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.

The Association Between Physical Activity and Cognition in a Racially/Ethnically Diverse Cohort of Older Adults: Results From the Kaiser Healthy Aging and Diverse Life Experiences Study.

OBJECTIVE: Most prior research on physical activity (PA) and cognition is based on predominantly white cohorts and focused on associations of PA with mean (average) cognition versus the distribution of cognition. Quantile regression offers a novel way to quantify how PA affects cognition across the entire distribution. METHODS: The Kaiser Healthy Aging and Diverse Life Experiences study includes 30% white, 19% black, 25% Asian, and 26% Latinx adults age 65+ living in Northern California (n = 1600). The frequency of light or heavy PA was summarized as 2 continuous variables. Outcomes were z-scored executive function, semantic memory, and verbal episodic memory. We tested associations of PA with mean cognition using linear regression and used quantile regression to estimate the association of PA with the 10th-90th percentiles of cognitive scores. RESULTS: Higher levels of PA were associated with higher mean semantic memory (b = 0.10; 95% CI: 0.06, 0.14) and executive function (b = 0.05; 95% CI: 0.01, 0.09). Associations of PA across all 3 cognitive domains were stronger at low quantiles of cognition. CONCLUSION: PA is associated with cognition in this racially/ethnically diverse sample and may have larger benefits for individuals with low cognitive scores, who are most vulnerable to dementia.

Evaluation of racial and ethnic heterogeneity in the associations of sleep quality and sleep apnea risk with cognitive function and cognitive decline.

INTRODUCTION: The prevalence of poor sleep quality and sleep apnea differs by race and ethnicity and may contribute to racial disparities in cognitive aging. We investigated whether sleep quality and sleep apnea risk were associated with cognitive function and decline and whether the associations differed by race/ethnicity. METHODS: Participants from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE; N = 1690; mean age: 75.7 years) study, a cohort of Asian, Black, Latino, and White participants, completed a modified Pittsburgh Sleep Quality Index assessing subjective sleep quality, latency, duration, disturbances, sleep medication use, and daytime dysfunction. Sleep apnea risk was measured by questions about snoring, tiredness, and whether apnea was observed. Executive function and verbal episodic memory were assessed at three time points over an average of 2.7 years with the Spanish and English Neuropsychological Assessment Scale. We fit linear mixed-effect models and stratified analyses by race/ethnicity. RESULTS: Higher sleep apnea risk was associated with faster declines in verbal episodic memory (ß^ sleep apnea = -0.02, 95% confidence interval [CI], -0.04, -0.001) but not in executive function. Poorer sleep quality was associated with lower levels of and faster decline in executive function but not in verbal episodic memory. Race/ethnicity modified these associations: compared to estimated effects among White participants, poorer global sleep quality (ß^ sleep*time = -0.02, 95% CI, -0.02, -0.01) was associated with larger effects on decline in executive function among Black participants. Estimated effects of some individual sleep quality components were also modified by race/ethnicity; for example, sleep medication use was associated with faster declines in executive function (ß^ sleep*time = -0.05, 95% CI, -0.07, -0.03) and verbal episodic memory ß^ sleep*time = -0.04, 95% CI, -0.07, -0.02) among Black participants compared to White participants. DISCUSSION: Observational evidence indicates sleep quality is a promising target for addressing racial/ethnic disparities in cognitive aging, especially among Black older adults. Highlights: Sleep apnea risk was associated with faster declines in verbal episodic memory but not executive function among all participants.Global sleep quality was associated with lower levels of and faster decline in executive function but not verbal episodic memory among all participants.Black older adults were particularly susceptible to the estimated adverse cognitive impacts of global sleep quality, particularly the use of sleep medication.

Unique Aspects of Hypertrophic Cardiomyopathy in Children.

