A study has found that exposure to air pollution can increase the risk of developing Lewy body dementia.Credit: Sonu Mehta/Hindustan Times/Shutterstock
An analysis of 56 million people has shown that exposure to air pollution increases the risk of developing a particular form of dementia, the third most common type after Alzheimer’s disease and vascular dementia.
The study, published in Science on 4 September1, suggests that there is a clear link between long-term exposure to PM2.5 — airborne particles that are smaller than 2.5 micrometres in diameter — and the development of dementia in people with Lewy body dementia or Parkinson’s disease.
The study found that PM2.5 exposure does not necessarily induce Lewy body dementia, but “accelerates the development,” in people who are already genetically predisposed to it, says Hui Chen, a clinician–neuroscientist at the University of Technology Sydney in Australia.
PM2.5 exposure
Lewy body dementia is an umbrella term for two different types of dementia: Parkinson’s disease with dementia, and dementia with Lewy bodies. In both cases, dementia is caused by the build-up of α-synuclein (αSyn) proteins into clumps, called Lewy bodies, in the brain’s nerve cells, which cause the cells to stop working and eventually die. Studies have suggested that long-term exposure to air pollution from car-exhaust, wildfires and factory fumes, is linked with increased risks of developing neurodegenerative illnesses, including Parkinson’s disease with dementia2.
Study co-author Xiaobo Mao, who researches neurodegenerative conditions at Johns Hopkins University in Baltimore, Maryland, says he and his colleagues wanted to determine if PM2.5 exposure also influenced the risk of developing Lewy body dementia. They analysed 2000–2014 hospital-admissions data from 56.5 million people with Lewy body dementia and Parkinson’s disease with or without dementia. The data served to identify people with severe neurological diseases.
They found that long-term PM2.5 exposure was associated with an increased risk of hospitalization for all three neurodegenerative conditions, including a 12% increased risk for severe dementia with Lewy bodies that required hospitalization. They noted that living in areas of higher PM2.5 exposure was linked with a higher relative risk of Lewy body dementia — including dementia with Lewy bodies and Parkinson’s disease dementia — compared with Parkinson’s without dementia.
Source: Ref. 1
The team then performed experiments in mice to investigate why exposure to air pollution affected dementia risk. Mice were exposed to PM2.5 pollution through their nostrils, then the researchers tested for behaviours linked with dementia-like problems. After ten months of PM2.5 exposure, mice showed behavioural challenges in maze exploration tests for spatial memory, and tasks that tested their recognition of new objects. At ten months, the team also observed a substantial increase in the build-up of αSyn in the animals’ brains.
Exposure to PM2.5 for ten months also caused the shrinkage of the medial temporal lobe in mice — a brain region which is responsible for memory formation and retrieval. In comparison, there were no changes to the brains of genetically modified mice lacking αSyn, suggesting the protein is required for neurodegenerative pathology.
The team also found clumps of αSyn in the gut and lungs of mice exposed to PM2.5, but not in the control or genetically modified mice. Mao says that αSyn acts like a seed, which can propagate and spread from the gut to the brain by way of the gut–brain axis, and eventually cause Alzheimer’s disease or Lewy body dementia. PM2.5 also accumulates in the lungs, causing inflammation before entering the bloodstream and crossing the blood–brain barrier.
Predisposition needed
The researchers next investigated gene-expression changes caused by PM2.5 exposure in mice and compared them with gene-expression changes observed in people with Lewy body dementia. They focused on the anterior cingulate cortex — a brain region linked with cognitive deficits in people with dementia. They found a strong correlation of gene-expression changes between PM2.5-exposed mice and people with Lewis body dementia and Parkinson’s disease with dementia, but no correlation with Parkinson’s disease without dementia.
