Ambient air pollutants as determinants of disparities in Alzheimer's disease and co-existing morbidity

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Abstract Ambient air contaminants have been associated with higher risk of Alzheimer's disease (AD), related dementia (ADRD), and cognitive impairment; however, how variations in air pollution levels contribute to geographic disparities in AD/ADRD risk and what mechanisms underlay these contributions remains unclear. The results of our parent grant showed that pre-existing arterial hypertension, diabetes mellitus, cerebrovascular, and chronic kidney diseases have a strong impact on racial disparities in AD/ADRD risk. These diseases in turn are associated with exposure to air contaminants, including particulate matter (PM2.5). The proposed one-year project is supplemental to Aim 3 of our parent grant. It will quantitatively evaluate the contributions of variations in PM2.5 levels to geographic disparities in AD/ADRD risk and survival via direct (exposure to PM2.5) and indirect (through the effects on co-existing diseases) mechanisms and identify age-, sex-, and race/ethnicity-specific populations at higher vulnerability to PM2.5 effects. The Aim of this project focuses on quantification of PM2.5 impacts and the role of co-existing diseases that are associated with higher AD risk on geographic disparities in AD/ADRD incidence and survival. The methods of causal mediation and decomposition analyses developed in our parent grant will be used to evaluate contributions of PM2.5 to disparities in AD/ADRD risk and patient survival and to identify the role co-existing diseases play in generating in such disparities. Traditional empiric and regression approaches, propensity-score based methods, and other methods of causal analysis will be used for quantifying the association between PM2.5 and AD/ADRD and to identify associated causal mechanisms. The Oaxaca-Blinder approach generalized for use of time-to-event data and the causal mediation analyses for binary mediators and time-to-event outcomes will be applied to explain the observed geographic disparities in terms of predictors. The expected outcome will provide quantitative information on the contribution of ambient PM2.5 to geographic disparities in AD/ADRD risk and survival in the U.S. population of older adults with specific focus on highly vulnerable population groups. This study will assess 1) if a small reduction of PM levels (that may not have visible impact on an individual level) can substantially reduce AD/ADRD risk on a population level; 2) if the levels of ambient air contaminants that are below the World Health Organization (WHO) standards contribute to increased risks of AD/ADRD; 3) which co-existing diseases contribute most to AD/ADRD risk through a PM2.5 - related pathway; and 4) how improving the air quality in specific geographic areas can reduce geographic disparities in AD/ADRD. The proposed research is relevant to the NIH/NIA mission and Strategic Directions for Research 2020-2025 on understanding health disparities related to aging and developing strategies to improve the health of older adults in diverse populations (Goal F).