PROJECT ABSTRACT Exposure to outdoor air pollution (AP) is a risk factor for “accelerated” aging and Alzheimer’s disease, but very few studies have used neuroimaging to define the mechanistic underpinnings of these relationships. Existing studies are further limited by the confluence of biopsychosocial factors that have been shown to modify systemic health consequences of air pollution but have not been modeled in studies of the brain. Finally, the lack of geospatial diversity in existing studies of air pollution and aging brain health raises numerous questions about the generalizability of existing neuroimaging findings that predominantly come from high-income countries with “low” annual levels of exposure. This proposal is designed to address these challenges and limitations through a new environmental working group within the ENIGMA consortium – ENIGMA-Environment – consisting of 46 individual cohorts from 21 countries. In this proposal we leverage unprecedented geospatial diversity to 1. Identify and characterize adverse effects of NO2, PM2.5 mass, and PM2.5 components on structural and diffusion MRI metrics in older adults, 2) Define and explain interactions between NO2, PM2.5, and BPS factors that underlie neurodegeneration in older adults, and 3) Determine the impact of NO2 and PM2.5 on gray and white matter trajectories across the lifespan. Outcomes will provide the first translatable model of AP neurotoxicity in the context of BPS variables, providing a transformative framework for enhanced detection of individuals at risk for “accelerated” brain aging and AD.

PROJECT NARRATIVE Exposure to outdoor air pollution is a risk factor for “accelerated” aging and Alzheimer’s disease, but very few studies have used neuroimaging to define the mechanistic underpinnings of these relationships. This proposal will address this gap through a new environmental working group within the ENIGMA consortium. This will be the first international study to assess how AP 1) affects the structural integrity of the CAN in older adults across geographically diverse datasets, 2) interacts with biopsychosocial factors to influence heterogeneity in AD risk within the aging brain, and 3) influences brain integrity across the life course.