A Decade Later on How to "Use It" So We Don't "Lose It": An Update on the Unanswered Questions about the Influence of Activity Participation on Cognitive Performance in Older Age.

Activity engagement is a modifiable factor that has been widely-cited as being good for the aging brain and cognition and represents a valuable target for reducing dementia risk. However, specific issues about activity engagement (mental, social, and physical) and cognition in older adulthood remain, and Bielak [Gerontology 2010;56: 507-519] reviewed seven major methodological and theoretical questions about this relationship. We present an updated reflection on these key questions, focusing on research published in the last 10 years. For some questions, a significant amount of work has been done and conclusions have become clearer; for others, there have been few additions to the literature and our knowledge remains much the same as it was a decade ago. We review the issues identified in the 2010 paper including the directionality and temporal nature of the relationship; whether specific activity domains offer different benefits to cognition and what domain(s) of cognition are affected; variation in the relation by age, gender, or education; potential mechanisms involved; and how activity engagement is assessed. For each, we present the most up-to-date research, discuss remaining challenges and possible future directions. This formal unifying of the information in the field is intended as a guide to support continued progress by spurring on studies addressing specific questions while reminding researchers of critical issues. We conclude with recommendations that future studies investigating the link between activity engagement and cognitive performance in adulthood should consider.

Towards an active and happy retirement? Changes in leisure activity and depressive symptoms during the retirement transition.

Objectives: Retirement is a major life transition in the second half of life, and it can be associated with changes in leisure activity engagement. Although theories of retirement adjustment have emphasized the need to find meaningful activities in retirement, little is known about the nature of changes in leisure activity during the retirement transition and their association with mental health.Methods: Based on four annual waves of the 'Health, Aging and Retirement Transitions in Sweden' study, we investigated the longitudinal association of leisure activity engagement and depressive symptoms using bivariate dual change score models. We distinguished intellectual, social, and physical activity engagement.Results: We found increases in all three domains of activity engagement after retirement. Although level and change of activity and depressive symptoms were negatively associated, the coupling parameters were not significant, thus the direction of effects remains unclear.Conclusion: The results highlight the need to consider the role of lifestyle changes for retirement adjustment and mental health.

Copenhagen Consensus statement 2019: physical activity and ageing.

From 19th to 22nd November 2018, 26 researchers representing nine countries and a variety of academic disciplines met in Snekkersten, Denmark, to reach evidence-based consensus about physical activity and older adults. It was recognised that the term 'older adults' represents a highly heterogeneous population. It encompasses those that remain highly active and healthy throughout the life-course with a high intrinsic capacity to the very old and frail with low intrinsic capacity. The consensus is drawn from a wide range of research methodologies within epidemiology, medicine, physiology, neuroscience, psychology and sociology, recognising the strength and limitations of each of the methods. Much of the evidence presented in the statements is based on longitudinal associations from observational and randomised controlled intervention studies, as well as quantitative and qualitative social studies in relatively healthy community-dwelling older adults. Nevertheless, we also considered research with frail older adults and those with age-associated neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, and in a few cases molecular and cellular outcome measures from animal studies. The consensus statements distinguish between physical activity and exercise. Physical activity is used as an umbrella term that includes both structured and unstructured forms of leisure, transport, domestic and work-related activities. Physical activity entails body movement that increases energy expenditure relative to rest, and is often characterised in terms of intensity from light, to moderate to vigorous. Exercise is defined as a subset of structured physical activities that are more specifically designed to improve cardiorespiratory fitness, cognitive function, flexibility balance, strength and/or power. This statement presents the consensus on the effects of physical activity on older adults' fitness, health, cognitive functioning, functional capacity, engagement, motivation, psychological well-being and social inclusion. It also covers the consensus on physical activity implementation strategies. While it is recognised that adverse events can occur during exercise, the risk can be minimised by carefully choosing the type of activity undertaken and by consultation with the individual's physician when warranted, for example, when the individual is frail, has a number of co-morbidities, or has exercise-related symptoms, such as chest pain, heart arrhythmia or dizziness. The consensus was obtained through an iterative process that began with the presentation of the state-of-the-science in each domain, followed by group and plenary discussions. Ultimately, the participants reached agreement on the 30-item consensus statements.

The Influence of Dyslexia Candidate Genes on Reading Skill in Old Age.

