Historical social and environmental determinants of memory decline and dementia among U.S. older adults.

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PROJECT SUMMARY/ABSTRACT Incidence of Alzheimer’s disease and related dementias (ADRD) is 40–100% higher among Black compared with White Americans. A key reason for this disparity may include residence in segregated, socially disadvan- taged, and polluted communities. Extant studies suggest that community socioeconomic deprivation is related to decreased brain volume, Alzheimer’s neuropathology, and poor cognitive function, and that fine particulate matter (PM2.5) may contribute to neurodegeneration. Early-life exposures may be particularly important, as early-life community-level disadvantage and ambient air pollution could disrupt the accumulation of cognitive reserve, reduce cognitive resilience, and dampen social trajectories. Community-level social factors and air pollution often co-occur; thus, comprehensive understanding of how these factors operate independently and synergistically requires rigorous evaluation of both. Moreover, identifying the extent to which these factors modify underlying genetic risk—APOE-ε4 genotype and ADRD polygenic risk scores—would inform under- standing of the etiology of ADRD. The overall objective of this application is to evaluate the effects of early-life community-level social and environmental factors on late-life ADRD and the extent to which these factors con- tribute to racial disparities on ADRD in a nationally representative sample. The central hypothesis is that early- life community-level social factors and ambient air pollution have independent and synergistic effects on late- life brain health and ADRD disparities. This project leverages the recently completed data linkage between the 1940 census and the national Health and Retirement Study (HRS) (n≈8,700). Participants in the HRS were an average age of 69 years at first memory assessment between 1995–1998, so HRS includes up to 23 years of longitudinal data on memory scores and dementia, and a subsample also has genotype information. The central hypothesis will be tested in four specific aims among Black and White HRS participants: (1) Investigate the effects of early-life community- level social factors on late-life cognitive health; (2) Examine the effects of early-life ambient air pollution expo- sure on late-life cognitive health; (3) Estimate synergistic effects of early-life community-level social factors and air pollution exposure on late-life cognitive health; and (4) Evaluate the extent to which early-life community- level social factors and exposure to ambient air pollution modify effects of ADRD genetic risk on late-life cogni- tive health. The proposed research is innovative because it assesses joint early-life social and environmental community-level exposures, including via novel air pollution metrics and late-1930s redlining, for ADRD. The proposed work is expected to advance the field by providing new policy-relevant evidence on potential strate- gies to prevent ADRD and eliminate ADRD disparities.