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PM2.5 Associated With Gray Matter Atrophy Reflecting Increased Alzheimer Risk in Older Women
Diana Younan1, Xinhui Wang2, Ramon Casanova2
1From the Departments of Preventive Medicine (D.Y., J.C.C) and Neurology (X.W., A.J.P., H.C.C., J.-C.C.) and the Center for Economic and Social Research (M.G.), University of Southern California, Los Angeles; Departments of Biostatistics and Data Science (R.C., R.B., S.A.G., S.S., D.P.B., M.A.E.), Psychiatry and Behavioral Medicine (S.R.R.), Social Sciences & Health Policy (S.A.S., S.R.R.), and Neurology (B.C.S.), Wake Forest School of Medicine, Winston-Salem, NC; Laboratory of Behavioral Neuroscience (S.M.R.), National Institute on Aging, Baltimore, MD; Department of Environmental Sciences and Engineering (M.L.S., W.V.), University of North Carolina, Chapel Hill; Departments of Health Research and Policy (Epidemiology) and Neurology and Neurological Sciences (V.W.H.), Stanford University, CA; Department of Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Center for Cognitive Neurology, Department of Neurology (J.S.), New York University Grossman School of Medicine, New York. dyounan@usc.edu.
Objective:
To examine whether late-life exposure to PM2.5 (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).
Methods:
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 PM2.5 preceding MRI-1. General linear models were used to examine the association between PM2.5 and AD-PS scores (baseline and 5-year standardized change), accounting for potential confounders and white matter lesion volumes.
Results:
For 1,365 women 77.9 ± 3.7 years of age in 2005 to 2006, there was no association between PM2.5 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 PM2.5 (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).
Conclusions:
Late-life exposure to PM2.5 is associated with increased neuroanatomic risk of AD, which may not be explained by available indicators of cerebrovascular damage.
