Association between late-life air pollution exposure and medial temporal lobe atrophy in older women

BackgroundAmbient air pollution exposures increase risk for Alzheimers 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. MethodTo 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 Womens Health Initiative Memory Study with two MRI brain scans (MRI-1: 2005-6; MRI-2: 2009-10; Mage 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 (PM2.5) and nitrogen dioxide (NO2) 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. ResultsOn average, MTL volume decreased by 0.53{+/-}1.00cm3 over 5 years. For each interquartile increase of PM2.5 (3.26{micro}g/m3) and NO2 (6.77ppb), adjusted MTL volume had greater shrinkage by 0.32cm3 (95%CI=[-0.43,-0.21]) and 0.12cm3 (95%CI=[-0.22,-0.01]), respectively. The exposure effects did not differ by APOE {varepsilon}4 genotype, sociodemographic, and cardiovascular risk factors, and remained among women with low-level PM2.5 exposure. Greater PHG atrophy was associated with higher PM2.5 (b=-0.24, 95%CI=[-0.29,-0.19]) and NO2 exposures (b=-0.09, 95%CI=[-0.14,-0.04]). Higher exposure to PM2.5 but not NO2 was also associated with greater ERC atrophy. Exposures were not associated with amygdala or hippocampal atrophy. ConclusionIn summary, higher late-life PM2.5 and NO2 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. HighlightsO_LIFirst longitudinal study on air pollution and medial temporal lobe (MTL) volume. C_LIO_LILate-life PM2.5 and NO2 associated with MTL atrophy over time in older women. C_LIO_LIHeterogeneous adverse effects were observed across different subregions of the MTL. C_LIO_LIResults not differ by APOE genotype, age, education, or cardiovascular risk factors. C_LIO_LIAdverse effects remained at low-level exposure compliant with regulatory standards. C_LI