Ambient air pollution and clinical dementia: systematic review and meta-analysis

OBJECTIVE: To investigate the role of air pollutants in risk of dementia, considering differences by study factors that could influence findings. DESIGN: Systematic review and meta-analysis. DATA SOURCES: EMBASE, PubMed, Web of Science, Psycinfo, and OVID Medline from database inception through July 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies that included adults (≥18 years), a longitudinal follow-up, considered US Environmental Protection Agency criteria air pollutants and proxies of traffic pollution, averaged exposure over a year or more, and reported associations between ambient pollutants and clinical dementia. Two authors independently extracted data using a predefined data extraction form and assessed risk of bias using the Risk of Bias In Non-randomised Studies of Exposures (ROBINS-E) tool. A meta-analysis with Knapp-Hartung standard errors was done when at least three studies for a given pollutant used comparable approaches. RESULTS: 2080 records identified 51 studies for inclusion. Most studies were at high risk of bias, although in many cases bias was towards the null. 14 studies could be meta-analysed for particulate matter <2.5 µm in diameter (PM(2.5)). The overall hazard ratio per 2 μg/m(3) PM(2.5) was 1.04 (95% confidence interval 0.99 to 1.09). The hazard ratio among seven studies that used active case ascertainment was 1.42 (1.00 to 2.02) and among seven studies that used passive case ascertainment was 1.03 (0.98 to 1.07). The overall hazard ratio per 10 μg/m(3) nitrogen dioxide was 1.02 ((0.98 to 1.06); nine studies) and per 10 μg/m(3) nitrogen oxide was 1.05 ((0.98 to 1.13); five studies). Ozone had no clear association with dementia (hazard ratio per 5 μg/m(3) was 1.00 (0.98 to 1.05); four studies). CONCLUSION: PM(2.5) might be a risk factor for dementia, as well as nitrogen dioxide and nitrogen oxide, although with more limited data. The meta-analysed hazard ratios are subject to limitations that require interpretation with caution. Outcome ascertainment approaches differ across studies and each exposure assessment approach likely is only a proxy for causally relevant exposure in relation to clinical dementia outcomes. Studies that evaluate critical periods of exposure and pollutants other than PM(2.5), and studies that actively assess all participants for outcomes are needed. Nonetheless, our results can provide current best estimates for use in burden of disease and regulatory setting efforts. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021277083.