Life-course exposure to air pollution and the risk of dementia in the Lothian Birth Cohort 1936

Background: Air pollution in later life has been associated with dementia; however, limited research has investigated the association between air pollution across the life course, either at specific life periods or cumulatively. The project investigates the association of air pollution with dementia via a life-course epidemiological approach.

Methods: Participants of the Lothian Birth Cohort, born in 1936, provided lifetime residential history in 2014. Participant's air pollution exposure for time periods 1935, 1950, 1970, 1980, 1990, 2001, and 2007 was modeled using an atmospheric chemistry transport model. Lifetime cumulative exposures were calculated as time-weighted mean exposure. Of 572 participants, 67 developed all-cause dementia [35 with Alzheimer's dementia (AD)] by wave 5 (~82 years). Cox proportional hazards and competing risk models assessed the association between all-cause dementia and AD with particulate matter (diameter of ≤2.5 µm) PM_2.5 and nitrogen dioxide (NO₂) exposure at specific life periods and cumulatively. False discovery rate (FDR) correction was applied for multiple testing.

Results: The mean follow-up was 11.26 years. One standard deviation (SD) higher exposure to air pollution in 1935 (PM_2.5 = 14.03 μg/m³, NO₂ = 5.35 μg/m³) was positively linked but not statistically significant to all-cause dementia [PM_2.5 hazard ratio (HR) = 1.16, 95% confidence interval (CI) = 0.90, 1.49; NO₂ HR = 1.13, 95% CI = 0.88, 1.47] and AD (PM_2.5 HR = 1.38, 95% CI = 1.00, 1.91; NO₂ HR = 1.35, 95% CI = 0.92, 1.99). In the competing risk model, one SD elevated PM_2.5 exposure (1.12 μg/m³) in 1990 was inversely associated with dementia (subdistribution HR = 0.82, 95% CI = 0.67, 0.99) at P = 0.034 but not after FDR correction (P _FDR = 0.442). Higher cumulative PM_2.5 per one SD was associated with an increased risk of all-cause dementia and AD for all accumulation models except for the early-life model.

Conclusion: The in-utero and early-life exposure to PM_2.5 and NO₂ was associated with higher AD and all-cause dementia risk, suggesting a sensitive/critical period. Cumulative exposure to PM_2.5 across the life course was associated with higher dementia risk. Midlife PM_2.5 exposure's negative association with all-cause dementia risk may stem from unaddressed confounders or bias.