Hypertrophic cardiomyopathy (HCM) is a primary heart muscle disease characterized by left ventricular hypertrophy that can be asymptomatic or with presentations that vary from left ventricular outflow tract obstruction, heart failure from diastolic dysfunction, arrhythmias, and/or sudden cardiac death. Children younger than 1 year of age tend to have worse outcomes and often have HCM secondary to inborn errors of metabolism or syndromes such as RASopathies. For children who survive or are diagnosed after 1 year of age, HCM outcomes are often favourable and similar to those seen in adults. This is because of sudden cardiac death risk stratification and medical and surgical innovations. Genetic testing and timely cardiac screening are paving the way for disease-modifying treatment as gene-specific therapies are being developed.

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.

Race, community disadvantage, and cognitive decline: Findings from KHANDLE and STAR.

INTRODUCTION: Community disadvantage is associated with late-life cognition. Few studies examine its contribution to racial disparities in cognition/cognitive change. METHODS: Inverse probability weighted models estimated expected mean differences in cognition/cognitive change attributed to residing in less advantaged communities, defined as cohort top quintile of Area Deprivation Indices (ADI): childhood 66-100; adulthood ADI 5-99). Interactions by race tested. RESULTS: More Black participants resided in less advantaged communities. Semantic memory would be lower if all participants had resided in less advantaged childhood (b = -0.16, 95% confidence interval [CI] = -0.30, -0.03) or adulthood (b = -0.14, 95% CI = -0.22, -0.04) communities. Race interactions indicated that, among Black participants, less advantaged childhood communities were associated with higher verbal episodic memory (interaction p-value = 0.007) and less advantaged adulthood communities were associated with lower semantic memory (interaction p-value = 0.002). DISCUSSION: Examining racial differences in levels of community advantage and late-life cognitive decline is a critical step toward unpacking community effects on cognitive disparities.

Symptomatic presentation influences outcomes in pediatric restrictive cardiomyopathy.

Introduction: Children with restrictive cardiomyopathy (RCM) traditionally have a poor prognosis, with most patients either dying or requiring heart transplantation within 2 years of diagnosis. The development of symptoms in RCM suggests advanced disease. However, as screening practices evolve and lead to diagnosis of early disease, identifying appropriate timing of transplant listing becomes increasingly important. In this context we compared outcomes of children with RCM presenting with clinical symptoms to those asymptomatic at initial presentation. Methods: This retrospective cohort study included 25 patients with RCM presenting to a quaternary care center between 2001 and 2018. Times to transplantation, death, and a composite outcome of adverse cardiac events (CPR, cardioversion, inotropic support, mechanical ventilation, mechanical support, or heart transplant) were compared between those symptomatic and asymptomatic at presentation. Results: At 2 years following diagnosis, patients asymptomatic at presentation had a significantly better transplant-free survival at 57% compared to 17% for symptomatic patients (p = 0.03). Those asymptomatic at diagnosis also had significantly improved cardiac event-free survival at 71% compared to symptomatic patients at 25% (p = 0.01). In multivariable analysis, cardiac symptoms at presentation remained an independent risk factor for heart-transplant or death [hazard ratio 5.17 (1.28-20.85), p = 0.02]. Conclusion: Patients with RCM who are symptomatic at time of diagnosis have significantly worse transplant-free survival and cardiac event-free survival. Given current practice variability in timing of transplant listing, the presence of any cardiac symptoms is an important negative prognostic marker and should prompt urgent transplant listing.

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.

Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study.

