Body mass index (BMI) is associated with cognitive abilities, but the nature of the relationship remains largely unexplored. We aimed to investigate the bidirectional relationship from midlife ...through late-life, while considering sex differences and genetic predisposition to higher BMI. We used data from 23,892 individuals of European ancestry from the Health and Retirement Study, with longitudinal data on BMI and three established cognitive indices: mental status, episodic memory, and their sum, called total cognition. To investigate the dynamic relationship between BMI and cognitive abilities, we applied dual change score models of change from age 50 through 89, with a breakpoint at age 65 or 70. Models were further stratified by sex and genetic predisposition to higher BMI using tertiles of a polygenic score for BMI (PGS
). We demonstrated bidirectional effects between BMI and all three cognitive indices, with higher BMI contributing to steeper decline in cognitive abilities in both midlife and late-life, and higher cognitive abilities contributing to less decline in BMI in late-life. The effects of BMI on change in cognitive abilities were more evident in men compared to women, and among those in the lowest tertile of the PGS
compared to those in the highest tertile, while the effects of cognition on BMI were similar across groups. In conclusion, these findings highlight a reciprocal relationship between BMI and cognitive abilities, indicating that the negative effects of a higher BMI persist from midlife through late-life, and that weight-loss in late-life may be driven by cognitive decline.
Abstract
Objectives
Loneliness may influence aging biomarkers related to cognitive functioning, for example, through accelerated DNA methylation (DNAm) aging.
Methods
In the present study, we tested ...whether six common DNAm age acceleration measures mediated the effects of baseline loneliness and five different longitudinal loneliness trajectories on general cognitive ability, immediate memory recall, delayed memory recall, and processing speed in 1,814 older adults in the Health and Retirement Study.
Results
We found that baseline loneliness and individuals who belong to the highest loneliness trajectories had poorer general cognitive ability and memory scores. Only DNAm age acceleration measures that index physiological comorbidities, unhealthy lifestyle factors (e.g., smoking), and mortality risk-mediated effects of baseline loneliness on general cognitive ability and memory functioning but not processing speed. These same DNAm measures mediated effects of the moderate-but-declining loneliness trajectory on cognitive functioning. Additionally, immediate and delayed memory scores were mediated by GrimAge Accel in the lowest and two highest loneliness trajectory groups. Total and mediated effects of loneliness on cognitive functioning outcomes were mainly accounted for by demographic, social, psychological, and physiological covariates, most notably self-rated health, depressive symptomatology, objective social isolation, and body mass index.
Discussion
Current findings suggest that DNAm biomarkers of aging, particularly GrimAge Accel, have promise for explaining the prospective association between loneliness and cognitive functioning outcomes.
Cigarette smoking is among the leading risk factors for mortality and morbidity. While men have a higher smoking prevalence, mechanistic experiments suggest that women are at higher risk for health ...problems due to smoking. Moreover, the comparison of smoking effects on multiple conditions and mortality for men and women has not yet been done in a population-based group with race/ethnic diversity. We used proportional hazards models and restricted mean survival time to assess differences in smoking effects by sex for multiple health outcomes using data from the U.S. Health and Retirement Study (HRS), a population-representative cohort of individuals aged 50+ (n = 22,708, 1992-2014). Men had experienced more smoking pack-years than women (22.0 vs 15.6 average pack-years). Age of death, onset of lung disorders, heart disease, stroke, and cancer showed dose-dependent effects of smoking for both sexes. Among heavy smokers (>28 pack-years) women had higher risk of earlier age of death (HR = 1.3, 95%CI:1.03-1.65) and stroke (HR = 1.37, 95%CI:1.02-1.83). Risk of cancer and heart disease did not differ by sex for smokers. Women had earlier age of onset for lung disorders (HR = 2.83, 95%CI:1.74-4.6), but men risk due to smoking were higher (Smoking-Sex interaction P<0.02) than women. Passive smoke exposure increased risk of earlier heart disease (HR = 1.33, 95%CI:1.07-1.65) and stroke (HR:1.54, 95%CI:1.07-2.22) for non-smokers, mainly in men. Smoking cessation after 15 years partially attenuated the deleterious smoking effects for all health outcomes. In sum, our results suggest that women are more vulnerable to ever smoking for earlier death and risk of stroke, but less vulnerable for lung disorders. From an epidemiological perspective, sex differences in smoking effects are important considerations that could underlie sex differences in health outcomes. These findings also encourage future mechanistic experiments to resolve potential mechanisms of sex-specific cigarette smoke toxicity.
The influence of genetic variation on the aging process, including the incidence and severity of age-related diseases, is complex. Here, we define the evolutionarily conserved mitochondrial enzyme ...ALH-6/ALDH4A1 as a predictive biomarker for age-related changes in muscle health by combining
genetics and a gene-wide association scanning (GeneWAS) from older human participants of the US Health and Retirement Study (HRS). In a screen for mutations that activate oxidative stress responses, specifically in the muscle of
, we identified 96 independent genetic mutants harboring loss-of-function alleles of
, exclusively. Each of these genetic mutations mapped to the ALH-6 polypeptide and led to the age-dependent loss of muscle health. Intriguingly, genetic variants in
show associations with age-related muscle-related function in humans. Taken together, our work uncovers mitochondrial
as a critical component to impact normal muscle aging across species and a predictive biomarker for muscle health over the lifespan.
