Dementia risk increased by air pollution

Nadine Osman

The air we breathe may be affecting more than our lungs—it could accelerate neurodegenerative disease. Two major studies, drawing on data from over 85 million people worldwide, provide compelling evidence that long-term exposure to fine particulate air pollution significantly increases dementia risk, with one study uncovering a particularly strong link to Lewy body dementia.

A landmark meta-analysis, published in The Lancet Planetary Health and led by the University of Cambridge, offers a global perspective by analysing data from over 29 million people across 51 studies. It concluded that exposure to fine Particulate Matter (PM2.5) and nitrogen dioxide (NO₂)—common pollutants from vehicle exhaust, industrial emissions, and fuel burning—is a major risk factor for dementia.

PM2.5 refers to tiny particles less than 2.5 micrometres in diameter, small enough to penetrate deep into the lungs and enter the bloodstream. Nitrogen dioxide (NO₂) is a toxic gas that can irritate the respiratory system and contribute to inflammation throughout the body. Both pollutants are believed to harm the brain by triggering systemic inflammation and oxidative stress—processes that damage neurones, impair blood flow, and accelerate cognitive decline. The study highlighted that these effects may be particularly harmful for vascular dementia, which arises from reduced blood flow to the brain.

Quantifying the risk, the analysis found that for every additional 10 micrograms per cubic metre of PM2.5, the likelihood of developing dementia rises by 17%. “Long-term exposure to outdoor air pollution is a risk factor for the onset of dementia in previously healthy adults,” stated lead author Dr Haneen Khreis. “Tackling air pollution can deliver long-term health, social, climate, and economic benefits.”

To understand the impact of the second study, it is crucial to understand its focus: Lewy body dementia (LBD). This progressive neurological disorder is the second most common form of dementia worldwide, after Alzheimer’s disease. LBD is caused by abnormal clumps of a protein called α-synuclein, which accumulate inside nerve cells; these clumps are known as Lewy bodies.

In a healthy brain, α-synuclein helps neurones communicate with each other. But when this protein misfolds and forms Lewy bodies, it interferes with normal brain function, leading to a complex mix of symptoms. These include cognitive decline, memory problems, vivid visual hallucinations, sleep disturbances, and movement difficulties similar to Parkinson’s disease, such as tremors and stiffness. LBD often overlaps with Parkinson’s disease dementia, which makes it particularly challenging to diagnose and manage.

While the Cambridge study examined dementia broadly, a separate investigation by Xiaodi Zhang and colleagues, published in Science and titled Lewy Body Dementia Promotion by Air Pollutants, focused specifically on LBD. Zhang’s team combined large-scale human data with laboratory experiments to explore how air pollution might trigger the disease. Using records from over 56 million U.S. Medicare patients, they found a clear link between exposure to fine particulate matter (PM2.5) and higher rates of LBD.

To investigate causation, they exposed mice to PM2.5, which resulted in memory and movement problems along with accumulation of α-synuclein. Crucially, mice genetically engineered to lack α-synuclein did not develop these issues, confirming the protein’s central role in the disease.

The study uncovered a critical mechanism: PM2.5 exposure triggers a distinct, toxic strain of α-synuclein, which the researchers called PM-PFF (PM2.5-induced preformed fibrils). These fibrils aggregate into Lewy bodies and directly cause the cognitive impairments characteristic of human LBD. Dr Hui Chen, a clinical neuroscientist on the study, explained, “The results in mice reflect what occurs in humans. PM2.5 exposure interacts with genetic predisposition—an inherited tendency to develop certain diseases—creating the perfect storm for neurodegenerative disease.”

In short, this research provides strong evidence that air pollution can initiate molecular changes in the brain, producing toxic α-synuclein fibrils that drive Lewy body dementia.

This alarming link is reinforced by research from across the globe. In the U.S., the Zhang study’s analysis provided massive-scale corroboration. In China, research has shown that even low concentrations of PM2.5 and NO₂ are associated with greater dementia risks, suggesting there may be no safe threshold for these pollutants. Furthermore, studies in Denmark found that even the country’s relatively low levels of air pollution were associated with dementia development, highlighting the need for continued air quality improvements even in less polluted regions.

Together, these comprehensive studies move beyond correlation to demonstrate a biological mechanism, showing air pollution is a serious and modifiable risk factor capable of triggering the protein misfolding at the heart of Lewy body dementia. The implication is clear: preventing dementia requires action far beyond the healthcare sector.

As Dr Christiaan Bredell, co-author of the Cambridge study, concluded, “Preventing dementia is not just the responsibility of healthcare. Urban planning, transport policy, and environmental regulation all have a significant role to play.” With millions worldwide at risk, the findings make one thing unequivocally clear: ensuring clean air is not just an environmental goal but a critical imperative for public brain health.

Feature image generated using ChatGPT.