BACKGROUND AND OBJECTIVES: Studies on the association between proton pump inhibitor (PPI) use and dementia report mixed results and do not examine the impact of cumulative PPI use. We evaluated the associations between current and cumulative PPI use and risk of incident dementia in the Atherosclerosis Risk in Communities (ARIC) Study. METHODS: These analyses used participants from a community-based cohort (ARIC) from the time of enrollment (1987-1989) through 2017. PPI use was assessed through visual medication inventory at clinic visits 1 (1987-1989) to 5 (2011-2013) and reported annually in study phone calls (2006-2011). This study uses ARIC visit 5 as baseline because this was the first visit in which PPI use was common. PPI use was examined 2 ways: current use at visit 5 and duration of use before visit 5 (from visit 1 to 2011, exposure categories: 0 day, 1 day-2.8 years, 2.8-4.4 years, >4.4 years). The outcome was incident dementia after visit 5. Cox proportional hazard models were used, adjusted for demographics, comorbid conditions, and other medication use. RESULTS: A total of 5,712 dementia-free participants at visit 5 (mean age 75.4 ± 5.1 years; 22% Black race; 58% female) were included in our analysis. The median follow-up was 5.5 years. The minimum cumulative PPI use was 112 days, and the maximum use was 20.3 years. There were 585 cases of incident dementia identified during follow-up. Participants using PPIs at visit 5 were not at a significantly higher risk of developing dementia during subsequent follow-up than those not using PPIs (hazard ratio (HR): 1.1 [95% confidence interval (CI) 0.9-1.3]). Those who used PPIs for >4.4 cumulative years before visit 5 were at 33% higher risk of developing dementia during follow-up (HR: 1.3 [95% CI 1.0-1.8]) than those reporting no use. Associations were not significant for lesser durations of PPI use. DISCUSSION: Future studies are needed to understand possible pathways between cumulative PPI use and the development of dementia. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the use of prescribed PPIs for >4.4 years by individuals aged 45 years and older is associated with a higher incidence of newly diagnosed dementia.

Heart Failure with Recovered Ejection Fraction in Patients with Vinculin Loss-of-function Variants.

Predictors of myocardial recovery in heart failure (HF) are poorly understood. We explored if vinculin (VCL) variants are associated with myocardial recovery in dilated cardiomyopathy (DCM). Six infants with DCM with a VCL loss-of-function (LOF) variant were identified. Median age at diagnosis was 2 months, median LV ejection fraction was 24%, and median LV end-diastolic diameter z-score was 10.8. All patients received HF medications. Five patients (83%) showed normalization of LV function at a median age of 2.7 years. One patient progressed to end-stage HF requiring heart transplant. This case series identified a unique phenotype of HF with reduced ejection fraction at presentation that evolved to HF with recovered EF in over 80% of infant DCM cases with LOF VCL variants. These findings have prognostic implications for counseling and management of VCL-associated DCM and highlight a possible genetic basis for HF with recovered ejection fraction.

Riding the merry-go-round of racial disparities in ADRD research.

INTRODUCTION: With the rapid expansion of the aging population, the burden of Alzheimer's disease related dementias (ADRD) is anticipated to increase in racialized and minoritized groups who are at disproportionately higher risk. To date, research emphasis has been on further characterizing the existence of racial disparities in ADRD through comparisons to groups racialized as White that are assumed to be normative. Much of the literature on this comparison insinuates that racialized and minoritized groups experience poorer outcomes due to genetics, culture, and/or health behaviors. METHODS: This perspective shines a light on a category of ADRD research that employs ahistorical methodological approaches to describe racial disparities in ADRD that puts us on a merry-go-round of research with no benefits to society. METHODS: This commentary provides historical context for the use of race in ADRD research and justification for the study of structural racism. The commentary concludes with recommendations to guide future research.

Efficacy of partial spraying of SumiShield, Fludora Fusion and Actellic against wild populations of Anopheles gambiae s.l. in experimental huts in Tiassalé, Côte d'Ivoire.

