Combined effects of particulate and gaseous pollutants on Alzheimer's disease-related brain imaging markers and...

The combined effects of various air pollutants on Alzheimer's disease (AD)-specific brain structural pathologies are poorly understood, and whether these effects lead to impairments in specific cognitive domains has not been determined. We examined the associations between exposure to air pollutant mixtures and subclinical AD-related brain imaging markers, and then assessed whether AD-specific cortical atrophy mediated the association between air pollution exposure and specific cognitive domains. This cross-sectional study included 649 adults without dementia (≥50 years) residing in 2 metropolitan and 2 small cities in the Republic of Korea, all of whom underwent brain magnetic resonance imaging scan and neuropsychological testing. The 5-year average concentrations of particulate and gaseous pollutants were estimated at participants' residential addresses. To estimate the combined effects of these pollutant mixtures, we applied Bayesian kernel machine regression (BKMR) to capture potential non-linearity and interaction effects, and quantile g-computation (QGcomp) to estimate overall mixture effects. We additionally performed partial least squares structural equation modeling to test mediation pathways via brain cortical atrophy in the association between air pollutant mixtures and cognitive domains. BKMR analysis indicated significant associations between air pollutant mixtures and AD-related imaging markers, while QGcomp analysis revealed associations with reduced whole-brain cortical thickness. NO₂ exhibited the most prominent effects on subclinical imaging markers. AD-specific cortical atrophy fully mediated the associations of air pollutant mixtures with language, visual memory, and frontal/executive functions, and partially mediated those with visuospatial function, with the greatest mediation effect observed for visuospatial function, followed by language, visual memory, and frontal/executive function. These findings suggest that exposure to air pollutant mixtures may be associated with AD-specific cortical atrophy and a subsequent decline in cognitive functions in dementia-free adults.