HOW DOES WILDFIRE SMOKE AFFECT THE BRAIN?
BREATHING DIRTY AIR MAY ACCELERATE AGING
BY ANTHONY WHITE AND LILIAN CALDERON-GARCIDUENAS

As the threat of wildfires grows, firefighters and affected communities grapple not only with the immediate threat of flames but also with the acute and chronic brain health effects of wildfire smoke.
While the physical dangers of smoke inhalation are well documented, the toll it takes on brain health remains a lesser-known consequence.
After sustained exposures to wildfire smoke, people complain of memory problems and mental fatigue. Routine tasks can demand heightened concentration and effort. Thought processes (known as cognitive function) appear to slow, suggesting impairment in information processing and decision-making abilities. Time and spatial perception can seem distorted, together with diminished attentional capacity.
David Vivian, an experienced Ranger with the Queensland Parks and Wildlife Service in Australia, has been exposed to smoke on many occasions, including heavy amounts of smoke inhalation when dealing with wildfires.
“When you ‘cop’ a lung full, it’s usually because you have made an error in judgement or because the situation has changed rapidly, or dramatically,” Vivian says. “Often the lapse in judgement is preceded by fatigue and stress. I believe that my cognitive functioning is at a reduced level in these situations; whether that is a direct cause of the smoke inhalation poses an interesting question.”
These effects of wildfire smoke are often referred to as brain fog, but the underlying action of the smoke impact on brain function is not well understood. If and how such effects lead to long-term changes to brain health is only just being investigated.
A starting point for understanding how wildfire smoke affects people’s brains could come from Metropolitan Mexico City, where we are studying the impact of air pollution on the brains of seemingly healthy children and young adults.
It turns out that breathing dirty air isn’t just a hit to your lungs; it’s like pressing the fast-forward button on brain aging. Imagine youthful minds showing cognitive deficits observed in people with Alzheimer’s disease (the most common form of dementia), while they’re still playing in the schoolyard; it’s as if air pollution stole their innocence. It is extremely sad to see a nine-year-old complaining she does not remember very much from her daily classroom lessons.
Some of the startling findings from our research in Metropolitan Mexico City include the demonstration of substantial structural brain changes in young people exposed to the high levels of air pollution. Twenty-two million residents have been exposed daily to sustained concentrations of fine particulate matter (PM 2.5) well above the current U.S. Environmental Protection Agency standard of 9 μg/m3 for the last three decades.

Wildfire smoke contains neurotoxic and inflammatory particles and chemicals that can enter the body and may travel to the brain via the bloodstream or through the nasal (olfactory) system. PM2.5 – particulate matter of up to 2.5 microns; UFP – ultrafine particles up to 0.1 micron; PAH – polyaromatic hydrocarbons; VOC – volatile organic compounds; NOx – nitric oxides; Cu Pd As (metals – copper, lead, arsenic).
Alzheimer’s disease is usually associated with ageing and affects people mostly in their 70s and 80s. However, forensic autopsy studies of children and young adults in Mexico City have shown the hallmarks of aberrant neural proteins as described in Alzheimer’s disease, Parkinson’s disease, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis, including accumulation of major abnormal brain proteins – hyperphosphorylated tau, beta-amyloid, alpha synuclein and TDP-43.
How is this relevant to understanding the effects of wildfire smoke from forests and savannahs on the brain? Wildfire smoke is a major form of particulate air pollution, hence smoke levels are measured as changes in air quality. Like city pollution, which is largely from traffic and industry, wildfire smoke contains a range of microscopic particles called particulate matter. It is generally considered that particulate matter with a diameter of up to 2.5 micrometers (which is less than 1/10th the thickness of a human hair), including the ultrafine particle fraction (below 0.1 micrometer in diameter), is toxic because it can enter deep into the lungs and cross the barrier from the lungs into the blood stream. There are a number of additional chemicals and compounds in wildfire smoke that can add to the toxic nature of the smoke, including volatile organic compounds, such as aldehydes, and alkanes, together with polycyclic aromatic hydrocarbons, various gases (carbon monoxide, sulphur dioxide, nitrogen oxides), and heavy metals such as copper, iron, manganese, and arsenic, some of which can be stripped from soils by hot fires.
