It has long been rather stunning to me how careless many people are about air pollution. One of the most important things that people shouldn’t do is drive with their windows down in areas with significant traffic (and thus significant amounts of air pollution from vehicles). The motive for caring is rather simple — air pollution’s negative impact on brain health means possibly reduced performance on a variety of tasks, and that can negatively correlate with achieving life goals, which in turn is detrimental to human happiness and satisfaction.
Long thought to primarily harm the lungs and cardiovascular system, air pollution is now catching the attention of neuroscientists and toxicologists.
The buzz of a leaf blower and its gaseous fumes fill the air outside a lab facility at the University of Washington in Seattle. Inside the building, neurotoxicologist Lucio Costa is investigating how polluted air—such as garden tool exhaust—could be bad for the brain.
Next to the building sits a 5,500-watt diesel generator, enclosed in a metal box. Pipes carry the diesel exhaust—the same stuff emitted by diesel engines in vehicles and heavy equipment—into the facility, across an exposed ceiling and into a room where plastic cages of mice are stacked high against the wall. Tubes filter the diesel exhaust through the cages, Costa explains, in an effort to mimic the contaminated air you might breathe while sitting in traffic or living near a busy road.
After spending most of his career studying mercury, pesticides, and flame retardants, Costa knows well that many toxins in the environment can hurt the brain. But only in the last several years has the possibility of air pollution as a culprit crossed his mind. A growing body of literature on the topic inspired him to begin research in this diesel lab. “For a long time, I thought that air pollution was affecting mostly the lungs and the cardiovascular system and not the brain,” says Costa. “So I stayed away from any issue related to air pollution.”
Now, mounting evidence seems to link a variety of neurological problems to dirty air. Troubling recent findings include hallmarks of Alzheimer’s disease found in the brains of children living in Mexico City (1) and a nearly doubled risk of dementias for older women in highly polluted parts of the United States (2). Costa’s own research has identified autism-like social and behavioral issues in mice exposed to diesel exhaust (3). Today, Costa is among a growing cadre of biologists, toxicologists, and doctors raising the alarm over this pervasive yet overlooked menace to our memory, attention, and behavior.
A Global Threat
Although the coronavirus disease 2019 (COVID-19) pandemic and associated “shelter in place” policies have reduced fossil fuel use to offer a temporary respite from extreme pollution in some places, most countries face an ongoing epidemic of dirty air as a result of growing urban congestion and an uptick in climate-driven wildfires, among other factors. Indoor air pollution further plagues many of the world’s poorest communities. Around 3 billion people cook indoors over open fires or stoves fueled by wood, biomass, kerosene, or coal. In 2018, the World Health Organization (WHO) identified air pollution as the second-largest risk factor for noncommunicable disease worldwide. And the WHO’s stats don’t include the full range of neurological effects now being discovered, notes neurotoxicologist Deborah Cory-Slechta at the University of Rochester in New York.
Globally, more than 90 percent of people breathe air that fails to meet WHO standards. That includes an estimated four in 10 people in the United States, although efforts such as the US Clean Air Act and its amendments of 1990 have helped. Between 2000 and 2016, the average concentration of particulate matter (PM) with a diameter of less than 2.5 micrometers (PM2.5), tiny particles produced by combustion, fell by around 40 percent in the United States. But the country’s overall air quality has worsened since 2016. Partly to blame is a rise in wildfire smoke, which is now responsible for an estimated 40 percent of particulate matter pollution.
Yet cleaner, healthier air remains achievable, notes Dean Schraufnagel, a pulmonologist at the University of Illinois at Chicago. “There are no death certificates that say air pollution exposure,” he says. “But we know that air pollution affects every organ in the body. If we stop the air pollution at its source, we can get strikingly important health benefits.”
Schraufnagel, also the director of the Forum of International Respiratory Societies, points to one easy target: idling diesel-powered school buses. A 2019 study out of Georgia in the United States found that districts that retrofitted school buses to reduce diesel emissions reported significant increases in students’ English test scores as well as smaller improvements in math (4).
The havoc air pollution can wreak on the brain is also a new area of interest for Schraufnagel, whose research and clinical practice has long focused on lung disease. Today, he is working with international organizations to get air pollution on the minds of not just pulmonologists but also neurologists and other medical experts. “This should be a call to action,” adds Schraufnagel.
