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

Significance

Identifying the culprits of PM _2.5 constituents that are most responsible for elevated risks of neurodegeneration is of paramount importance. We perform a US nationwide cohort study of the associations between PM _2.5 constituents and dementia and AD. Long-term exposure to PM _2.5 mass and major constituents, particularly from traffic and fossil fuel combustion sources, is significantly associated with elevated dementia or AD incidence. All constituents had largely linear concentration–response relationships at low concentrations for both end points, implying no safe level of air pollution for brain health. Using two independent exposure datasets allows us to examine the robustness of findings and thus strengthen the credibility of the evidence for the associations. Our results will facilitate targeted source-specific pollution control strategies.

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 (NO ₃ ⁻), sulfate (SO ₄ ²⁻), ammonium (NH ₄ ⁺), 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, SO ₄ ²⁻, and NH ₄ ⁺ for both end points (even after adjustments of other constituents), among which BC and SO ₄ 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 SO ₄ ²⁻, BC, and OM related to traffic and fossil fuel combustion might drive the observed associations.