From August 2020 to June 2021, we assessed the efficacy of SumiShield 50WG (clothianidin), Fludora Fusion 56.25WP-SB (mixture of clothianidin and deltamethrin) and Actellic 300CS (pirimiphos-methyl) in experimental huts when partially sprayed against wild, free-flying populations of Anopheles gambiae s.l. in Tiassalé, Côte d'Ivoire. A one-month baseline period of mosquito collections was conducted to determine mosquito density and resting behavior in unsprayed huts, after which two treatments of partial indoor residual spraying (IRS) were tested: spraying only the top half of walls + ceilings or only the bottom half of walls + ceilings. These were compared to fully sprayed applications using the three IRS insecticide formulations, during twenty nights per month of collection for nine consecutive months. Mortality was assessed at the time of collection, and after a 24 h holding period (Actellic) or up to 120 h (SumiShield and Fludora Fusion). Unsprayed huts were used as a negative control. The efficacy of each partially sprayed treatment of each insecticide was compared monthly to the fully sprayed huts over the study period with a non-inferiority margin set at 10%. The residual efficacy of each insecticide sprayed was also monitored. A total of 2197 Anopheles gambiae s.l. were collected during the baseline and 17,835 during the 9-month period after spraying. During baseline, 42.6% were collected on the bottom half versus 24.3% collected on the top half of the walls, and 33.1% on the ceilings. Over the nine-month post treatment period, 73.5% were collected on the bottom half of the wall, 11.6% collected on the top half and 14.8% on the ceilings. For Actellic, the mean mortality over the nine-month period was 88.5% [87.7, 89.3] for fully sprayed huts, 88.3% [85.1, 91.4] for bottom half + ceiling sprayed walls and 80.8% [74.5, 87.1] for the top half + ceiling sprayed huts. For Fludora Fusion an overall mean mortality of 85.6% [81.5, 89.7] was recorded for fully sprayed huts, 83.7% [82.9, 84.5] for bottom half + ceiling sprayed huts and 81.3% [79.6, 83.0] for the top half + ceiling sprayed huts. For SumiShield, the overall mean mortality was 86.7% [85.3, 88.1] for fully sprayed huts, 85.6% [85.4, 85.8] for the bottom half + ceiling sprayed huts and 76.9% [76.6, 77.3] for the top half + ceiling sprayed huts. For Fludora Fusion, both iterations of partial IRS were non-inferior to full spraying. However, for SumiShield and Actellic, this was true only for the huts with the bottom half + ceiling, reflecting the resting site preference of the local vectors. The results of this study suggest that partial spraying may be a way to reduce the cost of IRS without substantially compromising IRS efficacy.

Diversity of Studies on Neighborhood Greenspace and Brain Health by Racialized/Ethnic Group and Geographic Region: A Rapid Review.

Studies examining associations between greenspace and Alzheimer's disease and related dementia (ADRD) outcomes are rapidly on the rise, yet no known literature reviews have summarized the racialized/ethnic group and geographic variation of those published studies. This is a significant gap given the known disparities in both greenspace access and ADRD risk between racialized/ethnic groups and between developed versus developing countries. In this rapid literature review, we (1) describe the diversity of published greenspace-brain health studies with respect to racialized/ethnic groups and geographic regions; (2) determine the extent to which published studies have investigated racialized/ethnic group differences in associations; and (3) review methodological issues surrounding studies of racialized/ethnic group disparities in greenspace and brain health associations. Of the 57 papers meeting our inclusion criteria as of 4 March 2022, 21% (n = 12) explicitly identified and included individuals who were Black, Hispanic/Latinx, and/or Asian. Twenty-one percent of studies (n = 12) were conducted in developing countries (e.g., China, Dominican Republic, Mexico), and 7% (n = 4) examined racialized/ethnic group differences in greenspace-brain health associations. None of the studies were framed by health disparities, social/structural determinants of health, or related frameworks, despite the known differences in both greenspace availability/quality and dementia risk by racialized/ethnic group and geography. Studies are needed in developing countries and that directly investigate racialized/ethnic group disparities in greenspace-brain health associations to target and promote health equity.

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.

Association of Early Adulthood Hypertension and Blood Pressure Change With Late-Life Neuroimaging Biomarkers.

