks, including tasks of executive control and visuo-spatial skills, were assessed before, during, and after video game training. The trainees improved significantly in the measures of game performance. They also improved significantly more than the controls in a subset of the cognitive tasks, such as task switching, working memory, visual short term memory, and mental rotation. Trends in improvement were also observed, for the video game trainees, in inhibition and reasoning. Individual differences in changes in game performance were correlated with improvements in task-switching. The study has implications for the enhancement of executive control processes of older adults. PMID:19140648

  11. Quantitative T2 mapping of white matter: applications for ageing and cognitive decline.

    PubMed

    Knight, Michael J; McCann, Bryony; Tsivos, Demitra; Dillon, Serena; Coulthard, Elizabeth; Kauppinen, Risto A

    2016-08-01

    In MRI, the coherence lifetime T2 is sensitive to the magnetic environment imposed by tissue microstructure and biochemistry in vivo. Here we explore the possibility that the use of T2 relaxometry may provide information complementary to that provided by diffusion tensor imaging (DTI) in ageing of healthy controls (HC), Alzheimer's disease (AD) and mild cognitive impairment (MCI). T2 and diffusion MRI metrics were quantified in HC and patients with MCI and mild AD using multi-echo MRI and DTI. We used tract-based spatial statistics (TBSS) to evaluate quantitative MRI parameters in white matter (WM). A prolonged T2 in WM was associated with AD, and able to distinguish AD from MCI, and AD from HC. Shorter WM T2 was associated with better cognition and younger age in general. In no case was a reduction in T2 associated with poorer cognition. We also applied principal component analysis, showing that WM volume changes independently of  T2, MRI diffusion indices and cognitive performance indices. Our data add to the evidence that age-related and AD-related decline in cognition is in part attributable to WM tissue state, and much less to WM quantity. These observations suggest that WM is involved in AD pathology, and that T2 relaxometry is a potential imaging modality for detecting and characterising WM in cognitive decline and dementia. PMID:27384985

  12. Vitamin D as a marker of cognitive decline in elderly Indian population

    PubMed Central

    Vedak, Tejal Kanhaiya; Ganwir, Vaishali; Shah, Arun B.; Pinto, Charles; Lele, Vikram R.; Subramanyam, Alka; Shah, Hina; Deo, Sudha Shrikant

    2015-01-01

    Objectives: Very few studies in India have addressed the role of vitamin D in cognitive function. The present study was conducted to assess the serum levels of 25-hydroxyvitamin D (25(OH)D) and its association with markers of cognitive impairment and homocysteine levels in the elderly Indian population. Materials and Methods: The study population consisted of patients with dementia (Group A, n = 32), mild cognitive impairment (MCI; Group B, n = 24), and elderly age-matched controls (Group C, n = 30). Measurement of serum levels of 25(OH)D and total homocysteine were done. Results: Significant decreased concentration of 25(OH)D and increased concentration of homocysteine was observed. Association of serum levels of vitamin D with markers of cognitive decline as well as serum homocysteine levels was observed in patients with dementia and MCI when compared to controls. Conclusion: Correlation of vitamin D with markers of cognitive decline and homocysteine opens a new door for early diagnosis of cognitive impairment. PMID:26425010

  13. Quantitative T2 mapping of white matter: applications for ageing and cognitive decline

    NASA Astrophysics Data System (ADS)

    Knight, Michael J.; McCann, Bryony; Tsivos, Demitra; Dillon, Serena; Coulthard, Elizabeth; Kauppinen, Risto A.

    2016-08-01

    In MRI, the coherence lifetime T2 is sensitive to the magnetic environment imposed by tissue microstructure and biochemistry in vivo. Here we explore the possibility that the use of T2 relaxometry may provide information complementary to that provided by diffusion tensor imaging (DTI) in ageing of healthy controls (HC), Alzheimer’s disease (AD) and mild cognitive impairment (MCI). T2 and diffusion MRI metrics were quantified in HC and patients with MCI and mild AD using multi-echo MRI and DTI. We used tract-based spatial statistics (TBSS) to evaluate quantitative MRI parameters in white matter (WM). A prolonged T2 in WM was associated with AD, and able to distinguish AD from MCI, and AD from HC. Shorter WM T2 was associated with better cognition and younger age in general. In no case was a reduction in T2 associated with poorer cognition. We also applied principal component analysis, showing that WM volume changes independently of  T2, MRI diffusion indices and cognitive performance indices. Our data add to the evidence that age-related and AD-related decline in cognition is in part attributable to WM tissue state, and much less to WM quantity. These observations suggest that WM is involved in AD pathology, and that T2 relaxometry is a potential imaging modality for detecting and characterising WM in cognitive decline and dementia.

  14. Dietary patterns and cognitive decline in an Australian study of ageing.

    PubMed

    Gardener, S L; Rainey-Smith, S R; Barnes, M B; Sohrabi, H R; Weinborn, M; Lim, Y Y; Harrington, K; Taddei, K; Gu, Y; Rembach, A; Szoeke, C; Ellis, K A; Masters, C L; Macaulay, S L; Rowe, C C; Ames, D; Keogh, J B; Scarmeas, N; Martins, R N

    2015-07-01

    The aim of this paper was to investigate the association of three well-recognised dietary patterns with cognitive change over a 3-year period. Five hundred and twenty-seven healthy participants from the Australian Imaging, Biomarkers and Lifestyle study of ageing completed the Cancer Council of Victoria food frequency questionnaire at baseline and underwent a comprehensive neuropsychological assessment at baseline, 18 and 36 months follow-up. Individual neuropsychological test scores were used to construct composite scores for six cognitive domains and a global cognitive score. Based on self-reported consumption, scores for three dietary patterns, (1) Australian-style Mediterranean diet (AusMeDi), (2) western diet and (3) prudent diet were generated for each individual. Linear mixed model analyses were conducted to examine the relationship between diet scores and cognitive change in each cognitive domain and for the global score. Higher baseline adherence to the AusMeDi was associated with better performance in the executive function cognitive domain after 36 months in apolipoprotein E (APOE) ɛ4 allele carriers (P<0.01). Higher baseline western diet adherence was associated with greater cognitive decline after 36 months in the visuospatial cognitive domain in APOE ɛ4 allele non-carriers (P<0.01). All other results were not significant. Our findings in this well-characterised Australian cohort indicate that adherence to a healthy diet is important to reduce risk for cognitive decline, with the converse being true for the western diet. Executive function and visuospatial functioning appear to be particularly susceptible to the influence of diet.

  15. Preventing cognitive decline in older African Americans with mild cognitive impairment: design and methods of a randomized clinical trial.

    PubMed

    Rovner, Barry W; Casten, Robin J; Hegel, Mark T; Leiby, Benjamin E

    2012-07-01

    Mild Cognitive Impairment (MCI) affects 25% of older African Americans and predicts progression to Alzheimer's disease. An extensive epidemiologic literature suggests that cognitive, physical, and/or social activities may prevent cognitive decline. We describe the methods of a randomized clinical trial to test the efficacy of Behavior Activation to prevent cognitive decline in older African Americans with the amnestic multiple domain subtype of MCI. Community Health Workers deliver 6 initial in-home treatment sessions over 2-3 months and then 6 subsequent in-home booster sessions using language, materials, and concepts that are culturally relevant to older African Americans during this 24 month clinical trial. We are randomizing 200 subjects who are recruited from churches, senior centers, and medical clinics to Behavior Activation or Supportive Therapy, which controls for attention. The primary outcome is episodic memory as measured by the Hopkins Verbal Learning Test-Revised at baseline and at months 3, 12, 18, and 24. The secondary outcomes are general and domain-specific neuropsychological function, activities of daily living, depression, and quality-of-life. The negative results of recent clinical trials of drug treatments for MCI and Alzheimer's disease suggest that behavioral interventions may provide an alternative treatment approach to preserve cognition in an aging society.

  16. Performances on a cognitive theory of mind task: specific decline or general cognitive deficits? Evidence from normal aging.

    PubMed

    Fliss, Rafika; Lemerre, Marion; Mollard, Audrey

    2016-06-01

    Compromised theory of mind (ToM) can be explained either by a failure to implement specific representational capacities (mental state representations) or by more general executive selection demands. In older adult populations, evidence supporting affected executive functioning and cognitive ToM in normal aging are reported. However, links between these two functions remain unclear. In the present paper, we address these shortcomings by using a specific task of ToM and classical executive tasks. We studied, using an original cognitive ToM task, the effect of age on ToM performances, in link with the progressive executive decline. 96 elderly participants were recruited. They were asked to perform a cognitive ToM task, and 5 executive tests (Stroop test and Hayling Sentence Completion Test to appreciate inhibitory process, Trail Making Test and Verbal Fluency for shifting assessment and backward span dedicated to estimate working memory capacity). The results show changes in cognitive ToM performance according to executive demands. Correlational studies indicate a significant relationship between ToM performance and the selected executive measures. Regression analyzes demonstrates that level of vocabulary and age as the best predictors of ToM performance. The results are consistent with the hypothesis that ToM deficits are related to age-related domain-general decline rather than as to a breakdown in specialized representational system. The implications of these findings for the nature of social cognition tests in normal aging are also discussed. PMID:27277154

  17. Performances on a cognitive theory of mind task: specific decline or general cognitive deficits? Evidence from normal aging.

    PubMed

    Fliss, Rafika; Lemerre, Marion; Mollard, Audrey

    2016-06-01

    Compromised theory of mind (ToM) can be explained either by a failure to implement specific representational capacities (mental state representations) or by more general executive selection demands. In older adult populations, evidence supporting affected executive functioning and cognitive ToM in normal aging are reported. However, links between these two functions remain unclear. In the present paper, we address these shortcomings by using a specific task of ToM and classical executive tasks. We studied, using an original cognitive ToM task, the effect of age on ToM performances, in link with the progressive executive decline. 96 elderly participants were recruited. They were asked to perform a cognitive ToM task, and 5 executive tests (Stroop test and Hayling Sentence Completion Test to appreciate inhibitory process, Trail Making Test and Verbal Fluency for shifting assessment and backward span dedicated to estimate working memory capacity). The results show changes in cognitive ToM performance according to executive demands. Correlational studies indicate a significant relationship between ToM performance and the selected executive measures. Regression analyzes demonstrates that level of vocabulary and age as the best predictors of ToM performance. The results are consistent with the hypothesis that ToM deficits are related to age-related domain-general decline rather than as to a breakdown in specialized representational system. The implications of these findings for the nature of social cognition tests in normal aging are also discussed.

  18. Preventing cognitive decline in older African Americans with mild cognitive impairment: design and methods of a randomized clinical trial.

    PubMed

    Rovner, Barry W; Casten, Robin J; Hegel, Mark T; Leiby, Benjamin E

    2012-07-01

    Mild Cognitive Impairment (MCI) affects 25% of older African Americans and predicts progression to Alzheimer's disease. An extensive epidemiologic literature suggests that cognitive, physical, and/or social activities may prevent cognitive decline. We describe the methods of a randomized clinical trial to test the efficacy of Behavior Activation to prevent cognitive decline in older African Americans with the amnestic multiple domain subtype of MCI. Community Health Workers deliver 6 initial in-home treatment sessions over 2-3 months and then 6 subsequent in-home booster sessions using language, materials, and concepts that are culturally relevant to older African Americans during this 24 month clinical trial. We are randomizing 200 subjects who are recruited from churches, senior centers, and medical clinics to Behavior Activation or Supportive Therapy, which controls for attention. The primary outcome is episodic memory as measured by the Hopkins Verbal Learning Test-Revised at baseline and at months 3, 12, 18, and 24. The secondary outcomes are general and domain-specific neuropsychological function, activities of daily living, depression, and quality-of-life. The negative results of recent clinical trials of drug treatments for MCI and Alzheimer's disease suggest that behavioral interventions may provide an alternative treatment approach to preserve cognition in an aging society. PMID:22406101

  19. Vascular disease and risk factors are associated with cognitive decline in the alzheimer disease spectrum.

    PubMed

    Lorius, Natacha; Locascio, Joseph J; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A; Viswanathan, Anand; Marshall, Gad A

    2015-01-01

    We investigated the relationship between vascular disease and risk factors versus cognitive decline cross-sectionally and longitudinally in normal older control, mild cognitive impairment, and mild Alzheimer disease (AD) dementia subjects. A total of 812 participants (229 normal older control, 395 mild cognitive impairment, 188 AD) underwent cognitive testing, brain magnetic resonance imaging, and clinical evaluations at baseline and over a period of 3 years. General linear, longitudinal mixed-effects, and Cox proportional hazards models were used. Greater homocysteine level and white matter hyperintensity volume were associated with processing speed impairment (homocysteine: P=0.02; white matter hyperintensity: P<0.0001); greater Vascular Index score was associated with memory impairment (P=0.007); and greater number of apolipoprotein E ε4 (APOE4) alleles was associated with global cognitive impairment (P=0.007) at baseline. Apolipoprotein E ε4 was associated with greater rate of increase in global cognitive impairment (P=0.002) and processing speed impairment (P=0.001) over time, whereas higher total cholesterol was associated with greater rate of increase in global cognitive impairment (P=0.02) and memory impairment (P=0.06) over time. These results suggest a significant association of increased vascular disease and risk factors with cognitive impairment at baseline and over time in the AD spectrum in a sample that was selected to have low vascular burden at baseline.

  20. Baseline white matter microstructural integrity is not related to cognitive decline after 5 years: The RUN DMC study.

    PubMed

    van Uden, I W M; van der Holst, H M; Schaapsmeerders, P; Tuladhar, A M; van Norden, A G W; de Laat, K F; Norris, D G; Claassen, J A H R; van Dijk, E J; Richard, E; Kessels, R P C; de Leeuw, F-E

    2015-12-01

    •DTI can provide information on microstructural white matter integrity.•White matter microstructural integrity is not related to cognitive decline in SVD.•These results are in contrast with cross-sectional findings.•Other factors than white matter microstructural damage underlie this cognitive decline.

  1. The mismatch negativity as an index of cognitive decline for the early detection of Alzheimer's disease.

    PubMed

    Ruzzoli, Manuela; Pirulli, Cornelia; Mazza, Veronica; Miniussi, Carlo; Brignani, Debora

    2016-01-01

    Evidence suggests that Alzheimer's disease (AD) is part of a continuum, characterized by long preclinical phases before the onset of clinical symptoms. In several cases, this continuum starts with a syndrome, defined as mild cognitive impairment (MCI), in which daily activities are preserved despite the presence of cognitive decline. The possibility of having a reliable and sensitive neurophysiological marker that can be used for early detection of AD is extremely valuable because of the incidence of this type of dementia. In this study, we aimed to investigate the reliability of auditory mismatch negativity (aMMN) as a marker of cognitive decline from normal ageing progressing from MCI to AD. We compared aMMN elicited in the frontal and temporal locations by duration deviant sounds in short (400 ms) and long (4000 ms) inter-trial intervals (ITI) in three groups. We found that at a short ITI, MCI showed only the temporal component of aMMN and AD the frontal component compared to healthy elderly who presented both. At a longer ITI, aMMN was elicited only in normal ageing subjects at the temporal locations. Our study provides empirical evidence for the possibility to adopt aMMN as an index for assessing cognitive decline in pathological ageing. PMID:27616726

  2. Reduction of Endogenous Melatonin Accelerates Cognitive Decline in Mice in a Simulated Occupational Formaldehyde Exposure Environment

    PubMed Central

    Mei, Yufei; Duan, Chunli; Li, Xiaoxiao; Zhao, Yun; Cao, Fenghua; Shang, Shuai; Ding, Shumao; Yue, Xiangpei; Gao, Ge; Yang, Hui; Shen, Luxi; Feng, Xueyan; Jia, Jianping; Tong, Zhiqian; Yang, Xu

    2016-01-01

    Individuals afflicted with occupational formaldehyde (FA) exposure often suffer from abnormal behaviors such as aggression, depression, anxiety, sleep disorders, and in particular, cognitive impairments. Coincidentally, clinical patients with melatonin (MT) deficiency also complain of cognitive problems associated with the above mental disorders. Whether and how FA affects endogenous MT metabolism and induces cognitive decline need to be elucidated. To mimic occupational FA exposure environment, 16 healthy adult male mice were exposed to gaseous FA (3 mg/m3) for 7 consecutive days. Results showed that FA exposure impaired spatial memory associated with hippocampal neuronal death. Biochemical analysis revealed that FA exposure elicited an intensive oxidative stress by reducing systemic glutathione levels, in particular, decreasing brain MT concentrations. Inversely, intraperitoneal injection of MT markedly attenuated FA-induced hippocampal neuronal death, restored brain MT levels, and reversed memory decline. At tissue levels, injection of FA into the hippocampus distinctly reduced brain MT concentrations. Furthermore, at cellular and molecular levels, we found that FA directly inactivated MT in vitro and in vivo. These findings suggest that MT supplementation contributes to the rescue of cognitive decline, and may alleviate mental disorders in the occupational FA-exposed human populations. PMID:26938543

  3. Rate of cognitive decline during the premotor phase of essential tremor

    PubMed Central

    Louis, Elan D.; Sánchez-Ferro, Álvaro; Bermejo-Pareja, Félix

    2013-01-01

    Objective: To characterize the rate of cognitive decline during the premotor phase of essential tremor (ET) in comparison to prevalent ET cases and controls. Methods: In this population-based, prospective study of people aged 65 years and older (Neurological Disorders in Central Spain), a 37-item version of the Mini-Mental State Examination was administered at 2 visits (baseline and follow-up, approximately 3 years later). We compared the rate of cognitive decline in 3 groups: prevalent ET cases (i.e., participants diagnosed with ET at baseline and at follow-up), “premotor” ET cases (i.e., participants diagnosed with incident ET at follow-up, but not at baseline), and controls (i.e., participants not diagnosed with ET at baseline or follow-up). Results: The 2,375 participants included 135 prevalent ET cases, 56 premotor ET cases, and 2,184 controls. During the follow-up period of 3.4 ± 0.5 years (mean ± SD), the 37-item version of the Mini-Mental State Examination declined by 0.7 ± 3.3 points (0.2 ± 1.0 points/year) in prevalent ET cases, 1.1 ± 3.5 points (0.3 ± 1.0 points/year) in premotor ET cases, and 0.1 ± 3.9 points (0.0 ± 1.2 points/year) in controls (p = 0.014). The difference between premotor ET cases and controls was significant (p = 0.046), as was the difference between prevalent ET cases and controls (p = 0.027). Conclusions: In this prospective cohort, cognitive test scores in premotor and prevalent ET cases declined at a faster rate than in elders without this disease. A decline in global cognitive function may occur in a premotor phase of ET. PMID:23700331

  4. Optimizing Cognitive Development over the Life Course and Preventing Cognitive Decline: Introducing the Cognitive Health Environment Life Course Model (CHELM)

    ERIC Educational Resources Information Center

    Anstey, Kaarin J.

    2014-01-01

    Optimal cognitive development is defined in this article as the highest level of cognitive function reached in each cognitive domain given a person's biological and genetic disposition, and the highest possible maintenance of cognitive function over the adult life course. Theoretical perspectives underpinning the development of a framework…

  5. Compensatory larger cortical thickness in healthy elderly individuals with electroencephalographic risk for cognitive decline.

    PubMed

    Castro-Chavira, Susana A; Barrios, Fernando A; Pasaye, Erick H; Alatorre-Cruz, Graciela C; Fernández, Thalía

    2016-06-15

    Excess theta electroencephalographic (EEG) activity has been described as an accurate predictor for cognitive decline at least 7 years before symptom presentation. To test whether this predictor for cognitive decline correlates with structural changes in the brains of healthy elderly individuals, we compared the magnetic resonance structural images of healthy individuals with excess of theta activity [group with a risk for cognitive decline, risk group (RG); n=14] with healthy controls with normal EEG activity (control group; n=14). Neuropsychological and epidemiological analyses showed significant differences in only two features: more years of education and better performance in the visuospatial process task in the control group. Voxel-based morphometry results were not conclusive, but showed tendencies toward larger volumes in the prefrontal and parietal lobes, and smaller volumes in the right temporal lobe, right occipital lobe, and left cerebellum for the RG; these tendencies are in agreement with those proposed by the posterior-anterior shift in an aging model. Cortical-thickness analyses yielded a significant correlation between cortical thickness and years of education in the prefrontal and inferior-temporal regions, and larger cortical thickness in the RG, independent of age and years of education, in the right superior temporal region. These results suggest changes in the cortical thickness of structures related to memory and visuospatial functions in healthy, cognitively normal individuals before the appearance of cognitive decline. Thus, the performance of healthy elderly individuals with EEG risk may only be slightly different from normal because of compensation mechanisms allowing them to fulfill daily-life tasks, masking structural changes during preclinical neurocognitive disorders. PMID:27171033

  6. Glutamatergic regulation prevents hippocampal-dependent age-related cognitive decline through dendritic spine clustering

    PubMed Central

    Pereira, Ana C.; Lambert, Hilary K.; Grossman, Yael S.; Dumitriu, Dani; Waldman, Rachel; Jannetty, Sophia K.; Calakos, Katina; Janssen, William G.; McEwen, Bruce S.; Morrison, John H.

    2014-01-01

    The dementia of Alzheimer’s disease (AD) results primarily from degeneration of neurons that furnish glutamatergic corticocortical connections that subserve cognition. Although neuron death is minimal in the absence of AD, age-related cognitive decline does occur in animals as well as humans, and it decreases quality of life for elderly people. Age-related cognitive decline has been linked to synapse loss and/or alterations of synaptic proteins that impair function in regions such as the hippocampus and prefrontal cortex. These synaptic alterations are likely reversible, such that maintenance of synaptic health in the face of aging is a critically important therapeutic goal. Here, we show that riluzole can protect against some of the synaptic alterations in hippocampus that are linked to age-related memory loss in rats. Riluzole increases glutamate uptake through glial transporters and is thought to decrease glutamate spillover to extrasynaptic NMDA receptors while increasing synaptic glutamatergic activity. Treated aged rats were protected against age-related cognitive decline displayed in nontreated aged animals. Memory performance correlated with density of thin spines on apical dendrites in CA1, although not with mushroom spines. Furthermore, riluzole-treated rats had an increase in clustering of thin spines that correlated with memory performance and was specific to the apical, but not the basilar, dendrites of CA1. Clustering of synaptic inputs is thought to allow nonlinear summation of synaptic strength. These findings further elucidate neuroplastic changes in glutamatergic circuits with aging and advance therapeutic development to prevent and treat age-related cognitive decline. PMID:25512503

  7. EEG markers for cognitive decline in elderly subjects with subjective memory complaints.

    PubMed

    Alexander, David M; Arns, Martijn W; Paul, Robert H; Rowe, Donald L; Cooper, Nicholas; Esser, Aristide H; Fallahpour, Kamran; Stephan, Blossom C M; Heesen, Erica; Breteler, Rien; Williams, Leanne M; Gordon, Evian

    2006-03-01

    New treatments for Alzheimer's disease require early detection of cognitive decline. Most studies seeking to identify markers of early cognitive decline have focused on a limited number of measures. We sought to establish the profile of brain function measures which best define early neuropsychological decline. We compared subjects with subjective memory complaints to normative controls on a wide range of EEG derived measures, including a new measure of event-related spatio-temporal waves and biophysical modeling, which derives anatomical and physiological parameters based on subject's EEG measurements. Measures that distinguished the groups were then related to cognitive performance on a variety of learning and executive function tasks. The EEG measures include standard power measures, peak alpha frequency, EEG desynchronization to eyes-opening, and global phase synchrony. The most prominent differences in subjective memory complaint subjects were elevated alpha power and an increased number of spatio-temporal wave events. Higher alpha power and changes in wave activity related most strongly to a decline in verbal memory performance in subjects with subjective memory complaints, and also declines in maze performance and working memory reaction time. Interestingly, higher alpha power and wave activity were correlated with improved performance in reverse digit span in the subjective memory complaint group. The modeling results suggest that differences in the subjective memory complaint subjects were due to a decrease in cortical and thalamic inhibitory gains and slowed dendritic time-constants. The complementary profile that emerges from the variety of measures and analyses points to a nonlinear progression in electrophysiological changes from early neuropsychological decline to late-stage dementia, and electrophysiological changes in subjective memory complaint that vary in their relationships to a range of memory-related tasks. PMID:16544366

  8. Cognitive decline in dementia with Lewy bodies: a 5-year prospective cohort study

    PubMed Central

    Rongve, A; Soennesyn, H; Skogseth, Ragnhild; Oesterhus, Ragnhild; Hortobágyi, T; Ballard, Clive; Auestad, B H; Aarsland, D

    2016-01-01

    Objectives We report the cognitive decline in persons diagnosed with mild dementia with Lewy bodies (DLB) and mild Alzheimer's disease (AD) during 5 years of annual follow-ups. Methods Patients were recruited into the study from geriatric, psychiatric and neurology clinics in Western Norway during 2005–2013. They were diagnosed according to clinical consensus criteria, based on standardised clinical rating scales. Autopsy-based diagnoses were available for 20 cases. Cognitive decline for up to 5 years was assessed using the Clinical Dementia Rating (CDR) scale and the Mini-Mental State Examination (MMSE). Survival analysis including Cox regression (time to reach severe dementia) and linear mixed-effects (lme) modelling were used to model the decline on MMSE. Results At least one follow-up assessment was available for 67 patients with DLB and 107 patients with AD, with a median follow-up time of 4.3 years. The time to reach severe dementia was significantly shorter in DLB (median 1793 days) compared with AD (1947 days; p=0.033), and the difference remained significant in the multiple Cox regression analysis (HR=2.0, p<0.02). In the adjusted lme model, MMSE decline was faster in DLB (annual decline 4.4 points) compared with AD (3.2 points; p<0.008). Conclusions Our findings show that from the mild dementia stage, patients with DLB have a more rapid cognitive decline than in AD. Such prognostic information is vital for patients and families and crucial for planning clinical trials and enabling health economic modelling. PMID:26928028

  9. Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease

    PubMed Central

    Small, Gary W.; Ercoli, Linda M.; Silverman, Daniel H. S.; Huang, S.-C.; Komo, Scott; Bookheimer, Susan Y.; Lavretsky, Helen; Miller, Karen; Siddarth, Prabha; Rasgon, Natalie L.; Mazziotta, John C.; Saxena, Sanjaya; Wu, H. M.; Mega, Michael S.; Cummings, Jeffrey L.; Saunders, Ann M.; Pericak-Vance, Margaret A.; Roses, Allen D.; Barrio, Jorge R.; Phelps, Michael E.

    2000-01-01

    The major known genetic risk for Alzheimer's disease (AD), apolipoprotein E-4 (APOE-4), is associated with lowered parietal, temporal, and posterior cingulate cerebral glucose metabolism in patients with a clinical diagnosis of AD. To determine cognitive and metabolic decline patterns according to genetic risk, we investigated cerebral metabolic rates by using positron emission tomography in middle-aged and older nondemented persons with normal memory performance. A single copy of the APOE-4 allele was associated with lowered inferior parietal, lateral temporal, and posterior cingulate metabolism, which predicted cognitive decline after 2 years of longitudinal follow-up. For the 20 nondemented subjects followed longitudinally, memory performance scores did not decline significantly, but cortical metabolic rates did. In APOE-4 carriers, a 4% left posterior cingulate metabolic decline was observed, and inferior parietal and lateral temporal regions demonstrated the greatest magnitude (5%) of metabolic decline after 2 years. These results indicate that the combination of cerebral metabolic rates and genetic risk factors provides a means for preclinical AD detection that will assist in response monitoring during experimental treatments. PMID:10811879

  10. Decreased Self-Appraisal Accuracy on Cognitive Tests of Executive Functioning Is a Predictor of Decline in Mild Cognitive Impairment

    PubMed Central

    Scherling, Carole S.; Wilkins, Sarah E.; Zakrezewski, Jessica; Kramer, Joel H.; Miller, Bruce L.; Weiner, Michael W.; Rosen, Howard J.

    2016-01-01

    Objective: Mild cognitive impairment (MCI) in older individuals is associated with increased risk of progression to dementia. The factors predicting progression are not yet well established, yet cognitive performance, particularly for memory, is known to be important. Anosognosia, meaning lack of awareness of one’s impaired function, is commonly reported in dementia and is often also a feature of MCI, but its association with risk of progression is not well understood. In particular, self-appraisal measures provide an autonomous measure of insight abilities, without the need of an informant. Methods: The present study examined the utility of self-appraisal accuracy at baseline for predicting cognitive decline in 51 patients using an informant-free assessment method. Baseline task performance scores were compared to self-assessments of performance to yield a discrimination score (DS) for tasks tapping into memory and executive functions. Results: Linear regression revealed that a larger DS for executive function tasks in MCI predicted functional decline, independent of age, education, and baseline memory and executive task scores. Conclusion: These findings indicate that objective estimates of self-appraisal can be used to quantify anosognosia and increase predictive accuracy for decline in MCI. PMID:27458368

  11. Sex-specific risk of cardiovascular disease and cognitive decline: pregnancy and menopause

    PubMed Central

    2013-01-01

    Understanding the biology of sex differences is integral to personalized medicine. Cardiovascular disease and cognitive decline are two related conditions, with distinct sex differences in morbidity and clinical manifestations, response to treatments, and mortality. Although mortality from all-cause cardiovascular diseases has declined in women over the past five years, due in part to increased educational campaigns regarding the recognition of symptoms and application of treatment guidelines, the mortality in women still exceeds that of men. The physiological basis for these differences requires further research, with particular attention to two physiological conditions which are unique to women and associated with hormonal changes: pregnancy and menopause. Both conditions have the potential to impact life-long cardiovascular risk, including cerebrovascular function and cognition in women. This review draws on epidemiological, translational, clinical, and basic science studies to assess the impact of hypertensive pregnancy disorders on cardiovascular disease and cognitive function later in life, and examines the effects of post-menopausal hormone treatments on cardiovascular risk and cognition in midlife women. We suggest that hypertensive pregnancy disorders and menopause activate vascular components, i.e., vascular endothelium and blood elements, including platelets and leukocytes, to release cell-membrane derived microvesicles that are potential mediators of changes in cerebral blood flow, and may ultimately affect cognition in women as they age. Research into specific sex differences for these disease processes with attention to an individual’s sex chromosomal complement and hormonal status is important and timely. PMID:23537114

  12. Glucagon-like peptide-1, diabetes, and cognitive decline: possible pathophysiological links and therapeutic opportunities.

    PubMed

    Mossello, Enrico; Ballini, Elena; Boncinelli, Marta; Monami, Matteo; Lonetto, Giuseppe; Mello, Anna Maria; Tarantini, Francesca; Baldasseroni, Samuele; Mannucci, Edoardo; Marchionni, Niccolò

    2011-01-01

    Metabolic and neurodegenerative disorders have a growing prevalence in Western countries. Available epidemiologic and neurobiological evidences support the existence of a pathophysiological link between these conditions. Glucagon-like peptide 1 (GLP-1), whose activity is reduced in insulin resistance, has been implicated in central nervous system function, including cognition, synaptic plasticity, and neurogenesis. We review the experimental researches suggesting that GLP-1 dysfunction might be a mediating factor between Type 2 diabetes mellitus (T2DM) and neurodegeneration. Drug treatments enhancing GLP-1 activity hold out hope for treatment and prevention of Alzheimer's disease (AD) and cognitive decline.

  13. Neuropsychological Markers of Cognitive Decline in Persons With Alzheimer Disease Neuropathology.

    PubMed

    Hassenstab, Jason; Monsell, Sarah E; Mock, Charles; Roe, Catherine M; Cairns, Nigel J; Morris, John C; Kukull, Walter

    2015-11-01

    To evaluate cognitive performance among persons who did and did not develop clinical Alzheimer disease (AD) but had AD neuropathology at autopsy, we examined neuropsychological performance in cognitively healthy (Clinical Dementia Rating [CDR] = 0) participants who returned for at least 1 follow-up and died within 2 years of their last assessment. Nonprogressors remained at CDR = 0 until death; progressors developed symptomatic AD during life (CDR > 0). Cognitive performance at baseline was compared between progressors and nonprogressors on a global cognitive composite and 4 domain-specific composites (episodic memory, language, attention/working memory, and executive function). Models adjusted for age, education, sex, and non-AD neuropathology. Progressors (n = 173) had worse performance than nonprogressors (n = 141) in nearly all cognitive domains. Progressors scored lower on composites of global cognition (P < 0.001), executive function (P = 0.0006), language (P < 0.0001), and episodic memory (P = 0.0006) but not on attention/working memory (P = 0.91). These data indicate that individuals with underlying AD neuropathology who are clinically healthy but who later develop symptomatic AD have worse performance in a wide range of domains versus individuals with underlying AD neuropathology who are clinically healthy but do not become symptomatic during life. Therefore, subtle cognitive decline at baseline may indicate an increased risk of progression to symptomatic AD.

  14. Video games as a means to reduce age-related cognitive decline: attitudes, compliance, and effectiveness.

    PubMed

    Boot, Walter R; Champion, Michael; Blakely, Daniel P; Wright, Timothy; Souders, Dustin J; Charness, Neil

    2013-01-01

    Recent research has demonstrated broad benefits of video game play to perceptual and cognitive abilities. These broad improvements suggest that video game-based cognitive interventions may be ideal to combat the many perceptual and cognitive declines associated with advancing age. Furthermore, game interventions have the potential to induce higher rates of intervention compliance compared to other cognitive interventions as they are assumed to be inherently enjoyable and motivating. We explored these issues in an intervention that tested the ability of an action game and a "brain fitness" game to improve a variety of abilities. Cognitive abilities did not significantly improve, suggesting caution when recommending video game interventions as a means to reduce the effects of cognitive aging. However, the game expected to produce the largest benefit based on previous literature (an action game) induced the lowest intervention compliance. We explain this low compliance by participants' ratings of the action game as less enjoyable and by their prediction that training would have few meaningful benefits. Despite null cognitive results, data provide valuable insights into the types of video games older adults are willing to play and why. PMID:23378841

  15. Video games as a means to reduce age-related cognitive decline: attitudes, compliance, and effectiveness.

    PubMed

    Boot, Walter R; Champion, Michael; Blakely, Daniel P; Wright, Timothy; Souders, Dustin J; Charness, Neil

    2013-01-01

    Recent research has demonstrated broad benefits of video game play to perceptual and cognitive abilities. These broad improvements suggest that video game-based cognitive interventions may be ideal to combat the many perceptual and cognitive declines associated with advancing age. Furthermore, game interventions have the potential to induce higher rates of intervention compliance compared to other cognitive interventions as they are assumed to be inherently enjoyable and motivating. We explored these issues in an intervention that tested the ability of an action game and a "brain fitness" game to improve a variety of abilities. Cognitive abilities did not significantly improve, suggesting caution when recommending video game interventions as a means to reduce the effects of cognitive aging. However, the game expected to produce the largest benefit based on previous literature (an action game) induced the lowest intervention compliance. We explain this low compliance by participants' ratings of the action game as less enjoyable and by their prediction that training would have few meaningful benefits. Despite null cognitive results, data provide valuable insights into the types of video games older adults are willing to play and why.

  16. Video Games as a Means to Reduce Age-Related Cognitive Decline: Attitudes, Compliance, and Effectiveness

    PubMed Central

    Boot, Walter R.; Champion, Michael; Blakely, Daniel P.; Wright, Timothy; Souders, Dustin J.; Charness, Neil

    2013-01-01

    Recent research has demonstrated broad benefits of video game play to perceptual and cognitive abilities. These broad improvements suggest that video game-based cognitive interventions may be ideal to combat the many perceptual and cognitive declines associated with advancing age. Furthermore, game interventions have the potential to induce higher rates of intervention compliance compared to other cognitive interventions as they are assumed to be inherently enjoyable and motivating. We explored these issues in an intervention that tested the ability of an action game and a “brain fitness” game to improve a variety of abilities. Cognitive abilities did not significantly improve, suggesting caution when recommending video game interventions as a means to reduce the effects of cognitive aging. However, the game expected to produce the largest benefit based on previous literature (an action game) induced the lowest intervention compliance. We explain this low compliance by participants’ ratings of the action game as less enjoyable and by their prediction that training would have few meaningful benefits. Despite null cognitive results, data provide valuable insights into the types of video games older adults are willing to play and why. PMID:23378841

  17. Cancer, Coping, and Cognition: A Model for the Role of Stress Reactivity in Cancer-Related Cognitive Decline

    PubMed Central

    Andreotti, Charissa; Root, James C.; Ahles, Tim A.; McEwen, Bruce S.; Compas, Bruce E.

    2014-01-01

    Cognitive decline and accompanying neurological changes associated with non-CNS cancer diagnosis and treatment have been increasingly identified in a subset of patients. Initially believed to be due to neurotoxic effects of chemotherapy exposure, observation of cognitive decline in patients not treated with chemotherapy, cancer-diagnosed individuals prior to treatment, and patients receiving alternative treatment modalities (surgery, endocrine therapy, radiation), has led to investigation of additional potential etiologies and moderating factors. Stressful experiences have long been posited as a contributor to these cognitive changes. Through reciprocal connectivity with peripheral systems, the brain maintains a dynamic circuitry to adapt to stress (allostasis). However, overuse of this system leads to dysregulation and contributes to pathophysiology (allostatic load). At this time, little research has been conducted to systematically examine the role of allostatic load in cancer-related cognitive dysfunction. Here we integrate theories of stress biology, neuropsychology, and coping and propose a model through which individuals with a high level of allostatic load at diagnosis may be particularly vulnerable to the neurocognitive effects of cancer. Opportunities for future research to test and extend proposed mechanisms are discussed in addition to points of prevention and intervention based on individual variation in stress reactivity and coping skills. PMID:25286084

  18. Adverse Vascular Risk is Related to Cognitive Decline in Older Adults

    PubMed Central

    Jefferson, Angela L.; Hohman, Timothy J.; Liu, Dandan; Haj-Hassan, Shereen; Gifford, Katherine A.; Benson, Elleena M.; Skinner, Jeannine S.; Lu, Zengqi; Sparling, Jamie; Sumner, Emily C.; Bell, Susan; Ruberg, Frederick L.

    2014-01-01

    Background Cardiovascular disease (CVD) and related risk factors are associated with Alzheimer’s disease (AD). This association is less well-defined in normal cognition (NC) or prodromal AD (mild cognitive impairment (MCI)). Objective Cross-sectionally and longitudinally relate a vascular risk index to cognitive outcomes among elders free of clinical dementia. Methods 3117 MCI (74±8 years, 56% female) and 6603 NC participants (72±8 years, 68% female) were drawn from the National Alzheimer’s Coordinating Center. A composite measure of vascular risk was defined using the Framingham Stroke Risk Profile (FSRP) score (i.e., age, systolic blood pressure, anti-hypertensive medication, diabetes, cigarette smoking, CVD history, atrial fibrillation). Ordinary linear regressions and generalized linear mixed models related baseline FSRP to cross-sectional and longitudinal cognitive outcomes, separately for NC and MCI, adjusting for age, sex, race, education, and follow-up time (in longitudinal models). Results In NC participants, increasing FSRP was related to worse baseline global cognition, information processing speed, and sequencing abilities (p-values<0.0001) and a worse longitudinal trajectory on all cognitive measures (p-values<0.0001). In MCI, increasing FSRP correlated with worse longitudinal delayed memory (p=0.004). In secondary models using an age-excluded FSRP score, associations persisted in NC participants for global cognition, naming, information processing speed, and sequencing abilities. Conclusions An adverse vascular risk profile is associated with worse cognitive trajectory, especially global cognition, naming, and information processing speed, among NC elders. Future studies are needed to understand how effective management of CVD and related risk factors can modify cognitive decline to identify the ideal timeframe for primary prevention implementation. PMID:25471188

  19. The recency ratio as an index of cognitive performance and decline in elderly individuals.

    PubMed

    Bruno, Davide; Reichert, Chelsea; Pomara, Nunzio

    2016-11-01

    Individuals with Alzheimer's disease have been found to present a typical serial position curve in immediate recall tests, showing poor primacy performance and exaggerated recency recall. However, the recency advantage is usually lost after a delay. On this basis, we examined whether the recency ratio (Rr), calculated by dividing recency performance in an immediate memory task by recency performance in a delayed task, was a useful risk marker of cognitive decline. We tested whether change in Mini-Mental State Examination (MMSE) performance between baseline and follow-up was predicted by baseline Rr and found this to be the case (N = 245). From these analyses, we conclude that participants with high Rr scores, who show disproportionate recency recall in the immediate test compared to the delayed test, present signs of being at risk for cognitive decline or dysfunction.

  20. Hyperamylinemia as a risk factor for accelerated cognitive decline in diabetes.

    PubMed

    Ly, Han; Despa, Florin

    2015-01-01

    Type II diabetes increases the risk for cognitive decline via multiple traits. Amylin is a pancreatic hormone that has amyloidogenic and cytotoxic properties similar to the amyloid-β peptide. The amylin hormone is overexpressed in individuals with pre-diabetic insulin resistance or obesity leading to amylin oligomerization and deposition in pancreatic islets. Amylin oligomerization was implicated in the apoptosis of the insulin-producing β-cells. Recent studies showed that brain tissue from diabetic patients with cerebrovascular dementia or Alzheimer's disease contains significant deposits of oligomerized amylin. It has also been reported that the brain amylin deposition reduced exploratory drive, recognition memory and vestibulomotor function in a rat model that overexpresses human amylin in the pancreas. These novel findings are reviewed here and the hypothesis that type II diabetes is linked with cognitive decline by amylin accumulation in the brain is proposed. Deciphering the impact of hyperamylinemia on the brain is critical for both etiology and treatment of dementia.

  1. The relationship between long-term sunlight radiation and cognitive decline in the REGARDS cohort study

    NASA Astrophysics Data System (ADS)

    Kent, Shia T.; Kabagambe, Edmond K.; Wadley, Virginia G.; Howard, Virginia J.; Crosson, William L.; Al-Hamdan, Mohammad Z.; Judd, Suzanne E.; Peace, Fredrick; McClure, Leslie A.

    2014-04-01

    Sunlight may be related to cognitive function through vitamin D metabolism or circadian rhythm regulation. The analysis presented here sought to test whether ground and satellite measures of solar radiation are associated with cognitive decline. The study used a 15-year residential history merged with satellite and ground monitor data to determine sunlight (solar radiation) and air temperature exposure for a cohort of 19,896 cognitively intact black and white participants aged 45+ from the 48 contiguous United States. Exposures of 15, 10, 5, 2, and 1-year were used to predict cognitive status at the most recent assessment in logistic regression models; 1-year insolation and maximum temperatures were chosen as exposure measures. Solar radiation interacted with temperature, age, and gender in its relationships with incident cognitive impairment. After adjustment for covariates, the odds ratio (OR) of cognitive decline for solar radiation exposure below the median vs above the median in the 3rd tertile of maximum temperatures was 1.88 (95 % CI: 1.24, 2.85), that in the 2nd tertile was 1.33 (95 % CI: 1.09, 1.62), and that in the 1st tertile was 1.22 (95 % CI: 0.92, 1.60). We also found that participants under 60 years old had an OR = 1.63 (95 % CI: 1.20, 2.22), those 60-80 years old had an OR = 1.18 (95 % CI: 1.02, 1.36), and those over 80 years old had an OR = 1.05 (0.80, 1.37). Lastly, we found that males had an OR = 1.43 (95 % CI: 1.22, 1.69), and females had an OR = 1.02 (0.87, 1.20). We found that lower levels of solar radiation were associated with increased odds of incident cognitive impairment.

  2. ω-3 fatty acids in the prevention of cognitive decline in humans.

    PubMed

    Cederholm, Tommy; Salem, Norman; Palmblad, Jan

    2013-11-01

    The brain is a lipid-rich organ where docosahexaenoic acid (DHA) is enriched and where eicosapentaenoic acid (EPA) may have anti-inflammatory effects. The potential role for n-3 (ω-3) fatty acids such as DHA and EPA in the prevention of cognitive decline, including Alzheimer's disease (AD) has attracted major interest for the past 20 y. This review presents our understanding of recent observational, interventional, and experimental studies, with the aim of providing some answers to the following question: Can n-3 FA intake modulate cognitive function during aging? In longitudinal observation studies we mainly observe inverse relations between fish intake or serum concentrations of DHA and cognitive impairment. Intervention studies of EPA and DHA supplementation in healthy old individuals have been negative so far (i.e., after up to 2 years of treatment, no differences in cognitive decline between treated and nontreated participants have been observed). In studies that provided EPA and DHA to adults with mild cognitive impairment or age-related cognitive impairment the data seem to be positive. However, when patients with established AD were supplemented with EPA and DHA it appears no benefit was gained. For studies on healthy individuals, a major concern is that the treatment periods may have been too short. There might also be subgroup effects because of the carriage of apolipoprotein Eε4 alleles or risk factor burden. Experimental studies appear to be consistently positive (i.e., n-3 FA supplementation in rodents over a substantial portion of their lives reduces amyloid-β deposition and hippocampal neuron loss and improves cognitive functioning). We are getting closer to providing evidence-based recommendations on fish and fish oil intake to facilitate memory function during old age. In the meantime it is advised to follow the general CDC dietary recommendations of 2-3 fish meals per week or the equivalent intake of long chain n-3 fatty acids, particularly DHA

  3. Cerebral small vessel disease: Capillary pathways to stroke and cognitive decline

    PubMed Central

    Engedal, Thorbjørn S; Moreton, Fiona; Hansen, Mikkel B; Wardlaw, Joanna M; Dalkara, Turgay; Markus, Hugh S; Muir, Keith W

    2015-01-01

    Cerebral small vessel disease (SVD) gives rise to one in five strokes worldwide and constitutes a major source of cognitive decline in the elderly. SVD is known to occur in relation to hypertension, diabetes, smoking, radiation therapy and in a range of inherited and genetic disorders, autoimmune disorders, connective tissue disorders, and infections. Until recently, changes in capillary patency and blood viscosity have received little attention in the aetiopathogenesis of SVD and the high risk of subsequent stroke and cognitive decline. Capillary flow patterns were, however, recently shown to limit the extraction efficacy of oxygen in tissue and capillary dysfunction therefore proposed as a source of stroke-like symptoms and neurodegeneration, even in the absence of physical flow-limiting vascular pathology. In this review, we examine whether capillary flow disturbances may be a shared feature of conditions that represent risk factors for SVD. We then discuss aspects of capillary dysfunction that could be prevented or alleviated and therefore might be of general benefit to patients at risk of SVD, stroke or cognitive decline. PMID:26661176

  4. Early-Stage White Matter Lesions Detected by Multispectral MRI Segmentation Predict Progressive Cognitive Decline

    PubMed Central

    Jokinen, Hanna; Gonçalves, Nicolau; Vigário, Ricardo; Lipsanen, Jari; Fazekas, Franz; Schmidt, Reinhold; Barkhof, Frederik; Madureira, Sofia; Verdelho, Ana; Inzitari, Domenico; Pantoni, Leonardo; Erkinjuntti, Timo

    2015-01-01

    White matter lesions (WML) are the main brain imaging surrogate of cerebral small-vessel disease. A new MRI tissue segmentation method, based on a discriminative clustering approach without explicit model-based added prior, detects partial WML volumes, likely representing very early-stage changes in normal-appearing brain tissue. This study investigated how the different stages of WML, from a “pre-visible” stage to fully developed lesions, predict future cognitive decline. MRI scans of 78 subjects, aged 65–84 years, from the Leukoaraiosis and Disability (LADIS) study were analyzed using a self-supervised multispectral segmentation algorithm to identify tissue types and partial WML volumes. Each lesion voxel was classified as having a small (33%), intermediate (66%), or high (100%) proportion of lesion tissue. The subjects were evaluated with detailed clinical and neuropsychological assessments at baseline and at three annual follow-up visits. We found that voxels with small partial WML predicted lower executive function compound scores at baseline, and steeper decline of executive scores in follow-up, independently of the demographics and the conventionally estimated hyperintensity volume on fluid-attenuated inversion recovery images. The intermediate and fully developed lesions were related to impairments in multiple cognitive domains including executive functions, processing speed, memory, and global cognitive function. In conclusion, early-stage partial WML, still too faint to be clearly detectable on conventional MRI, already predict executive dysfunction and progressive cognitive decline regardless of the conventionally evaluated WML load. These findings advance early recognition of small vessel disease and incipient vascular cognitive impairment. PMID:26696814

  5. Impaired Olfaction and Risk for Delirium or Cognitive Decline After Cardiac Surgery

    PubMed Central

    Brown, Charles H.; Morrissey, Candice; Ono, Masahiro; Yenokyan, Gayane; Selnes, Ola A.; Walston, Jeremy; Max, Laura; LaFlam, Andrew; Neufeld, Karin; Gottesman, Rebecca F.; Hogue, Charles W.

