Cognition’s dependence on functional network integrity with age is conditional on structural network integrity

Decision letter: Stage-dependent differential influence of metabolic and structural networks on memory across Alzheimer’s disease continuum

ABSTRACTObjectives: Despite the evidence suggesting physical activity (PA) as a major factor for the prevention of age-related cognitive decline, only a few studies have systematically investigated the impact of leisure PA during the lifespan (LLPA). This study investigates the effects of LLPA on cognitive function (CF) and brain plasticity (BP) in old age.Method: Participants’ (n = 50, 72 ± 5 yrs, 27 females) LLPA energy expenditure and volume was assessed via a validated questionnaire investigating five epochs (14–80 yrs). Using current WHO PA recommendations as reference, participants were stratified into energy expenditure and volume groups. CF outcomes were attention, executive functions, working memory and memory. BP was assessed using magnetic resonance spectroscopy (MRSI) and brain derived neurotropic factor (BDNF).Results: Correlation analysis revealed associations of mean LLPA energy expenditure with attention (CF) and N-acetylaspartate to choline ratios (NAA/Cho) (MRSI). ANOVA revealed higher interference control performance (CF) and NAA/Cho in participants complying with current PA recommendations (2-3 h per week) compared to non-compliers. Further CF and BP outcomes including BDNF were not associated with LLPA.Conclusion: Lifelong adherence to minimum recommended PA seems to be associated with markers of cognitive function and neuronal integrity in old age.

Background: Previous studies examined midlife risk factors separately for old-age impaired physical and cognitive functioning. We determined the overlap of risk factors for both domains of functioning within the same setting.Methods: Biological and behavioral risk factors at age 50 years and cognitive and physical functioning were assessed 18 (SD = 5) years later in the Whitehall II study (N = 6,316). Impaired physical functioning was defined as ≥1 limitation on the activities of daily living scale. Impaired cognitive functioning was defined as Mini-Mental State Examination score <27. Two statistical analyses were employed: minimally adjusted analysis (for age, sex, and ethnicity) and mutually adjusted analysis (including all risk factors). Missing data on risk factors were imputed.Results: After confounder adjustment, impaired physical and cognitive functioning at older ages were predicted by hypertension (odds ratios [ORs] 1.80 95% confidence interval [CI] 1.39–2.33 and 1.57 95% CI 1.07–2.31, respectively), poor lung function (1.51 95% CI 1.28–1.78 and 1.31 95% CI 1.08–1.59), and physical inactivity, marginally in the case of cognitive function (1.50 95% CI 1.19–1.90 and 1.27 95% CI 0.99–1.62) at age 50 years. Impaired physical functioning but not cognitive functioning was additionally predicted by depression and higher body mass index (1.72 95% CI 1.46–2.03 and 1.29 95% CI 1.16–1.44, respectively).Conclusions: Several midlife risk factors are associated with impaired physical and cognitive functioning in old age, supporting a unified prevention policy. Analysis of 12 risk factors at age 50 suggests that strategies targeting physical inactivity, hypertension, and poor lung function will reduce impairments in both cognitive and physical functioning in old age.

People exposed to the 1944–1945 Dutch famine in early gestation performed worse on a selective attention task at age 58 and reported more cognitive problems at age 72. We here hypothesized that undernutrition in early gestation is associated with poorer cognitive functioning in older age and a higher rate of cognitive decline. We tested this hypothesis in the Dutch famine birth cohort in men and women combined and separately. We assessed cognitive function using a Stroop-like, trail-making and 15-word task (at ages 68 and 74) and the Montreal cognitive assessment as well as self-perceived cognitive problems (at age 74) in 73 men (n = 34) and women (n = 39). We compared cognitive function and decline (change in cognitive function between age 68 and 74) between those exposed in early gestation and those not exposed (born before or conceived after the famine). Although in both men and women cognitive function declined from age 68 to 74, cognitive task scores and the rate of decline did not differ between those exposed or unexposed to famine. At age 74, men exposed to famine in early gestation more often reported cognitive problems, although this was not statistically different from unexposed men (OR 3.1 [95%CI 0.7 to 13.0]). We did not find evidence of increased cognitive decline after prenatal undernutrition. Selective participation and mortality may have hampered our ability to detect potential true effects. The self-perceived cognitive problems among men who had been exposed to famine in early gestation might be an indication of future dementia risk.

Enrichment Effects on Adult Cognitive Development: Can the Functional Capacity of Older Adults Be Preserved and Enhanced?

