Timing and level of educational attainment and late-life cognition in the KHANDLE study.

INTRODUCTION: The timing of educational attainment may modify its effects on late-life cognition, yet most studies evaluate education only at a single time point. METHODS: Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study cohort participants (N = 554) reported educational attainment (dichotomized at any college education) at two time points, and we classified them as having low, high, or later-life high educational attainment. Linear mixed-effects models estimated associations between educational attainment change groups and domain-specific cognitive outcomes (z-standardized). RESULTS: Compared to low educational attainment, high (ß= 0.59 SD units; 95% confidence interval [CI]: 0.39, 0.79) and later-life high educational attainment (ß = 0.22; 95% CI: 0.00, 0.44) were associated with higher executive function. Only high educational attainment was associated with higher verbal episodic memory (ß = 0.27; 95% CI: 0.06, 0.48). DISCUSSION: Level and timing of educational attainment are both associated with domain-specific cognition. A single assessment for educational attainment may inadequately characterize protective associations with late-life cognition. HIGHLIGHTS: Few studies have examined both level and timing of educational attainment on cognition. Marginalized populations are more likely to attain higher education in adulthood. Higher educational attainment in late life is also associated with higher cognition.

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

INTRODUCTION: School-based social support for Black students may mediate or modify the association between school segregation and late-life cognition. METHODS: 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. RESULTS: 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 (ß = -0.18 [-0.34, -0.02]) and semantic memory z-scores (ß = -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. DISCUSSION: Early-childhood school segregation was associated with poorer cognitive function. Sources of resilience within racialized educational experiences should be further evaluated to bridge inequities. HIGHLIGHTS: 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.

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.

HbA1c variability associated with dementia risk in people with type 2 diabetes.

INTRODUCTION: Although poor glycemic control is associated with dementia, it is unknown if variability in glycemic control, even in those with optimal glycosylated hemoglobin A1c (HbA1c) levels, increases dementia risk. METHODS: Among 171,964 people with type 2 diabetes, we evaluated the hazard of dementia association with long-term HbA1c variability using five operationalizations, including standard deviation (SD), adjusting for demographics and comorbidities. RESULTS: The mean baseline age was 61 years (48% women). Greater HbA1c SD was associated with greater dementia hazard (adjusted hazard ratio = 1.15 [95% confidence interval: 1.12, 1.17]). In stratified analyses, higher HbA1c SD quintiles were associated with greater dementia hazard among those with a mean HbA1c < 6% (P = 0.0004) or 6% to 8% (P < 0.0001) but not among those with mean HbA1c ≥ 8% (P = 0.42). DISCUSSION: Greater HbA1c variability is associated with greater dementia risk, even among those with HbA1c concentrations at ideal clinical targets. These findings add to the importance and clinical impact of recommendations to minimize glycemic variability. HIGHLIGHTS: We observed a cohort of 171,964 people with type 2 diabetes (mean age 61 years). This cohort was based in Northern California between 1996 and 2018. We examined the association between glycosylated hemoglobin A1c (HbA1c) variability and dementia risk. Greater HbA1c variability was associated with greater dementia hazard. This was most evident among those with normal-low mean HbA1c concentrations.

Association of primary lifetime occupational cognitive complexity and cognitive decline in a diverse cohort: Results from the KHANDLE study.

INTRODUCTION: Higher occupational complexity has been linked to favorable cognitive outcomes, but rarely examined in racially and ethnically diverse populations. METHODS: In a diverse cohort (n = 1536), linear mixed-effects models estimated associations between main lifetime occupational complexity and domain-specific cognitive decline (z-standardized). Occupational complexity with data, people, and things were classified using the Dictionary of Occupational Titles. RESULTS: For occupational complexity with data, highest tertile (vs. lowest) was associated with higher baseline executive function (ß = 0.11; 95% confidence interval [CI] 0.00-0.22) and slower annual rate of decline (ß = 0.03; 95% CI 0.01-0.06), and higher baseline semantic memory (ß = 0.14; 95% CI 0.04-0.25). Highest tertile of occupational complexity with people was associated with higher baseline executive function (ß = 0.29; 95% CI 0.18-0.40), verbal episodic memory (ß = 0.12; 95% CI 0.00-0.24), and semantic memory (ß = 0.23; 95% CI 0.12-0.34). DISCUSSION: In a diverse cohort, higher occupational complexity is associated with better cognition. Findings should be verified in larger cohorts. HIGHLIGHT: Few studies have examined associations of occupational complexity with cognition in diverse populations. Racial and ethnic minorities are disproportionately exposed to lower occupational complexity. Occupational complexity with data and people are associated with better cognition.

