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Exposure to fine particulate air pollution (PM2.5) was associated with more advanced Alzheimer’s disease neuropathologic changes (ADNC) and faster cognitive decline, a large brain autopsy study showed.
Higher PM2.5 at a person’s last known address was associated with more severe amyloid and tau pathologies after just 1 year of exposure compared with changes observed in individuals exposed to lower levels of air pollution.
“This study shows that air pollution doesn’t just increase the risk of dementia — it actually makes Alzheimer’s disease worse,” Edward Lee, MD, PhD, co-director of the Institute on Aging at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, said in a news release. “As researchers continue to search for new treatments, it’s important to uncover all of the factors that contribute to the disease, including the influence of the environment in which they live.”
The study was published online on September 8 in JAMA Neurology.
Previous research evaluated a link between PM2.5 and ADNC but not to other dementia-related pathologies. The current study is the first to look at associations among PM2.5, neurodegenerative disease pathology, and cognitive and functional outcomes.
Investigators studied brain samples from 602 autopsies (mean age, 78 years; 55% men) from 1999 to 2022 from the Penn Medicine Brain Bank.
Investigators measured four tau, beta-amyloid, alpha-synuclein, and TDP-43 proteinopathies and assessed infarcts, amyloid angiopathy, and arteriosclerotic cerebrovascular lesions. They also investigated whether cerebrovascular pathology contributed to cognitive impairment.
Neuropathological outcomes included Thal amyloid phase, Braak stage, Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) score, level of ADNC, absence or presence of Lewey Body Disease, and LATE-NC stage.
Dementia was assessed using the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB).
Overall, the median CDR-SB score was 12, suggesting a moderate level of dementia. The most common diagnosis was AD (47%), followed by Parkinson’s disease (14%).
More than 50% of the total cohort had severe AD, including 71% who had Thal amyloid phase 4/5, 64% who had Braak stage V/VI, 64% who had a CERAD score of 3, and 62% who had high overall ADNC.
Investigators matched each individual’s geocoded residential addresses before death or before the last CDR-SB assessment (up to 5 years prior to death) to calculate 1-year mean PM2.5concentration exposure.
The median 1-year mean PM2.5 concentration before death was 9.4 µg/m3. In adjusted models, higher PM2.5 exposure correlated to increased odds of more severe AD neuropathology.
For example, for every 1 µg/m3 increase in 1-year mean PM2.5 exposure before death, researchers found a 17% higher odds of a higher Thal amyloid phase, 20% higher odds of higher Braak stage, 20% higher odds of lower CERAD score, and 19% increased odds of increased overall ADNC.
Each of these factors was significant (P < .001).
In the subgroup with data based on last CDR-SB assessment, researchers found similar associations with pollution exposure, again indicating greater cognitive and functional impairment with greater PM2.5 levels.
“Population-based autopsy studies are further needed to replicate our findings and better understand relationships among PM2.5 exposure, cognition, and neuropathology,” the authors noted.
Study limitations included lack of adjustment for physical and leisure activities, smoking or alcohol history, differences between urban and rural exposures, and other confounders. Nearly 95% of the cases were White individual, which could limit the generalizability of the findings. And a large proportion of autopsies that did not include cases with vascular dementia, which could have resulted in selection bias.
This study was supported by funding from the National Institutes of Health (NIH) and the National Institute of Environmental Health Sciences. Lee reported receiving grants from NIH during the conduct of the study and personal fees from Eli Lilly and Wavebreak Therapeutics outside the submitted work. Full disclosures are included in the original article.
