Race/ethnicity and Environmental Stressors: POtential drivers of Dementia and stroke inequities RESPOnD

Excess risk for Alzheimer’s disease-related dementias (ADRD) persists among older Black and Latino adults. ADRD prevention research has focused on individual vascular risk factors, with less attention to ubiquitous and modifiable environmental stressors. Environmental stressors may not only determine who is exposed to

vascular risk factors but also how severely those risk factors increase ADRD risk.1 Black and Latino individuals experience lower access to green space, higher exposure to air pollution, noise, extreme heat, neighborhood deprivation and violence. Prior evidence examining each of these environmental factors suggest adverse

associations with vascular risk factors for ADRD. Yet, environmental stressors are experienced in combination, rather than in isolation. It is critical to evaluate the joint impact of multiple domains of environment exposures as features of the external exposome. Even less is known about the differential impact of environmental

stressors by race/ethnicity and whether these differences account for ADRD disparities. To address this significant gap, our long-term goal is to quantify the impact of combined environmental stressors on stroke and vascular risk factors for ADRD. We will leverage resources from 3 U.S cohorts with substantial racial and

ethnic diversity, with up to 20-years of follow-up. In these cohorts, we have individual-level and objectively assessed cognitive level, cognitive decline, and neuroimaging biomarkers of ADRD in older adulthood. We hypothesize that individuals exposed to higher environmental stressors (lower access to green space, higher

exposure to air pollution, noise, extreme heat, neighborhood deprivation and violence) will have higher ADRD risk in older adulthood (Aim 1), and vascular risk burden at midlife (45-64-years; Aim 2). We also hypothesize that the association between the environmental stressors with ADRD and vascular risk factors will vary among

race and ethnicity sub-groups, and that a large fraction of dementia cases in the US will be associated with combined influence of modifiable environmental stressors, especially for Black and Latino individuals (Aim 3). We will leverage massive exposure datasets, coupled with individual-level data and advanced statistical

methods, to overcome the limitations of prior studies and provide actionable evidence on ubiquitous modifiable environmental stressors. We will identify combinations of modifiable environmental stressors that may reduce racial and ethnic disparities in ADRD and vascular mechanisms of ADRD. Our findings will provide a

foundation to develop actionable items to prevent or mitigate ADRD inequities. The comprehensive multi- dimensional spatial datasets and approaches developed in this project will be applicable to other epidemiological studies that consider biological and behavioral pathways through which environmental stress

affects neurovascular health.