Pragmatic approaches to handling practice effects in longitudinal cognitive aging research.

INTRODUCTION: The challenge of accounting for practice effects (PEs) when modeling cognitive change was amplified by the COVID-19 pandemic, which introduced period and mode effects that may bias the estimation of cognitive trajectory. METHODS: In three Kaiser Permanente Northern California prospective cohorts, we compared predicted cognitive trajectories and the association of grip strength with cognitive decline using three approaches: (1) no acknowledgment of PE, (2) inclusion of a wave indicator, and (3) constraining PE based on a preliminary model (APM) fit using a subset of the data. RESULTS: APM-based correction for PEs based on balanced, pre-pandemic data, and with current age as the timescale produced the smallest discrepancy between within-person and between-person estimated age effects. Estimated associations between grip strength and cognitive decline were not sensitive to the approach used. DISCUSSION: Constraining PEs based on a preliminary model is a flexible, pragmatic approach allowing for meaningful interpretation of cognitive change. HIGHLIGHTS: The magnitude of practice effects (PEs) varied widely by study. When PEs were present, the three PE approaches resulted in divergent estimated age-related cognitive trajectories. Estimated age-related cognitive trajectories were sometimes implausible in models that did not account for PEs. The associations between grip strength and cognitive decline did not differ by the PE approach used. Constraining PEs based on estimates from a preliminary model allows for a meaningful interpretation of cognitive change.

Eight-Year Depressive Symptom Trajectories and Incident Stroke: A 10-Year Follow-Up of the HRS (Health and Retirement Study).

BACKGROUND: Evidence suggests a link between depressive symptoms and risk of subsequent stroke. However, most studies assess depressive symptoms at only one timepoint, with few examining this relationship using repeatedly measured depressive symptoms. This study aimed to examine the relationship between depressive symptom trajectories and risk of incident stroke. METHODS: This prospective cohort included 12 520 US individuals aged ≥50 years enrolled in the Health and Retirement Study, free of stroke at study baseline (1998). We used the 8-item Center for Epidemiologic Studies Depression scale to assess depressive symptoms (high defined as ≥3 symptoms; low <3 symptoms) at 4 consecutive, biennial timepoints from 1998 to 2004. We assigned individuals to 5 predefined trajectories based on their scores at each timepoint (consistently low, decreasing, fluctuating, increasing, and consistently high). Using self-reported doctors' diagnoses, we assessed incident stroke over a subsequent 10-year period from 2006 to 2016. Cox regression models estimated the association of depressive symptom trajectories with risk of incident stroke, adjusting for demographics, health behaviors, and health conditions. RESULTS: During follow-up, 1434 incident strokes occurred. Compared with individuals with consistently low symptoms, individuals with consistently high depressive symptoms (adjusted hazard ratio, 1.18 [95% CI, 1.02-1.36]), increasing symptoms (adjusted hazard ratio, 1.31 [95% CI, 1.10-1.57]), and fluctuating symptoms (adjusted hazard ratio, 1.21 [95% CI, 1.01-1.46]) all had higher hazards of stroke onset. Individuals in the decreasing symptom trajectory group did not show increased stroke risk. CONCLUSIONS: Depressive symptom trajectories characterized by high symptoms at multiple timepoints were associated with increased stroke risk. However, a trajectory with depressive symptoms that started high but decreased over time was not associated with higher stroke risk. Given the remitting-relapsing nature of depressive symptoms, it is important to understand the relationship between depressive symptoms and stroke risk over time through repeated assessments.

