Function In Old Age Research Articles

Positive Aging Beyond “Success”: Towards a More Inclusive Perspective of High Level Functioning in Old Age

Successful aging is the ability to maintain low probability of disease and disability, high cognitive and physical functioning, and active engagement with life (Rowe & Kahn, 1999). These criteria allow for a minority of people to be classified as being “successful” and overlook the importance of psychological variables in balancing the weight of disease. A total of 1322 seniors (55 + years) were classified on their overall functioning according to core domains (health, psychological, cognitive, biobehavioural, social, personality). Findings support the idea that a broader perspective of aging outcomes, rather than success criteria, may better reflect reality.

Can we model a cognitive footprint of interventions and policies to help to meet the global challenge of dementia?

Can we model a cognitive footprint of interventions and policies to help to meet the global challenge of dementia?

Smoking and cognitive functioning at older ages: Evidence from the Health and Retirement Study

Abstract It has long been established that smoking has detrimental health effects on the human body and leads to early mortality. However, the evidence regarding the link between smoking behavior and cognitive function in old age is mixed. While nicotine has been shown to improve cognitive functioning in some medical studies, current smokers typically perform worse than non-smokers on cognitive tests in population based studies. We use the Health and Retirement Study to evaluate the role of unobserved factors in explaining these conflicting findings. Results from individual fixed effects models show that much of the lower cognitive function of current and former smokers relative to never smokers can be attributed to unobserved differences between these groups.

Blood Pressure Lowering Medication, Visit-to-Visit Blood Pressure Variability, and Cognitive Function in Old Age.

Visit-to-visit blood pressure (BP) variability is associated with cognitive impairment. We assessed to what extent the association between BP variability and cognitive impairment is mediated by the association of BP lowering medication (BPLM) with both BP variability and cognition. We studied 5,606 participants from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). BP was measured every 3 months during 3.2 years; BP variability was defined as the SD of BP measurements during follow-up. Cognitive function was assessed at baseline and during follow-up using the Stroop test, Letter-Digit Coding test, and immediate and delayed Picture-Word Learning tests. Multivariate regression models were used with and without adjustments for BPLM to calculate the percentage to which BPLM mediated the association between BP variability and cognition. Participants taking calcium antagonists had a higher score in baseline Letter-Digit Coding test (mean difference (95% confidence interval (CI) 0.45 (0.06; 0.88). Participants taking beta-blockers had a steeper decline in Stroop test (additional change per year (95% CI) 0.40 (0.09; 0.70) and Letter-Digit Coding test (0.08 (-0.15; -0.02)). Furthermore, a steeper decline in Stroop test was found in participants taking renin-angiotensin system (RAS) inhibitors (0.50 (0.16; 0.85). Systolic BP variability was higher in participants taking beta-blockers and RAS inhibitors (mean difference in systolic BP variability in mm Hg (95% CI) 0.75 (0.45; 1.04) and 1.37 (1.04; 1.71) respectively). Participants taking diuretics, calcium antagonists, and RAS inhibitors had a higher diastolic BP variability (mean difference in diastolic BP variability in mm Hg (95% CI) 0.27 (0.04; 0.49), 0.37 (0.12; 0.62) and 0.65 (0.37; 0.93) SD, respectively). Beta estimates remained essentially the same when we adjusted for BPLM in the association of BP variability with cognitive function. The association between BP variability and cognitive impairment was not mediated by BPLM.

Neural reorganization and compensation in aging.

According to prominent theories of aging, the brain may reorganize to compensate for neural deterioration and prevent or offset cognitive decline. A frequent and striking finding in functional imaging studies is that older adults recruit additional regions relative to young adults performing the same task. This is often interpreted as evidence for functional reorganization, suggesting that, as people age, different regions or networks may support the same cognitive functions. Associations between additional recruitment and better performance in older adults have led to the suggestion that the additional recruitment may contribute to preserved cognitive function in old age and may explain some of the variation among individuals in preservation of function. However, many alternative explanations are possible, and recent findings and methodological developments have highlighted the need for more systematic approaches to determine whether reorganization occurs with age and whether it benefits performance. We reevaluate current evidence for compensatory functional reorganization in the light of recent moves to address these challenges.

