The absolute and relative concentration-response patterns of exposure to ambient air pollutants and the risk of Alzheimer's disease

Background Existing literature lacks information on the relationship between exposure to ambient air contaminants and Alzheimer's disease (AD) risk represented by simultaneous assessment of absolute and relative concentration-response patterns. Objective This study quantifies fine particulate matter (PM 2.5 )-exposure and AD-risk relationships with detailed analyses of the role of methodologic limitations and sources of bias (e.g., population heterogeneity) and identifies notable subpopulation differences and subpopulations most vulnerable to PM 2.5 exposure. Methods Using Medicare and SEDAC data, we evaluated effects of PM 2.5 exposure on AD risk using absolute and relative concentration-response functions through, respectively, age-adjusted rates and Cox-model estimates by sex/race/ethnicity/exposure groups. Results Analyses demonstrated that chronic PM 2.5 exposure was significantly associated with increased AD risk, with substantial variation observed across sex and race/ethnicity-specific subgroups. Females showed higher absolute incidence, while males exhibited steeper relative risk increases with rising PM 2.5 concentrations. Native Americans, residing primarily in low-exposure areas, demonstrated the steepest rise in hazard with increasing PM 2.5 concentrations; Black and Asian subpopulations exhibited the lowest relative ratios. Nonlinearities were detected in exposure-response relationships. AD risk in Hispanics displayed notable geographic heterogeneity. Conclusions This study provides a background for evaluating health impacts of recent air-quality standards across the U.S. and their specific effects on AD risk in vulnerable subpopulation groups. Future research should employ more-flexible modeling techniques (e.g., spline-based or piecewise methods), integrate mechanistic studies, and utilize data on social determinants to further elucidate the biological and structural pathways linking PM 2.5 to AD diagnosis, explain observed disparities through associated risk factors, and identify causal factors mediating the relationship.