Heterogeneity in the effect of type 2 diabetes on dementia incidence in a diverse cohort of Asian American and non-Latino White older adults.

Dementia incidence is lower among Asian Americans than Whites, despite higher prevalence of type 2 diabetes, a well-known dementia risk factor. Determinants of dementia, including type 2 diabetes, have rarely been studied in Asian Americans. We followed 4,846 Chinese, 4,129 Filipino, 2,784 Japanese, 820 South Asian, and 123,360 non-Latino White members of a California-based integrated healthcare delivery system from 2002-2020. We estimated dementia incidence rates by race/ethnicity and type 2 diabetes status, and fit Cox proportional hazards and Aalen additive hazards models for the effect of type 2 diabetes (assessed 5 years before baseline) on age of dementia diagnosis controlling for sex/gender, educational attainment, nativity, height, race/ethnicity, and a race/ethnicity*diabetes interaction. Type 2 diabetes was associated with higher dementia incidence in Whites (hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.40-1.52). Compared with Whites, the estimated effect of diabetes was larger in South Asians (2.26 [1.48-3.44]), slightly smaller in Chinese (1.32 [1.08-1.62]) and Filipino (1.31 [1.08-1.60]), and similar in Japanese (1.44 [1.15-1.81]) individuals. Heterogeneity in this association across Asian subgroups may be related to type 2 diabetes severity. Understanding this heterogeneity may inform prevention strategies to prevent dementia for all racial and ethnic groups.

Estimating dementia incidence in insured older Asian Americans and Pacific Islanders in California: an application of inverse odds of selection weights.

Literature shows heterogeneous age-standardized dementia incidence rates across US Asian American, Native Hawaiian, and Pacific Islanders (AANHPI), but no estimates of population-representative dementia incidence exist due to lack of AANHPI longitudinal probability samples. We compared harmonized characteristics between AANHPI Kaiser Permanente Northern California members (KPNC cohort) and the target population of AANHPI 60+ with private or Medicare insurance using the California Health Interview Survey. We used stabilized inverse odds of selection weights (sIOSW) to estimate ethnicity-specific crude and age-standardized dementia incidence rates and cumulative risk by age 90 in the target population. Differences between the KPNC cohort and target population varied by ethnicity. sIOSW eliminated most differences in larger ethnic groups; some differences remained in smaller groups. Estimated crude dementia incidence rates using sIOSW (versus unweighted) were similar in Chinese, Filipinos, Pacific Islanders and Vietnamese, and higher in Japanese, Koreans, and South Asians. Unweighted and weighted age-standardized incidence rates differed for South Asians. Unweighted and weighted cumulative risk were similar for all groups. We estimated the first population-representative dementia incidence rates and cumulative risk in AANHPI ethnic groups. We encountered some estimation problems and weighted estimates were imprecise, highlighting challenges using weighting to extend inferences to target populations.

How Generalizable Are Findings from a Community-Based Prospective Cohort Study? Extending Estimates from the Adult Changes in Thought Study to Its Source Population.

Background: The Adult Changes in Thought (ACT) study is a cohort of Kaiser Permanente Washington members ages 65+ that began in 1994. Objective: We wanted to know how well ACT participants represented all older adults in the region, and how well ACT findings on eye disease and its relationship with Alzheimer's disease generalized to all older adults in the Seattle Metropolitan Region. Methods: We used participation weights derived from pooling ACT and Behavioral Risk Factor Surveillance System (BRFSS) data to estimate prevalences of common eye diseases and their associations with Alzheimer's disease incidence. Cox proportional hazards models accounted for age, education, smoking, sex, and APOE genotype. Confidence intervals for weighted analyses were bootstrapped to account for error in estimating the weights. Results: ACT participants were fairly similar to older adults in the region. The largest differences were more self-reported current cholesterol medication use in BRFSS and higher proportions with low education in ACT. Incorporating the weights had little impact on prevalence estimates for age-related macular degeneration or glaucoma. Weighted estimates were slightly higher for diabetic retinopathy (weighted 5.7% (95% Confidence Interval 4.3, 7.1); unweighted 4.1% (3.6, 4.6)) and cataract history (weighted 51.8% (49.6, 54.3); unweighted 48.6% (47.3, 49.9)). The weighted hazard ratio for recent diabetic retinopathy diagnosis and Alzheimer's disease was 1.84 (0.34, 4.29), versus 1.32 (0.87, 2.00) in unweighted ACT. Conclusions: Most, but not all, associations were similar after participation weighting. Even in community-based cohorts, extending inferences to broader populations may benefit from evaluation with participation weights.

