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

Article type: Research Article

Authors: Shaffer, Rachel M.^a | Li, Ge^{b; c; d} | Adar, Sara D.^e | Dirk Keene, C.^f | Latimer, Caitlin S.^f | Crane, Paul K.^g | Larson, Eric B.^{g; h} | Kaufman, Joel D.^{a; i} | Carone, Marco^j | Sheppard, Lianne^{a; j; *}

Affiliations: [a] Department of Environmental and Occupational Health Sciences, University of Washington School of Public Health, Seattle, WA, USA | [b] VA Northwest Network Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA | [c] Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA | [d] Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA | [e] Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA | [f] Division of Neuropathology, Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA | [g] School of Medicine, University of Washington, Seattle, WA, USA | [h] Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA | [i] Departments of Medicine and Epidemiology, University of Washington School of Public Health, Seattle, WA, USA | [j] Department of Biostatistics, University of Washington School of Public Health, Seattle, WA, USA

Correspondence: [*] Correspondence to: Lianne Sheppard, Hans J Rosling Center for Population Health, 3980 15th Ave NE, Box 351618, Seattle, WA 98195 1618, USA. E-mail: [email protected].

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

DOI: 10.3233/JAD-201005

Journal: Journal of Alzheimer's Disease, vol. 79, no. 4, pp. 1761-1773, 2021