Late-life Cognition Research Articles

A multilayer network analysis of Alzheimer's disease pathogenesis: Roles for p-tau, synaptic peptides, and physical activity.

In the aging brain, cognitive abilities emerge from the coordination of complex pathways arising from a balance between protective lifestyle and environmental factors and accumulation of neuropathologies. As part of the Rush Memory and Aging Project (n=440), we measured accelerometer-based actigraphy, cognitive performance, and after brain autopsy, selected reaction monitoring mass spectrometry. Multilevel network analysis was used to examine the relationships among the molecular machinery of vesicular neurotransmission, Alzheimer's disease (AD) neuropathology, cognition, and late-life physical activity. Synaptic peptides involved in neuronal secretory function were the most influential contributors to the multilayer network, reflecting the complex interdependencies among AD pathology, synaptic processes, and late-life cognition. Older adults with lower physical activity evidenced stronger adverse relationships among phosphorylated tau peptides, markers of synaptic integrity, and tangle pathology. Network-based approaches simultaneously model interdependent biological processes and advance understanding of the role of physical activity in age-associated cognitive impairment. Network-based approaches simultaneously model interdependent biological processes. Secretory synaptic peptides were influential contributors to the multilayer network. Older adults with lower physical activity had adverse relationships among pathology. There was interdependence among phosphorylated tau, synaptic integrity, and tangles. Network methods elucidate the role of physical activity in cognitive impairment.

Influence of intergenerational social mobility on brain structure and global cognition: findings from the Whitehall II study across 20years.

Whether changes in socioeconomic position (SEP) across generations, i.e. intergenerational social mobility, influence brain degeneration and cognition in later life is unclear. To examine the association of social mobility, brain grey matter structure and global cognition. We analysed T1 brain MRI data of 771 old adults (69.8 ± 5.2years) from the Whitehall II MRI substudy, with MRI data collected between 2012 and 2016. Social mobility was defined by SEP changes from their fathers' generation to mid-life status. Brain structural outcomes include grey matter (GM) volume and cortical thickness (CT) covering whole brain. Global cognition was measured by the Mini Mental State Examination. We firstly conducted analysis of covariance to identify regional difference of GM volume and cortical thickness across stable high/low and upward/downward mobility groups, followed with diagonal reference models studying the relationship between mobility and brain cognitive outcomes, apart from SEP origin and destination. We additionally conducted linear mixed models to check mobility interaction over time, where global cognition was derived from three phases across 2002 to 2017. Social mobility related to 48 out of the 136 GM volume regions and 4 out of the 68 CT regions. Declined volume was particularly seen in response to downward mobility, whereas no independent association of mobility with global cognition was observed. Despite no strong evidence supporting direct influence of mobility on global cognition in later life, imaging findings warranted a severe level of neurodegeneration due to downward mobility from their father's generation.

Examining the Role of Neuroticism Polygenic Risk in Late Life Cognitive Change: A UK Biobank Study.

Cognitive decline is a public health concern affecting about 50 million individuals worldwide. Neuroticism, defined as the trait disposition to experience intense and frequent negative emotions, has been associated with an increased risk of late-life cognitive decline. However, the underlying biological mechanisms of this association remain unknown. This study investigated the relationship between genetic predisposition to neuroticism, computed by polygenic risk score (PRS), and performance in cognitive domains of reasoning, processing speed, visual attention, and memory in individuals over age 60. The sample consisted of UK Biobank participants with genetic and cognitive data available (N = 10,737, 4686 females; mean age = 63.4 ± 2.71). The cognitive domains were assessed at baseline for all participants and seven years later for a subset (N = 645, 262 females; mean age = 62.9 ± 2.44). Neuroticism PRS was not associated cross-sectionally with cognitive measures (p > 0.05). However, the trajectory of change for processing speed (β = 0.020; 95% CI = [0.006, 0.035], adjusted p = 0.0148), visual attention (β = -0.077; 95% CI = [-0.0985, -0.0553], adjusted p = 1.412 × 10-11), and memory (β = -0.033; 95% CI = [-0.0535, -0.0131], adjusted p = 0.005) was significantly associated with neuroticism PRS. Specifically, a higher genetic predisposition to neuroticism was associated with less decline in these cognitive domains. This trend persisted after sensitivity analysis using complete cases, although it only remained nominally significant for visual attention.

