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

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 (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.

Results: On average, MTL volume decreased by 0.53±1.00cm³ over 5 years. For each interquartile increase of PM_2.5 (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. 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 NO₂ exposures (b=-0.09, 95%CI=[-0.14, -0.04]). Higher exposure to PM_2.5 but not NO₂ 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 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.