A growing number of studies at both the population level (epidemiological studies), and cellular level, are providing evidence that wildfire smoke is as toxic as anthropogenic (human made) particulate matter pollution, resulting from combustion of fossil fuels. These studies raise a major question regarding just how toxic is wildfire smoke to the brain: Can city pollution induce Alzheimer’s disease, Parkinson’s disease, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis-like changes in young people? Furthermore, there are important questions to answer about how different types of vegetation smoke affect humans, how the toxicity changes with distance from the fire, and the short- and long-term consequences of wildfire smoke exposure.
First, consider how wildfire smoke can get to the brain, or if it even needs to, to impact brain health. Unfortunately, there are multiple ways wildfire smoke can affect the brain, which may be surprising given that the brain is protected by a tight barrier between the blood vessels and the brain cells (neurons), logically called the blood-brain barrier. In theory, this barrier tightly controls the movement of all toxic chemicals into and out of the brain, however it turns out, the tiniest particles entering the blood circulation are very capable of damaging this precious blood-brain barrier and thus, renders the brain helpless and vulnerable to toxins and the particles themselves. The ultrafine particles travel free in the blood, but also in the red and white blood cells, so indeed the Trojan horse is at play to reach every single region of our brains.

In an interesting recent study, Raissa Gill, Robert Fleck and colleagues at University of Technology in Sydney measured the size of some particles collected from filters after the devastating 2019-2020 Black Summer bushfires that blanketed Sydney and much of Australia in wildfire smoke for several weeks. The researchers found that the diameter of the wildfire particles was substantially smaller than that of particles collected from reference sites that included predominantly traffic and other ambient sources of air pollution. This finding could suggest that wildfire smoke particles, being smaller, may have an increased ability to cross cell membranes and enter body organs including the brain. In addition, we know from studies in mice performed by David Scieszka and colleagues at University of New Mexico in 2022, that when exposed to wildfire smoke particles, the blood-brain barrier is disrupted. Thus, more toxic smoke particles in the blood can access the brain through the damaged barrier. But this can also allow access to inflammatory cells from the blood; this is exactly what Sciezka found in the mouse studies. Several different types of inflammatory cells (white blood cells) were shown to be invading the brain after exposure to the smoke; this coincided with inflammation in the brains of the mice, and damage to the neurons.
The lung-blood-brain route is not the only way wildfire smoke can reach the brain. Wildfire smoke might also be hitching a ride to our brains through the nerve fibers in our noses. The cells in the nose that sense smells are closely linked to the brain through a region called the olfactory bulb. This part of the brain is linked to other regions including the amygdala and hippocampus, which are highly involved in processing emotions and thought processes, memories, and learning. Unlike the blood brain barrier connection, the nasal (olfactory or the trigeminal) nerve systems are highways for the particles through their axons directly to the brain. But in terms of wildfire smoke pollution, if offers a potentially direct route for access of toxic particles into the brain.
Regardless of how the toxic wildfire smoke particles access the brain, there is increasing evidence that the particles are having important short- and long-term impacts on brain health. Studies investigating the cognitive function of people exposed to different forms of air pollution have found key links between wildfire smoke exposure and impairment of certain cognitive (thought) processes. A 2023 study by Boya Zhang and colleagues at the University of Michigan found that the two leading sources of PM2.5 associated with increased risk of dementia in the United States were agriculture and wildfires. The research, published in a JAMA Internal Medicine, points to the growing links between air pollution and Alzheimer’s disease. In fact, based on the study, the authors estimated that if there is a causal relationship between agriculture and wildfire smoke PM2.5 and onset of dementia, ~188,000 new cases of dementia could occur each year in the United States alone from these exposures. Another recent study by found that air pollution in the UK was the second greatest modifiable risk factor for dementia-linked changes in the brain, after diabetes. A modifiable risk factor means something that could potentially be avoided or controlled, compared to genetic makeup, which can’t be controlled. While the study did not specifically assess wildfire smoke pollution, when combined with studies such as the JAMA research, it’s clear that exposure to wildfire smoke could be a leading risk factor for dementia, and that this risk may increase further with the combination of more wildfires, other occupational exposures, traffic pollution, tobacco, and age.
