Abstract
BACKGROUND: Ambient air pollution exposures increase risk for Alzheimer's disease (AD) and related dementias, possibly due to structural changes in the medial temporal lobe (MTL). However, existing MRI studies examining exposure effects on the MTL were cross-sectional and focused on the hippocampus, yielding mixed results. METHOD: To determine whether air pollution exposures were associated with MTL atrophy over time, we conducted a longitudinal study including 653 cognitively unimpaired community-dwelling older women from the Women's Health Initiative Memory Study with two MRI brain scans (MRI-1: 2005-6; MRI-2: 2009-10; M(age) at MRI-1=77.3±3.5years). Using regionalized universal kriging models, exposures at residential locations were estimated as 3-year annual averages of fine particulate matter (PM(2.5)) and nitrogen dioxide (NO(2)) prior to MRI-1. Bilateral gray matter volumes of the hippocampus, amygdala, parahippocampal gyrus (PHG), and entorhinal cortex (ERC) were summed to operationalize the MTL. We used linear regressions to estimate exposure effects on 5-year volume changes in the MTL and its subregions, adjusting for intracranial volume, sociodemographic, lifestyle, and clinical characteristics. RESULTS: On average, MTL volume decreased by 0.53±1.00cm(3) over 5 years. For each interquartile increase of PM(2.5) (3.26μg/m(3)) and NO(2) (6.77ppb), adjusted MTL volume had greater shrinkage by 0.32cm(3) (95%CI=[-0.43, -0.21]) and 0.12cm(3) (95%CI=[-0.22, -0.01]), respectively. The exposure effects did not differ by APOE ε4 genotype, sociodemographic, and cardiovascular risk factors, and remained among women with low-level PM(2.5) exposure. Greater PHG atrophy was associated with higher PM(2.5) (b=-0.24, 95%CI=[-0.29, -0.19]) and NO(2) exposures (b=-0.09, 95%CI=[-0.14, -0.04]). Higher exposure to PM(2.5) but not NO(2) was also associated with greater ERC atrophy. Exposures were not associated with amygdala or hippocampal atrophy. CONCLUSION: In summary, higher late-life PM(2.5) and NO(2) exposures were associated with greater MTL atrophy over time in cognitively unimpaired older women. The PHG and ERC - the MTL cortical subregions where AD neuropathologies likely begin, may be preferentially vulnerable to air pollution neurotoxicity.