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What Is Pollution Doing to Our Brains? 'Exposomics' Reveals Links to Many Diseases

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Friday, April 12, 2024

B1992, burgeoning population, choking traffic, and explosive industrial growth in Mexico City had caused the United Nations to label it the most polluted urban area in the world. The problem was intensified because the high-altitude metropolis sat in a valley trapping that atmospheric filth in a perpetual toxic haze. Over the next few years, the impact could be seen not just in the blanket of smog overhead but in the city’s dogs, who had become so disoriented that some of them could no longer recognize their human families. In a series of elegant studies, the neuropathologist Lilian Calderón-Garcidueñas compared the brains of canines and children from “Makesicko City,” as the capital had been dubbed, to those from less polluted areas. What she found was terrifying: Exposure to air pollution in childhood decreases brain volume and heightens risk of several dreaded brain diseases, including Parkinson’s and Alzheimer’s, as an adult.Calderón-Garcidueñas, today head of the Environmental Neuroprevention Laboratory at the University of Montana, points out that the damaged brains she documented through neuroimaging in young dogs and humans aren’t just significant in later years; they play out in impaired memory and lower intelligence scores throughout life. Other studies have found that air pollution exposure later in childhood alters neural circuitry throughout the brain, potentially affecting executive function, including abilities like decision-making and focus, and raising the risk of psychiatric disorders.The stakes for all of us are enormous. In places like China, India, and the rest of the global south, air pollution, both indoor and outdoor, has steadily soared over the course of decades. According to the United Nations Foundation, “nearly half of the world’s population breathes toxic air each day, including more than 90 percent of children.” Some 2.3 billion people worldwide rely on solid fuels and open fires for cooking, the Foundation adds, making the problem far worse. The World Health Organization calculates about 3 million premature deaths, mostly in women and children, result from air pollution created by such cooking each year.On supporting science journalismIf you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.In the United States, meanwhile, average air pollution levels have decreased significantly since the passage of the Clean Air Act in 1970. But the key word is average. Millions of Americans are still breathing outdoor air loaded with inflammation-triggering ozone and fine particulate matter. These particles, known as PM2.5 (particles less than 2.5 micrometers in diameter), can affect the lungs and heart and are strongly associated with brain damage. Wildfires—like the ones that raged across Canada this past summer—are a major contributor of PM2.5. A recent study showed that pesticides, paints, cleaners, and other personal care products are another major—and under-recognized—source of PM2.5 and can raise the risk for numerous health problems, including brain-damaging strokes.Untangling the relationship between air pollution and the brain is complex. In the modern industrial world, we are all exposed to literally thousands of contaminants. And not every person exposed to a given pollutant will develop the same set of symptoms, impairments, or diseases—in part because of their genes, and in part because each exposure may occur at a different point in development or impact a different area of the body or brain. What’s more, social disparities are at play: Poorer populations almost always live closer to factories, toxins, and pollutants.The effort to figure it out and intervene has sparked a new field of study: exposomics, the science of environmental exposures and their effects on health, disease, and development. Exposomics draws on enormous datasets about the distribution of environmental toxins, genetic and cellular responses, and human behavioral patterns. There is a huge amount of information to parse, so researchers in the field are turning to another emerging science, artificial intelligence, to make sense of it all.“Anything from our external environment—the air we breathe, food we eat, the water we drink, the emotional stress that we face every day—all of that gets translated into our biology,” says Rosalind Wright, professor of pediatrics and co-director of the Institute for Exposomic Research at the Icahn School of Medicine at Mount Sinai in New York. “All these things plus genes themselves explain the patterns of risk we see.” When an exposure is constant and cumulative, or when it overwhelms our ability to adapt, or “when you’re a fetus in utero, when you’re an infant or in early childhood or in a critical period of growth,” it can have a particularly powerful effect on lifelong cognitive clarity and brain health.Neuroscientist Megan Herting at the University of Southern California (USC) has been studying the impact of air pollution on the developing brain. “Over the past few years, we have found that higher levels of PM2.5 exposure are linked to a number of differences in the shape, neural architecture, and functional organization of the developing brain, including altered patterns of cortical thickness and differences in the microstructure of gray and white matter,” she says. On the basis of neuroimaging of exposed youngsters, Herting and fellow researchers suspect the widespread differences in brain structure and function linked with air pollution may be early biomarkers for cognitive and emotional problems emerging later in life.That suspicion gains support from an international meta-analysis (a study of other studies) published in 2023 that correlated exposure to air pollution during critical periods of brain development in childhood and adolescence to risk of depression and suicidal behavior. The imaging parts of the studies showed changes in brain structure, including neurocircuitry potentially involved in movement disorders like Parkinson’s, and white matter of the prefrontal lobes, responsible for executive decision-making, attention, and self-control.In a 2023 study, Herting and colleagues tracked children transitioning into adolescence, when brains are in a sensitive period of development and thus especially vulnerable to long-term damage from toxins. Among brain regions developing during this period is the prefrontal cortex, which helps with cognitive control, self-regulation, decision-making, attention, and problem-solving, Herting says. “Your emotional reward systems are also still being refined,” she adds.Looking at scan data from more than 9,000 youngsters exposed to air pollution between ages 9 and 10 and following them over the next couple of years, the researchers found changes in connectivity between brain regions, with some regions having fewer connections and others having more connections than normal. Herting explains that these structural and functional connections allow us to function in our daily lives, but how or even whether the changes in circuitry have an impact, researchers do not yet know.The specific pollutants involved in the atypical brain circuits appear to be nitrogen dioxide, ozone, and PM2.5—the small particles that worry many researchers the most. Herting explains: Limits set on fine particulate matter are