Unraveling the dynamics of loneliness and cognition in late life: a cross-lagged panel model.

Loneliness and cognitive decline are pressing concerns among older adults, yet little research has explored cognition as a predictor of loneliness. This study investigates the dynamic relationship between loneliness and cognitive function in older adults using the random intercept cross-lagged panel model (RI-CLPM). Data were drawn from Waves 9-14 of the Health and Retirement Study (HRS), encompassing 8,473 individuals aged 65 years and older. Loneliness was assessed using the UCLA Loneliness Scale, and cognitive function was measured using immediate and delayed word recall and serial 7s from the HRS RAND file. Age, gender, education, marital status, self-health report, and depression were included as covariates. Using Mplus, we computed RI-CLPMs. The first three models were conducted on loneliness and cognitive functions. Then unconditional RI-CLPMs with no exogenous predictors were computed. Three conditional model results showed that age, gender, marital status, self-health report, and depression were significantly associated with loneliness in the first wave, but only age and self-health report were significantly associated with immediate and delayed word recall at the first wave, not with serial 7s. For carry-over effects, loneliness showed significant positive associations across consecutive waves, but cognitive functions showed significant positive associations just in the last two waves. Some spill-over effects were found between loneliness and cognitive functions. For within-person effects, although initially non-significant, a negative association between loneliness and immediate and delayed word recall emerged in later waves (11-12 and 13-14). The conditional models indicated that older age, not being married, male gender, low self-reported health, and high depression levels were positively associated with loneliness. However, only older age and lower self-reported health were positively linked to cognitive functions. This study underscores the link between loneliness and cognitive function decline in older adults, emphasizing the need to address loneliness to potentially reduce cognitive decline. Insights into demographic predictors of loneliness and cognitive function could inform targeted interventions for promoting successful aging.

School-based racial segregation, social support, and late-life cognitive function in the Study of Healthy Aging in African Americans (STAR).

School-based social support for Black students may mediate or modify the association between school segregation and late-life cognition. Study of Healthy Aging in African Americans participants (n=574) reported segregated school attendance and school-based social support. Associations of segregated schooling with domain-specific cognitive outcomes and effect modification or mediation by school-based social support were evaluated with linear mixed models. Segregated school attendance was associated with increased likelihood of school-based social support. Segregated (vs. desegregated in 6th grade) school attendance was associated with lower executive function (β =-0.18 [-0.34, -0.02]) and semantic memory z-scores (β =-0.31 [-0.48, -0.13]). Social support did not mediate these associations. Estimates for segregated school attendance were attenuated among those who felt supported, although there was limited evidence of statistically significant effect modification. Early-childhood school segregation was associated with poorer cognitive function. Sources of resilience within racialized educational experiences should be further evaluated to bridge inequities. School segregation is a form of structural racism that affected the educational experiences of Black youth with potentially lasting consequences for healthy brain aging. Black students who attended a segregated school experienced greater school-based social support, which may highlight a potential source of resilience and resistance against the effects of racism-related stressors on cognitive function. The estimated adverse association between attending a segregated school on cognition was larger for students without an adult at school who cared about them versus those with an adult at school who cared about them, but estimates were imprecise.

Place of Birth and Cognitive Function Among Older Americans: Findings From the Harmonized Cognitive Assessment Protocol.

