A comprehensive analysis involving over 56 million people has found that long-term exposure to fine air pollutants significantly increases the risk of developing Lewy body dementia — the third most common form of dementia after Alzheimer’s disease and vascular dementia. The findings, published on 4 September in Science, reveal that exposure to PM2.5 — airborne particles smaller than 2.5 micrometres in diameter — accelerates the onset of neurodegenerative diseases in genetically predisposed individuals.
The study, led by researchers from Johns Hopkins University and the University of Technology Sydney, found that PM2.5 exposure does not directly cause Lewy body dementia but worsens the condition in those already at risk. “We wanted to determine if PM2.5 exposure also influenced the risk of developing Lewy body dementia,” said Xiaobo Mao, a neurodegenerative disease researcher at Johns Hopkins University.
What Is Lewy Body Dementia?
Lewy body dementia encompasses two related conditions: Parkinson’s disease with dementia and dementia with Lewy bodies. Both are characterized by abnormal clumps of α-synuclein proteins forming in brain cells, disrupting their function and eventually causing cell death. Previous studies have hinted at links between air pollution from vehicles, industrial emissions, and wildfires and increased risks of neurological conditions, but this study is among the first to demonstrate a specific connection with Lewy body dementia.
Hospital Admissions and Pollution Exposure
The research team analyzed hospital admissions data spanning from 2000 to 2014, covering 56.5 million individuals with Parkinson’s disease and Lewy body dementia. They found that higher levels of PM2.5 exposure were associated with a 12% increased risk of hospitalization for severe dementia with Lewy bodies. Notably, individuals living in areas with higher PM2.5 concentrations had a greater relative risk of developing Lewy body dementia compared to Parkinson’s disease without dementia.
Mouse Experiments Confirm Findings
To understand the underlying mechanisms, the team exposed mice to PM2.5 pollution over a period of ten months. The animals displayed significant memory impairments in maze tests and object recognition challenges, accompanied by a notable increase in α-synuclein protein accumulation in the brain. The medial temporal lobe — a critical region for memory — also showed shrinkage.
In contrast, genetically modified mice lacking α-synuclein did not exhibit these changes, suggesting the protein’s central role in disease development. Clumps of α-synuclein were also detected in the gut and lungs, supporting the hypothesis that the protein spreads from the gut to the brain via the gut–brain axis.
“PM2.5 accumulates in the lungs, triggers inflammation, and crosses the blood–brain barrier, exacerbating neurodegeneration,” explained Mao.
Genetic Predisposition Matters
The study further examined gene-expression changes in the anterior cingulate cortex — a brain region associated with cognitive function — comparing PM2.5-exposed mice with individuals diagnosed with Lewy body dementia. The analysis revealed a strong correlation in gene-expression patterns, while no such correlation was found for Parkinson’s disease without dementia.
According to Hui Chen, a clinician-neuroscientist at the University of Technology Sydney, “The results in mice reflect what occurs in humans, where an individual already needs to be genetically susceptible for PM2.5 exposure to increase their risk.”
A Call for More Research
Chen noted that while the mechanism linking pollution to neurodegeneration is not entirely new, their findings highlight the need for greater awareness of air pollution as a risk factor. She also acknowledged limitations in the study’s methodology, as mice were exposed to high doses over a short time rather than continuous, low-dose exposure typical in human environments.
Mao emphasized that future research will focus on more accurate exposure models and investigate which specific components of PM2.5 might trigger neurodegenerative processes. “Our study has opened a window for more research to understand how air pollution causes neurodegenerative diseases,” he said.
Public Health Implications
With air pollution affecting billions worldwide, these findings underscore the urgent need to address environmental factors contributing to dementia. As populations age, identifying preventable risks such as PM2.5 exposure could be critical to developing strategies that delay or reduce the impact of neurodegenerative disorders.