School racial composition, effect modification by caring teacher/staff presence, and mid/late-life depressive symptoms: findings from the Study of Healthy Aging among African Americans.

For Black students in the United States, attending schools with a higher proportion of White students is associated with worse mental and physical health outcomes in adolescence/early adulthood. No prior studies evaluate K-12 school racial composition and later-life mental health. In a cohort of Black adults ages 50+ in Northern California who retrospectively self-reported school racial composition for grades 1, 6, 9, and 12, we assessed the association between attending a school with mostly Black students vs. not and mid/late-life depressive symptoms (8-item PROMIS depression score, standardized to US adult population) using age-, sex/gender-, southern US birth-, and parental education-adjusted generalized estimating equations, and assessed effect modification by caring teacher/staff presence. Later-life depressive symptoms were lower among those who attended schools with mostly Black students in grades 1 and 6 (b=-0.12, 95% CI: -0.23, 0.00 and b=-0.11, 95% CI: -0.22, 0.00, respectively). In grade 6, this difference was larger for students without an adult at school who cared about them (b=-0.29, 95% CI: -0.51, -0.07 vs. b=-0.04, 95% CI: -0.17, 0.09). Among Black Americans, attending early school with mostly Black students may have later life mental health benefits; this protective association appears more important for students without caring teachers/staff.

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.

Considerations for Use of Blood-Based Biomarkers in Epidemiologic Dementia Research.

Dementia represents a growing public health burden with large social, racial, and ethnic disparities. The etiology of dementia is poorly understood, and the lack of robust biomarkers in diverse, population-representative samples is a barrier to moving dementia research forward. Existing biomarkers and other measures of pathology-derived from neuropathology, neuroimaging, and cerebrospinal fluid samples-are commonly collected from predominantly White and highly educated samples drawn from academic medical centers in urban settings. Blood-based biomarkers are noninvasive and less expensive, offering promise to expand our understanding of the pathophysiology of dementia, including in participants from historically excluded groups. Although largely not yet approved by the Food and Drug Administration or used in clinical settings, blood-based biomarkers are increasingly included in epidemiologic studies on dementia. Blood-based biomarkers in epidemiologic research may allow the field to more accurately understand the multifactorial etiology and sequence of events that characterize dementia-related pathophysiological changes. As blood-based dementia biomarkers continue to be developed and incorporated into research and practice, we outline considerations for using them in dementia epidemiology, and illustrate key concepts with Alzheimer's Disease Neuroimaging Initiative (2003-present) data. We focus on measurement, including both validity and reliability, and on the use of dementia blood-based biomarkers to promote equity in dementia research and cognitive aging. This article is part of a Special Collection on Mental Health.

Association of cancer history with structural brain aging markers of Alzheimer's disease and related dementias risk.

INTRODUCTION: Cancer survivors are less likely than comparably aged individuals without a cancer history to develop Alzheimer's disease and related dementias (ADRD). METHODS: In the UK Biobank, we investigated associations between cancer history and five structural magnetic resonance imaging (MRI) markers for ADRD risk, using linear mixed-effects models to assess differences in mean values and quantile regression to examine whether associations varied across the distribution of MRI markers. RESULTS: Cancer history was associated with smaller mean hippocampal volume (b = -19 mm3 , 95% CI = -36, -1) and lower mean cortical thickness in the Alzheimer's disease signature region (b = -0.004 mm, 95% CI = -0.007, -0.000). Quantile regressions indicated individuals most vulnerable to ADRD were more affected by cancer history. DISCUSSION: Some brain MRI markers associated with ADRD risk were elevated in adults with a history of cancer. The magnitude of the adverse associations varied across quantiles of neuroimaging markers, and the pattern suggests possible harmful associations for individuals already at high ADRD risk. HIGHLIGHTS: We found no evidence of an inverse association between cancer history and ADRD-related neurodegeneration. Cancer history was associated with smaller mean hippocampal volume and lower mean cortical thickness in the Alzheimer's disease signature region. Quantile regressions indicated individuals most vulnerable to ADRD were more affected by cancer history.

