Long-term exposure to ambient particulate matter and its association with Alzheimer’s disease: influencing factors and a systematic review with meta-analysis

Abstract

Background: Alzheimer’s disease (AD) poses a pressing public health burden globally. Evidence linking long-term ambient particulate matter exposure to AD risk remains inconsistent, necessitating systematic quantification to inform prevention policies. Methods: We searched PubMed, Embase, Web of Science, and Cochrane Library up to September 2025 for cohort studies with ≥1 year of particulate exposure (PM2.5, PM10, NO2, NOx, O3) and incident/diagnosed AD. Quality was assessed via the Newcastle–Ottawa Scale (NOS), with random-effects models pooling hazard ratios (HRs) and 95% CIs; subgroup analyses explored heterogeneity by study design, region, and follow-up duration. Results: Twenty-five high-quality (NOS ≥ 7/9) cohort studies involving over 170 million participants were included. Meta-analyses showed higher AD risk with each 5 μg/m3 increase in PM2.5 (HR = 1.24, 95%CI: 1.10–1.39), 10 μg/m3 in PM10 (HR = 1.16, 95%CI: 1.01–1.33), 10 μg/m3 in NO2 (HR = 1.06, 95%CI: 1.00–1.12), and 10 μg/m3 in NOx (HR = 1.05, 95%CI: 1.03–1.07). For O3, four included studies showed no significant association (HR = 1.23, 95%CI: 0.65–2.31) with extremely high heterogeneity (I2 = 99.8%), indicating inadequate and unstable evidence. Subgroup analyses confirmed effect modification by study design, region, and follow-up duration; publication bias was low for most pollutants. Conclusion: We recommend high-risk population screening, stricter emission standards, and prioritizing emission reduction in AD primary prevention—aligning with global efforts to address environmental determinants of neurological health. Systematic review registration: PROSPERO with the registration number CRD420251174986, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251174986.