The mobility gap between older men and women: The embodiment of gender

ObjectivesTo present the study design and baseline results of the longitudinal International Mobility in Aging Study (IMIAS) on gender differences in physical performance and mobility disability prevalence in five diverse societies. MethodsData are from surveys on random samples of people aged 65–74 years at Canadian (Kingston, Ontario; Saint-Hyacinthe, Quebec), Mediterranean (Tirana, Albania) and Latin American sites (Natal, Brazil; Manizales, Colombia) (N=1995). Mobility disability was defined as reporting difficulty in walking 400m or climbing stairs. Activities of daily living (ADL) disability was based on any self-reported difficulty in five mobility-related ADLs. The short physical performance battery (SPPB) was used to assess physical performance. Poisson regression models were fitted to estimate prevalence ratios. ResultsAge-adjusted prevalence of low SPPB, mobility disability and ADL disability were higher in women than in men in all sites except for Kingston. After adjustment for education and income, gender differences in SPPB and ADL disability attenuated or disappeared in Saint-Hyacinthe and Manizales but remained large in Tirana and Natal and mobility disability remained more frequent in women than in men at all sites except Kingston. After further adjustment by chronic conditions and depressive symptoms, gender differences in mobility remained large at all sites except Kingston but only in Tirana did women have significantly poorer physical performance than men. DiscussionResults provide evidence for gender as a risk factor to explain poorer physical function in women and suggest that moving toward gender equality could attenuate the gender gap in physical function in old age.

Social cognition is not associated with cognitive reserve in older adults

Social and general cognitive abilities decline in late life. Those with high cognitive reserve display better general cognitive performance in old age; however, it is unknown whether this is also the case for social cognition. A total of 115 healthy older adults, aged 60–85 years (m = 44, f = 71) were assessed using The Awareness of Social Inference Test (TASIT-R; social cognition), the Lifetime of Experiences Questionnaire (LEQ; cognitive reserve), and the Wechsler Abbreviated Scale of Intelligence (WASI-II; general cognitive ability). The LEQ did not predict performance on any TASIT-R subtest: Emotion Evaluation Test (β = -.097, p = .325), Social Inference – Minimal (β = -.004, p = .972), or Social Inference – Enriched (β = -.016, p = .878). Sensitivity analyses using two alternative cognitive reserve measures, years of education and the National Adult Reading Test, supported these effects. Cognitive reserve was strongly related to WASI-II performance. Unlike general cognitive ability, social cognition appears unaffected by cognitive reserve. Findings contribute to the emerging understanding that cognitive reserve differentially affects individual cognitive domains, which has implications for the theoretical understanding of cognitive reserve and its brain correlates. Cognitive measures unbiased by cognitive reserve may serve as best indicators of brain health, free of compensatory mechanisms.

Gender- and region-dependent changes of redox biomarkers in the brain of successfully aging LOU/C rats

The LOU/C (LOU) rat is an obesity resistant strain with higher longevity and healthspan than common rats. The management of oxidative stress being important to successful aging, we characterized this process in the aging LOU rat. Male/female LOU rats were euthanized at 4, 20, and 29 months. Macrodissected hippocampus, striatum, parietal cortex, cerebellum were assayed for tissue concentrations of glutathione (GSH), gamma-glutamyl-cysteine-synthetase (γ-GCS), total thiols, protein carbonyls, mRNAs of clusterin and the known protective enzymes thioredoxine-1 (TRX-1), glutaredoxine-1 (GLRX-1), superoxide dismutase-1 (SOD-1). Brain levels of GSH, γ-GCS, total thiols remained constant with age, except for GSH and γ-GCS which decreases in females. Clusterin, TRX-1, GLRX-1, SOD-1 mRNA levels were maintained or increased in the hippocampus with age. Age-dependency of the markers differed between sexes, with SOD-1 and TRX-1 decreases out of hippocampus in females. Since antioxidants were reported to decrease with age in the brain of Wistar rats, maintenance of GSH levels and of protective enzymes mRNA levels in the LOU rat brain could contribute to the preservation of cognitive functions in old age. Altogether, the successful aging of LOU rats may, at least in part, involve the conservation of functional antioxidant mechanisms in the brain, supporting the oxidative stress theory of aging.