BackgroundNutrient status of B vitamins, particularly folate and vitamin B-12, may be related to cognitive ageing but epidemiological evidence remains inconclusive. ObjectiveThe aim of this study was to estimate the association of serum folate and vitamin B-12 concentrations with cognitive function in middle-aged and older adults from three Central and Eastern European populations. MethodsMen and women aged 45–69 at baseline participating in the Health, Alcohol and Psychosocial factors in Eastern Europe (HAPIEE) study were recruited in Krakow (Poland), Kaunas (Lithuania) and six urban centres in the Czech Republic. Tests of immediate and delayed recall, verbal fluency and letter search were administered at baseline and repeated in 2006–2008. Serum concentrations of biomarkers at baseline were measured in a sub-sample of participants. Associations of vitamin quartiles with baseline (n=4166) and follow-up (n=2739) cognitive domain-specific z-scores were estimated using multiple linear regression. ResultsAfter adjusting for confounders, folate was positively associated with letter search and vitamin B-12 with word recall in cross-sectional analyses. In prospective analyses, participants in the highest quartile of folate had higher verbal fluency (p<0.01) and immediate recall (p<0.05) scores compared to those in the bottom quartile. In addition, participants in the highest quartile of vitamin B-12 had significantly higher verbal fluency scores (β=0.12; 95% CI=0.02, 0.21). ConclusionsFolate and vitamin B-12 were positively associated with performance in some but not all cognitive domains in older Central and Eastern Europeans. These findings do not lend unequivocal support to potential importance of folate and vitamin B-12 status for cognitive function in older age. Long-term longitudinal studies and randomised trials are required before drawing conclusions on the role of these vitamins in cognitive decline.

Coffee drinking in middle age is not associated with cognitive performance in old age

Cognitive aging research is gaining societal and practical importance because of population aging. Current research is focused on describing age differences and age-related changes in cognitive performance, understanding potential causes underlying these differences and changes, and identifying factors that promote maintenance of cognitive functioning in old age. The goal of this research group is to showcase new developments in research studying age differences in cognitive performance and longitudinal cognitive change in the second half of life. Hülür et al. examine associations between midlife occupational factors and trajectories of cognitive change using data from the German Interdisciplinary Longitudinal Study of Adult Development and Aging (ILSE). Luo et al. use 12-year longitudinal data from 499 older participants in ILSE to study bidirectional associations between social relationships and cognitive performance. Small et al. examine the correspondence between objective and subjective cognitive performance, and measures of fatigue and depressed mood in experience sampling data from breast cancer survivors. Haas et al. compare laboratory and at-home online assessments of cognitive status and prospective memory over the adult lifespan and evaluate the quality of self-administered tests. The discussion by Elizabeth Stine-Morrow will focus on how these approaches contribute to our understanding of processes of cognitive aging and how they can be utilized to promote maintenance of cognitive functioning in old age.

Objectives Previous work has shown that high mental demands are associated with better cognitive functioning in old age. As there is a lack of a general conceptual framework for this association, the aim of the study was to investigate how mental demands and other work-related factors relate to cognitive functioning as a foundation for developing such a framework. Methods An expert panel discussion was conducted with the aim of determining relevant work-related factors, which were then tested in a survey with 346 employees aged 50+ years, who were actively working. Assessment of cognitive functioning comprised complex attention, executive function, learning/memory, language, perceptual-motor, and social cognition. Confirmatory factor analysis was conducted to confirm factor belonging. Associations with cognitive functioning were analyzed using structure equation modelling to confirm associations and to identify additional direct and indirect paths. Results Only 42.3% (22/52) of the work-related factors and 19.0% (4/21) of the mediating paths suggested by the experts were significant with respect to cognitive functioning. Factor analysis and structural equation modeling indicated that high mental demands are only associated with better cognitive functioning in old age to the extent that they are intellectually stimulating and this effect is embedded in individual capacities and the social context. Conclusion Based on the panel discussion and the empirical testing, we propose the Conceptual Framework of Social Dependency of Intellectual Stimulation on Cognitive Health. We recommend researchers and workplace health experts to pay attention to the component of this theory when assessing workplace risk.

To examine how visual impairment affects physical and cognitive function in old age. A longitudinal population-based prospective cohort study. General practitioner offices at six study centers in Germany. They were observed every 1.5 years over four waves. Individuals aged 77-101 at follow-up Wave 2 (N = 2,394). Physical and cognitive function were assessed using an adapted scale that had been previously developed, and visual impairment was rated on a Likert scale (none, mild, severe or profound). Adjusting for sociodemographic factors and comorbidity, linear fixed-effects regression showed that the onset of severe visual impairment was associated with a decline in physical function score in the total sample (β = -0.15, P = .01) and in women (β = -.15, P = .03). Moreover, the onset of severe visual impairment was associated with decline in cognitive function score in the total sample (β = -0.38, P < .001) and in women (β = -0.38, P < .001) and men (β = -0.37, P = .001). Visual impairment affects physical and cognitive function in old age. Interventional strategies to postpone visual impairment may contribute to maintaining physical and cognitive function.