Growing evidence suggests that place of birth (PoB) and related circumstances may have long-lasting and multiplicative contributions to various later-life outcomes. However, the specific contributions to different domains of cognitive function in late life remain less understood. This study investigated the extent to which state of birth contributes to a wide range of domains of later-life cognitive function. A nationally representative sample of Americans aged 65 and older (N = 3,333) from the Health and Retirement Study (HRS) Harmonized Cognitive Assessment Protocol (HCAP) was utilized. Cognitive function was assessed in HCAP and linked to HRS state of birth data to explore the contribution of PoB to later-life cognitive disparities. Regression-based Shapley decompositions were employed to quantify this contribution. PoB significantly contributed to all assessed cognitive domains including memory, executive function, language and fluency, visuospatial function, orientation, and general cognitive function. Geographic disparities in cognitive function were evident across PoB, with individuals born in U.S. southern states and foreign-born individuals performing worse than those born in other states. Overall, state of birth accounted for 2.2%-9.7% of the total variance in cognition after adjusting for age, sex, and race/ethnicity. This contribution declined to 2.0%-7.0% after further adjusting for comprehensive socioeconomic and health factors over the life course, and was robust to the control of current state of residence. PoB has lasting contributions to later-life cognition, with significant geographic disparities observed. Addressing these disparities requires more equalized place-based policies, resources, and early-life environments to promote health equity over the life course.

Racialized experience, biomarkers of lead exposure, and later-life cognition: a mediation analysis.

We evaluated the role of the neurotoxicant lead (Pb) in mediating racial disparities in later-life cognition in 1,085 non-Hispanic Black and 2,839 non-Hispanic white participants in NHANES (1999-2002, 2011-2014) 60+ years of age. We operationalized Black race as a marker for the experience of racialization and exposure to systemic racism. We estimated patella bone Pb via predictive models using blood Pb and demographics. Concurrent cognition (processing speed, sustained attention, working memory) was measured by the Digit Symbol Substitution Test (DSST) and a global measure combining four cognitive tests. To obtain the portion mediated, we used regression coefficients (race on Pb * Pb on cognitive score)/(race on cognitive score), adjusting for age, NHANES cycle, and sample weights. Other confounder adjustment (education, poverty income ratio, smoking) was limited to the mediator-outcome (i.e., Pb-cognition) pathway because these factors do not lie upstream of race and so cannot confound associations with race. Pb was estimated to mediate 0.6% of the association between race and global cognition, and 4% of the DSST. Our results suggest that later-life cognitive health disparities may be impacted by avoidable lead exposure driven by environmental injustice, noting that a large proportion of the pathway of systemic racism harming cognition remains.

Subjective hearing and memory problems are associated with dementia and cognition in later life.

Subjective hearing and memory problems are detectable earlier than objective measures of sensory loss and cognitive decline, which are known to be related to an increased risk of dementia in later life. Using a population-representative cohort of 6006 individuals (aged 50-75) we examined whether participants who self-reported hearing and short-term memory issues showed greater rates of dementia within 17 years of follow-up. A sub-cohort was tested for audiometric threshold and cognition after 14 years. Hearing and memory problems were associated with a greater risk of dementia (hazard ratios [HRs]=1.42 [95% confidence interval: 1.11-1.81], 1.57 [1.30-1.90]), and poorer cognition 14 years later. The risk was greatest in those reporting both problems (HR=1.99 [1.42-2.80]). At follow-up, the level of hearing loss was associated with lower cognitive scores. Self-reports of hearing and short-term memory problems are associated with poorer cognitive performance and a greater risk of dementia. Subjective assessments may have predictive power over more than a decade. In a sample of older adults subjective hearing and memory problems were associated with dementia risk.Cross-sectionally, the audiometric screening threshold was associated with cognitive test scores.Subjective sensory and memory loss questions are easy to implement and show good predictive power.

