Racial and ethnic differences in the association between depressive symptoms and cognitive outcomes in older adults: Findings from KHANDLE and STAR.

INTRODUCTION: Depressive symptoms are associated with higher risk of dementia, but how they impact cognition in diverse populations is unclear. METHODS: Asian, Black, Latino, or White participants (n = 2227) in the Kaiser Healthy Aging and Diverse Life Experiences (age 65+) and the Study of Healthy Aging in African Americans (age 50+) underwent up to three waves of cognitive assessments over 4 years. Multilevel models stratified by race/ethnicity were used to examine whether depressive symptoms were associated with cognition or cognitive decline and whether associations differed by race/ethnicity. RESULTS: Higher depressive symptoms were associated with lower baseline verbal episodic memory scores (-0.06, 95% CI: -0.12, -0.01; -0.15, 95% CI: -0.25, -0.04), and faster decline annually in semantic memory (-0.04, 95% CI: -0.07, -0.01; -0.10, 95% CI: -0.15, -0.05) for Black and Latino participants. Depressive symptoms were associated with lower baseline but not decline in executive function. DISCUSSION: Depressive symptoms were associated with worse cognitive outcomes, with some evidence of heterogeneity across racial/ethnic groups. HIGHLIGHTS: We examined whether baseline depressive symptoms were differentially associated with domain-specific cognition or cognitive decline by race/ethnicity. Depressive symptoms were associated with worse cognitive scores for all racial/ethnic groups across different domains examined. Higher depressive symptoms were associated with faster cognitive decline for semantic memory for Black and Latino participants. The results suggest a particularly harmful association between depressive symptoms and cognition in certain racial/ethnic groups.

Association between social vulnerability and place of death during the first 2 years of COVID-19 in Massachusetts.

We investigated the relationship between individual-level social vulnerability and place of death during the infectious disease emergency of the COVID-19 pandemic in Massachusetts. Our research represents a unique contribution by matching individual-level death certificates with COVID-19 test data to analyse differences in distributions of place of death.

Spouses of individuals living with mild cognitive impairment or dementia in the United States: A descriptive, population-based study.

BACKGROUND: Little is known about the population of individuals who live with a spouse with cognitive impairment (CI) or dementia. METHODS: Using the US Health and Retirement Study, 2000 to 2018, we estimated the population of adults ≥ 50 years old co-residing with a spouse with probable CI/dementia. We described their socio-demographic and health characteristics and quantified socio-demographic inequities. RESULTS: Among community-dwelling adults ≥ 50 years old, 6% of women and 4% of men co-resided with a spouse with probable CI/dementia. Among those who were married/partnered, the prevalence of spousal dementia was greater for Black and Hispanic adults compared to their White counterparts, and for those with lower versus higher educational attainment. Among spouses, activities of daily living disability, depression, and past 2-year hospitalization was common. DISCUSSION: Millions of older adults, disproportionately Black and Hispanic people and people with lower levels of educational attainment, live with a spouse with CI while also facing their own major health challenges.

Postsecondary Education and Late-life Cognitive Outcomes Among Black and White Participants in the Project Talent Aging Study: Can Early-life Cognitive Skills Account for Educational Differences in Late-life Cognition?

BACKGROUND: Higher education consistently predicts improved late-life cognition. Racial differences in educational attainment likely contribute to inequities in dementia risk. However, few studies of education and cognition have controlled for prospectively measured early-life confounders or evaluated whether the education late-life cognition association is modified by race/ethnicity. METHODS: Among 2343 Black and White Project Talent Aging Study participants who completed telephone cognitive assessments, we evaluated whether the association between years of education and cognition (verbal fluency, memory/recall, attention, and a composite cognitive measure) differed by race, and whether these differences persisted when adjusting for childhood factors, including the cognitive ability. RESULTS: In fully adjusted linear regression models, each additional year of education was associated with higher composite cognitive scores for Black [ß=0.137; 95% confidence interval (CI)=0.068, 0.206] and White respondents (ß=0.056; CI=0.034, 0.078) with an interaction with race ( P =0.03). Associations between education and memory/recall among Black adults (ß=0.036; CI=-0.037, 0.109) and attention among White adults (ß=0.022; CI=-0.002, 0.046) were nonsignificant. However, there were significant race-education interactions for the composite ( P =0.03) and attention measures ( P <0.001) but not verbal fluency ( P =0.61) or memory/recall ( P =0.95). CONCLUSION: Education predicted better overall cognition for both Black and White adults, even with stringent control for prospectively measured early-life confounders.

Does a Cancer Diagnosis in Mid-to-Later Life Modify Racial Disparities in Memory Aging?

