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.

Keywords: Alzheimer’s disease; PM2.5 constituents; air pollution; dementia; epidemiology.

Fig. 1.

Nationwide occurrences of first dementia events (A) and first Alzheimer’s disease events (B) per 100,000 Medicare beneficiaries across the contiguous United States (2000 to 2017), with a 3-y clean period considered.

Fig. 2.

Average concentrations of PM_2.5 major constituents (µg/m³), respectively derived from exposure I [van Donkelaar et al. (11)] (A) and exposure II [Amini et al. (12)] (B) across the contiguous United States from 2000 to 2017.

Fig. 3.

Hazard ratios of (A) dementia or (B) Alzheimer’s disease (AD) associated with per IQR or per 1 µg/m³ increase in annual mean concentration of each PM_2.5 major constituent, respectively, including BC, OM, soil dust (DUST), NO₃⁻, SO₄²⁻, and NH₄⁺. The dotted lines stand for the corresponding results for PM_2.5 mass. The estimated hazard ratios were obtained from single-constituent models, and error bars stand for the 95% CIs. The light and dark colors are used to distinguish air pollutants derived from two exposure models, with the light one indicating exposure I data (11) and the dark one indicating exposure II data (12). The corresponding hazard ratio values could be found in SI Appendix, Tables S3 and S4 (Model 1).

Fig. 4.

The concentration–response curves for each PM_2.5 constituent and dementia (A) and Alzheimer’s disease (B). The concentration–response curves, derived from the single-constituent models, are shown for the concentration ranges between 0.5th and 99.5th percentiles of the pollutants, i.e., with 1% poorly constrained extreme values excluded. For each constituent, the top panel used exposure I data (11) and the bottom panel used exposure II data (12).