    2014-01-01

    Summary Statement Impaired olfaction, identified in 33% of patients undergoing cardiac surgery, was associated with the adjusted risk for postoperative delirium but not cognitive decline. Objectives The prevalence and significance of impaired olfaction is not well characterized in patients undergoing cardiac surgery. Because impaired olfaction has been associated with underlying neurologic disease, impaired olfaction may identify patients who are vulnerable to poor neurological outcomes in the perioperative period. The objective of this study was to determine the prevalence of impaired olfaction among patients presenting for cardiac surgery and the independent association of impaired olfaction with postoperative delirium and cognitive decline. Design Nested prospective cohort study Setting Academic hospital Participants 165 patients undergoing coronary artery bypass and/or valve surgery Measurements Olfaction was measured using the Brief Smell Identification Test, with impaired olfaction defined as an olfactory score < 5th percentile of normative data. Delirium was assessed using a validated chart-review method. Cognitive performance was assessed using a neuropsychological testing battery at baseline and 4–6 weeks after surgery. Results Impaired olfaction was identified in 54 of 165 patients (33%) prior to surgery. Impaired olfaction was associated with increased adjusted risk for postoperative delirium (relative risk [RR] 1.90, 95% CI 1.17–3.09; P=0.009). There was no association between impaired olfaction and change in composite cognitive score in the overall study population. Conclusion Impaired olfaction is prevalent in patients undergoing cardiac surgery and is associated with increased adjusted risk for postoperative delirium, but not cognitive decline. Impaired olfaction may identify unrecognized vulnerability for postoperative delirium among patients undergoing cardiac surgery. PMID:25597555

  6. Bilingualism Does Not Alter Cognitive Decline or Dementia Risk among Spanish-Speaking Immigrants

    PubMed Central

    Zahodne, Laura B.; Schofield, Peter W.; Farrell, Meagan T.; Stern, Yaakov; Manly, Jennifer J.

    2013-01-01

    Objective Clinic-based studies suggest that dementia is diagnosed at older ages in bilinguals compared to monolinguals. The current study sought to test this hypothesis in a large, prospective, community-based study of initially non-demented Hispanic immigrants living in a Spanish-speaking enclave of Northern Manhattan. Method Participants included 1,067 participants in the Washington/Hamilton Heights Inwood Columbia Aging Project (WHICAP) who were tested in Spanish and followed at 18–24 month intervals for up to 23 years. Spanish-English bilingualism was estimated via both self-report and an objective measure of English reading level. Multilevel models for change estimated the independent effects of bilingualism on cognitive decline in four domains: episodic memory, language, executive function, and speed. Over the course of the study, 282 participants developed dementia. Cox regression was used to estimate the independent effect of bilingualism on dementia conversion. Covariates included country of origin, gender, education, time spent in the United States, recruitment cohort, and age at enrollment. Results Independent of the covariates, bilingualism was associated with better memory and executive function at baseline. However bilingualism was not independently associated with rates of cognitive decline or dementia conversion. Results were similar whether bilingualism was measured via self-report or an objective test of reading level. Conclusions This study does not support a protective effect of bilingualism on age-related cognitive decline or the development of dementia. In this sample of Hispanic immigrants, bilingualism is related to higher initial scores on cognitive tests and higher educational attainment and may not represent a unique source of cognitive reserve. PMID:24188113

  7. Early-Stage White Matter Lesions Detected by Multispectral MRI Segmentation Predict Progressive Cognitive Decline.

    PubMed

    Jokinen, Hanna; Gonçalves, Nicolau; Vigário, Ricardo; Lipsanen, Jari; Fazekas, Franz; Schmidt, Reinhold; Barkhof, Frederik; Madureira, Sofia; Verdelho, Ana; Inzitari, Domenico; Pantoni, Leonardo; Erkinjuntti, Timo

    2015-01-01

    White matter lesions (WML) are the main brain imaging surrogate of cerebral small-vessel disease. A new MRI tissue segmentation method, based on a discriminative clustering approach without explicit model-based added prior, detects partial WML volumes, likely representing very early-stage changes in normal-appearing brain tissue. This study investigated how the different stages of WML, from a "pre-visible" stage to fully developed lesions, predict future cognitive decline. MRI scans of 78 subjects, aged 65-84 years, from the Leukoaraiosis and Disability (LADIS) study were analyzed using a self-supervised multispectral segmentation algorithm to identify tissue types and partial WML volumes. Each lesion voxel was classified as having a small (33%), intermediate (66%), or high (100%) proportion of lesion tissue. The subjects were evaluated with detailed clinical and neuropsychological assessments at baseline and at three annual follow-up visits. We found that voxels with small partial WML predicted lower executive function compound scores at baseline, and steeper decline of executive scores in follow-up, independently of the demographics and the conventionally estimated hyperintensity volume on fluid-attenuated inversion recovery images. The intermediate and fully developed lesions were related to impairments in multiple cognitive domains including executive functions, processing speed, memory, and global cognitive function. In conclusion, early-stage partial WML, still too faint to be clearly detectable on conventional MRI, already predict executive dysfunction and progressive cognitive decline regardless of the conventionally evaluated WML load. These findings advance early recognition of small vessel disease and incipient vascular cognitive impairment. PMID:26696814

  8. Faster Rate of Cognitive Decline in Essential Tremor Cases than Controls: A Prospective Study

    PubMed Central

    Louis, Elan D.; Benito-León, Julián; Vega-Quiroga, Saturio; Bermejo-Pareja, Félix

    2010-01-01

    Background Mild cognitive deficits have been reported in essential tremor (ET); however, these cognitive deficits have been assessed in cross-sectional rather than longitudinal analyses. Objective To determine whether decline in cognitive test scores occurs at a faster rate in ET cases than controls. Methods In a population-based study of older people (≥65 years) in central Spain (Neurological Disorders in Central Spain, NEDICES), non-demented ET cases and controls were followed prospectively. Participants with baseline or incident Parkinson’s disease or dementia were excluded, as were participants who developed incident ET. At baseline (1994–1995) and at follow-up (1997–1998), a 37-item version of the Mini-Mental State Examination (37-MMSE) was administered. Results 2,319 participants (72.4 ± 5.8 years) included 135 prevalent ET cases and 2,184 controls. At baseline, the mean 37-MMSE in cases was 28.8 ± 5.8 vs. 30.2 ± 4.8 in controls (p = 0.02). During the three year follow-up period, the 37-MMSE declined by 0.70 ± 3.2 points in cases vs. 0.11 ± 3.8 points in controls (p = 0.03). In analyses that adjusted for age, education and other potential confounders, the case-control difference remained robust. Discussion In this population-based, prospective study of non-demented elders, baseline cognitive test scores were lower in ET cases than controls; moreover, during the three-year follow-up period, these scores declined at a rate that was seven-times faster in ET cases. This study provides evidence that cognitive deficits in ET are not static and they appear to be progressing at a faster rate than in elders without this disease. PMID:20561042

  9. Relationship between Inflammation and Oxidative Stress and Cognitive Decline in the Institutionalized Elderly

    PubMed Central

    Baierle, Marília; Nascimento, Sabrina N.; Moro, Angela M.; Brucker, Natália; Freitas, Fernando; Gauer, Bruna; Durgante, Juliano; Bordignon, Suelen; Zibetti, Murilo; Trentini, Clarissa M.; Duarte, Marta M. M. F.; Grune, Tilman; Breusing, Nicolle; Garcia, Solange C.

    2015-01-01

    Objective. Cognitive impairment reduces quality of life and is related to vascular and neurodegenerative disorders. However, there is also a close relationship between these diseases and oxidative stress. Thus, the purpose of this study was to assess whether inflammation and oxidative damage are associated with low cognitive performance in the elderly with different housing conditions. Methods. The study groups consisted of 32 institutionalized and 25 noninstitutionalized Brazilian elderly subjects. Oxidative damage, inflammation markers, and cognitive function were evaluated. Results. The results demonstrated pronounced oxidative stress in the institutionalized elderly group, which also had a lower antioxidant status compared to noninstitutionalized subjects. High levels of proinflammatory cytokines were also observed in the institutionalized elderly. Furthermore, the raised levels of inflammatory markers were correlated with increased oxidative stress, and both were associated with low cognitive performance. However, based on multiple linear regression analysis, oxidative stress appears to be the main factor responsible for the cognitive decline. Conclusions. The findings suggest that individuals with lower antioxidant status are more vulnerable to oxidative stress, which is associated with cognitive function, leading to reduced life quality and expectancy. PMID:25874023

  10. Inside the Diabetic Brain: Role of Different Players Involved in Cognitive Decline.

    PubMed

    Gaspar, Joana M; Baptista, Filipa I; Macedo, M Paula; Ambrósio, António F

    2016-02-17

    Diabetes mellitus is the most common metabolic disease, and its prevalence is increasing. A growing body of evidence, both in animal models and epidemiological studies, has demonstrated that metabolic diseases like obesity, insulin resistance, and diabetes are associated with alterations in the central nervous system (CNS), being linked with development of cognitive and memory impairments and presenting a higher risk for dementia and Alzheimer's disease. The rising prevalence of diabetes together with its increasing earlier onset suggests that diabetes-related cognitive dysfunction will increase in the near future, causing substantial socioeconomic impact. Decreased insulin secretion or action, dysregulation of glucose homeostasis, impairment in the hypothalamic-pituitary-adrenal axis, obesity, hyperleptinemia, and inflammation may act independently or synergistically to disrupt neuronal homeostasis and cause diabetes-associated cognitive decline. However, the crosstalk between those factors and the mechanisms underlying the diabetes-related CNS complications is still elusive. During the past few years, different strategies (neuroprotective and antioxidant drugs) have emerged as promising therapies for this complication, which still remains to be preventable or treatable. This Review summarizes fundamental past and ongoing research on diabetes-associated cognitive decline, highlighting potential contributors, mechanistic mediators, and new pharmacological approaches to prevent and/or delay this complication. PMID:26667832

  11. Sleep disturbances and cognitive decline: recommendations on clinical assessment and the management.

    PubMed

    Guarnieri, Biancamaria; Cerroni, Gianluigi; Sorbi, Sandro

    2015-01-01

    In 2004, in Genoa (Italy), the Italian Dementia Research Association (SINDem) was born. The first congress of this new scientific society took place in Rome in 2006. SINDem soon recognized the importance to investigate sleep problems in cognitive decline and created a national "sleep study group "composed by neurologists and sleep specialists. In 2012, The SINDem study group, in close relationship with the Italian Association of sleep medicine (AIMS), published the study "Prevalence of sleep disturbances in mild cognitive impairment and dementing disorders: a multicenter Italian clinical cross-sectional study on 431 patients ", confirming the high prevalence of sleep disturbances in a wide Italian population of persons with cognitive decline. The study was supported by a grant from the Italian Minister of Health and was conducted with the fundamental contribution of the Italian National Research Center (CNR). In 2014, the same group published the paper "Recommendations of the Sleep Study Group of the Italian Dementia Research Association (SINDem) on clinical assessment and management of sleep disorders in individuals with mild cognitive impairment and dementia: a clinical review". The recommendations are wide and directed to professionals (neurologists but not exclusively) to try to establish uniform levels of care, promote collaborative studies into areas of uncertainty, and define the qualitative characteristics of Dementia Reference Centers about sleep disturbances. PMID:26742676

  12. Age-related cognitive decline during normal aging: the complex effect of education.

    PubMed

    Ardila, A; Ostrosky-Solis, F; Rosselli, M; Gómez, C

    2000-08-01

    The purpose of this study was to further analyze the effects of education on cognitive decline during normal aging. An 806-subject sample was taken from five different Mexican regions. Participants ranged in age from 16 to 85 years. Subjects were grouped into four educational levels: illiterate, 1-4, 5-9, and 10 or more years of education, and four age ranges: 16-30, 31-50, 51-65, and 66-85 years. A brief neuropsychological test battery (NEUROPSI), standardized and normalized in Spanish, was administered. The NEUROPSI test battery includes assessment of orientation, attention, memory, language, visuoperceptual abilities, motor skills, and executive functions. In general, test scores were strongly associated with level of educational, and differences among age groups were smaller than differences among education groups. However, there was an interaction between age and education such as that among illiterate individuals scores of participants 31-50 years old were higher than scores of participants 16-30 years old for over 50% of the tests. Different patterns of interaction among educational groups were distinguished. It was concluded that: (a) The course of life-span changes in cognition are affected by education. Among individuals with a low level of education, best neuropsychological test performance is observed at an older age than among higher-educated subjects; and (b) there is not a single relationship between age-related cognitive decline and education, but different patterns may be found, depending upon the specific cognitive domain. PMID:14590204

  13. Senescent-induced dysregulation of cAMP/CREB signaling and correlations with cognitive decline

    PubMed Central

    Hansen, Rolf T.; Zhang, Han-Ting

    2013-01-01

    It is well known that alongside senescence there is a gradual decline in cognitive ability, most noticeably certain kinds of memory such as working, episodic, spatial, and long term memory. However, until recently, not much has been known regarding the specific mechanisms responsible for the decline in cognitive ability with age. Over the past decades, researchers have become more interested in cAMP signaling, and its downstream transcription factor cAMP response element binding protein (CREB) in the context of senescence. However, there is still a lack of understanding on what ultimately causes the cognitive deficits observed with senescence. This review will focus on the changes in intracellular signaling in the brain, more specifically, alterations in cAMP/CREB signaling in aging. In addition, the downstream effects of altered cAMP signaling on cognitive ability with age will be further discussed. Overall, understanding the senescent-related changes that occur in cAMP/CREB signaling could be important for the development of novel drug targets for both healthy aging, and pathological aging such as Alzheimer's disease. PMID:23623816

  14. Daily stress magnifies the association between cognitive decline and everyday memory problems: an integration of longitudinal and diary methods.

    PubMed

    Rickenbach, Elizabeth Hahn; Almeida, David M; Seeman, Teresa E; Lachman, Margie E

    2014-12-01

    We examined whether long-term fluid cognitive decline was associated with memory problems in everyday life, and whether stress plays a moderating role. We expected that the association between cognitive decline and everyday memory problems would be magnified in the context of self-reported and physiological stress. Data are from the Boston Longitudinal Study, a subsample of the Midlife in the United States study. Participants in the current study (n = 112) completed a battery of tests measuring fluid cognitive functioning at Time 1 (T1) and 2 (T2) over 10 years. At T2, participants completed weekly diaries of self-reported daily stressors and everyday memory problems for 12 consecutive weeks. Also at T2, participants provided 4 saliva samples over the course of 1 day to assess physiological stress using diurnal cortisol profiles [cortisol awakening response (CAR) and diurnal cortisol slope (DCS)]. Self-reported daily stressors and a less healthy DCS were associated with more everyday memory problems, and participants with greater cognitive decline reported more memory problems compared to those with less or no decline. Self-reported daily stressors and CAR moderated the relationship of cognitive decline and memory problems. As expected, more cognitive decline was associated with greater increases in memory problems on weeks when individuals reported more daily stressors and for individuals with a less healthy CAR. The current findings can inform interventions aimed to identify factors, such as daily stress, that contribute to daily functioning in the context of cognitive decline.

  15. Prospective memory on a novel clinical task in older adults with mild cognitive impairment and subjective cognitive decline

    PubMed Central

    Rabin, Laura A.; Chi, Susan Y.; Wang, Cuiling; Fogel, Joshua; Kann, Sarah J.; Aronov, Avner

    2014-01-01

    Despite the relevance of prospective memory to everyday functioning and the ability to live independently, prospective memory tasks are rarely incorporated into clinical evaluations of older adults. We investigated the validity and clinical utility of a recently developed measure, the Royal Prince Alfred Prospective Memory Test (RPA-ProMem), in a demographically diverse, non-demented, community-dwelling sample of 257 older adults (mean age = 80.78 years, 67.7% female) with amnestic mild cognitive impairment (aMCI, n = 18), non-amestic mild cognitive impairment (naMCI, n = 38), subjective cognitive decline (SCD, n = 83) despite intact performance on traditional episodic memory tests, and healthy controls (HC, n = 118). Those with aMCI and naMCI performed significantly worse than controls on the RPA-ProMem and its subtasks (time-based, event-based, short-term, long-term). Also, those with SCD scored significantly lower than controls on long-term, more naturalistic subtasks. Additional results supported the validity and inter-rater reliability of the RPA-ProMem and demonstrated a relation between test scores and informant reports of real-world functioning. The RPA-ProMem may help detect subtle cognitive changes manifested by individuals in the earliest stages of dementia, which may be difficult to capture with traditional episodic memory tests. Also, assessment of prospective memory can help guide the development of cognitive interventions for older adults at risk for dementia. PMID:24875614

  16. Empirically Defining Trajectories of Late-Life Cognitive and Functional Decline

    PubMed Central

    Hochstetler, Helen; Trzepacz, Paula T.; Wang, Shufang; Yu, Peng; Case, Michael; Henley, David B.; Degenhardt, Elisabeth; Leoutsakos, Jeannie-Marie; Lyketsos, Constantine G.

    2015-01-01

    Background: Alzheimer’s disease (AD) is associated with variable cognitive and functional decline, and it is difficult to predict who will develop the disease and how they will progress. Objective: This exploratory study aimed to define latent classes from participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database who had similar growth patterns of both cognitive and functional change using Growth Mixture Modeling (GMM), identify characteristics associated with those trajectories, and develop a decision tree using clinical predictors to determine which trajectory, as determined by GMM, individuals will most likely follow. Methods: We used ADNI early mild cognitive impairment (EMCI), late MCI (LMCI), AD dementia, and healthy control (HC) participants with known amyloid-β status and follow-up assessments on the Alzheimer’s Disease Assessment Scale - Cognitive Subscale or the Functional Activities Questionnaire (FAQ) up to 24 months postbaseline. GMM defined trajectories. Classification and Regression Tree (CART) used certain baseline variables to predict likely trajectory path. Results: GMM identified three trajectory classes (C): C1 (n = 162, 13.6%) highest baseline impairment and steepest pattern of cognitive/functional decline; C3 (n = 819, 68.7%) lowest baseline impairment and minimal change on both; C2 (n = 211, 17.7%) intermediate pattern, worsening on both, but less steep than C1. C3 had fewer amyloid- or apolipoprotein-E ɛ4 (APOE4) positive and more healthy controls (HC) or EMCI cases. CART analysis identified two decision nodes using the FAQ to predict likely class with 82.3% estimated accuracy. Conclusions: Cognitive/functional change followed three trajectories with greater baseline impairment and amyloid and APOE4 positivity associated with greater progression. FAQ may predict trajectory class. PMID:26639960

  17. Chronical sleep interruption-induced cognitive decline assessed by a metabolomics method.

    PubMed

    Feng, Li; Wu, Hong-wei; Song, Guang-qing; Lu, Cong; Li, Ying-hui; Qu, Li-na; Chen, Shan-guang; Liu, Xin-min; Chang, Qi

    2016-04-01

    Good sleep is necessary for optimal health, especially for mental health. Insomnia, sleep deprivation will make your ability to learn and memory impaired. Nevertheless, the underlying pathophysiological mechanism of sleep disorders-induced cognitive decline is still largely unknown. In this study, the sleep deprivation of animal model was induced by chronical sleep interruption (CSI), the behavioral tests, biochemical index determinations, and a liquid chromatography-mass spectrometry (LC-MS) based serum metabolic profiling analysis were performed to explore the effects of CSI on cognitive function and the underlying mechanisms. After 14-days CSI, the cognitive function of the mice was evaluated by new objects preference (NOP) task and temporal order judgment (TOJ) task. Serum corticosterone (CORT), and brain Malondialdehyde (MDA), Superoxide Dismutase (SOD), and Catalase (CAT) levels were determined by ELISA kits. Data were analyzed by Principal Component Analysis (PCA), Partial Least Squares project to latent structures-Discriminant Analysis (PLS-DA), and Student's t-test. We found that the cognitive function of the mice was significantly affected by CSI. Besides, levels of CORT and MDA were higher, and SOD and CAT were lower in CSI mice than those of control. Obvious body weight loss of CSI mice was also observed. Thirteen potential serum biomarkers including choline, valine, uric acid, allantoic acid, carnitines, and retinoids were identified. Affected metabolic pathways involve metabolism of purine, retinoid, lipids, and amino acid. These results showed that CSI can damage the cognitive performance notably. The cognitive decline may ascribe to excessive oxidative stress and a series of disturbed metabolic pathways. PMID:26747207

  18. Longitudinal Attentional Engagement Rescues Mice from Age-Related Cognitive Declines and Cognitive Inflexibility

    ERIC Educational Resources Information Center

    Matzel, Louis D.; Light, Kenneth R.; Wass, Christopher; Colas-Zelin, Danielle; Denman-Brice, Alexander; Waddel, Adam C.; Kolata, Stefan

    2011-01-01

    Learning, attentional, and perseverative deficits are characteristic of cognitive aging. In this study, genetically diverse CD-1 mice underwent longitudinal training in a task asserted to tax working memory capacity and its dependence on selective attention. Beginning at 3 mo of age, animals were trained for 12 d to perform in a dual radial-arm…

  19. Effects of a computer-based cognitive exercise program on age-related cognitive decline.

    PubMed

    Bozoki, Andrea; Radovanovic, Mirjana; Winn, Brian; Heeter, Carrie; Anthony, James C

    2013-01-01

    We developed a 'senior friendly' suite of online 'games for learning' with interactive calibration for increasing difficulty, and evaluated the feasibility of a randomized clinical trial to test the hypothesis that seniors aged 60-80 can improve key aspects of cognitive ability with the aid of such games. Sixty community-dwelling senior volunteers were randomized to either an online game suite designed to train multiple cognitive abilities, or to a control arm with online activities that simulated the look and feel of the games but with low level interactivity and no calibration of difficulty. Study assessment included measures of recruitment, retention and play-time. Cognitive change was measured with a computerized assessment battery administered just before and within two weeks after completion of the six-week intervention. Impediments to feasibility included: limited access to in-home high-speed internet, large variations in the amount of time devoted to game play, and a reluctance to pursue more challenging levels. Overall analysis was negative for assessed performance (transference effects) even though subjects improved on the games themselves. Post hoc analyses suggest that some types of games may have more value than others, but these effects would need to be replicated in a study designed for that purpose. We conclude that a six-week, moderate-intensity computer game-based cognitive intervention can be implemented with high-functioning seniors, but the effect size is relatively small. Our findings are consistent with Owen et al. (2010), but there are open questions about whether more structured, longer duration or more intensive 'games for learning' interventions might yield more substantial cognitive improvement in seniors.

  20. Cognitive decline in short and long sleepers: A prospective population-based study (NEDICES)

    PubMed Central

    Benito-León, Julián; Louis, Elan D.; Bermejo-Pareja, Félix

    2013-01-01

    Background It is not clear whether cognitive decline progresses more quickly in long sleepers than in short sleepers or than in participants with usual sleep duration. We assessed cognitive decline as a function of self-reported sleep duration in a prospective population-based cohort (NEDICES). Methods Participants were evaluated at baseline and 3 years later. Baseline demographic variables were recorded and participants indicated their daily sleep usual duration as the sum of nighttime sleep and daytime napping. The average daily total usual sleep duration was grouped into three categories: ≤5 hours (short sleepers), 6 to 8 hours (reference category), and ≥9 hours (long sleepers). At baseline and at follow-up, a 37-item version of the Mini-Mental State Examination (37-MMSE) was administered. Results The final sample, 2,715 participants (72.9±6.1 years), comprised 298 (11%) short sleepers, 1,086 (40%) long sleepers, and 1,331 (49%) in the reference group (6 to 8 hours). During the three year follow-up period, the 37-MMSE declined by 0.5±4.0 points in short sleepers, 0.6±4.3 points in long sleepers, and 0.2±3.8 points in the reference group (p=0.08). The difference between short sleepers and the reference group was not significant (p=0.142); however, the difference between long sleepers and the reference group was significant (p=0.040). In analyses adjusted for baseline age and other potential confounders, this difference remained robust. Conclusions In this study, cognitive test scores among long sleepers declined more rapidly than observed in a reference group. Additional studies are needed to confirm these results. PMID:24094933

  1. A randomized placebo-controlled trial of Ginkgo biloba for the prevention of cognitive decline

    PubMed Central

    Zitzelberger, T.; Oken, B.S.; Howieson, D.; Kaye, J.

    2009-01-01

    Objective To assess the feasibility, safety, and efficacy of Ginkgo biloba extract (GBE) on delaying the progression to cognitive impairment in normal elderly aged 85 and older. Methods Randomized, placebo-controlled, double-blind, 42-month pilot study with 118 cognitively intact subjects randomized to standardized GBE or placebo. Kaplan-Meier estimation, Cox proportional hazard, and random-effects models were used to compare the risk of progression from Clinical Dementia Rating (CDR) = 0 to CDR = 0.5 and decline in episodic memory function between GBE and placebo groups. Results In the intention-to-treat analysis, there was no reduced risk of progression to CDR = 0.5 (log-rank test, p = 0.06) among the GBE group. There was no less of a decline in memory function among the GBE group (p = 0.05). In the secondary analysis, where we controlled the medication adherence level, the GBE group had a lower risk of progression from CDR = 0 to CDR = 0.5 (HR = 0.33, p = 0.02), and a smaller decline in memory scores (p = 0.04). There were more ischemic strokes and TIAs in the GBE group (p = 0.01). Conclusions In unadjusted analyses, Ginkgo biloba extract (GBE) neither altered the risk of progression from normal to Clinical Dementia Rating (CDR) = 0.5, nor protected against a decline in memory function. Secondary analysis taking into account medication adherence showed a protective effect of GBE on the progression to CDR = 0.5 and memory decline. Results of larger prevention trials taking into account medication adherence may clarify the effectiveness of GBE. More stroke and TIA cases observed among the GBE group requires further study to confirm. PMID:18305231

  2. Superficial white matter as a novel substrate of age-related cognitive decline.

    PubMed

    Nazeri, Arash; Chakravarty, M Mallar; Rajji, Tarek K; Felsky, Daniel; Rotenberg, David J; Mason, Mikko; Xu, Li N; Lobaugh, Nancy J; Mulsant, Benoit H; Voineskos, Aristotle N

    2015-06-01

    Studies of diffusion tensor imaging have focused mainly on the role of deep white matter tract microstructural abnormalities associated with aging and age-related cognitive decline. However, the potential role of superficial white matter (SWM) in aging and, by extension, cognitive-aging, is less clear. Healthy individuals (n = 141; F/M: 66/75 years) across the adult lifespan (18-86 years) underwent diffusion tensor imaging and a battery of cognitive testing. SWM was assessed via a combination of probabilistic tractography and tract-based spatial statistics (TBSS). A widespread inverse relationship of fractional anisotropy (FA) values in SWM with age was observed. SWM-FA adjacent to the precentral gyri was associated with fine-motor-speed, whereas performance in visuomotor-attention/processing speed correlated with SWM-FA in all 4 lobes of the left-hemisphere and in right parieto-occipital SWM-FA (family-wise error corrected p < 0.05). Independent of deep white matter-FA, right frontal and right occipital SWM-FA-mediated age effects on motor-speed and visuomotor-attention/processing speed, respectively. Altogether, our results indicate that SWM-FA contributes uniquely to age-related cognitive performance, and should be considered as a novel biomarker of cognitive-aging. PMID:25834938

  3. Computerized assessment of communication for cognitive stimulation for people with cognitive decline using spectral-distortion measures and phylogenetic inference.

    PubMed

    Pham, Tuan D; Oyama-Higa, Mayumi; Truong, Cong-Thang; Okamoto, Kazushi; Futaba, Terufumi; Kanemoto, Shigeru; Sugiyama, Masahide; Lampe, Lisa

    2015-01-01

    Therapeutic communication and interpersonal relationships in care homes can help people to improve their mental wellbeing. Assessment of the efficacy of these dynamic and complex processes are necessary for psychosocial planning and management. This paper presents a pilot application of photoplethysmography in synchronized physiological measurements of communications between the care-giver and people with dementia. Signal-based evaluations of the therapy can be carried out using the measures of spectral distortion and the inference of phylogenetic trees. The proposed computational models can be of assistance and cost-effectiveness in caring for and monitoring people with cognitive decline. PMID:25803586

  4. Macronutrients, aluminium from drinking water and foods, and other metals in cognitive decline and dementia.

    PubMed

    Solfrizzi, Vincenzo; Colacicco, Anna Maria; D'Introno, Alessia; Capurso, Cristiano; Parigi, Angelo Del; Capurso, Sabrina A; Torres, Francesco; Capurso, Antonio; Panza, Francesco

    2006-11-01

    A possible role of the macronutrients and the basic elements of carbohydrates (glucose administration or depletion), proteins (amino acids such as tryptophan and tyrosine), and fat (unsaturated fatty acids) was recently proposed for age-related changes of cognitive function, and the cognitive decline of degenerative (AD) or vascular origin. The availability and utilization of glucose has been implicated in cognitive function not only as a result of nutritional and systemic metabolic conditions, but also, although speculatively, as a crucial phase of the mechanism of action of molecules used as cognitive-enhancers. Furthermore, many lines of evidence have focused on the importance of oxidative stress mechanisms and free radical damage in AD pathogenesis. In addition, epidemiological studies have recently reported an association between alcohol and the incidence of AD and predementia syndromes. Foods with large amounts of aluminium-containing additives or aluminium from drinking water may affect the risk of developing AD, aluminium more likely acting as a cofactor somewhere in the cascade of events leading to the demented brain. A role for other metals in dementia have been speculated, given the encouraging results reported from studies on peripheral zinc concentrations, zinc supplementation, serum copper, either bound with ceruloplasmin or not, and iron metabolism in AD. Nonetheless, more data are needed to support a possible role of these metals in dementing diseases. Healthy diets, antioxidant supplements, and the prevention of nutritional deficiencies or exposure to foods and water with high content of metals could be considered the first line of defence against the development and progression of cognitive decline.

  5. Macronutrients, aluminium from drinking water and foods, and other metals in cognitive decline and dementia.

    PubMed

    Solfrizzi, Vincenzo; Colacicco, Anna Maria; D'Introno, Alessia; Capurso, Cristiano; Parigi, Angelo Del; Capurso, Sabrina A; Torres, Francesco; Capurso, Antonio; Panza, Francesco

    2006-11-01

    A possible role of the macronutrients and the basic elements of carbohydrates (glucose administration or depletion), proteins (amino acids such as tryptophan and tyrosine), and fat (unsaturated fatty acids) was recently proposed for age-related changes of cognitive function, and the cognitive decline of degenerative (AD) or vascular origin. The availability and utilization of glucose has been implicated in cognitive function not only as a result of nutritional and systemic metabolic conditions, but also, although speculatively, as a crucial phase of the mechanism of action of molecules used as cognitive-enhancers. Furthermore, many lines of evidence have focused on the importance of oxidative stress mechanisms and free radical damage in AD pathogenesis. In addition, epidemiological studies have recently reported an association between alcohol and the incidence of AD and predementia syndromes. Foods with large amounts of aluminium-containing additives or aluminium from drinking water may affect the risk of developing AD, aluminium more likely acting as a cofactor somewhere in the cascade of events leading to the demented brain. A role for other metals in dementia have been speculated, given the encouraging results reported from studies on peripheral zinc concentrations, zinc supplementation, serum copper, either bound with ceruloplasmin or not, and iron metabolism in AD. Nonetheless, more data are needed to support a possible role of these metals in dementing diseases. Healthy diets, antioxidant supplements, and the prevention of nutritional deficiencies or exposure to foods and water with high content of metals could be considered the first line of defence against the development and progression of cognitive decline. PMID:17119295

  6. Relation between acute and long-term cognitive decline after surgery: Influence of metabolic syndrome☆

    PubMed Central

    Gambús, P.L; Trocóniz, I.F.; Feng, X.; Gimenez-Milá, M.; Mellado, R.; Degos, V.; Vacas, S.; Maze, M.

    2015-01-01

    Introduction The relationship between persistent postoperative cognitive decline and the more common acute variety remains unknown; using data acquired in preclinical studies of postoperative cognitive decline we attempted to characterize this relationship. Methods Low capacity runner (LCR) rats, which have all the features of the metabolic syndrome, were compared postoperatively with high capacity runner (HCR) rats for memory, assessed by trace fear conditioning (TFC) on the 7th postoperative day, and learning and memory (probe trial [PT]) assessed by the Morris water-maze (MWM) at three months postoperatively. Rate of learning (AL) data from the MWM test, were estimated by non-linear mixed effects modeling. The individual rat's TFC result at postoperative day (POD) 7 was correlated with its AL and PT from the MWM data sets at postoperative day POD 90. Results A single exponential decay model best described AL in the MWM with LCR and surgery (LCR–SURG) being the only significant covariates; first order AL rate constant was 0.07 s−1 in LCR–SURG and 0.16 s−1 in the remaining groups (p<0.05). TFC was significantly correlated with both AL (R = 0.74; p < 0.0001) and PT (R = 0.49; p < 0.01). Conclusion Severity of memory decline at 1 week after surgery presaged long-lasting deteriorations in learning and memory. PMID:26164200

  7. Does a physically active lifestyle attenuate decline in all cognitive functions in old age?

    PubMed

    Ballesteros, Soledad; Mayas, Julia; Reales, Jose Manuel

    2013-07-01

    In this study, the performance of a group of 20 physically active older adults was compared with that of a group of 20 sedentary healthy older adults while performing a series of cognitive tasks. These tasks were designed to assess processes that deteriorate most with age, namely executive control (assessed with the Wisconsin Card Sorting Task) and processing speed (simple and choice reaction time tasks). A repetition priming task that does not decline with age, involving attended and unattended picture outlines at encoding, was also included as a control task. The results show that a physically active lifestyle has a positive influence on executive control, processing speed, and controlled processing. As expected, a physically active lifestyle did not enhance repetition priming for attended stimuli, nor did it produce priming for unattended stimuli at encoding. Both groups exhibited robust priming for attended stimuli and no priming for unattended ones. Executive control functions are of vital importance for independent living in old age. These results have practical implications for enhancing the cognitive processes that decline most in old age. Promoting a physically active lifestyle throughout adulthood could significantly reduce the decline of effortful executive control functions in old age.

  8. Biochemical and neuroimaging studies in subjective cognitive decline: progress and perspectives.

    PubMed

    Sun, Yu; Yang, Fu-Chi; Lin, Ching-Po; Han, Ying

    2015-10-01

    Neurodegeneration due to Alzheimer's disease (AD) can progress over decades before dementia becomes apparent. Indeed, patients with mild cognitive impairment (MCI) already demonstrate significant lesion loads. In most cases, MCI is preceded by subjective cognitive decline (SCD), which is applied to individuals who have self-reported memory-related complaints and has been associated with a higher risk of future cognitive decline and conversion to dementia. Based on the schema of a well-received model of biomarker dynamics in AD pathogenesis, it has been postulated that SCD symptoms may result from compensatory changes in response to β-amyloid accumulation and neurodegeneration. Although SCD is considered a prodromal stage of MCI, it is also a common manifestation in old age, independent of AD, and the predictive value of SCD for AD pathology remains controversial. Here, we provide a review focused on the contributions of cross-sectional and longitudinal analogical studies of biomarkers and neuroimaging evidence in disentangling under what conditions SCD may be attributable to AD pathology. In conclusion, there is promising evidence indicating that clinicians should be able to differentiate pre-AD SCD based on the presence of pathophysiological biomarkers in cerebrospinal fluid (CSF) and neuroimaging. However, this neuroimaging approach is still at an immature stage without an established rubric of standards. A substantial amount of work remains in terms of replicating recent findings and validating the clinical utility of identifying SCD.

  9. Faster cognitive decline in the years prior to MR imaging is associated with smaller hippocampal volumes in cognitively healthy older persons

    PubMed Central

    Fleischman, Debra A.; Yu, Lei; Arfanakis, Konstantinos; Han, S. Duke; Barnes, Lisa L.; Arvanitakis, Zoe; Boyle, Patricia A.; Bennett, David A.

    2013-01-01

    Early identification of persons at risk for cognitive decline in aging is critical to optimizing treatment to delay or avoid a clinical diagnosis of mild cognitive impairment (MCI) or dementia due to Alzheimer's disease (AD). To accomplish early identification, it is essential that trajectories of cognitive change be characterized and associations with established biomarkers of MCI and AD be examined during the phase in which older persons are considered cognitively healthy. Here we examined the association of rate of cognitive decline in the years leading up to structural magnetic resonance imaging with an established biomarker, hippocampal volume. The sample comprised 211 participants of the Rush Memory and Aging Project who had an average of 5.5 years of cognitive data prior to structural scanning. Results showed that there was significant variability in the trajectories of cognitive change prior to imaging and that faster cognitive decline was associated with smaller hippocampal volumes. Domain-specific analyses suggested that this association was primarily driven by decline in working memory. The results emphasize the importance of closely examining cognitive change and its association with brain structure during the years in which older persons are considered cognitively healthy. PMID:23760360

  10. Compensatory mechanisms in higher-educated subjects with Alzheimer's disease: a study of 20 years of cognitive decline.

    PubMed

    Amieva, Hélène; Mokri, Hind; Le Goff, Mélanie; Meillon, Céline; Jacqmin-Gadda, Hélène; Foubert-Samier, Alexandra; Orgogozo, Jean-Marc; Stern, Yaakov; Dartigues, Jean-François

    2014-04-01

    A better knowledge of long-term trajectories of cognitive decline is a central feature of the study of the process leading to Alzheimer's dementia. Several factors may mitigate such decline, among which is education, a major risk factor for Alzheimer's disease. The aim of our work was to compare the pattern and duration of clinical trajectories before Alzheimer's dementia in individuals with low and high education within the PAQUID cohort involving 20 years of follow-up. The sample comprises 442 participants with incident Alzheimer's disease (27.2% were male)--171 with low education (mean age=86.2 years; standard deviation=5.3 years) and 271 with higher education (mean age=86.5; standard deviation=5.4)--and 442 control subjects matched according to age, sex and education. At each visit and up to the 20-year follow-up visit, several cognitive and clinical measures were collected and incident cases of Alzheimer's disease clinically diagnosed. The evolution of clinical measures in pre-demented subjects and matched controls was analysed with a semi-parametric extension of the mixed effects linear model. The results show that the first signs of cognitive decline occurred 15 to 16 years before achieving dementia threshold in higher-educated subjects whereas signs occurred at 7 years before dementia in low-educated subjects. There seemed to be two successive periods of decline in higher-educated subjects. Decline started ∼15 to 16 years before dementia with subtle impairment restricted to some cognitive tests and with no impact during the first 7 to 8 years on global cognition, cognitive complaints, or activities of daily living scales. Then, ∼7 years before dementia, global cognitive abilities begin to deteriorate, along with difficulties dealing with complex activities of daily living, the increase in self-perceived difficulties and depressive symptoms. By contrast, lower-educated subjects presented a single period of decline lasting ∼7 years, characterized by

  11. The Association of Age With Rate of Cognitive Decline in Elderly Individuals Residing in Supporting Care Facilities

    PubMed Central

    Ravona-Springer, Ramit; Luo, Xiaodong; Schmeidler, James; Wysocki, Michael; Lesser, Gerson T.; Rapp, Michael A.; Dahlman, Karen; Grossman, Hillel T.; Haroutunian, Vahram; Beeri, Michal Schnaider

    2012-01-01

    Objectives This study examines the effect of age on rate of cognitive decline in different stages of dementia, of nursing home and assisted-living residents. Methods In this longitudinal study, the Mini Mental State Examination (MMSE) was used to measure rate of cognitive decline in subjects who were nondemented [Clinical Dementia Rating (CDR)=0; n=353], questionably demented (CDR=0.5; n=121), or frankly demented (CDR≥1; n=213) at baseline. Results A generalized estimating equation was used to model the MMSE scores over time (mean follow-up 2.9±2.0 y). The generalized estimating equation model had the MMSE scores at successive follow-up time points as dependent variables and had linear and quadratic age, follow-up time from baseline, CDR at baseline, and all the interactions among them as independent variables, controlling for MMSE at baseline, sex, race, and education. The mean age of the entire sample was 85.2±7.4 years at baseline. There were no significant interactions of linear age effects with rate of cognitive decline. The analysis of interaction of quadratic age with rate of cognitive decline showed complex relationships: in the nondemented group, there was no substantial quadratic association of age with the rate of cognitive decline (P=0.13); in the questionable demented group, the oldest subjects declined relatively faster (P=0.02); and in the demented group, the youngest and oldest subjects tended to decline relatively less than subjects in the intermediate ages (P=0.07). Conclusions This study adds an additional aspect to the complexity of the association between age and rate of cognitive decline, showing that the direction and amplitude of this effect differs according to the stage along the course of cognitive decline. PMID:21572311

  12. Effects of vascular risk factors and APOE ε4 on white matter integrity and cognitive decline

    PubMed Central

    Fratiglioni, Laura; Laukka, Erika J.; Lövdén, Martin; Kalpouzos, Grégoria; Keller, Lina; Graff, Caroline; Salami, Alireza; Bäckman, Lars

    2015-01-01

    Objective: To investigate the effects of vascular risk factors and APOE status on white matter microstructure, and subsequent cognitive decline among older people. Methods: This study included 241 participants (age 60 years and older) from the population-based Swedish National Study on Aging and Care in Kungsholmen in central Stockholm, Sweden, who were free of dementia and stroke at baseline (2001–2004). We collected data through interviews, clinical examinations, and laboratory tests. We measured fractional anisotropy (FA) and mean diffusivity (MD) on diffusion tensor imaging, and estimated volume of white matter hyperintensities using automatic segmentation. We assessed global cognitive function with the Mini-Mental State Examination at baseline and at 3- and/or 6-year follow-up. We analyzed the data using multivariate linear regression and linear mixed models. Results: Heavy alcohol consumption, hypertension, and diabetes were significantly associated with lower FA or higher MD (p < 0.05). When aggregating heavy alcohol consumption, hypertension, and diabetes together with current smoking, having an increasing number of these 4 factors concurrently was associated with decreasing FA and increasing MD (ptrend < 0.01), independent of white matter hyperintensities. Vascular risk factors and APOE ε4 allele interacted to negatively affect white matter microstructure; having multiple (≥2) vascular factors was particularly detrimental to white matter integrity among APOE ε4 carriers. Lower tertile of FA and upper tertile of MD were significantly associated with faster Mini-Mental State Examination decline. Conclusions: Vascular risk factors are associated with reduced white matter integrity among older adults, which subsequently predicted faster cognitive decline. The detrimental effects of vascular risk factors on white matter microstructure were exacerbated among APOE ε4 carriers. PMID:25672924

  13. Autoimmune encephalitis: A potentially reversible cause of status epilepticus, epilepsy, and cognitive decline

    PubMed Central

    Pandit, Awadh Kishor; Ihtisham, Kavish; Garg, Ajay; Gulati, Sheffali; Padma, Madakasira Vasantha; Tripathi, Manjari

    2013-01-01

    Objectives: To review clinical characteristics and response to immunomodulation therapy in autoimmune encephalitis presenting with status epilepticus (SE), epilepsy, and cognitive decline. Design: Observational, prospective case series. Setting: All India Institute of Medical Sciences, New Delhi, India. Materials and Methods: Prospective analysis of 15 patients, who presented with SE, epilepsy, cognitive decline, and other neurological symptoms with positive autoantibodies. Demographic and clinical characteristics were recorded. Brain magnetic resonance imaging (MRI), cerebrospinal-fluid analysis (CSF), and tumor screening were done periodically. Treatment received and responses (categorized as per patients and treating doctor's information) were noted. Results: There were 15 (males = 10) patients of autoimmune encephalitis. The mean age of presentation was 24 years (range: 2-64 years). The most common onset was subacute (64%) and four (29%) patients presented as SE. Predominant clinical presentations were seizures (100%) almost of every semiology. CSF was done in 10 patients; it was normal in 60%. Brain MRI was done in all patients, in six (40%) it was normal, six (40%) showed T2W and FLAIR hyperintensities in bilateral limbic areas. Antibodies found were the N-methyl-D-aspartate receptor antibody in seven (50%), voltage-gated potassium channel antibody in five (36%), two of antiglutamic acid decarboxylase, and one patient with double stranded DNA (dsDNA) antibodies. None showed evidence of malignancy. Patients received immunotherapy, either steroids, intravenous immunoglobulin, or both. Follow-up showed significant improvement in majority of cases, neither further seizures nor relapse in nine (67%) cases. One death occurred, due to delayed presentation. Conclusions: Uncommon but potentially reversible causes of SE, epilepsy, and cognitive decline may be immune-related and high index of suspicion will prevent missing the diagnosis. PMID:24339583

  14. The relationship between long-term sunlight radiation and cognitive decline in the REGARDS cohort study.

    PubMed

    Kent, Shia T; Kabagambe, Edmond K; Wadley, Virginia G; Howard, Virginia J; Crosson, William L; Al-Hamdan, Mohammad Z; Judd, Suzanne E; Peace, Fredrick; McClure, Leslie A

    2014-04-01

    Sunlight may be related to cognitive function through vitamin D metabolism or circadian rhythm regulation. The analysis presented here sought to test whether ground and satellite measures of solar radiation are associated with cognitive decline. The study used a 15-year residential history merged with satellite and ground monitor data to determine sunlight (solar radiation) and air temperature exposure for a cohort of 19,896 cognitively intact black and white participants aged 45+ from the 48 contiguous United States. Exposures of 15, 10, 5, 2, and 1-year were used to predict cognitive status at the most recent assessment in logistic regression models; 1-year insolation and maximum temperatures were chosen as exposure measures. Solar radiation interacted with temperature, age, and gender in its relationships with incident cognitive impairment. After adjustment for covariates, the odds ratio (OR) of cognitive decline for solar radiation exposure below the median vs above the median in the 3rd tertile of maximum temperatures was 1.88 (95 % CI: 1.24, 2.85), that in the 2nd tertile was 1.33 (95 % CI: 1.09, 1.62), and that in the 1st tertile was 1.22 (95 % CI: 0.92, 1.60). We also found that participants under 60 years old had an OR = 1.63 (95 % CI: 1.20, 2.22), those 60-80 years old had an OR = 1.18 (95 % CI: 1.02, 1.36), and those over 80 years old had an OR = 1.05 (0.80, 1.37). Lastly, we found that males had an OR = 1.43 (95 % CI: 1.22, 1.69), and females had an OR = 1.02 (0.87, 1.20). We found that lower levels of solar radiation were associated with increased odds of incident cognitive impairment.

  15. Cognitive decline impairs financial and health literacy among community-based older persons without dementia

    PubMed Central

    Boyle, Patricia A.; Yu, Lei; Wilson, Robert S.; Segawa, Eisuke; Buchman, Aron S.; Bennett, David A.

    2013-01-01

    Literacy is an important determinant of health and well-being across the lifespan but is critical in aging, when many influential health and financial decisions are made. Prior studies suggest that older persons exhibit lower literacy than younger persons, particularly in the domains of financial and health literacy, but the reasons why remain unknown. The objectives of this study were to: a) examine pathways linking diverse resources (i.e., education, word knowledge, cognitive function, and decision making style) to health and financial literacy among older persons and determine the extent to which the relation of age with literacy represents a direct effect versus an indirect effect due to decrements in specific cognitive functions (i.e., executive functions and episodic memory), and b) test the hypothesis that declines in executive function and episodic memory are associated with lower literacy among older persons without dementia. 645 community-based older persons without dementia underwent detailed assessments of diverse resources, including education, word knowledge, cognitive function (i.e., executive function, episodic memory) and decision making style (i.e., risk aversion), and completed a measure of literacy that included items similar to those assessed in the Health and Retirement Study, such as numeracy, financial concepts such as compound inflation and knowledge of stocks and bonds, and important health concepts such as understanding of drug risk and Medicare Part D. Path analysis revealed a strong effect of age on literacy, with about half of the effect of age on literacy due to decrements in executive functions and episodic memory. In addition, executive function had an indirect effect on literacy via decision making style (i.e., risk aversion), and education and word knowledge had independent effects on literacy. Finally, among (n=447) persons with repeated cognitive assessments available for up to 14 years, regression analysis supported the

  16. Exploring Experiences and Perceptions of Aging and Cognitive Decline Across Diverse Racial and Ethnic Groups

    PubMed Central

    Roberts, Lisa R.; Schuh, Holly; Sherzai, Dean; Belliard, Juan Carlos; Montgomery, Susanne B.