A number of candidate genes for reading and language impairment have been replicated, primarily in samples of children with developmental disability or delay, although these genes are also supported in adolescent population samples. The present study used a systematic approach to test 14 of these candidate genes for association with reading assessed in late adulthood (two cohorts with mean ages of 70 and 79 years). Gene-sets (14 candidates, axon-guidance and neuron migration pathways) and individual SNPs within each gene of interest were tested for association using imputed data referenced to the 1000 genomes European panel. Using the results from the genome-wide association (GWA) meta-analysis of the two cohorts (N = 1217), a competitive gene-set analysis showed that the candidate gene-set was associated with the reading index (p = .016) at a family wise error rate corrected significance level. Neither axon guidance nor neuron migration pathways were significant. Whereas individual SNP associations within CYP19A1, DYX1C1, CNTNAP2 and DIP2A genes (p < .05) did not reach corrected significance their allelic effects were in the same direction as past available reports. These results suggest that reading skill in normal adults shares the same genetic substrate as reading in adolescents, and clinically disordered reading, and highlights the utility of adult samples to increase sample sizes in the genetic study of developmental disorders.

People's Beliefs and Expectations About How Cognitive Skills Change with Age: Evidence From a U.K.-Wide Aging Survey.

OBJECTIVE: We conducted a U.K.-wide survey to collect information on people's beliefs, fears, perceptions, and attitudes to cognitive aging. METHODS: This community-based aging survey included 3,146 adults aged 40 years and over. RESULTS: Respondents believed memory might be the earliest cognitive skill to decline (mean: 59.4 years), followed by speed of thinking (mean: 64.9). Those in their 40s were more pessimistic, because they estimated cognitive changes would start up to 15 years earlier than respondents aged over 70. Having a purpose in life, healthy eating, challenging the mind, sleep, and physical activity ranked higher in terms of perceived importance for maintaining or improving cognitive skills. However, less than 50% engaged in any of these activities. Although 91% believed there are things people can do to maintain or improve their cognitive skills, more than 40% were unsure or did not know how to do so. Respondents who strongly agreed that changes in cognitive skills might be a sign of something more serious were significantly more likely to do various activities to benefit their cognitive skills. CONCLUSION: Results suggest that people are less aware of the potential cognitive benefits of certain activities, such as exercise and diet. It is important to build awareness about the benefits of lifestyles and activities for cognitive health.

Genetic contributions to stability and change in intelligence from childhood to old age.

Understanding the determinants of healthy mental ageing is a priority for society today. So far, we know that intelligence differences show high stability from childhood to old age and there are estimates of the genetic contribution to intelligence at different ages. However, attempts to discover whether genetic causes contribute to differences in cognitive ageing have been relatively uninformative. Here we provide an estimate of the genetic and environmental contributions to stability and change in intelligence across most of the human lifetime. We used genome-wide single nucleotide polymorphism (SNP) data from 1,940 unrelated individuals whose intelligence was measured in childhood (age 11 years) and again in old age (age 65, 70 or 79 years). We use a statistical method that allows genetic (co)variance to be estimated from SNP data on unrelated individuals. We estimate that causal genetic variants in linkage disequilibrium with common SNPs account for 0.24 of the variation in cognitive ability change from childhood to old age. Using bivariate analysis, we estimate a genetic correlation between intelligence at age 11 years and in old age of 0.62. These estimates, derived from rarely available data on lifetime cognitive measures, warrant the search for genetic causes of cognitive stability and change.

A Tablet for Healthy Ageing: The Effect of a Tablet Computer Training Intervention on Cognitive Abilities in Older Adults.

OBJECTIVE: To test the efficacy of a tablet computer training intervention to improve cognitive abilities of older adults. DESIGN: Prospective randomized controlled trial. SETTING: Community-based aging intervention study, Edinburgh, UK. PARTICIPANTS: Forty-eight healthy older adults aged 65 to 76 years were recruited at baseline with no or minimal tablet experience; 43 completed follow-up testing. INTERVENTION: Twenty-two participants attended a weekly 2-hour class for 10 weeks during which they learned how to use a tablet and various applications on it. MEASUREMENTS: A battery of cognitive tests from the WAIS-IV measuring the domains of Verbal Comprehension, Perceptual Processing, Working Memory, and Processing Speed, as well as health, psychological, and well-being measures. RESULTS: A 2 × 2 mixed model ANOVA suggested that the tablet intervention group (N = 22) showed greater improvements in Processing Speed (η2 = 0.10) compared with controls (N = 21), but did not differ in Verbal Comprehension, Perceptual Processing, or Working Memory (η2 ranged from -0.03 to 0.04). CONCLUSIONS: Engagement in a new mentally challenging activity (tablet training) was associated with improved processing speed. Acquiring skills in later life, including those related to adopting new technologies, may therefore have the potential to reduce or delay cognitive changes associated with ageing. It is important to understand how the development of these skills might further facilitate everyday activities, and also improve older adults' quality of life.

