PROJECT SUMMARY ABSTRACT By 2050, racial disparities will persist among the projected 11 million adults with Alzheimer’s Disease and Related Dementias (AD/ADRD). Prior research links racial segregation to AD/ADRD, highlighting the need for structural solutions to mitigate the racially patterned cardiovascular disease (CVD) burden that accelerates AD/ADRD onset. Economic disinvestment prevents Black, poor, and Stroke Belt neighborhoods from investing in their local infrastructure, while systemic barriers lead to political disenfranchisement among the very historically excluded groups who would benefit most from effective health policy. However, it is not known how disinvestment and disenfranchisement—factors produced by structural racism—contribute to AD/ADRD disparities via excess CVD risk. This proposed K99/R00 harnesses the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study, Health and Retirement Study (HRS), and administrative claims from Medicare Beneficiaries. For my K99 phase, I will identify indicators of economic disinvestment and political disenfranchisement that worsen AD/ADRD trajectories and widen racial disparities in REGARDS and HRS. Then I will use these results to calculate the population attributable fraction of disinvestment and disenfranchisement on AD/ADRD among Medicare Beneficiaries. During my R00 phase, I will analyze the mediating role of CVD in associations of disinvestment or disenfranchisement and incident AD/ADRD in Medicare claims. Finally, I will utilize the CVD Policy Model to forecast nationwide community empowerment policies to reduce CVD risk factors for AD/ADRD up to three decades in the future. Building upon my foundation of data science, causal inference, and CVD epidemiology, my training plan consists of new knowledge domains: 1) AD/ADRD science, 2) spatial modeling, 3) Medicare claims, and 4) estimation of public health impact attainable with structural interventions. Based at the richly resourced University of California, San Francisco, I have assembled a team of distinguished mentors with the ideal combination of expertise to facilitate my success. The integrated science, training, mentorship, and professional development will prepare me for a faculty position at an R1 institution. My longterm goal is to become an independent investigator who develops interventions and policies to prevent AD/ADRD among low-income, Black, and Stroke Belt communities.

PROJECT NARRATIVE Limited evidence has operationalized how disinvestment or disenfranchisement —salient manifestations of structural racism— plausibly raise AD/ADRD risk via cardiovascular disease (CVD). The proposed research ultimately aims to simulate multilevel policies that reduce Black/White disparities in AD/ADRD.