Fine Particulate Matter and Dementia Incidence in the Adult Changes in Thought Study

BACKGROUND: Air pollution may be associated with elevated dementia risk. Prior research has limitations that may affect reliability, and no studies have evaluated this question in a population-based cohort of men and women in the United States. OBJECTIVES: We evaluated the association between time-varying, 10-y average fine particulate matter ([Formula: see text]) exposure and hazard of all-cause dementia. An additional goal was to understand how to adequately control for age and calendar-time-related confounding through choice of the time axis and covariate adjustment. METHODS: Using the Adult Changes in Thought (ACT) population-based prospective cohort study in Seattle, we linked spatiotemporal model-based [Formula: see text] exposures to participant addresses from 1978 to 2018. Dementia diagnoses were made using high-quality, standardized, consensus-based protocols at biennial follow-ups. We conducted multivariable Cox proportional hazards regression to evaluate the association between time-varying, 10-y average [Formula: see text] exposure and time to event in a model with age as the time axis, stratified by apolipoprotein E (APOE) genotype, and adjusted for sex, education, race, neighborhood median household income, and calendar time. Alternative models used calendar time as the time axis. RESULTS: We report 1,136 cases of incident dementia among 4,166 individuals with nonmissing APOE status. Mean [mean ± standard deviation (SD)] 10-y average [Formula: see text] was [Formula: see text]. Each [Formula: see text] increase in the moving average of 10-y [Formula: see text] was associated with a 16% greater hazard of all-cause dementia [1.16 (95% confidence interval: 1.03, 1.31)]. Results using calendar time as the time axis were similar. DISCUSSION: In this prospective cohort study with extensive exposure data and consensus-based outcome ascertainment, elevated long-term exposure to [Formula: see text] was associated with increased hazard of all-cause dementia. We found that optimal control of age and time confounding could be achieved through use of either age or calendar time as the time axis in our study. Our results strengthen evidence on the neurodegenerative effects of [Formula: see text]. https://doi.org/10.1289/EHP9018