Differential effects of enriched environment at work on cognitive decline in old age.

The aim of the present study was to investigate how different mentally demanding work conditions during the professional life-i.e., enriched environments at work-might influence the rate of cognitive decline in old age. Individuals (n = 1,054) of the Leipzig Longitudinal Study of the Aged, a representative population-based cohort study of individuals aged 75 years and older, underwent cognitive testing via the Mini-Mental State Examination (MMSE) in up to 6 measurement waves. Type and level of mentally demanding work conditions in the participants' former professional life were classified based on the O*NET job descriptor database. In multivariate mixed-model analyses (controlling for sociodemographic and health-related factors), a high level of mentally demanding work tasks stimulating verbal intelligence was significantly associated with a better cognitive functioning at baseline (on average 5 MMSE points higher) as well as a lower rate of cognitive decline (on average 2 MMSE points less) over the 8-year follow-up period compared with a low level. The rate of cognitive decline in old age was also significantly lower (on average 3 MMSE points less) in individuals who had a high level of mentally demanding work tasks stimulating executive functions than those who had a low level. The results suggest that a professional life enriched with work tasks stimulating verbal intelligence and executive functions may help to sustain a good cognitive functioning in old age (75+ years). The findings thus emphasize that today's challenging work conditions may also promote positive health effects.

The Association of Leisure Activities in Middle Adulthood with Cognitive Performance in Old Age: The Moderating Role of Educational Level

Background: One of the fundamental challenges for gerontological research is how to maintain and promote intact cognitive functioning in old age. Previous research revealed that high educational level, good health status, and an active lifestyle during adulthood seem to be protective against cognitive impairment in old age. However, up to now, a detailed examination of the interaction of these relations based on a broader variety of activities and considering past and current activities is missing. Objective: The present study set out to extend the literature by investigating in more detail the interactions of educational level and health status with a broad variety of past and current leisure activities in their association with cognitive functioning in a large sample of older adults with a wide age range. Methods: A total of 2,812 older adults (aged 65-101 years) served as the sample for the present study. A test on verbal abilities and one on processing speed were applied. In addition, individuals were retrospectively interviewed regarding their educational level, current general health status, and 18 leisure activities (in terms of currently performed activities and those that had been carried out at the age of 45 years). Results: Regressions indicated that engaging in more current activities and in more activities at the age of 45 years (both analyzed as an overall activity measure) was related to better cognitive performance in old age (r values up to 0.39, p values <0.001). These associations were more pronounced in individuals with a low (compared to a high) educational level. Conclusion: Present results suggest that an active lifestyle during middle adulthood may be related to better cognitive functioning in old age, particularly in individuals with a low educational level. These findings are discussed with respect to models of cognitive aging.

American Heart Association's Life's Simple 7: Avoiding Heart Failure and Preserving Cardiac Structure and Function