stricter in the United States than in most other countries but still inadequate. The U.S. Environmental Protection Agency currently limits annual average levels of the pollutant to 12 micrograms per cubic meter and permits daily spikes of up to 35 micrograms per cubic meter. Health organizations, on the other hand, have called for the agency to lower levels to 8 micrograms and 25 micrograms per cubic meter, respectively. Thus, even though it may be “safe” by EPA standards, “air quality across America is contributing to changes in brain networks during critical periods of childhood,” Herting says. And that may augur “increased risk for cognitive and emotional problems later in life.” She plans to follow her group of young people into adulthood, when advances in science and the passage of time should reveal more about the effect of air pollution exposure during adolescence.Other research shows that air pollution increases risk of psychiatric disorder as years go by. In work based on large datasets in the United States and Denmark, University of Chicago computational biologist Andrey Rzhetsky and colleagues found that bad air quality was associated with increased rates of bipolar disorder and depression in both countries, especially when exposure occurs early in life. Rzhetsky and his team used two major sources: in Denmark, the National Health Registry, which contains health data on every citizen from cradle to grave; and in the United States, insurance claims with medical history plus details such as county of residence, age, sex, and importantly, linkages to family—specifics that helped reveal genetic predisposition to develop a psychiatric condition during the first 10 years of life.“It's possible that the same environment will cause disease in one person but not in another because of predisposing genetic variants that are different in different people,” Rzhetsky says. “The different genetic predisposition, that’s one part of the puzzle. Another part is varying environment.”Indeed, these complex diseases are spreading much faster than genetics alone seems to explain. “We definitely don’t know for sure which pollutant is causal. We can’t really pinpoint a smoking gun,” Rzhetsky says. But one pesky culprit continues to prove statistically significant: “It looks like PM2.5 is one of those strong signals.” To figure it out specifically, we’ll need much more data, and exposomics will play a vital role."This is a wake-up call,” Frances Jensen told her fellow physicians at the American Neurological Society’s symposium on Neurologic Dark Matter in October 2022. The meeting was an exploration of the exposome –the sum of external factors that a person is exposed to during a lifetime— driving neurodegenerative disease. It was focused in no small part on air pollution. Jensen, a University of Pennsylvania neurologist and president of the American Neurological Association, argued that researchers need to pay more attention to contaminants because the sharp rise in the number of Parkinson’s diagnoses cannot be explained by the aging population alone. “Environmental exposures are lurking in the background, and they’re rising,” she said.Parkinson’s disease is already the second-most common neurodegenerative disease after Alzheimer’s. Symptoms, which can include uncontrolled movements, difficulty with balance, and memory problems, generally develop in people age 60 and older, but they can occur, though rarely, in people as young as 20. Could something in the air explain the increasing worldwide prevalence of Parkinson’s? Researchers have not identified one specific cause, but they know Parkinson’s symptoms result from degeneration of nerve cells in the substantia nigra, the part of the brain that produces dopamine and other signal-transmitting chemicals necessary for movement and coordination.A host of air pollution suspects are now thought to play a role in the loss of dopamine-producing cells, according to Emory University environmental health scientist W. Michael Caudle, who uses mass spectrometry to identify chemicals in our bodies. One suspect he’s looking at are lipopolysaccharides, compounds often found in air pollution and bacterial toxins. Although lipopolysaccharides cannot directly enter the brain, they inflame the liver. The liver then releases inflammatory molecules into the bloodstream, which interact with blood vessels in the blood-barrier. “Then the inflammatory response in the brain leads to loss of dopamine neurons, like that seen in Parkinson’s disease,” Caudle says.More evidence comes from neuroepidemiologist Brittany Krzyzanowski, based at the Barrow Neurological Institute in Phoenix. Krzyzanowski had an “aha!” moment when she saw a map highlighting the high risk of Parkinson’s disease in the Mississippi–Ohio River Valley, including areas of Tennessee and Kentucky. At first she wondered whether the Parkinson’s hotspot was due to pesticide use in the region. But then it hit her: The area also had a network of high-density roads, suggesting that air pollution could be involved. “The pollution in these areas may contain more combustion particles from traffic and heavy metals from manufacturing, which have been linked to cell death in the part of the brain involved in Parkinson’s disease,” she said.In a study published in Neurology in October 2023, Krzyzanowski and colleagues, using sophisticated geospatial analytic techniques, went on to show that those with median levels of air pollution have a 56 percent greater risk of developing Parkinson’s disease compared to those living in regions with the lowest level of air pollution. Along with the Mississippi-Ohio River Valley, other hotspots included central North Dakota, parts of Texas, Kansas, eastern Michigan, and the tip of Florida. People living in the western half of the U.S. are at a reduced risk of developing Parkinson’s disease compared with the rest of the nation.As to the hotspot in the Mississippi-Ohio River Valley, Parkinson’s there is 25% higher than in areas with the lowest air particulate matter. Aside from that, Krzyzanowski and her research team noted something especially odd: Frequency of the disease rose with the level of pollution, but then it plateaued even as air pollution continued to soar. One reason could be that other air pollution-linked diseases, including Alzheimer’s, are masking the emergence of Parkinson’s; another reason could be an unusual form of PM2.5. “Regional differences in Parkinson’s disease might reflect regional differences in the composition of the particulate matter, and some areas may have particulate matter containing more toxic components compared to other areas,” Krzyzanowsk says. Tapping the tenets of exposomics, she expects to explore these issues in the months and years ahead.The hunt is on for the connections between environmental factors and Alzheimer’s as well. USC neurogerontologist Caleb Finch has spent years studying dementia, especially Alzheimer’s disease, which affects more than six million Americans. As with Parkinson’s, Alzheimer’s numbers are rising in the United State and much of the world. Degenerative changes in neurons become increasingly frequent after the age of 60, yet half of the people who make it to 100 will not get dementia. Many factors could explain those discrepancies. Air pollution may be an important one, Finch says.Researchers like Finch and his USC colleague Jiu-Chiuan Chen are joining forces to explore the connections between environmental neurotoxins and