    2015-01-01

    Objective To explore how older adults from three prominent ethnoracial groups experience cognitive decline and aging. Method Semistructured key informant interviews (KIIs) and focus groups (FGs) were conducted with caregivers, experts, and older adults. Results (N = 75). Fifteen KIIs regarding cognitive aging issues were conducted among health care professionals and community-based agencies serving older adults. Eight FGs included family caregivers and physicians, and six FGs with Latino, African American, and White older adult community members. Major themes included (a) personal expectations about aging, (b) societal value of older adults, (c) model of care preferred, and (d) community concerns. An overarching theme was a sense of loss associated with aging; however, how this loss was experienced and dealt with varied. Discussion Distinct patterns of concerns and views are important to understand for the development of programs aimed at meeting the needs of diverse older adult community members to improve health outcomes. PMID:26925436

  17. Diabetes and cognitive decline in a French cohort of patients infected with HIV-1

    PubMed Central

    Richert, Laura; Thiébaut, Rodolphe; Bruyand, Mathias; Amieva, Hélène; Dauchy, Frédéric-Antoine; Dartigues, Jean-François; Neau, Didier; Morlat, Philippe; Dehail, Patrick; Dabis, François; Bonnet, Fabrice; Chêne, Geneviève

    2015-01-01

    Objective: We investigated the relationship of diabetes and prediabetes with cognitive performances, assessed through raw test and z scores and according to neurocognitive impairment (NCI) classification in a cohort of individuals infected with HIV. Methods: The ANRS CO3 Aquitaine cohort is a prospective hospital-based cohort of HIV-1–infected patients under routine clinical management in 6 public hospitals in southwestern France. Between 2007 and 2009, an ancillary study consisted of a neuropsychological battery of 10 tests at baseline and 2-year follow-up. The severity of NCI (normal, asymptomatic, mild, HIV dementia) was assessed according to international guidelines. Results: At baseline (400 patients, 33 with prediabetes, 39 with diabetes), in cross-sectional multivariable analyses, patients with diabetes performed significantly worse on 9 neuropsychological tests that assessed memory, executive functions, attention, psychomotor speed, language, and manual dexterity. Participants with prediabetes had worse performances compared with those who had normal glycemia in 5 tests. The longitudinal analysis of the association between glycemia status at baseline and change in cognitive performances over 2-year follow-up (n = 283) suggested that patients with diabetes also showed a slightly higher decline on 5 of the 10 tests, those involving executive functions and memory functioning. Glycemia status at baseline was not significantly associated with NCI severity in cross-sectional (p = 0.44) and longitudinal (p = 0.64) analyses. Conclusions: In this hospital-based cohort of people living with HIV, diabetes, but not the other cardiovascular risk factors, is associated with worse cognitive performances in several cognitive domains and with larger decline in fewer domains over the short term. PMID:26156515

  18. Monitoring the Early Signs of Cognitive Decline in Elderly by Computer Games: An MRI Study

    PubMed Central

    Sirály, Enikő; Szabó, Ádám; Szita, Bernadett; Kovács, Vivienne; Fodor, Zsuzsanna; Marosi, Csilla; Salacz, Pál; Hidasi, Zoltán; Maros, Viktor; Hanák, Péter; Csibri, Éva; Csukly, Gábor

    2015-01-01

    Background It is anticipated that current and future preventive therapies will likely be more effective in the early stages of dementia, when everyday functioning is not affected. Accordingly the early identification of people at risk is particularly important. In most cases, when subjects visit an expert and are examined using neuropsychological tests, the disease has already been developed. Contrary to this cognitive games are played by healthy, well functioning elderly people, subjects who should be monitored for early signs. Further advantages of cognitive games are their accessibility and their cost-effectiveness. Purpose The aim of the investigation was to show that computer games can help to identify those who are at risk. In order to validate games analysis was completed which measured the correlations between results of the 'Find the Pairs' memory game and the volumes of the temporal brain regions previously found to be good predictors of later cognitive decline. Participants and Methods 34 healthy elderly subjects were enrolled in the study. The volume of the cerebral structures was measured by MRI. Cortical reconstruction and volumetric segmentation were performed by Freesurfer. Results There was a correlation between the number of attempts and the time required to complete the memory game and the volume of the entorhinal cortex, the temporal pole, and the hippocampus. There was also a correlation between the results of the Paired Associates Learning (PAL) test and the memory game. Conclusions The results gathered support the initial hypothesis that healthy elderly subjects achieving lower scores in the memory game have increased level of atrophy in the temporal brain structures and showed a decreased performance in the PAL test. Based on these results it can be concluded that memory games may be useful in early screening for cognitive decline. PMID:25706380

  19. Disrupted White Matter Network and Cognitive Decline in Type 2 Diabetes Patients.

    PubMed

    Zhang, Junying; Liu, Zhen; Li, Zixiao; Wang, Yunxia; Chen, Yaojing; Li, Xin; Chen, Kewei; Shu, Ni; Zhang, Zhanjun

    2016-05-01

    Type 2 diabetes mellitus is accompanied by cognitive impairment and is associated with an increased risk of dementia. Damage to brain structures such as white matter network disruption may underlie this cognitive disturbance. In the present study, 886 non-diabetic and 163 type 2 diabetic participants completed a battery of neuropsychological tests. Among them, 38 diabetic patients and 34 non-diabetic participants that matched the patients for age/sex/education received a magnetic resonance imaging-based diffusion tensor imaging. Then we calculated the topological properties of the white matter network using a graph theoretical method to investigate network efficiency differences between groups. We found that type 2 diabetic patients had inferior performances compared to the non-diabetic controls, in several cognitive domains involving executive function, spatial processing, memory, and attention. We also found that diabetic patients exhibited a disrupted topological organization of the white matter network (including the global network properties, i.e., network strength, global efficiency, local efficiency and shortest path length, and the nodal efficiency of the right rolandic operculum) in the brain. Moreover, those global network properties and the nodal efficiency of the right rolandic operculum both had positive correlations with executive function in the patient group. The results suggest that type 2 diabetes mellitus leads to an alteration in the topological organization of the cortical white matter network and this alteration may account for the observed cognitive decline.

  20. Preclinical Magnetic Resonance Imaging and Spectroscopy Studies of Memory, Aging, and Cognitive Decline

    PubMed Central

    Febo, Marcelo; Foster, Thomas C.

    2016-01-01

    Neuroimaging provides for non-invasive evaluation of brain structure and activity and has been employed to suggest possible mechanisms for cognitive aging in humans. However, these imaging procedures have limits in terms of defining cellular and molecular mechanisms. In contrast, investigations of cognitive aging in animal models have mostly utilized techniques that have offered insight on synaptic, cellular, genetic, and epigenetic mechanisms affecting memory. Studies employing magnetic resonance imaging and spectroscopy (MRI and MRS, respectively) in animal models have emerged as an integrative set of techniques bridging localized cellular/molecular phenomenon and broader in vivo neural network alterations. MRI methods are remarkably suited to longitudinal tracking of cognitive function over extended periods permitting examination of the trajectory of structural or activity related changes. Combined with molecular and electrophysiological tools to selectively drive activity within specific brain regions, recent studies have begun to unlock the meaning of fMRI signals in terms of the role of neural plasticity and types of neural activity that generate the signals. The techniques provide a unique opportunity to causally determine how memory-relevant synaptic activity is processed and how memories may be distributed or reconsolidated over time. The present review summarizes research employing animal MRI and MRS in the study of brain function, structure, and biochemistry, with a particular focus on age-related cognitive decline. PMID:27468264

  1. A novel radial water tread maze tracks age-related cognitive decline in mice

    PubMed Central

    Pettan-Brewer, Christina; Touch, Dylan V.; Wiley, Jesse C.; Hopkins, Heather C.; Rabinovitch, Peter S.; Ladiges, Warren C.

    2013-01-01

    There is currently no treatment and cure for age-related dementia and cognitive impairment in humans. Mice suffer from age-related cognitive decline just as people do, but assessment is challenging because of cumbersome and at times stressful performance tasks. We developed a novel radial water tread (RWT) maze and tested male C57BL/6 (B6) and C57BL/6 x Balb/c F1 (CB6F1) mice at ages 4, 12, 20, and 28 months. B6 mice showed a consistent learning experience and memory retention that gradually decreased with age. CB6F1 mice showed a moderate learning experience in the 4 and 12 month groups, which was not evident in the 20 and 28 month groups. In conclusion, CB6F1 mice showed more severe age-related cognitive impairment compared to B6 mice and might be a suitable model for intervention studies. In addition, the RWT maze has a number of operational advantages compared to currently accepted tasks and can be used to assess age-related cognition impairment in B6 and CB6F1 mice as early as 12 months of age. PMID:24106580

  2. Preclinical Magnetic Resonance Imaging and Spectroscopy Studies of Memory, Aging, and Cognitive Decline.

    PubMed

    Febo, Marcelo; Foster, Thomas C

    2016-01-01

    Neuroimaging provides for non-invasive evaluation of brain structure and activity and has been employed to suggest possible mechanisms for cognitive aging in humans. However, these imaging procedures have limits in terms of defining cellular and molecular mechanisms. In contrast, investigations of cognitive aging in animal models have mostly utilized techniques that have offered insight on synaptic, cellular, genetic, and epigenetic mechanisms affecting memory. Studies employing magnetic resonance imaging and spectroscopy (MRI and MRS, respectively) in animal models have emerged as an integrative set of techniques bridging localized cellular/molecular phenomenon and broader in vivo neural network alterations. MRI methods are remarkably suited to longitudinal tracking of cognitive function over extended periods permitting examination of the trajectory of structural or activity related changes. Combined with molecular and electrophysiological tools to selectively drive activity within specific brain regions, recent studies have begun to unlock the meaning of fMRI signals in terms of the role of neural plasticity and types of neural activity that generate the signals. The techniques provide a unique opportunity to causally determine how memory-relevant synaptic activity is processed and how memories may be distributed or reconsolidated over time. The present review summarizes research employing animal MRI and MRS in the study of brain function, structure, and biochemistry, with a particular focus on age-related cognitive decline. PMID:27468264

  3. 75 FR 3243 - NIH State-of-the-Science Conference: Preventing Alzheimer's Disease and Cognitive Decline; Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-20

    ... HUMAN SERVICES National Institutes of Health NIH State-of-the-Science Conference: Preventing Alzheimer's... the ``NIH State-of-the-Science Conference: Preventing Alzheimer's Disease and Cognitive Decline'' to... state of cognitive impairment or into various forms of dementia, including Alzheimer's disease....

  4. Lipid Profiles and APOE4 Allele Impact Midlife Cognitive Decline in HIV-Infected Men on Antiretroviral Therapy

    PubMed Central

    Mukerji, Shibani S.; Locascio, Joseph J.; Misra, Vikas; Lorenz, David R.; Holman, Alex; Dutta, Anupriya; Penugonda, Sudhir; Wolinsky, Steven M.; Gabuzda, Dana

    2016-01-01

    Background. Dyslipidemia and apolipoprotein E4 (APOE ϵ4) allele are risk factors for age-related cognitive decline, but how these risks are modified by human immunodeficiency virus (HIV) infection is unclear. Methods. In a longitudinal nested study from the Multicenter AIDS Cohort Study, 273 HIV type 1–infected (HIV+) men aged 50–65 years with baseline HIV RNA <400 copies/mL and on continuous antiretroviral therapy (ART) in ≥95% of follow-up visits were matched by sociodemographic variables to 516 HIV-uninfected (HIV–) controls. The association between lipid markers (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides), APOE genotype, and cognitive decline in HIV infection was examined using mixed-effects models. Results. The median baseline age of participants was 51, 81% were white, and 89% had education >12 years. HIV+ men had similar baseline total cholesterol and LDL-C, but lower HDL-C and higher triglycerides than controls (P < .001). Higher total cholesterol and LDL-C were associated with faster rates of cognitive decline (P < .01), whereas higher HDL-C attenuated decline (P = .02) in HIV+ men. In HIV+ men with elevated cholesterol, statin use was associated with a slower estimated rate of decline (P = .02). APOE ϵ4 genotype accelerated cognitive decline in HIV+ but not HIV– men (P = .01), with trajectories diverging from HIV– ε4 carriers after age 50. Total cholesterol levels did not modify the association of ϵ4 genotype with decline (P = .9). Conclusions. Elevated cholesterol and APOE ϵ4 genotype are independent risk factors for cognitive decline in ART-adherent HIV+ men aged >50 years. Treatment of dyslipidemia may be an effective strategy to reduce cognitive decline in older HIV+ individuals. PMID:27448678

  5. Physical activity and inflammation: effects on gray-matter volume and cognitive decline in aging.

    PubMed

    Papenberg, Goran; Ferencz, Beata; Mangialasche, Francesca; Mecocci, Patrizia; Cecchetti, Roberta; Kalpouzos, Grégoria; Fratiglioni, Laura; Bäckman, Lars

    2016-10-01

    Physical activity has been positively associated with gray-matter integrity. In contrast, pro-inflammatory cytokines seem to have negative effects on the aging brain and have been related to dementia. It was investigated whether an inactive lifestyle and high levels of inflammation resulted in smaller gray-matter volumes and predicted cognitive decline across 6 years in a population-based study of older adults (n = 414). Self-reported physical activity (fitness-enhancing, health-enhancing, inadequate) was linked to gray-matter volume, such that individuals with inadequate physical activity had the least gray matter. There were no overall associations between different pro-and anti-inflammatory markers (IL-1β, IL-6, IL-10, IL-12p40, IL-12p70, G-CSF, and TNF-α) and gray-matter integrity. However, persons with inadequate activity and high levels of the pro-inflammatory marker IL-12p40 had smaller volumes of lateral prefrontal cortex and hippocampus and declined more on the Mini-Mental State Examination test over 6 years compared with physically inactive individuals with low levels of IL-12p40 and to more physically active persons, irrespective of their levels of IL-12p40. These patterns of data suggested that inflammation was particularly detrimental in inactive older adults and may exacerbate the negative effects of physical inactivity on brain and cognition in old age. Hum Brain Mapp 37:3462-3473, 2016. © 2016 Wiley Periodicals, Inc.

  6. A mutation in APP protects against Alzheimer's disease and age-related cognitive decline.

    PubMed

    Jonsson, Thorlakur; Atwal, Jasvinder K; Steinberg, Stacy; Snaedal, Jon; Jonsson, Palmi V; Bjornsson, Sigurbjorn; Stefansson, Hreinn; Sulem, Patrick; Gudbjartsson, Daniel; Maloney, Janice; Hoyte, Kwame; Gustafson, Amy; Liu, Yichin; Lu, Yanmei; Bhangale, Tushar; Graham, Robert R; Huttenlocher, Johanna; Bjornsdottir, Gyda; Andreassen, Ole A; Jönsson, Erik G; Palotie, Aarno; Behrens, Timothy W; Magnusson, Olafur T; Kong, Augustine; Thorsteinsdottir, Unnur; Watts, Ryan J; Stefansson, Kari

    2012-08-01

    The prevalence of dementia in the Western world in people over the age of 60 has been estimated to be greater than 5%, about two-thirds of which are due to Alzheimer's disease. The age-specific prevalence of Alzheimer's disease nearly doubles every 5 years after age 65, leading to a prevalence of greater than 25% in those over the age of 90 (ref. 3). Here, to search for low-frequency variants in the amyloid-β precursor protein (APP) gene with a significant effect on the risk of Alzheimer's disease, we studied coding variants in APP in a set of whole-genome sequence data from 1,795 Icelanders. We found a coding mutation (A673T) in the APP gene that protects against Alzheimer's disease and cognitive decline in the elderly without Alzheimer's disease. This substitution is adjacent to the aspartyl protease β-site in APP, and results in an approximately 40% reduction in the formation of amyloidogenic peptides in vitro. The strong protective effect of the A673T substitution against Alzheimer's disease provides proof of principle for the hypothesis that reducing the β-cleavage of APP may protect against the disease. Furthermore, as the A673T allele also protects against cognitive decline in the elderly without Alzheimer's disease, the two may be mediated through the same or similar mechanisms.

  7. Effects of education and race on cognitive decline: An integrative study of generalizability versus study-specific results.

    PubMed

    Gross, Alden L; Mungas, Dan M; Crane, Paul K; Gibbons, Laura E; MacKay-Brandt, Anna; Manly, Jennifer J; Mukherjee, Shubhabrata; Romero, Heather; Sachs, Bonnie; Thomas, Michael; Potter, Guy G; Jones, Richard N

    2015-12-01

    The objective of the study was to examine variability across multiple prospective cohort studies in level and rate of cognitive decline by race/ethnicity and years of education. We compare data across studies, we harmonized estimates of common latent factors representing overall or general cognitive performance, memory, and executive function derived from the: (a) Washington Heights, Hamilton Heights, Inwood Columbia Aging Project (N = 4,115), (b) Spanish and English Neuropsychological Assessment Scales (N = 525), (c) Duke Memory, Health, and Aging study (N = 578), and (d) Neurocognitive Outcomes of Depression in the Elderly (N = 585). We modeled cognitive change over age for cognitive outcomes by race, education, and study. We adjusted models for sex, dementia status, and study-specific characteristics. The results found that for baseline levels of overall cognitive performance, memory, and executive function, differences in race and education tended to be larger than between-study differences and consistent across studies. This pattern did not hold for rate of cognitive decline: effects of education and race/ethnicity on cognitive change were not consistently observed across studies, and when present were small, with racial/ethnic minorities and those with lower education declining at faster rates. In this diverse set of datasets, non-Hispanic Whites and those with higher education had substantially higher baseline cognitive test scores. However, differences in the rate of cognitive decline by race/ethnicity and education did not follow this pattern. This study suggests that baseline test scores and longitudinal change have different determinants, and future studies to examine similarities and differences of causes of cognitive decline in racially/ethnically and educationally diverse older groups is needed.

  8. Effects of education and race on cognitive decline: An integrative study of generalizability versus study-specific results.

    PubMed

    Gross, Alden L; Mungas, Dan M; Crane, Paul K; Gibbons, Laura E; MacKay-Brandt, Anna; Manly, Jennifer J; Mukherjee, Shubhabrata; Romero, Heather; Sachs, Bonnie; Thomas, Michael; Potter, Guy G; Jones, Richard N

    2015-12-01

    The objective of the study was to examine variability across multiple prospective cohort studies in level and rate of cognitive decline by race/ethnicity and years of education. We compare data across studies, we harmonized estimates of common latent factors representing overall or general cognitive performance, memory, and executive function derived from the: (a) Washington Heights, Hamilton Heights, Inwood Columbia Aging Project (N = 4,115), (b) Spanish and English Neuropsychological Assessment Scales (N = 525), (c) Duke Memory, Health, and Aging study (N = 578), and (d) Neurocognitive Outcomes of Depression in the Elderly (N = 585). We modeled cognitive change over age for cognitive outcomes by race, education, and study. We adjusted models for sex, dementia status, and study-specific characteristics. The results found that for baseline levels of overall cognitive performance, memory, and executive function, differences in race and education tended to be larger than between-study differences and consistent across studies. This pattern did not hold for rate of cognitive decline: effects of education and race/ethnicity on cognitive change were not consistently observed across studies, and when present were small, with racial/ethnic minorities and those with lower education declining at faster rates. In this diverse set of datasets, non-Hispanic Whites and those with higher education had substantially higher baseline cognitive test scores. However, differences in the rate of cognitive decline by race/ethnicity and education did not follow this pattern. This study suggests that baseline test scores and longitudinal change have different determinants, and future studies to examine similarities and differences of causes of cognitive decline in racially/ethnically and educationally diverse older groups is needed. PMID:26523693

  9. Genetic predisposition to higher production of interleukin-6 through -174 G > C polymorphism predicts global cognitive decline in oldest-old with cognitive impairment no dementia.

    PubMed

    Fraga, Vanessa G; Guimarães, Henrique C; Teixeira, Antônio L; Barbosa, Maira T; Mateo, Elvis C C; Carvalho, Maria G; Caramelli, Paulo; Gomes, Karina B

    2015-11-01

    Interleukin 6 (IL-6) is a pro-inflammatory cytokine upregulated in neurodegenerative contexts. The polymorphism IL-6 -174 G > C influences release levels of this cytokine. We aimed to evaluate the influence of IL-6 -174 G > C on global cognitive score of a group with cognitive impairment no dementia in one year of follow-up.Methods The subjects were categorized in two groups: short-term decline in global cognitive score and those with short-term stability or improvement. IL-6 174 G > C information were compared among these groups.Results We observed that individuals with cognitive impairment no dementia with GGlowergenotype were more frequent among global cognitive score non-decliners while carriers of at least one Chigherallele were more frequent in the group with global cognitive score decliners (p = 0.012; RR = 3.095 IC95%= 1.087-8.812).Conclusion These results suggest that the higher expression of IL-6 gene may be an independent risk factor for cognitive decline among individuals with cognitive impairment no dementia.

  10. Relative value of diverse brain MRI and blood-based biomarkers for predicting cognitive decline in the elderly

    NASA Astrophysics Data System (ADS)

    Madsen, Sarah K.; Ver Steeg, Greg; Daianu, Madelaine; Mezher, Adam; Jahanshad, Neda; Nir, Talia M.; Hua, Xue; Gutman, Boris A.; Galstyan, Aram; Thompson, Paul M.

    2016-03-01

    Cognitive decline accompanies many debilitating illnesses, including Alzheimer's disease (AD). In old age, brain tissue loss also occurs along with cognitive decline. Although blood tests are easier to perform than brain MRI, few studies compare brain scans to standard blood tests to see which kinds of information best predict future decline. In 504 older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we first used linear regression to assess the relative value of different types of data to predict cognitive decline, including 196 blood panel biomarkers, 249 MRI biomarkers obtained from the FreeSurfer software, demographics, and the AD-risk gene APOE. A subset of MRI biomarkers was the strongest predictor. There was no specific blood marker that increased predictive accuracy on its own, we found that a novel unsupervised learning method, CorEx, captured weak correlations among blood markers, and the resulting clusters offered unique predictive power.

  11. Faster cognitive decline in elders without dementia and decreased risk of cancer mortality

    PubMed Central

    Romero, Juan Pablo; Louis, Elan D.; Bermejo-Pareja, Félix

    2014-01-01

    Objective: To assess whether faster cognitive decline in elders without dementia is associated with decreased risk of cancer mortality. Methods: In this population-based, prospective study of 2,627 people without dementia aged 65 years and older (Neurological Disorders in Central Spain), a 37-item version of the Mini-Mental State Examination (37-MMSE) was administered at 2 visits (baseline and follow-up, approximately 3 years later). We divided change in 37-MMSE into tertiles (lower tertile ≥2 point improvement in score, higher tertile ≥2 point decline in score). Community-dwelling elders were followed for a median of 12.9 years, after which the death certificates of those who died were examined. Results: A total of 1,003 (38.2%) died, including 339 (33.8%) deaths among participants who were in the higher tertile of 37-MMSE change and 664 (66.2%) deaths among those in the remaining tertiles. Cancer was reported significantly less often in those in the higher tertile of MMSE change (20.6%) than in those in the remaining tertiles (28.6%): in an unadjusted Cox model, hazard ratio for cancer mortality in participants within the higher tertile = 0.75 (p = 0.04) compared with the participants within the remaining tertiles. In a Cox model that adjusted for a variety of demographic factors and comorbidities, hazard ratio for cancer mortality in participants within the higher tertile = 0.70 (p = 0.01). Conclusion: In this population-based, prospective study of community-dwelling elders without dementia, faster cognitive decline was associated with a decreased risk of cancer mortality. Further studies are required to elucidate this inverse association in elders without dementia. PMID:24719490

  12. Remedial Effects of Motivational Incentive on Declining Cognitive Control In Healthy Aging and Parkinson's Disease

    PubMed Central

    Harsay, Helga A.; Buitenweg, Jessika I. V.; Wijnen, Jasper G.; Guerreiro, Maria J. S.; Ridderinkhof, K. Richard

    2010-01-01

    The prospect of reward may provide a motivational incentive for optimizing goal-directed behavior. Animal work demonstrates that reward-processing networks and oculomotor-control networks in the brain are connected through the dorsal striatum, and that reward anticipation can improve oculomotor control via this nexus. Due perhaps to deterioration in dopaminergic striatal circuitry, goal-directed oculomotor control is subject to decline in healthy seniors, and even more in individuals with Parkinson's disease (PD). Here we examine whether healthy seniors and PD patients are able to utilize reward prospects to improve their impaired antisaccade performance. Results confirmed that oculomotor control declined in PD patients compared to healthy seniors, and in healthy seniors compared to young adults. However, the motivational incentive of reward expectation resulted in benefits in antisaccade performance in all groups alike. These findings speak against structural and non-modifiable decline in cognitive control functions, and emphasize the remedial potential of motivational incentive mechanisms in healthy as well as pathological aging. PMID:21060805

  13. Longitudinal Changes in Clock Drawing Test (CDT) Performance before and after Cognitive Decline

    PubMed Central

    Zhao, Qianhua; Hong, Zhen; Guo, Qihao

    2014-01-01

    Background Many scoring systems exist for clock drawing task variants. However, none of them are reliable in evaluating longitudinal changes of cognitive function. The purpose of this study is to create a simple yet optimal scoring procedure to evaluate cognitive decline using a clinic-based sample. Methods Clock-drawings from 121 participants (76 individuals with no dementia and later did not develop dementia after a mean 41.2-month follow-up, 45 individuals with no dementia became demented after a mean 42.3-month follow-up) were analyzed using t-test to determine a new and simplified CDT scoring system. The new scoring method was then compared with other commonly used systems. Results In the converters, there were only 7 items that are significantly different between the initial visits and the second visits. We propose a new scoring system that includes the seven critical items: numbers are equally spaced (12–3–6–9) (p = 0.031), the other eight numbers are marked (p = 0.022), numbers are clockwise (p = 0.002), all numbers are correct (p = 0.030), distance between numbers is constant (p = 0.016), clock has two hands (p = 0.000), arrows are drawn (p = 0.003). Compared with other traditionally used scoring methods, this based change clock drawing test (BCCDT) has one of the most balanced sensitivities/specificities with a clinic-based sample. Conclusions The new CDT scoring system provides further evidence in support of a simple and reliable clock-drawing scoring system in follow-up studies to evaluate cognitive decline, which can be used in assessing the efficacy of medicine. PMID:24874454

  14. Angiotensin-converting enzyme overexpression in myelomonocytes prevents Alzheimer’s-like cognitive decline

    PubMed Central

    Bernstein, Kenneth E.; Koronyo, Yosef; Salumbides, Brenda C.; Sheyn, Julia; Pelissier, Lindsey; Lopes, Dahabada H.J.; Shah, Kandarp H.; Bernstein, Ellen A.; Fuchs, Dieu-Trang; Yu, Jeff J.-Y.; Pham, Michael; Black, Keith L.; Shen, Xiao Z.; Fuchs, Sebastien; Koronyo-Hamaoui, Maya

    2014-01-01

    Cognitive decline in patients with Alzheimer’s disease (AD) is associated with elevated brain levels of amyloid β protein (Aβ), particularly neurotoxic Aβ1–42. Angiotensin-converting enzyme (ACE) can degrade Aβ1–42, and ACE overexpression in myelomonocytic cells enhances their immune function. To examine the effect of targeted ACE overexpression on AD, we crossed ACE10/10 mice, which overexpress ACE in myelomonocytes using the c-fms promoter, with the transgenic APPSWE/PS1ΔE9 mouse model of AD (AD+). Evaluation of brain tissue from these AD+ACE10/10 mice at 7 and 13 months revealed that levels of both soluble and insoluble brain Aβ1–42 were reduced compared with those in AD+ mice. Furthermore, both plaque burden and astrogliosis were drastically reduced. Administration of the ACE inhibitor ramipril increased Aβ levels in AD+ACE10/10 mice compared with the levels induced by the ACE-independent vasodilator hydralazine. Overall, AD+ACE10/10 mice had less brain-infiltrating cells, consistent with reduced AD-associated pathology, though ACE-overexpressing macrophages were abundant around and engulfing Aβ plaques. At 11 and 12 months of age, the AD+ACE10/WT and AD+ACE10/10 mice were virtually equivalent to non-AD mice in cognitive ability, as assessed by maze-based behavioral tests. Our data demonstrate that an enhanced immune response, coupled with increased myelomonocytic expression of catalytically active ACE, prevents cognitive decline in a murine model of AD. PMID:24487585

  15. Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study

    PubMed Central

    Dublin, Sascha; Yu, Onchee; Walker, Rod; Anderson, Melissa; Hubbard, Rebecca A; Crane, Paul K; Larson, Eric B

    2016-01-01

    Objective To determine whether higher cumulative use of benzodiazepines is associated with a higher risk of dementia or more rapid cognitive decline. Design Prospective population based cohort. Setting Integrated healthcare delivery system, Seattle, Washington. Participants 3434 participants aged ≥65 without dementia at study entry. There were two rounds of recruitment (1994-96 and 2000-03) followed by continuous enrollment beginning in 2004. Main outcomes measures The cognitive abilities screening instrument (CASI) was administered every two years to screen for dementia and was used to examine cognitive trajectory. Incident dementia and Alzheimer’s disease were determined with standard diagnostic criteria. Benzodiazepine exposure was defined from computerized pharmacy data and consisted of the total standardized daily doses (TSDDs) dispensed over a 10 year period (a rolling window that moved forward in time during follow-up). The most recent year was excluded because of possible use for prodromal symptoms. Multivariable Cox proportional hazard models were used to examine time varying use of benzodiazepine and dementia risk. Analyses of cognitive trajectory used linear regression models with generalized estimating equations. Results Over a mean follow-up of 7.3 years, 797 participants (23.2%) developed dementia, of whom 637 developed Alzheimer’s disease. For dementia, the adjusted hazard ratios associated with cumulative benzodiazepine use compared with non-use were 1.25 (95% confidence interval 1.03 to 1.51) for 1-30 TSDDs; 1.31 (1.00 to 1.71) for 31-120 TSDDs; and 1.07 (0.82 to 1.39) for ≥121 TSDDs. Results were similar for Alzheimer’s disease. Higher benzodiazepine use was not associated with more rapid cognitive decline. Conclusion The risk of dementia is slightly higher in people with minimal exposure to benzodiazepines but not with the highest level of exposure. These results do not support a causal association between benzodiazepine use and

  16. Cardiovascular Risk Factors Promote Brain Hypoperfusion Leading to Cognitive Decline and Dementia

    PubMed Central

    de la Torre, Jack C.

    2012-01-01

    Heart disease is the major leading cause of death and disability in the world. Mainly affecting the elderly population, heart disease and its main outcome, cardiovascular disease, have become an important risk factor in the development of cognitive decline and Alzheimer's disease (AD). This paper examines the evidence linking chronic brain hypoperfusion induced by a variety of cardiovascular deficits in the development of cognitive impairment preceding AD. The evidence indicates a strong association between AD and cardiovascular risk factors, including ApoE4, atrial fibrillation, thrombotic events, hypertension, hypotension, heart failure, high serum markers of inflammation, coronary artery disease, low cardiac index, and valvular pathology. In elderly people whose cerebral perfusion is already diminished by their advanced age, additional reduction of cerebral blood flow stemming from abnormalities in the heart-brain vascular loop ostensibly increases the probability of developing AD. Evidence also suggests that a neuronal energy crisis brought on by relentless brain hypoperfusion may be responsible for protein synthesis abnormalities that later result in the classic neurodegenerative lesions involving the formation of amyloid-beta plaques and neurofibrillary tangles. Insight into how cardiovascular risk factors can induce progressive cognitive impairment offers an enhanced understanding of the multifactorial pathophysiology characterizing AD and ways at preventing or managing the cardiovascular precursors of this dementia. PMID:23243502

  17. Human-specific derived alleles of CD33 and other genes protect against postreproductive cognitive decline

    PubMed Central

    Schwarz, Flavio; Springer, Stevan A.; Altheide, Tasha K.; Varki, Nissi M.; Gagneux, Pascal; Varki, Ajit

    2016-01-01

    The individuals of most vertebrate species die when they can no longer reproduce. Humans are a rare exception, having evolved a prolonged postreproductive lifespan. Elders contribute to cooperative offspring care, assist in foraging, and communicate important ecological and cultural knowledge, increasing the survival of younger individuals. Age-related deterioration of cognitive capacity in humans compromises these benefits and also burdens the group with socially costly members. We investigated the contribution of the immunoregulatory receptor CD33 to a uniquely human postreproductive disease, Alzheimer’s dementia. Surprisingly, even though selection at advanced age is expected to be weak, a CD33 allele protective against Alzheimer’s disease is derived and unique to humans and favors a functional molecular state of CD33 resembling that of the chimpanzee. Thus, derived alleles may be compensatory and restore interactions altered as a consequence of human-specific brain evolution. We found several other examples of derived alleles at other human loci that protect against age-related cognitive deterioration arising from neurodegenerative disease or cerebrovascular insufficiency. Selection by inclusive fitness may be strong enough to favor alleles protecting specifically against cognitive decline in postreproductive humans. Such selection would operate by maximizing the contributions of postreproductive individuals to the fitness of younger kin. PMID:26621708

  18. Neutrophils promote Alzheimer's disease-like pathology and cognitive decline via LFA-1 integrin.

    PubMed

    Zenaro, Elena; Pietronigro, Enrica; Della Bianca, Vittorina; Piacentino, Gennj; Marongiu, Laura; Budui, Simona; Turano, Ermanna; Rossi, Barbara; Angiari, Stefano; Dusi, Silvia; Montresor, Alessio; Carlucci, Tommaso; Nanì, Sara; Tosadori, Gabriele; Calciano, Lucia; Catalucci, Daniele; Berton, Giorgio; Bonetti, Bruno; Constantin, Gabriela

    2015-08-01

    Inflammation is a pathological hallmark of Alzheimer's disease, and innate immune cells have been shown to contribute to disease pathogenesis. In two transgenic models of Alzheimer's disease (5xFAD and 3xTg-AD mice), neutrophils extravasated and were present in areas with amyloid-β (Aβ) deposits, where they released neutrophil extracellular traps (NETs) and IL-17. Aβ42 peptide triggered the LFA-1 integrin high-affinity state and rapid neutrophil adhesion to integrin ligands. In vivo, LFA-1 integrin controlled neutrophil extravasation into the CNS and intraparenchymal motility. In transgenic Alzheimer's disease models, neutrophil depletion or inhibition of neutrophil trafficking via LFA-1 blockade reduced Alzheimer's disease-like neuropathology and improved memory in mice already showing cognitive dysfunction. Temporary depletion of neutrophils for 1 month at early stages of disease led to sustained improvements in memory. Transgenic Alzheimer's disease model mice lacking LFA-1 were protected from cognitive decline and had reduced gliosis. In humans with Alzheimer's disease, neutrophils adhered to and spread inside brain venules and were present in the parenchyma, along with NETs. Our results demonstrate that neutrophils contribute to Alzheimer's disease pathogenesis and cognitive impairment and suggest that the inhibition of neutrophil trafficking may be beneficial in Alzheimer's disease.

  19. Lifelong bilingualism contributes to cognitive reserve against white matter integrity declines in aging.

    PubMed

    Gold, Brian T; Johnson, Nathan F; Powell, David K

    2013-11-01

    Recent evidence suggests that lifelong bilingualism may contribute to cognitive reserve (CR) in normal aging. However, there is currently no neuroimaging evidence to suggest that lifelong bilinguals can retain normal cognitive functioning in the face of age-related neurodegeneration. Here we explored this issue by comparing white matter (WM) integrity and gray matter (GM) volumetric patterns of older adult lifelong bilinguals (N=20) and monolinguals (N=20). The groups were matched on a range of relevant cognitive test scores and on the established CR variables of education, socioeconomic status and intelligence. Participants underwent high-resolution structural imaging for assessment of GM volume and diffusion tensor imaging (DTI) for assessment of WM integrity. Results indicated significantly lower microstructural integrity in the bilingual group in several WM tracts. In particular, compared to their monolingual peers, the bilingual group showed lower fractional anisotropy and/or higher radial diffusivity in the inferior longitudinal fasciculus/inferior fronto-occipital fasciculus bilaterally, the fornix, and multiple portions of the corpus callosum. There were no group differences in GM volume. Our results suggest that lifelong bilingualism contributes to CR against WM integrity declines in aging.

  20. Human-specific derived alleles of CD33 and other genes protect against postreproductive cognitive decline.

    PubMed

    Schwarz, Flavio; Springer, Stevan A; Altheide, Tasha K; Varki, Nissi M; Gagneux, Pascal; Varki, Ajit

    2016-01-01

    The individuals of most vertebrate species die when they can no longer reproduce. Humans are a rare exception, having evolved a prolonged postreproductive lifespan. Elders contribute to cooperative offspring care, assist in foraging, and communicate important ecological and cultural knowledge, increasing the survival of younger individuals. Age-related deterioration of cognitive capacity in humans compromises these benefits and also burdens the group with socially costly members. We investigated the contribution of the immunoregulatory receptor CD33 to a uniquely human postreproductive disease, Alzheimer's dementia. Surprisingly, even though selection at advanced age is expected to be weak, a CD33 allele protective against Alzheimer's disease is derived and unique to humans and favors a functional molecular state of CD33 resembling that of the chimpanzee. Thus, derived alleles may be compensatory and restore interactions altered as a consequence of human-specific brain evolution. We found several other examples of derived alleles at other human loci that protect against age-related cognitive deterioration arising from neurodegenerative disease or cerebrovascular insufficiency. Selection by inclusive fitness may be strong enough to favor alleles protecting specifically against cognitive decline in postreproductive humans. Such selection would operate by maximizing the contributions of postreproductive individuals to the fitness of younger kin. PMID:26621708

  1. The involvement of homocysteine in stress-induced Aβ precursor protein misprocessing and related cognitive decline in rats.

    PubMed

    Xie, Fang; Zhao, Yun; Ma, Jing; Gong, Jing-Bo; Wang, Shi-Da; Zhang, Liang; Gao, Xiu-Jie; Qian, Ling-Jia

    2016-09-01

    Chronic stress is a risk factor in the development of cognitive decline and even Alzheimer's disease (AD), although its underlying mechanism is not fully understood. Our previous data demonstrated that the level of homocysteine (Hcy) was significantly elevated in the plasma of stressed animals, which suggests the possibility that Hcy is a link between stress and cognitive decline. To test this hypothesis, we compared the cognitive function, plasma concentrations of Hcy, and the brain beta-amyloid (Aβ) level between rats with or without chronic unexpected mild stress (CUMS). A lower performance by rats in behavioral tests indicated that a significant cognitive decline was induced by CUMS. Stress also disturbed the normal processing of Aβ precursor protein (APP) and resulted in the accumulation of Aβ in the brains of rats, which showed a positive correlation with the hyperhomocysteinemia (HHcy) that appeared in stressed rats. Hcy-targeting intervention experiments were used to verify further the involvement of Hcy in stress-induced APP misprocessing and related cognitive decline. The results showed that diet-induced HHcy could mimic the cognitive impairment and APP misprocessing in the same manner as CUMS, while Hcy reduction by means of vitamin B complex supplements and betaine could alleviate the cognitive deficits and dysregulation of Aβ metabolism in CUMS rats. Taken together, the novel evidence from our present study suggests that Hcy is likely to be involved in chronic stress-evoked APP misprocessing and related cognitive deficits. Our results also suggested the possibility of Hcy as a target for therapy and the potential value of vitamin B and betaine intake in the prevention of stress-induced cognitive decline.

  2. The involvement of homocysteine in stress-induced Aβ precursor protein misprocessing and related cognitive decline in rats.

    PubMed

    Xie, Fang; Zhao, Yun; Ma, Jing; Gong, Jing-Bo; Wang, Shi-Da; Zhang, Liang; Gao, Xiu-Jie; Qian, Ling-Jia

    2016-09-01

    Chronic stress is a risk factor in the development of cognitive decline and even Alzheimer's disease (AD), although its underlying mechanism is not fully understood. Our previous data demonstrated that the level of homocysteine (Hcy) was significantly elevated in the plasma of stressed animals, which suggests the possibility that Hcy is a link between stress and cognitive decline. To test this hypothesis, we compared the cognitive function, plasma concentrations of Hcy, and the brain beta-amyloid (Aβ) level between rats with or without chronic unexpected mild stress (CUMS). A lower performance by rats in behavioral tests indicated that a significant cognitive decline was induced by CUMS. Stress also disturbed the normal processing of Aβ precursor protein (APP) and resulted in the accumulation of Aβ in the brains of rats, which showed a positive correlation with the hyperhomocysteinemia (HHcy) that appeared in stressed rats. Hcy-targeting intervention experiments were used to verify further the involvement of Hcy in stress-induced APP misprocessing and related cognitive decline. The results showed that diet-induced HHcy could mimic the cognitive impairment and APP misprocessing in the same manner as CUMS, while Hcy reduction by means of vitamin B complex supplements and betaine could alleviate the cognitive deficits and dysregulation of Aβ metabolism in CUMS rats. Taken together, the novel evidence from our present study suggests that Hcy is likely to be involved in chronic stress-evoked APP misprocessing and related cognitive deficits. Our results also suggested the possibility of Hcy as a target for therapy and the potential value of vitamin B and betaine intake in the prevention of stress-induced cognitive decline. PMID:27435080

  3. Decline in Cognitive Function and Risk of Elder Self-Neglect: Finding from the Chicago Health Aging Project

    PubMed Central

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

    2010-01-01

    Objectives This study aimed to examine the longitudinal association between decline in cognitive function and risk of elder self-neglect in a community-dwelling population. Design Prospective population-based study Setting Geographically-defined community in Chicago. Participants Community-dwelling subjects reported to the social services agency from 1993–2005 for self-neglect who also participated in the Chicago Health Aging Project (CHAP). Of the 5,519 participants in the Chicago Health Aging Project, 1,017 were reported to social services agency for suspected elder self-neglect from 1993–2005. Measurements Reported elder self-neglect was identified by social services agency. The primary predictor was decline in cognitive function assessed using the Mini-Mental State Examination (MMSE), the Symbol Digit Modalities Test (Executive Function), and both 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. Results After adjusting for potential confounding factors, decline in global cognitive function, MMSE or episodic memory was not independently associated with increased risk of reported and confirmed elder self-neglect. Decline in executive function was associated with increased risk of reported and confirmed elder self-neglect. Decline in global cognitive function was associated with increased risk of greater self-neglect severity (PE=0.76, SE=0.31, p=0.014). Conclusion Decline in executive function was associated with increased risk of reported and confirmed elder self-neglect. Decline in global cognitive function was associated with increased risk of greater self-neglect severity. PMID:21143438

  4. An application of Pavlovian principles to the problems of obesity and cognitive decline.

    PubMed

    Davidson, T L; Sample, C H; Swithers, S E

    2014-02-01

    An enormous amount of research has been aimed at identifying biological and environmental factors that are contributing to the current global obesity pandemic. The present paper reviews recent findings which suggest that obesity is attributable, at least in part, to a disruption of the Pavlovian control of energy regulation. Within our framework, this disruption occurs when (a) consumption of sweet-tasting, but low calorie or noncaloric, foods and beverages reduces the ability of sweet tastes to predict the postingestive caloric consequences of intake and (b) consuming diets high in saturated fat and sugar (a.k.a., Western diet) impairs hippocampal-dependent learning and memory processes that are involved with the use of interoceptive "satiety" signals to anticipate when food and eating are not followed by appetitive postingestive outcomes. The paper concludes with discussion of a "vicious-cycle" model which links obesity to cognitive decline.

  5. Shared Neuropathological Characteristics of Obesity, Type 2 Diabetes and Alzheimer's Disease: Impacts on Cognitive Decline.

    PubMed

    Walker, Jennifer M; Harrison, Fiona E

    2015-09-01

    In the past few decades, the prevalence of obesity and type 2 diabetes mellitus (T2DM), as well as older individuals at risk for Alzheimer's disease (AD), has increased. While the consumption of diets high in fat (total and saturated) have been linked to increased risk of AD, diets rich in antioxidants, polyunsaturated fats, and omega-3 fatty acids are associated with decreased risk. Additionally, AD patients are at increased risk for developing T2DM. Recent research suggests that there are stronger similarities between AD and T2DM than have previously been considered. Here we review the neurocognitive and inflammatory effects of high-fat diet consumption, its relationship to AD, and the treatment potential of dietary interventions that may decrease risk of cognitive decline and other associated neuropathological changes, such as insulin resistance, oxidative stress, and chronic inflammatory processes.

  6. Shared Neuropathological Characteristics of Obesity, Type 2 Diabetes and Alzheimer's Disease: Impacts on Cognitive Decline.

    PubMed

    Walker, Jennifer M; Harrison, Fiona E

    2015-09-01

    In the past few decades, the prevalence of obesity and type 2 diabetes mellitus (T2DM), as well as older individuals at risk for Alzheimer's disease (AD), has increased. While the consumption of diets high in fat (total and saturated) have been linked to increased risk of AD, diets rich in antioxidants, polyunsaturated fats, and omega-3 fatty acids are associated with decreased risk. Additionally, AD patients are at increased risk for developing T2DM. Recent research suggests that there are stronger similarities between AD and T2DM than have previously been considered. Here we review the neurocognitive and inflammatory effects of high-fat diet consumption, its relationship to AD, and the treatment potential of dietary interventions that may decrease risk of cognitive decline and other associated neuropathological changes, such as insulin resistance, oxidative stress, and chronic inflammatory processes. PMID:26340637

  7. An Application of Pavlovian Principles to the Problems of Obesity and Cognitive Decline

    PubMed Central

    Davidson, T. L.; Sample, C. H.; Swithers, S. E.

    2013-01-01

    An enormous amount of research has been aimed at identifying biological and environmental factors that are contributing to the current global obesity pandemic. The present paper reviews recent findings which suggest that obesity is attributable, at least in part, to a disruption of the Pavlovian control of energy regulation. Within our framework, this disruption occurs when (a) consumption of sweet-tasting, but low calorie or noncaloric, foods and beverages reduces the ability of sweet tastes to predict the postingestive caloric consequences of intake and (b) consuming diets high in saturated fat and sugar (a.k.a., Western diet) impairs hippocampal-dependent learning and memory processes that are involved with the use of interoceptive “satiety” signals to anticipate when food and eating are not followed by appetitive postingestive outcomes. The paper concludes with discussion of a “vicious-cycle’ model which links obesity to cognitive decline. PMID:23887140

  8. Physical activity and inflammation: effects on gray-matter volume and cognitive decline in aging.

    PubMed

    Papenberg, Goran; Ferencz, Beata; Mangialasche, Francesca; Mecocci, Patrizia; Cecchetti, Roberta; Kalpouzos, Grégoria; Fratiglioni, Laura; Bäckman, Lars

    2016-10-01

    Physical activity has been positively associated with gray-matter integrity. In contrast, pro-inflammatory cytokines seem to have negative effects on the aging brain and have been related to dementia. It was investigated whether an inactive lifestyle and high levels of inflammation resulted in smaller gray-matter volumes and predicted cognitive decline across 6 years in a population-based study of older adults (n = 414). Self-reported physical activity (fitness-enhancing, health-enhancing, inadequate) was linked to gray-matter volume, such that individuals with inadequate physical activity had the least gray matter. There were no overall associations between different pro-and anti-inflammatory markers (IL-1β, IL-6, IL-10, IL-12p40, IL-12p70, G-CSF, and TNF-α) and gray-matter integrity. However, persons with inadequate activity and high levels of the pro-inflammatory marker IL-12p40 had smaller volumes of lateral prefrontal cortex and hippocampus and declined more on the Mini-Mental State Examination test over 6 years compared with physically inactive individuals with low levels of IL-12p40 and to more physically active persons, irrespective of their levels of IL-12p40. These patterns of data suggested that inflammation was particularly detrimental in inactive older adults and may exacerbate the negative effects of physical inactivity on brain and cognition in old age. Hum Brain Mapp 37:3462-3473, 2016. © 2016 Wiley Periodicals, Inc. PMID:27159568

  9. Weight loss and rapid cognitive decline in community-dwelling patients with Alzheimer's disease.

    PubMed

    Soto, Maria E; Secher, Marion; Gillette-Guyonnet, Sophie; Abellan van Kan, Gabor; Andrieu, Sandrine; Nourhashemi, Fati; Rolland, Yves; Vellas, Bruno

    2012-01-01

    Weight loss is a frequent complication of Alzheimer's disease (AD) and a strong predictor of adverse outcomes in patients suffering from this disease. The aim of this study was to determine whether weight loss was a predictor of rapid cognitive decline (RCD) in AD. Four hundred fourteen community-dwelling ambulatory patients with a diagnosis of probable AD and a Mini-Mental State Examination (MMSE) score between 10 and 26 from the REAL.FR (REseau sur la maladie d'ALzheimer FRançais) cohort were studied and followed up during 4 years. Patients were classified in 2 groups according to weight loss defined by a loss of 4% or more during the first year of follow-up. RCD was defined as the loss of 3 points or more in MMSE over 6 months. The incidence of RCD was determined among both groups over the last 3 years of follow-up. MMSE, Katz's Activity of Daily Living scale, Mini-Nutritional Assessment scale, co-morbidities, behavioral and psychological symptoms of dementia, medication, level of education, living arrangement, and caregiver's burden were assessed every 6 months. Eighty-seven patients (21.0%) lost 4% or more of their initial weight during the first year. The incidence of RCD for all patients was 57.6 (95% confidence interval (CI) = 51.6-64.8) per 100 person-year (median follow-up of 15.1 months). In Cox proportional hazards models, after controlling for potential confounders, weight loss was a significant predictor factor of RCD (adjusted hazard ratio (HR) = 1.50, 95% CI = 1.04-2.17). In conclusion, weight loss predicted RCD in this cohort. Whether the prevention of weight loss (by improving nutritional status) impacts cognitive decline remains an open question.