BACKGROUND: It is unknown whether an incident cancer diagnosis differentially impacts acute and long-term memory aging between older White and Black Americans. METHODS: Incident cancer diagnoses and memory (immediate and delayed recall, combined with proxy-reported memory) were assessed at biennial study interviews in the US Health and Retirement Study (N=14,235, 1998-2016). We used multivariable segmented linear mixed-effects models to evaluate the rate of change in standardized memory score (SD/decade) in the years before, acutely at the time of, and in the years following an incident cancer diagnosis, compared to cancer-free adults, by race. RESULTS: Black participants experienced faster memory decline than White participants (cancer-free group: -1.211 vs. -1.077; P<0.0001). An incident cancer diagnosis was associated with an acute memory drop in White, but not Black participants (-0.065 vs. 0.024; P<0.0001). However, White cancer survivors experienced slower memory decline than cancer-free White adults before and after diagnosis, but this memory advantage was not observed among Black cancer survivors. CONCLUSIONS: Racial disparities in memory aging are not modified by an incident cancer diagnosis. The acute cancer-related memory decline and long-term memory advantage experienced by White, but not Black, cancer survivors relative to cancer-free older adults, requires further investigation.

Association of Social Integration with Cognitive Status in a Multi-Ethnic Cohort: Results From the Kaiser Healthy Aging and Diverse Life Experiences Study.

We evaluated overall and race-specific relationships between social integration and cognition in older adults. Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) cohort participants included 1343 Asian, Black, Latino, or non-Latino White Kaiser Permanente Northern California members. We estimated the effect of social integration on verbal episodic memory, semantic memory, and executive function derived from the Spanish and English Neuropsychological Assessment (SENAS) Scales. Social integration scores included marital status; volunteer activity; and contact with children, relatives, friends, and confidants. We estimated covariate-adjusted linear mixed-effects models for baseline and 17-month follow-up cognition. Social integration was associated with higher baseline cognitive scores (average  ß = 0.066 (95% confidence interval: 0.040, 0.092)) overall and in each racial/ethnic group. The association did not vary by race/ethnicity. Social integration was not associated with the estimated rate of cognitive change. In this cohort, more social integration was similarly associated with better late-life cognition across racial/ethnic groups.

Tutorial on directed acyclic graphs.

Directed acyclic graphs (DAGs) are an intuitive yet rigorous tool to communicate about causal questions in clinical and epidemiologic research and inform study design and statistical analysis. DAGs are constructed to depict prior knowledge about biological and behavioral systems related to specific causal research questions. DAG components portray who receives treatment or experiences exposures; mechanisms by which treatments and exposures operate; and other factors that influence the outcome of interest or which persons are included in an analysis. Once assembled, DAGs - via a few simple rules - guide the researcher in identifying whether the causal effect of interest can be identified without bias and, if so, what must be done either in study design or data analysis to achieve this. Specifically, DAGs can identify variables that, if controlled for in the design or analysis phase, are sufficient to eliminate confounding and some forms of selection bias. DAGs also help recognize variables that, if controlled for, bias the analysis (e.g., mediators or factors influenced by both exposure and outcome). Finally, DAGs help researchers recognize insidious sources of bias introduced by selection of individuals into studies or failure to completely observe all individuals until study outcomes are reached. DAGs, however, are not infallible, largely owing to limitations in prior knowledge about the system in question. In such instances, several alternative DAGs are plausible, and researchers should assess whether results differ meaningfully across analyses guided by different DAGs and be forthright about uncertainty. DAGs are powerful tools to guide the conduct of clinical research.

Physical Performance and Cognition in a Diverse Cohort: Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study.

BACKGROUND: The authors assessed the cross-sectional association of physical function measures with cognition in the Kaiser Healthy Aging and Diverse Life Experiences Cohort. METHODS: Analyses included 1369 participants (24% Asian, 26% Black, 18% Latino, 32% White). Grip strength was measured using a hand-held dynamometer (kilograms) and gait speed was measured over a 4-m walk (seconds/meter). The Spanish and English Neuropsychological Assessment Scales was used to evaluate cognitive domains of executive function, semantic memory, and verbal episodic memory. Physical function measures (per SD) were associated with cognitive test z-scores in linear regression models adjusted for demographic, behavioral, and clinical factors. Racial/ethnic differences were tested using interaction terms and stratification. RESULTS: Stronger grip was associated with better executive function [ß=0.10 (95% confidence interval, 0.05-0.15)], semantic memory [ß=0.13 (0.09-0.18)] and verbal episodic memory [ß=0.07 (0.02-0.13)] with no racial/ethnic differences. Faster gait was associated with better executive function [ß=0.29 (0.22-0.36)], semantic memory [ß=0.23 (0.16-0.30)], and verbal episodic memory [ß=0.20 (0.13-0.27)]; however, the association between gait speed and executive function varied by race/ethnicity with the strongest associations in Asians and Whites. CONCLUSION: Across race/ethnicity, grip strength and gait speed were associated with cognition with racial/ethnic differences in the association of gait speed and executive function.

Do the Benefits of Educational Attainment for Late-life Cognition Differ by Racial/Ethnic Group?: Evidence for Heterogenous Treatment Effects in the Kaiser Healthy Aging and Diverse Life Experience (KHANDLE) Study.

