Associations of air pollution with all-cause dementia, Alzheimer’s disease, and vascular dementia: a prospective cohort study based on 437,932 participants from the UK biobank

OBJECTIVE: To prospectively assess whether air pollution, including PM(2.5), PM(10), and NOx, is associated with the risk of all-cause dementia, Alzheimer’s disease (AD), and vascular dementia, and to investigate the potential relationship between air pollution and genetic susceptibility in the development of AD. METHODS AND RESULTS: Our study included 437,932 participants from the UK Biobank with a median follow-up period of over 10 years. Using a Cox proportional hazards model, we found that participants exposed to PM(2.5) levels of ≥10 μg/m(3) had a higher risk of developing all-cause dementia (HR = 1.1; 95% CI: 1.05–1.28; p < 0.05) compared to the group exposed to PM(2.5) levels of <10 μg/m(3). However, there was no significant association between PM(10) levels of ≥15 μg/m(3) and the risk of all-cause dementia, AD, or vascular dementia when compared to the group exposed to PM(10) levels of <15 μg/m(3). On the other hand, participants exposed to NOx levels of ≥50 μg/m(3) had a significantly higher risk of all-cause dementia (HR = 1.14; 95% CI: 1.02–1.26; p < 0.05) and AD (HR = 1.26; 95% CI: 1.08–1.48; p < 0.05) compared to the group exposed to NOx levels of <50 μg/m(3). Furthermore, we examined the combined effect of air pollution (PM(2.5), PM(10), and NOx) and Alzheimer’s disease genetic risk score (AD-GRS) on the development of AD using a Cox proportional hazards model. Among participants with a high AD-GRS, those exposed to NOx levels of ≥50 μg/m(3) had a significantly higher risk of AD compared to those in the group exposed to NOx levels of <50 μg/m(3) (HR = 1.36; 95% CI: 1.03–1.18; p < 0.05). Regardless of air pollutant levels (PM(2.5), PM(10), or NOx), participants with a high AD-GRS had a significantly increased risk of developing AD. Similar results were obtained when assessing multiple variables using inverse probability of treatment weighting (IPTW). CONCLUSION: Our findings indicate that individuals living in areas with PM(2.5) levels of ≥10 μg/m(3) or NOx levels of ≥50 μg/m(3) are at a higher risk of developing all-cause dementia. Moreover, individuals with a high AD-GRS demonstrated an increased risk of developing AD, particularly in the presence of NOx ≥ 50 μg/m(3).