ObjectivesTo examine the long-term association between leisure activities in adulthood and cognitive function in old age while recognizing gender differences in activity profiles.MethodsThe sample included 340 cognitively healthy twins enrolled in the OCTO-Twin Study, a longitudinal study on cognitive aging. Leisure activity was measured in midlife and cognitive function in old age (mean age 83). Leisure activities covered the domains of domestic, intellectual–cultural, and self-improvement activities. The cognitive assessments comprised 5 measurement occasions (2-year intervals) covering verbal ability, spatial ability, memory, and speed. The association between leisure activity and cognitive function was estimated separately for the genders using growth curve models, adjusting for age and education.ResultsMen and women had the same level of total leisure activity but differed in activity profiles and in the associations between activity and cognitive function. Higher engagement in self-improvement among men was related to higher level of cognitive functioning. Among women, intellectual–cultural activity was related to better verbal ability and memory. Concerning trajectories of cognitive function, domestic activity among men was related to less decline in speed, whereas for women it was related to steeper decline in spatial ability and memory. Further, higher intellectual–cultural activity among women was related to steeper decline in memory.DiscussionCognitively stimulating activities (i.e., self-improvement and intellectual–cultural), might increase cognitive reserve whereas less cognitively stimulating activities (i.e., domestic) do not. Gender differences should be considered when examining lifestyle factors in relation to cognitive aging.

The expanded lifespan of people, while a positive advance, has also amplified the prevalence of age-related disorders, which include mild cognitive impairment, dementia, and Alzheimer’s disease. Therefore, competent therapies that could improve the healthspan of people have great significance. Some of the dietary and pharmacological approaches that augment the lifespan could also preserve improved cognitive function in old age. Metformin, a drug widely used for treating diabetes, is one such candidate that could alleviate age-related cognitive dysfunction. However, the possible use of metformin to alleviate age-related cognitive dysfunction has met with conflicting results in human and animal studies. While most clinical studies have suggested the promise of metformin to maintain better cognitive function and reduce the risk for developing dementia and Alzheimer’s disease in aged diabetic people, its efficacy in the nondiabetic population is still unclear. Moreover, a previous animal model study implied that metformin could adversely affect cognitive function in the aged. However, a recent animal study using multiple behavioral tests has reported that metformin treatment in late middle age improved cognitive function in old age. The study also revealed that cognition-enhancing effects of metformin in aged animals were associated with the activation of the energy regulator adenosine monophosphate-activated protein kinase, diminished neuroinflammation, inhibition of the mammalian target of rapamycin signaling, and augmented autophagy in the hippocampus. The proficiency of metformin to facilitate these favorable modifications in the aged hippocampus likely underlies its positive effect on cognitive function. Nonetheless, additional studies probing the outcomes of different doses and durations of metformin treatment at specific windows in the middle and old age across sex in nondiabetic and non-obese prototypes are required to substantiate the promise of metformin to maintain better cognitive function in old age.

Decision letter: Disruption in structural–functional network repertoire and time-resolved subcortical fronto-temporoparietal connectivity in disorders of consciousness

A growing body of literature suggests that physical activity might alleviate the age-related neurodegeneration and decline of cognitive function. However, most of this evidence is based on data investigating the association of exercise interventions or current physical activity behavior with cognitive function in elderly subjects. We performed a systematic review and hypothesize that physical activity during the adult life span is connected with maintained domain-specific cognitive functions during late adulthood defined as age 60+ years. We performed a systematic literature search up to November 2017 in PubMed, Web of Science, and Google Scholar without language limitations for studies analyzing the association of leisure physical activity during the adult life span (age 18+years) and domain-specific cognitive functions in older adults (age 60+years). The literature review yielded 14,294 articles and after applying inclusion and exclusion criteria, nine cross-sectional and 14 longitudinal studies were included. Moderate- and vigorous-intensity leisure physical activity was associated with global cognitive function and specific cognitive domains including executive functions and memory but not attention or working memory. Most studies assessed mid- to late-adulthood physical activity, thus information concerning the influence of young adult life-span physical activity is currently lacking. Observational evidence that moderate- and vigorous-intensity leisure physical activity is beneficially associated with maintained cognitive functions during old age is accumulating. Further studies are necessary to confirm a causal link by assessing objective physical activity data and the decline of cognitive functions at multiple time points during old age.

Objectives: This research study aimed to compare and analyze changes in health related lifestyles in middle age and the relevant association of cognitive function in old age. Methods: The change in health-related lifestyles and the influence on cognitive function between the first and eighth panels of 3,404 participants aged 45 to 64 were examined using multiple regression analysis. Results: First, improved health behavior for 14 years, but health status and social networks and social activities decreased. Second, older age, low levels of education, depression, and diabetes were found to be related to cognitive deterioration. Third, the predictive factors of middle age that affect cognitive decline in old age were low education level, physical activity time of 150 minutes or more, and diagnosis of diabetes. Moreover, regular health examinations and one or more organizational activities in a month appeared to have a positive effect on cognitive function in old age. Conclusion: These findings highlight the significance of health behavior and health management and the need for intervention in middle-aged people who are experiencing various life tasks and chronic diseases in order to maintain cognitive function in old age.