Coupled changes in brain white matter microstructure and fluid intelligence in later life.

Understanding aging-related cognitive decline is of growing importance in aging societies, but relatively little is known about its neural substrates. Measures of white matter microstructure are known to correlate cross-sectionally with cognitive ability measures, but only a few small studies have tested for longitudinal relations among these variables. We tested whether there were coupled changes in brain white matter microstructure indexed by fractional anisotropy (FA) and three broad cognitive domains (fluid intelligence, processing speed, and memory) in a large cohort of human participants with longitudinal diffusion tensor MRI and detailed cognitive data taken at ages 73 years (n = 731) and 76 years (n = 488). Longitudinal changes in white matter microstructure were coupled with changes in fluid intelligence, but not with processing speed or memory. Individuals with higher baseline white matter FA showed less subsequent decline in processing speed. Our results provide evidence for a longitudinal link between changes in white matter microstructure and aging-related cognitive decline during the eighth decade of life. They are consistent with theoretical perspectives positing that a corticocortical "disconnection" partly explains cognitive aging.

Social resources and cognitive ageing across 30 years: the Glostrup 1914 Cohort.

BACKGROUND: to examine associations between social resources and cognitive ageing over 30 years. METHODS: participants in the Glostrup 1914 Cohort, a year of birth sample, completed a standardarised battery of cognitive ability tests every 10 years from age 50 to 80, summarised as general cognitive ability. Participants also provided information concerning a range of social resources, including marital status and living arrangements from age 50, and from age 70, details regarding social support, social contact and loneliness. RESULTS: across the follow-up, participants were less likely to be married, falling from 85.0 to 40.4% between ages 50 and 80, while the proportion of those living alone increased from 13.1 to 54.2%. In separate growth curve models, being married, living with others and not feeling lonely were all associated with higher cognitive ability level, while more telephone contact had a negative association. Marital status (at ages 50 and 60) and loneliness at age 70 were the only social resources associated with cognitive change; married individuals and those not feeling lonely experienced less cognitive decline. When the social resources showing significant associations were considered together (and accounting for sex, education and social class), loneliness was associated with lower cognitive ability level and greater cognitive decline, while married individuals experienced less decline. CONCLUSIONS: in a relatively large cohort followed for up to 30 years, marital status and loneliness were associated with cognitive ability or change. Interventions designed to reduce loneliness in older adults might be supported as one avenue to reduce cognitive ageing.

Genetic associations for activated partial thromboplastin time and prothrombin time, their gene expression profiles, and risk of coronary artery disease.

Activated partial thromboplastin time (aPTT) and prothrombin time (PT) are clinical tests commonly used to screen for coagulation-factor deficiencies. One genome-wide association study (GWAS) has been reported previously for aPTT, but no GWAS has been reported for PT. We conducted a GWAS and meta-analysis to identify genetic loci for aPTT and PT. The GWAS for aPTT was conducted in 9,240 individuals of European ancestry from the Atherosclerosis Risk in Communities (ARIC) study, and the GWAS for PT was conducted in 2,583 participants from the Genetic Study of Three Population Microisolates in South Tyrol (MICROS) and the Lothian Birth Cohorts (LBC) of 1921 and 1936. Replication was assessed in 1,041 to 3,467 individuals. For aPTT, previously reported associations with KNG1, HRG, F11, F12, and ABO were confirmed. A second independent association in ABO was identified and replicated (rs8176704, p = 4.26 × 10(-24)). Pooling the ARIC and replication data yielded two additional loci in F5 (rs6028, p = 3.22 × 10(-9)) and AGBL1 (rs2469184, p = 3.61 × 10(-8)). For PT, significant associations were identified and confirmed in F7 (rs561241, p = 3.71 × 10(-56)) and PROCR/EDEM2 (rs2295888, p = 5.25 × 10(-13)). Assessment of existing gene expression and coronary artery disease (CAD) databases identified associations of five of the GWAS loci with altered gene expression and two with CAD. In summary, eight genetic loci that account for ∼29% of the variance in aPTT and two loci that account for ∼14% of the variance in PT were detected and supported by functional data.

Brain volumetric changes and cognitive ageing during the eighth decade of life.

