Best Rogowski Clare B, Bredell Christiaan, Shi Yan, Tien-Smith Alexandra, Szybka Magdalena, Fung Kwan Wai, Hong Lucy, Phillips Veronica, Jovanovic Andersen Zorana, Sharp Stephen J, Woodcock James, Brayne Carol, Navaratnam Annalan, Khreis Haneen
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.
University of Cambridge School of Clinical Medicine, Cambridge, UK; Hinchingbrooke Hospital, North West Anglia NHS Foundation Trust, Huntingdon, UK.
Lancet Planet Health. 2025 Jul;9(7):101266. doi: 10.1016/S2542-5196(25)00118-4. Epub 2025 Jul 24.
A rapidly evolving evidence base suggests that exposure to outdoor air pollution is a risk factor for the onset of dementia, with an upturn in publications since 2022. We sought to synthesise and critically assess this evidence base accounting for the latest studies.
In this systematic review and meta-analysis, we searched MEDLINE, Embase, Cochrane Library, CINAHL, Global Health, PsycINFO, Scopus, and Web of Science Core Collection from database inception up to Oct 23, 2023, for primary observational studies of adults (aged ≥18 years) that provided a quantitative analysis of the association between long-term (≥1 year) exposure to outdoor air pollutants and a subsequent physician diagnosis of dementia. When three or more independent studies reported an exposure-outcome pair, effect estimates of the association were extracted and harmonised to a prespecified exposure increment, and included in inverse-variance weighted random-effects meta-analyses. Between-study inconsistency was assessed using the I statistic and the Cochran Q test. Study-level risk of bias and confidence in the overall body of evidence were assessed with the Office of Health Assessment and Translation tool, and publication bias was examined. The protocol for this review was registered with PROSPERO, CRD42023414413.
The search generated 15 619 records, of which 51 studies met the inclusion criteria for data extraction. After excluding studies due to population overlap and missing continuous effect estimates, 32 studies reported on exposure-outcome pairs that met the threshold of three or more studies, and were included in meta-analyses of adjusted effect estimates for incident dementia and/or in subgroup analyses of dementia subtypes. In meta-analyses of incident dementia, we identified a dementia diagnosis to be significantly associated with long-term exposure to PM (21 studies, n=24 030 527, pooled adjusted hazard ratio (HR) per 5 μg/m increase in exposure, 1·08 [95% CI 1·02-1·14]; I=95%), nitrogen dioxide (16 studies, n=17 228 429, pooled adjusted HR per 10 μg/m increase, 1·03 [1·01-1·05]; I=84%), and black carbon/PM (six studies, n=19 421 865, pooled adjusted HR per 1 μg/m increase, 1·13 [1·01-1·27]; I=97%). We found no significant association for exposure to nitrogen oxides (five studies, n=241 409, pooled adjusted HR per 10 μg/m increase, 1·05 [0·97-1·13]; I=44%), PM (four studies, n=246 440, pooled adjusted HR per 15 μg/m increase, 1·52 [0·80-2·87]; I=82%), or annual ozone (four studies, n=419 972, pooled adjusted HR per 45 μg/m increase, 0·82 [0·35-1·92]; I=69%), with moderate to considerable heterogeneity between studies in these pooled analyses. Of the 32 studies overall, three (9%) had a probably high risk of bias in one of seven domains; all other studies had ratings of probably to definitely low risk of bias. The overall certainty of evidence of studies in the systematic review was moderate.
This analysis adds to the body of evidence that outdoor air pollutants are risk factors for dementia, indicating that reduced exposure to pollution could reduce dementia rates and stricter air quality standards would likely provide substantial health, social, and economic benefits.
European Research Council under the Horizon 2020 research and innovation programme and the EU's Horizon Europe Framework Programme.
快速发展的证据表明，暴露于室外空气污染是痴呆症发病的一个风险因素，自2022年以来相关出版物有所增加。我们试图综合并批判性地评估这一证据基础，同时纳入最新研究。
在这项系统评价和荟萃分析中，我们检索了MEDLINE、Embase、Cochrane图书馆、CINAHL、全球健康数据库、PsycINFO、Scopus和科学网核心合集，检索时间从数据库建立至2023年10月23日，以查找关于成年人（年龄≥18岁）的原发性观察性研究，这些研究对长期（≥1年）暴露于室外空气污染物与随后医生诊断为痴呆症之间的关联进行了定量分析。当三项或更多独立研究报告了暴露-结果对时，提取关联的效应估计值，并将其统一到预先指定的暴露增量，纳入逆方差加权随机效应荟萃分析。使用I统计量和Cochrane Q检验评估研究间的不一致性。使用健康评估与转化办公室工具评估研究水平的偏倚风险和对整体证据的信心，并检查发表偏倚。本综述的方案已在PROSPERO注册，注册号为CRD42023414413。
检索共生成15619条记录，其中51项研究符合数据提取的纳入标准。在排除因人群重叠和缺少连续效应估计值的研究后，32项研究报告了符合三项或更多研究阈值的暴露-结果对，并被纳入新发痴呆症调整效应估计值的荟萃分析和/或痴呆症亚型的亚组分析。在新发痴呆症的荟萃分析中，我们发现痴呆症诊断与长期暴露于颗粒物（21项研究，n=24030527，暴露每增加5μg/m³的合并调整风险比（HR）为1.08 [95%CI 1.02-1.14]；I=95%）、二氧化氮（16项研究，n=17228429，暴露每增加10μg/m³的合并调整HR为1.03 [1.01-1.05]；I=84%）和黑碳/颗粒物（6项研究，n=19421865，暴露每增加1μg/m³的合并调整HR为1.13 [1.01-1.27]；I=97%）显著相关。我们发现暴露于氮氧化物（5项研究，n=241409，暴露每增加10μg/m³的合并调整HR为1.05 [0.97-1.13]；I=44%）、颗粒物（4项研究，n=246440，暴露每增加15μg/m³的合并调整HR为1.52 [0.80-2.87]；I=82%）或年度臭氧（4项研究，n=419972，暴露每增加45μg/m³的合并调整HR为0.82 [0.35-1.92]；I=69%）与痴呆症无显著关联，在这些汇总分析中研究间存在中度至相当大的异质性。在总共32项研究中，三项（9%）在七个领域之一中可能存在高偏倚风险；所有其他研究的偏倚风险评分为可能至肯定低风险。系统评价中研究证据的总体确定性为中等。
该分析进一步补充了证据，表明室外空气污染物是痴呆症的风险因素，这表明减少污染暴露可能降低痴呆症发病率，更严格的空气质量标准可能带来重大的健康、社会和经济效益。
欧洲研究理事会的“地平线2020”研究与创新计划以及欧盟的“地平线欧洲”框架计划。
