Outdoor Air Pollution, Perivascular Space Morphology, and Cognition in Preadolescence

Background Ambient air pollution exposure is associated with structural brain differences and poorer cognition in children; however, mechanisms of toxicity remain unclear. Perivascular spaces (PVSs), key for brain waste clearance, may play a role in the neurotoxicity caused by air pollution. This study explored associations between air pollution exposure, PVS morphology, and cognition in preadolescents.Methods We analyzed cross-sectional Adolescent Brain Cognitive Development (ABCD) Study data from 6949 9- to 10-year-old participants. Annual average exposures to fine particulate matter (PM2.5), ozone, nitrogen dioxide, and 15 PM2.5 components were estimated using spatiotemporal models mapped to residential addresses. PVS count and volume were derived from T1-weighted and T2-weighted magnetic resonance imaging, and cognition was estimated using NIH Toolbox scores. Linear mixed-effects models examined independent associations between air pollution, PVS, and cognition; weighted quantile sum regression assessed coexposure effects of PM2.5 mixtures.Results Linear models revealed that exposures to zinc (Zn), ammonium (NH4 +), and bromine were positively associated with PVS count in several regions. Higher PVS count in 5 key regions was associated with poorer cognitive performance across several NIH Toolbox domains. Higher calcium, Zn, and NH4 + exposures were associated with poorer cognition (false discovery rate-corrected p p 2.5 mixtures were associated with higher temporal and cingulate PVS counts and poorer working memory and crystallized intelligence (p Conclusions Outdoor air pollution was associated with higher PVS count and reduced cognition, suggesting that brain clearance may be a novel mechanism linking pollution to neurodevelopmental harm in preadolescents.