Importance: The association between hypertension developed before midlife and late-life brain health is understudied and, because of the cardioprotective benefits of estrogen before menopause, may differ by sex. Objective: To assess the association of early adulthood hypertension and blood pressure (BP) change with late-life neuroimaging biomarkers and examine potential sex differences. Design, Setting, and Participants: This cohort study used data from the Study of Healthy Aging in African Americans (STAR) and Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study, which were harmonized longitudinal cohorts of racially and ethnically diverse adults aged 50 years and older from the San Francisco Bay area and Sacramento Valley in California. The STAR was conducted from November 6, 2017, to November 5, 2021, and the KHANDLE study was conducted from April 27, 2017, to June 15, 2021. The current study included 427 participants from the KHANDLE and STAR studies who received health assessments between June 1, 1964, and March 31, 1985. Regional brain volumes and white matter (WM) integrity were measured via magnetic resonance imaging between June 1, 2017, and March 1, 2022. Exposures: Hypertension status (normotension, transition to hypertension, and hypertension) and BP change (last measure minus first measure) were assessed at 2 multiphasic health checkups (MHCs; 1964-1985) in early adulthood (ages 30-40 years). Main Outcomes and Measures: Regional brain volumes and WM integrity were measured using 3T magnetic resonance imaging and z standardized. General linear models adjusted for potential confounders (demographic characteristics and study [KHANDLE or STAR]) were used to assess the association of hypertension and BP change with neuroimaging biomarkers. Sex interactions were tested. Results: Among 427 participants, median (SD) ages were 28.9 (7.3) years at the first MHC, 40.3 (9.4) years at the last MHC, and 74.8 (8.0) years at neuroimaging. A total of 263 participants (61.6%) were female and 231 (54.1%) were Black. Overall, 191 participants (44.7%) had normotension, 68 (15.9%) transitioned to hypertension, and 168 (39.3%) had hypertension. Compared with participants who had normotension, those who had hypertension and those who transitioned to hypertension had smaller cerebral volumes (hypertension: ß = -0.26 [95% CI, -0.41 to -0.10]; transition to hypertension: ß = -0.23 [95% CI, -0.44 to -0.23]), with similar differences in cerebral gray matter volume (hypertension: ß = -0.32 [95% CI, -0.52 to -0.13]; transition to hypertension: ß = -0.30 [95% CI, -0.56 to -0.05]), frontal cortex volume (hypertension: ß = -0.43 [95% CI, -0.63 to -0.23]; transition to hypertension: ß = -0.27 [95% CI, -0.53 to 0]), and parietal cortex volume (hypertension: ß = -0.22 [95% CI, -0.42 to -0.02]; transition to hypertension: ß = -0.29 [95% CI, -0.56 to -0.02]). Participants with hypertension also had smaller hippocampal volume (ß = -0.22; 95% CI, -0.42 to -0.02), greater ventricular volumes (lateral ventricle: ß = 0.44 [95% CI, 0.25-0.63]; third ventricle: ß = 0.20 [95% CI, 0.01-0.39]), larger free water volume (ß = 0.35; 95% CI, 0.18-0.52), and lower fractional anisotropy (ß = -0.26; 95% CI, -0.45 to -0.08) than those who had normotension. Holding hypertension status constant, a 5-mm Hg increase in systolic BP was associated with smaller temporal cortex volume (ß = -0.03; 95% CI, -0.06 to -0.01), while a 5-mm Hg increase in diastolic BP was associated with smaller parietal cortex volume (ß = -0.06; 95% CI, -0.10 to -0.02). The negative association of hypertension and BP change with regional brain volumes appeared stronger in men than women for some regions. Conclusions and Relevance: In this cohort study, early adulthood hypertension and BP change were associated with late-life volumetric and WM differences implicated in neurodegeneration and dementia. Sex differences were observed for some brain regions whereby hypertension and increasing BP appeared more detrimental for men. These findings suggest that prevention and treatment of hypertension in early adulthood is important for late-life brain health, particularly among men.

The structural and social determinants of Alzheimer's disease related dementias.

INTRODUCTION: The projected growth of Alzheimer's disease (AD) and AD-related dementia (ADRD) cases by midcentury has expanded the research field and impelled new lines of inquiry into structural and social determinants of health (S/SDOH) as fundamental drivers of disparities in AD/ADRD. METHODS: In this review, we employ Bronfenbrenner's ecological systems theory as a framework to posit how S/SDOH impact AD/ADRD risk and outcomes. RESULTS: Bronfenbrenner defined the "macrosystem" as the realm of power (structural) systems that drive S/SDOH and that are the root cause of health disparities. These root causes have been discussed little to date in relation to AD/ADRD, and thus, macrosystem influences, such as racism, classism, sexism, and homophobia, are the emphasis in this paper. DISCUSSION: Under Bronfenbrenner's macrosystem framework, we highlight key quantitative and qualitative studies linking S/SDOH with AD/ADRD, identify scientific gaps in the literature, and propose guidance for future research. HIGHLIGHTS: Ecological systems theory links structural/social determinants to AD/ADRD. Structural/social determinants accrue and interact over the life course to impact AD/ADRD. Macrosystem is made up of societal norms, beliefs, values, and practices (e.g., laws). Most macro-level determinants have been understudied in the AD/ADRD literature.