Later-life changes in brain tissue volumes--decreases in the volume of healthy grey and white matter and increases in the volume of white matter hyperintensities (WMH)--are strong candidates to explain some of the variation in ageing-related cognitive decline. We assessed fluid intelligence, memory, processing speed, and brain volumes (from structural MRI) at mean age 73 years, and at mean age 76 in a narrow-age sample of older individuals (n = 657 with brain volumetric data at the initial wave, n = 465 at follow-up). We used latent variable modeling to extract error-free cognitive levels and slopes. Initial levels of cognitive ability were predictive of subsequent brain tissue volume changes. Initial brain volumes were not predictive of subsequent cognitive changes. Brain volume changes, especially increases in WMH, were associated with declines in each of the cognitive abilities. All statistically significant results were modest in size (absolute r-values ranged from 0.114 to 0.334). These results build a comprehensive picture of macrostructural brain volume changes and declines in important cognitive faculties during the eighth decade of life.

Examining associations between sexual behaviours and quality of life in older adults.

BACKGROUND: while sexual behaviours are potentially important for quality of life in older adults, they are under-researched. The current study examined associations between frequency and importance of sexual behaviours and quality of life in older adults. METHOD: one hundred and thirty-three participants (mean 74 years, SD = 7.1) provided information about the frequency with which they participated in six sexual behaviours and the perceived importance of these: touching/holding hands, embracing/hugging, kissing, mutual stroking, masturbating and intercourse. Participants also completed the WHO Quality of Life scale, providing an overall quality of life score, in addition to the domains of physical health, psychological health, social relationships and environment. Participants provided information on their marital status, living arrangements and self-reported health. RESULTS: both the frequency and importance of sexual behaviours were moderately positively correlated with quality of life (r = 0.52 and 0.47, respectively, both P < 0.001). In separate regression analyses, the frequency of sexual behaviours was a significant predictor of quality of life in the social relationships domain (ß = 0.225, P < 0.05), and the importance of sexual behaviours was associated with the psychological domain (ß = 0.151, P < 0.05), independent of the presence of a spouse/partner and self-reported health. CONCLUSIONS: with ageing trends, a broader understanding of the factors that influence quality of life in older adults is increasingly important. The current findings suggest that aspects of sexual behaviour and quality of life were positively associated. Researchers are encouraged to consider aspects of sex and sexuality when exploring determinants of well-being in later life.

Beyond a bigger brain: Multivariable structural brain imaging and intelligence.

People with larger brains tend to score higher on tests of general intelligence (g). It is unclear, however, how much variance in intelligence other brain measurements would account for if included together with brain volume in a multivariable model. We examined a large sample of individuals in their seventies (n = 672) who were administered a comprehensive cognitive test battery. Using structural equation modelling, we related six common magnetic resonance imaging-derived brain variables that represent normal and abnormal features-brain volume, cortical thickness, white matter structure, white matter hyperintensity load, iron deposits, and microbleeds-to g and to fluid intelligence. As expected, brain volume accounted for the largest portion of variance (~ 12%, depending on modelling choices). Adding the additional variables, especially cortical thickness (+~ 5%) and white matter hyperintensity load (+~ 2%), increased the predictive value of the model. Depending on modelling choices, all neuroimaging variables together accounted for 18-21% of the variance in intelligence. These results reveal which structural brain imaging measures relate to g over and above the largest contributor, total brain volume. They raise questions regarding which other neuroimaging measures might account for even more of the variance in intelligence.

Circulating inflammatory markers are associated with magnetic resonance imaging-visible perivascular spaces but not directly with white matter hyperintensities.

BACKGROUND AND PURPOSE: White matter hyperintensities (WMH) and perivascular spaces (PVS) are features of small vessel disease, found jointly on MRI of older people. Inflammation is a prominent pathological feature of small vessel disease. We examined the association between inflammation, PVS, and WMH in the Lothian Birth Cohort 1936 (N=634). METHODS: We measured plasma fibrinogen, C-reactive protein, and interleukin-6 and rated PVS in 3 brain regions. We measured WMH volumetrically and visually using the Fazekas scale. We derived latent variables for PVS, WMH, and Inflammation from measured PVS, WMH, and inflammation markers and modelled associations using structural equation modelling. RESULTS: After accounting for age, sex, stroke, and vascular risk factors, PVS were significantly associated with WMH (ß=0.47; P<0.0001); Inflammation was weakly but significantly associated with PVS (ß=0.12; P=0.048), but not with WMH (ß=0.02; P=NS). CONCLUSIONS: Circulating inflammatory markers are weakly associated with MR-visible PVS, but not directly with WMH. Longitudinal studies should examine whether visible PVS predate WMH progression and whether inflammation modulators can prevent small vessel disease.

Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory.

Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.

Potential effect of skull thickening on the associations between cognition and brain atrophy in ageing.

