Alzheimer’s Disease Exacerbated by Air Pollution, Autopsy Study Suggests— Brain changes were more severe in people exposed to higher levels of fine particulate matter

by Judy George, Deputy Managing Editor, MedPage September 8, 2025 • 3 min read

Key Takeaways

• Air quality was tied to Alzheimer’s disease pathology and cognitive function in an autopsy study.
• Alzheimer’s neuropathology mediated most of air pollution’s relationship with cognition.
• Air pollution is known as a key global modifiable risk factor for dementia prevention.

Worse outdoor air quality was tied to worse Alzheimer’s disease pathology in older adults, an autopsy study showed.

Among 602 autopsy cases, higher exposure to fine particulate matter less than 2.5 μm (PM_2.5) before death raised the odds of more severe Alzheimer’s disease neuropathologic change (OR 1.19, 95% CI 1.11-1.28), said Edward Lee, MD, PhD, of the University of Pennsylvania Perelman School of Medicine in Philadelphia, and co-authors.

In a subset of 287 cases with Clinical Dementia Rating Sum of Boxes (CDR-SB) scores, higher PM_2.5 exposure also was associated with greater cognitive and functional impairment (β=0.48, 95% CI 0.22-0.74).

Overall, 63% of the association between higher PM_2.5 exposure and greater cognitive and functional impairment was mediated by Alzheimer’s disease neuropathologic change (β=0.30, 95% CI 0.04-0.53), the researchers reported in JAMA Neurologyopens in a new tab or window.

The study highlights how larger autopsy studies may be able to shed light on possible mechanisms linking environmental risk and brain disease, Lee noted.

“Using statistical models, we found that the negative effect of air pollution on cognitive function in our cohort was largely mediated by this increase in Alzheimer’s disease pathology,” he told MedPage Today.

“This suggests that one way air pollution negatively affects your brain is by exacerbating Alzheimer’s disease,” he continued. “Undoubtedly, there are likely other mechanisms as well, such as the exacerbation of cerebrovascular disease, but the focus of this study was mainly on neurodegenerative processes such as Alzheimer’s disease.”

The findings come on the heels of research published in Scienceopens in a new tab or window last week tying PM_2.5 exposure to the development of Lewy body dementia. Several prior studiesopens in a new tab or window have linked air quality with cognition, and the Lancet Commission lists air pollution as a key global modifiable risk factoropens in a new tab or window for dementia prevention.

Lee and co-authors evaluated data from autopsy cases collected from 1999 to 2022 at the University of Pennsylvania. Participants included 602 cases, including people with common forms of dementia or movement disorders and controls. Findings were adjusted for demographic factors and APOE4 gene status.

Dementia severity was assessed by CDR-SB scores, which measure cognitive and functional domains. One-year mean PM_2.5 concentration before death or before the last CDR-SB test was estimated with a prediction modelopens in a new tab or window at participants’ residential addresses.

The researchers graded or staged 10 dementia-associated neuropathologic measures representing Alzheimer’s disease, Lewy body disease, limbic-predominant age-related TDP-43 encephalopathy, and cerebrovascular disease. Measures included four proteinopathies (tau, beta-amyloid, alpha-synuclein, and TDP-43) and three cerebrovascular lesions (infarcts, amyloid angiopathy, and arteriolosclerosis).

Median age at death was 78 years and 54.5% of the cohort was male. Most participants were white (94.4%) and median education was 16 years. Just over half of all participants (53.2%) had at least one APOE4 allele. Cases came from 11 states, with most from Pennsylvania.

More than half of the cohort exhibited severe Alzheimer’s pathology measures, with 62.3% showing high overall Alzheimer’s disease neuropathologic change, and high Thal amyloid phases, Braak stages, and Consortium to Establish a Registry for Alzheimer’s Disease scores.

The study had several limitations, the researchers acknowledged. The autopsy cohort was skewed demographically and results may not apply to others. The cohort included a large proportion of cases through research programs enriched for Alzheimer’s dementia which did not enroll people with vascular dementia.

“Due to the rarity of cerebrovascular pathology in our cohort, we likely underestimated the true associations between PM_2.5 and cerebrovascular disease, which have been strongly supported by epidemiologic studies,” Lee and colleagues wrote.

Other confounding variables may have influenced results, they added.Judy George covers neurology and neuroscience news for MedPage Today, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more. Follow

Disclosures

This study was supported by funding from the NIH and the National Institute of Environmental Health Sciences.

Lee reported grants from the NIH and personal fees from Eli Lilly and WaveBreak Therapeutics.

Co-authors reported relationships with the NIH, Prevail, Passage Bio, Denali, CervoMed, Alector, the State of Pennsylvania, Eli Lilly, Beckman Coulter, and GSK.Primary SourceJAMA NeurologySource Reference: Kim B, et al “Ambient air pollution and the severity of Alzheimer disease neuropathology” JAMA Neurol 2025: DOI: 10.1001/jamaneurol.2025.3316.

https://www.medpagetoday.com/neurology/alzheimersdisease/117365