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

Abstract

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/m³ 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/m³ nitrogen dioxide was 1.02 ((0.98 to 1.06); nine studies) and per 10 μg/m³ nitrogen oxide was 1.05 ((0.98 to 1.13); five studies). Ozone had no clear association with dementia (hazard ratio per 5 μg/m³ 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.

Fig 1

Flowchart of literature search

Fig 2

Graphical representation of exposure and outcome assessment in studies with active ascertainment included in the meta-analyses. Red lines indicate period of exposure assessment and circles indicate outcome assessment and follow-up visits. For Grande 2020, visits occurred every six years for participants ages 60-77 years old indicated by the closed circles and every three years for older participants, indicated by the open circles.

Fig 3

Graphical representation of exposure and outcome assessment in studies that used passive ascertainment included in the meta-analyses. Purple lines indicate period of outcome assessment and red lines indicate exposure assessment

Fig 4

Random effects meta-analysis for PM_2.5. Diamond size represents the relative weight of the studies. Study specific estimates are scaled to a standard unit change of 2 μg/m³. PM_2.5=particulate matter <2.5 µm in diameter

Fig 5

Random effects meta-analysis for NO₂, NO_x, and O₃. Shaded boxes represent the relative weight of the studies. Study specific estimates for each pollutant are scaled to a standard unit change of 10 μg/m³ NO₂, 10 μg/m³ NO_x, and 5 μg/m³ O₃. NO₂=nitrogen dioxide; NO_x=nitrogen oxide; O₃=ozone

Fig 6

PM_2.5 estimates by region. Region was characterised as North America, Europe, or Asia. Diamond sizes represent the relative weight of the studies. Study specific estimates are scaled to a standard unit change of 2 μg/m³ change in PM_2.5. PM_2.5=particulate matter <2.5 µm in diameter

Fig 7

PM_2.5 estimates by outcome ascertainment. Active ascertainment studies were those that estimated associations from established cohort studies; Passive ascertainment studies made use of data such as claims and medical records. Diamond sizes represent the relative weight of the studies. Study specific estimates are scaled to a standard unit change of 2 μg/m³ change in PM_2.5. PM_2.5=particulate matter <2.5 µm in diameter