Youthful Processing Speed in Older Adults: Genetic, Biological, and Behavioral Predictors of Cognitive Processing Speed Trajectories in Aging.

Objective: To examine the impact of genetic, inflammatory, cardiovascular, lifestyle, and neuroanatomical factors on cognitive processing speed (CPS) change over time in functionally intact older adults. Methods: This observational study conducted over two time points, included 120 community dwelling cognitively normal older adults between the ages of 60 and 80 from the University of California San Francisco Memory and Aging Center. Participants were followed with composite measures of CPS, calculated based on norms for 20-30 year-olds. Variables of interest were AD risk genes (APOE, CR1), markers of inflammation (interleukin 6) and cardiovascular health (BMI, LDL, HDL, mean arterial pressure, fasting insulin), self-reported physical activity, and corpus callosum (CC) volumes. The sample was divided into three groups: 17 "resilient-agers" with fast and stable processing speed; 56 "average-agers" with average and stable processing speed; and 47 "sub-agers" with average baseline speed who were slower at follow-up. Results: Resilient-agers had larger baseline CC volumes than sub-agers (p < 0.05). Resilient-agers displayed lower levels of interleukin-6 (IL-6) and insulin (ps < 0.05) than sub-agers, and reported more physical activity than both average- and sub-agers (ps < 0.01). In a multinomial logistic regression, physical activity and IL-6 predicted average- and sub-ager groups. Resilient-agers displayed a higher frequency of APOE e4 and CR1 AA/AG alleles. Conclusion: Robust and stable CPS is associated with larger baseline CC volumes, lower levels of inflammation and insulin, and greater self-reported physical activity. These findings highlight the relevance of neuroanatomical, biological, and lifestyle factors in the identification and prediction of heterogeneous cognitive aging change over time

The relationship between cognition and mortality in a community sample of older adults

Cognitive performance has previously been shown to be associated with time to death in a broad range of studies. There are multiple perspectives that have been used to better understand this relationship, including identifying the types of cognitive abilities that predict mortality, investigating potential mechanisms that might explain the relationship, examining whether level of ability or changes in ability are responsible for the association, assessing evidence of terminal decline and exploring patterns of late-life decline. It is also important to rule out the confounding of the relationship between cognition and time to death by other factors such as mental health. Five research articles investigated multiple aspects of the relationship between cognition and mortality using the Canberra Longitudinal Study cohort, a sample of 896 community-dweIIing Australians aged 70 and older. Findings suggested that fluid inteIIigence was a better predictor of mortality than crystaIIised inteIIigence. While socioeconomic status, health behaviours and health status accounted for some of the variance in the relationship, certain domains of cognitive ability including processing speed and global ability had an independent effect on mortality. Using unbiased estimates of cognitive change, it was found that initial cognitive performance was a better predictor of mortality, particularly cardiovascular mortality, than the rate of change in ability. However, there was evidence of terminal decline in the sample, with decline accelerating two-to four-fold, beginning 6-8 years prior to death across various abilities. Although education modified the time course of terminal decline, the effects were not consistent with the predictions of the cognitive reserve hypothesis. Age-related decline in ability could not be attributed to common biological constraints, as little evidence was found for late-life dedifferentiation of abilities after accounting for dementia. FinaIIy, depression and anxiety had no significant association with mortality after accounting for physical health, indicating that the cognition-mortality relationship did not result from confounding by mental health status. Overall, late-life cognitive performance appears to be related to mortality partly because it reflects life-long outcomes from a range of health behaviours, disease states, educational experience and socioeconomic background. In addition, pathological events including dementia and cardiovascular changes may contribute to the decline of cognitive performance that occurs in proximity to death. However, beyond these influences, there is an aspect of cognitive ability that is independently predictive of mortality

Household Environments and Functional Decline Among Middle-Aged and Older Adults in China

This thesis investigates the associations between household social, economic, and physical environment conditions and the trajectory of self-reported functional limitations over time among middle-aged and older adults in China. Despite the increasing interest in the impact of household environments on functional decline, most existing studies are cross-sectional or concern changes in functioning observed in two waves of surveys, and they primarily focus on the influence of one condition. This thesis explores how the trajectory of functional decline is influenced jointly by multiple household factors, including living arrangement, annual living expenditure per capita, indoor air pollution resulting from solid fuels, and housing quality. To analyze the data, a linear growth curve model is applied to four waves of surveys of 13,564 respondents aged 45 years and older from the China Health and Retirement Longitudinal Study (CHARLS) conducted between 2011 and 2018. The study finds that female and older respondents experience faster functional decline compared to male and younger respondents, but there is no significant urban-rural difference in the rate of decline. Living alone, particularly for rural, female, and older respondents, is associated with a faster functional decline when compared to living with a spouse and without children. Improved housing quality is linked to a slower functional decline. Living with young descendants and without adult children for urban residents, and living with a lower expenditure per capita for younger respondents, are associated with a faster functional decline. Discussions are given for expected and unexpected results, the limitations and implications of this study