Social Determinants of Health at Older Ages: The Long Arm of Early and Middle Adulthood.

This article discusses the impacts of midlife social exposures on health in later life, especially for women. Of particular interest is the period of early adulthood. Social epidemiology and life course frameworks help reveal how workplace exposures, family dynamics, and public policies related to work and family shape opportunities in midlife that have long-run health consequences. This is especially important for American women, who have experienced health disadvantages over the last decades compared to women in similarly advanced industrialized countries. In most countries, single women are especially at high risk for poor health at older ages, and job strain can elevate future risks particularly for this subpopulation. Public policies such as maternity leave can reduce risks for poor mental health outcomes among working mothers 30 to 40 years after childbirth, suggesting that the period of early and middle adulthood may influence health trajectories well into old age.

Chronic loneliness and the risk of incident stroke in middle and late adulthood: a longitudinal cohort study of U.S. older adults.

Background: Loneliness has been implicated as a stroke risk factor, yet studies have examined loneliness at only one time point. The association of loneliness changes and risk of incident stroke remains understudied. Our aim was to examine the association of loneliness with incident stroke, particularly the role of loneliness chronicity. Methods: This prospective cohort study examined data from the Health and Retirement Study during 2006-2018. For analyses examining baseline loneliness only, we included U.S. adults aged 50 years or older and stroke-free at baseline and excluded individuals missing data on loneliness and those who experienced death at baseline. For analyses examining loneliness changes over two time points, we included those aged 50 years or older at baseline and stroke-free through the exposure measurement period. Individuals missing a loneliness scale measure or those who experienced death during the exposure measurement period were excluded. Loneliness was measured with the 3-item Revised UCLA Loneliness Scale. We constructed loneliness scores (range 3-9), dichotomized loneliness measures (high vs low using a >6 cutoff), and loneliness patterns across two time points (consistently low, remitting, recent onset, consistently high). Cox regression models estimated associations of baseline loneliness (N = 12,161) with incident stroke over a 10-12-year period, and loneliness change patterns (N = 8936) with incident stroke over a subsequent 6-8-year period, adjusting for demographics, health behaviors and health conditions. Findings: Higher loneliness scores at baseline were associated with incident stroke for continuous (hazard ratio [HR]: 1.05, 95% confidence interval [CI]: 1.01-1.08) and dichotomized (HR: 1.25, 95% CI: 1.06-1.47) loneliness measures, and persisted after adjustment for social isolation but not depressive symptoms. Only individuals with a consistently high loneliness pattern over time (vs consistently low) had significantly higher incident stroke risk (HR: 1.56, 95% CI: 1.11-2.18) after adjusting for depressive symptoms and social isolation. Interpretation: Chronic loneliness was associated with higher stroke risk independent of depressive symptoms or social isolation. Addressing loneliness may have an important role in stroke prevention, and repeated assessments of loneliness over time may help identify those particularly at risk. Funding: National Institute on Aging (NIA U01AG009740).

State-Level Indicators of Childhood Educational Quality and Incident Dementia in Older Black and White Adults.

