# Long-Term Urban Air Pollution Drives Multi-Stage Neuropsychiatric Disorder Trajectories: A Prospective Cohort Study

## TL;DR

Long-term exposure to air pollution is linked to increased risk and progression of neuropsychiatric disorders, with Alzheimer's disease showing the strongest association.

## Contribution

This study identifies multi-stage progression patterns of neuropsychiatric disorders linked to air pollution using a large cohort and multi-state modeling.

## Key findings

- PM2.5 and NOx exposure significantly increases the risk of transitioning to mood disorders (stage 1) with hazard ratios of 1.28 and 1.10 respectively.
- Alzheimer’s disease showed the strongest and most consistent association with air pollution across all stages of disorder progression.
- Subgroup analyses revealed higher vulnerability among females, younger individuals, and socioeconomically deprived populations.

## Abstract

Neuropsychiatric disorders constitute an escalating public health challenge worldwide, with growing evidence suggesting that environmental factors like air pollution may contribute substantially. This prospective cohort study investigated the associations between long-term exposure to fine particulate matter (PM2.5) and nitrogen oxides (NOx) and the progression of eight neuropsychiatric disorders among 502,356 UK Biobank participants. Using multi-state models, we analyzed three distinct trajectory stages: stage 1 (transition from baseline healthy status to PHQ-4-positive mood disorders), stage 2 (transition from baseline to ICD-10-diagnosed disorders), and stage 3 (progression from PHQ-4-positive status to clinical diagnosis). Nonlinear exposure–response relationships were subsequently characterized using restricted cubic spline (RCS) regression models. The findings indicated that exposure to both PM2.5 and NOx per IQR increase was strongly associated with stage 1, with a corresponding hazard ratio of 1.28 (95% CI: 1.27–1.30) and 1.10 (95% CI: 1.09–1.11). Across the three stages, the risk pattern evolved from being broadly significant to one characterized by disease-specific significance. Alzheimer’s disease was consistently identified as the condition with the strongest association and highest risk linked to air pollution. Specifically, hazard ratios across stages were as follows: 1.08–1.13 in stage 2 and 1.14–1.20 in stage 3 for PM2.5; and 1.04–1.05 in stage 2 and 1.05–1.10 in stage 3 for NOx. Subgroup analyses identified heightened vulnerability in females (particularly subjects with depression, Parkinson’s disease, and sleep disorders), younger individuals, and socioeconomically deprived populations. These findings underscore the importance of considering air pollution as a modifiable risk factor in the prevention of neuropsychiatric disorders.