Perceived but not objective measures of neighborhood safety and food environments are associated with longitudinal changes in processing speed among urban older adults

BackgroundAlthough a growing body of literature documents the importance of neighborhood effects on late-life cognition, little is known about the relative strength of objective and subjective neighborhood measures on late-life cognitive changes. This study examined effects of objective and subjective neighborhood measures in three neighborhood domains (neighborhood safety, physical disorder, food environments) on longitudinal changes in processing speed, an early marker of cognitive aging and impairment.MethodsThe analysis sample included 306 community-dwelling older adults enrolled in the Einstein Aging Study (mean age = 77, age range = 70 to 91; female = 67.7%; non-Hispanic White: 45.1%, non-Hispanic Black: 40.9%). Objective and subjective measures of neighborhood included three neighborhood domains (i.e., neighborhood safety, physical disorder, food environments). Processing speed was assessed using a brief Symbol Match task (unit: second), administered on a smartphone device six times a day for 16 days and repeated annually for up to five years. Years from baseline was used as the within-person time index.ResultsResults from mixed effects models showed that subjective neighborhood safety (β= -0.028) and subjective availability of healthy foods (β= -0.028) were significantly associated with less cognitive slowing over time. When objective and subjective neighborhood measures were simultaneously examined, subjective availability of healthy foods remained significant (β= -0.028) after controlling for objective availability of healthy foods. Associations of objective neighborhood crime and physical disorder with processing speed seemed to be confounded by individual-level race and socioeconomic status; after controlling for these confounders, none of objective neighborhood measures showed significant associations with processing speed.ConclusionSubjective neighborhood safety and subjective availability of healthy foods, rather than objective measures, were associated with less cognitive slowing over time over a five-year period. Perception of one’s neighborhood may be a more proximal predictor of cognitive health outcomes as it may reflect one’s experiences in the environment. It would be important to improve our understanding of both objective and subjective neighborhood factors to improve cognitive health among older adults.

Association of Childhood Exposure to School Racial Segregation with Late-Life Cognitive Outcomes among Older Americans.

Disparities in cognition, including dementia occurrence, persist between White and Black older adults, and are possibly influenced by early educational differences stemming from structural racism. However, the relationship between school racial segregation and later-life cognition remains underexplored. To investigate the association between childhood contextual exposure to school racial segregation and cognitive outcomes in later life. Data from 16,625 non-Hispanic White (hereafter, White) and 3,335 non-Hispanic Black (hereafter, Black) Americans aged 65 or older were analyzed from the Health and Retirement Study. State-level White-Black dissimilarity index for public elementary schools in the late 1960s (range: 0-100) was used to measure school segregation. States were categorized into high segregation (383.6) and low segregation (<83.6) based on the top quintile. Cognitive scores, cognitive impairment (with or without dementia), and dementia were assessed using the Telephone Interview for Cognitive Status (TICS) and proxy assessment. Multilevel regression analyses were conducted, adjusting for demographic covariates, socioeconomic status, and health factors. Stratified analyses by race were performed. The mean (SD) age of participants was 78.5 (5.7) years, and 11,208 (56.2%) were female. Participants exposed to high segregation exhibited lower cognitive scores (12.6 vs. 13.6; P<0.001) and higher prevalence of cognitive impairment (50.8% vs 41.4%; P<0.001) and dementia (26.0% vs. 19.5%; P<0.001), compared to those with low segregation exposure. Multilevel analyses revealed a significant negative association between school segregation and later-life cognitive even after adjusting sequentially for potential confounders, and these associations were stronger among Black than White participants. Notably, in the fully adjusted model, Black participants exposed to high segregation displayed significantly lower cognitive scores (-0.51; 95% CI: -0.94, -0.09) and higher likelihood of cognitive impairment (adjusted Odds Ratio [aOR]: 1.45, 95% CI: 1.22, 1.72) and dementia (aOR: 1.31, 95% CI: 1.06, 1.63). Our study underscores that childhood exposure to state-level school segregation is associated with late-life cognition, especially for Black Americans. Given the rising trend of school segregation in the US, educational policies aimed at reducing segregation are crucial to address health inequities. Clinicians can leverage patients' early-life educational circumstances to promote screening, prevention, and management of cognitive disorders.