BackgroundMany people may underappreciate the role of lifestyle in avoiding heart failure. We estimated whether greater adherence in middle age to American Heart Association's Life's Simple 7 guidelines—on smoking, body mass, physical activity, diet, cholesterol, blood pressure, and glucose—is associated with lower lifetime risk of heart failure and greater preservation of cardiac structure and function in old age. MethodsWe studied the population-based Atherosclerosis Risk in Communities Study cohort of 13,462 adults ages 45-64 years in 1987-1989. From the 1987-1989 risk factor measurements, we created a Life's Simple 7 score (range 0-14, giving 2 points for ideal, 1 point for intermediate, and 0 points for poor components). We identified 2218 incident heart failure events using surveillance of hospital discharge and death codes through 2011. In addition, in 4855 participants free of clinical cardiovascular disease in 2011-2013, we performed echocardiography from which we quantified left ventricular hypertrophy and diastolic dysfunction. ResultsOne in four participants (25.5%) developed heart failure through age 85 years. Yet, this lifetime heart failure risk was 14.4% for those with a middle-age Life's Simple 7 score of 10-14 (optimal), 26.8% for a score of 5-9 (average), and 48.6% for a score of 0-4 (inadequate). Among those with no clinical cardiovascular event, the prevalence of left ventricular hypertrophy in late life was approximately 40% as common, and diastolic dysfunction was approximately 60% as common, among those with an optimal middle-age Life's Simple 7 score, compared with an inadequate score. ConclusionsGreater achievement of American Heart Association's Life's Simple 7 in middle age is associated with a lower lifetime occurrence of heart failure and greater preservation of cardiac structure and function.

White matter integrity supports BOLD signal variability and cognitive performance in the aging human brain.

Decline in cognitive performance in old age is linked to both suboptimal neural processing in grey matter (GM) and reduced integrity of white matter (WM), but the whole-brain structure-function-cognition associations remain poorly understood. Here we apply a novel measure of GM processing–moment-to-moment variability in the blood oxygenation level-dependent signal (SDBOLD)—to study the associations between GM function during resting state, performance on four main cognitive domains (i.e., fluid intelligence, perceptual speed, episodic memory, vocabulary), and WM microstructural integrity in 91 healthy older adults (aged 60-80 years). We modeled the relations between whole-GM SDBOLD with cognitive performance using multivariate partial least squares analysis. We found that greater SDBOLD was associated with better fluid abilities and memory. Most of regions showing behaviorally relevant SDBOLD (e.g., precuneus and insula) were localized to inter- or intra-network “hubs” that connect and integrate segregated functional domains in the brain. Our results suggest that optimal dynamic range of neural processing in hub regions may support cognitive operations that specifically rely on the most flexible neural processing and complex cross-talk between different brain networks. Finally, we demonstrated that older adults with greater WM integrity in all major WM tracts had also greater SDBOLD and better performance on tests of memory and fluid abilities. We conclude that SDBOLD is a promising functional neural correlate of individual differences in cognition in healthy older adults and is supported by overall WM integrity.

Hispanic Older Adult Health & Longevity in the United States: Current Patterns & Concerns for the Future.

The Hispanic population aged sixty-five and over - the most socioeconomically disadvantaged subset of America's elderly - is projected to quintuple between 2012 and 2050. While current longevity patterns for Hispanics relative to whites are favorable, old-age functioning and disability patterns for Hispanics are unfavorable and have serious implications for caregivers; families; and local, state, and federal governments. Troubling signs for the future Hispanic population (which are shared to varying degrees with other vulnerable groups) include the unresolved legal status of unauthorized immigrants, continued low levels of insurance coverage even after health care reform, some unfavorable trends in health behaviors, and continued disadvantages in educational attainment and income relative to whites. We urge policy-makers to deal with these potentially problematic health and well-being issues. Not doing so could have detrimental consequences for the future of the Hispanic population as well as other at-risk groups and, by extension, the U.S. elderly population as a whole.

Near-infrared light increases ATP, extends lifespan and improves mobility in aged Drosophila melanogaster.

Ageing is an irreversible cellular decline partly driven by failing mitochondrial integrity. Mitochondria accumulate DNA mutations and reduce ATP production necessary for cellular metabolism. This is associated with inflammation. Near-infrared exposure increases retinal ATP in old mice via cytochrome c oxidase absorption and reduces inflammation. Here, we expose fruitflies daily to 670 nm radiation, revealing elevated ATP and reduced inflammation with age. Critically, there was a significant increase in average lifespan: 100–175% more flies survived into old age following 670 nm exposure and these had significantly improved mobility. This may be a simple route to extending lifespan and improving function in old age.

