Associations and biological pathways between joint exposure to ambient air pollutants and brain disorders: a...

A growing body of evidence suggests that air pollution is associated with an increased risk of brain disorders, yet evidence on combined exposure remains limited and mechanisms are unclear. Using UK Biobank data, we constructed a composite air pollution score (APS) by calculating a weighted sum of PM_2.5, PM_2.5-10, PM₁₀, NO_x, and NO₂ concentrations. Cox proportional hazards regression models were used to examine associations between APS and brain disorders. Due to temporal ambiguity that precluded causal inference, mediation analyses were exploratory, aiming to identify biomarkers along the air pollution-to-brain disorder pathway rather than to establish causality. After full adjustment, compared with the lowest APS quartile, the HRs (95% CIs) for brain disorders were 1.004 (0.975-1.035), 1.048 (1.017-1.080), and 1.043 (1.010-1.077) for the second, third, and fourth quartiles, respectively. Each increment of 12 units in APS (per interquartile range) elevated risks of brain disorders (HR = 1.022, 95% CI = 1.008-1.036), neurological disorders (HR = 1.036, 95% CI = 1.010-1.062), and psychiatric disorders (HR = 1.031, 95% CI = 1.013-1.049). Metabolites, erythrocyte-related biomarkers, and liver and renal biomarkers were identified as potential pathway markers. These findings identify potential targets for early detection and prevention of brain disorders and carry public health significance.