Fine Particulate Matter and Markers of Alzheimer's Disease Neuropathology at Autopsy in a Community-Based Cohort

Abstract

Background: Evidence links fine particulate matter (PM2.5) to Alzheimer's disease (AD), but no community-based prospective cohort studies in older adults have evaluated the association between long-term exposure to PM2.5 and markers of AD neuropathology at autopsy.

Objective: Using a well-established autopsy cohort and new spatiotemporal predictions of air pollution, we evaluated associations of 10-year PM2.5 exposure prior to death with Braak stage, Consortium to Establish a Registry for AD (CERAD) score, and combined AD neuropathologic change (ABC score).

Methods: We used autopsy specimens (N = 832) from the Adult Changes in Thought (ACT) study, with enrollment ongoing since 1994. We assigned long-term exposure at residential address based on two-week average concentrations from a newly developed spatiotemporal model. To account for potential selection bias, we conducted inverse probability weighting. Adjusting for covariates with tiered models, we performed ordinal regression for Braak and CERAD and logistic regression for dichotomized ABC score.

Results: 10-year average (SD) PM2.5 from death across the autopsy cohort was 8.2 (1.9) μg/m3. Average age (SD) at death was 89 (7) years. Each 1μg/m3 increase in 10-year average PM2.5 prior to death was associated with a suggestive increase in the odds of worse neuropathology as indicated by CERAD score (OR: 1.35 (0.90, 1.90)) but a suggestive decreased odds of neuropathology as defined by the ABC score (OR: 0.79 (0.49, 1.19)). There was no association with Braak stage (OR: 0.99 (0.64, 1.47)).

Conclusion: We report inconclusive associations between PM2.5 and AD neuropathology at autopsy among a cohort where 94% of individuals experienced 10-year exposures below the current EPA standard. Prior studies of AD risk factors and AD neuropathology are similarly inconclusive, suggesting alternative mechanistic pathways for disease or residual confounding.

Keywords: Air pollution; Alzheimer’s disease; autopsy; dementia; neuropathology; particulate matter.

Figure 1:

10-year average PM_2.5 exposure by Year of Death in the Autopsy Cohort. In each boxplot, the middle line represents the median value; the edges of the box represent the 25^th and 75^th percentiles, and the whiskers extended up to 1.5 times the interquartile range (IQR). Points represent outlier observations outside this range.

Figure 2:. Association between 1 μg/m³ increase in 10-year average exposure to PM_2.5 and AD neuropathology at autopsy.

Box indicates a priori model. M1: sex, APOE-ε4 status, age at death; M2 (a priori): M1 + year of death, educational degree, neighborhood median household income; M3: M2 + race, smoking pack years, regular exercise; M4: M3 + BMI, diabetes, hypertension, and cardiovascular disease.