Association of Long-term Exposure to Ambient Air Pollution With Cognitive Decline and Alzheimer’s Disease–Related Amyloidosis

Air pollution induces neurotoxic reactions and may exert adverse effects on cognitive health. We aimed to investigate whether air pollutants accelerate cognitive decline and affect neurobiological signatures of Alzheimer's disease (AD).We used a population-based cohort from the Chinese Longitudinal Healthy Longevity Survey with 31,573 participants and a 10-year follow-up (5878 cognitively unimpaired individuals in Chinese Longitudinal Healthy Longevity Survey followed for 5.95 ± 2.87 years), and biomarker-based data from the Chinese Alzheimer's Biomarker and Lifestyle study including 1131 participants who underwent cerebrospinal fluid measurements of AD-related amyloid-β (Aβ) and tau proteins. Cognitive impairment was determined by education-corrected performance on the China-Modified Mini-Mental State Examination. Annual exposures to fine particulate matter (PM2.5), ground-level ozone (O3), and nitrogen dioxide (NO2) were estimated at areas of residence. Exposures were aggregated as 2-year averages preceding enrollments using Cox proportional hazards or linear models.Long-term exposure to PM2.5 (per 20 μg/m3) increased the risk of cognitive impairment (hazard ratio, 1.100; 95% CI: 1.026-1.180), and similar associations were observed from separate cross-sectional analyses. Exposures to O3 and NO2 yielded elevated risk but with nonsignificant estimates. Individuals exposed to high PM2.5 manifested increased amyloid burdens as reflected by cerebrospinal fluid-AD biomarkers. Moreover, PM2.5 exposure-associated decline in global cognition was partly explained by amyloid pathology as measured by cerebrospinal fluid-Aβ42/Aβ40, P-tau/Aβ42, and T-tau/Aβ42, with mediation proportions ranging from 16.95% to 21.64%.Long-term exposure to PM2.5 contributed to the development of cognitive decline, which may be partly explained by brain amyloid accumulation indicative of increased AD risk.