Objective: To examine whether late-life exposure to PM_2.5 (particulate matter with aerodynamic diameters <2.5-µm) contributes to progressive brain atrophy predictive of Alzheimer’s disease (AD) using a community-dwelling cohort of women (aged 71-89) with up to two brain MRI scans (MRI-1: 2005-6; MRI-2: 2010-11).

Methods: AD pattern similarity (AD-PS) scores, developed by supervised machine learning and validated with MRI data from the AD Neuroimaging Initiative, was used to capture high-dimensional gray matter atrophy in brain areas vulnerable to AD (e.g., amygdala, hippocampus, parahippocampal gyrus, thalamus, inferior temporal lobe areas and midbrain). Based on participants’ addresses and air monitoring data, we employed a spatiotemporal model to estimate 3-year average exposure to PM_2.5 preceding MRI-1. General linear models were used to examine the association between PM_2.5 and AD-PS scores (baseline [n=1365] and 5-year standardized change [n=712]), accounting for potential confounders and white matter lesion volumes.

Results: There was no association between PM_2.5 and baseline AD-PS score in cross-sectional analyses. Longitudinally, each interquartile range increase of PM_2.5 (2.82-µg/m3) was associated with increased AD-PS scores during the follow-up, equivalent to a 24% (hazard ratio=1.24; 95% CI: 1.14, 1.34) increase in AD risk over 5-years. This association remained after adjustment for socio-demographics, intracranial volume, lifestyle, clinical characteristics, and white matter lesions, and was present with levels below US regulatory standards (<12-µg/m3).

Conclusions: Late-life exposure to PM_2.5 is associated with increased neuroanatomical risk of AD, which may not be explained by available indicators of cerebrovascular damage.