Long-term exposure to fine particulate matter and nitrogen dioxide may be associated with a higher risk of developing dementia with Lewy bodies and Parkinson's disease–related dementia in a nationwide Danish study.
Investigators conducted a time-matched, nested case-control study using Danish national registry data from 2001 to 2021. The analysis included 3,024 patients with dementia with Lewy bodies and 3,808 patients with Parkinson's disease–related dementia, each matched with 10 controls by age, sex, and calendar time. They estimated 10-year exposures to particulate matter smaller than 2.5 μm (PM2.5) and nitrogen dioxide (NO2) using residential address histories linked to Danish air pollution modeling systems.
Following adjustment for socioeconomic characteristics, psychiatric history, medical comorbidities, and neighborhood-level socioeconomic measures, every 5 μg/m³ increase in PM2.5 exposure was associated with 3.7 times the odds of dementia with Lewy bodies and 2.4 times the odds of Parkinson's disease–related dementia, while every 10 μg/m³ increase in NO2 exposure was associated with nearly twice the odds of dementia with Lewy bodies and modestly higher odds of Parkinson's disease–related dementia.
The exposure-response relationship remained evident when pollutant exposure was analyzed by quintiles. Patients in the highest PM2.5 exposure group had approximately twice the odds of both dementia outcomes compared with those in the lowest exposure group. For NO2 exposure, the association appeared more consistent for dementia with Lewy bodies compared with for Parkinson's disease–related dementia.
In sex-stratified analyses, the direction of the associations remained unchanged. The magnitude of the association for dementia with Lewy bodies appeared greater among male patients, whereas associations for Parkinson's disease–related dementia appeared greater among female patients.
When PM2.5 and NO2 were included in the same model, both pollutants remained associated with dementia with Lewy bodies, but only PM2.5 remained associated with Parkinson's disease–related dementia. The investigators noted a substantial correlation between the pollutants, limiting interpretation of their independent effects.
The investigators said prior studies have linked PM2.5 exposure with cortical amyloid-beta plaque burden and both PM2.5 and NO2 exposure with olfactory dysfunction. They suggested that the olfactory system may serve as a gateway providing pollutants access to the brain.
The study was limited by reliance on registry-based diagnoses that may have underestimated milder cases and by lack of validated coding for dementia with Lewy bodies and Parkinson's disease–related dementia. The investigators also lacked information on occupational exposures and lifestyle factors associated with dementia risk. Because the study was observational, the findings did not establish causation.
“In this case-control study using a population-based sample of Danish older adults, we found that exposures to ambient PM2.5 or NO2 were each associated with increased risks of developing [dementia with Lewy bodies] and [Parkinson's disease–related dementia],” wrote lead study author Dimitry S. Davydow, MD, MPH, of the Department of Psychiatry at the University of Florida College of Medicine, and colleagues. “The magnitude of the observed associations of exposure to PM2.5 or NO2 with risk of [dementia with Lewy bodies] and [Parkinson's disease–related dementia] was increased for both diseases but more so in [dementia with Lewy bodies].”
Full disclosures of the study authors can be found in the study.
Source: JAMA Network Open