Physical Activity and Nutrition INfluences in Ageing: Current Findings from the PANINI Project

Background: The ageing of the population is a global challenge and the period of life spent in good health, although increasing, is not keeping pace with lifespan. Consequently, understanding the important factors that contribute to healthy ageing and validating interventions and influencing policy to promote healthy ageing are vital research priorities. Method: The PANINI project is a collaboration of 20 partners across Europe examining the influence of physical activity and nutrition in ageing. Methods utilised encompass the biological to the social, from genetics to the influence of social context. For example, epigenetic, immunological, and psychological assessments, and nutritional and sports science-based interventions have been used among older adults, as well as mathematical modelling and epidemiology. The projects are multi-disciplinary and examine health outcomes in ageing from a range of perspectives. Results: The results discussed here are those emerging thus far in PANINI from 11 distinct programmes of research within PANINI as well as projects cross-cutting the network. New approaches, and the latest results are discussed. Conclusions: The PANINI project has been addressing the impact of physical activity and nutrition on healthy ageing from diverse but interlinked perspectives. It emphasises the importance of using standardized measures and the advantages of combining data to compare biomarkers and interventions across different settings and typologies of older adults. As the projects conclude, the current results and final data will form part of a shared dataset, which will be made open access for other researchers into ageing processes.On behalf of the PANINI Consortiu

Obesity and Physical Functioning: Associations with Cognition in the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) Cohort

The current study reviewed mechanisms through which obesity influences cognitive performance as well as explored the dynamic relationship between body weight, physical performance, and cognition in the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) trial over a 10-year period. Findings from the study highlight the complex relationship between physical health and cognitive performance in older adults and suggest that higher body mass index (BMI) at baseline was associated with both cognitive and functional performance. Results from Aim 1 suggest that better performance on multiple cognitive domains was associated with attenuated declines in BMI over 10 years. Furthermore, attenuated cognitive declines were associated with a greater increase in BMI. Analyses from Aim 2 explored the mediated effect of grip-strength on weight-related changes in BMI. Findings revealed that a higher BMI at baseline was associated with better grip strength at baseline and accelerated declines in grip strength over time; whereas higher grip strength at baseline was associated with slower declines in cognition over time. Slower declines in grip strength were associated with slower declines in memory and reasoning. There was an indirect effect of BMI on cognition through changes in grip strength in the memory and reasoning outcomes, such that, a higher BMI was associated with accelerated declines in grip strength, which in turn were associated with accelerated declines in cognition. These findings are provocative given the large body of research in older adults suggesting that excess weight is protective against cognitive declines

Cognitive Reserve in Model Systems for Mechanistic Discovery: The Importance of Longitudinal Studies.

The goal of this review article is to provide a resource for longitudinal studies, using animal models, directed at understanding and modifying the relationship between cognition and brain structure and function throughout life. We propose that forthcoming longitudinal studies will build upon a wealth of knowledge gleaned from prior cross-sectional designs to identify early predictors of variability in cognitive function during aging, and characterize fundamental neurobiological mechanisms that underlie the vulnerability to, and the trajectory of, cognitive decline. Finally, we present examples of biological measures that may differentiate mechanisms of the cognitive reserve at the molecular, cellular, and network level

Area deprivation across the life course and physical capability in mid-life: findings from the 1946 British Birth Cohort

Physical capability in later life is influenced by factors occurring across the life course, yet exposures to area conditions have only been examined cross-sectionally. Data from the National Survey of Health and Development, a longitudinal study of a 1946 British birth cohort, were used to estimate associations of area deprivation (defined as percentage of employed people working in partly skilled or unskilled occupations) at ages 4, 26, and 53 years (residential addresses linked to census data in 1950, 1972, and 1999) with 3 measures of physical capability at age 53 years: grip strength, standing balance, and chair-rise time. Cross-classified multilevel models with individuals nested within areas at the 3 ages showed that models assessing a single time point underestimate total area contributions to physical capability. For balance and chair-rise performance, associations with area deprivation in midlife were robust to adjustment for individual socioeconomic position and prior area deprivation (mean change for a 1-standard-deviation increase: balance, −7.4% (95% confidence interval (CI): −12.8, −2.8); chair rise, 2.1% (95% CI: −0.1, 4.3)). In addition, area deprivation in childhood was related to balance after adjustment for childhood socioeconomic position (−5.1%, 95% CI: −8.7, −1.6). Interventions aimed at reducing midlife disparities in physical capability should target the socioeconomic environment of individuals—for standing balance, as early as childhood