decline in brain health. It’s a challenging project, since air pollution levels and specific pollutants vary on fine scales and can change from hour to hour in many areas of the globe. On the basis of brain scans of hundreds of people over a range of geographic areas, this much we know: “People living in areas of high levels of air pollution and who have been studied on three continents showed accelerated arterial disease, heart attacks, and strokes, and faster cognitive decline,” Finch says.Not everyone reacts the same way when exposed to pollutants, of course. Greatest risk for Alzheimer’s seems to hit people who have a genetic variant known as apolipoprotein E (APOE4), which is involved in making proteins that help carry cholesterol and other types of fat in the bloodstream. About 25 percent of people have one copy of that gene, and 2 to 3 percent carry two copies. But inheriting the gene alone doesn’t determine a person’s Alzheimer’s risk. Environmental exposures count too.A recent study by Chen, Finch, and colleagues published in the Journal of Alzheimer’s Disease looked at associations between air pollution exposure and early signs of Alzheimer’s in 1,100 men, all around age 56 when the study began. By age 68, test subjects with high PM2.5 exposures had the worst scores in verbal fluency. People exposed to high levels of nitrogen dioxide (NO2) air pollution were also linked to worsened episodic memory. The men who had APOE4 genes had the worst scores in executive function. The evidence indicates that the process by which air pollution interacts with genetic risk to cause Alzheimer’s in later life may begin in the middle years, at least for men.A separate USC study of more than 2,000 women found that when air quality improved, cognitive decline in older women slowed. When exposure to pollutants like PM2.5 and NO2 dropped by a few micrograms per cubic foot a year over the course of six years, the women in the study tested as being a year or so younger than their real age. This suggests that when exposure air pollution is lowered, dementia risk can go down.In parallel, an international study by the Lancet Commission concluded that the risk of dementia, including Alzheimer’s, can be lowered by modifying or avoiding 12 risk factors: hypertension, hearing impairment, smoking, obesity, depression, low social contact, low level of education, physical inactivity, diabetes, excessive alcohol consumption, traumatic brain injury—and air pollution. Together, the 12 modifiable risk factors account for around 40 percent of worldwide dementias, which theoretically could be prevented or delayed.In light of all this, Finch and Duke University social scientist Alexander Kulminski have proposed the “Alzheimer’s disease exposome” to assess environmental factors that interact with genes to cause dementia. Where medicines have failed, exposomics just might help. Studies of Swedish twins show that half of individual differences in Alzheimer’s risk may be environmental, and thus modifiable; and while vast sums of research funding have been poured into the genetic roots of the disease, it could be that altering the exposome would provide a better preventive than all the ongoing drug trials to date. Environmental toxins broadly disrupt cell repair and protective mechanisms in the brain, the researchers point out. And factors like obesity and stress contribute to chronic inflammation, which likely damages neurons’ ability to function and communicate. The research framework of the Alzheimer's disease exposome offers a comprehensive, systematic approach to the environmental underpinnings of Alzheimer's risk over individuals’ lifespans—from the time they are pre-fertilized gametes to life as a fetus in the womb to childhood and beyond.For three decades, Rosalind Wright at Mount Sinai has wanted to trace critical problems in neurodevelopment and neurodegeneration to pollutants—from highway emissions to heavy metals to specific household chemicals and a host of other factors—but the mass of data has been overwhelming. With the advent of artificial intelligence (AI) and sophisticated neuroimaging technology, high-precision research using vast genomic databanks is finally possible. “I knew we needed to ask these kinds of questions, but I didn't have the tools to do it. Now we do and it’s very exciting,” Wright says.Using machine learning—an AI approach to data analysis—Wright looks at giant datasets that include the precise location of an individual’s residence as well as the myriad of pollutants he or she encounters. “It's no different fundamentally from other statistical models we use,” she says. “It’s just that this one has been developed to be able to take in bigger and bigger data, more and more types of exposures.” The resulting data breakdown should tell us which factors drive which types of risk for which people. That information will help people know where they should target their efforts to reduce exposures to risky pollutants, and ultimately how to lower risk of impairment and disease, brain or otherwise.The tools used by Wright and her colleagues are being trained on diseases like Alzheimer’s. If you put genes and the environment together, “you start to see who might be at higher risk and also what underlying mechanisms might be driving it in different ways in different populations,” Wright says. The exposome could also explains more subtle cognitive effects of pollution that may emerge over long periods, such as harms to attention, intelligence, and performance.To address environmental brain risks, it’s important to know which pollutants are present—another target of exposomic research. In the United States, the EPA has placed stationary environmental monitors all over our major cities, conducting daily measurements of small particulates from traffic and industry, along with secondary chemicals that emerge as a result. There are also thousands of satellites all over the globe calibrating heat waves that can alter how the pollutants react with each other.Pioneers like Wright are just starting to chart the terrain of environmental exposures that affect the brain. “As we measure more and more of the exposome, we may be able to tailor prevention and intervention strategies. New weapons include a silicone bracelet that we have in the laboratory. You wear it and it will tell us what pollutants you are exposed to,” Wright says. She also is exploring more ways to collect data on the toxins people have already encountered: “With a single strand of hair, we can tell you what you’ve been exposed to. Hair grows about a centimeter a month, so if we get a hair from a pregnant woman and she has nine centimeters of hair, we can go back a full nine months, over the entire life of the fetus. Or we can create a life-long exposome history when a child loses a tooth at age six.”“We're designed to be pretty resilient,” Wright adds. The problem comes when the exposures are chronic and accumulative and overwhelm our ability to adapt. We’re not going to fix everything, “but if I know more about myself than before, that empowers me to think, ‘I’m optimizing the balance, and I’m intervening as best I can.’ ”Additional reporting and editing was done by Margaret Hetherman.This story is part of a series of OpenMind essays, podcasts, and videos supported by a generous grant from the Pulitzer Center's Truth Decay initiative.This story originally appeared on OpenMind, a digital magazine tackling science controversies and deceptions.

