PM_2.5 Associated With Gray Matter Atrophy Reflecting Increased Alzheimer Risk in Older Women.

Abstract

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 disease (AD) using a community-dwelling cohort of women (age 70-89 years) with up to 2 brain MRI scans (MRI-1, 2005-2006; MRI-2, 2010-2011). AD pattern similarity (AD-PS) scores, developed by supervised machine learning and validated with MRI data from the Alzheimer's Disease Neuroimaging Initiative, were 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). Using participants' addresses and air monitoring data, we implemented 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 and 5-year standardized change), accounting for potential confounders and white matter lesion volumes. For 1,365 women 77.9 ± 3.7 years of age in 2005 to 2006, there was no association between PM_2.5 and baseline AD-PS score in cross-sectional analyses (β = -0.004; 95% confidence interval [CI] -0.019 to 0.011). 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 (n = 712, age 77.4 ± 3.5 years). This association remained after adjustment for sociodemographics, intracranial volume, lifestyle, clinical characteristics, and white matter lesions and was present with levels below US regulatory standards (<12 µg/m³). Late-life exposure to PM_2.5 is associated with increased neuroanatomic risk of AD, which may not be explained by available indicators of cerebrovascular damage.