Relationships of Residential Distance to Major Traffic Roads with Dementia Incidence and Brain Structure Measures: Mediation Role of Air Pollution.

Background: Uncertainty exists regarding the operating pathways between near-roadway exposure and dementia incidence. We intend to examine relationships between proximity to major roadways with dementia incidence and brain MRI structure measures, and potential mediation roles of air and noise pollution. Methods: The cohort study was based on the UK Biobank. Baseline survey was conducted from 2006 to 2010, with linkage to electronic health records conducted for follow-up. Residential distance to major roadways was ascertained residential address postcode. A land use regression model was applied for estimating traffic-related air pollution at residence. Dementia incidence was ascertained using national administrative databases. Brain MRI measures were derived as image-derived phenotypes, including total brain, white matter, gray matter, and peripheral cortical gray matter. Results: We included 460,901 participants [mean (SD) age: 57.1 (8.1) years; men: 45.7%]. Compared with individuals living >1,000 m from major traffic roads, living ≤1,000 m was associated with a 13% to 14% higher dementia risk, accounting for 10% of dementia cases. Observed association between residential distance and dementia was substantially mediated by traffic-related air pollution, mainly nitrogen dioxide (proportion mediated: 63.6%; 95% CI, 27.0 to 89.2%) and PM 2.5 (60.9%, 26.8 to 87.0%). The shorter residential distance was associated with smaller volumes of brain structures, which was also mediated by traffic-related air pollutants. No significant mediation role was observed of noise pollution. Conclusions: The shorter residential distance to major roads was associated with elevated dementia incidence and smaller brain structure volumes, which was mainly mediated by traffic-related air pollution.