  10. Opportunities for New Insights on the Life-Course Risks and Outcomes of Cognitive Decline in the Kavli HUMAN Project

    PubMed Central

    Langa, Kenneth M.; Cutler, David

    2015-01-01

    Abstract The Kavli HUMAN Project (KHP) will provide groundbreaking insights into how biological, medical, and social factors interact and impact the risks for cognitive decline from birth through older age. It will richly measure the effect of cognitive decline on the ability to perform key activities of daily living. In addition, due to its family focus, the KHP will measure the impact on family members, including the amount of time that family members spend providing care to older adults with dementia. It will also clarify the division of caregiving duties among family members and the effects on caregivers' work, family life, and balance thereof. At the same time, for care that the family cannot provide, it will clarify the extent to which cognitive decline impacts healthcare utilization and end-of-life decision making. PMID:26487988

  11. Deep Brain Stimulation and Cognitive Decline in Parkinson’s Disease: A Clinical Review

    PubMed Central

    Massano, João; Garrett, Carolina

    2012-01-01

    Parkinson’s disease is a common and often debilitating disorder, with a growing prevalence accompanying global population aging. Current drug therapy is not satisfactory enough for many patients, especially after a few years of symptom progression. This is mainly due to the motor complications that frequently emerge as disease progresses. Deep brain stimulation (DBS) is a useful therapeutic option in carefully selected patients that significantly improves motor symptoms, functional status, and quality of life. However, cognitive impairment may limit patient selection for DBS, as patients need to have sufficient mental capabilities in order to understand the procedure, as well as its benefits and limitations, and cooperate with the medical team throughout the process of selection, surgery, and postsurgical follow-up. On the other hand it has been observed that certain aspects of cognitive performance may decline after DBS, namely when the therapeutic target is the widely used subthalamic nucleus. These are important pieces of information for patients, their families, and health care professionals. This manuscript reviews these aspects and their clinical implications. PMID:22557991

  12. Luteinizing hormone as a key player in the cognitive decline of Alzheimer's disease.

    PubMed

    Burnham, Veronica L; Thornton, Janice E

    2015-11-01

    This article is part of a Special Issue "SBN 2014". Alzheimer's disease is one of the most prevalent and costly neurological diseases in the world. Although decades of research have focused on understanding Alzheimer's disease pathology and progression, there is still a great lack of clinical treatments for those who suffer from it. One of the factors most commonly associated with the onset of Alzheimer's disease is a decrease in levels of gonadal hormones, such as estrogens and androgens. Despite the correlational and experimental data which support the role of these hormones in the etiology of Alzheimer's disease, clinical trials involving their reintroduction through hormone therapy have had varied results and these gonadal hormones often have accompanying health risks. More recently, investigation has turned toward other hormones in the hypothalamic-pituitary-gonadal axis that are disrupted by age-related decreases in gonadal hormones. Specifically, luteinizing hormone, which is increased with age in both men and women (in response to removal of negative feedback), has surfaced as a potentially powerful player in the risk and onset of Alzheimer's disease. Mounting evidence in basic research and epidemiological studies supports the role of elevated luteinizing hormone in exacerbating age-related cognitive decline in both males and females. This review summarizes the recent developments involving luteinizing hormone in increasing the cognitive deficits and molecular pathology characteristic of Alzheimer's disease.

  13. Longitudinal Progression of Cognitive Decline Correlates with Changes in the Spatial Pattern of Brain 18F-FDG PET

    PubMed Central

    Shokouhi, Sepideh; Claassen, Daniel; Kang, Hakmook; Ding, Zhaohua; Rogers, Baxter; Mishra, Arabinda; Riddle, William R.

    2014-01-01

    Evaluating the symptomatic progression of mild cognitive impairment (MCI) caused by Alzheimer disease (AD) is practically accomplished by tracking performance on cognitive tasks, such as the Alzheimer Disease Assessment Scale’s cognitive subscale (ADAS_cog), the Mini-Mental Status Examination (MMSE), and the Functional Activities Questionnaire (FAQ). The longitudinal relationships between cognitive decline and metabolic function as assessed using 18F-FDG PET are needed to address both the cognitive and the biologic progression of disease state in individual subjects. We conducted an exploratory investigation to evaluate longitudinal changes in brain glucose metabolism of individual subjects and their relationship to the subject’s changes of cognitive status. Methods We describe a method to determine correlations in 18F-FDG spatial distribution over time. This parameter is termed the regional 18F-FDG time correlation coefficient (rFTC). By using linear mixed-effects models, we determined the difference in the rFTC decline rate between controls and subjects at high risk of developing AD, such as individuals with MCI or the presence of apolipoprotein E (APOE)–ε4 allele. The association between each subject’s rFTC and performance on cognitive tests (ADAS_cog, MMSE, and FAQ) was determined with 2 different correlation methods. All subject data were downloaded from the Alzheimer Disease Neuroimaging Initiative. Results The rFTC values of controls remained fairly constant over time (−0.003 annual change; 95% confidence interval, −0.010– 0.004). In MCI patients, the rFTC declined faster than in controls by an additional annual change of −0.02 (95% confidence interval, −0.030 to −0.010). In MCI patients, the decline in rFTC was associated with cognitive decline (ADAS_cog, P = 0.011; FAQ, P = 0.0016; MMSE, P = 0.004). After a linear effect of time was accounted for, visit-to-visit changes in rFTC correlated with visit-to-visit changes in all 3 cognitive

  14. CSF Apo-E levels associate with cognitive decline and MRI changes

    PubMed Central

    Toledo, Jon B.; Da, Xiao; Weiner, Michael W.; Wolk, David A.; Xie, Sharon X.; Arnold, Steven E.; Davatzikos, Christos; Shaw, Leslie M.; Trojanowski, John Q.

    2014-01-01

    Apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for Alzheimer’s disease (AD) and it is thought to do so by modulating levels of the its product, apolipoprotein E (Apo-E), and regulating amyloid-β (Aβ) clearance. However, information on clinical and biomarker correlates of Apo-E proteins is scarce. We examined the relationship of cerebrospinal fluid (CSF) and plasma Apo-E protein levels, and APOE genotype to cognition and AD biomarker changes in 311 AD Neuroimaging Initiative (ADNI) subjects with CSF Apo-E measurements and 565 subjects with plasma Apo-E measurements. At baseline, higher CSF Apo-E levels were associated with higher total and phosphorylated CSF tau levels. CSF Apo-E levels were associated with longitudinal cognitive decline, MCI conversion to dementia, and grey matter atrophy rate in total tau/Aβ1–42 ratio and APOE genotype adjusted analyses. In analyses stratified by APOE genotype, our results were only significant in the group without the ε4 allele. Baseline CSF Apo-E levels did not predict longitudinal CSF Aβ or tau changes. Plasma Apo-E levels show a mild correlation with CSF Apo-E levels, but were not associated with longitudinal cognitive and MRI changes. Based on our analyses, we speculate that increased CSF Apo-E2 or -E3 levels might represent a protective response to injury in AD and may have neuroprotective effects by decreasing neuronal damage independent of tau and amyloid deposition in addition to its effects on amyloid clearance. PMID:24385135

  15. Memory Decline in Peri- and Post-menopausal Women: The Potential of Mind-Body Medicine to Improve Cognitive Performance.

    PubMed

    Sliwinski, Jim R; Johnson, Aimee K; Elkins, Gary R

    2014-01-01

    Cognitive decline is a frequent complaint during the menopause transition and among post-menopausal women. Changes in memory correspond with diminished estrogen production. Further, many peri- and post-menopausal women report sleep concerns, depression, and hot flashes, and these factors may contribute to cognitive decline. Hormone therapy can increase estrogen but is contraindicated for many women. Mind-body medicine has been shown to have beneficial effects on sleep, mood, and hot flashes, among post-menopausal women. Further, mind-body medicine holds potential in addressing symptoms of cognitive decline post-menopause. This study proposes an initial framework for how mind-body interventions may improve cognitive performance and inform future research seeking to identify the common and specific factors associated with mind-body medicine for addressing memory decline in peri- and post-menopausal women. It is our hope that this article will eventually lead to a more holistic and integrative approach to the treatment of cognitive deficits in peri- and post-menopausal women.

  16. Summary of the evidence on modifiable risk factors for cognitive decline and dementia: A population-based perspective.

    PubMed

    Baumgart, Matthew; Snyder, Heather M; Carrillo, Maria C; Fazio, Sam; Kim, Hye; Johns, Harry

    2015-06-01

    An estimated 47 million people worldwide are living with dementia in 2015, and this number is projected to triple by 2050. In the absence of a disease-modifying treatment or cure, reducing the risk of developing dementia takes on added importance. In 2014, the World Dementia Council (WDC) requested the Alzheimer's Association evaluate and report on the state of the evidence on modifiable risk factors for cognitive decline and dementia. This report is a summary of the Association's evaluation, which was presented at the October 2014 WDC meeting. The Association believes there is sufficient evidence to support the link between several modifiable risk factors and a reduced risk for cognitive decline, and sufficient evidence to suggest that some modifiable risk factors may be associated with reduced risk of dementia. Specifically, the Association believes there is sufficiently strong evidence, from a population-based perspective, to conclude that regular physical activity and management of cardiovascular risk factors (diabetes, obesity, smoking, and hypertension) reduce the risk of cognitive decline and may reduce the risk of dementia. The Association also believes there is sufficiently strong evidence to conclude that a healthy diet and lifelong learning/cognitive training may also reduce the risk of cognitive decline.

  17. Association between Exposure to the Chinese Famine in Different Stages of Early Life and Decline in Cognitive Functioning in Adulthood

    PubMed Central

    Wang, Chao; An, Yu; Yu, Huanling; Feng, Lingli; Liu, Quanri; Lu, Yanhui; Wang, Hui; Xiao, Rong

    2016-01-01

    Objective: To investigate whether exposure to the Chinese Famine in different life stages of early life is associated with cognitive functioning decline in adulthood. Methods: We recruited 1366 adults born between 1950 and 1964 and divided them into fetal-exposed, early childhood-exposed (1–3 years old during the famine), mid childhood-exposed (4–6 years old during the famine), late childhood-exposed (7–9 years old during the famine), and non-exposed groups. A selection of cognitive tests was administered to assess their cognitive performance. Association between malnutrition in different famine exposure periods and adult cognitive performance was estimated by multivariate logistic and multiple linear regression analyses. Results: There were significant differences in cognitive performance between subjects exposed to famine during different life stages. For the general cognitive tests, fetal-exposed period was associated with decreased scores of the Mini-Mental State Examination (MMSE), and late childhood-exposed with decreased scores of the Montreal Cognitive Assessment (MoCA). We also found exposure to famine during mid and late childhood was associated with worse performance on the Stroop color and word test. Conclusion: Famine exposure in utero and during childhood is associated with overall and specific cognitive decline, affecting selective attention and response inhibition particularly. PMID:27471454

  18. Religiosity is negatively associated with later-life intelligence, but not with age-related cognitive decline.

    PubMed

    Ritchie, Stuart J; Gow, Alan J; Deary, Ian J

    2014-09-01

    A well-replicated finding in the psychological literature is the negative correlation between religiosity and intelligence. However, several studies also conclude that one form of religiosity, church attendance, is protective against later-life cognitive decline. No effects of religious belief per se on cognitive decline have been found, potentially due to the restricted measures of belief used in previous studies. Here, we examined the associations between religiosity, intelligence, and cognitive change in a cohort of individuals (initial n = 550) with high-quality measures of religious belief taken at age 83 and multiple cognitive measures taken in childhood and at four waves between age 79 and 90. We found that religious belief, but not attendance, was negatively related to intelligence. The effect size was smaller than in previous studies of younger participants. Longitudinal analyses showed no effect of either religious belief or attendance on cognitive change either from childhood to old age, or across the ninth decade of life. We discuss differences between our cohort and those in previous studies - including in age and location - that may have led to our non-replication of the association between religious attendance and cognitive decline.

  19. Insulin-Like Growth Factor-1 but Not Insulin Predicts Cognitive Decline in Huntington’s Disease

    PubMed Central

    Youssov, Katia; Dolbeau, Guillaume; Cleret, Laurent; Bourhis, Marie-Laure; Azulay, Jean-Philippe; Krystkowiak, Pierre; Verny, Christophe; Morin, Françoise; Moutereau, Stéphane; Bachoud-Lévi, Anne-Catherine; Maison, Patrick

    2016-01-01

    Background Huntington's disease (HD) is one of several neurodegenerative disorders that have been associated with metabolic alterations. Changes in Insulin Growth Factor 1 (IGF-1) and/or insulin input to the brain may underlie or contribute to the progress of neurodegenerative processes. Here, we investigated the association over time between changes in plasma levels of IGF-1 and insulin and the cognitive decline in HD patients. Methods We conducted a multicentric cohort study in 156 patients with genetically documented HD aged from 22 to 80 years. Among them, 146 patients were assessed at least twice with a follow-up of 3.5 ± 1.8 years. We assessed their cognitive decline using the Unified Huntington’s Disease Rating Scale, and their IGF-1 and insulin plasmatic levels, at baseline and once a year during the follow-up. Associations were evaluated using a mixed-effect linear model. Results In the cross-sectional analysis at baseline, higher levels of IGF-1 and insulin were associated with lower cognitive scores and thus with a higher degree of cognitive impairment. In the longitudinal analysis, the decrease of all cognitive scores, except the Stroop interference, was associated with the IGF-1 level over time but not of insulin. Conclusions IGF-1 levels, unlike insulin, predict the decline of cognitive function in HD. PMID:27627435

  20. Gait dyspraxia as a clinical marker of cognitive decline in Down syndrome: A review of theory and proposed mechanisms.

    PubMed

    Anderson-Mooney, Amelia J; Schmitt, Frederick A; Head, Elizabeth; Lott, Ira T; Heilman, Kenneth M

    2016-04-01

    Down syndrome (DS) is the most common genetic cause of intellectual disability in children. With aging, DS is associated with an increased risk for Alzheimer's disease (AD). The development of AD neuropathology in individuals with DS can result in further disturbances in cognition and behavior and may significantly exacerbate caregiver burden. Early detection may allow for appropriate preparation by caregivers. Recent literature suggests that declines in gait may serve as an early marker of AD-related cognitive disorders; however, this relationship has not been examined in individuals with DS. The theory regarding gait dyspraxia and cognitive decline in the general population is reviewed, and potential applications to the population with individuals with DS are highlighted. Challenges and benefits in the line of inquiry are discussed. In particular, it appears that gait declines in aging individuals with DS may be associated with known declines in frontoparietal gray matter, development of AD-related pathology, and white matter losses in tracts critical to motor control. These changes are also potentially related to the cognitive and functional changes often observed during the same chronological period as gait declines in adults with DS. Gait declines may be an early marker of cognitive change, related to the development of underlying AD-related pathology, in individuals with DS. Future investigations in this area may provide insight into the clinical changes associated with development of AD pathology in both the population with DS and the general population, enhancing efforts for optimal patient and caregiver support and propelling investigations regarding safety/quality of life interventions and disease-modifying interventions. PMID:26930369

  1. Review of information and communication technology devices for monitoring functional and cognitive decline in Alzheimer's disease clinical trials.

    PubMed

    Pillai, Jagan A; Bonner-Jackson, Aaron

    2015-01-01

    Detecting and monitoring early cognitive impairment in Alzheimer's disease (AD) is a significant need in the field of AD therapeutics. Successful AD clinical trial designs have to overcome challenges related to the subtle nature of early cognitive changes. Continuous unobtrusive assessments using Information and Communication Technology (ICT) devices to capture markers of intra-individual change over time to assess cognitive and functional disability therefore offers significant benefits. We review the literature and provide an overview on randomized clinical trials in AD that use intelligent systems to monitor functional decline, as well as strengths, weaknesses, and future directions for the use of ICTs in a new generation of AD clinical trials. PMID:25708378

  2. Detection of Outliers Due to Participants’ Non-Adherence to Protocol in a Longitudinal Study of Cognitive Decline

    PubMed Central

    Shipley, Martin J.; Welch, Catherine; Kivimaki, Mika; Singh-Manoux, Archana

    2015-01-01

    Background Participants’ non adherence to protocol affects data quality. In longitudinal studies, this leads to outliers that can be present at the level of the population or the individual. The purpose of the present study is to elaborate a method for detection of outliers in a study of cognitive ageing. Methods In the Whitehall II study, data on a cognitive test battery have been collected in 1997-99, 2002-04, 2007-09 and 2012-13. Outliers at the 2012-13 wave were identified using a 4-step procedure: (1) identify cognitive tests with potential non-adherence to protocol, (2) choose a prediction model between a simple model with socio-demographic covariates and one that also includes health behaviours and health measures, (3) define an outlier using a studentized residual, and (4) study the impact of exclusion of outliers by estimating the effect of age and diabetes on cognitive decline. Results 5516 participants provided cognitive data in 2012-13. Comparisons of rates of annual decline over the first three and all four waves of data suggested outliers in three of the 5 tests. Mean residuals for the 2012-13 wave were larger for the basic compared to the more complex prediction model (all p<0.001), leading us to use the latter for the identification of outliers. Residuals greater than two standard deviation of residuals identified approximately 7% of observations as being outliers. Removal of these observations from the analyses showed that both age and diabetes had associations with cognitive decline similar to that observed with the first three waves of data; these associations were weaker or absent in non-cleaned data. Conclusions Identification of outliers is important as they obscure the effects of known risk factor and introduce bias in the estimates of cognitive decline. We showed that an informed approach, using the range of data collected in a longitudinal study, may be able to identify outliers. PMID:26161552

  3. Describing the Sequence of Cognitive Decline in Alzheimer’s Disease Patients: Results from an Observational Study

    PubMed Central

    Henneges, Carsten; Reed, Catherine; Chen, Yun-Fei; Dell’Agnello, Grazia; Lebrec, Jeremie

    2016-01-01

    Background: Improved understanding of the pattern of cognitive decline in Alzheimer’s disease (AD) would be useful to assist primary care physicians in explaining AD progression to patients and caregivers. Objective: To identify the sequence in which cognitive abilities decline in community-dwelling patients with AD. Methods: Baseline data were analyzed from 1,495 patients diagnosed with probable AD and a Mini-Mental State Examination (MMSE) score ≤ 26 enrolled in the 18-month observational GERAS study. Proportional odds logistic regression models were applied to model MMSE subscores (orientation, registration, attention and concentration, recall, language, and drawing) and the corresponding subscores of the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog), using MMSE total score as the index of disease progression. Probabilities of impairment start and full impairment were estimated at each MMSE total score level. Results: From the estimated probabilities for each MMSE subscore as a function of the MMSE total score, the first aspect of cognition to start being impaired was recall, followed by orientation in time, attention and concentration, orientation in place, language, drawing, and registration. For full impairment in subscores, the sequence was recall, drawing, attention and concentration, orientation in time, orientation in place, registration, and language. The sequence of cognitive decline for the corresponding ADAS-cog subscores was remarkably consistent with this pattern. Conclusion: The sequence of cognitive decline in AD can be visualized in an animation using probability estimates for key aspects of cognition. This might be useful for clinicians to set expectations on disease progression for patients and caregivers. PMID:27079700

  4. Longitudinal cerebral diffusion changes reflect progressive decline of language and cognition.

    PubMed

    Frings, Lars; Dressel, Katharina; Abel, Stefanie; Mader, Irina; Glauche, Volkmar; Weiller, Cornelius; Hüll, Michael

    2013-12-30

    Language deficits are regularly found in cortical neurodegenerative diseases. The progression of language deficits shows a considerable inter-individual variability even within one diagnostic group. We aimed at detecting patterns of altered diffusion as well as atrophy of cerebral gray and white matter which underlie ongoing language-related deterioration in patients with cortical neurodegenerative diseases. Diffusion tensor imaging and T1-weighted MRI data of 26 patients with clinically diagnosed neurodegenerative disorders were acquired at baseline and 14 months later in this prospective study. Language functions were assessed with a confrontation naming test and the Token Test. Diffusion and voxel-based morphometric measures were calculated and correlates of language performance were evaluated. Across all patients, the naming impairment was related to diffusion (false discovery rate-corrected P<0.05 at baseline) and atrophy abnormalities (family-wise error (FWE)-corrected P<0.05 at follow-up) primarily in the left temporal lobe. Deficits in the Token Test were correlated with predominantly left frontal MRI abnormalities (FWE-corrected P<0.05). The Token Test performance decline over 14 months was accompanied by further increasing abnormalities in the frontal cortex, left caudate, parietal cortex (all FWE-corrected P<0.05), and posterior callosal body (FWE-corrected P=0.055). Both diffusion and structural MRI were apt to elucidate the underpinnings of inter-individual differences in language-related deficits and to detect longitudinal changes that accompanied ongoing cognition and language decline, with mean diffusivity appearing most sensitive. This might indicate the usefulness of diffusion measures as markers for successful intervention in therapy studies. PMID:24144508

  5. Cognitive decline is associated with reduced surface GluR1 expression in the hippocampus of aged rats.

    PubMed

    Yang, Yuan-Jian; Chen, Hai-Bo; Wei, Bo; Wang, Wei; Zhou, Ping-Liang; Zhan, Jin-Qiong; Hu, Mao-Rong; Yan, Kun; Hu, Bin; Yu, Bin

    2015-03-30

    Individual differences in cognitive aging exist in humans and in rodent populations, yet the underlying mechanisms remain largely unclear. Activity-dependent delivery of GluR1-containing AMPA receptor (AMPARs) plays an essential role in hippocampal synaptic plasticity, learning and memory. We hypothesize that alterations of surface GluR1 expression in the hippocampus might correlate with age-related cognitive decline. To test this hypothesis, the present study evaluated the cognitive function of young adult and aged rats using Morris water maze. After the behavioral test, the surface expression of GluR1 protein in hippocampal CA1 region of rats was determined using Western blotting. The results showed that the surface expression of GluR1 in the hippocampus of aged rats that are cognitively impaired was much lower than that of young adults and aged rats with preserved cognitive abilities. The phosphorylation levels of GluR1 at Ser845 and Ser831 sites, which promote the synaptic delivery of GluR1, were also selectively decreased in the hippocampus of aged-impaired rats. Correlation analysis reveals that greater decrease in surface GluR1 expression was associated with worse behavioral performance. These results suggest that reduced surface GluR1 expression may contribute to cognitive decline that occurs in normal aging, and different pattern of surface GluR1 expression might be responsible for the individual differences in cognitive aging. PMID:25697598

  6. Phytoestrogen consumption and risk for cognitive decline and dementia: With consideration of thyroid status and other possible mediators.

    PubMed

    Soni, M; White, L R; Kridawati, A; Bandelow, S; Hogervorst, E

    2016-06-01

    It is predicted that around 20% of the worlds population will be age 60 or above by 2050. Prevalence of cognitive decline and dementia is high in older adults and modifiable dietary factors may be able to reduce risk for these conditions. Phytoestrogens are bioactive plant chemicals found in soy, which have a similarity in structure to natural estradiol (the most abundant circulating estrogen). This structural likeness enables phytoestrogens to interact with estrogen receptors in the brain, potentially affecting cognition. However, findings in this domain are largely inconsistent, with approximately 50% of studies showing positive effects of phytoestrogens on cognition and the other half resulting in null/negative findings. This paper provides an updated review of the relationship between consumption of phytoestrogens and risk for cognitive decline and/or dementia. In particular, possible mediators were identified to explain discrepant findings and for consideration in future research. A case can be made for a link between phytoestrogen consumption, thyroid status and cognition in older age, although current findings in this area are very limited. Evidence suggests that inter-individual variants that can affect phytoestrogen bioavailability (and thus cognitive outcome) include age and ability to breakdown ingested phytoestrogens into their bioactive metabolites. Factors of the study design that must be taken into account are type of soy product, dosage, frequency of dietary intake and type of cognitive test used. Guidelines regarding optimal phytoestrogen dosage and frequency of intake are yet to be determined. PMID:26535810

  7. Phytoestrogen consumption and risk for cognitive decline and dementia: With consideration of thyroid status and other possible mediators.

    PubMed

    Soni, M; White, L R; Kridawati, A; Bandelow, S; Hogervorst, E

    2016-06-01

    It is predicted that around 20% of the worlds population will be age 60 or above by 2050. Prevalence of cognitive decline and dementia is high in older adults and modifiable dietary factors may be able to reduce risk for these conditions. Phytoestrogens are bioactive plant chemicals found in soy, which have a similarity in structure to natural estradiol (the most abundant circulating estrogen). This structural likeness enables phytoestrogens to interact with estrogen receptors in the brain, potentially affecting cognition. However, findings in this domain are largely inconsistent, with approximately 50% of studies showing positive effects of phytoestrogens on cognition and the other half resulting in null/negative findings. This paper provides an updated review of the relationship between consumption of phytoestrogens and risk for cognitive decline and/or dementia. In particular, possible mediators were identified to explain discrepant findings and for consideration in future research. A case can be made for a link between phytoestrogen consumption, thyroid status and cognition in older age, although current findings in this area are very limited. Evidence suggests that inter-individual variants that can affect phytoestrogen bioavailability (and thus cognitive outcome) include age and ability to breakdown ingested phytoestrogens into their bioactive metabolites. Factors of the study design that must be taken into account are type of soy product, dosage, frequency of dietary intake and type of cognitive test used. Guidelines regarding optimal phytoestrogen dosage and frequency of intake are yet to be determined.

  8. Needs in Nursing Homes and Their Relation with Cognitive and Functional Decline, Behavioral and Psychological Symptoms

    PubMed Central

    Ferreira, Ana Rita; Dias, Cláudia Camila; Fernandes, Lia

    2016-01-01

    Unmet needs are becoming acknowledged as better predictors of the worst prognostic outcomes than common measures of functional or cognitive decline. Their accurate assessment is a pivotal component of effective care delivery, particularly in institutionalized care where little is known about the needs of its residents, many of whom suffer from dementia and show complex needs. The aims of this study were to describe the needs of an institutionalized sample and to analyze its relationship with demographic and clinical characteristics. A cross-sectional study was conducted with a sample from three nursing homes. All residents were assessed with a comprehensive protocol that included Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS-15), Neuropsychiatric Inventory (NPI) and Adults and Older Adults Functional Inventory (IAFAI). To identify needs, the Camberwell Assessment of Need for the Elderly (CANE) was used. The final sample included 175 residents with a mean age of 81 standard deviation (SD = 10) years. From these, 58.7% presented cognitive deficit (MMSE) and 45.2% depressive symptoms (GDS). Statistically significant negative correlations were found between MMSE score and met (rs = −0.425), unmet (rs = −0.369) and global needs (rs = −0.565). Data also showed significant correlations between depressive symptoms and unmet (rs = 0.683) and global needs (rs = 0.407), and between behavioral and psychological symptoms (BPSD) and unmet (rs = 0.181) and global needs (rs = 0.254). Finally, significant correlations between functional impairment and met (rs = 0.642), unmet (rs = 0.505) and global needs (rs = 0.796) were also found. These results suggest that in this sample, more unmet needs are associated with the worst outcomes measured. This is consistent with previous findings and seems to demonstrate that the needs of those institutionalized elderly remain under-diagnosed and untreated. PMID:27148044

  9. Is It Possible to Delay or Prevent Age-Related Cognitive Decline?

    PubMed

    Michel, Jean-Pierre

    2016-09-01

    Already in the 90s, Khachaturian stated that postponing dementia onset by five years would decrease the prevalence of the late onset dementia by 50%. After two decades of lack of success in dementia drug discovery and development, and knowing that worldwide, currently 36 million patients have been diagnosed with Alzheimer's disease, a number that will double by 2030 and triple by 2050, the World Health Organization and the Alzheimer's Disease International declared that prevention of cognitive decline was a 'public health priority.' Numerous longitudinal studies and meta-analyses were conducted to analyze the risk and protective factors for dementia. Among the 93 identified risk factors, seven major modifiable ones should be considered: low education, sedentary lifestyle, midlife obesity, midlife smoking, hypertension, diabetes, and midlife depression. Three other important modifiable risk factors should also be added to this list: midlife hypercholesterolemia, late life atrial fibrillation, and chronic kidney disease. After their identification, numerous authors attempted to establish dementia risk scores; however, the proposed values were not convincing. Identifying the possible interventions, able to either postpone or delay dementia has been an important challenge. Observational studies focused on a single life-style intervention increased the global optimism concerning these possibilities. However, a recent extensive literature review of the randomized control trials (RCTs) conducted before 2014 yielded negative results. The first results of RCTs of multimodal interventions (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, Multidomain Alzheimer Prevention Study, and Prediva) brought more optimism. Lastly, interventions targeting compounds of beta amyloid started in 2012 and no results have yet been published.

  10. Is It Possible to Delay or Prevent Age-Related Cognitive Decline?

    PubMed Central

    2016-01-01

    Already in the 90s, Khachaturian stated that postponing dementia onset by five years would decrease the prevalence of the late onset dementia by 50%. After two decades of lack of success in dementia drug discovery and development, and knowing that worldwide, currently 36 million patients have been diagnosed with Alzheimer's disease, a number that will double by 2030 and triple by 2050, the World Health Organization and the Alzheimer's Disease International declared that prevention of cognitive decline was a 'public health priority.' Numerous longitudinal studies and meta-analyses were conducted to analyze the risk and protective factors for dementia. Among the 93 identified risk factors, seven major modifiable ones should be considered: low education, sedentary lifestyle, midlife obesity, midlife smoking, hypertension, diabetes, and midlife depression. Three other important modifiable risk factors should also be added to this list: midlife hypercholesterolemia, late life atrial fibrillation, and chronic kidney disease. After their identification, numerous authors attempted to establish dementia risk scores; however, the proposed values were not convincing. Identifying the possible interventions, able to either postpone or delay dementia has been an important challenge. Observational studies focused on a single life-style intervention increased the global optimism concerning these possibilities. However, a recent extensive literature review of the randomized control trials (RCTs) conducted before 2014 yielded negative results. The first results of RCTs of multimodal interventions (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, Multidomain Alzheimer Prevention Study, and Prediva) brought more optimism. Lastly, interventions targeting compounds of beta amyloid started in 2012 and no results have yet been published. PMID:27688858

  11. Is It Possible to Delay or Prevent Age-Related Cognitive Decline?

    PubMed

    Michel, Jean-Pierre

    2016-09-01

    Already in the 90s, Khachaturian stated that postponing dementia onset by five years would decrease the prevalence of the late onset dementia by 50%. After two decades of lack of success in dementia drug discovery and development, and knowing that worldwide, currently 36 million patients have been diagnosed with Alzheimer's disease, a number that will double by 2030 and triple by 2050, the World Health Organization and the Alzheimer's Disease International declared that prevention of cognitive decline was a 'public health priority.' Numerous longitudinal studies and meta-analyses were conducted to analyze the risk and protective factors for dementia. Among the 93 identified risk factors, seven major modifiable ones should be considered: low education, sedentary lifestyle, midlife obesity, midlife smoking, hypertension, diabetes, and midlife depression. Three other important modifiable risk factors should also be added to this list: midlife hypercholesterolemia, late life atrial fibrillation, and chronic kidney disease. After their identification, numerous authors attempted to establish dementia risk scores; however, the proposed values were not convincing. Identifying the possible interventions, able to either postpone or delay dementia has been an important challenge. Observational studies focused on a single life-style intervention increased the global optimism concerning these possibilities. However, a recent extensive literature review of the randomized control trials (RCTs) conducted before 2014 yielded negative results. The first results of RCTs of multimodal interventions (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, Multidomain Alzheimer Prevention Study, and Prediva) brought more optimism. Lastly, interventions targeting compounds of beta amyloid started in 2012 and no results have yet been published. PMID:27688858

  12. Is It Possible to Delay or Prevent Age-Related Cognitive Decline?

    PubMed Central

    2016-01-01

    Already in the 90s, Khachaturian stated that postponing dementia onset by five years would decrease the prevalence of the late onset dementia by 50%. After two decades of lack of success in dementia drug discovery and development, and knowing that worldwide, currently 36 million patients have been diagnosed with Alzheimer's disease, a number that will double by 2030 and triple by 2050, the World Health Organization and the Alzheimer's Disease International declared that prevention of cognitive decline was a 'public health priority.' Numerous longitudinal studies and meta-analyses were conducted to analyze the risk and protective factors for dementia. Among the 93 identified risk factors, seven major modifiable ones should be considered: low education, sedentary lifestyle, midlife obesity, midlife smoking, hypertension, diabetes, and midlife depression. Three other important modifiable risk factors should also be added to this list: midlife hypercholesterolemia, late life atrial fibrillation, and chronic kidney disease. After their identification, numerous authors attempted to establish dementia risk scores; however, the proposed values were not convincing. Identifying the possible interventions, able to either postpone or delay dementia has been an important challenge. Observational studies focused on a single life-style intervention increased the global optimism concerning these possibilities. However, a recent extensive literature review of the randomized control trials (RCTs) conducted before 2014 yielded negative results. The first results of RCTs of multimodal interventions (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, Multidomain Alzheimer Prevention Study, and Prediva) brought more optimism. Lastly, interventions targeting compounds of beta amyloid started in 2012 and no results have yet been published.

  13. Processing Speed, Inhibitory Control, and Working Memory: Three Important Factors to Account for Age-Related Cognitive Decline

    ERIC Educational Resources Information Center

    Pereiro Rozas, Arturo X.; Juncos-Rabadan, Onesimo; Gonzalez, Maria Soledad Rodriguez

    2008-01-01

    Processing speed, inhibitory control and working memory have been identified as the main possible culprits of age-related cognitive decline. This article describes a study of their interrelationships and dependence on age, including exploration of whether any of them mediates between age and the others. We carried out a LISREL analysis of the…

  14. A[Beta] Deposits in Older Non-Demented Individuals with Cognitive Decline Are Indicative of Preclinical Alzheimer's Disease

    ERIC Educational Resources Information Center

    Villemagne, V. L.; Pike, K. E.; Darby, D.; Maruff, P.; Savage, G.; Ng, S.; Ackermann, U.; Cowie, T. F.; Currie, J.; Chan, S. G.; Jones, G.; Tochon-Danguy, H.; O'Keefe, G.; Masters, C. L.; Rowe, C. C.

    2008-01-01

    Approximately 30% of healthy persons aged over 75 years show A[beta] deposition at autopsy. It is postulated that this represents preclinical Alzheimer's disease (AD). We evaluated the relationship between A[beta] burden as assessed by PiB PET and cognitive decline in a well-characterized, non-demented, elderly cohort. PiB PET studies and…

  15. Omega-3 fatty acids and risk of cognitive decline in the elderly: a meta-analysis of randomized controlled trials.

    PubMed

    Zhang, Xiao-Wei; Hou, Wen-Shang; Li, Min; Tang, Zhen-Yu

    2016-02-01

    Evidence has demonstrated that omega-3 fatty acids intake may be associated with age-related cognitive decline. However, randomized controlled trials (RCTs) have drawn inconsistent conclusions. We performed a meta-analysis to assess the association between omega-3 fatty acids and risk of cognitive decline in the elderly. A strategic literature search of PubMed, EMBASE, and Cochrane Library (updated to December 2014) was performed. We retrieved six randomized controlled studies as eligible for our meta-analysis. Among these six studies, the duration time ranged from 3 to 40 months. The dose of omega-3 fatty acids (DHA + EPA) ranged from 400 to 1800 mg. The result of our meta-analysis expressed that omega-3 fatty acids statistically decrease the rate of cognitive decline in MMSE score (WMD = 0.15, [0.05, 0.25]; p = 0.003). In conclusion, our meta-analysis indicated that omega-3 fatty acids may help to prevent cognitive decline in the elderly.

  16. Longitudinal telomere length shortening and cognitive and physical decline in later life: The Lothian Birth Cohorts 1936 and 1921

    PubMed Central

    Harris, Sarah E.; Marioni, Riccardo E.; Martin-Ruiz, Carmen; Pattie, Alison; Gow, Alan J.; Cox, Simon R.; Corley, Janie; von Zglinicki, Thomas; Starr, John M.; Deary, Ian J.

    2016-01-01

    Telomere length is hypothesised to be a biological marker of both cognitive and physical ageing. Here we measure telomere length, and cognitive and physical abilities at mean ages 70, 73 and 76 years in the Lothian Birth Cohort 1936 (LBC1936), and at mean ages 79, 87, 90 and 92 years in the Lothian Birth Cohort 1921 (LBC1921). We investigate whether telomere length change predicts change in cognitive and physical abilities. In LBC1936 telomere length decreased by an average of 65 base pairs per year and in LBC1921 by 69 base pairs per year. However, change in telomere length did not predict change in cognitive or physical abilities. This study shows that, although cognitive ability, walking speed, lung function and grip strength all decline with age, they do so independently of telomere length shortening. PMID:26876762

  17. Longitudinal telomere length shortening and cognitive and physical decline in later life: The Lothian Birth Cohorts 1936 and 1921.

    PubMed

    Harris, Sarah E; Marioni, Riccardo E; Martin-Ruiz, Carmen; Pattie, Alison; Gow, Alan J; Cox, Simon R; Corley, Janie; von Zglinicki, Thomas; Starr, John M; Deary, Ian J

    2016-03-01

    Telomere length is hypothesised to be a biological marker of both cognitive and physical ageing. Here we measure telomere length, and cognitive and physical abilities at mean ages 70, 73 and 76 years in the Lothian Birth Cohort 1936 (LBC1936), and at mean ages 79, 87, 90 and 92 years in the Lothian Birth Cohort 1921 (LBC1921). We investigate whether telomere length change predicts change in cognitive and physical abilities. In LBC1936 telomere length decreased by an average of 65 base pairs per year and in LBC1921 by 69 base pairs per year. However, change in telomere length did not predict change in cognitive or physical abilities. This study shows that, although cognitive ability, walking speed, lung function and grip strength all decline with age, they do so independently of telomere length shortening.

  18. Impact of the hypothalamic-pituitary-adrenal/gonadal axes on trajectory of age-related cognitive decline.

    PubMed

    Conrad, Cheryl D; Bimonte-Nelson, Heather A

    2010-01-01

    Life expectancies have increased substantially in the last century, dramatically amplifying the proportion of individuals who will reach old age. As individuals age, cognitive ability declines, although the rate of decline differs amongst the forms of memory domains and for different individuals. Memory domains especially impacted by aging are declarative and spatial memories. The hippocampus facilitates the formation of declarative and spatial memories. Notably, the hippocampus is particularly vulnerable to aging. Genetic predisposition and lifetime experiences and exposures contribute to the aging process, brain changes and subsequent cognitive outcomes. In this review, two factors to which an individual is exposed, the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-gonadal (HPG) axis, will be considered regarding the impact of age on hippocampal-dependent function. Spatial memory can be affected by cumulative exposure to chronic stress via glucocorticoids, released from the HPA axis, and from gonadal steroids (estrogens, progesterone and androgens) and gonadotrophins, released from the HPG axis. Additionally, this review will discuss how these hormones impact age-related hippocampal function. We hypothesize that lifetime experiences and exposure to these hormones contribute to the cognitive makeup of the aged individual, and contribute to the heterogeneous aged population that includes individuals with cognitive abilities as astute as their younger counterparts, as well as individuals with severe cognitive decline or neurodegenerative disease.

  19. Amyloid burden, neuronal function, and cognitive decline in middle-aged adults at risk for Alzheimer's disease.

    PubMed

    Okonkwo, Ozioma C; Oh, Jennifer M; Koscik, Rebecca; Jonaitis, Erin; Cleary, Caitlin A; Dowling, N Maritza; Bendlin, Barbara B; Larue, Asenath; Hermann, Bruce P; Barnhart, Todd E; Murali, Dhanabalan; Rowley, Howard A; Carlsson, Cynthia M; Gallagher, Catherine L; Asthana, Sanjay; Sager, Mark A; Christian, Brad T; Johnson, Sterling C

    2014-04-01

    The relative influence of amyloid burden, neuronal structure and function, and prior cognitive performance on prospective memory decline among asymptomatic late middle-aged individuals at risk for Alzheimer's disease (AD) is currently unknown. We investigated this using longitudinal cognitive data from 122 middle-aged adults (21 "Decliners" and 101 "Stables") enrolled in the Wisconsin Registry for Alzheimer's Prevention who underwent multimodality neuroimaging [11C-Pittsburgh Compound B (PiB), 18F-fluorodeoxyglucose (FDG), and structural/functional magnetic resonance imaging (fMRI)] 5.7 ± 1.4 years (range = 2.9-8.9) after their baseline cognitive assessment. Covariate-adjusted regression analyses revealed that the only imaging measure that significantly distinguished Decliners from Stables (p = .027) was a Neuronal Function composite derived from FDG and fMRI. In contrast, several cognitive measures, especially those that tap episodic memory, significantly distinguished the groups (p's<.05). Complementary receiver operating characteristic curve analyses identified the Brief Visuospatial Memory Test-Revised (BVMT-R) Total (.82 ± .05, p < .001), the BVMT-R Delayed Recall (.73 ± .06, p = .001), and the Reading subtest from the Wide-Range Achievement Test-III (.72 ± .06, p = .002) as the top three measures that best discriminated the groups. These findings suggest that early memory test performance might serve a more clinically pivotal role in forecasting future cognitive course than is currently presumed.

  20. High-mobility Group Box 1 Protein Initiates Postoperative Cognitive Decline by Engaging Bone Marrow-derived Macrophages

    PubMed Central

    Vacas, Susana; Degos, Vincent; Tracey, Kevin J.; Maze, Mervyn

    2014-01-01

    Background Aseptic trauma engages the innate immune response to trigger a neuroinflammatory reaction that results in postoperative cognitive decline. We sought to determine whether high-mobility group box 1 protein (HMGB1), an ubiquitous nucleosomal protein, initiates this process through activation and trafficking of circulating bone marrow-derived macrophages to the brain. Methods The effects of HMGB1 on memory (using trace fear conditioning) were tested in adult C57BL/6J male mice; separate cohorts were tested after bone marrow-derived macrophages were depleted by clodrolip. The effect of anti-HMGB1 neutralizing antibody on the inflammatory and behavioral responses to tibial surgery were investigated. Results A single injection of HMGB1 caused memory decline, as evidenced by a decrease in freezing time (52 ± 11% vs. 39 ± 5%; n = 16-17); memory decline was prevented when bone marrow-derived macrophages were depleted (39 ± 5% vs. 50 ± 9%; n = 17). Disabling HMGB1 with a blocking monoclonal antibody, before surgery, reduced postoperative memory decline (52 ± 11% vs. 29 ± 5%, n = 15-16); also, hippocampal expression of monocyte chemotactic protein-1 (MCP-1) was prevented by the neutralizing antibody (n = 6). Neither the systemic nor the hippocampal inflammatory responses to surgery occurred in mice pre-treated with anti-HMGB1 neutralizing antibody (n = 6). Discussion Postoperative neuroinflammation and cognitive decline can be prevented by abrogating the effects of HMGB1. Following the earlier characterization of the resolution of surgery-induced memory decline, the mechanisms of its initiation are now described. Together, these data may be used to preoperatively test the risk to surgical patients for the development of exaggerated and prolonged postoperative memory decline that is reflected in delirium and postoperative cognitive dysfunction, respectively. PMID:24162463

  1. Hearing, Cognition, and Healthy Aging: Social and Public Health Implications of the Links between Age-Related Declines in Hearing and Cognition

    PubMed Central

    Pichora-Fuller, M. Kathleen; Mick, Paul; Reed, Marilyn

    2015-01-01

    Sensory input provides the signals used by the brain when listeners understand speech and participate in social activities with other people in a range of everyday situations. When sensory inputs are diminished, there can be short-term consequences to brain functioning, and long-term deprivation can affect brain neuroplasticity. Indeed, the association between hearing loss and cognitive declines in older adults is supported by experimental and epidemiologic evidence, although the causal mechanisms remain unknown. These interactions of auditory and cognitive aging play out in the challenges confronted by people with age-related hearing problems when understanding speech and engaging in social interactions. In the present article, we use the World Health Organization's International Classification of Functioning, Disability and Health and the Selective Optimization with Compensation models to highlight the importance of adopting a healthy aging perspective that focuses on facilitating active social participation by older adults. First, we examine epidemiologic evidence linking ARHL to cognitive declines and other health issues. Next, we examine how social factors influence and are influenced by auditory and cognitive aging and if they may provide a possible explanation for the association between ARHL and cognitive decline. Finally, we outline how audiologists could reposition hearing health care within the broader context of healthy aging. PMID:27516713

  2. Hearing, Cognition, and Healthy Aging: Social and Public Health Implications of the Links between Age-Related Declines in Hearing and Cognition.

    PubMed

    Pichora-Fuller, M Kathleen; Mick, Paul; Reed, Marilyn

    2015-08-01

    Sensory input provides the signals used by the brain when listeners understand speech and participate in social activities with other people in a range of everyday situations. When sensory inputs are diminished, there can be short-term consequences to brain functioning, and long-term deprivation can affect brain neuroplasticity. Indeed, the association between hearing loss and cognitive declines in older adults is supported by experimental and epidemiologic evidence, although the causal mechanisms remain unknown. These interactions of auditory and cognitive aging play out in the challenges confronted by people with age-related hearing problems when understanding speech and engaging in social interactions. In the present article, we use the World Health Organization's International Classification of Functioning, Disability and Health and the Selective Optimization with Compensation models to highlight the importance of adopting a healthy aging perspective that focuses on facilitating active social participation by older adults. First, we examine epidemiologic evidence linking ARHL to cognitive declines and other health issues. Next, we examine how social factors influence and are influenced by auditory and cognitive aging and if they may provide a possible explanation for the association between ARHL and cognitive decline. Finally, we outline how audiologists could reposition hearing health care within the broader context of healthy aging. PMID:27516713

  3. Hearing, Cognition, and Healthy Aging: Social and Public Health Implications of the Links between Age-Related Declines in Hearing and Cognition.

    PubMed

    Pichora-Fuller, M Kathleen; Mick, Paul; Reed, Marilyn

    2015-08-01

    Sensory input provides the signals used by the brain when listeners understand speech and participate in social activities with other people in a range of everyday situations. When sensory inputs are diminished, there can be short-term consequences to brain functioning, and long-term deprivation can affect brain neuroplasticity. Indeed, the association between hearing loss and cognitive declines in older adults is supported by experimental and epidemiologic evidence, although the causal mechanisms remain unknown. These interactions of auditory and cognitive aging play out in the challenges confronted by people with age-related hearing problems when understanding speech and engaging in social interactions. In the present article, we use the World Health Organization's International Classification of Functioning, Disability and Health and the Selective Optimization with Compensation models to highlight the importance of adopting a healthy aging perspective that focuses on facilitating active social participation by older adults. First, we examine epidemiologic evidence linking ARHL to cognitive declines and other health issues. Next, we examine how social factors influence and are influenced by auditory and cognitive aging and if they may provide a possible explanation for the association between ARHL and cognitive decline. Finally, we outline how audiologists could reposition hearing health care within the broader context of healthy aging.

  4. Loss in Executive Functioning Best Explains Changes in Pain Responsiveness in Patients with Dementia-Related Cognitive Decline

    PubMed Central

    Kunz, Miriam; Mylius, Veit; Schepelmann, Karsten; Lautenbacher, Stefan

    2015-01-01

    There is ample evidence that dementia changes the processing of pain. However, it is not known whether this change in pain processing is related to the general decline in cognitive functioning or whether it may be related to specific domains of cognitive functioning. With the present study we tried to answer this question. We assessed different cognitive domains (orientation, memory, abstract thinking/executive function, aphasia and apraxia, and information processing speed) in 70 older patients with cognitive impairment (mild cognitive impairment up to moderate degrees of dementia). Pain responsiveness was assessed by measuring the nociceptive flexion reflex (NFR) threshold and facial responses to noxious electrical stimulation. Using regression analyses, we assessed which domain of cognitive functioning best predicted variance in pain responsiveness. Variance in pain responsiveness (NFR and facial expressions) was best explained by those items assessing executive functioning even when controlling for overall cognitive performance and memory functioning. The close association between executive functioning and pain responsiveness suggests that dementia-related neurodegeneration in prefrontal areas might result not only in reduced executive functioning but also in a loss of pain inhibitory potency, rendering the patient more vulnerable to pain. Our findings also suggest that pain assessment in dementia should be regularly completed by tests of cognitive functions. PMID:26788018

  5. Loss in Executive Functioning Best Explains Changes in Pain Responsiveness in Patients with Dementia-Related Cognitive Decline.

    PubMed

    Kunz, Miriam; Mylius, Veit; Schepelmann, Karsten; Lautenbacher, Stefan

    2015-01-01

    There is ample evidence that dementia changes the processing of pain. However, it is not known whether this change in pain processing is related to the general decline in cognitive functioning or whether it may be related to specific domains of cognitive functioning. With the present study we tried to answer this question. We assessed different cognitive domains (orientation, memory, abstract thinking/executive function, aphasia and apraxia, and information processing speed) in 70 older patients with cognitive impairment (mild cognitive impairment up to moderate degrees of dementia). Pain responsiveness was assessed by measuring the nociceptive flexion reflex (NFR) threshold and facial responses to noxious electrical stimulation. Using regression analyses, we assessed which domain of cognitive functioning best predicted variance in pain responsiveness. Variance in pain responsiveness (NFR and facial expressions) was best explained by those items assessing executive functioning even when controlling for overall cognitive performance and memory functioning. The close association between executive functioning and pain responsiveness suggests that dementia-related neurodegeneration in prefrontal areas might result not only in reduced executive functioning but also in a loss of pain inhibitory potency, rendering the patient more vulnerable to pain. Our findings also suggest that pain assessment in dementia should be regularly completed by tests of cognitive functions. PMID:26788018

  6. A call for comparative effectiveness research to learn whether routine clinical care decisions can protect from dementia and cognitive decline.

