PROJECT SUMMARY/ABSTRACT Alzheimer’s disease (AD) is a major public health burden that disproportionately affects women. Women in the U.S. have experienced structural barriers, which prevent them from accessing health enhancing opportunities and resources, that may have a negative impact on their AD risk. For Black women, the societal disadvantages associated with being a woman are further compounded by those associated with being Black. Little has been done to understand the link between these structural inequalities and sex/gender differences in AD. Differences between men and women are assumed to be primarily biological in nature (e.g., due to effects of sex-steroid hormones) and socially driven heterogeneity among women has been largely ignored. To move the field forward, researchers interested in sex/gender differences in AD must identify and understand the structural drivers of cognitive health inequalities between men and women. The scientific objective of this research plan is to determine whether structural determinants influence sex/gender inequalities in AD outcomes. This project applies an intersectionality approach that examines how multiple experiences of structural-level discrimination and inequality (i.e., structural sexism, structural racism) overlap and interact to produce disparate cognitive health outcomes among non-Latinx Black and White women and men. Aim 1 (K99) focuses on determining the extent to which state-level structural sexism and racism influences cognitive trajectories among sex/gender-by- race groups. Aim 2 (R00) proposes to investigate whether sex/gender inequalities in cognitive reserve varies across levels of structural sexism and racism exposure. This proposal leverages cognitive trajectory and AD- biomarker data from five cohort and nationally representative longitudinal studies: Washington Heights-Inwood Community Aging Project (WHICAP), Offspring study, Minority Aging Research Study (MARS), Health and Retirement Study (HRS), and Reasons for Geographic and Racial Differences in Stroke (REGARDS). State- level indicators of structural sexism and racism will be used. State-of-the-art statistical methods will be employed to examine intersectionality that have been previously used in public health research, but that have not yet been applied to longitudinal cognitive aging outcomes. This research plan is complemented by a training plan that builds on the candidate’s background in cognitive aging, health disparities, and advanced statistical methods and includes new training in (1) cutting-edge analytic intersectionality techniques, (2) measuring and modeling structural determinants of health, (3) sex/gender differences in AD-biomarkers, and (4) causal inference methods. The combined research and training plans will prepare the applicant for a successful independent research career focused on identifying macro-social and biological determinants of sex/gender inequalities in AD.

PROJECT NARRATIVE Alzheimer’s disease (AD) is a major public health burden that disproportionately affects women. Structural barriers that prevent women from accessing health enhancing opportunities and resources may be important drivers of AD risk. The proposed study will elucidate the structural determinants underlying sex/gender inequalities in AD and inform structural-level interventions to improve late-life cognitive health among women.