Association of Long-Term Air Pollution Exposure with Dementia-Related Neuropathologies at Autopsy in a Community-Based Cohort

ObjectiveTo evaluate long-term antemortem exposure to four pollutants in relation to Alzheimers disease (AD), cerebrovascular, and other dementia-related neuropathologies, measured at autopsy. DesignRetrospective cohort study. SettingIndividual participant data from four Rush Alzheimers Disease Center (RADC) longitudinal cohort studies: Memory and Aging Project, Minority Aging Research Study, Rush Clinical Core, and Latino Core. The cohorts enrolled participants residing in Chicago, Illinois (USA), including its metropolitan area and suburbs, and in outlying areas of Illinois. Participants909 decedents from the four RADC cohorts who underwent brain autopsy. SettingRADC cohorts are drawn from northeastern Illinois (IL) and Chicago metropolitan, suburban, and outlying areas of IL. ParticipantsAll participants were aged >60 years at enrollment. Analyses included 909 decedents with air pollution exposure measures who underwent autopsies prior to 2020 (of 3,579 who enrolled by the end of 2019); all autopsies were from community-based cohorts. ExposuresExposure to fine particulate matter (PM2.5; particles <2.5 m in aerodynamic diameter), nitrogen dioxide (NO2), oxides of nitrogen (NOx; nitrous oxide and NO2 combined), and ground-level ozone (O3) during the five years preceding death. Exposures were estimated with validated models developed for both the conterminous USA and the Chicago metropolitan area. Main Outcomes and MeasuresTwelve dementia-related neuropathologies measured by a neuropathologist at autopsy: Alzheimers disease neuropathology (ADNC), {beta}-amyloid density, tau tangle density, cerebral arteriolosclerosis, cerebral atherosclerosis, cerebral amyloid angiopathy, chronic cerebral infarctions (microscopic and gross), hippocampal sclerosis, Lewy bodies and limbic predominant age-related TDP-43 encephalopathy (LATE-NC). ResultsExposure to PM2.5 and NO2, as measured using Chicago-specific models, were both associated with higher tau tangle density [mean difference per 2.5 {micro}g/m3 PM2.5 = 0.25 tangles/mm2, (95% confidence interval [CI], -0.05 to 0.56); mean difference per 5 ppb NO2 = 0.10 tangles/mm2, (95% CI -0.07 to 0.28)]. PM2.5 exposure was associated with higher prevalence of arteriolosclerosis [prevalence ratio (PR) per 2.5 {micro}g/m3 = 1.51 (95% CI, 1.02 to 2.24)]. Both PM2.5 and NOx exposure were associated with higher prevalence of cerebral atherosclerosis [PR per 2.5 {micro}g/m3 PM2.5 = 1.41 (95% CI, 0.93 to 2.13); PR per 5 ppb NOx = 1.10 (95% CI, 0.98 to 1.23)]. None of the exposures was clearly adversely associated with the other neuropathologic outcomes, including {beta}-amyloid density and ADNC. Conclusion and RelevanceHigher exposure to PM2.5 was associated with cerebral arteriolosclerosis and atherosclerosis at death, consistent with the known vascular toxicity of this pollutant.