Air pollution ups risk of Alzheimer’s disease

Exposure to fine particulate matter PM_2.5 may elevate the risk for Alzheimer’s disease (AD), mainly through direct pathways instead of mediation by common comorbidities, suggests a study.

“Notably, the association was modestly stronger among individuals with stroke, suggesting heightened vulnerability in this subgroup,” said the investigators, who conducted a nationwide cohort study on 27.7 million US Medicare beneficiaries aged ≥65 years from 2000 to 2018.

High-resolution air pollution datasets were used to examine exposure to PM_2.5, and Cox proportional hazards models were applied to explore the relationships between exposure to PM_2.5, incident AD, and comorbidities. Finally, mediation analysis and stratified analyses were conducted to assess the potential for comorbidities to modify and mediate the association between PM_2.5 and AD.

Nearly 3 million incident cases of AD were identified. In the overall population, exposure to PM_2.5 (5-year moving average prior to AD onset) significantly correlated with a higher risk of AD (hazard ratio [HR] per interquartile range [IQR, 3.8 µg/m³] increase, 1.085, 95 percent confidence interval [CI], 1.078‒1.091). [PLoS Med 2026;23:e1004912]

A slightly more pronounced association was observed among individuals with stroke (HR per IQR increase, 1.105, 95 percent CI, 1.096‒1.114). However, there was little effect modification for hypertension and depression.

Furthermore, PM_2.5 exposure also showed a significant association with elevated risks of hypertension, depression, and stroke, all of which correlated with increased AD risk. However, minimal mediation effects were noted, with 1.6 percent of the link between PM_2.5 and incident AD mediated by hypertension, 4.2 percent by stroke, and 2.1 percent by depression.

“Our findings suggest that reducing air pollution could benefit cognitive health broadly across older adults, while targeted interventions may be especially important for those with cerebrovascular disease or multiple chronic conditions,” the investigators said.

Previous research

The findings also support those of earlier studies that found an association between PM_2.5 and increased AD risk. For instance, Shi and colleagues conducted a large national cohort study using the same Medicare database and reported an HR per IQR increase in 5-year average PM_2.5 of 1.078 for AD. [Nat Commun 2021;12:6754]

Likewise, a systematic review and meta-analysis reported a pooled HR of 3.26 (95 percent CI, 1.20‒5.31) for AD per 10-μg/m³ increase in PM_2.5 exposure. This result was consistent with another meta-analysis that found a similar HR of 3.26 (95 percent CI, 0.84‒12.74). [Environ Res 2019;177:108638; Sci Total Environ 2019;655:1240-1248]

“Additionally, our results support existing evidence of the association between PM_2.5 exposure and the risks of depression, hypertension, and stroke,” the investigators said. [Environ Health Perspect 2016;124:1414-1420; Environ Int 2022;170:107594; JAMA Netw Open 2023;6:e2253668]

“All these three comorbidities are also significantly linked to a higher risk of AD in our data and previous research using the same Medicare data,” they added. [Alzheimers Dement 2023;19:1858-1864]

As mentioned, these associations indicate the possibility of mediation. The current findings add to existing mediation literature by “formally modelling and quantifying the relationships between PM_2.5, these comorbidities, and AD in a large national cohort, and requiring a clear temporal ordering of exposure, mediators, and outcomes,” according to the investigators.

The present study was limited by the use of administrative claims data and potential exposure misclassification from area-level estimates of PM_2.5.