    PubMed

    Dacks, Penny A; Armstrong, Joshua J; Brannan, Stephen K; Carman, Aaron J; Green, Allan M; Kirkman, M Sue; Krakoff, Lawrence R; Kuller, Lewis H; Launer, Lenore J; Lovestone, Simon; Merikle, Elizabeth; Neumann, Peter J; Rockwood, Kenneth; Shineman, Diana W; Stefanacci, Richard G; Velentgas, Priscilla; Viswanathan, Anand; Whitmer, Rachel A; Williamson, Jeff D; Fillit, Howard M

    2016-01-01

    Common diseases like diabetes, hypertension, and atrial fibrillation are probable risk factors for dementia, suggesting that their treatments may influence the risk and rate of cognitive and functional decline. Moreover, specific therapies and medications may affect long-term brain health through mechanisms that are independent of their primary indication. While surgery, benzodiazepines, and anti-cholinergic drugs may accelerate decline or even raise the risk of dementia, other medications act directly on the brain to potentially slow the pathology that underlies Alzheimer's and other dementia. In other words, the functional and cognitive decline in vulnerable patients may be influenced by the choice of treatments for other medical conditions. Despite the importance of these questions, very little research is available. The Alzheimer's Drug Discovery Foundation convened an advisory panel to discuss the existing evidence and to recommend strategies to accelerate the development of comparative effectiveness research on how choices in the clinical care of common chronic diseases may protect from cognitive decline and dementia.

  7. A call for comparative effectiveness research to learn whether routine clinical care decisions can protect from dementia and cognitive decline.

    PubMed

    Dacks, Penny A; Armstrong, Joshua J; Brannan, Stephen K; Carman, Aaron J; Green, Allan M; Kirkman, M Sue; Krakoff, Lawrence R; Kuller, Lewis H; Launer, Lenore J; Lovestone, Simon; Merikle, Elizabeth; Neumann, Peter J; Rockwood, Kenneth; Shineman, Diana W; Stefanacci, Richard G; Velentgas, Priscilla; Viswanathan, Anand; Whitmer, Rachel A; Williamson, Jeff D; Fillit, Howard M

    2016-01-01

    Common diseases like diabetes, hypertension, and atrial fibrillation are probable risk factors for dementia, suggesting that their treatments may influence the risk and rate of cognitive and functional decline. Moreover, specific therapies and medications may affect long-term brain health through mechanisms that are independent of their primary indication. While surgery, benzodiazepines, and anti-cholinergic drugs may accelerate decline or even raise the risk of dementia, other medications act directly on the brain to potentially slow the pathology that underlies Alzheimer's and other dementia. In other words, the functional and cognitive decline in vulnerable patients may be influenced by the choice of treatments for other medical conditions. Despite the importance of these questions, very little research is available. The Alzheimer's Drug Discovery Foundation convened an advisory panel to discuss the existing evidence and to recommend strategies to accelerate the development of comparative effectiveness research on how choices in the clinical care of common chronic diseases may protect from cognitive decline and dementia. PMID:27543171

  8. Pulse Pressure Is Associated With Early Brain Atrophy and Cognitive Decline: Modifying Effects of APOE-ε4.

    PubMed

    Nation, Daniel A; Preis, Sarah R; Beiser, Alexa; Bangen, Katherine J; Delano-Wood, Lisa; Lamar, Melissa; Libon, David J; Seshadri, Sudha; Wolf, Philip A; Au, Rhoda

    2016-01-01

    We investigated whether midlife pulse pressure is associated with brain atrophy and cognitive decline, and whether the association was modified by apolipoprotein-E ε4 (APOE-ε4) and hypertension. Participants (549 stroke-free and dementia-free Framingham Offspring Cohort Study participants, age range=55.0 to 64.9 y) underwent baseline neuropsychological and magnetic resonance imaging (subset, n=454) evaluations with 5- to 7-year follow-up. Regression analyses investigated associations between baseline pulse pressure (systolic-diastolic pressure) and cognition, total cerebral volume and temporal horn ventricular volume (as an index of smaller hippocampal volume) at follow-up, and longitudinal change in these measures. Interactions with APOE-ε4 and hypertension were assessed. Covariates included age, sex, education, assessment interval, and interim stroke. In the total sample, baseline pulse pressure was associated with worse executive ability, lower total cerebral volume, and greater temporal horn ventricular volume 5 to 7 years later, and longitudinal decline in executive ability and increase in temporal horn ventricular volume. Among APOE-ε4 carriers only, baseline pulse pressure was associated with longitudinal decline in visuospatial organization. Findings indicate arterial stiffening, indexed by pulse pressure, may play a role in early cognitive decline and brain atrophy in mid to late life, particularly among APOE-ε4 carriers. PMID:27556935

  9. Vascular Risk as a Predictor of Cognitive Decline in a Cohort of Elderly Patients with Mild to Moderate Dementia

    PubMed Central

    Curiati, Pedro K.; Magaldi, Regina M.; Suemoto, Claudia K.; Bottino, Cassio M.C.; Nitrini, Ricardo; Farfel, José Marcelo; Jacob-Filho, Wilson

    2014-01-01

    Background/Aims The purpose of our study was to evaluate vascular risk factors and other clinical variables as predictors of cognitive and functional decline in elderly patients with mild to moderate dementia. Methods The clinical characteristics of 82 elderly patients (mean age 79.0 ± 5.9 years; 67.1% females) with mild to moderate dementia were obtained at baseline, including years of education, Framingham Coronary Heart Disease Risk score, Hachinski Ischemic Score (HIS), Clinical Dementia Rating (CDR), Mini-Mental State Examination (MMSE) score, Functional Activities Questionnaire (FAQ) score, Burden Interview Scale score, and Neuropsychiatric Inventory (NPI) score. Changes in MMSE and FAQ scores over time were assessed annually. The association between baseline clinical variables and cognitive and functional decline was investigated during 3 years of follow-up through the use of generalized linear mixed effects models. Results A trend was found towards steeper cognitive decline in patients with less vascular burden according to the HIS (β = 0.056, p = 0.09), better cognitive performance according to the CDR score (β = 0.313, p = 0.06) and worse caregiver burden according to the Burden Interview Scale score (β = −0.012, p = 0.07) at baseline. Conclusion Further studies with larger samples are necessary to confirm and expand our findings. PMID:25493090

  10. The mismatch negativity as an index of cognitive decline for the early detection of Alzheimer’s disease

    PubMed Central

    Ruzzoli, Manuela; Pirulli, Cornelia; Mazza, Veronica; Miniussi, Carlo; Brignani, Debora

    2016-01-01

    Evidence suggests that Alzheimer’s disease (AD) is part of a continuum, characterized by long preclinical phases before the onset of clinical symptoms. In several cases, this continuum starts with a syndrome, defined as mild cognitive impairment (MCI), in which daily activities are preserved despite the presence of cognitive decline. The possibility of having a reliable and sensitive neurophysiological marker that can be used for early detection of AD is extremely valuable because of the incidence of this type of dementia. In this study, we aimed to investigate the reliability of auditory mismatch negativity (aMMN) as a marker of cognitive decline from normal ageing progressing from MCI to AD. We compared aMMN elicited in the frontal and temporal locations by duration deviant sounds in short (400 ms) and long (4000 ms) inter-trial intervals (ITI) in three groups. We found that at a short ITI, MCI showed only the temporal component of aMMN and AD the frontal component compared to healthy elderly who presented both. At a longer ITI, aMMN was elicited only in normal ageing subjects at the temporal locations. Our study provides empirical evidence for the possibility to adopt aMMN as an index for assessing cognitive decline in pathological ageing. PMID:27616726

  11. Inflammation and interleukin-1 signaling network contribute to depressive symptoms but not cognitive decline in old age.

    PubMed

    van den Biggelaar, Anita H J; Gussekloo, Jacobijn; de Craen, Anton J M; Frölich, Marijke; Stek, Max L; van der Mast, Roos C; Westendorp, Rudi G J

    2007-07-01

    The association between inflammation and neuropsychiatric symptoms in old age is generally accepted but poorly understood. The purpose of this study was to examine whether inflammation precedes depressive symptoms and cognitive decline in old age, and to identify specific inflammatory pathways herein. We measured serum C-reactive protein (CRP) and lipopolysaccharide-induced production of Interleukin (IL)-1beta, IL-6, Tumor Necrosis Factor (TNF)-alpha, IL-1 receptor antagonist (ra), and IL-10 levels in 85-year-old participants free from neuropsychiatric symptoms at baseline (n=267). Participants were prospectively followed for depressive symptoms (Geriatric Depression Scale) and cognitive functioning (Mini Mental State Examination) from 85 to 90 years. Higher baseline CRP levels preceded accelerated increase in depressive symptoms (p<0.001). A higher production capacity of the pro-inflammatory cytokine IL-1beta preceded a greater increase of depressive symptoms (p=0.06), whereas that of its natural antagonist IL-1ra preceded a smaller increase of depressive symptoms (p=0.003). There was no relation of CRP, IL-1beta, and IL-1ra with cognitive decline. Our findings show that in old age inflammatory processes contribute to the development of depressive symptoms but not cognitive decline. A high innate IL-1ra to IL-1beta production capacity reflects a better ability to neutralize inflammation and may therefore protect against depressive symptoms. PMID:17350781

  12. Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment

    PubMed Central

    Oulhaj, Abderrahim; Jernerén, Fredrik; Refsum, Helga; Smith, A. David; de Jager, Celeste A.

    2016-01-01

    A randomized trial (VITACOG) in people with mild cognitive impairment (MCI) found that B vitamin treatment to lower homocysteine slowed the rate of cognitive and clinical decline. We have used data from this trial to see whether baseline omega-3 fatty acid status interacts with the effects of B vitamin treatment. 266 participants with MCI aged ≥70 years were randomized to B vitamins (folic acid, vitamins B6 and B12) or placebo for 2 years. Baseline cognitive test performance, clinical dementia rating (CDR) scale, and plasma concentrations of total homocysteine, total docosahexaenoic and eicosapentaenoic acids (omega-3 fatty acids) were measured. Final scores for verbal delayed recall, global cognition, and CDR sum-of-boxes were better in the B vitamin-treated group according to increasing baseline concentrations of omega-3 fatty acids, whereas scores in the placebo group were similar across these concentrations. Among those with good omega-3 status, 33% of those on B vitamin treatment had global CDR scores >0 compared with 59% among those on placebo. For all three outcome measures, higher concentrations of docosahexaenoic acid alone significantly enhanced the cognitive effects of B vitamins, while eicosapentaenoic acid appeared less effective. When omega-3 fatty acid concentrations are low, B vitamin treatment has no effect on cognitive decline in MCI, but when omega-3 levels are in the upper normal range, B vitamins interact to slow cognitive decline. A clinical trial of B vitamins combined with omega-3 fatty acids is needed to see whether it is possible to slow the conversion from MCI to AD. PMID:26757190

  13. Incident Subjective Cognitive Decline Does Not Predict Mortality in the Elderly – Results from the Longitudinal German Study on Ageing, Cognition, and Dementia (AgeCoDe)

    PubMed Central

    Roehr, Susanne; Luck, Tobias; Heser, Kathrin; Fuchs, Angela; Ernst, Annette; Wiese, Birgitt; Werle, Jochen; Bickel, Horst; Brettschneider, Christian; Koppara, Alexander; Pentzek, Michael; Lange, Carolin; Prokein, Jana; Weyerer, Siegfried; Mösch, Edelgard; König, Hans-Helmut; Maier, Wolfgang; Scherer, Martin

    2016-01-01

    Objective Subjective cognitive decline (SCD) might represent the first symptomatic representation of Alzheimer’s disease (AD), which is associated with increased mortality. Only few studies, however, have analyzed the association of SCD and mortality, and if so, based on prevalent cases. Thus, we investigated incident SCD in memory and mortality. Methods Data were derived from the German AgeCoDe study, a prospective longitudinal study on the epidemiology of mild cognitive impairment (MCI) and dementia in primary care patients over 75 years covering an observation period of 7.5 years. We used univariate and multivariate Cox regression analyses to examine the relationship of SCD and mortality. Further, we estimated survival times by the Kaplan Meier method and case-fatality rates with regard to SCD. Results Among 971 individuals without objective cognitive impairment, 233 (24.0%) incidentally expressed SCD at follow-up I. Incident SCD was not significantly associated with increased mortality in the univariate (HR = 1.0, 95% confidence interval = 0.8–1.3, p = .90) as well as in the multivariate analysis (HR = 0.9, 95% confidence interval = 0.7–1.2, p = .40). The same applied for SCD in relation to concerns. Mean survival time with SCD was 8.0 years (SD = 0.1) after onset. Conclusion Incident SCD in memory in individuals with unimpaired cognitive performance does not predict mortality. The main reason might be that SCD does not ultimately lead into future cognitive decline in any case. However, as prevalence studies suggest, subjectively perceived decline in non-memory cognitive domains might be associated with increased mortality. Future studies may address mortality in such other cognitive domains of SCD in incident cases. PMID:26766555

  14. Ergothioneine levels in an elderly population decrease with age and incidence of cognitive decline; a risk factor for neurodegeneration?

    PubMed

    Cheah, Irwin K; Feng, Lei; Tang, Richard M Y; Lim, Keith H C; Halliwell, Barry

    2016-09-01

    Ergothioneine (ET), a naturally occurring thione, can accumulate in the human body at high concentrations from diet. Following absorption via a specific transporter, OCTN1, ET may accumulate preferentially in tissues predisposed to higher levels of oxidative stress and inflammation. Given its potential cytoprotective effects, we examined how ET levels change with age. We found that whole blood ET levels in elderly individuals decline significantly beyond 60 years of age. Additionally, a subset of these subjects with mild cognitive impairment had significantly lower plasma ET levels compared with age-matched subjects. This decline suggests that deficiency in ET may be a risk factor, predisposing individuals to neurodegenerative diseases. PMID:27444382

  15. Subjective Cognitive Decline in Older Adults: An Overview of Self-Report Measures Used Across 19 International Research Studies.

    PubMed

    Rabin, Laura A; Smart, Colette M; Crane, Paul K; Amariglio, Rebecca E; Berman, Lorin M; Boada, Mercé; Buckley, Rachel F; Chételat, Gaël; Dubois, Bruno; Ellis, Kathryn A; Gifford, Katherine A; Jefferson, Angela L; Jessen, Frank; Katz, Mindy J; Lipton, Richard B; Luck, Tobias; Maruff, Paul; Mielke, Michelle M; Molinuevo, José Luis; Naeem, Farnia; Perrotin, Audrey; Petersen, Ronald C; Rami, Lorena; Reisberg, Barry; Rentz, Dorene M; Riedel-Heller, Steffi G; Risacher, Shannon L; Rodriguez, Octavio; Sachdev, Perminder S; Saykin, Andrew J; Slavin, Melissa J; Snitz, Beth E; Sperling, Reisa A; Tandetnik, Caroline; van der Flier, Wiesje M; Wagner, Michael; Wolfsgruber, Steffen; Sikkes, Sietske A M

    2015-09-24

    Research increasingly suggests that subjective cognitive decline (SCD) in older adults, in the absence of objective cognitive dysfunction or depression, may be a harbinger of non-normative cognitive decline and eventual progression to dementia. Little is known, however, about the key features of self-report measures currently used to assess SCD. The Subjective Cognitive Decline Initiative (SCD-I) Working Group is an international consortium established to develop a conceptual framework and research criteria for SCD (Jessen et al., 2014, Alzheimers Dement 10, 844-852). In the current study we systematically compared cognitive self-report items used by 19 SCD-I Working Group studies, representing 8 countries and 5 languages. We identified 34 self-report measures comprising 640 cognitive self-report items. There was little overlap among measures- approximately 75% of measures were used by only one study. Wide variation existed in response options and item content. Items pertaining to the memory domain predominated, accounting for about 60% of items surveyed, followed by executive function and attention, with 16% and 11% of the items, respectively. Items relating to memory for the names of people and the placement of common objects were represented on the greatest percentage of measures (56% each). Working group members reported that instrument selection decisions were often based on practical considerations beyond the study of SCD specifically, such as availability and brevity of measures. Results document the heterogeneity of approaches across studies to the emerging construct of SCD. We offer preliminary recommendations for instrument selection and future research directions including identifying items and measure formats associated with important clinical outcomes.

  16. Subjective Cognitive Decline in Older Adults: An Overview of Self-Report Measures Used Across 19 International Research Studies

    PubMed Central

    Rabin, Laura A.; Smart, Colette M.; Crane, Paul K.; Amariglio, Rebecca E.; Berman, Lorin M.; Boada, Mercè; Buckley, Rachel F.; Chételat, Gaël; Dubois, Bruno; Ellis, Kathryn A.; Gifford, Katherine A.; Jefferson, Angela L.; Jessen, Frank; Katz, Mindy J.; Lipton, Richard B.; Luck, Tobias; Maruff, Paul; Mielke, Michelle M.; Molinuevo, José Luis; Naeem, Farnia; Perrotin, Audrey; Petersen, Ronald C.; Rami, Lorena; Reisberg, Barry; Rentz, Dorene M.; Riedel-Heller, Steffi G.; Risacher, Shannon L.; Rodriguez, Octavio; Sachdev, Perminder S.; Saykin, Andrew J.; Slavin, Melissa J.; Snitz, Beth E.; Sperling, Reisa A.; Tandetnik, Caroline; van der Flier, Wiesje M.; Wagner, Michael; Wolfsgruber, Steffen; Sikkes, Sietske A.M.

    2015-01-01

    Research increasingly suggests that subjective cognitive decline (SCD) in older adults, in the absence of objective cognitive dysfunction or depression, may be a harbinger of non-normative cognitive decline and eventual progression to dementia. Little is known, however, about the key features of self-report measures currently used to assess SCD. The Subjective Cognitive Decline Initiative (SCD-I) Working Group is an international consortium established to develop a conceptual framework and research criteria for SCD (Jessen et al., 2014, Alzheimers Dement 10, 844–852). In the current study we systematically compared cognitive self-report items used by 19 SCD-I Working Group studies, representing 8 countries and 5 languages. We identified 34 self-report measures comprising 640 cognitive self-report items. There was little overlap among measures—approximately 75% of measures were used by only one study. Wide variation existed in response options and item content. Items pertaining to the memory domain predominated, accounting for about 60% of items surveyed, followed by executive function and attention, with 16% and 11% of the items, respectively. Items relating to memory for the names of people and the placement of common objects were represented on the greatest percentage of measures (56% each). Working group members reported that instrument selection decisions were often based on practical considerations beyond the study of SCD specifically, such as availability and brevity of measures. Results document the heterogeneity of approaches across studies to the emerging construct of SCD. We offer preliminary recommendations for instrument selection and future research directions including identifying items and measure formats associated with important clinical outcomes. PMID:26402085

  17. Evolving Evidence for the Value of Neuroimaging Methods and Biological Markers in Subjects Categorized with Subjective Cognitive Decline.

    PubMed

    Lista, Simone; Molinuevo, Jose L; Cavedo, Enrica; Rami, Lorena; Amouyel, Philippe; Teipel, Stefan J; Garaci, Francesco; Toschi, Nicola; Habert, Marie-Odile; Blennow, Kaj; Zetterberg, Henrik; O'Bryant, Sid E; Johnson, Leigh; Galluzzi, Samantha; Bokde, Arun L W; Broich, Karl; Herholz, Karl; Bakardjian, Hovagim; Dubois, Bruno; Jessen, Frank; Carrillo, Maria C; Aisen, Paul S; Hampel, Harald

    2015-09-24

    There is evolving evidence that individuals categorized with subjective cognitive decline (SCD) are potentially at higher risk for developing objective and progressive cognitive impairment compared to cognitively healthy individuals without apparent subjective complaints. Interestingly, SCD, during advancing preclinical Alzheimer's disease (AD), may denote very early, subtle cognitive decline that cannot be identified using established standardized tests of cognitive performance. The substantial heterogeneity of existing SCD-related research data has led the Subjective Cognitive Decline Initiative (SCD-I) to accomplish an international consensus on the definition of a conceptual research framework on SCD in preclinical AD. In the area of biological markers, the cerebrospinal fluid signature of AD has been reported to be more prevalent in subjects with SCD compared to healthy controls; moreover, there is a pronounced atrophy, as demonstrated by magnetic resonance imaging, and an increased hypometabolism, as revealed by positron emission tomography, in characteristic brain regions affected by AD. In addition, SCD individuals carrying an apolipoprotein ɛ4 allele are more likely to display AD-phenotypic alterations. The urgent requirement to detect and diagnose AD as early as possible has led to the critical examination of the diagnostic power of biological markers, neurophysiology, and neuroimaging methods for AD-related risk and clinical progression in individuals defined with SCD. Observational studies on the predictive value of SCD for developing AD may potentially be of practical value, and an evidence-based, validated, qualified, and fully operationalized concept may inform clinical diagnostic practice and guide earlier designs in future therapy trials. PMID:26402088

  18. Amyloid burden, neuronal function, and cognitive decline in middle-aged adults at risk for Alzheimer’s disease

    PubMed Central

    Okonkwo, Ozioma C.; Oh, Jennifer M.; Koscik, Rebecca; Jonaitis, Erin; Cleary, Caitlin A.; Dowling, N. Maritza; Bendlin, Barbara B.; LaRue, Asenath; Hermann, Bruce P.; Barnhart, Todd E.; Murali, Dhanabalan; Rowley, Howard A.; Carlsson, Cynthia M.; Gallagher, Catherine L.; Asthana, Sanjay; Sager, Mark A.; Christian, Brad T.; Johnson, Sterling C.

    2014-01-01

    The relative influence of amyloid burden, neuronal structure and function, and prior cognitive performance on prospective memory decline among asymptomatic late middle-aged individuals at risk for Alzheimer’s disease (AD) is currently unknown. We investigated this using longitudinal cognitive data from 122 middle-aged adults (21 “Decliners” and 101 “Stables”) enrolled in the Wisconsin Registry for Alzheimer’s Prevention who underwent multimodality neuroimaging (11C-Pittsburgh Compound B (PiB), 18F-fluorodeoxyglucose (FDG), and structural/functional MRI) 5.7±1.4 years (range=2.9–8.9) after their baseline cognitive assessment. Covariate-adjusted regression analyses revealed that the only imaging measure that significantly distinguished Decliners from Stables (p=.027) was a Neuronal Function composite derived from FDG and fMRI. In contrast, several cognitive measures, especially those that tap episodic memory, significantly distinguished the groups (p’s < .05). Complementary receiver operating characteristic curve analyses identified the Brief Visuospatial Memory Test-Revised (BVMT-R) Total (.82±.05, p<.001), the BVMT-R Delayed Recall (.73±.06, p=.001), and the Reading subtest from the Wide-Range Achievement Test-III (.72±.06, p=.002) as the top three measures that best discriminated the groups. These findings suggest that early memory test performance might serve a more clinically-pivotal role in forecasting future cognitive course than is currently presumed. PMID:24621494

  19. Vascular disease and risk factors are associated with cognitive decline in the Alzheimer’s disease spectrum

    PubMed Central

    Lorius, Natacha; Locascio, Joseph J.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.; Viswanathan, Anand; Marshall, Gad A.

    2015-01-01

    We investigated the relationship between vascular disease and risk factors versus cognitive decline cross-sectionally and longitudinally in normal older control (NC), mild cognitive impairment (MCI), and mild Alzheimer’s disease (AD) dementia subjects. 812 participants (229 NC, 395 MCI, 188 AD) underwent cognitive testing, brain magnetic resonance imaging, and clinical evaluations at baseline and over a period of 3 years. General linear, longitudinal mixed effects, and Cox proportional hazards models were used. Greater homocysteine level and white matter hyperintensity (WMH) volume were associated with processing speed impairment (homocysteine: p=0.02; WMH: p<0.0001); greater vascular index score was associated with memory impairment (p=0.007); and greater number of apolipoprotein E ε4 (APOE4) alleles was associated with global cognitive impairment (p=0.007) at baseline. APOE4 was associated with greater rate of increase in global cognitive impairment (p=0.002) and processing speed impairment (p=0.001) over time, while higher total cholesterol was associated with greater rate of increase in global cognitive impairment (p=0.02) and memory impairment (p=0.06) over time. These results suggest a significant association of increased vascular disease and risk factors with cognitive impairment at baseline and over time in the AD spectrum in a sample that was selected to have low vascular burden at baseline. PMID:24787033

  20. Cognitive decline in the elderly after surgery and anaesthesia: results from the Oxford Project to Investigate Memory and Ageing (OPTIMA) cohort.

    PubMed

    Patel, D; Lunn, A D; Smith, A D; Lehmann, D J; Dorrington, K L

    2016-10-01

    Concerns have been raised about the effects on cognition of anaesthesia for surgery, especially in elderly people. We recorded cognitive decline in a cohort of 394 people (198 women) with median (IQR) age at recruitment of 72.6 (66.6-77.8) years, of whom 109 had moderate or major surgery during a median (IQR) follow-up of 4.1 (2.0-7.6) years. Cognitive decline was more rapid in people who on recruitment were: older, p = 0.0003; male, p = 0.027; had worse cognition, p < 0.0001; or carried the ε4 allele of apoliprotein E (APOEε4), p = 0.008; and after an operation if cognitive impairment was already diagnosed, p = 0.0001. Cognitive decline appears to accelerate after surgery in elderly patients diagnosed with cognitive impairment, but not other elderly patients. PMID:27501155

  1. Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer’s Disease and Vascular Dementia: a Retrospective Study

    PubMed Central

    Pilon, Marie-Hélène; Poulin, Stéphane; Fortin, Marie-Pierre; Houde, Michèle; Verret, Louis; Bouchard, Rémi W.; Laforce, Robert

    2016-01-01

    Few studies have explored the rate of cognitive decline and caregiver burden within the context of a specialized memory clinic. When this was done, the focus was largely on functional decline related to Alzheimer’s disease (AD). Our goal was to compare the longitudinal decline of AD patients to those with Vascular Dementia (VaD) on Mini-Mental State Examination (MMSE). We further explored the differential impact on caregiver burden. We retrospectively studied 237 charts from patients seen at our Memory Clinic between 2006 and 2012. The data was collected over 17 years. Cohorts were formed by excluding conditions other than AD and VaD, and including patients who had been assessed at least twice with the MMSE (AD: n = 83; mean age: 67.7 yo; VaD: n = 32; mean age: 73.3yo). A small group of 36 caregivers was surveyed by phone to explore caregiver burden. Results indicated that the natural history of MMSE changes in AD patients differed significantly from that of patients with VaD (F = 10.41, p<0.0014), with AD patients showing more cognitive decline over time. Sadness, stress/anxiety, fatigue, and sleep disorders were reported as the main preoccupations by caregivers and its impact was rated as ‘severe’ in 50% of cases. Altogether, this study provides further insight into the natural history of cognitive decline in AD and VaD. Future studies should explore the progression of dementing disorders in larger cohorts using prospective methodological designs. PMID:27747317

  2. Apathy and cognitive and functional decline in community-dwelling older adults: Results from the Baltimore ECA longitudinal study

    PubMed Central

    Clarke, Diana E.; Ko, Jean Y.; Lyketsos, Constantine; Rebok, George W.; Eaton, William W.

    2010-01-01

    Background Apathy, a complex neuropsychiatric syndrome, commonly affects patients with Alzheimer’s disease. Prevalence estimates for apathy range widely and are based on cross-sectional data and / or clinic samples. This study examines the relationships between apathy and cognitive and functional declines in non-depressed community-based older adults. Methods Data on 1,136 community-dwelling adults age 50 and older from the Baltimore Epidemiologic Catchment Area (ECA) study, with 1 and 13 years of follow-up, were used. Apathy was assessed with a subscale of items from the General Health Questionnaire. Chi-square, t-tests, logistic regression, and Generalized Estimating Equations were used to accomplish the study’s objectives. Results The prevalence of apathy at Wave 1 was 23.7%. Compared to those without, individuals with apathy were on average older, more likely to be female, and have lower MMSE scores and impairments in basic and instrumental functioning at baseline. Apathy was significantly associated with cognitive decline (OR = 1.65, 95% CI = 1.06, 2.60) and declines in instrumental (OR = 4.42; 95% CI = 2.65, 7.38) and basic (OR=2.74; 95%CI= 1.35, 5.57) function at 1 year follow-up, even after adjustment for baseline age, level of education, race, and depression at follow-up. At 13 years of follow-up, apathetic individuals were not at greater risk for cognitive decline but were 2-fold more likely to have functional decline. Incidence of apathy at 1- year follow up and 13- year follow-up was respectively, 22.6% and 29.4%. Conclusions These results underline the public health importance of apathy and the need for further population-based studies in this area. PMID:20478091

  3. Dietary Patterns High in Red Meat, Potato, Gravy, and Butter Are Associated with Poor Cognitive Functioning but Not with Rate of Cognitive Decline in Very Old Adults1234

    PubMed Central

    Davies, Karen; Adamson, Ashley; Kirkwood, Thomas; Hill, Tom R; Siervo, Mario; Mathers, John C; Jagger, Carol

    2016-01-01

    Background: Healthy dietary patterns (DPs) have been linked to better cognition and reduced risk of dementia in older adults, but their role in cognitive functioning and decline in the very old (aged ≥85 y) is unknown. Objective: We investigated the association between previously established DPs from the Newcastle 85+ Study and global and attention-specific cognition over 5 y. Methods: We followed up with 302 men and 489 women (1921 birth cohort from Northeast United Kingdom) for change in global cognition [measured by the Standardized Mini-Mental State Examination (SMMSE)] over 5 y and attention (assessed by the cognitive drug research attention battery) over 3 y. We used 2-step clustering to derive DPs and mixed models to determine the relation between DPs and cognition in the presence of the dementia susceptibility gene. Results: Previously, we characterized 3 DPs that differed in intake of red meat, potato, gravy, and butter and varied with key health measures. When compared with participants in DP1 (high red meat) and DP3 (high butter), participants in DP2 (low meat) had higher SMMSE scores at baseline (P < 0.001) and follow-ups, and better initial attention (P < 0.05). Membership in DP1 and DP3 was associated with overall worse SMMSE scores (β = 0.09, P = 0.01 and β = 0.08, P = 0.02, respectively) than membership in DP2 after adjustment for sociodemographic factors, lifestyle, multimorbidity, and body mass index (BMI). Additional adjustment for apolipoprotein (apoE) ε4 genotype attenuated the association to nonsignificant in women but not in men in DP1 (β = 0.13, P = 0.02). Participants in DP1 and DP3 also had overall worse concentration (β = 0.04, P = 0.002 and β = 0.028, P = 0.03, respectively) and focused attention (β = 0.02, P = 0.01 and β = 0.02, P = 0.03, respectively), irrespective of apoE ε4 genotype, but similar rate of decline in all cognitive measures over time. Conclusion: DPs high in red meat, potato, gravy (DP1), or butter (DP3) were

  4. Computer Simulations of Loss of Organization of Neurons as a Model for Age-related Cognitive Decline

    NASA Astrophysics Data System (ADS)

    Cruz, Luis; Fengometidis, Elene; Jones, Frank; Jampani, Srinivas

    2011-03-01

    In normal aging, brains suffer from progressive cognitive decline not linked with loss of neurons common in neurodegenerative disorders such as Alzheimer's disease. However, in some brain areas neurons have lost positional organization specifically within microcolumns: arrays of interconnected neurons which may constitute fundamental computational units in the brain. This age-related loss of organization, likely a result of micron-sized random displacements in neuronal positions, is hypothesized to be a by-product of the loss of support from the surrounding medium, including dendrites. Using a dynamical model applied to virtual 3D representation of neuronal arrangements, that previously showed loss of organization in brains of cognitively tested rhesus monkeys, the relationship between these displacements and changes to the surrounding dendrite network are presented. The consequences of these displacements on the structure of the dendritic network, with possible disruptions in signal synchrony important to cognitive function, are discussed. NIH R01AG021133.

  5. Age-Related Decline in Brain Resources Modulates Genetic Effects on Cognitive Functioning

    PubMed Central

    Lindenberger, Ulman; Nagel, Irene E.; Chicherio, Christian; Li, Shu-Chen; Heekeren, Hauke R.; Bäckman, Lars

    2008-01-01

    Individual differences in cognitive performance increase from early to late adulthood, likely reflecting influences of a multitude of factors. We hypothesize that losses in neurochemical and anatomical brain resources in normal aging modulate the effects of common genetic variations on cognitive functioning. Our hypothesis is based on the assumption that the function relating brain resources to cognition is nonlinear, so that genetic differences exert increasingly large effects on cognition as resources recede from high to medium levels in the course of aging. Direct empirical support for this hypothesis comes from a study by Nagel et al. (2008), who reported that the effects of the Catechol-O-Methyltransferase (COMT) gene on cognitive performance are magnified in old age and interacted with the Brain-Derived Neurotrophic Factor (BDNF) gene. We conclude that common genetic polymorphisms contribute to the increasing heterogeneity of cognitive functioning in old age. Extensions of the hypothesis to other polymorphisms are discussed. (150 of 150 words) PMID:19225597

  6. Bone Mineral Density and Cognitive Decline in Elderly Women: Results from the InCHIANTI Study.

    PubMed

    Laudisio, Alice; Fontana, Davide Onofrio; Rivera, Chiara; Ruggiero, Carmelinda; Bandinelli, Stefania; Gemma, Antonella; Ferrucci, Luigi; Antonelli Incalzi, Raffaele

    2016-05-01

    Osteoporosis and cognitive impairment, which are highly prevalent conditions in elderly populations, share several risk factors. This study aims at evaluating the association of bone mineral density (BMD) with prevalent and incident cognitive impairment after a 3-year follow-up. We studied 655 community-dwelling women aged 65+ participating in the InCHIANTI study, who had been followed for 3 years. Total, trabecular, and cortical BMD were estimated by peripheral quantitative computed tomography using standard transverse scans at 4 and 38 % of the tibial length. Cognitive performance was evaluated using the Mini-Mental State Examination and the Trail Making Tests (TMT) A and B; a MMSE score <24 was adopted to define cognitive impairment. The TMT A-B score was calculated as the difference between TMT-A and TMT-B times (ΔTMT). The association of cognitive performance after 3 years with baseline indices of BMD was assessed by logistic and linear regression analyses. Cortical, but not trabecular, BMD was independently associated with incident cognitive impairment (OR 0.93, 95 % CI 0.88-0.98; P = 0.012), worsening cognitive performance (OR 0.96, 95 % CI 0.92-0.98; P = 0.039), and worsening performance in ΔTMT (OR 0.96, 95 % CI 0.92-0.99; P = 0.047). Increasing cortical BMD tertiles was associated with decreasing probability of incident cognitive impairment (P for linear trend =0.001), worsening cognitive performance (P = 0.013), and a worsening performance below the median value (P for linear trend <0.0001). In older women, low BMD might represent an independent and early marker of subsequent cognitive impairment. Physicians should assess and monitor cognitive performance in the routine management of elderly women with osteoporosis. PMID:26713334

  7. An examination of Bayesian statistical approaches to modeling change in cognitive decline in an Alzheimer’s disease population

    PubMed Central

    Bartolucci, Al; Bae, Sejong; Singh, Karan; Griffith, H. Randall

    2009-01-01

    The mini mental state examination (MMSE) is a common tool for measuring cognitive decline in Alzhiemer’s Disease (AD) subjects. Subjects are usually observed for a specified period of time or until death to determine the trajectory of the decline which for the most part appears to be linear. However, it may be noted that the decline may not be modeled by a single linear model over a specified period of time. There may be a point called a change point where the rate or gradient of the decline may change depending on the length of time of observation. A Bayesian approach is used to model the trajectory and determine an appropriate posterior estimate of the change point as well as the predicted model of decline before and after the change point. Estimates of the appropriate parameters as well as their posterior credible regions or regions of interest are established. Coherent prior to posterior analysis using mainly non informative priors for the parameters of interest is provided. This approach is applied to an existing AD database. PMID:20161460

  8. Age-related changes in synaptic markers and monocyte subsets link the cognitive decline of APPSwe/PS1 mice

    PubMed Central

    Naert, Gaëlle; Rivest, Serge

    2012-01-01

    Alzheimer's disease (AD) is characterized by a progressive memory decline and numerous pathological abnormalities, including amyloid β (Aβ) accumulation in the brain and synaptic dysfunction. Here we wanted to study whether these brain changes were associated with alteration in the population of monocyte subsets since accumulating evidence supports the concept that the innate immune system plays a role in the etiology of this disease. We then determined the immune profile together with expression of genes encoding synaptic proteins and neurotrophins in APPSwe/PS1 mice and their age-matched wild-type (WT) littermates. We found that the progressive cognitive decline and the dramatic decrease in the expression of numerous synaptic markers and neurotrophins correlated with a major defect in the subset of circulating inflammatory monocytes. Indeed the number of CX3CR1lowLy6-ChighCCR2+Gr1+ monocytes remained essentially similar between 5 weeks and 6 months of age in APPSwe/PS1 mice, while these cells significantly increased in 6-month-old WT littermates. Of great interest is that the onset of cognitive decline was closely associated with the accumulation of soluble Aβ, disruption of synaptic activity, alteration in the BDNF system, and a defective production in the subset of CX3CR1lowLy6-ChighCCR2+Gr1+ monocytes. However, these memory impairments can be prevented or restored by boosting the monocytic production, using a short treatment of macrophage colony-stimulating factor (M-CSF). In conclusion, low CCR2+ monocyte production by the hematopoietic system may be a direct biomarker of the cognitive decline in a context of AD. PMID:23125823

  9. The Cerebrospinal Fluid Neurogranin/BACE1 Ratio is a Potential Correlate of Cognitive Decline in Alzheimer’s Disease

    PubMed Central

    De Vos, Ann; Struyfs, Hanne; Jacobs, Dirk; Fransen, Erik; Klewansky, Tom; De Roeck, Ellen; Robberecht, Caroline; Van Broeckhoven, Christine; Duyckaerts, Charles; Engelborghs, Sebastiaan; Vanmechelen, Eugeen

    2016-01-01

    Background: In diagnosing Alzheimer’s disease (AD), ratios of cerebrospinal fluid (CSF) biomarkers, such as CSF Aβ1-42/tau, have an improved diagnostic performance compared to the single analytes, yet, still a limited value to predict cognitive decline. Since synaptic dysfunction/loss is closely linked to cognitive impairment, synaptic proteins are investigated as candidate CSF AD progression markers. Objective: We studied CSF levels of the postsynaptic protein neurogranin and protein BACE1, predominantly localized presynaptically, and their relation to CSF total-tau, Aβ1-42, Aβ1-40, and Aβ1-38. All six analytes were considered as single parameters as well as ratios. Methods: Every ELISA involved was based on monoclonal antibodies, including the BACE1 and neurogranin immunoassay. The latter specifically targets neurogranin C-terminally truncated at P75, a more abundant species of the protein in CSF. We studied patients with MCI due to AD (n = 38) and 50 dementia due to AD patients, as well as age-matched cognitively healthy elderly (n = 20). A significant subset of the patients was followed up by clinical and neuropsychologically (MMSE) examinations for at least one year. Results: The single analytes showed statistically significant differences between the clinical groups, but the ratios of analytes indeed had a higher diagnostic performance. Furthermore, only the ratio of CSF neurogranin trunc P75/BACE1 was significantly correlated with the yearly decline in MMSE scores in patients with MCI and dementia due to AD, pointing toward the prognostic value of the ratio. Conclusion: This is the first study demonstrating that the CSF neurogranin trunc P75/BACE1 ratio, reflecting postsynaptic/presynaptic integrity, is related to cognitive decline. PMID:27392859

  10. A randomized controlled trial investigating the neurocognitive effects of Lacprodan® PL-20, a phospholipid-rich milk protein concentrate, in elderly participants with age-associated memory impairment: the Phospholipid Intervention for Cognitive Ageing Reversal (PLICAR): study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Age-related cognitive decline (ARCD) is of major societal concern in an ageing population, with the development of dietary supplements providing a promising avenue for amelioration of associated deficits. Despite initial interest in the use of phospholipids (PLs) for ARCD, in recent years there has been a hiatus in such research. Because of safety concerns regarding PLs derived from bovine cortex, and the equivocal efficacy of soybean-derived PLs, there is an important need for the development of new PL alternatives. Phospholipids derived from milk proteins represent one potential candidate treatment. Methods In order to reduce the effects of age-associated memory impairment (AAMI) the Phospholipid Intervention for Cognitive Ageing Reversal (PLICAR) was developed to test the efficacy of a milk protein concentrate rich in natural, non-synthetic milk phospholipids (Lacprodan® PL-20). PLICAR is a randomized, double-blind, placebo-controlled parallel-groups study where 150 (N = 50/group) AAMI participants aged > 55 years will be randomized to receive a daily supplement of Lacprodan® PL-20 or one of two placebos (phospholipid-free milk protein concentrate or inert rice starch) over a 6-month (180-day) period. Participants will undergo testing at baseline, 90 days and 180 days. The primary outcome is a composite memory score from the Rey Auditory Verbal Learning Test. Secondary outcomes include cognitive (verbal learning, working memory, prospective and retrospective memory, processing speed and attention), mood (depression, anxiety, stress and visual analogue scales), cardiovascular (blood pressure, blood velocity and pulse wave pressure), gastrointestinal microbiota and biochemical measures (oxidative stress, inflammation, B vitamins and Homocysteine, glucoregulation and serum choline). Allelic differences in the Apolipoprotein E and (APOE) and Methylenetetrahydrofolate reductase (MTHFR) gene will be included for subgroup analysis. A subset (N

  11. Consumption of green tea, but not black tea or coffee, is associated with reduced risk of cognitive decline.

    PubMed

    Noguchi-Shinohara, Moeko; Yuki, Sohshi; Dohmoto, Chiaki; Ikeda, Yoshihisa; Samuraki, Miharu; Iwasa, Kazuo; Yokogawa, Masami; Asai, Kimiko; Komai, Kiyonobu; Nakamura, Hiroyuki; Yamada, Masahito

    2014-01-01

    Our objective was to determine whether the consumption of green tea, coffee, or black tea influences the incidence of dementia and mild cognitive impairment (MCI) in older people. We conducted a population-based prospective study with Japanese residents aged >60 years from Nakajima, Japan (the Nakajima Project). Participants received an evaluation of cognitive function and blood tests. The consumption of green tea, coffee, and black tea was also evaluated at baseline. Of 723 participants with normal cognitive function at a baseline survey (2007-2008), 490 completed the follow up survey in 2011-2013. The incidence of dementia during the follow-up period (mean ± SD: 4.9 ± 0.9 years) was 5.3%, and that of MCI was 13.1%. The multiple-adjusted odds ratio for the incidence of overall cognitive decline (dementia or MCI) was 0.32 (95% CI: 0.16-0.64) among individuals who consumed green tea every day and 0.47 (95% CI: 0.25-0.86) among those who consumed green tea 1-6 days per week compared with individuals who did not consume green tea at all. The multiple-adjusted odds ratio for the incidence of dementia was 0.26 (95% CI: 0.06-1.06) among individuals who consumed green tea every day compared with those who did not consume green tea at all. No association was found between coffee or black tea consumption and the incidence of dementia or MCI. Our results indicate that green tea consumption is significantly associated with reduced risk of cognitive decline, even after adjustment for possible confounding factors.

  12. Increased levels of plasma amyloid-beta are related to cortical thinning and cognitive decline in cognitively normal elderly subjects.

    PubMed

    Llado-Saz, Sandra; Atienza, Mercedes; Cantero, Jose L

    2015-10-01

    Plasma levels of circulating amyloid-beta (Aβ) peptides are of particular interest in Alzheimer' disease, but little is known about cognitive and cortical correlates of peripheral Aβ levels in normal aging. Here, we compared cognitive functioning, vascular risk factors, and patterns of cortical thickness between cognitively intact elderly subjects with low (N = 60) and high (N = 60) plasma Aβ levels (cutoffs: 225 pg/mL and 23 pg/mL for Aβ1-40 and Aβ1-42, respectively). Overall, subjects with high Aβ levels showed lower cognitive performance and thinner cortex than those with low Aβ levels. More specifically, subjects with high Aβ1-40 showed bilateral thinning of the prefrontal cortex, poorer objective memory, slower processing speed, and lower nonverbal reasoning skills, whereas subjects with high Aβ1-42 had thinner temporal lobe, poorer everyday memory, and increased levels of homocysteine. Overall, these results suggest that high plasma Aβ levels in normal elderly subjects are associated with subclinical markers of vulnerable aging, which may be helpful at predicting different trajectories of aging in cognitively intact older adults. PMID:26182906

  13. The Possible Link between GABAergic Dysfunction and Cognitive Decline in a Patient with Idiopathic Hypoparathyroidism.

    PubMed

    Terada, Tatsuhiro; Kakimoto, Akihiro; Yoshikawa, Etsuji; Kono, Satoshi; Bunai, Tomoyasu; Hosoi, Yasushi; Sakao-Suzuki, Makiko; Konishi, Takashi; Miyajima, Hiroaki; Ouchi, Yasuomi

    2015-01-01

    Idiopathic hypoparathyroidism (IHP) is accompanied by cognitive impairment. We report the case of a 70-year-old IHP patient with cognitive disturbance. Brain computed tomography showed bilateral calcification in basal ganglia, thalamus, and cerebellum. Neuropsychological assessment revealed low scores for intelligence, memory, and perseverative errors. Brain positron emission tomography showed a significant reduction in [(18)F]-Fludeoxyglucose (FDG) uptake in bilateral frontal, left temporal and parietal cortices, along with a marked reduction in [(11)C]-flumazenil binding in left frontal, temporal, parietal, and bilateral cerebellum. These findings suggest cognitive impairment in IHP may be ascribed to GABAergic dysfunction, thus leading to, or coexisting with, cerebral hypometabolism.

  14. Disruptions in brain networks of older fallers are associated with subsequent cognitive decline: a 12-month prospective exploratory study.

    PubMed

    Hsu, Chun Liang; Voss, Michelle W; Handy, Todd C; Davis, Jennifer C; Nagamatsu, Lindsay S; Chan, Alison; Bolandzadeh, Niousha; Liu-Ambrose, Teresa

    2014-01-01

    Cognitive impairment and impaired mobility are major public health concerns. There is growing recognition that impaired mobility is an early biomarker of cognitive impairment and dementia. The neural basis for this association is currently unclear. We propose disrupted functional connectivity as a potential mechanism. In this 12-month prospective exploratory study, we compared functional connectivity of four brain networks- the default mode network (DMN), fronto-executive network (FEN), fronto-parietal network (FPN), and the primary motor sensory network (SMN)--between community-dwelling older adults with ≥ two falls in the last 12 months and their non-falling counterparts (≤ one fall in the last 12 months). Functional connectivity was examined both at rest and during a simple motor tapping task. Compared with non-fallers, fallers showed more connectivity between the DMN and FPN during right finger tapping (p  = 0.04), and significantly less functional connectivity between the SMN and FPN during rest (p ≤ 0.05). Less connectivity between the SMN and FPN during rest was significantly associated with greater decline in both cognitive function and mobility over the12-month period (r =  -0.32 and 0.33 respectively; p ≤ 0.04). Thus, a recent history of multiple falls among older adults without a diagnosis of dementia may indicate sub-clinical changes in brain function and increased risk for subsequent decline.

  15. Cognitive Decline and Reorganization of Functional Connectivity in Healthy Aging: The Pivotal Role of the Salience Network in the Prediction of Age and Cognitive Performances

    PubMed Central

    La Corte, Valentina; Sperduti, Marco; Malherbe, Caroline; Vialatte, François; Lion, Stéphanie; Gallarda, Thierry; Oppenheim, Catherine; Piolino, Pascale

    2016-01-01

    Normal aging is related to a decline in specific cognitive processes, in particular in executive functions and memory. In recent years a growing number of studies have focused on changes in brain functional connectivity related to cognitive aging. A common finding is the decreased connectivity within multiple resting state networks, including the default mode network (DMN) and the salience network. In this study, we measured resting state activity using fMRI and explored whether cognitive decline is related to altered functional connectivity. To this end we used a machine learning approach to classify young and old participants from functional connectivity data. The originality of the approach consists in the prediction of the performance and age of the subjects based on functional connectivity by using a machine learning approach. Our findings showed that the connectivity profile between specific networks predicts both the age of the subjects and their cognitive abilities. In particular, we report that the connectivity profiles between the salience and visual networks, and the salience and the anterior part of the DMN, were the features that best predicted the age. Moreover, independently of the age of the subject, connectivity between the salience network and various specific networks (i.e., visual, frontal) predicted episodic memory skills either based on a standard assessment or on an autobiographical memory task, and short-term memory binding. Finally, the connectivity between the salience and the frontal networks predicted inhibition and updating performance, but this link was no longer significant after removing the effect of age. Our findings confirm the crucial role of episodic memory and executive functions in cognitive aging and suggest a pivotal role of the salience network in neural reorganization in aging.