INTRODUCTION: Educational attainment is associated with late-life cognitive performance and dementia; few studies have examined diverse racial/ethnic groups to assess whether the association differs by race/ethnicity. METHODS: We investigated whether the association between educational attainment and cognition differed between White, Black, Asian, and Latino participants in the Kaiser Healthy Aging and Diverse Life Experiences study (n=1348). Covariate-adjusted multivariable linear regression models examined domains of verbal episodic memory, semantic memory, and executive functioning. RESULTS: We observed significant effect heterogeneity by race/ethnicity only for verbal episodic memory (P=0.0198), for which any schooling between high school and college was beneficial for White, Asian, and Black participants, but not Latino participants. We found no evidence of heterogeneity for semantic memory or executive function. DISCUSSION: With the exception of Latino performance on verbal episodic memory, more education consistently predicted better cognitive scores to a similar extent across racial/ethnic groups, despite likely heterogenous educational and social experiences.

Gut Bacterial Diversity and Growth among Preschool Children in Burkina Faso.

There is a lack of empirical, prospective human data on the gut microbiome and its relationship with growth, especially in low- and middle-income countries. We prospectively assessed the association between gut microbial diversity and short-term growth in a cohort of preschool children in Burkina Faso to better characterize whether there is any evidence that changes in gut microbial diversity may affect growth. Data were obtained from a randomized controlled trial evaluating the effect of antibiotic administration on gut microbial diversity in preschool children. We followed up the enrolled children for 35 days, with anthropometric measurements at baseline and day 35 and microbial diversity measured at baseline and day 9 (analytic sample, N = 155). We estimated linear mixed-effects regression models with household random intercepts to assess the association of Simpson's and Shannon's alpha diversity with measures of change in anthropometry (e.g., ponderal growth since baseline) and absolute anthropometric measurements (e.g., day 35 weight). We did not find evidence that alpha gut microbial diversity was associated with growth or absolute anthropometric measurements after adjusting for confounding variables. Effect estimates were close to the null (P ≥ 0.15 for all fully adjusted comparisons), with the association between Simpson's alpha diversity and day 35 height (cm) farthest from the null (coefficient = -0.03, 95% CI: -0.07, 0.01). The change in gut microbial diversity also was not associated with the change in anthropometry in crude or adjusted models. Future research is needed to explore whether gut diversity has an impact on growth over a longer time period, in both healthy and malnourished children.

Elevated Depressive Symptoms and the Risk of Stroke among the Mexican Older Population.

BACKGROUND/OBJECTIVES: Several longitudinal studies in high-income countries suggest that depression increases stroke risk. However, few prior studies have evaluated this association in low- and middle-income countries (LMICs), where rapidly aging populations may have markedly different vascular risk profiles. DESIGN: Prospective cohort study. SETTING: The Mexican Health and Aging Study is a national population-based study of older adults in Mexico. PARTICIPANTS: A total of 10,693 Mexican adults aged 50 and older enrolled in 2001 with no history of prior stroke. MEASUREMENTS: Depressive symptoms were assessed with a modified 9-item Centers for Epidemiologic Studies Depression Scale (elevated depressive symptom cutoff ≥5) in 2001 and 2003. We evaluated associations between baseline and short-term (2-year) changes in elevated depressive symptoms (categorized as stable low, recently remitted, recent-onset, or stable high symptoms) with incident self-reported or next-of-kin reported doctor-diagnosed stroke through 2015 using Cox proportional hazards models and sensitivity analyses applying inverse probability weights. RESULTS: Over an average follow-up of 11.4 years (standard deviation = 4.2), 10,693 respondents reported 546 incident strokes. Individuals with elevated baseline depressive symptoms experienced a moderately higher hazard of incident stroke (hazard ratio [HR] = 1.13; 95% confidence interval [CI] = .95-1.36) compared with those without elevated baseline depressive symptoms. In analyses of short-term changes in elevated depressive symptoms (n = 8,808; 414 incident stokes), participants with recent-onset (HR = 1.38; 95% CI = 1.06-1.81) or stable high (HR = 1.42; 95% CI = 1.10-1.84) elevated depressive symptoms had a greater hazard of incident stroke compared to those with stable low/no depressive symptoms, whereas recently remitted (HR = 1.01; 95% CI = .74-1.37) symptoms was not associated with stroke hazard. CONCLUSION: Strategies to reduce depressive symptoms merit evaluation as approaches to prevent stroke in middle-income countries. Findings are similar to those in high-income countries but should be replicated in other LMICs.

Will biomarker-based diagnosis of Alzheimer's disease maximize scientific progress? Evaluating proposed diagnostic criteria.

A recently published framework for the diagnosis of Alzheimer's disease (AD) in research studies would allow diagnosis on the sole basis of two biomarkers (ß-amyloid and pathologic tau), even in people with no objective or subjective memory or cognitive changes. This revision will have substantial implications for future Alzheimer's research, and the changes should be rigorously evaluated before widespread adoption. We propose three principles for evaluating any revision to diagnostic frameworks for AD: (1) does the revision improve the validity of the diagnosis; (2) does the revision improve the reliability or reduce the expense of the diagnosis; and (3) will the revision foster innovative and rigorous research across populations. The new diagnostic framework is unlikely to achieve any of these goals. Instead, it has the potential to handicap future researchers, and slow progress towards identifying effective strategies to prevent or treat AD.