The new science of "exposomics" shows how air pollution contributes to Alzheimer’s, Parkinson’s, bipolar disorder and other brain diseases

B1992, burgeoning population, choking traffic, and explosive industrial growth in Mexico City had caused the United Nations to label it the most polluted urban area in the world. The problem was intensified because the high-altitude metropolis sat in a valley trapping that atmospheric filth in a perpetual toxic haze. Over the next few years, the impact could be seen not just in the blanket of smog overhead but in the city’s dogs, who had become so disoriented that some of them could no longer recognize their human families. In a series of elegant studies, the neuropathologist Lilian Calderón-Garcidueñas compared the brains of canines and children from “Makesicko City,” as the capital had been dubbed, to those from less polluted areas. What she found was terrifying: Exposure to air pollution in childhood decreases brain volume and heightens risk of several dreaded brain diseases, including Parkinson’s and Alzheimer’s, as an adult.

Calderón-Garcidueñas, today head of the Environmental Neuroprevention Laboratory at the University of Montana, points out that the damaged brains she documented through neuroimaging in young dogs and humans aren’t just significant in later years; they play out in impaired memory and lower intelligence scores throughout life. Other studies have found that air pollution exposure later in childhood alters neural circuitry throughout the brain, potentially affecting executive function, including abilities like decision-making and focus, and raising the risk of psychiatric disorders.

The stakes for all of us are enormous. In places like China, India, and the rest of the global south, air pollution, both indoor and outdoor, has steadily soared over the course of decades. According to the United Nations Foundation, “nearly half of the world’s population breathes toxic air each day, including more than 90 percent of children.” Some 2.3 billion people worldwide rely on solid fuels and open fires for cooking, the Foundation adds, making the problem far worse. The World Health Organization calculates about 3 million premature deaths, mostly in women and children, result from air pollution created by such cooking each year.


On supporting science journalism

If you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.


In the United States, meanwhile, average air pollution levels have decreased significantly since the passage of the Clean Air Act in 1970. But the key word is average. Millions of Americans are still breathing outdoor air loaded with inflammation-triggering ozone and fine particulate matter. These particles, known as PM2.5 (particles less than 2.5 micrometers in diameter), can affect the lungs and heart and are strongly associated with brain damage. Wildfires—like the ones that raged across Canada this past summer—are a major contributor of PM2.5. A recent study showed that pesticides, paints, cleaners, and other personal care products are another major—and under-recognized—source of PM2.5 and can raise the risk for numerous health problems, including brain-damaging strokes.

Untangling the relationship between air pollution and the brain is complex. In the modern industrial world, we are all exposed to literally thousands of contaminants. And not every person exposed to a given pollutant will develop the same set of symptoms, impairments, or diseases—in part because of their genes, and in part because each exposure may occur at a different point in development or impact a different area of the body or brain. What’s more, social disparities are at play: Poorer populations almost always live closer to factories, toxins, and pollutants.

The effort to figure it out and intervene has sparked a new field of study: exposomics, the science of environmental exposures and their effects on health, disease, and development. Exposomics draws on enormous datasets about the distribution of environmental toxins, genetic and cellular responses, and human behavioral patterns. There is a huge amount of information to parse, so researchers in the field are turning to another emerging science, artificial intelligence, to make sense of it all.

“Anything from our external environment—the air we breathe, food we eat, the water we drink, the emotional stress that we face every day—all of that gets translated into our biology,” says Rosalind Wright, professor of pediatrics and co-director of the Institute for Exposomic Research at the Icahn School of Medicine at Mount Sinai in New York. “All these things plus genes themselves explain the patterns of risk we see.” When an exposure is constant and cumulative, or when it overwhelms our ability to adapt, or “when you’re a fetus in utero, when you’re an infant or in early childhood or in a critical period of growth,” it can have a particularly powerful effect on lifelong cognitive clarity and brain health.