Premenopausal bilateral oophorectomy and brain white matter brain integrity in later-life.

Premenopausal bilateral oophorectomy (PBO) is associated with later-life cognition, but the underlying brain changes remain unclear. We assessed the impact of PBO and PBO age on white matter integrity. Female participants with regional diffusion tensor imaging (DTI) metrics of fractional anisotropy (FA) and mean diffusivity (MD) were included (22 with PBO<40 years; 43 with PBO 40-45 years; 39 with PBO 46-49 years; 907 referents without PBO<50 years). Linear regression models adjusted for age and apolipoprotein E (APOE) genotype. Females with PBO<40 years, compared to referents, had lower FA and higher MD in the anterior corona radiata, genu of the corpus collosum, inferior fronto-occipital fasciculus, superior occipital, and superior temporal white matter. Females who underwent PBO between 45 and 49 also had some changes in white matter integrity. Females who underwent PBO<40 years had reduced white matter integrity across multiple regions in later-life. These results are important for females considering PBO for noncancerous conditions. Females with premenopausal bilateral oophorectomy (PBO)<40 years had lower FA versus referents. Females with PBO<40 years had higher MD in many regions versus referents. Adjusting for estrogen replacement therapy use did not attenuate results. Females with PBO 45-49 years also had some white matter changes versus referents.

Longitudinal associations of reproductive factors and exogeneous estrogens with neuroimaging biomarkers of Alzheimer's disease and cerebrovascular disease.

Female-specific reproductive factors and exogeneous estrogen use are associated with cognition in later life. However, the underlying mechanisms are not understood. The present study aimed to investigate the effect of reproductive factors on neuroimaging biomarkers of Alzheimer's disease (AD) and cerebrovascular pathologies. We evaluated 389 females (median age of 71.7 years) enrolled in the Mayo Clinic Study of Aging with reproductive history data and longitudinal magnetic resonance imaging (MRI) scans. We used linear mixed effect models to examine the associations between reproductive factors and changes in neuroimaging measures. Ever hormonal contraception (HC) use was longitudinally associated with higher fractional anisotropy across the corpus callosum, lower white matter hyperintensity (WMH) volume, and greater cortical thickness in an AD meta-region of interest (ROI). The initiation of menopausal hormone therapy (MHT)>5 years post menopause was associated with higher WMH volume. HC use and initiation of MHT>5 years post menopause were generally associated with neuroimaging biomarkers of cerebrovascular pathologies. Hormonal contraception use was associated with better brain white matter (WM) integrity. Initiation of menopausal hormone therapy>5 years post menopause was associated with worsening brain WM integrity. Hormonal contraception use was associated with greater cortical thickness. Ages at menarche and menopause and number of pregnancies were not associated with imaging measures. There were few associations between reproductive factors or exogenous estrogens and amyloid or tau PET.

Early-Life Circumstances and Racial Disparities in Cognition Among Older Adults in the US