Air pollution is a cocktail of suspended gases, solids, and liquid particles. While this mix contains numerous hazardous ingredients, such as ozone, sulfur dioxide, and carbon monoxide, the component that appears most concerning for the brain is PM.
The US Environmental Protection Agency (EPA) regulates PM10 and PM2.5, defined as particles less than 10 and 2.5 micrometers in diameter, respectively. PM2.5, also known as fine particulate matter, generally comes from smoke, dust, and vehicle exhaust. Because PM2.5 is so tiny—30 times smaller than the width of the average human hair—it can remain airborne for long periods of time, infiltrate buildings, and penetrate the body. Ultrafine particles, which measure less than 0.1 micrometer across, may be even worse offenders. Yet the miniscule mass of these particles makes them difficult to monitor. They remain unregulated by the EPA.
Fine and ultrafine particulate matter tends to circumvent the mechanisms that the human body has evolved to deflect, detain, and destroy unwelcome visitors. “The health effects of air pollution are all about particle size,” says Cory-Slechta. Studies suggest that these tiny particles can even go up the nose and be carried straight to the brain via the olfactory nerve (5)—hence bypassing the blood–brain barrier. And they don’t travel alone. On their surfaces these particles carry contaminants, from dioxins and other chemical compounds to metals such as iron and lead. “PM is simply acting as a vector,” says Masashi Kitazawa, a molecular neuropathologist at the University of California, Irvine. “It might be a number of chemicals that get into the brain and act in different ways to cause damage.”
Because of their large surface area relative to their volume, the smallest particles are the biggest offenders. Cory-Slechta’s research has largely focused on lead and mercury, neurotoxic metals that are abundant in air pollution. “Ultrafine particles are like little Trojan horses,” she says. “Pretty much every metal known to humans is on these.”
Metal-toting particles that reach the brain can directly damage neurons. Both the particles themselves and their toxic hitchhikers can also cause widespread harm by dysregulating the activation of microglia, the immune cells in the brain. Microglia may mistake the intruders for pathogens, releasing chemicals to try to kill them. Those chemicals can accumulate and trigger inflammation. And chronic inflammation in the brain has been implicated in neurodegeneration (6).
Particles may also afflict the brain via the bloodstream. Research shows that small particles can slip through the plasma membrane of alveoli—the tiny air sacs in the lungs—and get picked up by capillaries. The particles are then distributed around the body in the blood. Although some of these particles may eventually breach the blood–brain barrier, a pollutant need not enter the brain to cause trouble there. The immune system can react to particles in the lung or bloodstream, too, triggering widespread inflammation that affects the brain.
Even an ingested particle could have indirect neurological effects, via the gut. Researchers now recognize strong connections between the gut microbiome and the brain (7), and studies show that delivering fine particles to the gut can cause systemic inflammation (8).
In January 2010, Cory-Slechta received a surprising request from some University of Rochester environmental medicine colleagues. Typically, the group researched the effects of air pollution on the lungs and hearts of adult animals. But they had just exposed a group of newborn mice and asked Cory-Slechta’s team to look at the brains.
At first she didn’t think much of the request. Cory-Slechta was much more concerned about deadly lead exposure in children, her research focus at the time. “I didn’t think of air pollution as a big problem for the brain,” she says. Then she examined the animals’ tissue. “It was eye-opening. I couldn’t find a brain region that didn’t have some kind of inflammation.”
Her team followed up with their own studies. In addition to inflammation, they saw classic behavioral and biochemical features of autism, attention-deficit disorder, and schizophrenia in mice exposed to pollutants during the first days after birth. The mouse brains had noticeably less white matter, particularly in the corpus callosum connecting the right and left cerebral hemispheres. In work published last November, Cory-Slechta’s group further linked short-term exposures to air pollution with impaired learning and memory in aged mice, based on measures of spontaneous movement, navigation of a maze, short-term object recognition, and the ability to discriminate odors (9). The concentrations of particulate matter used, she notes, “easily include sitting in traffic in major cities.”
Research in Ontario, Canada, found that living farther away from a major road lowered the risk of developing dementia (13). A study of nearly 3,000 Barcelona schoolchildren found that those attending schools with more traffic pollution had slower cognitive development (14). And in the United States, a study found that living in locations where ambient particulate matter exceeded EPA recommendations nearly doubled women’s risk of developing dementia. When those researchers looked specifically at older women with two copies of the APOE4 gene variant, a strong genetic factor for Alzheimer’s disease, the dementia risk associated with living in those locations jumped almost threefold (2).