Association of lower dementia risk with improved air quality in older women

Background Late‐life ambient air pollution is a novel risk factor for brain aging. Air quality improvement has been associated with improved cardiopulmonary health and reduced mortality; however, whether it is associated with reduced dementia risk is unknown. Method We studied a geographically‐diverse cohort from the Women’s Health Initiative Memory Study‐Epidemiology of Cognitive Health Outcomes (WHIMS‐ECHO). Participants included 2239 older women (aged 74‐92) without dementia at WHIMS‐ECHO enrollment in 2008‐12. Incident dementia cases, based on DSM‐IV criteria, were centrally‐adjudicated annually (2008‐18). Yearly mean concentrations of ambient PM2.5 (fine particulate matter) and NO2 at residential locations were estimated using validated regionalized universal kriging models. These annual estimates were then averaged over 3‐year periods at both immediately preceding (recent exposure) and 10 years prior to (remote exposure) WHIMS‐ECHO enrollment. Individual‐level improved air quality was defined as reduction from remote to recent exposures. We used Cox proportional hazard models to estimate the hazard ratios (HR) for dementia risk associated with air quality measures, adjusting for sociodemographic, lifestyle, and clinical characteristics. We incorporated inverse‐probability weighting to account for differential attrition during the follow up. Models were replicated using multiple imputation to include those with missing air pollution and covariate data as sensitivity analyses. Results We identified 398 incident dementia cases during median 6.1 years of follow up (interquartile range [IQR]=5.2 years). PM2.5 and NO2 reduced significantly over the 10 years before WHIMS‐ECHO enrollment. Greater improvement in air quality was significantly associated with reduced dementia risks (HRPM2.5=0.80 per IQR=1.78µg/m3, 95% confidence interval [CI]=[0.71, 0.91]; HRNO2=0.80 per IQR=3.91ppb, 95%CI=[0.71, 0.90]), equivalent to the lower risk observed in women 2.4 years younger at baseline. There was some evidence that recent PM2.5 exposure was associated with higher dementia risk (HRPM2.5=1.16 per IQR=2.90µg/m3, 95%CI=[0.98, 1.38]), but the lower dementia risk associated with improved air quality remained after further adjusting for the recent exposure effects. The observed associations did not substantially differ by age, education, geographic region, APOE e4 genotypes, or cardiovascular risk factors. Similar results were found in the sensitivity analyses using multipl