Associations of long-term exposure to low-level PM2.5 and brain disorders in 260,922 middle-aged and older adults

Long-term exposure to high-level ambient PM2.5 was associated with increased risks of brain disorders, while the associations remain uncertain of the exposure lower than current air quality standards in numerous countries. This study aimed to assess the effects of PM2.5 exposure on the brain system in the population with annual mean concentrations ≤15 μg/m3. We analyzed data from 260,922 participants without preexisting brain diseases at baseline in the UK Biobank. The geographical distribution of PM2.5 in 2010 was estimated by a land use regression model and linked with individual residential address. We investigated associations of ambient PM2.5 with incident neurological (dementia, Parkinson's diseases [PD], epilepsy, and migraine) and psychiatric (major depressive disorder [MDD] and anxiety disorder) diseases through Cox proportional hazard models. We further estimated the links with brain imaging phenotypes by neuroimaging analysis. Results showed that in the population with PM2.5 concentrations ≤15 μg/m3, each interquartile range (IQR, 1.28 μg/m3) increment in PM2.5 was related to incidence risks of dementia, epilepsy, migraine, MDD, and anxiety disorder with hazard ratios of 1.08 (95% confidence interval (CI): 1.03, 1.13), 1.12 (1.05, 1.20), 1.07 (1.00, 1.13), 1.06 (1.03, 1.09), and 1.05 (1.02, 1.08), respectively. We did not observe a significant association with PD. The association with dementia was stronger among the population with poor cardiovascular health (measured by Life's Essential 8) than the counterpart (P for interaction=0.037). Likewise, per IQR increase was associated with specific brain imaging phenotypes, including volumes of total brain (β=-0.036; 95% CI: -0.050, -0.022), white matter (-0.030; -0.046, -0.014), grey matter (-0.030; -0.042, -0.017), respectively. The findings suggest long-term exposure to ambient PM2.5 at low-level still has an adverse impact on the neuro-psychiatric system. The brain-relevant epidemiological assessment suggests that each country should update the standard for ambient PM2.5 following the World Health Organization Air Quality Guidelines 2021.