Childhood adversity and late-life cognitive and brain health in a diverse cohort.

Introduction: Childhood adversity harms neurodevelopment. Literature on late-life brain health is limited, and findings on late-life cognition are mixed.

Methods: Pooling data from Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) and Study of Healthy Aging in African Americans (STAR) cohorts, we assessed the impact of childhood adversity (factor score from seven self-reported items) on (a) executive function and verbal memory decline using linear mixed effects models (n = 2447), (b) structural magnetic resonance imaging (MRI) using linear regression (n = 618), and (c) amyloid positron emission tomography (PET) using generalized linear models (n = 331), all adjusting for early-life demographic and socioeconomic confounders.

The link Between traumatic experiences and health in late life: challenges and opportunities for US-based longitudinal aging cohorts.

Trauma, defined as exposure to actual or threatened death, serious injury or sexual violence, is a pervasive, major public health challenge that disproportionately burdens socially disadvantaged groups and has known consequences for health outcomes in early and midlife. Despite plausible mechanisms by which trauma may also be a critically important risk factor for health outcomes in late life, there is presently a lack of literature evaluating the consequences of trauma on aging related health outcomes and inequities, such as dementia. In this commentary, we (a) discuss drivers of the paucity of epidemiological evidence on trauma and health outcomes in late life, namely a lack of available data, supported by detailed review of trauma measures, including interpersonal violence-a particularly common form of trauma-in seven established longitudinal aging cohort studies in the United States (US); (b) address four common concerns about the inclusion of trauma measures in cohort studies; and (c) suggest ways forward, including specific assessment tools to measure interpersonal violence after a structured review of the PhenX Toolkit, to facilitate critical research to understand the impact of trauma on outcomes in late life.

Methods for Extending Inferences From Observational Studies: Considering Causal Structures, Identification Assumptions, and Estimators.

Most prior work in quantitative approaches to generalizability and transportability emphasizes extending causal effect estimates from randomized trials to target populations. Extending findings from observational studies is also of scientific interest, and identifiability assumptions and estimation methods differ from randomized settings when there is selection on both the exposure and exposure-outcome mediators in combination with exposure-outcome confounders (and both confounders and mediators can modify exposure-outcome effects). We argue that this causal structure is common in observational studies, particularly in the field of life course epidemiology, for example, when extending estimates of the effect of an early-life exposure on a later-life outcome from a cohort enrolled in midlife or late life.

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.

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 among 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 4846 Chinese, 4129 Filipino, 2784 Japanese, 820 South Asian, and 123 360 non-Latino White members of a California-based integrated health-care delivery system from 2002 to 2020.

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.

School racial/ethnic composition, effect modification by caring teacher/staff presence, and mid-/late-life depressive symptoms: findings from the Study of Healthy Aging in 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. To our knowledge, no prior studies have evaluated the association between school racial/ethnic composition from kindergarten through grade 12 and later-life mental health. In a cohort of Black adults aged ≥50 years in Northern California who retrospectively reported (2017-2020) school racial/ethnic composition for grades 1, 6, 9, and 12, we assessed the association between attending a school with mostly Black students versus not and mid-/late-life depressive symptoms (8-item Patient-Reported Outcomes Measurement Information System (PROMIS) depression score, standardized to the 2000 US adult population) using age-, sex/gender-, southern US birth-, and parental education-adjusted generalized estimating equations, and assessed effect modification by the presence of a caring teacher/staff member.

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.

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.

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.

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.

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 mm , 95% CI = -36, -1) and lower mean cortical thickness in the Alzheimer's disease signature region (b = -0.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Cognitive impairment in racially/ethnically diverse older adults: Accounting for sources of diagnostic bias.

Introduction: The Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study enrolled Asian, Black, Latino, and White adults ages 65+ without prior dementia diagnosis (N = 1709). We evaluated the prevalence of cognitive impairment (mild cognitive impairment or dementia) accounting for potential biases.

Methods: A random subgroup (N = 541) received clinical evaluation and others were evaluated if they failed a cognitive screen.