How Low Should We Go to Prevent Brain Aging Associated with Exposure to Ambient Fine Particles?

Abstract Background Late‐life exposure to PM 2.5 is a risk factor for Alzheimer’s disease (AD) and related dementias. Accelerated brain aging associated with PM 2.5 exposure likely takes place at preclinical stage. In Feb.2024, US EPA lowered the annual standard for fine particulate matter (PM 2.5 ) from 12‐ to 9‐µg/m 3 . Whether the new exposure standard is sufficient to protect the aging brain is unclear. Method This current study examined whether PM 2.5 ‐associated brain aging is present at lower‐level exposures. We used longitudinal data from older women (n = 421; aged 77.3±3.5) enrolled in the Women’s Health Initiative Memory Study MRI‐1 (2005‐6) and MRI‐2 (2009‐10), living at locations with PM 2.5 below 12‐µg/m 3 (including 130 complying with EPA’s new standard) and without MCI, dementia or stroke prior to MRI‐1. PM 2.5 exposures at residential locations were estimated as 3‐year annual averages prior to MRI‐1, based on validated regionalized universal kriging models. AD pattern similarity (AD‐PS) scores, developed by supervised machine learning and validated with ADNI data, were used to assess AD‐related neurodegeneration. Bilateral gray matter volumes of the hippocampus, amygdala, parahippocampal gyrus (PHG), and entorhinal cortex were summed to define the regional volume of medial temporal lobe (MTL). We used linear regressions to estimate exposure effects on 5‐year changes in the AD‐PS scores and atrophies of MTL and its subregions, adjusting for intracranial volume, sociodemographic, lifestyle, and clinical characteristics. Result During 5 years of follow‐up, on average AD‐PS scores increased by 0.16±0.15, while MTL volume shrank by 0.42±1.02 cm 3 . Among older women with PM 2.5 <12‐µg/m 3 , each 1‐µg/m 3 increment was associated with increased AD‐PS scores (β AD‐PS = 0.013, 95%CI = [0.003, 0.021], p<0.01) and additional MTL shrinkage (β MTL = ‐0.079, 95%CI = [‐0.138, ‐0.019], p = 0.01; primarily affecting PHG), equivalent to 3.0%‐3.6% higher dementia risks. PM 2.5 exposure < 9‐µg/m 3 remained significantly associated with progressive PHG atrophy (β PHG = ‐0.087, 95%CI = [‐0.169, ‐0.005], p = 0.04), but the associations with increased AD‐PS score or progressive MTL atrophy had less precise effect estimates. Further restricting the analyses to older women who remained cognitively normal at MRI‐2 did not materially change the results. Conclusion Our study supports EPA’s new decision to lower PM 2.5 standard, but could not rule out the possibility of neurotoxic effects on aging brain with PM 2.5 <9‐µg/m 3 .