  16. Cognitive Decline and Reorganization of Functional Connectivity in Healthy Aging: The Pivotal Role of the Salience Network in the Prediction of Age and Cognitive Performances

    PubMed Central

    La Corte, Valentina; Sperduti, Marco; Malherbe, Caroline; Vialatte, François; Lion, Stéphanie; Gallarda, Thierry; Oppenheim, Catherine; Piolino, Pascale

    2016-01-01

    Normal aging is related to a decline in specific cognitive processes, in particular in executive functions and memory. In recent years a growing number of studies have focused on changes in brain functional connectivity related to cognitive aging. A common finding is the decreased connectivity within multiple resting state networks, including the default mode network (DMN) and the salience network. In this study, we measured resting state activity using fMRI and explored whether cognitive decline is related to altered functional connectivity. To this end we used a machine learning approach to classify young and old participants from functional connectivity data. The originality of the approach consists in the prediction of the performance and age of the subjects based on functional connectivity by using a machine learning approach. Our findings showed that the connectivity profile between specific networks predicts both the age of the subjects and their cognitive abilities. In particular, we report that the connectivity profiles between the salience and visual networks, and the salience and the anterior part of the DMN, were the features that best predicted the age. Moreover, independently of the age of the subject, connectivity between the salience network and various specific networks (i.e., visual, frontal) predicted episodic memory skills either based on a standard assessment or on an autobiographical memory task, and short-term memory binding. Finally, the connectivity between the salience and the frontal networks predicted inhibition and updating performance, but this link was no longer significant after removing the effect of age. Our findings confirm the crucial role of episodic memory and executive functions in cognitive aging and suggest a pivotal role of the salience network in neural reorganization in aging. PMID:27616991

  17. Cognitive Decline and Reorganization of Functional Connectivity in Healthy Aging: The Pivotal Role of the Salience Network in the Prediction of Age and Cognitive Performances.

    PubMed

    La Corte, Valentina; Sperduti, Marco; Malherbe, Caroline; Vialatte, François; Lion, Stéphanie; Gallarda, Thierry; Oppenheim, Catherine; Piolino, Pascale

    2016-01-01

    Normal aging is related to a decline in specific cognitive processes, in particular in executive functions and memory. In recent years a growing number of studies have focused on changes in brain functional connectivity related to cognitive aging. A common finding is the decreased connectivity within multiple resting state networks, including the default mode network (DMN) and the salience network. In this study, we measured resting state activity using fMRI and explored whether cognitive decline is related to altered functional connectivity. To this end we used a machine learning approach to classify young and old participants from functional connectivity data. The originality of the approach consists in the prediction of the performance and age of the subjects based on functional connectivity by using a machine learning approach. Our findings showed that the connectivity profile between specific networks predicts both the age of the subjects and their cognitive abilities. In particular, we report that the connectivity profiles between the salience and visual networks, and the salience and the anterior part of the DMN, were the features that best predicted the age. Moreover, independently of the age of the subject, connectivity between the salience network and various specific networks (i.e., visual, frontal) predicted episodic memory skills either based on a standard assessment or on an autobiographical memory task, and short-term memory binding. Finally, the connectivity between the salience and the frontal networks predicted inhibition and updating performance, but this link was no longer significant after removing the effect of age. Our findings confirm the crucial role of episodic memory and executive functions in cognitive aging and suggest a pivotal role of the salience network in neural reorganization in aging. PMID:27616991

  18. Beneficial effects of multisensory and cognitive stimulation on age-related cognitive decline in long-term-care institutions

    PubMed Central

    De Oliveira, Thaís Cristina Galdino; Soares, Fernanda Cabral; De Macedo, Liliane Dias E Dias; Diniz, Domingos Luiz Wanderley Picanço; Bento-Torres, Natáli Valim Oliver; Picanço-Diniz, Cristovam Wanderley

    2014-01-01

    The aim of the present report was to evaluate the effectiveness and impact of multisensory and cognitive stimulation on improving cognition in elderly persons living in long-term-care institutions (institutionalized [I]) or in communities with their families (noninstitutionalized [NI]). We compared neuropsychological performance using language and Mini-Mental State Examination (MMSE) test scores before and after 24 and 48 stimulation sessions. The two groups were matched by age and years of schooling. Small groups of ten or fewer volunteers underwent the stimulation program, twice a week, over 6 months (48 sessions in total). Sessions were based on language and memory exercises, as well as visual, olfactory, auditory, and ludic stimulation, including music, singing, and dance. Both groups were assessed at the beginning (before stimulation), in the middle (after 24 sessions), and at the end (after 48 sessions) of the stimulation program. Although the NI group showed higher performance in all tasks in all time windows compared with I subjects, both groups improved their performance after stimulation. In addition, the improvement was significantly higher in the I group than the NI group. Language tests seem to be more efficient than the MMSE to detect early changes in cognitive status. The results suggest the impoverished environment of long-term-care institutions may contribute to lower cognitive scores before stimulation and the higher improvement rate of this group after stimulation. In conclusion, language tests should be routinely adopted in the neuropsychological assessment of elderly subjects, and long-term-care institutions need to include regular sensorimotor, social, and cognitive stimulation as a public health policy for elderly persons. PMID:24600211

  19. Beneficial effects of multisensory and cognitive stimulation on age-related cognitive decline in long-term-care institutions.

    PubMed

    De Oliveira, Thaís Cristina Galdino; Soares, Fernanda Cabral; De Macedo, Liliane Dias E Dias; Diniz, Domingos Luiz Wanderley Picanço; Bento-Torres, Natáli Valim Oliver; Picanço-Diniz, Cristovam Wanderley

    2014-01-01

    The aim of the present report was to evaluate the effectiveness and impact of multisensory and cognitive stimulation on improving cognition in elderly persons living in long-term-care institutions (institutionalized [I]) or in communities with their families (noninstitutionalized [NI]). We compared neuropsychological performance using language and Mini-Mental State Examination (MMSE) test scores before and after 24 and 48 stimulation sessions. The two groups were matched by age and years of schooling. Small groups of ten or fewer volunteers underwent the stimulation program, twice a week, over 6 months (48 sessions in total). Sessions were based on language and memory exercises, as well as visual, olfactory, auditory, and ludic stimulation, including music, singing, and dance. Both groups were assessed at the beginning (before stimulation), in the middle (after 24 sessions), and at the end (after 48 sessions) of the stimulation program. Although the NI group showed higher performance in all tasks in all time windows compared with I subjects, both groups improved their performance after stimulation. In addition, the improvement was significantly higher in the I group than the NI group. Language tests seem to be more efficient than the MMSE to detect early changes in cognitive status. The results suggest the impoverished environment of long-term-care institutions may contribute to lower cognitive scores before stimulation and the higher improvement rate of this group after stimulation. In conclusion, language tests should be routinely adopted in the neuropsychological assessment of elderly subjects, and long-term-care institutions need to include regular sensorimotor, social, and cognitive stimulation as a public health policy for elderly persons. PMID:24600211

  20. Hyperphosphorylated tau in patients with refractory epilepsy correlates with cognitive decline: a study of temporal lobe resections.

    PubMed

    Tai, Xin You; Koepp, Matthias; Duncan, John S; Fox, Nick; Thompson, Pamela; Baxendale, Sallie; Liu, Joan Y W; Reeves, Cheryl; Michalak, Zuzanna; Thom, Maria

    2016-09-01

    SEE BERNASCONI DOI101093/AWW202 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Temporal lobe epilepsy, the most prevalent form of chronic focal epilepsy, is associated with a high prevalence of cognitive impairment but the responsible underlying pathological mechanisms are unknown. Tau, the microtubule-associated protein, is a hallmark of several neurodegenerative diseases including Alzheimer's disease and chronic traumatic encephalopathy. We hypothesized that hyperphosphorylated tau pathology is associated with cognitive decline in temporal lobe epilepsy and explored this through clinico-pathological study. We first performed pathological examination on tissue from 33 patients who had undergone temporal lobe resection between ages 50 and 65 years to treat drug-refractory temporal lobe epilepsy. We identified hyperphosphorylated tau protein using AT8 immunohistochemistry and compared this distribution to Braak patterns of Alzheimer's disease and patterns of chronic traumatic encephalopathy. We quantified tau pathology using a modified tau score created specifically for analysis of temporal lobectomy tissue and the Braak staging, which was limited without extra-temporal brain areas available. Next, we correlated tau pathology with pre- and postoperative cognitive test scores and clinical risk factors including age at time of surgery, duration of epilepsy, history of secondary generalized seizures, history of head injury, handedness and side of surgery. Thirty-one of 33 cases (94%) showed hyperphosphorylated tau pathology in the form of neuropil threads and neurofibrillary tangles and pre-tangles. Braak stage analysis showed 12% of our epilepsy cohort had a Braak staging III-IV compared to an age-matched non-epilepsy control group from the literature (8%). We identified a mixture of tau pathology patterns characteristic of Alzheimer's disease and chronic traumatic encephalopathy. We also found unusual patterns of subpial tau deposition, sparing of the hippocampus and

  1. Hyperphosphorylated tau in patients with refractory epilepsy correlates with cognitive decline: a study of temporal lobe resections.

    PubMed

    Tai, Xin You; Koepp, Matthias; Duncan, John S; Fox, Nick; Thompson, Pamela; Baxendale, Sallie; Liu, Joan Y W; Reeves, Cheryl; Michalak, Zuzanna; Thom, Maria

    2016-09-01

    SEE BERNASCONI DOI101093/AWW202 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Temporal lobe epilepsy, the most prevalent form of chronic focal epilepsy, is associated with a high prevalence of cognitive impairment but the responsible underlying pathological mechanisms are unknown. Tau, the microtubule-associated protein, is a hallmark of several neurodegenerative diseases including Alzheimer's disease and chronic traumatic encephalopathy. We hypothesized that hyperphosphorylated tau pathology is associated with cognitive decline in temporal lobe epilepsy and explored this through clinico-pathological study. We first performed pathological examination on tissue from 33 patients who had undergone temporal lobe resection between ages 50 and 65 years to treat drug-refractory temporal lobe epilepsy. We identified hyperphosphorylated tau protein using AT8 immunohistochemistry and compared this distribution to Braak patterns of Alzheimer's disease and patterns of chronic traumatic encephalopathy. We quantified tau pathology using a modified tau score created specifically for analysis of temporal lobectomy tissue and the Braak staging, which was limited without extra-temporal brain areas available. Next, we correlated tau pathology with pre- and postoperative cognitive test scores and clinical risk factors including age at time of surgery, duration of epilepsy, history of secondary generalized seizures, history of head injury, handedness and side of surgery. Thirty-one of 33 cases (94%) showed hyperphosphorylated tau pathology in the form of neuropil threads and neurofibrillary tangles and pre-tangles. Braak stage analysis showed 12% of our epilepsy cohort had a Braak staging III-IV compared to an age-matched non-epilepsy control group from the literature (8%). We identified a mixture of tau pathology patterns characteristic of Alzheimer's disease and chronic traumatic encephalopathy. We also found unusual patterns of subpial tau deposition, sparing of the hippocampus and

  2. Age-Related Decline in Cognitive Pain Modulation Induced by Distraction: Evidence From Event-Related Potentials.

    PubMed

    Zhou, Shu; Després, Olivier; Pebayle, Thierry; Dufour, André

    2015-09-01

    Distraction is known to reduce perceived pain but not always efficiently. Overlapping cognitive resources play a role in both pain processing and executive functions. We hypothesized that with aging, the analgesic effects of cognitive modulation induced by distraction would be reduced as a result of functional decline of frontal networks. Twenty-eight elderly and 28 young participants performed a tonic heat pain test with and without distraction (P + D vs P condition), and 2 executive tasks involving the frontal network (1-back [working memory] and go/no-go [response inhibition]), during which event-related potentials were recorded. A significant age-related difference in modulatory effect was observed during the pain-distraction test, with the older group reporting higher pain perception than the younger group during the P + D than during the P condition. Greater brain activity of early processes (P2 component) in both go/no-go and 1-back tasks correlated with less perceived pain during distraction in younger participants. For later processes, more cognitive control and attentional resources (increased N2 and P3 amplitude) needed for working memory processes were associated with greater pain perception in the older group. Inhibition processes were related to conscious distraction estimation in both groups. These findings indicate that cognitive processes subtended by resources in the frontal network, particularly working memory processes, are elicited more in elderly than in younger individuals for pain tolerance when an irrelevant task is performed simultaneously. Perspective: This study suggests that age-related declines in pain modulation are caused by functional degeneration of frontal cerebral networks, which may contribute to a higher prevalence of chronic pain. Analyzing the impact of frontal network function on pain modulation may assist in the development of more effective targeted treatment plans. PMID:26080043

  3. Post-Concussion Cognitive Declines and Symptomatology Are Not Related to Concussion Biomechanics in High School Football Players

    PubMed Central

    Eckner, James T.; Surma, Tyler; Kutcher, Jeffrey S.

    2011-01-01

    Abstract Concussion is a major public health concern with nearly 4 million injuries occurring each year in the United States. In the acute post-injury stage, concussed individuals demonstrate cognitive function and motor control declines as well as reporting increased symptoms. Researchers have hypothesized that the severity of these impairments is related to impact magnitude. Using the Head Impact Telemetry System (HITS) to record head impact biomechanics, we sought to correlate pre- and post-concussive impact characteristics with declines in cognitive performance and increases in concussion-related symptoms. Over four seasons, 19 high school football athletes wearing instrumented helmets sustained 20 diagnosed concussions. Each athlete completed a baseline computer-based symptom and cognitive assessment during the pre-season and a post-injury assessment within 24 h of injury. Correlational analyses identified no significant relationships between symptoms and cognitive performance change scores and impact biomechanics (i.e., time from session start until injury, time from the previous impact, peak linear acceleration, peak rotational acceleration, and HIT severity profile [HITsp]). Nor were there any significant relationships between change scores and the number of impacts, cumulative linear acceleration, cumulative rotational acceleration, or cumulative HITsp values associated with all impacts prior to or following the injury. This investigation is the first to examine the relationship between concussion impact characteristics, including cumulative impact profiles, and post-morbid outcomes in high school athletes. There appears to be no association between head impact biomechanics and post-concussive outcomes. As such, the use of biomechanical variables to predict injury severity does not appear feasible at this time. PMID:21644811

  4. Exercise reduces diet-induced cognitive decline and increases hippocampal brain-derived neurotrophic factor in CA3 neurons

    PubMed Central

    Noble, Emily E.; Mavanji, Vijayakumar; Little, Morgan R.; Billington, Charles J.; Kotz, Catherine M.; Wang, ChuanFeng

    2014-01-01

    Background Previous studies have shown that a western diet impairs, whereas physical exercise enhances hippocampus-dependent learning and memory. Both diet and exercise influence expression of hippocampal brain-derived neurotrophic factor (BDNF), which is associated with improved cognition. We hypothesized that exercise reverses diet-induced cognitive decline while increasing hippocampal BDNF. Methods To test the effects of exercise on hippocampal-dependent memory, we compared cognitive scores of Sprague-Dawley rats exercised by voluntary running wheel (RW) access or forced treadmill (TM) to sedentary (Sed) animals. Memory was tested by two-way active avoidance test (TWAA), in which animals are exposed to a brief shock in a specific chamber area. When an animal avoids, escapes or has reduced latency to do either, this is considered a measure of memory. In a second experiment, rats were fed either a high-fat diet or control diet for 16 weeks, then randomly assigned to running wheel access or sedentary condition, and TWAA memory was tested once a week for seven weeks of exercise intervention. Results Both groups of exercised animals had improved memory as indicated by reduced latency to avoid and escape shock, and increased avoid and escape episodes (p<0.05). Exposure to a high-fat diet resulted in poor performance during both the acquisition and retrieval phases of the memory test as compared to controls. Exercise reversed high-fat diet-induced memory impairment, and increased brain-derived neurotrophic factor (BDNF) in neurons of the hippocampal CA3 region. Conclusions These data suggest that exercise improves memory retrieval, particularly with respect to avoiding aversive stimuli, and may be beneficial in protecting against diet induced cognitive decline, likely via elevated BDNF in neurons of the CA3 region. PMID:24755094

  5. Post-concussion cognitive declines and symptomatology are not related to concussion biomechanics in high school football players.

    PubMed

    Broglio, Steven P; Eckner, James T; Surma, Tyler; Kutcher, Jeffrey S

    2011-10-01

    Concussion is a major public health concern with nearly 4 million injuries occurring each year in the United States. In the acute post-injury stage, concussed individuals demonstrate cognitive function and motor control declines as well as reporting increased symptoms. Researchers have hypothesized that the severity of these impairments is related to impact magnitude. Using the Head Impact Telemetry System (HITS) to record head impact biomechanics, we sought to correlate pre- and post-concussive impact characteristics with declines in cognitive performance and increases in concussion-related symptoms. Over four seasons, 19 high school football athletes wearing instrumented helmets sustained 20 diagnosed concussions. Each athlete completed a baseline computer-based symptom and cognitive assessment during the pre-season and a post-injury assessment within 24 h of injury. Correlational analyses identified no significant relationships between symptoms and cognitive performance change scores and impact biomechanics (i.e., time from session start until injury, time from the previous impact, peak linear acceleration, peak rotational acceleration, and HIT severity profile [HITsp]). Nor were there any significant relationships between change scores and the number of impacts, cumulative linear acceleration, cumulative rotational acceleration, or cumulative HITsp values associated with all impacts prior to or following the injury. This investigation is the first to examine the relationship between concussion impact characteristics, including cumulative impact profiles, and post-morbid outcomes in high school athletes. There appears to be no association between head impact biomechanics and post-concussive outcomes. As such, the use of biomechanical variables to predict injury severity does not appear feasible at this time.

  6. Is Metformin-Induced Vitamin B12 Deficiency Responsible for Cognitive Decline in Type 2 Diabetes?

    PubMed Central

    Khattar, Deepti; Khaliq, Farah; Vaney, Neelam; Madhu, S. V.

    2016-01-01

    Introduction: Diabetes mellitus has its deleterious effects on various aspects of cognition such as memory function, executive function, and information-processing speed. The present study aims to assess cognition in diabetes patients and also tries to find its association with Vitamin B12 deficiency induced by metformin. Materials and Methods: Thirty diabetics taking metformin and thirty nondiabetic controls were enrolled. Event-related potentials (ERPs) and serum Vitamin B12 levels were evaluated in them. Results: Vitamin B12 levels were found to be deficient, and latencies of waves P200 and P300 were prolonged in the diabetics as compared to the controls. The dose and duration of metformin had no association with the ERPs. Conclusions: Although the Vitamin B12 levels were deficient in diabetics on metformin, this is not the reason behind the cognitive impairment found in them. PMID:27570337

  7. Management Strategy, the CEO's Cognitive Style and Organizational Growth/Decline.

    ERIC Educational Resources Information Center

    Neumann, Yoram; Finaly-Neumann, Edith

    1994-01-01

    Develops a model linking organizational growth and decline to competitive strategy, the strategy-making process, and the chief executive officer's personal characteristics. The model was empirically tested for private liberal arts colleges. Enrollment growth is associated with focused strategy, the CEO's innovative style, differentiation, and…

  8. Respiratory training as strategy to prevent cognitive decline in aging: a randomized controlled trial

    PubMed Central

    Ferreira, Leandro; Tanaka, Kátia; Santos-Galduróz, Ruth Ferreira; Galduróz, José Carlos Fernandes

    2015-01-01

    Background Inadequate oxygenation may cause lesions and brain atrophy during aging. Studies show a positive association between pulmonary function and the cognitive performance of individuals from middle age on. Objective To investigate the effect of aerobic physical exercises and respiratory training on the blood oxygenation, pulmonary functions, and cognition of the elderly. Design This was a randomized and controlled trial with three parallel groups. A total of 195 community-dwelling elderly were assessed for eligibility; only n=102 were included and allocated into the three groups, but after 6 months, n=68 were analyzed in the final sample. Participants were randomized into a social interaction group (the control group), an aerobic exercise group (the “walking” group), or a respiratory training group (the “breathing” group). The main outcome measures were the Wechsler Adult Intelligence Scale, Wechsler Memory Scale, Wisconsin Card Sorting Test, respiratory muscular strength, cirtometry (thoracic–abdominal circumference); oxygen saturation in arterial blood (SpO2), and hemogram. Results No differences were observed for any of the blood parameters. Aerobic exercise and respiratory training were effective in improving the pulmonary parameters. Better cognitive performance was observed for the breathing group as regards abstraction and mental flexibility. The walking group remained stable in the cognitive performance of most of the tests, except attention. The control group presented worst performance in mental manipulation of information, abstraction, mental flexibility, and attention. Conclusion Our results showed that both the walking and breathing groups presented improvement of pulmonary function. However, only the breathing group showed improved cognitive function (abstraction, mental flexibility). The improvement in cognitive functions cannot be explained by blood parameters, such as SpO2, erythrocytes, hemoglobin, and hematocrit. PMID:25848235

  9. Age-Related Declines in General Cognitive Abilities of Balb/C Mice and General Activity Are Associated with Disparities in Working Memory, Body Weight, and General Activity

    ERIC Educational Resources Information Center

    Matzel, Louis D.; Grossman, Henya; Light, Kenneth; Townsend, David; Kolata, Stefan

    2008-01-01

    A defining characteristic of age-related cognitive decline is a deficit in general cognitive performance. Here we use a testing and analysis regimen that allows us to characterize the general learning abilities of young (3-5 mo old) and aged (19-21 mo old) male and female Balb/C mice. Animals' performance was assessed on a battery of seven diverse…

  10. Coffee, tea, and caffeine consumption and prevention of late-life cognitive decline and dementia: a systematic review.

    PubMed

    Panza, F; Solfrizzi, V; Barulli, M R; Bonfiglio, C; Guerra, V; Osella, A; Seripa, D; Sabbà, C; Pilotto, A; Logroscino, G

    2015-03-01

    A prolonged preclinical phase of more than two decades before the onset of dementia suggested that initial brain changes of Alzheimer's disease (AD) and the symptoms of advanced AD may represent a unique continuum. Given the very limited therapeutic value of drugs currently used in the treatment of AD and dementia, preventing or postponing the onset of AD and delaying or slowing its progression are becoming mandatory. Among possible reversible risk factors of dementia and AD, vascular, metabolic, and lifestyle-related factors were associated with the development of dementia and late-life cognitive disorders, opening new avenues for the prevention of these diseases. Among diet-associated factors, coffee is regularly consumed by millions of people around the world and owing to its caffeine content, it is the best known psychoactive stimulant resulting in heightened alertness and arousal and improvement of cognitive performance. Besides its short-term effect, some case-control and cross-sectional and longitudinal population-based studies evaluated the long-term effects on brain function and provided some evidence that coffee, tea, and caffeine consumption or higher plasma caffeine levels may be protective against cognitive impairment/decline and dementia. In particular, several cross-sectional and longitudinal population-based studies suggested a protective effect of coffee, tea, and caffeine use against late-life cognitive impairment/decline, although the association was not found in all cognitive domains investigated and there was a lack of a distinct dose-response association, with a stronger effect among women than men. The findings on the association of coffee, tea, and caffeine consumption or plasma caffeine levels with incident mild cognitive impairment and its progression to dementia were too limited to draw any conclusion. Furthermore, for dementia and AD prevention, some studies with baseline examination in midlife pointed to a lack of association, although

  11. Cognitive decline is mediated by gray matter changes during middle age.

    PubMed

    Ferreira, Daniel; Molina, Yaiza; Machado, Alejandra; Westman, Eric; Wahlund, Lars-Olof; Nieto, Antonieta; Correia, Rut; Junqué, Carme; Díaz-Flores, Lucio; Barroso, José

    2014-05-01

    The present theoretical framework of Alzheimer's disease proposes that pathophysiological changes occur 10-20 years before the diagnosis of dementia. We addressed the question of how age-related changes in gray matter mediate the cognitive performance during middle age. Eighty-two participants (40-50 years, ±2) were assessed with a comprehensive neuropsychological battery covering a broad spectrum of cognitive domains and components. Mediation effects were studied with hierarchical regression and bootstrapping analysis. Results showed that more vulnerable cognitive components were related to executive functioning and in a lesser degree to processing speed. Age-related differences in gray matter mainly involved the frontal lobes. Moreover, age-related differences in visuoconstructive, visuospatial functions, reaction time, and mental flexibility and executive control were mediated by several gray matter regions. It is important to increase the knowledge of the impact of brain changes on cognitive function during middle age. To define the early stages of the aging process may allow early detection of pathologic changes and therapeutic interventions.

  12. Cohort Differences in Cognitive Aging and Terminal Decline in the Seattle Longitudinal Study

    ERIC Educational Resources Information Center

    Gerstorf, Denis; Ram, Nilam; Hoppmann, Christiane; Willis, Sherry L.; Schaie, K. Warner

    2011-01-01

    Life span researchers have long been interested in how and why fundamental aspects of human ontogeny differ between cohorts of people who have lived through different historical epochs. When examined at the same age, later born cohorts are often cognitively and physically fitter than earlier born cohorts. Less is known, however, about cohort…

  13. Secular Declines in Cognitive Test Scores: A Reversal of the Flynn Effect

    ERIC Educational Resources Information Center

    Teasdale, Thomas W.; Owen, David R.

    2008-01-01

    Scores on cognitive tests have been very widely reported to have increased through the decades of the last century, a generational phenomenon termed the "Flynn Effect" since it was most comprehensively documented by James Flynn in the 1980's. There has, however, been very little evidence concerning any continuity of the effect specifically into…

  14. Neuroprotective and nootropic activity of Clitorea ternatea Linn.(Fabaceae) leaves on diabetes induced cognitive decline in experimental animals

    PubMed Central

    Talpate, Karuna A.; Bhosale, Uma A.; Zambare, Mandar R.; Somani, Rahul S

    2014-01-01

    Purpose: Ethanol extract of Clitorea ternatea (EECT) was evaluated in diabetes-induced cognitive decline rat model for its nootropic and neuroprotective activity. Materials and Methods: Effect on spatial working memory, spatial reference memory and spatial working-reference memory was evaluated by Y maze, Morris water maze and Radial arm maze respectively. Neuroprotective effects of EECT was studied by assaying acetylcholinesterase, lipid peroxide, superoxide dismutase (SOD), total nitric oxide (NO), catalase (CAT) and glutathione (GSH) levels in the brain of diabetic rats. Results: The EECT (200 and 400 mg/kg) was found to cause significant increase in spatial working memory (P < 0.05), spatial reference memory (P < 0.001) and spatial working-reference (P < 0.001) in retention trials on Y maze, Morris water maze and Radial arm maze respectively. Whereas significant decrease in acetylcholinesterase activity (P < 0.05), lipid peroxide (P < 0.001), total NO (P < 0.001) and significant increase in SOD, CAT and GSH levels was observed in animals treated with EECT (200 and 400 mg/kg) compared to diabetic control group. Conclusions: The present data indicates that Clitorea ternatea tenders protection against diabetes induced cognitive decline and merits the need for further studies to elucidate its mode of action. PMID:24459404

  15. A critical review of Vitamin C for the prevention of age-related cognitive decline and Alzheimer’s disease

    PubMed Central

    Harrison, Fiona E

    2013-01-01

    Antioxidants in the diet have long been thought to confer some level of protection against the oxidative damage that is involved in the pathology of Alzheimer’s disease as well as general cognitive decline in normal aging. Nevertheless, support for this hypothesis in the literature is equivocal. In the case of vitamin C (ascorbic acid) in particular, lack of consideration of some of the specific features of vitamin C metabolism has led to studies in which classification of participants according to vitamin C status is inaccurate, and the absence of critical information precludes the drawing of appropriate conclusions. Vitamin C levels in plasma are not always reported, and estimated daily intake from food diaries may not be accurate or reflect actual plasma values. The ability to transport ingested vitamin C from the intestines into blood is limited by the saturable sodium-dependent vitamin C transporter (SVCT1) and thus very high intakes, and the use of supplements are often erroneously considered to be of greater benefit that they really are. The current review documents differences among the studies in terms of vitamin C status of participants. Overall, there is a large body of evidence that maintaining healthy vitamin C levels can have a protective function against age-related cognitive decline and Alzheimer’s disease, but avoiding vitamin C deficiency is likely to be more beneficial than taking supplements on top of a normal, healthy diet. PMID:22366772

  16. Correcting Bias Caused by Missing Data in the Estimate of the Effect of Apolipoprotein ε4 on Cognitive Decline.

    PubMed

    Hall, Charles B; Lipton, Richard B; Katz, Mindy J; Wang, Cuiling

    2015-01-01

    Longitudinal administration of neuropsychological instruments are often used to assess age-related changes in cognition. Informative loss to follow-up may bias the results of these studies. Herein, we use auxiliary data to adjust for informative loss to follow-up. In the Einstein Aging Study, memory was assessed annually in a community sample of adults age 70+, free of dementia at baseline, using the free recall from the Free and Cued Selective Reminding Test, and via telephone using the Memory Impairment Screen for Telephone (the auxiliary data). Joint linear mixed models were used to assess how the effect of the APOE ε4 genotype may be affected by informative missingness in the in-person data. A total of 620 EAS participants contributed 2085 person years of follow-up to the analyses. Memory decline rates estimated in joint models were 19% greater in ε4 negative participants and 27% greater in ε4 positive participants compared to traditional approaches; the effect of APOE ε4 on memory decline was 37% greater. Joint modeling methods can help address bias caused by informative missing data in the estimation of the effect of risk factors on cognitive change, and may be applicable to a broader range of outcomes in longitudinal aging studies. PMID:25389642

  17. The omega-6/omega-3 ratio and dementia or cognitive decline: a systematic review on human studies and biological evidence.

    PubMed

    Loef, Martin; Walach, Harald

    2013-01-01

    It has been suggested that the intake of certain fatty acids may influence the risk of dementia. However, current reviews have focused only on the therapeutic effects of omega-3 fatty acids, mostly as supplements. To date, the evidence for the relevance of the omega-6/omega-3 ratio has been neglected. Therefore, we searched the databases Alois, Medline, Biosis, Embase, Cochrane Central Register of Controlled Trials, and The Cochrane Database of Systematic Reviews for "essential fatty acids" and "dementia" and aimed to conduct a comprehensive review across study types. All studies that reported on the association between the n-6/n-3 ratio and dementia or cognitive decline were selected. In the 13 animal studies we examined, the dietary n-6/n-3 ratio was shown to affect brain composition, Alzheimer's disease pathology, and behavior. Our review of the 14 studies in humans that fulfilled the selection criteria (7 prospective studies, 3 cross-sectional studies, 1 controlled trial, 3 case-control studies) provided evidence, albeit limited, supporting an association between the n-6/n-3 ratio, cognitive decline, and incidence of dementia. This review supports growing evidence of a positive association between the dietary n-6/n-3 ratio and the risk of Alzheimer's disease.

  18. Correcting bias caused by missing data in the estimate of the effect of apolipoprotein ε4 on cognitive decline

    PubMed Central

    Hall, Charles B.; Lipton, Richard B.; Katz, Mindy J.; Wang, Cuiling

    2014-01-01

    Objective Longitudinal administration of neuropsychological instruments are often used to assess age-related changes in cognition. Informative loss to follow-up may bias the results of these studies. Herein, we use auxiliary data to adjust for informative loss to follow-up. Method In the Einstein Aging Study, memory was assessed annually in a community sample of adults age 70+, free of dementia at baseline, using the free recall from the Free and Cued Selective Reminding Test, and via telephone using the Memory Impairment Screen for Telephone (the auxiliary data). Joint linear mixed models were used to assess how the effect of the APOE ε4 genotype may be affected by informative missingness in the in-person data. Results 620 EAS participants contributed 2085 person years of follow-up to the analyses. Memory decline rates estimated in joint models were 19% greater in ε4 negative participants and 27% greater in ε4 positive participants compared to traditional approaches; the effect of APOE ε4 on memory decline was 37% greater. Conclusions Joint modelling methods can help address bias caused by informative missing data in the estimation of the effect of risk factors on cognitive change, and may be applicable to a broader range of outcomes in longitudinal aging studies. PMID:25389642

  19. A low glycaemic index breakfast cereal preferentially prevents children's cognitive performance from declining throughout the morning.

    PubMed

    Ingwersen, Jeanet; Defeyter, Margaret Anne; Kennedy, David O; Wesnes, Keith A; Scholey, Andrew B

    2007-07-01

    This study investigated whether the glycaemic index (GI) of breakfast cereal differentially affects children's attention and memory. Using a balanced cross-over design, on two consecutive mornings 64 children aged 6-11 years were given a high GI cereal and a low GI cereal in a counterbalanced order. They performed a series of computerised tests of attention and memory, once prior to breakfast and three times following breakfast at hourly intervals. The results indicate that children's performance declines throughout the morning and that this decline can be significantly reduced following the intake of a low GI cereal as compared with a high GI cereal on measures of accuracy of attention (M=-6.742 and -13.510, respectively, p<0.05) and secondary memory (M=-30.675 and -47.183, respectively, p<0.05). PMID:17224202

  20. Treating vascular risk factors and maintaining vascular health: Is this the way towards successful cognitive ageing and preventing cognitive decline?

    PubMed Central

    Alagiakrishnan, K; McCracken, P; Feldman, H

    2006-01-01

    Dementia is a progressive disorder that typically worsens with time and from which recovery is unlikely. The incidence of dementia increases exponentially with ageing and is an important public health challenge. There is now growing evidence for the role of vascular factors in Alzheimer's disease, mixed dementia (Alzheimer's disease with cerebrovascular disease), and of course vascular dementia. With the rising prevalence of vascular disease, there are increasing numbers of people who are identified to be at risk of cognitive impairment. By changing modifiable vascular risk factors, there is emerging evidence that it may be possible to prevent or delay the expression and progression of dementia. PMID:16461472

  1. Diffusion Tensor Imaging of Normal-Appearing White Matter as Biomarker for Radiation-Induced Late Delayed Cognitive Decline

    SciTech Connect

    Chapman, Christopher H.; Nagesh, Vijaya; Sundgren, Pia C.; Buchtel, Henry; Chenevert, Thomas L.; Junck, Larry; Lawrence, Theodore S.; Tsien, Christina I.; Cao, Yue

    2012-04-01

    Purpose: To determine whether early assessment of cerebral white matter degradation can predict late delayed cognitive decline after radiotherapy (RT). Methods and Materials: Ten patients undergoing conformal fractionated brain RT participated in a prospective diffusion tensor magnetic resonance imaging study. Magnetic resonance imaging studies were acquired before RT, at 3 and 6 weeks during RT, and 10, 30, and 78 weeks after starting RT. The diffusivity variables in the parahippocampal cingulum bundle and temporal lobe white matter were computed. A quality-of-life survey and neurocognitive function tests were administered before and after RT at the magnetic resonance imaging follow-up visits. Results: In both structures, longitudinal diffusivity ({lambda}{sub Double-Vertical-Line }) decreased and perpendicular diffusivity ({lambda}{sub Up-Tack }) increased after RT, with early changes correlating to later changes (p < .05). The radiation dose correlated with an increase in cingulum {lambda}{sub Up-Tack} at 3 weeks, and patients with >50% of cingula volume receiving >12 Gy had a greater increase in {lambda}{sub Up-Tack} at 3 and 6 weeks (p < .05). The post-RT changes in verbal recall scores correlated linearly with the late changes in cingulum {lambda}{sub Double-Vertical-Line} (30 weeks, p < .02). Using receiver operating characteristic curves, early cingulum {lambda}{sub Double-Vertical-Line} changes predicted for post-RT changes in verbal recall scores (3 and 6 weeks, p < .05). The neurocognitive test scores correlated significantly with the quality-of-life survey results. Conclusions: The correlation between early diffusivity changes in the parahippocampal cingulum and the late decline in verbal recall suggests that diffusion tensor imaging might be useful as a biomarker for predicting late delayed cognitive decline.

  2. Adrenergic Drugs Blockers or Enhancers for Cognitive Decline ? What to Choose for Alzheimer's Disease Patients?

    PubMed

    Femminella, Grazia D; Leosco, Dario; Ferrara, Nicola; Rengo, Giuseppe

    2016-01-01

    The adrenergic system has an important role in normal central nervous system function as well as in brain disease. The locus coeruleus, the main source of norepinephrine in brain, is involved in the regulation of learning and memory, reinforcement of sleep-wake cycle and synaptic plasticity. In Alzheimer's disease, locus coeruleus degeneration is observed early in the course of the disease, years before the onset of clinical cognitive signs, with neurofibrillary detected at the stage of mild cognitive impairment, preceding amyloid deposition. Thus, in the last years, a great interest has grown in evaluating the possibility of central adrenergic system modulation as a therapeutic tool in Alzheimer's disease. However, evidences do not show univocal results, with some studies suggesting that adrenergic stimulation might be beneficial in Alzheimer's Disease and some others favoring adrenergic blockade. In this review, we summarize data from both hypothesis and describe the pathophysiological role of the adrenergic system in neurodegeneration. PMID:27189470

  3. Fatty acid status and its relationship to cognitive decline and homocysteine levels in the elderly.

    PubMed

    Baierle, Marília; Vencato, Patrícia H; Oldenburg, Luiza; Bordignon, Suelen; Zibetti, Murilo; Trentini, Clarissa M; Duarte, Marta M M F; Veit, Juliana C; Somacal, Sabrina; Emanuelli, Tatiana; Grune, Tilman; Breusing, Nicolle; Garcia, Solange C

    2014-09-01

    Polyunsaturated fatty acids (PUFAs), especially the n-3 series, are known for their protective effects. Considering that cardiovascular diseases are risk factors for dementia, which is common at aging, the aim of this study was to evaluate whether fatty acid status in the elderly was associated with cognitive function and cardiovascular risk. Forty-five elderly persons (age ≥ 60 years) were included and divided into two groups based on their Mini-Mental Status Examination score adjusted for educational level: the case group (n = 12) and the control group (n = 33). Serum fatty acid composition, homocysteine (Hcy), hs-CRP, lipid profile and different cognitive domains were evaluated. The case group, characterized by reduced cognitive performance, showed higher levels of 14:0, 16:0, 16:1n-7 fatty acids and lower levels of 22:0, 24:1n-9, 22:6n-3 (DHA) and total PUFAs compared to the control group (p < 0.05). The n-6/n-3 ratio was elevated in both study groups, whereas alterations in Hcy, hs-CRP and lipid profile were observed in the case group. Cognitive function was positively associated with the 24:1n-9, DHA and total n-3 PUFAs, while 14:0, 16:0 and 16:1n-7 fatty acids, the n-6/n-3 ratio and Hcy were inversely associated. In addition, n-3 PUFAs, particularly DHA, were inversely associated with cardiovascular risk, assessed by Hcy levels in the elderly. PMID:25221976

  4. What physical performance measures predict incident cognitive decline among intact older adults? A 4.4year follow up study.

    PubMed

    Veronese, Nicola; Stubbs, Brendon; Trevisan, Caterina; Bolzetta, Francesco; De Rui, Marina; Solmi, Marco; Sartori, Leonardo; Musacchio, Estella; Zambon, Sabina; Perissinotto, Egle; Crepaldi, Gaetano; Manzato, Enzo; Sergi, Giuseppe

    2016-08-01

    Reductions in physical performance, cognitive impairment (CI) and decline (CD), are common in older age, but few prospective cohort studies have considered the relationship between these domains. In this study we investigated whether reduced physical performance and low handgrip/lower limbs strength, could predict a higher incidence of CI/CD during a 4-year follow-up among a cohort of elderly individuals. From 3099 older community-dwelling individuals initially enrolled in the Progetto Veneto Anziani (PRO.V.A.) study, 1249 participants without CI at the baseline were included (mean age 72.2years, 59.5% females). Physical performance measures included the Short Physical Performance Battery (SPPB), 4m gait speed, chair stands time, leg extension and flexion, handgrip strength, and 6-Minute Walking Test (6MWT), categorized in gender-specific tertiles. CI was defined as a Mini-Mental State Examination (MMSE) score below 24; CD a decline of 3 or more points in the MMSE without CI. At baseline, participants developing CI during follow-up scored significantly worse across all physical performance measures compared to those that retained normal cognitive status. After adjusting for potential confounders, a significant trend for MMSE changes was noted for all physical performance tests, except for the SPPB and chair stands time. Multinomial logistic regression revealed that slow gait speed at baseline significantly predicted CD at follow up. Poor SPPB performance and slower gait speed predicted the onset of CI at the follow-up. In conclusion, slow walking speed appears to be the best independent predictor of poor cognitive status over a 4.4-year follow-up, while other items of SPPB were also significantly associated with CI.

  5. The Impact of Age on Cognition.

    PubMed

    Murman, Daniel L

    2015-08-01

    This article reviews the cognitive changes that occur with normal aging, the structural and functional correlates of these cognitive changes, and the prevalence and cognitive effects of age-associated diseases. Understanding these age-related changes in cognition is important given our growing elderly population and the importance of cognition in maintaining functional independence and effective communication with others. The most important changes in cognition with normal aging are declines in performance on cognitive tasks that require one to quickly process or transform information to make a decision, including measures of speed of processing, working memory, and executive cognitive function. Cumulative knowledge and experiential skills are well maintained into advanced age. Structural and function changes in the brain correlate with these age-related cognitive changes, including alterations in neuronal structure without neuronal death, loss of synapses, and dysfunction of neuronal networks. Age-related diseases accelerate the rate of neuronal dysfunction, neuronal loss, and cognitive decline, with many persons developing cognitive impairments severe enough to impair their everyday functional abilities. There is emerging evidence that healthy lifestyles may decrease the rate of cognitive decline seen with aging and help delay the onset of cognitive symptoms in the setting of age-associated diseases. PMID:27516712

  6. Renal Cell Carcinoma Presenting with Paraneoplastic Hallucinations and Cognitive Decline from Limbic Encephalitis.

    PubMed

    Harrison, Joshua W; Cherukuri, Ramesh; Buchan, Debra

    2015-07-01

    We present a 66-year-old woman with 2 months of visual hallucinations, unintentional weight loss, and short-term memory decline, whose clinical presentation and EEG supported a diagnosis of limbic encephalitis. Subsequent evaluation for a paraneoplastic etiology revealed a renal mass, which was resected and identified as clear cell renal carcinoma. The patient's clinical condition improved after resection of the mass. When patients present with incongruous subacute neuropsychiatric symptoms, clinicians should be mindful of paraneoplastic neurological disorders, as early diagnosis and treatment of malignancy may lead to symptomatic improvement.

  7. Renal Cell Carcinoma Presenting with Paraneoplastic Hallucinations and Cognitive Decline from Limbic Encephalitis.

    PubMed

    Harrison, Joshua W; Cherukuri, Ramesh; Buchan, Debra

    2015-07-01

    We present a 66-year-old woman with 2 months of visual hallucinations, unintentional weight loss, and short-term memory decline, whose clinical presentation and EEG supported a diagnosis of limbic encephalitis. Subsequent evaluation for a paraneoplastic etiology revealed a renal mass, which was resected and identified as clear cell renal carcinoma. The patient's clinical condition improved after resection of the mass. When patients present with incongruous subacute neuropsychiatric symptoms, clinicians should be mindful of paraneoplastic neurological disorders, as early diagnosis and treatment of malignancy may lead to symptomatic improvement. PMID:25608740

  8. SIRT1 in the brain—connections with aging-associated disorders and lifespan

    PubMed Central

    Ng, Fanny; Wijaya, Laura; Tang, Bor Luen

    2015-01-01

    The silent mating type information regulation 2 proteins (sirtuins) 1 of class III histone deacetylases (HDACs) have been associated with health span and longevity. SIRT1, the best studied member of the mammalian sirtuins, has a myriad of roles in multiple tissues and organs. However, a significant part of SIRT1’s role that impinges on aging and lifespan may lie in its activities in the central nervous system (CNS) neurons. Systemically, SIRT1 influences energy metabolism and circadian rhythm through its activity in the hypothalamic nuclei. From a cell biological perspective, SIRT1 is a crucial component of multiple interconnected regulatory networks that modulate dendritic and axonal growth, as well as survival against stress. This neuronal cell autonomous activity of SIRT1 is also important for neuronal plasticity, cognitive functions, as well as protection against aging-associated neuronal degeneration and cognitive decline. We discuss recent findings that have shed light on the various activities of SIRT1 in the brain, which collectively impinge on aging-associated disorders and lifespan. PMID:25805970

  9. Uncovering Molecular Biomarkers That Correlate Cognitive Decline with the Changes of Hippocampus' Gene Expression Profiles in Alzheimer's Disease

    PubMed Central

    Gómez Ravetti, Martín; Rosso, Osvaldo A.; Berretta, Regina; Moscato, Pablo

    2010-01-01

    Background Alzheimer's disease (AD) is characterized by a neurodegenerative progression that alters cognition. On a phenotypical level, cognition is evaluated by means of the MiniMental State Examination (MMSE) and the post-morten examination of Neurofibrillary Tangle count (NFT) helps to confirm an AD diagnostic. The MMSE evaluates different aspects of cognition including orientation, short-term memory (retention and recall), attention and language. As there is a normal cognitive decline with aging, and death is the final state on which NFT can be counted, the identification of brain gene expression biomarkers from these phenotypical measures has been elusive. Methodology/Principal Findings We have reanalysed a microarray dataset contributed in 2004 by Blalock et al. of 31 samples corresponding to hippocampus gene expression from 22 AD subjects of varying degree of severity and 9 controls. Instead of only relying on correlations of gene expression with the associated MMSE and NFT measures, and by using modern bioinformatics methods based on information theory and combinatorial optimization, we uncovered a 1,372-probe gene expression signature that presents a high-consensus with established markers of progression in AD. The signature reveals alterations in calcium, insulin, phosphatidylinositol and wnt-signalling. Among the most correlated gene probes with AD severity we found those linked to synaptic function, neurofilament bundle assembly and neuronal plasticity. Conclusions/Significance A transcription factors analysis of 1,372-probe signature reveals significant associations with the EGR/KROX family of proteins, MAZ, and E2F1. The gene homologous of EGR1, zif268, Egr-1 or Zenk, together with other members of the EGR family, are consolidating a key role in the neuronal plasticity in the brain. These results indicate a degree of commonality between putative genes involved in AD and prion-induced neurodegenerative processes that warrants further investigation

  10. Blood Biomarkers Associated with Cognitive Decline in Early Stage and Drug-Naive Parkinson’s Disease Patients

    PubMed Central

    Santiago, Jose A.; Potashkin, Judith A.

    2015-01-01

    Early diagnosis of Parkinson’s disease (PD) continues to be a major challenge in the field. The lack of a robust biomarker to detect early stage PD patients has considerably slowed the progress toward the development of potential therapeutic agents. We have previously evaluated several RNA biomarkers in whole blood from participants enrolled in two independent clinical studies. In these studies, PD patients were medicated, thus, expression of these biomarkers in de novo patients remains unknown. To this end, we tested ten RNA biomarkers in blood samples from 99 untreated PD patients and 101 HC nested in the cross-sectional Parkinson’s Progression Markers Initiative by quantitative real-time PCR. One biomarker out of ten, COPZ1 trended toward significance (nominal p = 0.009) when adjusting for age, sex, and educational level. Further, COPZ1, EFTUD2 and PTBP1 mRNAs correlated with clinical features in PD patients including the Hoehn and Yahr scale, Movement Disorder Society revision of Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and Montreal Cognitive Assessment (MoCA) score. Levels of EFTUD2 and PTBP1 were significantly higher in cognitively normal PD patients (PD-CN) compared to cognitively impaired PD patients (PD-MCI). Interestingly, blood glucose levels were significantly higher in PD and PD-MCI patients (≥ 100 mg/dL, pre-diabetes) compared to HC. Collectively, we report the association of three RNA biomarkers, COPZ1, EFTUD2 and PTBP1 with clinical features including cognitive decline in early drug-naïve PD patients. Further, our results show that drug-naïve PD and PD-MCI patients have glucose levels characteristic of pre-diabetes patients, suggesting that impaired glucose metabolism is an early event in PD. Evaluation of these potential biomarkers in a larger longitudinal study is warranted. PMID:26566043

  11. ROLE OF SOLUBLE EPOXIDE HYDROLASE IN AGE-RELATED VASCULAR COGNITIVE DECLINE

    PubMed Central

    Nelson, Jonathan W.; Young, Jennifer M.; Borkar, Rohan; Woltjer, Randy L.; Quinn, Joseph F.; Silbert, Lisa C.; Grafe, Marjorie R.; Alkayed, Nabil J.