ImportanceGiven the critical role of neurocognitive development in early life, understanding the association between early-life circumstances and racial disparities in cognition has important implications.ObjectiveTo assess whether racial differences in early-life circumstances are collectively and individually associated with racial disparities in late-life cognition among older adults in the US.Design, Setting, and ParticipantsThis cross-sectional study used comprehensive life history data from the Health and Retirement Study, a nationally representative survey of US adults 50 years or older. Data analyses were performed from August 9, 2022, to January 20, 2024.Main Outcomes and MeasuresRacial differences in early-life circumstances and racial disparities in late-life cognition were investigated using a Blinder-Oaxaca decomposition regression model. Cognitive outcomes, including cognitive score and cognitive impairment, were evaluated using the Telephone Interview for Cognitive Status. Early-life educational experiences were primary explanatory variables; early-life cohort, regional, financial, health, trauma, family relationship factors, and educational attainment were additional explanatory variables; demographic and genetic factors were covariates.ResultsThe study sample comprised 9015 participants; 1634 non-Hispanic Black (hereafter, Black) individuals (18.1%) and 7381 non-Hispanic White (hereafter, White) individuals (81.9%). Among Black participants, the mean (SD) age was 69.2 (9.2) years and 1094 (67.0%) were women. Among White participants, the mean (SD) age was 73.2 (10.1) years and 4410 (59.7%) were women. Cognitive scores (scale, 0-27) were significantly lower among Black participants (13.5 [95% CI, 13.3-13.7] points) than among White participants (15.8 [95% CI, 15.7-15.9] points), while the prevalence of cognitive impairment (cognitive score <12) was significantly higher among Black participants (33.6 [95% CI, 31.3-35.9] percentage points [ppt]) than among White participants (16.4 [95% CI, 15.6-17.2] ppt). Substantial racial differences were observed in early-life circumstances. Overall, differences in early-life circumstances were associated with 61.5% of the racial disparities in cognitive score (1.4 [95% CI, 0.88-2.0] points), and 82.3% of the racial disparities in cognitive impairment (14.2 [95% CI, 8.8-19.5] ppt), respectively. In multivariable analyses, early-life educational experiences were associated with 35.2% of the disparities in cognitive score and 48.6% in cognitive impairment. Notably, school racial segregation (all segregated schooling before college) was associated with 28.8% to 39.7% of the racial disparities in cognition. These findings were consistent in a series of sensitivity analyses.Conclusions and RelevanceThe findings of this cross-sectional study suggest that less favorable early-life circumstances are associated with clinically meaningful racial disparities in late-life cognition. Policies that improve educational equity have the potential to reduce racial disparities in cognition in older ages. Clinicians may leverage early-life circumstances to promote the screening, prevention, and interventions of cognitive impairment more efficiently, thereby promoting health equity.

Development and validation of the Michigan Chronic Disease Simulation Model (MICROSIM).

Strategies to prevent or delay Alzheimer's disease and related dementias (AD/ADRD) are urgently needed, and blood pressure (BP) management is a promising strategy. Yet the effects of different BP control strategies across the life course on AD/ADRD are unknown. Randomized trials may be infeasible due to prolonged follow-up and large sample sizes. Simulation analysis is a practical approach to estimating these effects using the best available existing data. However, existing simulation frameworks cannot estimate the effects of BP control on both dementia and cardiovascular disease. This manuscript describes the design principles, implementation details, and population-level validation of a novel population-health microsimulation framework, the MIchigan ChROnic Disease SIMulation (MICROSIM), for The Effect of Lower Blood Pressure over the Life Course on Late-life Cognition in Blacks, Hispanics, and Whites (BP-COG) study of the effect of BP levels over the life course on dementia and cardiovascular disease. MICROSIM is an agent-based Monte Carlo simulation designed using computer programming best practices. MICROSIM estimates annual vascular risk factor levels and transition probabilities in all-cause dementia, stroke, myocardial infarction, and mortality in a nationally representative sample of US adults 18+ using the National Health and Nutrition Examination Survey (NHANES). MICROSIM models changes in risk factors over time, cognition and dementia using changes from a pooled dataset of individual participant data from 6 US prospective cardiovascular cohort studies. Cardiovascular risks were estimated using a widely used risk model and BP treatment effects were derived from meta-analyses of randomized trials. MICROSIM is an extensible, open-source framework designed to estimate the population-level impact of different BP management strategies and reproduces US population-level estimates of BP and other vascular risk factors levels, their change over time, and incident all-cause dementia, stroke, myocardial infarction, and mortality.

GBA moderates cognitive reserve's effect on cognitive function in patients with Parkinson's disease.

