Accelerated biological aging and brain structural alterations linking air pollution to dementia risk: a prospective cohort study

Objectives To examine the association of air pollution with dementia and brain structural alternations, and further to explore the mediating role of accelerated biological aging and brain atrophy in the air pollution-dementia association. Design A prospective cohort study. Setting and participants A total of 488,348 UK Biobank participants without dementia were included at baseline. Exposure Air pollution, including PM 2.5 , PM 10 , PM 2.5 absorbance, NO 2, and NO x . Measurements Cox proportional hazards regression models were used to evaluate the association between air pollution and incident dementia, while linear regression models were used to assess its associations with global and 80 regional brain structures. The mediating roles of biological aging acceleration (measured by Klemera-Doubal method Biological Age [KDM-BA] and PhenoAge) and brain structures in the air pollution-dementia association were evaluated using structural equation modeling (SEM). Results Compared to participants with the lowest tertile of air pollution exposure, those in the highest exposure group had higher risks of dementia (HR [95%CI]: 1.14 [1.08, 1.21] for PM 2.5 ; 1.09 [1.03, 1.16] for PM 10 ; 1.09 [1.03, 1.16] for PM 2.5 absorbance; 1.20 [1.13, 1.28] for NO 2 ; and 1.14 [1.08, 1.21] for NO X ). Air pollution exposure was inversely associated with global and several regional brain structural alterations. SEM revealed a consistent mediating pathway that integrates biological aging and brain structural alterations in the association between air pollution exposure and the risk of dementia. Conclusions Our findings support the association between air pollution and dementia, as well as a reduction in global and several regional brain volumes. Notably, biological age acceleration and brain atrophy mediated the air pollution-dementia association.