    2014-01-01

    P450 eicosanoids are important regulators of the cerebral microcirculation, but their role in cerebral small vessel disease is unclear. We tested the hypothesis that vascular cognitive impairment (VCI) is linked to reduced cerebral microvascular eicosanoid signaling. We analyzed human brain tissue from individuals formerly enrolled in the Oregon Brain Aging Study, who had a history of cognitive impairment histopathological evidence of microvascular disease. VCI subjects had significantly higher lesion burden both on premortem MRI and postmortem histopathology compared to age- and sex-matched controls. Mass spectrometry-based eicosanoid analysis revealed that 14,15-dihydroxyeicosatrienoic acid (DHET) was elevated in cortical brain tissue from VCI subjects. Immunoreactivity of soluble epoxide hydrolase (sEH), the enzyme responsible for 14,15-DHET formation, was localized to cerebral microvascular endothelium, and was enhanced in microvessels of affected tissue. Finally, we evaluated the genotype frequency of two functional single nucleotide polymorphisms of sEH gene EPHX2 in VCI and control groups. Our findings support a role for sEH and a potential benefit from sEH inhibitors in age-related VCI. PMID:25277097

  12. The impact of environmental risk factors on HIV-associated cognitive decline in children.

    PubMed

    Hochhauser, C J; Gaur, S; Marone, R; Lewis, M

    2008-07-01

    Both the human immunodeficiency virus (HIV) and environmental stress have been independently associated with decreased cognitive functioning in children. Given that they are also known to have a strong relationship with each other, the present study sought to test the hypothesis that children in conditions of high environmental risk would be at greater risk for the cognitive complications related to immunosuppression. A retrospective review was conducted to examine the records of 141 children treated at a large pediatric AIDS clinic from 1993 to 2000. CD4+ lymphocyte levels were recorded from laboratory results and IQ scores were recorded from routine psychological evaluations. Key indicators of environmental risk were collected and combined into one measure of overall environmental risk. Pearson product moment correlations were conducted to examine the relationship between environmental risk, age-adjusted CD4 and IQ. Results indicated a significant correlation between CD4 and IQ, with higher levels of immunocompetence predicting higher IQ scores. When subjects were dichotomized based on their environmental risk score, there was no relationship between CD4 count and IQ in the low environmental risk group. In contrast, CD4 was positively associated with IQ in the high environmental risk group. It is proposed that this may be due to gp120 levels in immunocompromised children being particularly toxic to the hippocampus and cortex under conditions of high stress but not so under conditions of low stress.

  13. CANTAB object recognition and language tests to detect aging cognitive decline: an exploratory comparative study

    PubMed Central

    Cabral Soares, Fernanda; de Oliveira, Thaís Cristina Galdino; de Macedo, Liliane Dias e Dias; Tomás, Alessandra Mendonça; Picanço-Diniz, Domingos Luiz Wanderley; Bento-Torres, João; Bento-Torres, Natáli Valim Oliver; Picanço-Diniz, Cristovam Wanderley

    2015-01-01

    Objective The recognition of the limits between normal and pathological aging is essential to start preventive actions. The aim of this paper is to compare the Cambridge Neuropsychological Test Automated Battery (CANTAB) and language tests to distinguish subtle differences in cognitive performances in two different age groups, namely young adults and elderly cognitively normal subjects. Method We selected 29 young adults (29.9±1.06 years) and 31 older adults (74.1±1.15 years) matched by educational level (years of schooling). All subjects underwent a general assessment and a battery of neuropsychological tests, including the Mini Mental State Examination, visuospatial learning, and memory tasks from CANTAB and language tests. Cluster and discriminant analysis were applied to all neuropsychological test results to distinguish possible subgroups inside each age group. Results Significant differences in the performance of aged and young adults were detected in both language and visuospatial memory tests. Intragroup cluster and discriminant analysis revealed that CANTAB, as compared to language tests, was able to detect subtle but significant differences between the subjects. Conclusion Based on these findings, we concluded that, as compared to language tests, large-scale application of automated visuospatial tests to assess learning and memory might increase our ability to discern the limits between normal and pathological aging. PMID:25565785

  14. Long-term association of food and nutrient intakes with cognitive and functional decline: a 13-year follow-up study of elderly French women.

    PubMed

    Vercambre, Marie-Noël; Boutron-Ruault, Marie-Christine; Ritchie, Karen; Clavel-Chapelon, Françoise; Berr, Claudine

    2009-08-01

    The objective of the present study was to determine the potential long-term impact of dietary habits on age-related decline among 4809 elderly women (born between 1925 and 1930) in the 'Etude Epidémiologique de Femmes de la Mutuelle Générale de l'Education Nationale' (E3N) study, a French epidemiological cohort. In 1993, an extensive diet history self-administered questionnaire was sent to all participants, and in 2006 another questionnaire on instrumental activities of daily living (IADL) and recent cognitive change was sent to a close relative or friend of each woman. Logistic models adjusted for socio-demographic, lifestyle and health factors were performed to evaluate associations between habitual dietary intakes and two outcomes of interest based on the informant response: recent cognitive decline and IADL impairment. Recent cognitive decline was associated with lower intakes of poultry, fish, and animal fats, as well as higher intakes of dairy desserts and ice-cream. IADL impairment was associated with a lower intake of vegetables. The odds of recent cognitive decline increased significantly with decreasing intake of soluble dietary fibre and n-3 fatty acids but with increasing intake of retinol. The odds of IADL impairment increased significantly with decreasing intakes of vitamins B2, B6 and B12. These results are consistent with a possible long-term neuroprotective effect of dietary fibre, n-3 polyunsaturated fats and B-group vitamins, and support dietary intervention to prevent cognitive decline. PMID:19203415

  15. Prevalence of Cognitive Impairment in Recently Diagnosed Type 2 Diabetes Patients: Are Chronic Inflammatory Diseases Responsible for Cognitive Decline?

    PubMed Central

    Lavielle, Pilar; Talavera, Juan O.; Reynoso, Nancy; González, Marissa; Gómez-Díaz, Rita A.; Cruz, Miguel; Vázquez, Felipe; Wacher, Niels H.

    2015-01-01

    Objective To estimate the prevalence of cognitive impairment (CI) among patients recently diagnosed with type 2 diabetes (RDD) and to identify any relationships between CI and RDD comorbidities. Methods: One thousand seven hundred twelve patients with RDD participated in a cross-sectional study. The patients’ sociodemographic and clinical data were registered. Results The sample population had an average age of 51 ± 11 years, and 63.26% of the patients were female. CI was diagnosed in 38 patients (2.2%) and was more common among both females (2.8% vs. 1.3%, p = 0.063) and the elderly (0% at an age ≤ 30 years vs. 10.4% at an age > 70 years, p = 0.0001). Rheumatoid arthritis (present in 15.8% vs. absent in 2.1%) and asthma (13% vs. 2.1%) correlated significantly with CI based on the results of our logistic regression analysis. Conclusion Age, female gender, rheumatoid arthritis and asthma are risk factors for CI in the setting of RDD. PMID:26517541

  16. Risk Factors for Late-Life Cognitive Decline and Variation with Age and Sex in the Sydney Memory and Ageing Study

    PubMed Central

    Lipnicki, Darren M.; Sachdev, Perminder S.; Crawford, John; Reppermund, Simone; Kochan, Nicole A.; Trollor, Julian N.; Draper, Brian; Slavin, Melissa J.; Kang, Kristan; Lux, Ora; Mather, Karen A.; Brodaty, Henry

    2013-01-01

    Introduction An aging population brings increasing burdens and costs to individuals and society arising from late-life cognitive decline, the causes of which are unclear. We aimed to identify factors predicting late-life cognitive decline. Methods Participants were 889 community-dwelling 70–90-year-olds from the Sydney Memory and Ageing Study with comprehensive neuropsychological assessments at baseline and a 2-year follow-up and initially without dementia. Cognitive decline was considered as incident mild cognitive impairment (MCI) or dementia, as well as decreases in attention/processing speed, executive function, memory, and global cognition. Associations with baseline demographic, lifestyle, health and medical factors were determined. Results All cognitive measures showed decline and 14% of participants developed incident MCI or dementia. Across all participants, risk factors for decline included older age and poorer smelling ability most prominently, but also more education, history of depression, being male, higher homocysteine, coronary artery disease, arthritis, low health status, and stroke. Protective factors included marriage, kidney disease, and antidepressant use. For some of these factors the association varied with age or differed between men and women. Additional risk and protective factors that were strictly age- and/or sex-dependent were also identified. We found salient population attributable risks (8.7–49.5%) for older age, being male or unmarried, poor smelling ability, coronary artery disease, arthritis, stroke, and high homocysteine. Discussion Preventing or treating conditions typically associated with aging might reduce population-wide late-life cognitive decline. Interventions tailored to particular age and sex groups may offer further benefits. PMID:23799051

  17. Exploratory decision-making as a function of lifelong experience, not cognitive decline.

    PubMed

    Blanco, Nathaniel J; Love, Bradley C; Ramscar, Michael; Otto, A Ross; Smayda, Kirsten; Maddox, W Todd

    2016-03-01

    Older adults perform worse than younger adults in some complex decision-making scenarios, which is commonly attributed to age-related declines in striatal and frontostriatal processing. Recently, this popular account has been challenged by work that considered how older adults' performance may differ as a function of greater knowledge and experience, and by work showing that, in some cases, older adults outperform younger adults in complex decision-making tasks. In light of this controversy, we examined the performance of older and younger adults in an exploratory choice task that is amenable to model-based analyses and ostensibly not reliant on prior knowledge. Exploration is a critical aspect of decision-making poorly understood across the life span. Across 2 experiments, we addressed (a) how older and younger adults differ in exploratory choice and (b) to what extent observed differences reflect processing capacity declines. Model-based analyses suggested that the strategies used by the 2 groups were qualitatively different, resulting in relatively worse performance for older adults in 1 decision-making environment but equal performance in another. Little evidence was found that differences in processing capacity drove performance differences. Rather the results suggested that older adults' performance might result from applying a strategy that may have been shaped by their wealth of real-word decision-making experience. While this strategy is likely to be effective in the real world, it is ill suited to some decision environments. These results underscore the importance of taking into account effects of experience in aging studies, even for tasks that do not obviously tap past experiences.

  18. Exploratory Decision-Making as a Function of Lifelong Experience, Not Cognitive Decline

    PubMed Central

    2016-01-01

    Older adults perform worse than younger adults in some complex decision-making scenarios, which is commonly attributed to age-related declines in striatal and frontostriatal processing. Recently, this popular account has been challenged by work that considered how older adults’ performance may differ as a function of greater knowledge and experience, and by work showing that, in some cases, older adults outperform younger adults in complex decision-making tasks. In light of this controversy, we examined the performance of older and younger adults in an exploratory choice task that is amenable to model-based analyses and ostensibly not reliant on prior knowledge. Exploration is a critical aspect of decision-making poorly understood across the life span. Across 2 experiments, we addressed (a) how older and younger adults differ in exploratory choice and (b) to what extent observed differences reflect processing capacity declines. Model-based analyses suggested that the strategies used by the 2 groups were qualitatively different, resulting in relatively worse performance for older adults in 1 decision-making environment but equal performance in another. Little evidence was found that differences in processing capacity drove performance differences. Rather the results suggested that older adults’ performance might result from applying a strategy that may have been shaped by their wealth of real-word decision-making experience. While this strategy is likely to be effective in the real world, it is ill suited to some decision environments. These results underscore the importance of taking into account effects of experience in aging studies, even for tasks that do not obviously tap past experiences. PMID:26726916

  19. APPLYING SPARSE CODING TO SURFACE MULTIVARIATE TENSOR-BASED MORPHOMETRY TO PREDICT FUTURE COGNITIVE DECLINE

    PubMed Central

    Zhang, Jie; Stonnington, Cynthia; Li, Qingyang; Shi, Jie; Bauer, Robert J.; Gutman, Boris A.; Chen, Kewei; Reiman, Eric M.; Thompson, Paul M.; Ye, Jieping; Wang, Yalin

    2016-01-01

    Alzheimer’s disease (AD) is a progressive brain disease. Accurate diagnosis of AD and its prodromal stage, mild cognitive impairment, is crucial for clinical trial design. There is also growing interests in identifying brain imaging biomarkers that help evaluate AD risk presymptomatically. Here, we applied a recently developed multivariate tensor-based morphometry (mTBM) method to extract features from hippocampal surfaces, derived from anatomical brain MRI. For such surface-based features, the feature dimension is usually much larger than the number of subjects. We used dictionary learning and sparse coding to effectively reduce the feature dimensions. With the new features, an Adaboost classifier was employed for binary group classification. In tests on publicly available data from the Alzheimers Disease Neuroimaging Initiative, the new framework outperformed several standard imaging measures in classifying different stages of AD. The new approach combines the efficiency of sparse coding with the sensitivity of surface mTBM, and boosts classification performance. PMID:27499829

  20. An Unusual Presentation of Neurocysticercosis: A Space-Occupying Lesion in the Fourth Ventricle Associated with Progressive Cognitive Decline.

    PubMed

    Kurz, Carolin; Schmidt, Veronika; Poppert, Holger; Wilkins, Patricia; Noh, John; Poppert, Sven; Schlegel, Jürgen; Delbridge, Claire; da Costa, Clarissa Prazeres; Winkler, Andrea S

    2016-01-01

    We communicate a case of a middle-aged Brazilian patient with an unusual presentation of fourth ventricular neurocysticercosis: occurrence of two intraventricular cysts at different locations in the brain within 2 years and cognitive decline as the only neurological symptom. Neurocysticercosis was confirmed by magnetic resonance imaging, serology, histology, and genetic analysis. Neurocysticercosis should be considered as a differential diagnosis in cases with atypical neurologic or psychiatric symptoms, atypical neuroimaging and travel history. Especially, fourth ventricular cysts carry the risk of obstructive hydrocephalus and brainstem compression and therefore should be extirpated completely. If complete removal of the cystic structures cannot be proven in cases with surgically treated neurocysticercosis, anthelminthic therapy and thorough follow-up examinations should be conducted.

  1. Apigenin attenuates diabetes-associated cognitive decline in rats via suppressing oxidative stress and nitric oxide synthase pathway.

    PubMed

    Mao, Xiao-Yuan; Yu, Jing; Liu, Zhao-Qian; Zhou, Hong-Hao

    2015-01-01

    Our present investigation aimed to determine the neuroprotection of apigenin (API) against diabetes-associated cognitive decline (DACD) a diabetic rat model and exploring its potential mechanism. Diabetic rat model was induced by intraperitoneal injection of streptozotocin. All experiment animals treated with vehicle or API by doses of 10, 20 and 40 mg/kg for seven weeks. Firstly, the body weight and blood glucose levels were detected. We used Morris water maze test to evaluate learning and memory function. The oxidative indicators (malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH)), cNOS, iNOS, caspase-3 and caspase-9 were measured in cerebral cortex and hippocampus using corresponding commercial kits. API can increase body weight, reduce the blood glucose levels, and improve the cognitive function in rats induced by diabetes. API decrease the MDA content, and increase SOD activity and GSH level of diabetic animals in the cerebral cortex and hippocampus of diabetic rats. Meanwhile, constitutive nitric oxide synthase (cNOS), inducible nitric oxide synthase (iNOS), caspase-3/9 were markedly exhibited in the cerebral cortex and hippocampus of diabetic rats. In summary, our current work discloses that API attenuates DACD in rats via suppressing oxidative stress, nitric oxide and apoptotic cascades synthase pathway. PMID:26629041

  2. Plasma Metabolomic Profiling of Patients with Diabetes-Associated Cognitive Decline

    PubMed Central

    Zhan, Libin; Lu, Xiaoguang; Liang, Lina; Su, Benli; Sui, Hua; Gao, Zhengnan; Li, Yuzhong; Liu, Ying; Wu, Benhui; Liu, Qigui

    2015-01-01

    Diabetes related cognitive dysfunction (DACD), one of the chronic complications of diabetes, seriously affect the quality of life in patients and increase family burden. Although the initial stage of DACD can lead to metabolic alterations or potential pathological changes, DACD is difficult to diagnose accurately. Moreover, the details of the molecular mechanism of DACD remain somewhat elusive. To understand the pathophysiological changes that underpin the development and progression of DACD, we carried out a global analysis of metabolic alterations in response to DACD. The metabolic alterations associated with DACD were first investigated in humans, using plasma metabonomics based on high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis. The related pathway of each metabolite of interest was searched in database online. The network diagrams were established KEGGSOAP software package. Receiver operating characteristic (ROC) analysis was used to evaluate diagnostic accuracy of metabolites. This is the first report of reliable biomarkers of DACD, which were identified using an integrated strategy. The identified biomarkers give new insights into the pathophysiological changes and molecular mechanisms of DACD. The disorders of sphingolipids metabolism, bile acids metabolism, and uric acid metabolism pathway were found in T2DM and DACD. On the other hand, differentially expressed plasma metabolites offer unique metabolic signatures for T2DM and DACD patients. These are potential biomarkers for disease monitoring and personalized medication complementary to the existing clinical modalities. PMID:25974350

  3. Multi-modal imaging predicts memory performance in normal aging and cognitive decline.

    PubMed

    Walhovd, K B; Fjell, A M; Dale, A M; McEvoy, L K; Brewer, J; Karow, D S; Salmon, D P; Fennema-Notestine, C

    2010-07-01

    This study (n=161) related morphometric MR imaging, FDG-PET and APOE genotype to memory scores in normal controls (NC), mild cognitive impairment (MCI) and Alzheimer's disease (AD). Stepwise regression analyses focused on morphometric and metabolic characteristics of the episodic memory network: hippocampus, entorhinal, parahippocampal, retrosplenial, posterior cingulate, precuneus, inferior parietal, and lateral orbitofrontal cortices. In NC, hippocampal metabolism predicted learning; entorhinal metabolism predicted recognition; and hippocampal metabolism predicted recall. In MCI, thickness of the entorhinal and precuneus cortices predicted learning, while parahippocampal metabolism predicted recognition. In AD, posterior cingulate cortical thickness predicted learning, while APOE genotype predicted recognition. In the total sample, hippocampal volume and metabolism, cortical thickness of the precuneus, and inferior parietal metabolism predicted learning; hippocampal volume and metabolism, parahippocampal thickness and APOE genotype predicted recognition. Imaging methods appear complementary and differentially sensitive to memory in health and disease. Medial temporal and parietal metabolism and morphometry best explained memory variance. Medial temporal characteristics were related to learning, recall and recognition, while parietal structures only predicted learning.

  4. [Cognitive decline in Alzheimer's disease. A follow three or more years of a sample of patients].

    PubMed

    Conde-Sala, Josep Lluís; Garre-Olmo, Josep; Vilalta-Franch, Joan; Llinàs-Reglà, Jordi; Turró-Garriga, Oriol; Lozano-Gallego, Manuela; Hernández-Ferràndiz, Marta; Pericot-Nierga, Imma; López-Pousa, Secundino

    2013-06-16

    Introduccion. Las tasas de declive cognitivo en los pacientes con enfermedad de Alzheimer presentan variaciones debido a diversos factores. Objetivo. Determinar la influencia de la edad, escolaridad, genero, actividades de la vida diaria (AVD) e inhibidores de la acetilcolinesterasa (IAChE) y memantina en el ritmo y tasas de declive cognitivo. Pacientes y metodos. Estudio retrospectivo de una muestra de 383 pacientes con enfermedad de Alzheimer, con evaluaciones neuropsicologicas durante un periodo superior a tres años. Se utilizo como medida cognitiva el Cambridge Cognitive Examination (CAMCOG). Se agruparon los pacientes segun su tasa de declive anual (TDA) y se realizaron analisis bivariante y de regresion lineal multivariante utilizando como variable dependiente la diferencia de puntuaciones en el CAMCOG (basal-final). Resultados. La menor edad (beta = –0,23; p < 0,001), la mayor escolaridad (beta = 0,26; p < 0,001) y el mayor deterioro de las AVD (beta = 0,24; p < 0,001) estuvieron asociados a un mayor declive en todos los pacientes. Los farmacos tuvieron un efecto benefico (beta = –0,18; p = 0,011) en el grupo con menor y mas lento declive (TDA < 5%). Conclusiones. La menor edad, la mayor escolaridad y el deterioro de las AVD se relacionan con un mayor declive cognitivo. Los IAChE y la memantina tuvieron un efecto benefico, enlenteciendo el declive en el grupo de pacientes con menor TDA.

  5. IL-33 ameliorates Alzheimer’s disease-like pathology and cognitive decline

    PubMed Central

    Fu, Amy K. Y.; Hung, Kwok-Wang; Yuen, Michael Y. F.; Zhou, Xiaopu; Mak, Deejay S. Y.; Chan, Ivy C. W.; Cheung, Tom H.; Zhang, Baorong; Fu, Wing-Yu; Liew, Foo Y.; Ip, Nancy Y.

    2016-01-01

    Alzheimer’s disease (AD) is a devastating condition with no known effective treatment. AD is characterized by memory loss as well as impaired locomotor ability, reasoning, and judgment. Emerging evidence suggests that the innate immune response plays a major role in the pathogenesis of AD. In AD, the accumulation of β-amyloid (Aβ) in the brain perturbs physiological functions of the brain, including synaptic and neuronal dysfunction, microglial activation, and neuronal loss. Serum levels of soluble ST2 (sST2), a decoy receptor for interleukin (IL)-33, increase in patients with mild cognitive impairment, suggesting that impaired IL-33/ST2 signaling may contribute to the pathogenesis of AD. Therefore, we investigated the potential therapeutic role of IL-33 in AD, using transgenic mouse models. Here we report that IL-33 administration reverses synaptic plasticity impairment and memory deficits in APP/PS1 mice. IL-33 administration reduces soluble Aβ levels and amyloid plaque deposition by promoting the recruitment and Aβ phagocytic activity of microglia; this is mediated by ST2/p38 signaling activation. Furthermore, IL-33 injection modulates the innate immune response by polarizing microglia/macrophages toward an antiinflammatory phenotype and reducing the expression of proinflammatory genes, including IL-1β, IL-6, and NLRP3, in the cortices of APP/PS1 mice. Collectively, our results demonstrate a potential therapeutic role for IL-33 in AD. PMID:27091974

  6. Does exercise protect from cognitive decline by altering brain cytokine and apoptotic protein levels? A systematic review of the literature.

    PubMed

    Packer, N; Pervaiz, N; Hoffman-Goetz, L

    2010-01-01

    Regular exercise is thought to provide protection against age-related cognitive decline and possibly reduce risk of dementias. The mechanisms for the exercise protective effects are not known although changes in inflammatory cytokine levels may be involved. We conducted a systematic review of the literature to assess (1) the effects of exercise on cytokines in the brain, (2) the methodological rigour of studies which have examined these exercise effects and (3) the potential role of regular exercise in reducing the pro-inflammatory cytokine milieu that may contribute to dementia. We also reviewed the effects of exercise on concurrent pro and anti-apoptotic protein expression in the brain as related to cytokine changes. Five databases were searched until January 2010 with an initial 630 articles identified; 61 articles were retrieved of which 10 met study inclusion criteria. Investigations of both acute and chronic (training) exercise were assessed for methodological quality using a modified PEDro scale. Two studies were carried out with human participants and eight with mouse or rat models; studies differed markedly in design and methodological rigour; the types, intensities and durations of exercise, the cytokine and apoptotic proteins measured, and the regions of the brain (or proxy compartments) sampled. Despite variations in design, specific cytokine outcomes, and exercise type, the 10 studies provide limited evidence that acute strenuous exercise increases and exercise training decreases pro-inflammatory cytokines centrally. Two animal studies relate training associated decreases in pro-inflammatory cytokines with improved cognitive function using behavioural assessments such as the Morris maze. Recommendations for the design of future research on exercise, central cytokines, and cognition are offered.

  7. Over the hill at 24: persistent age-related cognitive-motor decline in reaction times in an ecologically valid video game task begins in early adulthood.

    PubMed

    Thompson, Joseph J; Blair, Mark R; Henrey, Andrew J

    2014-01-01

    Typically studies of the effects of aging on cognitive-motor performance emphasize changes in elderly populations. Although some research is directly concerned with when age-related decline actually begins, studies are often based on relatively simple reaction time tasks, making it impossible to gauge the impact of experience in compensating for this decline in a real world task. The present study investigates age-related changes in cognitive motor performance through adolescence and adulthood in a complex real world task, the real-time strategy video game StarCraft 2. In this paper we analyze the influence of age on performance using a dataset of 3,305 players, aged 16-44, collected by Thompson, Blair, Chen & Henrey [1]. Using a piecewise regression analysis, we find that age-related slowing of within-game, self-initiated response times begins at 24 years of age. We find no evidence for the common belief expertise should attenuate domain-specific cognitive decline. Domain-specific response time declines appear to persist regardless of skill level. A second analysis of dual-task performance finds no evidence of a corresponding age-related decline. Finally, an exploratory analyses of other age-related differences suggests that older participants may have been compensating for a loss in response speed through the use of game mechanics that reduce cognitive load.

  8. Over the Hill at 24: Persistent Age-Related Cognitive-Motor Decline in Reaction Times in an Ecologically Valid Video Game Task Begins in Early Adulthood

    PubMed Central

    Thompson, Joseph J.; Blair, Mark R.; Henrey, Andrew J.

    2014-01-01

    Typically studies of the effects of aging on cognitive-motor performance emphasize changes in elderly populations. Although some research is directly concerned with when age-related decline actually begins, studies are often based on relatively simple reaction time tasks, making it impossible to gauge the impact of experience in compensating for this decline in a real world task. The present study investigates age-related changes in cognitive motor performance through adolescence and adulthood in a complex real world task, the real-time strategy video game StarCraft 2. In this paper we analyze the influence of age on performance using a dataset of 3,305 players, aged 16-44, collected by Thompson, Blair, Chen & Henrey [1]. Using a piecewise regression analysis, we find that age-related slowing of within-game, self-initiated response times begins at 24 years of age. We find no evidence for the common belief expertise should attenuate domain-specific cognitive decline. Domain-specific response time declines appear to persist regardless of skill level. A second analysis of dual-task performance finds no evidence of a corresponding age-related decline. Finally, an exploratory analyses of other age-related differences suggests that older participants may have been compensating for a loss in response speed through the use of game mechanics that reduce cognitive load. PMID:24718593

  9. Over the hill at 24: persistent age-related cognitive-motor decline in reaction times in an ecologically valid video game task begins in early adulthood.

    PubMed

    Thompson, Joseph J; Blair, Mark R; Henrey, Andrew J

    2014-01-01

    Typically studies of the effects of aging on cognitive-motor performance emphasize changes in elderly populations. Although some research is directly concerned with when age-related decline actually begins, studies are often based on relatively simple reaction time tasks, making it impossible to gauge the impact of experience in compensating for this decline in a real world task. The present study investigates age-related changes in cognitive motor performance through adolescence and adulthood in a complex real world task, the real-time strategy video game StarCraft 2. In this paper we analyze the influence of age on performance using a dataset of 3,305 players, aged 16-44, collected by Thompson, Blair, Chen & Henrey [1]. Using a piecewise regression analysis, we find that age-related slowing of within-game, self-initiated response times begins at 24 years of age. We find no evidence for the common belief expertise should attenuate domain-specific cognitive decline. Domain-specific response time declines appear to persist regardless of skill level. A second analysis of dual-task performance finds no evidence of a corresponding age-related decline. Finally, an exploratory analyses of other age-related differences suggests that older participants may have been compensating for a loss in response speed through the use of game mechanics that reduce cognitive load. PMID:24718593

  10. Cognitive and Functional Decline among Individuals 50 Years of Age or Older in Cambé, Paraná, Brazil: A Population-Based Study

    PubMed Central

    Cabrera, Marcos Aparecido Sarria; Bortoletto, Maira Aira Sayuri Sakay; de Souza, Regina Kazue Tanno; Prina, Douglas Manuel Carrapeiro; Vieira, Maria Cristina Umpierrez; Silva, Ana Maria Rigo

    2016-01-01

    Aims To identify the frequency of cognitive and functional decline (CFD) among adults 50 years of age and older by a population-based study. Methods Cognitive function was analyzed by the Mini-Mental State Examination, and the functional conditions were based on instrumental activities of daily living (IADL). Cases of CFD included individuals with cognitive decline and 2 or more compromised IADL. Results A total of 693 individuals were studied. The frequency of CFD was 16.3%. A low socioeconomic profile was associated with greater CFD independent of gender, age, education, and presence of depression (OR = 2.46; 95% CI: 1.53-3.97). Conclusions These data show a high frequency of CFD among adults 50 years and older. Individuals with less education and a lower socioeconomic level exhibited poorer cognitive and functional conditions. PMID:27350779

  11. Self-reported change in quality of life with retirement and later cognitive decline: prospective data from the Nurses’ Health Study

    PubMed Central

    Vercambre, Marie-Noël; Okereke, Olivia I.; Kawachi, Ichiro; Grodstein, Francine; Kang, Jae H.

    2016-01-01

    To investigate whether a positive transition into retirement may be associated with later cognitive ageing, we included a subset of 4,926 Nurses’ Health Study participants who retired from work at ages 60–69, then provided a subjective assessment of the change in overall quality of life (QOL) with retirement. Subsequently (range: 1 month to 4.7 years later), when all were aged 70+ years, they completed a baseline telephone cognitive battery evaluating global cognition, episodic memory and executive function. They had up to three follow-up cognitive assessments. Controlling for various occupational factors before retirement and socioeconomic, lifestyle, and health-related factors as of the baseline cognitive assessment, we used generalized linear models for repeated measures to estimate mean differences in rates of cognitive decline across categories of QOL transition at retirement: “worse”, “same” or “better”. Over a median 6 years of follow-up, the global cognitive score change was −0.123 on average. Compared with women who reported no change in QOL at retirement (31%), women who reported improvement (61%) showed a significantly slower rate of cognitive decline (difference= +0.011 95% CI =0.004, 0.019). This mean difference was equivalent to that observed between women who were 2 years apart in age. No significant differences in cognitive decline rates were observed for the women who reported worsened QOL (8%). Secondary analyses to address possible reverse causation showed robust associations. A positive transition into retirement was associated with better maintenance of cognitive function over time in aging women. These findings need to be replicated in other populations. PMID:27060944

  12. Cohorts based on Decade of Death: No Evidence for Secular Trends Favoring Later Cohorts in Cognitive Aging and Terminal Decline in the AHEAD Study

    PubMed Central

    Hülür, Gizem; Infurna, Frank J.; Ram, Nilam; Gerstorf, Denis

    2012-01-01

    Studies of birth-year cohorts examined over the same age range often report secular trends favoring later-born cohorts, who are cognitively fitter and show less steep cognitive declines than earlier-born cohorts. However, there is initial evidence that those advantages of later-born cohorts do not carry into the last years of life, suggesting that pervasive mortality-related processes minimize differences that were apparent earlier in life. Elaborating this work from an alternative perspective on cohort differences, we compared rates of cognitive aging and terminal decline in episodic memory between cohorts based on the year participants had died, earlier (between 1993 and 1999) or later in historical time (between 2000 and 2010). Specifically, we compared trajectories of cognitive decline in two death-year cohorts of participants in the Asset and Health Dynamics among the Oldest Old (AHEAD) Study that were matched on age at death and education and controlled for a variety of additional covariates. Results revealed little evidence of secular trends favoring later cohorts. To the contrary, the cohort that died in the 2000s showed a less favorable trajectory of age-related memory decline than the cohort who died in the 1990s. In examinations of change in relation to time-to-death, the cohort dying in the 2000s experienced even steeper terminal declines than the cohort dying in the 1990s. We suggest that secular increases in “manufacturing” survival may exacerbate age- and mortality-related cognitive declines among the oldest old. PMID:23046001

  13. Nox-2-Mediated Phenotype Loss of Hippocampal Parvalbumin Interneurons Might Contribute to Postoperative Cognitive Decline in Aging Mice

    PubMed Central

    Qiu, Li-Li; Luo, Dan; Zhang, Hui; Shi, Yun S.; Li, Yan-Jun; Wu, Dan; Chen, Jiang; Ji, Mu-Huo; Yang, Jian-Jun

    2016-01-01

    Postoperative cognitive decline (POCD) is a common complication following anesthesia and surgery, especially in elderly patients; however, the precise mechanisms of POCD remain unclear. Here, we investigated whether nicotinamide adenine dinucleotide phosphate (NADPH) oxidase mediated-abnormalities in parvalbumin (PV) interneurons play an important role in the pathophysiology of POCD. The animal model was established using isoflurane anesthesia and exploratory laparotomy in 16-month-old male C57BL/6 mice. For interventional experiments, mice were chronically treated with the NADPH oxidase inhibitor apocynin (APO). Open field and fear conditioning behavioral tests were performed on day 6 and 7 post-surgery, respectively. In a separate experiment, brain tissue was harvested and subjected to biochemical analysis. Primary hippocampal neurons challenged with lipopolysaccharide (LPS) in vitro were used to investigate the mechanisms underlying the oxidative stress-induced abnormalities in PV interneurons. Our results showed that anesthesia and surgery induced significant hippocampus-dependent memory impairment, which was accompanied by PV interneuron phenotype loss and increased expression of interleukin-1β (IL-1β), markers of oxidative stress and NADPH oxidase 2 (Nox2) in the hippocampus. In addition, LPS exposure increased Nox2 level and decreased the expression of PV and the number of excitatory synapses onto PV interneurons in the primary hippocampal neurons. Notably, treatment with APO reversed these abnormalities. Our study suggests that Nox2-derived reactive oxygen species (ROS) production triggers, at least in part, anesthesia- and surgery-induced hippocampal PV interneuron phenotype loss and consequent cognitive impairment in aging mice. PMID:27790135

  14. Fifteen-Year Follow-Up of 92 Hospitalized Adults with Down's Syndrome: Incidence of Cognitive Decline, Its Relationship to Age and Neuropathology

    ERIC Educational Resources Information Center

    Margallo-Lana, M. L.; Moore, P. B.; Kay, D. W. K.; Perry, R. H.; Reid, B. E.; Berney, T. P.; Tyrer, S. P.

    2007-01-01

    Background: The clinical and neuropathological features associated with dementia in Down's syndrome (DS) are not well established. Aims: To examine clinico-pathological correlations and the incidence of cognitive decline in a cohort of adults with DS. Method: A total of 92 hospitalized persons with DS were followed up from 1985 to December 2000.…

  15. Flying solo: A review of the literature on wayfinding for older adults experiencing visual or cognitive decline.

    PubMed

    Bosch, Sheila J; Gharaveis, Arsalan

    2017-01-01

    Accessible tourism is a growing market within the travel industry, but little research has focused on travel barriers for older adults who may be experiencing visual and cognitive decline as part of the normal aging process, illness, or other disabling conditions. Travel barriers, such as difficulty finding one's way throughout an airport, may adversely affect older adults' travel experience, thereby reducing their desire to travel. This review of the literature investigates wayfinding strategies to ensure that older passengers who have planned to travel independently can do so with dignity. These include facility planning and design strategies (e.g., layout, signage) and technological solutions. Although technological approaches, such as smart phone apps, appear to offer the most promising new solutions for enhancing airport navigation, more traditional approaches, such as designing facilities with an intuitive building layout, are still heavily relied upon in the aviation industry. While there are many design guidelines for enhancing wayfinding for older adults, many are not based on scientific investigation.

  16. Is there a decline in cognitive functions after combined electroconvulsive therapy and antipsychotic therapy in treatment-refractory schizophrenia?

    PubMed

    Pawełczyk, Agnieszka; Kołodziej-Kowalska, Emilia; Pawełczyk, Tomasz; Rabe-Jabłońska, Jolanta

    2015-03-01

    An analysis of literature shows that there is still little evidence concerning the efficacy of electroconvulsive therapy (ECT) combined with antipsychotic therapy in a group of treatment-resistant schizophrenia patients. More precisely, its influence on cognitive functions is still equivocal. The aim of this study was to assess the influence of ECT combined with antipsychotic therapy on working memory, attention, and executive functions in a group of treatment-refractory schizophrenia patients. Twenty-seven patients completed the study: 14 men and 13 women, aged 21 to 55 years (mean age, 32.8 years), diagnosed with treatment-resistant schizophrenia. Each patient underwent a course of ECT sessions and was treated with antipsychotic medications. Before the ECT and within 3 days after the last ECT session, the participants were assessed with the following neuropsychological tests: Trail Making Test (TMT) and Wisconsin Cart Sorting Test (WCST). There were no significant differences in the TMT and WCST results after combined ECT and antipsychotic therapy in treatment-refractory schizophrenia patients. According to the results of the neuropsychological tests, there was no decline in attention, executive functions, or working memory. The current study shows no significant difference in attention, working memory, or executive functions after treatment with a combination of electroconvulsive and antipsychotic therapy. This suggests that combined electroconvulsive therapy may not have a negative influence on the neuropsychological functioning of patients with treatment resistant schizophrenia.

  17. Modulation of Mitochondrial Complex I Activity Averts Cognitive Decline in Multiple Animal Models of Familial Alzheimer's Disease

    PubMed Central

    Zhang, Liang; Zhang, Song; Maezawa, Izumi; Trushin, Sergey; Minhas, Paras; Pinto, Matthew; Jin, Lee-Way; Prasain, Keshar; Nguyen, Thi D.T.; Yamazaki, Yu; Kanekiyo, Takahisa; Bu, Guojun; Gateno, Benjamin; Chang, Kyeong-Ok; Nath, Karl A.; Nemutlu, Emirhan; Dzeja, Petras; Pang, Yuan-Ping; Hua, Duy H.; Trushina, Eugenia

    2015-01-01

    Development of therapeutic strategies to prevent Alzheimer's disease (AD) is of great importance. We show that mild inhibition of mitochondrial complex I with small molecule CP2 reduces levels of amyloid beta and phospho-Tau and averts cognitive decline in three animal models of familial AD. Low-mass molecular dynamics simulations and biochemical studies confirmed that CP2 competes with flavin mononucleotide for binding to the redox center of complex I leading to elevated AMP/ATP ratio and activation of AMP-activated protein kinase in neurons and mouse brain without inducing oxidative damage or inflammation. Furthermore, modulation of complex I activity augmented mitochondrial bioenergetics increasing coupling efficiency of respiratory chain and neuronal resistance to stress. Concomitant reduction of glycogen synthase kinase 3β activity and restoration of axonal trafficking resulted in elevated levels of neurotrophic factors and synaptic proteins in adult AD mice. Our results suggest that metabolic reprogramming induced by modulation of mitochondrial complex I activity represents promising therapeutic strategy for AD. PMID:26086035

  18. Flying solo: A review of the literature on wayfinding for older adults experiencing visual or cognitive decline.

    PubMed

    Bosch, Sheila J; Gharaveis, Arsalan

    2017-01-01

    Accessible tourism is a growing market within the travel industry, but little research has focused on travel barriers for older adults who may be experiencing visual and cognitive decline as part of the normal aging process, illness, or other disabling conditions. Travel barriers, such as difficulty finding one's way throughout an airport, may adversely affect older adults' travel experience, thereby reducing their desire to travel. This review of the literature investigates wayfinding strategies to ensure that older passengers who have planned to travel independently can do so with dignity. These include facility planning and design strategies (e.g., layout, signage) and technological solutions. Although technological approaches, such as smart phone apps, appear to offer the most promising new solutions for enhancing airport navigation, more traditional approaches, such as designing facilities with an intuitive building layout, are still heavily relied upon in the aviation industry. While there are many design guidelines for enhancing wayfinding for older adults, many are not based on scientific investigation. PMID:27633229

  19. Neurological Soft Signs in Aging, Mild Cognitive Impairment, and Alzheimer’s Disease – The Impact of Cognitive Decline and Cognitive Reserve

    PubMed Central

    Urbanowitsch, Nadja; Degen, Christina; Toro, Pablo; Schröder, Johannes

    2015-01-01

    Objectives: Neurological soft signs (NSS), i.e., minor motor and sensory changes, are a common feature in severe psychiatric disorders. We sought to establish the frequency of NSS in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) on basis of a large population-based sample and to identify their neuropsychological correlates including cognitive reserve. Methods: Neurological soft signs were examined using an abbreviated version of the Heidelberg NSS Scale in 221 “old” participants born between 1930 and 1932 (63 with MCI, 15 with AD, 143 healthy old controls) and 256 healthy “young” participants (born between 1950 and 1952) of the population-based interdisciplinary longitudinal study of aging. Subjects received thorough neuropsychological testing; years of school education were used as a proxy for cognitive reserve. Results: Neurological soft signs scores were significantly (p < 0.001) higher in the AD patients (5.6 ± 3.11) than in the healthy old controls (2.8 ± 1.90) and in the MCI patients (3.0 ± 1.96). This result was confirmed after years of school education, which were inversely correlated (r = −0.25; p < 0.001) with NSS were entered as a covariate. In the patients, but not in the controls, NSS were significantly correlated with deficits in executive functioning and visuospatial functioning. Comparison of NSS scores between “old” (2.84 ± 1.9) and “young” (2.46 ± 1.97) controls yielded only minor, non-significant differences after education (13.86 ± 3.0 vs. 14.61 ± 2.48 years, respectively) was controlled for. Conclusion: Our results demonstrate that NSS are frequently found in mild AD, but not in MCI. NSS refer to frontal-executive deficits and visuospatial dysfunction rather than age per se and can be partly compensated for by cognitive reserve. PMID:25717306

  20. Motor Phenotype of Decline in Cognitive Performance among Community-Dwellers without Dementia: Population-Based Study and Meta-Analysis

    PubMed Central

    Beauchet, Olivier; Allali, Gilles; Montero-Odasso, Manuel; Sejdić, Ervin; Fantino, Bruno; Annweiler, Cédric

    2014-01-01

    Background Decline in cognitive performance is associated with gait deterioration. Our objectives were: 1) to determine, from an original study in older community-dwellers without diagnosis of dementia, which gait parameters, among slower gait speed, higher stride time variability (STV) and Timed Up & Go test (TUG) delta time, were most strongly associated with lower performance in two cognitive domains (i.e., episodic memory and executive function); and 2) to quantitatively synthesize, with a systematic review and meta-analysis, the association between gait performance and cognitive decline (i.e., mild cognitive impairment (MCI) and dementia). Methods Based on a cross-sectional design, 934 older community-dwellers without dementia (mean±standard deviation, 70.3±4.9years; 52.1% female) were recruited. A score at 5 on the Short Mini-Mental State Examination defined low episodic memory performance. Low executive performance was defined by clock-drawing test errors. STV and gait speed were measured using GAITRite system. TUG delta time was calculated as the difference between the times needed to perform and to imagine the TUG. Then, a systematic Medline search was conducted in November 2013 using the Medical Subject Heading terms “Delirium,” “Dementia,” “Amnestic,” “Cognitive disorders” combined with “Gait” OR “Gait disorders, Neurologic” and “Variability.” Findings A total of 294 (31.5%) participants presented decline in cognitive performance. Higher STV, higher TUG delta time, and slower gait speed were associated with decline in episodic memory and executive performances (all P-values <0.001). The highest magnitude of association was found for higher STV (effect size  =  −0.74 [95% Confidence Interval (CI): −1.05;−0.43], among participants combining of decline in episodic memory and in executive performances). Meta-analysis underscored that higher STV represented a gait biomarker in patients with MCI (effect size  =  0

  1. Dysfunctional Sensory Modalities, Locus Coeruleus, and Basal Forebrain: Early Determinants that Promote Neuropathogenesis of Cognitive and Memory Decline and Alzheimer's Disease.

    PubMed

    Daulatzai, Mak Adam

    2016-10-01

    Sporadic Alzheimer's disease (AD) is a devastating neurodegenerative disorder. It is essential to unravel its etiology and pathogenesis. This should enable us to study the presymptomatic stages of the disease and to analyze and reverse the antemortem behavioral, memory, and cognitive dysfunction. Prima facie, an ongoing chronic vulnerability involving neural insult may lead normal elderly to mild cognitive impairment (MCI) and then to AD. Development of effective preventive and therapeutic strategies to thwart the disease pathology obviously requires a thorough delineation of underlying disruptive neuropathological processes. Our sensory capacity for touch, smell, taste, hearing, and vision declines with advancing age. Declines in different sensory attributes are considered here to be the primary "first-tier pathologies." Olfactory loss is among the first clinical signs of neurodegenerative diseases including AD and Parkinson's disease (PD). Sensory dysfunction in the aged promotes pathological disturbances in the locus coeruleus, basal forebrain, entorhinal cortex, hippocampus, and several key areas of neocortex and brainstem. Hence, sensory dysfunction is the pivotal factor that may upregulate cognitive and memory dysfunction. The age-related constellation of comorbid pathological factors may include apolipoprotein E (APOE) genotype, obesity, diabetes, hypertension, alcohol abuse, head trauma, and obstructive sleep apnea. The concepts and trajectories delineated here are the dynamic pillars of the current hypothesis presented-it postulates that the sensory decline, in conjunction with the above pathologies, is crucial in triggering neurodegeneration and promoting cognitive/memory dysfunction in aging and AD. The application of this thesis can be important in formulating new multifactorial preventive and treatment strategies (suggested here) in order to attenuate cognitive and memory decline and ameliorate pathological dysfunction in aging, MCI, and AD.

  2. Dysfunctional Sensory Modalities, Locus Coeruleus, and Basal Forebrain: Early Determinants that Promote Neuropathogenesis of Cognitive and Memory Decline and Alzheimer's Disease.

    PubMed

    Daulatzai, Mak Adam

    2016-10-01

    Sporadic Alzheimer's disease (AD) is a devastating neurodegenerative disorder. It is essential to unravel its etiology and pathogenesis. This should enable us to study the presymptomatic stages of the disease and to analyze and reverse the antemortem behavioral, memory, and cognitive dysfunction. Prima facie, an ongoing chronic vulnerability involving neural insult may lead normal elderly to mild cognitive impairment (MCI) and then to AD. Development of effective preventive and therapeutic strategies to thwart the disease pathology obviously requires a thorough delineation of underlying disruptive neuropathological processes. Our sensory capacity for touch, smell, taste, hearing, and vision declines with advancing age. Declines in different sensory attributes are considered here to be the primary "first-tier pathologies." Olfactory loss is among the first clinical signs of neurodegenerative diseases including AD and Parkinson's disease (PD). Sensory dysfunction in the aged promotes pathological disturbances in the locus coeruleus, basal forebrain, entorhinal cortex, hippocampus, and several key areas of neocortex and brainstem. Hence, sensory dysfunction is the pivotal factor that may upregulate cognitive and memory dysfunction. The age-related constellation of comorbid pathological factors may include apolipoprotein E (APOE) genotype, obesity, diabetes, hypertension, alcohol abuse, head trauma, and obstructive sleep apnea. The concepts and trajectories delineated here are the dynamic pillars of the current hypothesis presented-it postulates that the sensory decline, in conjunction with the above pathologies, is crucial in triggering neurodegeneration and promoting cognitive/memory dysfunction in aging and AD. The application of this thesis can be important in formulating new multifactorial preventive and treatment strategies (suggested here) in order to attenuate cognitive and memory decline and ameliorate pathological dysfunction in aging, MCI, and AD. PMID

  3. Environmental enrichment as a method to improve cognitive function. What can we learn from animal models?

    PubMed

    Fischer, Andre

    2016-05-01

    There is substantial evidence that physical and cognitive exercise can enhance memory function in rodents as well as in humans. In addition various behaviors associated with physical activity have been associated with an increased cognitive reserve and a lower risk to develop age-associated memory decline and age-associated neurodegenerative diseases such as Alzheimer's disease. To better understand the molecular mechanisms that increase brain plasticity in response to exercise will therefore help to develop effective therapeutic strategies to treat memory decline. Here we review the currently available data with a specific focus on neurodegenerative diseases.

  4. One-trial 10-item free-recall performance in Taiwanese elderly and near-elderly: A potential screen for cognitive decline.

    PubMed

    Tractenberg, Rochelle E; Aisen, Paul S; Chuang, Yi-Li

    2005-01-01

    To explore a one-trial 10-item free-recall test as a potential dementia screening tool, we analyzed recall scores and individualized serial position effects in near-elderly (N = 2,336) and elderly (N = 2,371) participants in a population-based survey in Taiwan. Age and sex were significantly associated with recall score [younger > older (p < 0.001); men > women (p < 0.001)]; after controlling for gender and age group, weak association between recall and education was still observed. By contrast, serial position effects (SPEs), defined for each participant and analyzed aggregated over each age group, were not associated with education and tended not to be associated with sex. Primacy effects were observed in 67 to 80 percent, and recency effects were observed in 41 to 54 percent of respondents. Because SPEs were defined for each respondent, we could determine that loss of the primacy effect was associated with significantly larger losses in total recall score in elderly persons who had exhibited both SPEs at the first survey, as compared to those who maintained both SPEs at successive surveys (p < 0.01). Elderly subjects showed slight longitudinal decline in free recall. A one-trial 10-item free-recall test demonstrated age-related cognitive decline in this Taiwanese population survey cohort; SPEs at the individual level may be useful markers for important cognitive change and warrant further study and benchmarking against valid and reliable tests of memory and cognitive decline.

  5. GxE interactions between FOXO genotypes and drinking tea are significantly associated with prevention of cognitive decline in advanced age in China.

    PubMed

    Zeng, Yi; Chen, Huashuai; Ni, Ting; Ruan, Rongping; Feng, Lei; Nie, Chao; Cheng, Lingguo; Li, Yang; Tao, Wei; Gu, Jun; Land, Kenneth C; Yashin, Anatoli; Tan, Qihua; Yang, Ze; Bolund, Lars; Yang, Huanming; Hauser, Elizabeth; Willcox, D Craig; Willcox, Bradley J; Tian, Xiao-Li; Vaupel, James W

    2015-04-01

    Logistic regression analysis based on data from 822 Han Chinese oldest old aged 92+ demonstrated that interactions between carrying FOXO1A-266 or FOXO3-310 or FOXO3-292 and tea drinking at around age 60 or at present time were significantly associated with lower risk of cognitive disability at advanced ages. Associations between tea drinking and reduced cognitive disability were much stronger among carriers of the genotypes of FOXO1A-266 or FOXO3-310 or FOXO3-292 compared with noncarriers, and it was reconfirmed by analysis of three-way interactions across FOXO genotypes, tea drinking at around age 60, and at present time. Based on prior findings from animal and human cell models, we postulate that intake of tea compounds may activate FOXO gene expression, which in turn may positively affect cognitive function in the oldest old population. Our empirical findings imply that the health benefits of particular nutritional interventions, including tea drinking, may, in part, depend upon individual genetic profiles.