Neuroscientist Megan Herting at the University of Southern California (USC) has been studying the impact of air pollution on the developing brain. “Over the past few years, we have found that higher levels of PM2.5 exposure are linked to a number of differences in the shape, neural architecture, and functional organization of the developing brain, including altered patterns of cortical thickness and differences in the microstructure of gray and white matter,” she says. On the basis of neuroimaging of exposed youngsters, Herting and fellow researchers suspect the widespread differences in brain structure and function linked with air pollution may be early biomarkers for cognitive and emotional problems emerging later in life.

That suspicion gains support from an international meta-analysis (a study of other studies) published in 2023 that correlated exposure to air pollution during critical periods of brain development in childhood and adolescence to risk of depression and suicidal behavior. The imaging parts of the studies showed changes in brain structure, including neurocircuitry potentially involved in movement disorders like Parkinson’s, and white matter of the prefrontal lobes, responsible for executive decision-making, attention, and self-control.

In a 2023 study, Herting and colleagues tracked children transitioning into adolescence, when brains are in a sensitive period of development and thus especially vulnerable to long-term damage from toxins. Among brain regions developing during this period is the prefrontal cortex, which helps with cognitive control, self-regulation, decision-making, attention, and problem-solving, Herting says. “Your emotional reward systems are also still being refined,” she adds.

Looking at scan data from more than 9,000 youngsters exposed to air pollution between ages 9 and 10 and following them over the next couple of years, the researchers found changes in connectivity between brain regions, with some regions having fewer connections and others having more connections than normal. Herting explains that these structural and functional connections allow us to function in our daily lives, but how or even whether the changes in circuitry have an impact, researchers do not yet know.

The specific pollutants involved in the atypical brain circuits appear to be nitrogen dioxide, ozone, and PM2.5—the small particles that worry many researchers the most. Herting explains: Limits set on fine particulate matter are stricter in the United States than in most other countries but still inadequate. The U.S. Environmental Protection Agency currently limits annual average levels of the pollutant to 12 micrograms per cubic meter and permits daily spikes of up to 35 micrograms per cubic meter. Health organizations, on the other hand, have called for the agency to lower levels to 8 micrograms and 25 micrograms per cubic meter, respectively. Thus, even though it may be “safe” by EPA standards, “air quality across America is contributing to changes in brain networks during critical periods of childhood,” Herting says. And that may augur “increased risk for cognitive and emotional problems later in life.” She plans to follow her group of young people into adulthood, when advances in science and the passage of time should reveal more about the effect of air pollution exposure during adolescence.

Other research shows that air pollution increases risk of psychiatric disorder as years go by. In work based on large datasets in the United States and Denmark, University of Chicago computational biologist Andrey Rzhetsky and colleagues found that bad air quality was associated with increased rates of bipolar disorder and depression in both countries, especially when exposure occurs early in life. Rzhetsky and his team used two major sources: in Denmark, the National Health Registry, which contains health data on every citizen from cradle to grave; and in the United States, insurance claims with medical history plus details such as county of residence, age, sex, and importantly, linkages to family—specifics that helped reveal genetic predisposition to develop a psychiatric condition during the first 10 years of life.

“It's possible that the same environment will cause disease in one person but not in another because of predisposing genetic variants that are different in different people,” Rzhetsky says. “The different genetic predisposition, that’s one part of the puzzle. Another part is varying environment.”

Indeed, these complex diseases are spreading much faster than genetics alone seems to explain. “We definitely don’t know for sure which pollutant is causal. We can’t really pinpoint a smoking gun,” Rzhetsky says. But one pesky culprit continues to prove statistically significant: “It looks like PM2.5 is one of those strong signals.” To figure it out specifically, we’ll need much more data, and exposomics will play a vital role.

"This is a wake-up call,” Frances Jensen told her fellow physicians at the American Neurological Society’s symposium on Neurologic Dark Matter in October 2022. The meeting was an exploration of the exposome –the sum of external factors that a person is exposed to during a lifetime— driving neurodegenerative disease. It was focused in no small part on air pollution. Jensen, a University of Pennsylvania neurologist and president of the American Neurological Association, argued that researchers need to pay more attention to contaminants because the sharp rise in the number of Parkinson’s diagnoses cannot be explained by the aging population alone. “Environmental exposures are lurking in the background, and they’re rising,” she said.

Parkinson’s disease is already the second-most common neurodegenerative disease after Alzheimer’s. Symptoms, which can include uncontrolled movements, difficulty with balance, and memory problems, generally develop in people age 60 and older, but they can occur, though rarely, in people as young as 20. Could something in the air explain the increasing worldwide prevalence of Parkinson’s? Researchers have not identified one specific cause, but they know Parkinson’s symptoms result from degeneration of nerve cells in the substantia nigra, the part of the brain that produces dopamine and other signal-transmitting chemicals necessary for movement and coordination.

A host of air pollution suspects are now thought to play a role in the loss of dopamine-producing cells, according to Emory University environmental health scientist W. Michael Caudle, who uses mass spectrometry to identify chemicals in our bodies. One suspect he’s looking at are lipopolysaccharides, compounds often found in air pollution and bacterial toxins. Although lipopolysaccharides cannot directly enter the brain, they inflame the liver. The liver then releases inflammatory molecules into the bloodstream, which interact with blood vessels in the blood-barrier. “Then the inflammatory response in the brain leads to loss of dopamine neurons, like that seen in Parkinson’s disease,” Caudle says.