Cognitive reserve (CR) involves an individual's ability to maintain cognitive vitality over their lifespan. Glucocerebrosidase (GBA) gene mutations contribute to additional effects on cognitive function in Parkinson's disease (PD) patients, but the interplay between GBA mutations and CR remains unclear. We investigated the interactions among CR, GBA, and diseases, aiming to examine whether the CR established at different stages interacts with specific genotypes to affect cognitive function. Three hundred and eighteen participants' CR indicators (i.e., education, occupation, and social function) and comprehensive neuropsychological function (i.e., tests for executive function, attention/working memory, visuospatial function, memory, and language) were evaluated. We found that CR established in a specific life stage influences the individual's cognitive function, particularly in PD, based on their distinct GBA rs9628662 genotypes. Attention/working memory and memory performance are affected by occupational complexity in midlife in PD patients with the GG genotype (q < 0.0001; q < 0.0001) and healthy adults with the T genotype (q = 0.0440; q < 0.0001). Language is influenced by early education and occupation, and the effects of occupation are also observed in PD patients with the GG genotype (q = 0.0040) and in healthy adults carrying the T genotype (q = 0.0040). CR, established at different life stages, can be influenced by the GBA rs9628662 genotype, impacting later-life cognition. Validating genotypes and incorporating genotype information when assessing cognitive reserve effects is crucial and can enhance targeted cognitive training.

The Mediating Effects of Education and Occupational Complexity Between Race and Longitudinal Change in Late Life Cognition in ACTIVE.

This study examined educational and occupational inequality as two aspects of social determinants of health that might mediate the longitudinal relationship between racialization and late life cognitive level and change. Participants were 2371 individuals racialized as Black and White from the ACTIVE study who provided occupational data. Data were analyzed from baseline and five assessments over 10-years using structural equation modeling. Black/White race served as the predictor, occupational complexity (OC) and years of education as mediators, and cognitive (memory, reasoning, and speed of processing) intercept, linear slope, and quadratic slope as the dependent variables. Black/White race showed significant indirect associations through education and OC on level of performance in cognition, linear change in reasoning and memory, and quadratic change in reasoning. Education and OC accounted for 11-16% of the association between race and cognitive level and represent modifiable social determinants of health that are associated with disparities in cognitive aging.

Late Life Cognitive Function Trajectory Among the Chinese Oldest-Old Population—A Machine Learning Approach

ABSTRACT Informed by the biopsychosocial framework, our study uses the Chinese Longitudinal Healthy Longevity Survey (CLHLS) dataset to examine cognitive function trajectories among the oldest-old (80+). Employing K-means clustering, we identified two latent groups: High Stability (HS) and Low Stability (LS). The HS group maintained satisfactory cognitive function, while the LS group exhibited consistently low function. Lasso regression revealed predictive factors, including socioeconomic status, biological conditions, mental health, lifestyle, psychological, and behavioral factors. This data-driven approach sheds light on cognitive aging patterns and informs policies for healthy aging. Our study pioneers non-parametric machine learning methods in this context.

Histories of neighborhood socioeconomic status contribute to race differences in later-life cognition.

Neighborhood characteristics are increasingly implicated in cognitive health disparities, but no research has investigated how the historical context of neighborhoods shapes these disparities. Four hundred sixty-four Black (55%) and White older adults (Mage=63.6) were drawn from the Michigan Cognitive Aging Project, a community-based, prospective study of older adults. Participants' addresses at baseline (2017-2020) were geocoded and linked to 2000-2017 measures of neighborhood socioeconomic status (NSES): disadvantage [NDis] and affluence [NAff]. Latent class growth analysis (LCGA) characterized 18 interpolated year trajectories of NSES across 1344 census tracts. Path analysis examined whether NSES trajectory classes mediated the association between race and a global cognition composite. LCGA identified three NDis and two NAff trajectory classes, which were associated with participant race. Only one NDis class was associated with cognition, and it mediated the association between the Black race and cognition. Disinvestment in neighborhoods may be particularly salient in race disparities in cognitive function. Race is implicated in the likelihood of living in more disadvantaged neighborhoods. Historical trends in neighborhood disadvantage are associated with cognitive function in older adulthood. Identifying patterns of neighborhood change may inform neighborhood-level interventions.

