by Raphaël Cayrol, University of Luxembourg

Hypothesized pathogenic pathways taken by fine particulate matter (PM2.5) to cause cognitive impairment. PM2.5, particulate matter with a diameter of 2.5 µm and smaller. Two main hypotheses exist regarding the underlying mechanisms of how inflammatory processes are involved in the pathogenic effects of PM2.5 on the development of neurodegenerative diseases: The first hypothesis suggests that PM2.5 may take a direct route via the bloodstream (systemic route) or the olfactory nerve (olfactory route), crossing the blood–brain barrier and causing local inflammatory effects in the brain. The second hypothesis proposes that PM2.5 may induce (chronic) systemic inflammation, which subsequently leads to impairments in the brain (peripheral inflammatory effects). Credit: Alzheimer’s & Dementia (2024). DOI: 10.1002/alz.14320

Air pollution is often viewed as an outdoor hazard and a threat to respiratory health. Emerging research shows that air pollution may also affect our brain health. Fine particulate matter (PM2.5), is a complex mixture of many chemicals that can be inhaled deep into the lungs. While PM2.5 exposure has long been linked to tissue damage and inflammation in the lung, its role in cognitive decline is only now gaining attention.

Researchers from the universities of Rostock, Bonn and Luxembourg have uncovered a potential link: systemic inflammation, driven by an increase in monocytes—a type of white blood cells—may be a key mediator in how PM2.5 exposure contributes to cognitive impairment. The study is published in the journal Alzheimer’s & Dementia.

Fine particulate matter and its impact on brain health

PM2.5 are fine airborne particles small enough to enter the lungs and even the bloodstream, posing significant health risks. Long-term exposure has been linked to neurodegenerative diseases like Alzheimer’s and Parkinson’s, resulting in air pollution being listed as one of the modifiable risk factors in the recent report of The Lancet commission on dementia prevention, intervention and care. However, the mechanisms through which PM2.5 affects cognitive function remain poorly understood.

While most studies on cognitive decline focus on elderly people, there is growing evidence that chronic low-level exposure to PM2.5 may also affect younger adults. Investigating these effects across a broader demographic may reveal how early and midlife exposure contributes to long-term cognitive outcomes.

To explore this, the researchers analyzed data from over 66,000 participants in the Dutch Lifelines cohort. Combining adult participants’ blood analysis and cognitive testing over a period of 10 years (2006–2015) with air pollution data at their home address from the ELAPSE project, they uncovered new insights into the mechanisms underlying the effect of PM2.5 exposure on brain health.

The role of white blood cells in cognitive impairment

The researchers found that PM2.5 exposure correlates with a decline in cognitive processing time (CPT), a measure of how quickly the brain can respond to stimuli. Interestingly, an increase in white blood cell count, particularly monocytes, the largest subtype involved in immune responses, mediated a significant part of this effect.

“Systemic inflammation may act as a key intermediary, linking PM2.5 exposure to impaired cognitive function,” explains Dr. Benjamin Aretz, research scientist at the University Hospital Bonn and first author of the study. This is the first large-scale study to directly tie changes in the number of white blood cells to the cognitive effects of fine particulate matter.

Inflammation: The missing link?

While PM2.5 can directly affect the brain by crossing the blood-brain barrier and triggering local inflammation, this study highlights the broader systemic inflammation upon exposure.

“We hypothesize that the number of white blood cells rises in response to pollutants,” details Prof. Gabriele Doblhammer, group leader at the DZNE in Rostock.

“Inflammation was already shown to play an important role in the development of neurodegenerative diseases. Hence, the inflammation we see in response to air pollution may disrupt immune functions in the brain, thereby indirectly impairing cognitive health.”

Understanding the mechanisms to develop preventive action

As populations age and urbanization increases, understanding and addressing the role of air pollution in neurodegenerative diseases will be more important than ever.

“Given the strong correlation between air pollution and cognitive deficits, further studies are essential to pinpoint which pollutants and cellular mechanisms mediate this effect,” concludes Prof. Michael Heneka, director of the Luxembourg Centre for Systems Biomedicine (LCSB) at the University of Luxembourg and senior author of the study.

Such markers could inform future public health policies aimed at mitigating the brain health risks posed by long-term PM2.5 exposure.