Air pollution exposure is associated with widespread cortical thinning in cognitively unimpaired older women

Background Late‐life ambient air pollution exposures are associated with increased Alzheimer’s disease (AD) risk1. Cortical thinning in temporal areas vulnerable to AD is associated with memory decline, neuropathological changes, and increased AD risk. However, most neuroimaging studies on air pollution neurotoxicity analyzed volumetric indices that are not sensitive to early cortical changes, and focused on discrete regions of interest (ROI) selected a priori rather than taking an ROI approach across the whole brain. Therefore, the mechanisms linking exposures to early neuropathological processes in older age are poorly understood. Method We examined data from 1068 cognitively unimpaired women from the Women’s Health Initiative Memory Study who underwent neuroimaging in 2005‐6 (Meanage = 77.8±3.7). Long‐term residential exposures to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) were quantified as the 3‐year average of monthly estimates prior to MRI using spatiotemporal models with regionalized universal kriging. Brain scans were processed using FreeSurfer‐v.5.3.0 to estimate cortical thickness in 34 bilateral regions parcellated with the Desikan‐Killiany atlas. Exposure effects on AD‐vulnerable regions were assessed by calculating an AD signature (higher value representing thicker cortices) of surface‐area‐weighted thickness in the bilateral entorhinal, fusiform, inferior temporal, and middle temporal cortices2. We used linear mixed models to estimate exposure effects on standardized regional cortical thickness and the AD signature, adjusting for sociodemographic, lifestyle, and clinical characteristics, and a random effect for scanner manufacturer. Result After adjusting for covariates and multiple comparisons using the False discovery rate (FDR) method, higher exposures to PM2.5 and NO2 were associated with thinner cortices in at least 31 brain regions (FDR‐adjusted p’s