The effects of age-stereotyped stimuli on older people’s self-perceptions of age and grip strength

Background: The psychology of ageing has shown that over time, changes in lifestyle and attitudes influence an individual’s ageing experience (Deary et al. 2009). Recent statistics show that over 18% of the UK population are currently considered ‘old’ (Office of National Statistics, 2018), therefore it is becoming a priority that misconceptions and age-stereotypes relating to health and functioning during the ageing process are investigated to explore their possible affects. Objectives: The current thesis has 4 key aims, which are to: (1) Determine whether a natural association exists between functional health (as measured by grip strength) and self-perceptions of age in younger and older adults; (2) Develop a bespoke implicit age-stereotype priming task, which addresses 3 commonly cited limitations of previous literature, and present UK generated age-stereotyped word primes; (3) Investigate (using this improved method) the effects of negative, positive and neutral age-stereotyped word primes on younger and older adults’ grip strength (GS) and self-perceptions of own ageing experience; and (4) Establish whether individual differences leave some older adults more vulnerable to the effects of age-stereotypes. Method: Participants were asked to self-report selfperceptions of age, to perform a simple grasping task to measure grip strength, and to complete an implicit age-stereotype word priming task. Results: Positive selfperceptions of age were positively correlated with higher GS amongst older adults only, independent of increasing older age. Exposure to negative age-stereotyped word primes significantly reduced both GS and self-perceptions of age in the older group only, whilst positive age-stereotyped word primes significantly increased GS. The former effect was significantly stronger than the latter. Mediation analysis confirmed that self-perceptions of age mediate the association between age-stereotyped word primes and GS. The age stereotyped word primes acted as an intervention which either increased or decreased older adults’ self-perceptions of age (depending on the valence of the prime words), which in turn then either improved or weakened GS levels during the grasping task. Results also revealed that individual differences leave some older adults more vulnerable to the effects of age-stereotypes; those with lower self-perceptions of age are more vulnerable to the effects of negative ageing stereotyped word primes (experiencing significantly larger declines in GS), whilst also gaining the least benefit from positive age-stereotyped word primes (experiencing the smallest increase in GS). Cumulative analysis showed that those with lower self-perceptions of age also required exposure to a fewer number of implicit negative age-stereotype word primes to significantly reduce GS in comparison to those with higher self-perceptions of age (i.e., they are also vulnerable to the cumulative effects of negative age-stereotypes). Conversely, when those with lower self-perceptions of age were exposed to positive age-stereotype word primes, not only did they experience smaller improvements to GS, but importantly they also require exposure to more positive implicit age-stereotype word primes to improve GS in comparison to those with higher self-perceptions of age. Discussion: I argue that the findings of this thesis are applicable to and informative for researchers, policy makers, and clinicians when attempting to identify those older adults most at risk of experiencing declines in functional health as a result of vulnerability to the effects of age-stereotypes. The current thesis findings also highlight approaches for early intervention in order to increase functional health through promotion of positive age-stereotypes

Cognitive and brain structural effects of long-term high-effort endurance exercise in older adults: are there measurable benefits?

Age-related decline in cognitive performance and brain structure can be offset by increased exercise. Little is known, however, about the cognitive and brain structural consequences of long-term high-effort endurance exercise. In a cross-sectional design, we recruited older adults who had been engaging in high-effort endurance exercise over at least twenty years, and compared their cognitive performance and brain structure with a non-sedentary control group similar in age, sex, education, IQ, depression levels, and other lifestyle factors. We hypothesized that long-term high-effort endurance exercise would protect against the age-related decline in memory, attention, and brain structure. Our findings, in contrast to previous studies, indicated that those participating in long-term high-effort endurance exercise, when compared without confounds to non-sedentary control volunteers, showed no differences on measures of speed of processing, executive function, incidental memory, episodic memory, working memory, or visual search. On measures of prospective memory, long-term exercisers performance suggested a self-imposed increase in effort, which did not impact on ability to complete the PM task. In complex attention tasks, they displayed a differential strategy to controls. Structurally, long-term exercisers only displayed higher diffuse axial diffusivity, an index of axonal integrity, than controls, but this did not correlate with any cognitive differences