BACKGROUND: intracranial volume (ICV) is commonly used as a marker of premorbid brain size in neuroimaging studies as it is thought to remain fixed throughout adulthood. However, inner skull table thickening would encroach on ICV and could mask actual brain atrophy. OBJECTIVE: we investigated the effect that thickening might have on the associations between brain atrophy and cognition. METHODS: the sample comprised 57 non-demented older adults who underwent structural brain MRI at mean age 72.7 ± 0.7 years and were assessed on cognitive ability at mean age 11 and 73 years. Principal component analysis was used to derive factors of general cognitive ability (g), information processing speed and memory from the recorded cognitive ability data. The total brain tissue volume and ICV with (estimated original ICV) and without (current ICV) adjusting for the effects of inner table skull thickening were measured. General linear modelling was used to test for associations. RESULTS: all cognitive ability variables were significantly (P < 0.01) associated with percentage total brain volume in ICV measured without adjusting for skull thickening (g: η(2) = 0.177, speed: η(2) = 0.264 and memory: η(2) = 0.132). After accounting for skull thickening, only speed was significantly associated with percentage total brain volume in ICV (η(2) = 0.085, P = 0.034), not g or memory. CONCLUSIONS: not accounting for skull thickening when computing ICV can distort the association between brain atrophy and cognitive ability in old age. Larger samples are required to determine the true effect.

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

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.

A Scoping Review on the Opportunities for Social Engagement and Cognitive Frailty in Older Adults.

Cognitive frailty (CF) is defined as the clinical syndrome of the combination of physical frailty and cognitive impairment, without dementia. Numerous risk factors for CF have been previously identified but this scoping review focusses on the critical need for social engagement and the association with cognition. The focus of this scoping review on the opportunity for social engagement rather than on perception or experience of loneliness. Based on the results of 55 studies were synthesised into four social engagement categories, namely participation, household, network, and habitat. Social engagement is associated with maintaining or improving cognition, particularly through active participation in social roles. Habitat (i.e., rural or urban settings) also influences cognition and the challenge is to enable social participation.

Understanding exogenous factors and biological mechanisms for cognitive frailty: A multidisciplinary scoping review.

Cognitive frailty (CF) is the conjunction of cognitive impairment without dementia and physical frailty. While predictors of each element are well-researched, mechanisms of their co-occurrence have not been integrated, particularly in terms of relationships between social, psychological, and biological factors. This interdisciplinary scoping review set out to categorise a heterogenous multidisciplinary literature to identify potential pathways and mechanisms of CF, and research gaps. Studies were included if they used the definition of CF OR focused on conjunction of cognitive impairment and frailty (by any measure), AND excluded studies on specific disease populations, interventions, epidemiology or prediction of mortality. Searches used Web of Science, PubMed and Science Direct. Search terms included "cognitive frailty" OR (("cognitive decline" OR "cognitive impairment") AND (frail*)), with terms to elicit mechanisms, predictors, causes, pathways and risk factors. To ensure inclusion of animal and cell models, keywords such as "behavioural" or "cognitive decline" or "senescence", were added. 206 papers were included. Descriptive analysis provided high-level categorisation of determinants from social and environmental through psychological to biological. Patterns distinguishing CF from Alzheimer's disease were identified and social and psychological moderators and mediators of underlying biological and physiological changes and of trajectories of CF development were suggested as foci for further research.

Perceptions of risk and coping strategies during the COVID-19 pandemic among women and older adults.

The world's health, economic, and social systems have been adversely impacted by the COVID-19 pandemic. With lockdown measures being a common response strategy in most countries, many individuals were faced with financial and mental health challenges. The current study explored the effect of the COVID-19 pandemic on the psychological well-being, perception of risk factors and coping strategies of two vulnerable groups in Malaysia, namely women and older adults from low-income households (USD592). A purposive sample of 30 women and 30 older adults was interviewed via telephone during Malaysia's Movement Control Order (MCO) regarding the challenges they faced throughout the pandemic. Thematic analysis was subsequently conducted to identify key themes. The themes identified from the thematic analysis indicated a degree of overlap between both groups. For women, seven themes emerged: 1) Psychological challenges due to COVID-19 pandemic, 2) Family violence, 3) Finance and employment related stress and anxiety, 4) Women's inequality and prejudice, 5) Coping strategies, 6) Professional support, and 7) Women's empowerment. Similarly, there were six themes for the older adults: 1) Adverse emotional experiences from COVID-19, 2) Threats to health security, 3) Loss of social connections, 4) Government aid to improve older adults' psychological well-being, 5) Psychological support from family members and pets, and 6) Self-reliance, religion, and spirituality. The findings provide valuable information on the specific burdens faced by these groups, and support psychological interventions and mitigations that would be appropriate to improve well-being during the recovery phase.