Importance: Higher educational attainment is associated with reduced dementia risk, but the role of educational quality is understudied, presenting a major evidence gap, especially as it may contribute to racial inequities. Objective: To evaluate the association between state-level educational quality during childhood and dementia risk. Design, Setting, and Participants: This cohort study analyzed longitudinal data collected from January 1, 1997, through December 31, 2019 (23-year follow-up period). The sample comprised members of Kaiser Permanente Northern California (KPNC), a large integrated health care delivery system, who completed an optional survey during 1964-1972. Eligible individuals were US born; non-Hispanic Black or non-Hispanic White; aged 65 years or older as of January 1, 1996; were still alive; and did not have a dementia diagnosis or lapse in KPNC membership greater than 90 days between January 1 and December 31, 1996. Exposures: Historical state-level administrative indicators of school quality (school term length, student-teacher ratio, and attendance rates) linked to participants using birth state and birth year (with a 6-year lag) and divided into tertiles using the pooled sample. Main Outcomes and Measures: Dementia diagnoses from electronic health records between 1997 and 2019 were analyzed between March 1 and August 31, 2022. The associations of educational quality with incident dementia were estimated using Cox proportional hazards regression models. Results: Among 21 450 KPNC members who participated in the optional survey, individuals born before availability of educational quality records (n = 87) and missing educational attainment (n = 585) were excluded. The final analytic sample was 20 778 individuals (56.5% women, 43.5% men; mean [SD] age, 74.7 [6.5] years; 18.8% Black; 81.2% White; 41.0% with less than high school education). Among Black individuals, 76.2% to 86.1% (vs 20.8%-23.3% of White individuals) attended schools in states in the lowest educational quality tertiles. Highest (vs lowest) educational quality tertiles were associated with lower dementia risk (student-teacher ratio: hazard ratio [HR], 0.88 [95% CI, 0.83-0.94]; attendance rates: HR, 0.80 [95% CI, 0.73-0.88]; term length: HR, 0.79 [95% CI, 0.73-0.86]). Effect estimates did not differ by race and were not attenuated by adjustment for educational attainment. Conclusions and Relevance: In this cohort study, lower state-average educational quality was more common among Black individuals and associated with higher dementia risk. Differential investment in high-quality education due to structural racism may contribute to dementia disparities.

Rural residence across the life course and late-life cognitive decline in KHANDLE: A causal inference study.

Background: Modifiable risks for dementia are more prevalent in rural populations, yet there is a dearth of research examining life course rural residence on late-life cognitive decline. Methods: The association of rural residence and socioeconomic status (SES) in childhood and adulthood with late-life cognitive domains (verbal episodic memory, executive function, and semantic memory) and cognitive decline in the Kaiser Healthy Aging and Diverse Life Experiences cohort was estimated using marginal structural models with stabilized inverse probability weights. Results: After adjusting for time-varying SES, the estimated marginal effect of rural residence in childhood was harmful for both executive function (ß = -0.19, 95% confidence interval [CI] = -0.32, -0.06) and verbal episodic memory (ß = -0.22, 95% CI = -0.35, -0.08). Effects of adult rural residence were imprecisely estimated with beneficial point estimates for both executive function (ß = 0.19; 95% CI = -0.07, 0.44) and verbal episodic memory (ß = 0.24, 95% CI = -0.07, 0.55). Conclusions: Childhood rurality is associated with poorer late-life cognition independent of SES.

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, LatinX, or White participants (n=2,227) 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 four 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 LatinX participants. Depressive symptoms were associated with lower baseline but not decline in executive function. DISCUSSION: Depressive symptoms were associated with worse cognitive domains, with some evidence of heterogeneity across racial/ethnic groups.

Associations Between Marijuana Use and Involuntary Job Loss in the United States: Representative Longitudinal and Cross-Sectional Samples.

OBJECTIVE: To investigate whether marijuana use is associated with involuntary job loss. METHODS: Multivariable survey logistic analysis of longitudinal (2001 to 2002/2003 to 2004) and cross-sectional data (2012 to 2013) from National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). RESULTS: Marijuana use increased for all user groups with most workers who use marijuana using marijuana monthly (2.7% in 2001 to 2002 and 10.8% in 2012 to 2013). Past year marijuana users in 2001 to 2002 had higher odds of involuntary job loss in 2003 to 2004 (odds ratio [OR] 1.27; 95% confidence interval [CI] 1.13 to 1.41). Daily marijuana use is associated with higher odds of job loss in adjusted analyses using longitudinal (OR 2.18; 95%CI 1.71 to 2.77) and cross-sectional data (OR 1.40; 95%CI 1.06 to 1.86). Income significantly modifies these effects. CONCLUSIONS: Findings indicate that job loss may be an overlooked social cost of marijuana use for US workers. Future studies using an occupational health perspective are needed.