Sex differences in associations between APOE ε2 and longitudinal cognitive decline.

INTRODUCTION: We examined whether sex modifies the association between APOE ε2 and cognitive decline in two independent samples. METHODS: We used observational data from cognitively unimpaired non-Hispanic White (NHW) and non-Hispanic Black (NHB) adults. Linear mixed models examined interactive associations of APOE genotype (ε2 or ε4 carrier vs. ε3/ε3) and sex on cognitive decline in NHW and NHB participants separately. RESULTS: In both Sample 1 (N = 9766) and Sample 2 (N = 915), sex modified the association between APOE ε2 and cognitive decline in NHW participants. Specifically, relative to APOE ε3/ε3, APOE ε2 protected against cognitive decline in men but not women. Among APOE ε2 carriers, men had slower decline than women. Among APOE ε3/ε3 carriers, cognitive trajectories did not differ between sexes. There were no sex-specific associations of APOE ε2 with cognition in NHB participants (N = 2010). DISCUSSION: In NHW adults, APOE ε2 may protect men but not women against cognitive decline. HIGHLIGHTS: We studied sex-specific apolipoprotein E (APOE) ε2 effects on cognitive decline. In non-Hispanic White (NHW) adults, APOE ε2 selectively protects men against decline. Among men, APOE ε2 was more protective than APOE ε3/ε3. In women, APOE ε2 was no more protective than APOE ε3/ε3. Among APOE ε2 carriers, men had slower decline than women. There were no sex-specific APOE ε2 effects in non-Hispanic Black (NHB) adults.

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.

Neighborhood socioeconomic status and segregation linked to cognitive decline.

Introduction: Few longitudinal studies have examined the joint impact of neighborhood segregation and neighborhood socioeconomic status (NSES) in cognitive decline over time. Methods: This study included non-Hispanic White (NHW, n = 209) and Black participants (n = 118) whose cognition was evaluated as part of an ongoing longitudinal study. Four distinct categories of segregation and NSES were evaluated for their association with cognitive outcomes (episodic memory, semantic memory, executive function, and spatial ability) using race-specific mixed-effects models. Results: Compared to Black participants living in higher segregation-lower NSES areas, Black participants living in lower segregation-lower NSES areas or higher segregation-higher NSES areas experienced slower decline in episodic memory over time. Compared to NHW participants living in higher segregation-lower NSES areas, NHWs living in lower segregation-higher NSES areas experienced faster decline in spatial ability. Discussion: Segregation and NSES are differentially associated with cognition depending on participant race. Further research is needed to replicate study results.

Evaluating interpersonal discrimination and depressive symptoms as partial mediators of the effects of education on cognition: Evidence from the Study of Healthy Aging in African Americans (STAR).

INTRODUCTION: Education is correlated with positive health outcomes, but associations are sometimes weaker among African Americans. The extent to which exposure to discrimination and depressive symptoms attenuates the education-cognition link has not been investigated. METHODS: Study of Healthy Aging in African Americans (STAR) participants (n = 764; average age 69 years) completed the Spanish and English Neuropsychological Assessment Scales. We assessed everyday and major lifetime discrimination and depressive symptoms as mediators of education effects on cognition using G-estimation with measurement error corrections. RESULTS: Education was correlated with greater major lifetime and everyday discrimination but lower depressive symptoms. Accounting for discrimination and depressive symptoms slightly reduced the estimated effect of education on cognition. The estimated total effect of graduate education (vs