We leveraged a unique school‐based longitudinal cohort—the Project Talent Aging Study—to examine whether attending higher quality schools is associated with cognitive performance among older adults ...in the United States (mean age = 74.8). Participants (n = 2,289) completed telephone neurocognitive testing. Six indicators of high school quality, reported by principals at the time of schooling, were predictors of respondents’ cognitive function 58 years later. To account for school‐clustering, multilevel linear and logistic models were applied. We found that attending schools with a higher number of teachers with graduate training was the clearest predictor of later‐life cognition, and school quality mattered especially for language abilities. Importantly, Black respondents (n = 239; 10.5 percentage) were disproportionately exposed to low quality high schools. Therefore, increased investment in schools, especially those that serve Black children, could be a powerful strategy to improve later life cognitive health among older adults in the United States.
To explain the ethnic paradox of mental health in aging, we evaluated whether Black and Latinx older adults experience (1) fewer depressive symptoms (DepSx), but more physical problems, and (2) ...greater psychological resilience as a result of life stressors than White older adults.
DepSx, physical health, and recent stress were obtained biennially from 25,893 older adults (77% White, 15% Black, 9% Latinx) in the U.S. Health and Retirement Study, across 16 years. Psychological resilience, lifetime stress, and discrimination experiences were available for 13,655 individuals. We conducted mixed-effects and linear regression analyses.
For Blacks and Latinxs, experiencing more-than-usual stress events was associated with less increase in DepSx compared to Whites, although on average Blacks and Latinxs experience more DepSx. Black adults showed worse physical health than White adults and weaker effects of stress on psychological resilience despite experiencing more stress of all types. Findings were mixed for Latinxs.
Studying effects of time-varying stress on changes in health and multiple stressors on psychological resilience by race/ethnicity elucidates mechanisms for later-age health disparities.
Cross-sectional evaluations of stress and psychological health in a clinical setting may provide incomplete appraisals of health risks for Black and Latinx older Americans.
Objectives: We evaluated whether the effects of recent stressful life events (SLEs) and early childhood adversities (ECAs) on depressive symptoms are consistent between men and women and across older ...age, and whether there was evidence for the following: stress sensitization, whereby the psychological impact of SLEs is greater for individuals with ECAs compared with those without; or stress proliferation effect, whereby those with ECAs are more likely to report more SLEs than those without ECAs to effect depressive symptoms.
Method: ECAs, SLEs in the past two years, and current depressive symptoms through a modified CES-D were obtained from 11,873 individuals participating in a population representative study of older adults, yielding 82,764 observations. Mixed-effects regression models on depressive symptoms were constructed to control for multiple observations per participant and evaluate within-person effects over time, thereby reducing bias from reverse causation.
Results: Results suggest a stress proliferation effect and do not support stress sensitization. ECAs contribute to vulnerability for depressive symptoms, with a dosage effect for each additional ECA. Recent SLEs result in greater depressive symptom risk, with stable effects over age and dosage effects for each additional SLE that were smaller than the effects of ECAs among men, but not women. Belonging to an ethnic minority group, having less education, and less household income at baseline were associated with greater depressive symptom risk.
Conclusions: Findings suggest the importance of addressing early childhood adversity and sociodemographic factors, among at-risk older adults to mitigate life-course stress proliferative processes and thereby reduce disparate risk for depression in older age.
INTRODUCTION
We address the extent to which adolescent cognition predicts dementia risk in later life, mediated by educational attainment and occupational complexity.
METHODS
Using data from Project ...Talent Aging Study (PTAS), we fitted two structural equation models to test whether adolescent cognition predicts cognitive impairment (CI) and Ascertain Dementia 8 (AD8) status simultaneously (NCognitive Assessment = 2477) and AD8 alone (NQuestionnaire = 6491) 60 years later, mediated by education and occupational complexity. Co‐twin control analysis examined 82 discordant pairs for CI/AD8.
RESULTS
Education partially mediated the effect of adolescent cognition on CI in the cognitive assessment aample and AD8 in the questionnaire sample (Ps < 0.001). Within twin pairs, differences in adolescent cognition were small, but intrapair differences in education predicted CI status.
DISCUSSION
Adolescent cognition predicted dementia risk 60 years later, partially mediated through education. Educational attainment, but not occupational complexity, contributes to CI risk beyond its role as a mediator of adolescent cognition, further supported by the co‐twin analyses.
Highlights
Project Talent Aging Study follows enrollees from high school for nearly 60 years.
General cognitive ability in high school predicts later‐life cognitive impairment.
Low education is a risk partially due to its association with cognitive ability.
Abstract
Objectives
Individuals with more education are at lower risk of developing multiple, different age-related diseases than their less-educated peers. A reason for this might be that ...individuals with more education age slower. There are 2 complications in testing this hypothesis. First, there exists no definitive measure of biological aging. Second, shared genetic factors contribute toward both lower educational attainment and the development of age-related diseases. Here, we tested whether the protective effect of educational attainment was associated with the pace of aging after accounting for genetic factors.
Methods
We examined data from 5 studies together totaling almost 17,000 individuals with European ancestry born in different countries during different historical periods, ranging in age from 16 to 98 years old. To assess the pace of aging, we used DunedinPACE, a DNA methylation algorithm that reflects an individual’s rate of aging and predicts age-related decline and Alzheimer’s disease and related disorders. To assess genetic factors related to education, we created a polygenic score based on the results of a genome-wide association study of educational attainment.
Results
Across the 5 studies, and across the life span, higher educational attainment was associated with a slower pace of aging even after accounting for genetic factors (meta-analysis effect size = −0.20; 95% confidence interval CI: −0.30 to −0.10; p = .006). Further, this effect persisted after taking into account tobacco smoking (meta-analysis effect size = −0.13; 95% CI: −0.21 to −0.05; p = .01).
Discussion
These results indicate that higher levels of education have positive effects on the pace of aging, and that the benefits can be realized irrespective of individuals’ genetics.
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