More evidence comes from neuroepidemiologist Brittany Krzyzanowski, based at the Barrow Neurological Institute in Phoenix. Krzyzanowski had an “aha!” moment when she saw a map highlighting the high risk of Parkinson’s disease in the Mississippi–Ohio River Valley, including areas of Tennessee and Kentucky. At first she wondered whether the Parkinson’s hotspot was due to pesticide use in the region. But then it hit her: The area also had a network of high-density roads, suggesting that air pollution could be involved. “The pollution in these areas may contain more combustion particles from traffic and heavy metals from manufacturing, which have been linked to cell death in the part of the brain involved in Parkinson’s disease,” she said.

In a study published in Neurology in October 2023, Krzyzanowski and colleagues, using sophisticated geospatial analytic techniques, went on to show that those with median levels of air pollution have a 56 percent greater risk of developing Parkinson’s disease compared to those living in regions with the lowest level of air pollution. Along with the Mississippi-Ohio River Valley, other hotspots included central North Dakota, parts of Texas, Kansas, eastern Michigan, and the tip of Florida. People living in the western half of the U.S. are at a reduced risk of developing Parkinson’s disease compared with the rest of the nation.

As to the hotspot in the Mississippi-Ohio River Valley, Parkinson’s there is 25% higher than in areas with the lowest air particulate matter. Aside from that, Krzyzanowski and her research team noted something especially odd: Frequency of the disease rose with the level of pollution, but then it plateaued even as air pollution continued to soar. One reason could be that other air pollution-linked diseases, including Alzheimer’s, are masking the emergence of Parkinson’s; another reason could be an unusual form of PM2.5. “Regional differences in Parkinson’s disease might reflect regional differences in the composition of the particulate matter, and some areas may have particulate matter containing more toxic components compared to other areas,” Krzyzanowsk says. Tapping the tenets of exposomics, she expects to explore these issues in the months and years ahead.

The hunt is on for the connections between environmental factors and Alzheimer’s as well. USC neurogerontologist Caleb Finch has spent years studying dementia, especially Alzheimer’s disease, which affects more than six million Americans. As with Parkinson’s, Alzheimer’s numbers are rising in the United State and much of the world. Degenerative changes in neurons become increasingly frequent after the age of 60, yet half of the people who make it to 100 will not get dementia. Many factors could explain those discrepancies. Air pollution may be an important one, Finch says.

Researchers like Finch and his USC colleague Jiu-Chiuan Chen are joining forces to explore the connections between environmental neurotoxins and decline in brain health. It’s a challenging project, since air pollution levels and specific pollutants vary on fine scales and can change from hour to hour in many areas of the globe. On the basis of brain scans of hundreds of people over a range of geographic areas, this much we know: “People living in areas of high levels of air pollution and who have been studied on three continents showed accelerated arterial disease, heart attacks, and strokes, and faster cognitive decline,” Finch says.

Not everyone reacts the same way when exposed to pollutants, of course. Greatest risk for Alzheimer’s seems to hit people who have a genetic variant known as apolipoprotein E (APOE4), which is involved in making proteins that help carry cholesterol and other types of fat in the bloodstream. About 25 percent of people have one copy of that gene, and 2 to 3 percent carry two copies. But inheriting the gene alone doesn’t determine a person’s Alzheimer’s risk. Environmental exposures count too.

A recent study by Chen, Finch, and colleagues published in the Journal of Alzheimer’s Disease looked at associations between air pollution exposure and early signs of Alzheimer’s in 1,100 men, all around age 56 when the study began. By age 68, test subjects with high PM2.5 exposures had the worst scores in verbal fluency. People exposed to high levels of nitrogen dioxide (NO2) air pollution were also linked to worsened episodic memory. The men who had APOE4 genes had the worst scores in executive function. The evidence indicates that the process by which air pollution interacts with genetic risk to cause Alzheimer’s in later life may begin in the middle years, at least for men.

A separate USC study of more than 2,000 women found that when air quality improved, cognitive decline in older women slowed. When exposure to pollutants like PM2.5 and NO2 dropped by a few micrograms per cubic foot a year over the course of six years, the women in the study tested as being a year or so younger than their real age. This suggests that when exposure air pollution is lowered, dementia risk can go down.

In parallel, an international study by the Lancet Commission concluded that the risk of dementia, including Alzheimer’s, can be lowered by modifying or avoiding 12 risk factors: hypertension, hearing impairment, smoking, obesity, depression, low social contact, low level of education, physical inactivity, diabetes, excessive alcohol consumption, traumatic brain injury—and air pollution. Together, the 12 modifiable risk factors account for around 40 percent of worldwide dementias, which theoretically could be prevented or delayed.

In light of all this, Finch and Duke University social scientist Alexander Kulminski have proposed the “Alzheimer’s disease exposome” to assess environmental factors that interact with genes to cause dementia. Where medicines have failed, exposomics just might help. Studies of Swedish twins show that half of individual differences in Alzheimer’s risk may be environmental, and thus modifiable; and while vast sums of research funding have been poured into the genetic roots of the disease, it could be that altering the exposome would provide a better preventive than all the ongoing drug trials to date. Environmental toxins broadly disrupt cell repair and protective mechanisms in the brain, the researchers point out. And factors like obesity and stress contribute to chronic inflammation, which likely damages neurons’ ability to function and communicate. The research framework of the Alzheimer's disease exposome offers a comprehensive, systematic approach to the environmental underpinnings of Alzheimer's risk over individuals’ lifespans—from the time they are pre-fertilized gametes to life as a fetus in the womb to childhood and beyond.

