An assessment of the mediating role of hypertension in the effect of long-term air pollution exposure on dementia

Background:Growing evidence links air pollution exposure to the risk of dementia. We hypothesized that hypertension may partially mediate this effect.Methods:We previously documented an association between air pollution and dementia in the Ginkgo Evaluation of Memory Study, a randomized, placebo-controlled trial of 3069 adults >= 75 years across four US sites who were evaluated for dementia every 6 months from 2000-2008. We utilized a two-stage regression approach for causal mediation analysis to decompose the total effect of air pollution on dementia into its natural direct and indirect effect through prevalent hypertension. Exposure to air pollution in the 10 or 20 years before enrollment was assigned using estimates from fine-scale spatial-temporal models for PM2.5, PM10, and NO2. We used Poisson regression models for hypertension and Cox proportional hazard models for time-to-incident all-cause dementia, adjusting for a priori confounders.Results:Participants were free of mild cognitive impairment at baseline (n = 2564 included in analyses); 69% had prevalent hypertension at baseline. During follow-up, 12% developed all-cause dementia (Alzheimer's disease [AD] = 212; vascular dementia with or without AD [VaD/AD mixed] = 97). We did not find an adverse effect of any air pollutant on hypertension. Hypertension was associated with VaD/AD mixed (HR, 1.92 [95% CI = 1.14, 3.24]) but not AD. We did not observe mediation through hypertension for the effect of any pollutant on dementia outcomes.Conclusions:The lack of mediated effect may be due to other mechanistic pathways and the minimal effect of air pollution on hypertension in this cohort of older adults.