What is the association between adverse childhood experiences and late-life cognitive decline? Study of Healthy Aging in African Americans (STAR) cohort study.

OBJECTIVES: Adverse childhood experiences (ACEs) are associated with higher risk of chronic disease, but little is known about the association with late life cognitive decline. We examined the longitudinal association between ACEs and late-life cognitive decline in the Study of Healthy Aging in African Americans (STAR). DESIGN: Linear mixed models with random intercepts and slope examined the association of individual and composite ACEs with cognitive change adjusting for years from baseline (timescale), baseline age, sex, parental education, childhood socioeconomic status and childhood social support. Participants reported whether they had experienced nine types of ACEs. Executive function and verbal episodic memory were measured up to three times over a 3-year period using the Spanish and English Neuropsychological Assessment Scales. SETTINGS: Kaiser Permanente Northern California members living in the Bay Area. PARTICIPANTS: STAR is a cohort study of cognitive ageing launched in 2018 that has enrolled 764 black Americans ages ≥50 years (mean age=67.5; SD=8.5). RESULTS: Twenty-one per cent of participants reported no ACEs, 24% one ACE, 20% two ACEs, 17% three ACEs and 17% four or more ACEs. Compared with no ACEs, two ACEs (ß=0.117; 95% CI 0.052 to 0.182), three ACEs (ß=0.075; 95% CI 0.007 to 0.143) and four or more ACEs (ß=0.089; 95% CI 0.002 to 0.158) were associated with less decline in executive function. There were no significant associations between number of ACEs and baseline or longitudinal verbal episodic memory or between individual ACEs and executive function or verbal episodic memory. CONCLUSION: In this cohort of older black Americans, there was no association between ACEs and baseline cognition or cognitive change in verbal episodic memory; however, experiencing ≥ 2 ACEs was associated with less decline in executive function. These results may indicate that participants who survived to age 50+ and experienced ACEs may have cognitive resilience that warrants further investigation.

Metformin Cessation and Dementia Incidence.

Importance: Prior studies suggested that metformin may be associated with reduced dementia incidence, but associations may be confounded by disease severity and prescribing trends. Cessation of metformin therapy in people with diabetes typically occurs due to signs of kidney dysfunction but sometimes is due to less serious adverse effects associated with metformin. Objective: To investigate the association of terminating metformin treatment for reasons unrelated to kidney dysfunction with dementia incidence. Design, Setting, and Participants: This cohort study was conducted at Kaiser Permanente Northern California, a large integrated health care delivery system, among a cohort of metformin users born prior to 1955 without history of diagnosed kidney disease at metformin initiation. Dementia follow-up began with the implementation of electronic health records in 1996 and continued to 2020. Data were analyzed from November 2021 through September 2023. Exposures: A total of 12 220 early terminators, individuals who stopped metformin with normal estimated glomerular filtration rate (eGFR), were compared with routine metformin users, who had not yet terminated metformin treatment or had terminated (with or without restarting) after their first abnormal eGFR measurement. Early terminators were matched with routine users of the same age and gender who had diabetes for the same duration. Main outcomes and measures: The outcome of interest was all-cause incident dementia. Follow-up for early terminators and their matched routine users was started at age of termination for the early terminator. Survival models adjusted for sociodemographic characteristics and comorbidities at the time of metformin termination (or matched age). Mediation models with HbA1c level and insulin usage 1 and 5 years after termination tested whether changes in blood glucose or insulin usage explained associations between early termination of metformin and dementia incidence. Results: The final analytic sample consisted of 12 220 early terminators (5640 women [46.2%]; mean [SD] age at start of first metformin prescription, 59.4 [9.0] years) and 29 126 routine users (13 582 women [46.6%]; mean [SD] age at start of first metformin prescription, 61.1 [8.9] years). Early terminators had 1.21 times the hazard of dementia diagnosis compared with routine users (hazard ratio, 1.21; 95% CI, 1.12 to 1.30). In mediation analysis, contributions to this association by changes in HbA1c level or insulin use ranged from no contribution (0.00 years; 95% CI, -0.02 to 0.02 years) for insulin use at 5 years after termination to 0.07 years (95% CI, 0.02 to 0.13 years) for HbA1c level at 1 year after termination, suggesting that the association was largely independent of changes in HbA1c level and insulin usage. Conclusions and Relevance: In this study, terminating metformin treatment was associated with increased dementia incidence. This finding may have important implications for clinical treatment of adults with diabetes and provides additional evidence that metformin is associated with reduced dementia risk.

