Incident dementia and long-term exposure to constituents of fine particle air pollution: A national cohort study in the United States

Abstract

Growing evidence suggests that fine particulate matter (PM_2.5) likely increases the risks of dementia, yet little is known about the relative contributions of different constituents. Here, we conducted a nationwide population-based cohort study (2000 to 2017) by integrating the Medicare Chronic Conditions Warehouse database and two independently sourced datasets of high-resolution PM_2.5 major chemical composition, including black carbon (BC), organic matter (OM), nitrate (NO₃^-), sulfate (SO₄^2-), ammonium (NH₄⁺), and soil dust (DUST). To investigate the impact of long-term exposure to PM_2.5 constituents on incident all-cause dementia and Alzheimer's disease (AD), hazard ratios for dementia and AD were estimated using Cox proportional hazards models, and penalized splines were used to evaluate potential nonlinear concentration-response (C-R) relationships. Results using two exposure datasets consistently indicated higher rates of incident dementia and AD for an increased exposure to PM_2.5 and its major constituents. An interquartile range increase in PM_2.5 mass was associated with a 6 to 7% increase in dementia incidence and a 9% increase in AD incidence. For different PM_2.5 constituents, associations remained significant for BC, OM, SO₄^2-, and NH₄⁺ for both end points (even after adjustments of other constituents), among which BC and SO₄^2- showed the strongest associations. All constituents had largely linear C-R relationships in the low exposure range, but most tailed off at higher exposure concentrations. Our findings suggest that long-term exposure to PM_2.5 is significantly associated with higher rates of incident dementia and AD and that SO₄^2-, BC, and OM related to traffic and fossil fuel combustion might drive the observed associations.