For three decades, Rosalind Wright at Mount Sinai has wanted to trace critical problems in neurodevelopment and neurodegeneration to pollutants—from highway emissions to heavy metals to specific household chemicals and a host of other factors—but the mass of data has been overwhelming. With the advent of artificial intelligence (AI) and sophisticated neuroimaging technology, high-precision research using vast genomic databanks is finally possible. “I knew we needed to ask these kinds of questions, but I didn't have the tools to do it. Now we do and it’s very exciting,” Wright says.

Using machine learning—an AI approach to data analysis—Wright looks at giant datasets that include the precise location of an individual’s residence as well as the myriad of pollutants he or she encounters. “It's no different fundamentally from other statistical models we use,” she says. “It’s just that this one has been developed to be able to take in bigger and bigger data, more and more types of exposures.” The resulting data breakdown should tell us which factors drive which types of risk for which people. That information will help people know where they should target their efforts to reduce exposures to risky pollutants, and ultimately how to lower risk of impairment and disease, brain or otherwise.

The tools used by Wright and her colleagues are being trained on diseases like Alzheimer’s. If you put genes and the environment together, “you start to see who might be at higher risk and also what underlying mechanisms might be driving it in different ways in different populations,” Wright says. The exposome could also explains more subtle cognitive effects of pollution that may emerge over long periods, such as harms to attention, intelligence, and performance.

To address environmental brain risks, it’s important to know which pollutants are present—another target of exposomic research. In the United States, the EPA has placed stationary environmental monitors all over our major cities, conducting daily measurements of small particulates from traffic and industry, along with secondary chemicals that emerge as a result. There are also thousands of satellites all over the globe calibrating heat waves that can alter how the pollutants react with each other.

Pioneers like Wright are just starting to chart the terrain of environmental exposures that affect the brain. “As we measure more and more of the exposome, we may be able to tailor prevention and intervention strategies. New weapons include a silicone bracelet that we have in the laboratory. You wear it and it will tell us what pollutants you are exposed to,” Wright says. She also is exploring more ways to collect data on the toxins people have already encountered: “With a single strand of hair, we can tell you what you’ve been exposed to. Hair grows about a centimeter a month, so if we get a hair from a pregnant woman and she has nine centimeters of hair, we can go back a full nine months, over the entire life of the fetus. Or we can create a life-long exposome history when a child loses a tooth at age six.”

“We're designed to be pretty resilient,” Wright adds. The problem comes when the exposures are chronic and accumulative and overwhelm our ability to adapt. We’re not going to fix everything, “but if I know more about myself than before, that empowers me to think, ‘I’m optimizing the balance, and I’m intervening as best I can.’ ”

Additional reporting and editing was done by Margaret Hetherman.

This story is part of a series of OpenMind essays, podcasts, and videos supported by a generous grant from the Pulitzer Center's Truth Decay initiative.

This story originally appeared on OpenMind, a digital magazine tackling science controversies and deceptions.

Read the full story here.
Photos courtesy of

Environmental Agency Denies Petition to Designate Big Hole River as Impaired by Nutrient Pollution

Montana’s environmental regulator has denied a petition to designate the Big Hole River as impaired by nitrogen and phosphorus

