Neurotoxicology. 2025 Dec 31:103378. doi: 10.1016/j.neuro.2025.103378. Online ahead of print.
ABSTRACT
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, previous MRI studies examining exposure effects on the MTL were cross-sectional and mostly focused on the hippocampus, yielding mixed results. We addressed these limitations using longitudinal data collected from 653 cognitively unimpaired community-dwelling women from the Women's Health Initiative Memory Study with two MRI scans (Mage at MRI-1=77.3±3.5years). We used linear regressions to examine relationships between 3-year annual average exposures to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) prior to MRI-1, and 5-year volume changes in the bilateral hippocampus, amygdala, parahippocampal gyrus (PHG), and entorhinal cortex (ERC), which were summed to operationalize MTL volume. Covariates included intracranial volume, sociodemographic, lifestyle, and clinical characteristics. For each interquartile increase of PM2.5 (3.26µg/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. Exposure effects did not differ by APOE ε4 genotype, sociodemographic, or cardiovascular risk factors. Subregionally, higher PM2.5 was associated with greater PHG and ERC atrophy, and higher NO2 was associated with greater PHG atrophy. Brain associations with PM2.5 were not significant among women residing in locations that met air quality standards (PM2.5<9µg/m3). Collectively, late-life PM2.5 and NO2 exposures were associated with greater MTL atrophy in cognitively unimpaired older women, especially in the PHG and ERC. These cortical MTL subregions are among the earliest affected by AD neuropathology - and may be preferentially vulnerable to air pollution neurotoxicity.
PMID:41482168 | DOI:10.1016/j.neuro.2025.103378