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.

Association between cancer and dementia risk in the UK Biobank: evidence of diagnostic bias.

Epidemiological studies have identified an inverse association between cancer and dementia. Underlying methodological biases have been postulated, yet no studies have systematically investigated the potential for each source of bias within a single dataset. We used the UK Biobank to compare estimates for the cancer-dementia association using different analytical specifications designed to sequentially address multiple sources of bias, including competing risk of death, selective survival, confounding bias, and diagnostic bias. We included 140,959 UK Biobank participants aged ≥ 55 without dementia before enrollment and with linked primary care data. We used cancer registry data to identify cancer cases prevalent before UK Biobank enrollment and incident cancer diagnosed after enrollment. We used Cox models to evaluate associations of prevalent and incident cancer with all-cause dementia, Alzheimer's disease (AD), and vascular dementia. We used time-varying models to evaluate diagnostic bias. Over a median follow-up of 12.3 years, 3,310 dementia cases were diagnosed. All-site incident cancer was positively associated with all-cause dementia incidence (hazard ratio [HR] = 1.14, 95% CI: 1.02-1.29), but prevalent cancer was not (HR = 1.04, 95% CI: 0.92-1.17). Results were similar for vascular dementia. AD was not associated with prevalent or incident cancer. Dementia diagnosis was substantially elevated in the first year after cancer diagnosis (HR = 1.83, 95% CI: 1.42-2.36), after which the association attenuated to null, suggesting diagnostic bias. Following a cancer diagnosis, health care utilization or cognitive consequences of diagnosis or treatment may increase chance of receiving a dementia diagnosis, creating potential diagnostic bias in electronic health records-based studies.

Comparison of Imputation Strategies for Incomplete Longitudinal Data in Life-Course Epidemiology.

Incomplete longitudinal data are common in life-course epidemiology and may induce bias leading to incorrect inference. Multiple imputation (MI) is increasingly preferred for handling missing data, but few studies explore MI-method performance and feasibility in real-data settings. We compared 3 MI methods using real data under 9 missing-data scenarios, representing combinations of 10%, 20%, and 30% missingness and missing completely at random, at random, and not at random. Using data from Health and Retirement Study (HRS) participants, we introduced record-level missingness to a sample of participants with complete data on depressive symptoms (1998-2008), mortality (2008-2018), and relevant covariates. We then imputed missing data using 3 MI methods (normal linear regression, predictive mean matching, variable-tailored specification), and fitted Cox proportional hazards models to estimate effects of 4 operationalizations of longitudinal depressive symptoms on mortality. We compared bias in hazard ratios, root mean square error, and computation time for each method. Bias was similar across MI methods, and results were consistent across operationalizations of the longitudinal exposure variable. However, our results suggest that predictive mean matching may be an appealing strategy for imputing life-course exposure data, given consistently low root mean square error, competitive computation times, and few implementation challenges.

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.

Education, incident cancer, and rate of memory decline in a national sample of US adults in mid-to-later-life.