Other studies have shown links between exposure to wildfire smoke and impaired ability to perform thinking-related tasks, in adults and youth, and from short- and long-term exposure. Although the effects of wildfire smoke on brain development (termed neurodevelopment) in the fetus, infants and children have been poorly studied, some studies have shown ultrafine particles and industrial nanoparticles reach fetal brains early and thus, particulate matter exposures, including wildfire exposure, could indeed impair early brain development. Likewise, several studies have shown a relationship between air pollution and Parkinson’s disease, however, there has been no dedicated research into whether wildfire smoke air pollution is a contributing factor.
How does the wildfire smoke cause these changes to our brains? Studies suggest that ultrafine particulate matter reaches blood vessels, neurons and glial cells and cause significant subcellular damage to both critical organelles (cellular machinery) and cell and nuclear membranes. Wildfire smoke drives inflammatory changes in the brain. It remains uncertain whether this inflammation comes directly from toxic interactions between the brain’s immune cells, through invasion of the brain by white blood cells, or impacts on the brain from other inflammatory molecules in the blood (called cytokines), triggered by smoke particles in the lung or blood. Our research lab has found that exposing human brain immune cells grown in a dish to a preparation of wildfire smoke resulted in a major release of an inflammatory cytokine that is known to have an important role in Alzheimer’s dementia brain inflammation. When we performed the same test with vehicle exhaust pollution, we did not see the same outcome, suggesting that human brain immune cells may respond differently (and worse?) to wildfire smoke pollution. We also observed greater effects of the wildfire smoke on brain immune cells from older people versus young people.
Air pollution particles such as those that occur in wildfire smoke are also known to directly affect neurons in the brain (the cells that control learning, thinking, and memory processes). Studies have shown PM2.5 to affect signaling processes within neurons and between them, causing changes to the critical connections between neurons (synapses). The same particles can impair other brain cell functions including one called autophagy, which is a process through which brain cells remove waste material from the brain. Impairment of this process can lead to accumulation of toxic proteins and other substances that can ultimately kill neurons. Likewise, the smoke particles can impair energy production in brain cells by interfering with a key energy producing organelle, called mitochondria. This is the powerhouse of the cell, and neurons, are very energy hungry, requiring a lot of power to maintain all the connections and electrical activity that leads to our thought patterns. Impairment of the mitochondria, which involves oxidative stress (increase in free radicals) can lead to lack of energy and consequently breakdown of the connections between neurons.
Wildfire smoke is also a known risk factor for stroke that can occur in the brain due to blockage of blood vessels and therefore block oxygen and nutrients from reaching brain cells, or through hemorrhaging of vessels (where a vessel ruptures and blood leaks uncontrollably into the brain causing neuronal death). Studies have found that wildfire smoke increases the likelihood of stroke, potentially through oxidative stress, and inflammation.
Another important factor that is rarely considered is that excessive heat can induce similar effects on the brain as wildfire smoke, and increasingly, extreme heat or heatwaves are occurring in unison with exposure to wildfire smoke; add to this is the extremely high temperatures to which wildland firefighters can be exposed together with wildfire smoke exposure.
Extreme heat can generate brain inflammatory changes, affect micro vessels and impair function of neurons, leading to poorer cognitive function – all changes that are also induced by wildfire smoke. How these factors work in combination, and whether there are amplifying effects rather than just additive effects is unknown and requires research.
