Long-Term Exposure to PM2.5 Constituents, Genetic Susceptibility, and Incident Dementia: A Prospective Cohort Study among 0.2 Million Older Adults

Abstract

Fine particulate matter, known as PM_2.5, is recognized as a risk factor for dementia. However, the specific linkage between PM_2.5 constituents and dementia is not well understood. We conducted a cohort of 217,336 participants of the UK Biobank to explore the association of long-term exposure to PM_2.5 constituents with all-cause dementia, Alzheimer’s disease (AD), and vascular dementia. We estimated PM_2.5 constituents based on residential addresses by an evaluation model and used time-varying Cox models and Quantile g-computation models to assess the effects of individual constituents and their mixtures. Genetic susceptibility to dementia was assessed using a polygenic risk score, and its multiplicative and additive interactions with PM_2.5 constituents were analyzed. Our results showed that black carbon (BC), ammonium (NH₄⁺), organic matter (OM), and sulfate (SO₄^2–) were positively associated with all-cause dementia, while BC and OM were linked to AD, with BC being the most influential. The combined effect of PM_2.5 constituents and genetic risk was stronger than their individual effect. This study offers new insights into the association between PM_2.5 constituents and dementia, especially those from fuel combustion and automobile exhaust, and highlights the need for effective prevention strategies.