Racial Disparities in Cognitive Health Among Older Americans: The Role of Debt-Asset Profiles During Preretirement Age.

Low-cost debt can potentially enhance wealth and indirectly benefit health, yet Black Americans disproportionately lack this type of debt, which may constrain their ability to accumulate wealth throughout their lives and across generations. Our objectives are to develop a novel debt-asset measure, use it to quantify the Black-White differential in debt-asset profiles, and estimate its contribution to the racial gap in cognition. Using the Health and Retirement Study (1998-2020), we grouped individuals based on debt and asset information during the preretirement period of ages 55-61, including the absence of debt and the relative amount of debt compared to assets. Linear mixed models were used to examine the extent to which cognition in later life (ages 62-80) differs across these debt-asset profiles and its role in explaining the racial disparity in cognition. Compared with Whites, Blacks were more likely to fall into categories characterized by high debt-to-asset ratio (DAR) or limited asset ownership. Low-asset nonborrowers displayed the poorest cognition, followed closely by high-DAR borrowers. The Black-White differential in debt-asset profiles contributed to the racial gap in cognition. There were 2unfavorable debt-asset profiles: high debt relative to assets and little or no debt due to a lack of assets, which was more prevalent among Blacks than Whites. We discuss how institutional and structural racism shapes Black-White disparities in debt-asset profiles, such as limited access to borrowing opportunities, thereby contributing to health inequalities, including cognition.

Physical Activity and Cognitive Decline Among Older Adults

Physical activity is associated with the risk for cognitive decline, but much of the evidence in this domain comes from studies with short follow-ups, which is prone to reverse causation bias. To examine how length of follow-up, baseline age, physical activity amount, and study quality modify the longitudinal associations of physical activity with cognition. Observational studies of adults with a prospective follow-up of at least 1 year, a valid baseline cognitive measure or midlife cohort, and an estimate of the association of baseline physical activity and follow-up cognition were sought from PsycInfo, Scopus, CINAHL, Web of Science, SPORTDiscus, and PubMed, with the final search conducted on November 2, 2022. Two independent researchers screened titles with abstracts and full-text reports. Two reviewers independently assessed study quality and extracted data. Pooled estimates of association were calculated with random-effects meta-analyses. An extensive set of moderators, funnel plots, and scatter plots of physical activity amount were examined. This study is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Pooled estimates of the associations between physical activity and global cognition, as well as specific cognitive domains, were examined. A total of 104 studies with 341 471 participants were assessed. Analysis of binary outcomes included 45 studies with 102 452 individuals, analysis of follow-up global cognition included 14 studies with 41 045 individuals, and analysis of change in global cognition included 25 studies with 67 463 individuals. Physical activity was associated with a decreased incidence of cognitive impairment or decline after correction for funnel plot asymmetry (pooled risk ratio, 0.97; 95% CI, 0.97-0.99), but there was no significant association in follow-ups longer than 10 years. Physical activity was associated with follow-up global cognition (standardized regression coefficient, 0.03; 95% CI, 0.02-0.03) and change in global cognition (standardized regression coefficient, 0.01; 95% CI, 0.01 to 0.02) from trim-and-fill analyses, with no clear dose-response or moderation by follow-up length, baseline age, study quality or adjustment for baseline cognition. The specific cognitive domains associated with physical activity were episodic memory (standardized regression coefficient, 0.03; 95% CI, 0.02-0.04) and verbal fluency (standardized regression coefficient, 0.05; 95% CI, 0.03-0.08). In this meta-analysis of the association of physical activity with cognitive decline, physical activity was associated with better late-life cognition, but the association was weak. However, even a weak association is important from a population health perspective.