What do we need to do now? There needs to be an expansion of wildfire smoke health impact studies from focusing on (often short term) impacts such as respiratory health (although obviously this is also very important), to cover other critical targets of smoke pollution, especially the brain. Wildland fire authorities do not want to find ourselves in the situation that currently exists with traumatic brain injury and contact sports, where we are only now waking up to the damage that related knocks to the head can cause, including increased likelihood of dementia and neurodegenerative diseases later in life. There is enough evidence now that there are potentially significant impacts of wildfire smoke on the brain, and further studies and actions are urgently needed. What isn’t known is the answer to key questions such as what components of wildfire smoke are the most damaging to the brain, what level of exposure is harmful, is it similar to other health impacts or very different, what are the time frames. Does a single exposure matter, or does it take years of repeated exposures to have a serious impact on brain health? Is there a threshold cumulative particulate matter dose beyond which the damage is progressive and irreversible? What about exposures in people who already have a neuropsychiatric illness –does wildfire smoke have a greater effect in
Ultimately, we hope a test can be developed to allow current or past firefighters to determine their risk levels for brain impacts of wildfire smoke . . .
such people? There is also potential difficulty understanding the overlap between psychological effects of wildfire smoke exposure, such as post-traumatic stress (PTS), and physiopathological effects (actual toxic effects of the smoke), as both factors can induce similar impacts on the brain.
Our research groups are two of several internationally that are building programs in this important area. While we are investigating the direct toxic and inflammatory effects of wildfire smoke on human brain cells, we are also in the planning stages of extending this to try to understand the risk of neurological illness in wildland firefighters, and especially whether there is an increased risk of dementia, and what additional factors may affect this, such as age, location, and time spent fighting fire.
Ultimately, we hope a test can be developed to allow current or past firefighters to determine their risk levels for brain impacts of wildfire smoke; this testing could be extended to members of the community who are increasingly exposed to high levels of wildfire smoke. In Metropolitan Mexico City we already know that there does not need to be a huge cumulative PM2.5 dose to develop the hallmarks of overlapping fatal pathologies; 11-month-old children are already showing a complex neurodegenerative picture.
In the meantime, aside from wearing the recommended protections against inhalation of smoke, and trying, where possible, to avoid breathing wildfire smoke, firefighters should consider recording their exposure to wildfire smoke. Firefighters’ notes don’t need to be extensive or detailed, but a record of where and when exposure to smoke occurred could help researchers compare exposures to potential impact on the brain.
The mother of one of the authors succumbed to the ravages of dementia. While she was not a wildland firefighter, she spent her life in a kitchen often filled with woodsmoke from a leaky woodstove burning local eucalypt firewood. Whether there was a relationship between the two is something the family will never know, but with ongoing research, hopefully we will be able to better determine the risks for people exposed to woodsmoke, whether that be outdoors or indoors, and that could potentially allow people to avoid some of these risks. With the rapidly increasing exposure to wildfire smoke air pollution, this knowledge is becoming increasingly urgent.

Lilian Calderón-Garcidueñas grew up in a small Gulf of Mexico town, the oldest daughter of two young physicians. She was raised in a nurturing environment where the daily contact with patients was the rule and over dinner conversations were delightful ways to start her in medical and literature subjects, two main interests of her parents. She knew she wanted to be a physician by the time she finished middle school and she started medical school at age 15. The following year, she was the TA to the Chair of Embryology at the National University Medical School in Mexico City and started her lifelong passion for teaching. Her first day as a TA in medical school surrounded by ~40 much older first year students, she was told she was in the wrong place, the middle school was three blocks away. Her love for exploring disease causes started in medical school and she decided to pursue her studies in the United States and Canada. Her pathology and neuropathology training at the University of Toronto were followed by her fellowship at Harvard University and her first position as an assistant professor at Northwestern University in Chicago. She earned an American Board in Anatomical Pathology and Neuropathology in 1981. Literature was always in her mind, so she went back to school and earned a BS in English Literature and a MA in Comparative Literature in 1997. Her interest for clinical environmental research took her back to Chapel Hill, North Carolina, where she earned a PhD in Toxicology in 2001, followed by three years as a postdoctoral fellow in Environmental Pathology. She loves her work, her teaching is key to her way to transmit her contagious enthusiasm for medicine, science and her research work, and in her free time she paints, cooks and tenders her vegetable garden and cooks some more.