INTRODUCTION: Middle-aged and older adults who develop cancer experience memory loss following diagnosis, but memory decline in the years before and after cancer diagnosis is slower compared to their cancer-free counterparts. Educational attainment strongly predicts memory function during aging, but it is unclear whether education protects against memory loss related to cancer incidence or modifies long-term memory trajectories in middle-aged and older cancer survivors. MATERIALS AND METHODS: Data were from 14,449 adults (3,248 with incident cancer, excluding non-melanoma skin cancer) aged 50+ in the population-based US Health and Retirement Study from 1998 to 2016. Memory was assessed every two years as a composite of immediate and delayed word recall tests and proxy assessments for impaired individuals. Memory scores all time points were standardized at to the baseline distribution. Using multivariate-adjusted linear mixed-effects models, we estimated rates of memory decline in the years before cancer diagnosis, shortly after diagnosis, and in the years after diagnosis. We compared rates of memory decline between incident cancer cases and age-matched cancer-free adults, overall and according to level of education (<12 years, "low"; 12 to <16 years, "intermediate"; ≥16 years, "high"). RESULTS: Incident cancer diagnoses were followed by short-term declines in memory averaging 0.06 standard deviation (SD) units (95% confidence interval [CI]: -0.084, -0.036). Those with low education experienced the strongest magnitude of short-term decline in memory after diagnosis (-0.10 SD units, 95% CI: -0.15, -0.05), but this estimate was not statistically significantly different from the short-term decline in memory experienced by those with high education (-0.04 SD units, 95% CI: -0.08, 0.01; p-value for education as an effect modifier = 0.15). In the years prior to and following an incident cancer diagnosis, higher educational attainment was associated with better memory, but it did not modify the difference in rate of long-term memory decline between cancer survivors and those who remained cancer-free. DISCUSSION: Education was associated with better memory function over time among both cancer survivors and cancer-free adults aged 50 and over. Low education may be associated with a stronger short-term decline in memory after a cancer diagnosis.

Association of Education With Dementia Incidence Stratified by Ethnicity and Nativity in a Cohort of Older Asian American Individuals.

Importance: High education protects against dementia, but returns on educational attainment may be different across sociodemographic groups owing to various social factors. Asian American individuals are a growing and diverse group, but little research has assessed dementia determinants in this population. Objective: To examine the association of education with dementia in a large cohort of Asian American individuals, stratifying by ethnicity and nativity. Design, Setting, and Participants: This cohort study used electronic health record (EHR) and survey data from the Research Program on Genes, Environment, and Health and the California Men's Health Study surveys (2002-2020). Data are from Kaiser Permanente Northern California, an integrated health care delivery system. This study used a volunteer sample who completed the surveys. Participants included Chinese, Filipino, and Japanese individuals who were aged 60 to less than 90 years without a dementia diagnosis in the EHR at the time of the survey (baseline) and who had 2 years of health plan coverage before baseline. Data analysis was performed from December 2021 to December 2022. Exposures: The main exposure was educational attainment (college degree or higher vs less than a college degree), and the main stratification variables were Asian ethnicity and nativity (born in the US or born outside the US). Main Outcomes and Measures: The primary outcome was incident dementia diagnosis in the EHR. Dementia incidence rates were estimated by ethnicity and nativity, and Cox proportional hazards and Aalen additive hazards models were fitted for the association of college degree or higher vs less than a college degree with time to dementia, adjusting for age (timescale), sex, nativity, and an interaction between nativity and college degree. Results: Among 14 749 individuals, the mean (SD) age at baseline was 70.6 (7.3) years, 8174 (55.4%) were female, and 6931 (47.0%) had attained a college degree. Overall, among individuals born in the US, those with a college degree had 12% lower dementia incidence (HR, 0.88; 95% CI, 0.75-1.03) compared with those without at least a college degree, although the confidence interval included the null. The HR for individuals born outside the US was 0.82 (95% CI, 0.72-0.92; P = .46 for the college degree by nativity interaction). The findings were similar across ethnicity and nativity groups except for Japanese individuals born outside the US. Conclusions and Relevance: These findings suggest that college degree attainment was associated with lower dementia incidence, with similar associations across nativity. More work is needed to understand determinants of dementia in Asian American individuals and to elucidate mechanisms linking educational attainment and dementia.

Neighborhood disadvantage and dementia incidence in a cohort of Asian American and non-Latino White older adults in Northern California.

