Breathing in common air pollutants over many years can significantly increase the risk of developing certain neurodegenerative diseases, and the environment has been implicated in contributing to cognitive decline. New research published in JAMA network open found that long-term exposure to particulate matter and nitrogen dioxide is associated with increased rates of Lewy body dementia and Parkinson’s disease dementia. These results suggest that improving air quality may act as a preventive measure to protect brain health in older adults.
Lewy body dementia and Parkinson’s disease dementia are related neurological conditions that significantly affect memory, thinking, and behavior. Both diseases involve an abnormal accumulation of a specific protein called alpha-synuclein in the brain. Proteins are microscopic structures that perform important functions within our cells. When these proteins misfold and clump together, they disrupt normal cell activity and ultimately cause brain cells to die.
In Lewy body dementia, clumps of these proteins usually cause early cognitive impairment, hallucinations, and unpredictable changes in alertness. In Parkinson’s disease, the damage initially affects movement, causing tremors and stiffness, but as the disease spreads to the brain, many patients eventually develop dementia. Researchers hope to identify environmental factors that may cause this destructive protein buildup. If external factors are contributing to these illnesses, changing your environment may help prevent symptoms from developing.
Dimitri S. Davideau, a psychiatrist and researcher at the University of Florida School of Medicine, led the investigation into these environmental factors. He collaborated with Gregory M. Ponton, a psychiatrist at the University of Florida, and a team of environmental scientists and epidemiologists at Aarhus University in Denmark. They aimed to track exposure to pollution over time and see how it affects older people. The research team focused specifically on two ubiquitous pollutants that are present in nearly every modern city.
The first pollutant, particulate matter, is made up of airborne particles that are much thinner than a human hair. These particles are so small that they can be inhaled deep into the lungs and easily enter the bloodstream. The second pollutant is nitrogen dioxide, a toxic reddish-brown gas. Both of these substances are primarily produced by combustion processes, such as the combustion of fossil fuels in car engines and power plants.
The brain is normally protected from harmful substances in the blood by a strict biological filter known as the blood-brain barrier. Some incredibly small particles and gases can bypass this defense system and enter directly into brain tissue. When these pollutants enter the body, they can trigger an aggressive immune response from the brain’s defense cells. Chronic inflammation caused by this immune response can damage neurons and promote protein misfolding.
Another place these pollutants can enter is the human nose. The olfactory system, which handles the sense of smell, provides a direct neural pathway from the external environment to the brain. People with Lewy body dementia or Parkinson’s disease often lose their sense of smell in the early stages of the disease. High levels of air pollution are also associated with a decreased sense of smell, suggesting that the nasal passages may be a gateway for toxic particles.
To investigate these patterns, the research team analyzed Denmark’s national health and population records. They collected anonymized data on more than 2 million Danish citizens between the ages of 65 and 95 between 2001 and 2021. Denmark maintains a comprehensive health registry that tracks medical diagnoses and residential addresses for its entire population. This detailed record-keeping allowed the researchers to trace back the patients’ lives with considerable accuracy.
From this vast dataset, researchers identified just over 3,000 people diagnosed with Lewy body dementia. They also found about 3,800 people diagnosed with Parkinson’s disease dementia. The researchers matched each of these patients with 10 control subjects who did not have either condition. Control subjects were chosen to be of the exact same gender and born within 14 days of the matched patient.
The team then had to calculate how much pollutant each person inhaled over time. They used a high-resolution mapping system that models air pollution levels across Denmark on a very local scale. By combining this environmental data with the subjects’ past residential addresses, we calculated each person’s average exposure over a 10-year period. This average covers the entire 10 years just before the dementia diagnosis was recorded.
The researchers adjusted their statistical model to account for a variety of background factors that can influence brain health. It included the individual’s socio-economic status, including highest level of education, employment status, and income bracket. They also took into account the general economic conditions of the subjects’ neighborhoods. Finally, a detailed medical history was included, taking into account other physical illnesses and previous psychiatric illnesses.
This data reveals a clear link between increased pollution levels and increased risk of dementia. With each small increase in particulate matter concentration, the risk of developing Lewy body dementia almost quadruples. This similar increase in particulate matter was associated with more than twice the risk of developing Parkinson’s disease dementia.
Exposure to nitrogen dioxide showed a similar, albeit slightly less dramatic, pattern in the analysis. A constant increase in the average concentration of this gas nearly doubles the chance of developing Lewy body dementia. For Parkinson’s disease dementia, increased gas exposure corresponds to a 14% higher risk. In both cases, Lewy body dementia was more strongly associated with pollution than dementia associated with Parkinson’s disease.
The researchers also grouped subjects based on total pollution exposure to look for consistent dose-response relationships. They compared people breathing the dirtiest air to those enjoying the cleanest air. The group with the most exposure to fine particulate matter had more than twice the risk of both types of dementia compared to the group with the least exposure.
“These are pollutants that most people are exposed to every day,” said Dimitry S. Davideau, MD, MPH, the Lauren and Lee Fixel Professor of Neurological Disorders at UC Health’s Norman Fixel Institute for Neurological Diseases. “They come from things like traffic, transportation and other forms of combustion.”
“While this study does not prove causation, it does show a clear association between exposure to air pollution and increased risk for these dementias,” said Gregory Ponton, MD, MHS, Lewis and Roberta Fixell Endowed Chair. “This is an important step in understanding how environmental factors contribute to disease development.”
This study relies heavily on diagnoses made in hospitals and specialty clinics, which has some limitations. This means the researchers may have missed cases of milder dementia or patients who did not seek specialized medical care. If milder cases are missing from the registry, the accurate risk calculation may be slightly underestimated in the final analysis.
The research team also lacked access to certain personal information that regularly impacts the health status of older adults. The national database does not record lifestyle habits such as diet, alcohol intake, or daily exercise habits. The register also does not provide details about specific occupational hazards, meaning the team cannot account for people working in heavily contaminated industrial environments.
Additionally, particulate matter and nitrogen dioxide are often emitted from the exact same sources, such as highway traffic. These two pollutants often exist together in the air, making it very difficult to distinguish their effects on the human body. The researchers noted that these factors can act together to cause neurological damage.
Future research could investigate exactly how these invisible particles initiate the neurodegenerative process at the cellular level. Scientists want to investigate whether blocking the brain’s inflammatory response could slow or stop the damage caused by inhaled pollutants. Further research could also examine how pesticides such as insecticides, in combination with air pollution, affect brain health across the lifespan.
The authors of the study, “Air Pollutant Exposure and Lewy Bodies and Parkinson’s Disease-Associated Dementia,” are Dimitry S. Davideau, Gregory M. Ponton, Michael S. Okun, Melissa J. Armstrong, and Teresa Wimberly. – Böttger, Camilla Giels, Lise-Marie Frohn, Jørgen Brandt, Julie Wellenberg Dreyer, Jacob Christensen, Carsten Bocker Pedersen and Henriette Tisted Horsdal.