Genetics and Functional Imaging: Effects of APOE, BDNF, COMT, and KIBRA in Aging

Increasing evidence from cross-sectional and longitudinal molecular-genetic studies suggests that effects of common genetic variations on cognitive functioning increase with aging. We review the influence of candidate genes on brain functioning in old age, focusing on four genetic variations that have been extensively investigated: APOE, BDNF, COMT, and KIBRA. Similar to the behavioral evidence, there are reports from age-comparative studies documenting stronger genetic effects on measures of brain functioning in older adults compared to younger adults. This pattern suggests disproportionate impairments of neural processing among older individuals carrying disadvantageous genotypes. We discuss various factors, including gene-gene interactions, study population characteristics, lifestyle factors, and diseases, that need to be considered in future studies and may help understand inconsistent findings in the extant literature.

Aberrant post-translational modifications compromise human myosin motor function in old age.

Novel experimental methods, including a modified single fiber in vitro motility assay, X-ray diffraction experiments, and mass spectrometry analyses, have been performed to unravel the molecular events underlying the aging-related impairment in human skeletal muscle function at the motor protein level. The effects of old age on the function of specific myosin isoforms extracted from single human muscle fiber segments, demonstrated a significant slowing of motility speed (P < 0.001) in old age in both type I and IIa myosin heavy chain (MyHC) isoforms. The force-generating capacity of the type I and IIa MyHC isoforms was, on the other hand, not affected by old age. Similar effects were also observed when the myosin molecules extracted from muscle fibers were exposed to oxidative stress. X-ray diffraction experiments did not show any myofilament lattice spacing changes, but unraveled a more disordered filament organization in old age as shown by the greater widths of the 1, 0 equatorial reflections. Mass spectrometry (MS) analyses revealed eight age-specific myosin post-translational modifications (PTMs), in which two were located in the motor domain (carbonylation of Pro79 and Asn81) and six in the tail region (carbonylation of Asp900, Asp904, and Arg908; methylation of Glu1166; deamidation of Gln1164 and Asn1168). However, PTMs in the motor domain were only observed in the IIx MyHC isoform, suggesting PTMs in the rod region contributed to the observed disordering of myosin filaments and the slowing of motility speed. Hence, interventions that would specifically target these PTMs are warranted to reverse myosin dysfunction in old age.

Resveratrol prevents age-related memory and mood dysfunction with increased hippocampal neurogenesis and microvasculature, and reduced glial activation.

Greatly waned neurogenesis, diminished microvasculature, astrocyte hypertrophy and activated microglia are among the most conspicuous structural changes in the aged hippocampus. Because these alterations can contribute to age-related memory and mood impairments, strategies efficacious for mitigating these changes may preserve cognitive and mood function in old age. Resveratrol, a phytoalexin found in the skin of red grapes having angiogenic and antiinflammatory properties, appears ideal for easing these age-related changes. Hence, we examined the efficacy of resveratrol for counteracting age-related memory and mood impairments and the associated detrimental changes in the hippocampus. Two groups of male F344 rats in late middle-age having similar learning and memory abilities were chosen and treated with resveratrol or vehicle for four weeks. Analyses at ~25 months of age uncovered improved learning, memory and mood function in resveratrol-treated animals but impairments in vehicle-treated animals. Resveratrol-treated animals also displayed increased net neurogenesis and microvasculature, and diminished astrocyte hypertrophy and microglial activation in the hippocampus. These results provide novel evidence that resveratrol treatment in late middle age is efficacious for improving memory and mood function in old age. Modulation of the hippocampus plasticity and suppression of chronic low-level inflammation appear to underlie the functional benefits mediated by resveratrol.