  6. GxE interactions between FOXO genotypes and drinking tea are significantly associated with prevention of cognitive decline in advanced age in China.

    PubMed

    Zeng, Yi; Chen, Huashuai; Ni, Ting; Ruan, Rongping; Feng, Lei; Nie, Chao; Cheng, Lingguo; Li, Yang; Tao, Wei; Gu, Jun; Land, Kenneth C; Yashin, Anatoli; Tan, Qihua; Yang, Ze; Bolund, Lars; Yang, Huanming; Hauser, Elizabeth; Willcox, D Craig; Willcox, Bradley J; Tian, Xiao-Li; Vaupel, James W

    2015-04-01

    Logistic regression analysis based on data from 822 Han Chinese oldest old aged 92+ demonstrated that interactions between carrying FOXO1A-266 or FOXO3-310 or FOXO3-292 and tea drinking at around age 60 or at present time were significantly associated with lower risk of cognitive disability at advanced ages. Associations between tea drinking and reduced cognitive disability were much stronger among carriers of the genotypes of FOXO1A-266 or FOXO3-310 or FOXO3-292 compared with noncarriers, and it was reconfirmed by analysis of three-way interactions across FOXO genotypes, tea drinking at around age 60, and at present time. Based on prior findings from animal and human cell models, we postulate that intake of tea compounds may activate FOXO gene expression, which in turn may positively affect cognitive function in the oldest old population. Our empirical findings imply that the health benefits of particular nutritional interventions, including tea drinking, may, in part, depend upon individual genetic profiles. PMID:24895270

  7. Long-term ginsenoside Rg1 supplementation improves age-related cognitive decline by promoting synaptic plasticity associated protein expression in C57BL/6J mice.

    PubMed

    Yang, Lumeng; Zhang, Jing; Zheng, Kunmu; Shen, Hui; Chen, Xiaochun

    2014-03-01

    In aging individuals, age-related cognitive decline is the most common cause of memory impairment. Among the remedies, ginsenoside Rg1, a major active component of ginseng, is often recommended for its antiaging effects. However, its role in improving cognitive decline during normal aging remains unknown and its molecular mechanism partially understood. This study employed a scheme of Rg1 supplementation for female C57BL/6J mice, which started at the age of 12 months and ended at 24 months, to investigate the effects of Rg1 supplementation on the cognitive performance. We found that Rg1 supplementation improved the performance of aged mice in behavior test and significantly upregulated the expression of synaptic plasticity-associated proteins in hippocampus, including synaptophysin, N-methyl-D-aspartate receptor subunit 1, postsynaptic density-95, and calcium/calmodulin-dependent protein kinase II alpha, via promoting mammalian target of rapamycin pathway activation. These data provide further support for Rg1 treatment of cognitive degeneration during aging.

  8. Current evidence for the clinical use of long-chain polyunsaturated n-3 fatty acids to prevent age-related cognitive decline and Alzheimer's disease.

    PubMed

    Dacks, P A; Shineman, D W; Fillit, H M

    2013-03-01

    An NIH State of the Science Conference panel concluded in 2010 that insufficient evidence is available to recommend the use of any primary prevention therapy for Alzheimer's disease or cognitive decline with age. Despite the insufficient evidence, candidate therapies with varying levels of evidence for safety and efficacy are taken by the public and discussed in the media. One example is the long-chain n-3 (omega-3) polyunsaturated fatty acids (n-3 LC-PUFA), DHA and EPA, found in some fish and dietary supplements. With this report, we seek to provide a practical overview and rating of the level and type of available evidence that n-3 LC-PUFA supplements are safe and protective against cognitive aging and Alzheimer's disease, with additional discussion of the evidence for effects on quality of life, vascular aging, and the rate of aging. We discuss available sources, dose, bioavailability, and variables that may impact the response to n-3 LC-PUFA treatment such as baseline n-3 LC-PUFA status, APOE ε4 genotype, depression, and background diet. Lastly, we list ongoing clinical trials and propose next research steps to validate these fatty acids for primary prevention of cognitive aging and dementia. Of particular relevance, epidemiology indicates a higher risk of cognitive decline in people in the lower quartile of n-3 LC-PUFA intake or blood levels but these populations have not been specifically targeted by RCTs. PMID:23459977

  9. Current evidence for the clinical use of long-chain polyunsaturated n-3 fatty acids to prevent age-related cognitive decline and Alzheimer's disease.

    PubMed

    Dacks, P A; Shineman, D W; Fillit, H M

    2013-03-01

    An NIH State of the Science Conference panel concluded in 2010 that insufficient evidence is available to recommend the use of any primary prevention therapy for Alzheimer's disease or cognitive decline with age. Despite the insufficient evidence, candidate therapies with varying levels of evidence for safety and efficacy are taken by the public and discussed in the media. One example is the long-chain n-3 (omega-3) polyunsaturated fatty acids (n-3 LC-PUFA), DHA and EPA, found in some fish and dietary supplements. With this report, we seek to provide a practical overview and rating of the level and type of available evidence that n-3 LC-PUFA supplements are safe and protective against cognitive aging and Alzheimer's disease, with additional discussion of the evidence for effects on quality of life, vascular aging, and the rate of aging. We discuss available sources, dose, bioavailability, and variables that may impact the response to n-3 LC-PUFA treatment such as baseline n-3 LC-PUFA status, APOE ε4 genotype, depression, and background diet. Lastly, we list ongoing clinical trials and propose next research steps to validate these fatty acids for primary prevention of cognitive aging and dementia. Of particular relevance, epidemiology indicates a higher risk of cognitive decline in people in the lower quartile of n-3 LC-PUFA intake or blood levels but these populations have not been specifically targeted by RCTs.

  10. Demographic Features and Neuropsychological Correlates in a Cohort of 200 Patients with Vascular Cognitive Decline Due to Cerebral Small Vessel Disease

    PubMed Central

    Issac, Thomas Gregor; Chandra, Sadanandavalli Retnaswami; Rajeswaran, Jamuna; Christopher, Rita; Philip, Mariamma

    2016-01-01

    Introduction: Vascular dementia is the second most common form of dementia and is potentially reversible. Small vessel disease (SVD) closely mimics degenerative dementia in view of its sub-acute onset and progressive course. Therefore, unlike large vessel disease, Hachinski Ischemic scale score may not always reflect vascular cognitive decline resulting in diagnostic and therapeutic confusions. Therefore, there is a need for detailed neuropsychological assessment for various cognitive domains for early identification of vascular cognitive decline as it carries a very good long term prognosis for cognitive morbidity, unlike degenerative dementias. Patients and Methods: This prospective study involves thorough domain based neuropsychological assessment of patients with a radiological diagnosis of SVD involving the following parameters-digit forward and backward, category fluency, color trails, stick test, logical memory test, and bender gestalt test. Magnetic resonance imaging scans done using 3-tesla machines and SVD graded using Fazekas visual scale. Results: The mean Hachinskis score was less sensitive for differentiating vascular dementia from degenerative dementia. However, the domain based neuropsychological scores were highly sensitive showing statistically significant impairment in all 6 domains tested and compared with Fazekas 1-3 grades in imaging. Discussion and Conclusion: This study aimed at establishing an early diagnosis of vascular mild cognitive impairment using domain wise neuropsychological testing and correlating it with radiological scores. Hachinskis score is more sensitive for large vessel disease in view of acute onset and step-like progression as against steady progression in SVD. However, domain-wise testing was highly sensitive in identifying early cognitive impairment in patients with SVD, and early therapeutic interventions are highly rewarding. PMID:27114624

  11. The Role of Vascular Endothelial Growth Factor in Neurodegeneration and Cognitive Decline: Exploring Interactions with Biomarkers of Alzheimer’s Disease

    PubMed Central

    Hohman, Timothy J.; Bell, Susan P.; Jefferson, Angela L.

    2015-01-01

    Importance A subset of older adults present post-mortem with Alzheimer’s disease (AD) pathologic features but without any significant clinical manifestation of dementia. Vascular endothelial growth factor (VEGF) has been implicated in staving off AD-related neurodegeneration. Objective Evaluate whether VEGF levels are associated with brain aging outcomes (hippocampal volume, cognition). Further evaluate whether VEGF modifies relations between AD biomarkers and brain aging outcomes. Design Biomarker analysis using neuroimaging and neuropsychological outcomes from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Setting Prospective longitudinal study across North America. Participants Participants were drawn from the ADNI and included individuals with normal cognition (n=90), mild cognitive impairment (n=130), and AD (n=59). Main Outcome Measures Cerebrospinal fluid (CSF) VEGF was cross-sectionally related to brain aging outcomes (hippocampal volume, episodic memory, executive function) using a general linear model and longitudinally using mixed-effects regression. AD biomarker (CSF amyloid-β42 and total tau) x VEGF interactions evaluated the effect of VEGF on brain aging outcomes in the presence of enhanced AD biomarkers. Results VEGF was associated with baseline hippocampal volume (p=0.009), longitudinal hippocampal atrophy (p=0.01), and longitudinal decline in memory (p<0.0001) and executive function (p=0.003). VEGF interacted with tau in predicting longitudinal hippocampal atrophy (p<0.0001), memory decline (p=0.01), and executive function decline (p=0.0002). VEGF interacted with amyloid-β42 in predicting longitudinal memory decline (p=0.01). Conclusions Elevated CSF VEGF was associated with more optimal brain aging in vivo. The neuroprotective effect appeared strongest in the presence of enhanced AD biomarkers, suggesting that VEGF may be particularly beneficial in individuals showing early hallmarks of the AD cascade. Future work should evaluate

  12. Intranasal Insulin Prevents Cognitive Decline, Cerebral Atrophy and White Matter Changes in Murine Type I Diabetic Encephalopathy

    ERIC Educational Resources Information Center

    Francis, George J.; Martinez, Jose A.; Liu, Wei Q.; Xu, Kevin; Ayer, Amit; Fine, Jared; Tuor, Ursula I.; Glazner, Gordon; Hanson, Leah R.; Frey, William H., II; Toth, Cory

    2008-01-01

    Insulin deficiency in type I diabetes may lead to cognitive impairment, cerebral atrophy and white matter abnormalities. We studied the impact of a novel delivery system using intranasal insulin (I-I) in a mouse model of type I diabetes (streptozotocin-induced) for direct targeting of pathological and cognitive deficits while avoiding potential…

  13. A Meta-Analysis of Cognitive Impairment and Decline Associated with Adjuvant Chemotherapy in Women with Breast Cancer

    PubMed Central

    Ono, Miyuki; Ogilvie, James M.; Wilson, Jennifer S.; Green, Heather J.; Chambers, Suzanne K.; Ownsworth, Tamara; Shum, David H. K.

    2015-01-01

    A meta-analysis was performed to quantify the magnitude and nature of the association between adjuvant chemotherapy and performance on a range of cognitive domains among breast cancer patients. A total of 27 studies (14 cross-sectional, 8 both cross-sectional and prospective, and 5 prospective) were included in the analyses, involving 1562 breast cancer patients who had undergone adjuvant chemotherapy and 2799 controls that included breast cancer patients who did not receive adjuvant chemotherapy. A total of 737 effect sizes (Cohen’s d) were calculated for cross-sectional and prospective longitudinal studies separately and classified into eight cognitive domains. The mean effect sizes varied across cross-sectional and prospective longitudinal studies (ranging from −1.12 to 0.62 and −0.29 to 1.12, respectively). Each cognitive domain produced small effect sizes for cross-sectional and prospective longitudinal studies (ranging from −0.25 to 0.41). Results from cross-sectional studies indicated a significant association between adjuvant chemotherapy and cognitive impairment that held across studies with varied methodological approaches. For prospective studies, results generally indicated that cognitive functioning improved over time after receiving adjuvant chemotherapy. Greater cognitive impairment was reported in cross-sectional studies comparing chemotherapy groups with healthy control groups. Results suggested that cognitive impairment is present among breast cancer patients irrespective of a history of chemotherapy. Prospective longitudinal research is warranted to examine the degree and persisting nature of cognitive impairment present both before and after chemotherapy, with comparisons made to participants’ cognitive function prior to diagnosis. Accurate understanding of the effects of chemotherapy is essential to enable informed decisions regarding treatment and to improve quality of life among breast cancer patients. PMID:25806355

  14. Monocyte Phenotype and Polyfunctionality Are Associated With Elevated Soluble Inflammatory Markers, Cytomegalovirus Infection, and Functional and Cognitive Decline in Elderly Adults.

    PubMed

    de Pablo-Bernal, Rebeca Sara; Cañizares, Julio; Rosado, Isaac; Galvá, María Isabel; Alvarez-Ríos, Ana Isabel; Carrillo-Vico, Antonio; Ferrando-Martínez, Sara; Muñoz-Fernández, María Ángeles; Rafii-El-Idrissi Benhnia, Mohammed; Pacheco, Yolanda María; Ramos, Raquel; Leal, Manuel; Ruiz-Mateos, Ezequiel

    2016-05-01

    Monocytes are mediators of the inflammatory response and include three subsets: classical, intermediate, and nonclassical. Little is known about the phenotypical and functional age-related changes in monocytes and their association with soluble inflammatory biomarkers, cytomegalovirus infection, and functional and mental decline. We assayed the activation ex vivo and the responsiveness to TLR2 and TLR4 agonists in vitro in the three subsets and assessed the intracellular production of IL1-alpha (α), IL1-beta (β), IL-6, IL-8, TNF-α, and IL-10 of elderly adults (median 83 [67-90] years old;n= 20) compared with young controls (median 35 [27-40] years old;n= 20). Ex vivo, the elderly adults showed a higher percentage of classical monocytes that expressed intracellular IL1-α (p= .001), IL1-β (p= .001), IL-6 (p= .002), and IL-8 (p= .007). Similar results were obtained both for the intermediate and nonclassical subsets and in vitro. Polyfunctionality was higher in the elderly adults. The functionality ex vivo was strongly associated with soluble inflammatory markers. The activation phenotype was independently associated with the anti-cytomegalovirus IgG levels and with functional and cognitive decline. These data demonstrate that monocytes are key cell candidates for the source of the high soluble inflammatory levels. Our findings suggest that cytomegalovirus infection might be a driving force in the activation of monocytes and is associated with the functional and cognitive decline. PMID:26286603

  15. Monocyte Phenotype and Polyfunctionality Are Associated With Elevated Soluble Inflammatory Markers, Cytomegalovirus Infection, and Functional and Cognitive Decline in Elderly Adults.

    PubMed

    de Pablo-Bernal, Rebeca Sara; Cañizares, Julio; Rosado, Isaac; Galvá, María Isabel; Alvarez-Ríos, Ana Isabel; Carrillo-Vico, Antonio; Ferrando-Martínez, Sara; Muñoz-Fernández, María Ángeles; Rafii-El-Idrissi Benhnia, Mohammed; Pacheco, Yolanda María; Ramos, Raquel; Leal, Manuel; Ruiz-Mateos, Ezequiel

    2016-05-01

    Monocytes are mediators of the inflammatory response and include three subsets: classical, intermediate, and nonclassical. Little is known about the phenotypical and functional age-related changes in monocytes and their association with soluble inflammatory biomarkers, cytomegalovirus infection, and functional and mental decline. We assayed the activation ex vivo and the responsiveness to TLR2 and TLR4 agonists in vitro in the three subsets and assessed the intracellular production of IL1-alpha (α), IL1-beta (β), IL-6, IL-8, TNF-α, and IL-10 of elderly adults (median 83 [67-90] years old;n= 20) compared with young controls (median 35 [27-40] years old;n= 20). Ex vivo, the elderly adults showed a higher percentage of classical monocytes that expressed intracellular IL1-α (p= .001), IL1-β (p= .001), IL-6 (p= .002), and IL-8 (p= .007). Similar results were obtained both for the intermediate and nonclassical subsets and in vitro. Polyfunctionality was higher in the elderly adults. The functionality ex vivo was strongly associated with soluble inflammatory markers. The activation phenotype was independently associated with the anti-cytomegalovirus IgG levels and with functional and cognitive decline. These data demonstrate that monocytes are key cell candidates for the source of the high soluble inflammatory levels. Our findings suggest that cytomegalovirus infection might be a driving force in the activation of monocytes and is associated with the functional and cognitive decline.

  16. Creutzfeldt-Jakob Disease as a Cause of Cognitive Decline and Seizures in the Elderly: Diagnostic Pointers and Strategy for Investigation

    PubMed Central

    Williams, R.; Cresswell, F.; McClure, M.; Lane, R.

    2011-01-01

    Cognitive decline affects one in twenty people over the age of 65. There is often a paucity of clues as to the underlying pathology, and while the diagnosis will usually prove to be either Alzheimer's disease or vascular dementia, there may be clinical features suggesting rarer alternatives. This case of a 71-year-old lady with a 3-month history of progressive cognitive decline illustrates clinical features suggestive of Creutzfeltd-Jakob disease such as rapid decline in conscious level and myoclonic jerking. Diagnosis was confirmed by 3 means: (1) Electroencephalogram demonstrating periodic sharp wave complexes, (2) MRI brain showing cortical ribboning and high signal in the caudate nucleus, and (3) presence of protein S100 and protein14-3-3 in the cerebrospinal fluid. Postmortem brain histology confirmed a typical spongiform encephalopathy. Establishing an underlying aetiology is dementia is important not only for prognostic reasons but in order to detect potentially reversible causes. In cases of an atypical dementing illness our proposed investigations may assist in confirming or excluding underlying Creutzfeltd-Jakob disease. PMID:22194754

  17. Level of Cognitive Performance as a Correlate and Predictor of Health Behaviors that Protect against Cognitive Decline in Late Life: The Path through Life Study

    ERIC Educational Resources Information Center

    Anstey, Kaarin J.; Low, Lee-Fay; Christensen, Helen; Sachdev, Perminder

    2009-01-01

    There is a lack of information on how cognitive ability relates to both health behaviors and change in health behaviors over time. This study examined verbal ability and processing speed as predictors of health behaviors in the PATH Through Life Study that includes cohorts aged in their 20s, 40s and 60s. Higher cognitive scores were associated…

  18. Nutritional Status is Associated with Faster Cognitive Decline and Worse Functional Impairment in the Progression of Dementia: The Cache County Dementia Progression Study1.

    PubMed

    Sanders, Chelsea; Behrens, Stephanie; Schwartz, Sarah; Wengreen, Heidi; Corcoran, Chris D; Lyketsos, Constantine G; Tschanz, JoAnn T

    2016-02-27

    Nutritional status may be a modifiable factor in the progression of dementia. We examined the association of nutritional status and rate of cognitive and functional decline in a U.S. population-based sample. Study design was an observational longitudinal study with annual follow-ups up to 6 years of 292 persons with dementia (72% Alzheimer's disease, 56% female) in Cache County, UT using the Mini-Mental State Exam (MMSE), Clinical Dementia Rating Sum of Boxes (CDR-sb), and modified Mini Nutritional Assessment (mMNA). mMNA scores declined by approximately 0.50 points/year, suggesting increasing risk for malnutrition. Lower mMNA score predicted faster rate of decline on the MMSE at earlier follow-up times, but slower decline at later follow-up times, whereas higher mMNA scores had the opposite pattern (mMNA by time β= 0.22, p = 0.017; mMNA by time2 β= -0.04, p = 0.04). Lower mMNA score was associated with greater impairment on the CDR-sb over the course of dementia (β= 0.35, p <  0.001). Assessment of malnutrition may be useful in predicting rates of progression in dementia and may provide a target for clinical intervention.

  19. Age-related decline in verbal learning is moderated by demographic factors, working memory capacity, and presence of amnestic mild cognitive impairment.

    PubMed

    Constantinidou, Fofi; Zaganas, Ioannis; Papastefanakis, Emmanouil; Kasselimis, Dimitrios; Nidos, Andreas; Simos, Panagiotis G

    2014-09-01

    Age-related memory changes are highly varied and heterogeneous. The study examined the rate of decline in verbal episodic memory as a function of education level, auditory attention span and verbal working memory capacity, and diagnosis of amnestic mild cognitive impairment (a-MCI). Data were available on a community sample of 653 adults aged 17-86 years and 70 patients with a-MCI recruited from eight broad geographic areas in Greece and Cyprus. Measures of auditory attention span and working memory capacity (digits forward and backward) and verbal episodic memory (Auditory Verbal Learning Test [AVLT]) were used. Moderated mediation regressions on data from the community sample did not reveal significant effects of education level on the rate of age-related decline in AVLT indices. The presence of a-MCI was a significant moderator of the direct effect of Age on both immediate and delayed episodic memory indices. The rate of age-related decline in verbal episodic memory is normally mediated by working memory capacity. Moreover, in persons who display poor episodic memory capacity (a-MCI group), age-related memory decline is expected to advance more rapidly for those who also display relatively poor verbal working memory capacity.

  20. Nutritional Status is Associated with Faster Cognitive Decline and Worse Functional Impairment in the Progression of Dementia: The Cache County Dementia Progression Study1.

    PubMed

    Sanders, Chelsea; Behrens, Stephanie; Schwartz, Sarah; Wengreen, Heidi; Corcoran, Chris D; Lyketsos, Constantine G; Tschanz, JoAnn T

    2016-02-27

    Nutritional status may be a modifiable factor in the progression of dementia. We examined the association of nutritional status and rate of cognitive and functional decline in a U.S. population-based sample. Study design was an observational longitudinal study with annual follow-ups up to 6 years of 292 persons with dementia (72% Alzheimer's disease, 56% female) in Cache County, UT using the Mini-Mental State Exam (MMSE), Clinical Dementia Rating Sum of Boxes (CDR-sb), and modified Mini Nutritional Assessment (mMNA). mMNA scores declined by approximately 0.50 points/year, suggesting increasing risk for malnutrition. Lower mMNA score predicted faster rate of decline on the MMSE at earlier follow-up times, but slower decline at later follow-up times, whereas higher mMNA scores had the opposite pattern (mMNA by time β= 0.22, p = 0.017; mMNA by time2 β= -0.04, p = 0.04). Lower mMNA score was associated with greater impairment on the CDR-sb over the course of dementia (β= 0.35, p <  0.001). Assessment of malnutrition may be useful in predicting rates of progression in dementia and may provide a target for clinical intervention. PMID:26967207

  1. Prevention of Decline in Cognition after Stroke Trial (PODCAST): a study protocol for a factorial randomised controlled trial of intensive versus guideline lowering of blood pressure and lipids

    PubMed Central

    2013-01-01

    Background Stroke is a common cause of cognitive impairment and dementia. However, effective strategies for reducing the risk of post-stroke dementia remain undefined. Potential strategies include intensive lowering of blood pressure and/or lipids. Methods/Design Design: multi-centre prospective randomised open-label blinded-endpoint controlled partial-factorial phase IV trial in secondary and primary care. Participants: 100 participants from 30 UK Stroke Research Network sites who are post- ischemic stroke or intracerebral haemorrhage by three to seven months. Interventions - all patients (1:1): intensive versus guideline blood pressure lowering (target systolic < 125 mmHg versus < 140 mmHg). Interventions - ischemic stroke (1:1): intensive versus guideline lipid lowering (target low density lipoprotein-cholesterol (LDL-c) < 1.4 mmol/l versus < 3 mmol/l). Hypotheses: does ‘intensive’ blood pressure lowering therapy and/or ‘intensive’ lipid control reduce cognitive decline and dementia in people with ischemic stroke; and does ‘intensive’ blood pressure lowering therapy reduce cognitive decline and dementia in patients with hemorrhagic stroke. Primary outcome: Addenbrooke’s Cognitive Examination-Revised. Secondary outcomes: feasibility of recruitment and retention of participants, tolerability and safety of the interventions, achieving and maintaining the blood pressure and lipid targets, maintaining differences in systolic blood pressure (> 10 mmHg) and low density lipoprotein-cholesterol (> 1 mmol/l) between the treatment groups, and performing clinic and telephone follow-up of cognition measures. Randomisation: using stratification, minimization and simple randomization. Blinding: participants receive open-label management. Cognition is assessed both unblinded (in clinic) and blinded (by telephone) to treatment. Adjudication of events (dementia, vascular, serious adverse events) is blinded to management. Discussion The PODCAST

  2. A role for HLA-DRB1*1101 and DRB1*0801 in cognitive ability and its decline with age.

    PubMed

    Payton, Antony; Dawes, Piers; Platt, Hazel; Morton, Cynthia C; Moore, David R; Massey, Jonathan; Horan, Michael; Ollier, William; Munro, Kevin J; Pendleton, Neil

    2016-03-01

    Cognitive abilities (memory, processing speed, vocabulary, and fluid intelligence) are correlated with educational attainment and occupational status, as well as physical and mental health. The variation in cognitive abilities observed within a population has a substantial genetic contribution (heritability ∼50%) and yet the identification of genetic polymorphisms from both genome-wide association and candidate studies have to date only uncovered a limited number of genetic variants that exert small genetic effects. Here we impute human leukocyte antigens (HLA) using existing genome-wide association data from 1,559 non-pathological elderly volunteers who have been followed for changes in cognitive functioning between a 12- and 18-year period. Specifically, we investigate DRB1*05 (*11/*12) and DRB1*01, which have previously been associated with cognitive ability. We also analyze DRB1*0801, which shares close sequence homology with DRB1*1101. Together with DRB1*1101, DRB1*0801 has been associated with several diseases including multiple sclerosis and primary biliary cirrhosis, which themselves are associated with cognitive impairment. We observed that both DRB1*0801 and DRB1*1101 were significantly associated with vocabulary ability (cross-sectional and longitudinal scores) and that the effects were in opposite directions with DRB1*0801 associated with lower score and faster decline. This opposing affect is similar to that reported by other groups in systemic lupus erythematosus, type 1 diabetes, and primary biliary cirrhosis. DRB1*0801 was also significantly associated with reduced memory ability. We observed no associations between cognitive abilities and DRB1*01 or DRB1*12. PMID:26473500

  3. Patterns of Age-Associated Degeneration Differ in Shoulder Muscles

    PubMed Central

    Raz, Yotam; Henseler, Jan F.; Kolk, Arjen; Riaz, Muhammad; van der Zwaal, Peer; Nagels, Jochem; Nelissen, Rob G. H. H.; Raz, Vered

    2015-01-01

    Shoulder complaints are common in the elderly and hamper daily functioning. These complaints are often caused by tears in the muscle-tendon units of the rotator cuff (RC). The four RC muscles stabilize the shoulder joint. While some RC muscles are frequently torn in shoulder complaints others remain intact. The pathological changes in RC muscles are poorly understood. We investigated changes in RC muscle pathology combining radiological and histological procedures. We measured cross sectional area (CSA) and fatty infiltration from Magnetic Resonance Imaging with Arthrography (MRA) in subjects without (N = 294) and with (N = 109) RC-tears. Normalized muscle CSA of the four RC muscles and the deltoid shoulder muscle were compared and age-associated patterns of muscle atrophy and fatty infiltration were constructed. We identified two distinct age-associated patterns: in the supraspinatus and subscapularis RC muscles CSAs continuously declined throughout adulthood, whereas in the infraspinatus and deltoid reduced CSA was prominent from midlife onwards. In the teres minor, CSA was unchanged with age. Most importantly, age-associated patterns were highly similar between subjects without RC tear and those with RC-tears. This suggests that extensive RC muscle atrophy during aging could contribute to RC pathology. We compared muscle pathology between torn infraspinatus and non-torn teres minor and the deltoid in two patients with a massive RC-tear. In the torn infraspinatus we found pronounced fatty droplets, an increase in extracellular collagen-1, a loss of myosin heavy chain-1 expression in myofibers and an increase in Pax7-positive cells. However, the adjacent intact teres minor and deltoid exhibited healthy muscle features. This suggests that satellite cells and the extracellular matrix may contribute to extensive muscle fibrosis in torn RC. We suggest that torn RC muscles display hallmarks of muscle aging whereas the teres minor could represent an aging

  4. Patterns of Age-Associated Degeneration Differ in Shoulder Muscles.

    PubMed

    Raz, Yotam; Henseler, Jan F; Kolk, Arjen; Riaz, Muhammad; van der Zwaal, Peer; Nagels, Jochem; Nelissen, Rob G H H; Raz, Vered

    2015-01-01

    Shoulder complaints are common in the elderly and hamper daily functioning. These complaints are often caused by tears in the muscle-tendon units of the rotator cuff (RC). The four RC muscles stabilize the shoulder joint. While some RC muscles are frequently torn in shoulder complaints others remain intact. The pathological changes in RC muscles are poorly understood. We investigated changes in RC muscle pathology combining radiological and histological procedures. We measured cross sectional area (CSA) and fatty infiltration from Magnetic Resonance Imaging with Arthrography (MRA) in subjects without (N = 294) and with (N = 109) RC-tears. Normalized muscle CSA of the four RC muscles and the deltoid shoulder muscle were compared and age-associated patterns of muscle atrophy and fatty infiltration were constructed. We identified two distinct age-associated patterns: in the supraspinatus and subscapularis RC muscles CSAs continuously declined throughout adulthood, whereas in the infraspinatus and deltoid reduced CSA was prominent from midlife onwards. In the teres minor, CSA was unchanged with age. Most importantly, age-associated patterns were highly similar between subjects without RC tear and those with RC-tears. This suggests that extensive RC muscle atrophy during aging could contribute to RC pathology. We compared muscle pathology between torn infraspinatus and non-torn teres minor and the deltoid in two patients with a massive RC-tear. In the torn infraspinatus we found pronounced fatty droplets, an increase in extracellular collagen-1, a loss of myosin heavy chain-1 expression in myofibers and an increase in Pax7-positive cells. However, the adjacent intact teres minor and deltoid exhibited healthy muscle features. This suggests that satellite cells and the extracellular matrix may contribute to extensive muscle fibrosis in torn RC. We suggest that torn RC muscles display hallmarks of muscle aging whereas the teres minor could represent an aging

  5. Ginkgo for elderly people with dementia and age-associated memory impairment: a randomized clinical trial.

    PubMed

    van Dongen, Martien; van Rossum, Erik; Kessels, Alphons; Sielhorst, Hilde; Knipschild, Paul

    2003-04-01

    Preparations based on special extracts of the Ginkgo biloba tree are popular in various European countries. Previous studies have suggested the clinical efficacy of Ginkgo in patients with dementia, cerebral insufficiency, or related cognitive decline. However, most of these studies did not fulfill the current methodologic requirements. We assessed the efficacy of the G. biloba special extract EGb 761 in patients with dementia and age-associated memory impairment in relation to dose and duration of treatment. Our study was a 24-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. Study participants were elderly patients with dementia (Alzheimer disease or vascular dementia) or age-associated memory impairment (AAMI). A total of 214 participants, recruited from 39 homes for the elderly in the Netherlands, were randomly allocated to Ginkgo (either 240 mg/d or 160 mg/d) or placebo (0 mg/d). After 12 weeks, the subjects in the two Ginkgo groups were randomized to continued Ginkgo treatment or placebo treatment. Primary outcome measures in this study were the Syndrome Kurz Test (SKT; psychometric functioning), the Clinical Global Impression of change (CGI-2; psychopathology, assessed by nursing staff), and the Nuremberg Gerontopsychological Rating Scale for Activities of Daily Living (NAI-NAA; behavioral functioning). One hundred twenty-three patients received Ginkgo (n=79, 240 and 160 mg/d combined) or placebo (n=44) during the 24-week intervention period. We found no statistically significant differences in mean change of scores between Ginkgo and placebo. The differences were SKT: +0.4 (90% confidence interval [CI] -0.9-1.7); CGI-2: +0.1 (90% CI -0.3-0.4), and NAI-NAA: -0.4 (90% CI -1.9-1.2). A positive difference is in favor of Ginkgo. Neither the dementia subgroup (n=36) nor the AAMI subgroup (n=87) experienced a significant effect of Ginkgo treatment. There was no dose-effect relationship and no effect of prolonged Ginkgo

  6. History of childhood physical trauma is related to cognitive decline in individuals with ultra-high risk for psychosis.

    PubMed

    Üçok, Alp; Kaya, Hatice; Uğurpala, Can; Çıkrıkçılı, Uğur; Ergül, Ceylan; Yokuşoğlu, Çağdaş; Bülbül, Öznur; Direk, Nese

    2015-12-01

    The aim of this study was to investigate the relationship between childhood trauma (CT) and cognitive functioning in individuals with ultra-high risk for psychosis (UHR). Fifty-three individuals at UHR for psychosis were administered a neurocognitive battery that assessed attention, processing speed, verbal learning, memory, working memory, interference inhibition, and sustained attention. The CT was assessed using the short-version Childhood Trauma Questionnaire (CTQ). We dichotomized the sample by using cut-off scores for the presence of emotional, physical and sexual trauma, and physical and emotional neglect. Those with a history of physical trauma performed worse on the Digit Span Forward test, Trail making B (time), Stroop test (difference between color and word reading times), and completed categories of the Wisconsin Card Sorting Test (WCST). Physical trauma scores were correlated with WCST-completed categories, Digit Span Forward and Stroop test scores. Physical neglect scores were negatively correlated with Digit Span Forward Test scores. Most of the significant dose–response relationships between cognitive impairment and different subtypes of CT were found only in men. There was no difference between those with and without other kinds of childhood abuse or neglect in terms of cognitive impairment. Our findings suggest that a history of physical trauma has a negative impact on cognitive function in individuals at UHR for psychosis.

  7. ZiBuPiYin Recipe Protects db/db Mice from Diabetes-Associated Cognitive Decline through Improving Multiple Pathological Changes

    PubMed Central

    Zhan, Libin; Zhou, Yan; Zheng, Luping; Sun, Xiaoxin; Gong, Jin; Sui, Hua; Jiang, Rujiao; Zhang, Fuliang; Zhang, Lin

    2014-01-01

    Multiple organ systems, including the brain, which undergoes changes that may increase the risk of cognitive decline, are adversely affected by diabetes mellitus (DM). Here, we demonstrate that type 2 diabetes mellitus (T2DM) db/db mice exhibited hippocampus-dependent memory impairment, which might associate with a reduction in dendritic spine density in the pyramidal neurons of brain, Aβ1-42 deposition in the prefrontal cortex (PFC) and hippocampus, and a decreased expression of neurostructural proteins including microtubule-associated protein (MAP2), a marker of dendrites, and postsynaptic density 95 (PSD95), a marker of excitatory synapses. To investigate the effects of the ZiBuPiYin recipe (ZBPYR), a traditional Chinese medicine recipe, on diabetes-related cognitive decline (DACD), db/db mice received daily administration of ZBPYR over an experimental period of 6 weeks. We then confirmed that ZBPYR rescued learning and memory performance impairments, reversed dendritic spine loss, reduced Aβ1-42 deposition and restored the expression levels of MAP2 and PSD95. The present study also revealed that ZBPYR strengthened brain leptin and insulin signaling and inhibited GSK3β overactivity, which may be the potential mechanism or underlying targets of ZBPYR. These findings conclude that ZBPYR prevents DACD, most likely by improving dendritic spine density and attenuating brain leptin and insulin signaling pathway injury. Our findings provide further evidence for the effects of ZBPYR on DACD. PMID:24614172

  8. Aluminum and silica in drinking water and the risk of Alzheimer's disease or cognitive decline: findings from 15-year follow-up of the PAQUID cohort.

    PubMed

    Rondeau, Virginie; Jacqmin-Gadda, Hélène; Commenges, Daniel; Helmer, Catherine; Dartigues, Jean-François

    2009-02-15

    The authors examined associations between exposure to aluminum or silica from drinking water and risk of cognitive decline, dementia, and Alzheimer's disease among elderly subjects followed for 15 years (1988-2003). They actively searched for incident cases of dementia among persons aged 65 years or over living in 91 civil drinking-water areas in southern France. Two measures of exposure to aluminum were assessed: geographic exposure and individual exposure, taking into account daily consumption of tap water and bottled water. A total of 1,925 subjects who were free of dementia at baseline and had reliable water assessment data were analyzed. Using random-effects models, the authors found that cognitive decline with time was greater in subjects with a higher daily intake of aluminum from drinking water (>or=0.1 mg/day, P=0.005) or higher geographic exposure to aluminum. Using a Cox model, a high daily intake of aluminum was significantly associated with increased risk of dementia. Conversely, an increase of 10 mg/day in silica intake was associated with a reduced risk of dementia (adjusted relative risk =0.89, P=0.036). However, geographic exposure to aluminum or silica from tap water was not associated with dementia. High consumption of aluminum from drinking water may be a risk factor for Alzheimer's disease.

  9. Prevention of age-associated dementia.

    PubMed

    Mohajeri, M Hasan; Leuba, Genevieve

    2009-10-28

    The advancement of medical sciences during the last century has resulted in a considerable increase in life expectancy. As more people live to old age, one of the most fundamental questions of the 21st century is whether the number of individuals suffering from dementia will also continue to increase. Alzheimer's disease (AD) accounts for the majority of cases of dementia in the elderly, but there is currently no curative treatment available. Several strategies have been introduced for treatment, the most recent strategy of which was the immunization of patients using antibodies against Abeta, which is a naturally occurring, even though misfolded peptide in the AD brain. Both active and passive immunization routes have been shown to reduce the pathology associated with Abeta accumulation in brains of genetically designed animal models. However, despite tremendous efforts, no unequivocal proof of therapeutic efficacy could be shown in AD patients. Particularly, the persistence of the neurofibrillary tangles in immunized brains and the issue of inducing cerebral amyloid angiopathy are major limiting factors of antibody therapy. Furthermore, physical activity, a healthy immune system and nutritional habits are suggested to protect against the onset of age-associated dementia. Thus, accumulative evidence suggests that an early integrated strategy, combining pharmacological, immunological, nutritional and life-style factors, is the most pragmatic approach to delay the onset and progression of age-associated dementia.

  10. 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine improves cognitive decline by enhancing long-term depression.

    PubMed

    Yaguchi, Takahiro; Nagata, Tetsu; Nishizaki, Tomoyuki

    2009-12-01

    1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPhtCho) (1 microM) enhanced long-term depression (LTD), a synaptic plasticity relevant to learning and memory, in the CA1 region of rat hippocampal slices, where expression of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunit GluR1 on the plasma membrane was decreased. In the water maze test, oral administration with POPhtCho (5 mg/kg) significantly shortened the prolonged retention latency for rats intraperitoneally injected with scopolamine (1 mg/kg), while the acquisition latency was not affected. For humans with mild cognitive impairment and dementia (average of Mini Mental State Examination score, 18), oral intake with POPhtCho (300 mg/day, once after breakfast) everyday raised the score to over 20, corresponding to normal cognitive functions, throughout 6 months after intake. The results of the present study, thus, indicate that POPhtCho could ameliorate cognitive disorders, possibly by enhancing LTD. PMID:19482045

  11. Age-related cognitive decline and electroencephalogram slowing in Down's syndrome as a model of Alzheimer's disease.

    PubMed

    Soininen, H; Partanen, J; Jousmäki, V; Helkala, E L; Vanhanen, M; Majuri, S; Kaski, M; Hartikainen, P; Riekkinen, P

    1993-03-01

    We studied quantitative electroencephalogram and neuropsychological performance in an aging series of 31 patients with Down's syndrome and compared the findings with those of 36 patients with probable Alzheimer's disease and age-matched controls. We found an age-related decline of cortical functions and slowing of the electroencephalogram in Down's syndrome patients aged from 20 to 60 years. Slowing of the electroencephalogram, i.e. the decrease of the peak frequency, was significantly related to Mini-Mental status scores, and visual, praxic and speech functions, as well as memory in the Down patients, similar to the Alzheimer patients. Similar correlations were not demonstrated for young or elderly controls. This study provides neuropsychological and electrophysiological data to suggest that studying Down's syndrome patients of different ages can serve as a model for progression of Alzheimer's disease. PMID:8469312

  12. Direct medical costs and source of cost differences across the spectrum of cognitive decline: A population-based study

    PubMed Central

    Leibson, Cynthia L.; Long, Kirsten Hall; Ransom, Jeanine E.; Roberts, Rosebud O.; Hass, Steven L.; Duhig, Amy M.; Smith, Carin Y.; Emerson, Jane A.; Pankratz, V. Shane; Petersen, Ronald C.

    2015-01-01

    BACKGROUND Objective cost estimates and source of cost differences are needed across the spectrum of cognition, including cognitively normal (CN), mild-cognitive-impairment (MCI), newly-discovered dementia, and prevalent dementia. METHODS Subjects were a subset of the Mayo Clinic Study of Aging stratified-random sampling of Olmsted County, MN, residents aged 70-89 years. A neurologist reviewed provider-linked medical records to identify prevalent-dementia (review date=index). Remaining subjects were invited to participate in prospective clinical/neuropsychological assessments; participants were categorized as CN, MCI, or newly-discovered-dementia (assessment date=index). Costs for medical services/procedures 1-year pre-index (excluding indirect and long-term care costs) were estimated using line-item provider-linked administrative data. We estimated contributions of care-delivery site and comorbid conditions (including and excluding neuropsychiatric diagnoses) to between-category cost differences. RESULTS Annual mean medical costs for CN, MCI, newly-discovered-dementia, and prevalent-dementia were $6,042, $6,784, $9,431, $11,678 respectively. Hospital inpatient costs contributed 70% of total costs for prevalent dementia and accounted for differences between CN and both prevalent and newly-discovered dementia. Ambulatory costs accounted for differences between CN and MCI. Age-, sex-, education-adjusted differences reached significance for CN versus newly-discovered and prevalent-dementia and for MCI versus prevalent-dementia. After considering all comorbid diagnoses, between-category differences were reduced (e.g., prevalent-dementia minus MCI (from $4,842 to $3,575); newly-discovered-dementia minus CN (from $3,578 to$711). Following exclusion of neuropsychiatric diagnoses from comorbidity adjustment, between-category differences tended to revert to greater differences. CONCLUSIONS Cost estimates did not differ significantly between CN and MCI. Substantial

  13. Age-Associated Increase in BMP Signaling Inhibits Hippocampal Neurogenesis.

    PubMed

    Yousef, Hanadie; Morgenthaler, Adam; Schlesinger, Christina; Bugaj, Lukasz; Conboy, Irina M; Schaffer, David V

    2015-05-01

    Hippocampal neurogenesis, the product of resident neural stem cell proliferation and differentiation, persists into adulthood but decreases with organismal aging, which may contribute to the age-related decline in cognitive function. The mechanisms that underlie this decrease in neurogenesis are not well understood, although evidence in general indicates that extrinsic changes in an aged stem cell niche can contribute to functional decline in old stem cells. Bone morphogenetic protein (BMP) family members are intercellular signaling proteins that regulate stem and progenitor cell quiescence, proliferation, and differentiation in various tissues and are likewise critical regulators of neurogenesis in young adults. Here, we establish that BMP signaling increases significantly in old murine hippocampi and inhibits neural progenitor cell proliferation. Furthermore, direct in vivo attenuation of BMP signaling via genetic and transgenic perturbations in aged mice led to elevated neural stem cell proliferation, and subsequent neurogenesis, in old hippocampi. Such advances in our understanding of mechanisms underlying decreased hippocampal neurogenesis with age may offer targets for the treatment of age-related cognitive decline.

  14. Slowing of Hippocampal Activity Correlates with Cognitive Decline in Early Onset Alzheimer's Disease. An MEG Study with Virtual Electrodes.

    PubMed

    Engels, Marjolein M A; Hillebrand, Arjan; van der Flier, Wiesje M; Stam, Cornelis J; Scheltens, Philip; van Straaten, Elisabeth C W

    2016-01-01

    Pathology in Alzheimer's disease (AD) starts in the entorhinal cortex and hippocampus. Because of their deep location, activity from these areas is difficult to record with conventional electro- or magnetoencephalography (EEG/MEG). The purpose of this study was to explore hippocampal activity in AD patients and healthy controls using "virtual MEG electrodes". We used resting-state MEG recordings from 27 early onset AD patients [age 60.6 ± 5.4, 12 females, mini-mental state examination (MMSE) range: 19-28] and 26 cognitively healthy age- and gender-matched controls (age 61.8 ± 5.5, 14 females). Activity was reconstructed using beamformer-based virtual electrodes for 78 cortical regions and 6 hippocampal regions. Group differences in peak frequency and relative power in six frequency bands were identified using permutation testing. For the patients, spearman correlations between the MMSE scores and peak frequency or relative power were calculated. Moreover, receiver operator characteristic curves were plotted to estimate the diagnostic accuracy. We found a lower hippocampal peak frequency in AD compared to controls, which, in the patients, correlated positively with MMSE [r(25) = 0.61; p < 0.01] whereas hippocampal relative theta power correlated negatively with MMSE [r(25) = -0.54; p < 0.01]. Cortical peak frequency was also lower in AD in association areas. Furthermore, cortical peak frequency correlated positively with MMSE [r(25) = 0.43; p < 0.05]. In line with this finding, relative theta power was higher in AD across the cortex, and relative alpha and beta power was lower in more circumscribed areas. The average cortical relative theta power was the best discriminator between AD and controls (sensitivity 82%; specificity 81%). Using beamformer-based virtual electrodes, we were able to detect hippocampal activity in AD. In AD, this hippocampal activity is slowed, and correlates better with cognition than the (slowed) activity in cortical areas. On the other

  15. Slowing of Hippocampal Activity Correlates with Cognitive Decline in Early Onset Alzheimer's Disease. An MEG Study with Virtual Electrodes.

    PubMed

    Engels, Marjolein M A; Hillebrand, Arjan; van der Flier, Wiesje M; Stam, Cornelis J; Scheltens, Philip; van Straaten, Elisabeth C W

    2016-01-01

    Pathology in Alzheimer's disease (AD) starts in the entorhinal cortex and hippocampus. Because of their deep location, activity from these areas is difficult to record with conventional electro- or magnetoencephalography (EEG/MEG). The purpose of this study was to explore hippocampal activity in AD patients and healthy controls using "virtual MEG electrodes". We used resting-state MEG recordings from 27 early onset AD patients [age 60.6 ± 5.4, 12 females, mini-mental state examination (MMSE) range: 19-28] and 26 cognitively healthy age- and gender-matched controls (age 61.8 ± 5.5, 14 females). Activity was reconstructed using beamformer-based virtual electrodes for 78 cortical regions and 6 hippocampal regions. Group differences in peak frequency and relative power in six frequency bands were identified using permutation testing. For the patients, spearman correlations between the MMSE scores and peak frequency or relative power were calculated. Moreover, receiver operator characteristic curves were plotted to estimate the diagnostic accuracy. We found a lower hippocampal peak frequency in AD compared to controls, which, in the patients, correlated positively with MMSE [r(25) = 0.61; p < 0.01] whereas hippocampal relative theta power correlated negatively with MMSE [r(25) = -0.54; p < 0.01]. Cortical peak frequency was also lower in AD in association areas. Furthermore, cortical peak frequency correlated positively with MMSE [r(25) = 0.43; p < 0.05]. In line with this finding, relative theta power was higher in AD across the cortex, and relative alpha and beta power was lower in more circumscribed areas. The average cortical relative theta power was the best discriminator between AD and controls (sensitivity 82%; specificity 81%). Using beamformer-based virtual electrodes, we were able to detect hippocampal activity in AD. In AD, this hippocampal activity is slowed, and correlates better with cognition than the (slowed) activity in cortical areas. On the other

  16. Cognitive control adjustments in healthy older and younger adults: Conflict adaptation, the error-related negativity (ERN), and evidence of generalized decline with age.

    PubMed

    Larson, Michael J; Clayson, Peter E; Keith, Cierra M; Hunt, Isaac J; Hedges, Dawson W; Nielsen, Brent L; Call, Vaughn R A

    2016-03-01

    Older adults display alterations in neural reflections of conflict-related processing. We examined response times (RTs), error rates, and event-related potential (ERP; N2 and P3 components) indices of conflict adaptation (i.e., congruency sequence effects) a cognitive control process wherein previous-trial congruency influences current-trial performance, along with post-error slowing, correct-related negativity (CRN), error-related negativity (ERN) and error positivity (Pe) amplitudes in 65 healthy older adults and 94 healthy younger adults. Older adults showed generalized slowing, had decreased post-error slowing, and committed more errors than younger adults. Both older and younger adults showed conflict adaptation effects; magnitude of conflict adaptation did not differ by age. N2 amplitudes were similar between groups; younger, but not older, adults showed conflict adaptation effects for P3 component amplitudes. CRN and Pe, but not ERN, amplitudes differed between groups. Data support generalized declines in cognitive control processes in older adults without specific deficits in conflict adaptation.

  17. Assessing executive functioning: on the validity, reliability, and sensitivity of a click/point random number generation task in healthy adults and patients with cognitive decline.

    PubMed

    Maes, Joseph H R; Eling, Paul A T M; Reelick, Miriam F; Kessels, Roy P C

    2011-03-01

    In random number generation (RNG) tasks, used to assess executive functioning, participants are asked to generate a random sequence of digits at a paced rate, either verbally or by writing. Some previous studies used an alternative format in