Abstract
BACKGROUND: Residential environmental factors-including air pollution, traffic, greenspace, and bluespace-have been increasingly linked to dementia risk, yet the joint impacts and biological pathways remain underexplored. This study aimed to examine the associations between these diverse residential exposures and all-cause and cause-specific dementia, while exploring the mediating roles of plasma metabolites and telomere length.
METHODS: Using the UK Biobank (UKB) cohort, we analyzed 317,498 participants free of dementia at baseline. Exposures were assessed via geographic and model-based data, and outcomes included all-cause dementia (ACD), Alzheimer’s disease (AD), vascular dementia (VaD), and other dementia subtypes (O). Cox proportional hazards models were applied to estimate the associations between exposures and dementia outcomes. Separate mediation analyses were conducted to examine the potential mediating roles of plasma metabolites and telomere length.
RESULTS: Pollutant exposures, especially NO₂ and PM10, were consistently associated with higher dementia risk, with age-specific patterns. Greenspace showed inverse associations, notably for ACD and VaD, while traffic proximity elevated VaD risk. Exploratory mediation suggested 49 metabolites for the PM2.5-10-ACD association in participants under 65, with the largest proportions for Omega-3 % (33.29 %) and S-VLDL-TG% (32.99 %).
CONCLUSION: Air pollution, especially particulate matter, was significantly associated with dementia risk, partially mediated by metabolic pathways. These findings underscore the importance of environmental interventions in dementia prevention.