INTRODUCTION: Some evidence suggests that neighborhood socioeconomic disadvantage is associated with dementia-related outcomes. However, prior research is predominantly among non-Latino Whites. METHODS: We evaluated the association between neighborhood disadvantage (Area Deprivation Index [ADI]) and dementia incidence in Asian American (n = 18,103) and non-Latino White (n = 149,385) members of a Northern California integrated health care delivery system aged 60 to 89 at baseline. Race/ethnicity-specific Cox proportional hazards models adjusted for individual-level age, sex, socioeconomic measures, and block group population density estimated hazard ratios (HRs) for dementia. RESULTS: Among non-Latino Whites, ADI was associated with dementia incidence (most vs. least disadvantaged ADI quintile HR = 1.09, 95% confidence interval [CI] = 1.02-1.15). Among Asian Americans, associations were close to null (e.g., most vs. least disadvantaged ADI quintile HR = 1.01, 95% CI = 0.85-1.21). DISCUSSION: ADI was associated with dementia incidence among non-Latino Whites but not Asian Americans. Understanding the potentially different mechanisms driving dementia incidence in these groups could inform dementia prevention efforts.

Sufficient component cause simulations: an underutilized epidemiologic teaching tool.

Simulation studies are a powerful and important tool in epidemiologic teaching, especially for understanding causal inference. Simulations using the sufficient component cause framework can provide students key insights about causal mechanisms and sources of bias, but are not commonly used. To make them more accessible, we aim to provide an introduction and tutorial on developing and using these simulations, including an overview of translation from directed acyclic graphs and potential outcomes to sufficient component causal models, and a summary of the simulation approach. Using the applied question of the impact of educational attainment on dementia, we offer simple simulation examples and accompanying code to illustrate sufficient component cause-based simulations for four common causal structures (causation, confounding, selection bias, and effect modification) often introduced early in epidemiologic training. We show how sufficient component cause-based simulations illuminate both the causal processes and the mechanisms through which bias occurs, which can help enhance student understanding of these causal structures and the distinctions between them. We conclude with a discussion of considerations for using sufficient component cause-based simulations as a teaching tool.

Accounting for lack of representation in dementia research: Generalizing KHANDLE study findings on the prevalence of cognitive impairment to the California older population.

INTRODUCTION: Most dementia studies are not population-representative; statistical tools can be applied to samples to obtain critically-needed population-representative estimates, but are not yet widely used. METHODS: We pooled data from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study and the California Behavioral Risk Factor Surveillance System (CA-BRFSS), a population-representative study. Using weights accounting for sociodemographic/health differences between KHANDLE and CA-BRFSS, we estimated cognitive impairment prevalence and age- and sex-adjusted racial/ethnic inequalities in California adults 65+ without prior dementia diagnosis. RESULTS: After weighting KHANDLE, the estimated cognitive impairment prevalence in California was 20.3% (95% confidence interval 17.8-23.0); unweighted prevalence was 24.8% (23.1%-26.6%). Inequalities (larger prevalences) were observed among Black and Asian groups versus whites. DISCUSSION: We used a novel statistical approach to estimate population-representative cognitive impairment prevalence and inequalities. Such statistical tools can help obtain population-representative estimates from existing studies and inform efforts to reduce racial/ethnic disparities.

The role of nativity in heterogeneous dementia incidence in a large cohort of three Asian American groups and white older adults in California.

INTRODUCTION: Literature shows lower dementia incidence in Asian American groups versus whites, varying by Asian ethnicity. One hypothesized driver is nativity differences (eg, healthy immigrant effect). METHODS: We followed a cohort of 6243 Chinese, 4879 Filipino, 3256 Japanese, and 141,158 white Kaiser Permanente Northern California members for incident dementia (2002 to 2020), estimating age-adjusted dementia incidence rates by ethnicity and nativity, and hazard ratios (HR) for nativity on dementia incidence using ethnicity-stratified age- and sex-adjusted Cox proportional hazards models. RESULTS: Dementia incidence appeared higher in foreign- versus US-born Filipinos (HR, 95% confidence interval: 1.39, 1.02 to 1.89); differences were small in Japanese (1.07, 0.88 to 1.30) and Chinese (1.07, 0.92 to 1.24). No nativity differences were observed among whites (1.00, 0.95 to 1.04). DISCUSSION: Nativity does not explain lower dementia incidence in Asian Americans versus whites, but may contribute to heterogeneity across Asian ethnicities. Future research should explore differential impacts of social and cardiometabolic factors.