Cognitive reserve in the healthy elderly: cognitive and psychological factors

Abstract Cognitive reserve (CR) helps explain the mismatch between expected cognitive decline and observed maintenance of cognitive functioning in older age. Factors such as education, literacy, lifestyle, and social networking are usually considered to be proxies of CR and its variability between individuals. A more direct approach to examine CR is through the assessment of capacity to gain from practice in a standardized challenging cognitive task that demands activation of cognitive resources. In this study, we applied a testing-the-limits paradigm to a group of 136 healthy elderly subjects (60–75 years) and additionally examined the possible contribution of complex mental activities and quality of sleep to cognitive performance gain. We found a significant but variable gain and identified verbal memory, cognitive flexibility, and problem-solving as important factors. This outcome is in line with our earlier study on CR in healthy mental aging. Interestingly and contrary to expectations, our analysis revealed that complex mental activities and sleep quality do not significantly influence CR. Best subset regression showed that better verbal memory and higher cognitive flexibility were related to high CR, which could also be seen when contrasting “high” and “low” cognitive performers; again, complex mental activities and sleep quality did not contribute to this measure of CR. In conclusion, the results of this study support and extend previous findings on CR in older age; further, they underline the need for improvements in existing protocols for assessing CR in a dynamic manner.

Does food insufficiency in childhood contribute to dementia in later life?

BackgroundDespite several studies attempting to identify the risk factors for dementia, little is known about the impact of childhood living conditions on cognitive function in later life. The present study aims to examine the unique contribution of food insufficiency in childhood to dementia in old age.MethodsData for this study of 2,745 older Malaysians aged 60 years and older was obtained from a national survey entitled “Mental Health and Quality of Life of Older Malaysians” conducted from 2003 through 2005 using a cross-sectional design. The Geriatric Mental State-Automated Geriatric Examination for Computer Assisted Taxonomy was used to measure dementia. A multiple binary logistic regression using Statistical Package for Social Sciences version 21 was conducted to assess the unique effect of food insufficiency in childhood on developing dementia in old age.ResultsA notably higher prevalence of dementia was found in respondents who indicated they had experienced food insufficiency in childhood than in their food-sufficient counterparts (23.5% versus 14.3%). The findings from multiple logistic regression analysis revealed that food insufficiency in childhood would independently increase the risk of developing dementia in old age by 81%, after adjusting for sociodemographic factors (odds ratio =1.81, 95% confidence interval 1.13–2.92, P<0.01).ConclusionFindings from the present study showing that food insufficiency in early life significantly contributes to dementia in later life highlight the importance of childhood living conditions in maintaining cognitive function in old age. It is, therefore, suggested that older adults with childhood food insufficiency might be targeted for programs designed to prevent dementia.

Hippocampal Extracellular Matrix Levels and Stochasticity in Synaptic Protein Expression Increase with Age and Are Associated with Age-dependent Cognitive Decline

Age-related cognitive decline is a serious health concern in our aging society. Decreased cognitive function observed during healthy brain aging is most likely caused by changes in brain connectivity and synaptic dysfunction in particular brain regions. Here we show that aged C57BL/6J wild-type mice have hippocampus-dependent spatial memory impairments. To identify the molecular mechanisms that are relevant to these memory deficits, we investigated the temporal profile of mouse hippocampal synaptic proteome changes at 20, 40, 50, 60, 70, 80, 90, and 100 weeks of age. Extracellular matrix proteins were the only group of proteins that showed robust and progressive up-regulation over time. This was confirmed by immunoblotting and histochemical analysis, which indicated that the increased levels of hippocampal extracellular matrix might limit synaptic plasticity as a potential cause of age-related cognitive decline. In addition, we observed that stochasticity in synaptic protein expression increased with age, in particular for proteins that were previously linked with various neurodegenerative diseases, whereas low variance in expression was observed for proteins that play a basal role in neuronal function and synaptic neurotransmission. Together, our findings show that both specific changes and increased variance in synaptic protein expression are associated with aging and may underlie reduced synaptic plasticity and impaired cognitive performance in old age.