Montana’s environmental regulator has denied a petition to designate the Big Hole River as impaired by nitrogen and phosphorus, throwing a wrench in environmentalists’ efforts to put the blue-ribbon fishery on a “pollution diet.”Upper Missouri Waterkeeper and the Big Hole River Foundation contend that excess nutrients are creating regular summertime algal blooms that can stretch for more than a mile, robbing fish and the macroinvertebrate bugs they eat of the oxygen they need to thrive. The groups argue in the petition they sent to the Montana Department of Environmental Quality last month that an impairment designation would direct the agency to identify and work to reduce the river’s pollution sources in an effort to rebalance the river’s aquatic ecosystem.On April 14, about a month after receiving the 32-page petition, DEQ wrote that it “cannot grant” the group’s petition. The agency’s letter doesn’t quibble with the groups’ findings, which were detailed in a five-year data collection effort. Instead, the agency suggested that legislation passed in 2021 has tied its hands. “As a result of Senate Bill 358, passed during the 2021 Legislative Session … DEQ is unable to base nutrient assessment upon the numeric nutrient criteria,” the letter, signed by DEQ Director Sonja Nowakowski, reads. In an April 23 conversation with Montana Free Press, Upper Missouri Waterkeeper Executive Director Guy Alsentzer criticized the agency’s decision, arguing that it did not use the best available science and applied “illogical and disingenuous” reasoning in its denial. “EPA already took action and struck down Senate Bill 358 from the 2021 session,” Alsentzer said, referencing federal regulators’ oversight of state laws and rules governing water quality. “Numeric criteria are applicable.”A spokesperson for the EPA confirmed Alsentzer’s assertion, writing in an April 24 email to MTFP that numeric nutrient standards for nitrogen and phosphorus the agency approved a decade ago “remain in effect for Clean Water Act purposes” and will remain so “unless or until the EPA approves the removal of the currently applicable numeric nutrient criteria and approves revised water quality standards.”A DEQ spokesperson did not directly answer MTFP’s questions about what water quality standards DEQ is using to assess Montana waterways and determine whether permittees are complying with state and federal regulations.The agency wrote in an email that no permitted pollution sources under its regulatory oversight are discharging into the Big Hole, suggesting that its enforcement role is limited. The agency also wrote that an impairment designation is not required to implement water quality improvement projects such as creating riparian buffers, improving forest roads, or creating shaded areas. “Watershed partners may begin actively working on nonpoint source pollution reduction projects at any time,” DEQ spokesperson Madison McGeffers wrote to MTFP. “There is nothing standing in the way of starting work on these types of projects to improve water quality. In fact, the Big Hole River Watershed Committee is actively implementing its Watershed Restoration Plan with funds and support from DEQ Nonpoint Source & Wetland Section’s 319 program.”Alsentzer countered that a science-based cleanup plan and greater accountability will benefit the Big Hole regardless of whether nutrients are flowing into the river from a pipe or entering via more diffuse and harder-to-regulate channels.“You can’t get to that if you don’t recognize that you’ve got a problem we need to solve,” he said, adding that an impairment designation “unlocks pass-through funding to the tune of millions of dollars.”Addressing manmade threats to the Big Hole should be a priority for DEQ, given local communities’ economic reliance on a healthy river, he added.“It’s just a real tragic state of affairs when you have a blue-ribbon trout fishery in a very rural county that’s essentially having its livelihood flushed down the drain because we can’t get our agencies to actually implement baseline river protections (and) use science-based standards,” Alsentzer said. “When people try to do the work for the agency and help them, they’re getting told to go pound sand. I think that’s wrong.”Two years ago, Montana Fish, Wildlife and Parks biologists recorded historically low numbers of brown trout along some stretches of the Big Hole. Anglers and conservationists floated a number of possible contributing factors, ranging from pathogens and drought conditions to angling pressure and unmitigated pollution. Save Wild Trout, a nonprofit formed in 2023 to understand which factors merit further investigation, described the 2023 southwestern Montana fishery “collapse” as a “canary in the coal mine moment.”In response to the 2023 population slump, Gov. Greg Gianforte announced the launch of a multiyear research effort on Jefferson Basin rivers that FWP is coordinating with Montana State University. Narrative Standards For ‘Undesirable Aquatic Life’ DEQ’s letter to Upper Missouri Waterkeeper and the Big Hole River Foundation leaves open the possibility of a future impairment designation based on narrative water quality standards. After mentioning the 2021 legislation, Nowakowski wrote that the agency reviewed the submitted data “along with other readily available data, in consideration of the state’s established narrative criteria.”The letter goes on to outline the additional material petitioners would need to submit for the agency to evaluate an impairment designation using narrative criteria, which establish that surface waters must be “free from substances” that “create conditions which produce undesirable aquatic life.”In an April 22 letter, Upper Missouri Waterkeeper and the Big Hole River Foundation addressed the petition denial in two parts. First, the groups argued that numeric nutrient standards apply. Second, they resubmitted material — photos, emails, a macroinvertebrate report, and “Aquatic Plant Visual Assessment Forms” — to support an impairment designation under the looser narrative standards. “We encourage DEQ to do the right thing, use all available science to determine the Big Hole River impaired for nutrients, and commit to working with petitioners and other (stakeholders) in addressing the pollution sources undermining this world-class waterway and harming the diverse uses it supports,” the letter says. Alsentzer noted that he has set up a meeting with the EPA to discuss DEQ’s treatment of the petition and its description of applicable water quality standards.The dispute over numeric nutrient standards comes shortly after the Legislature passed another bill seeking to repeal them. Any day now, Gianforte is expected to sign House Bill 664, which bears a striking similarity to 2021’s Senate Bill 358. HB 664 has garnered support from Nowakowski, who described it as a “time travel” bill that will return the state to “individual, site-by-site” regulations in lieu of more broadly applicable numeric standards. This story was originally published by Montana Free Press and distributed through a partnership with The Associated Press.Copyright 2025 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.Photos You Should See - Feb. 2025

Supreme Court justices consider reviving industry bid to ax California clean car rule

The Supreme Court on Wednesday heard oral arguments in a case that could revive a bid by fuel producers to ax California’s clean car standards. The court was not considering the legality of the standards themselves, which ​​require car companies to sell new vehicles in the state that produce less pollution — including by mandating...

The Supreme Court on Wednesday heard oral arguments in a case that could revive a bid by fuel producers to ax California’s clean car standards. The court was not considering the legality of the standards themselves, which ​​require car companies to sell new vehicles in the state that produce less pollution — including by mandating a significant share of cars sold to be electric or hybrid.  Instead, the Supreme Court was considering whether the fuel industry had the authority to bring the lawsuit at all. A lower court determined that the producers, which include numerous biofuel companies and trade groups representing both them and the makers of gasoline, did not have standing to bring the case. Some of the justices were quiet, so it’s difficult to predict what the ultimate outcome of the case will be. However, others appeared critical of the federal government and California’s arguments that the fuel producers do not have the right to bring a suit. Justice Brett Kavanaugh in particular noted that the Environmental Protection Agency (EPA) itself did not initially try to have the case tossed on that basis.  “Isn't that a tell here? I mean, EPA, as you, of course, know, routinely raises standing objections when there's even — even a hint of a question about it,” Kavanaugh said.  The fuel producers argued that while it was technically the auto industry that was being regulated, the market was being “tilted” against them as well by California’s rule, which was also adopted by other states. The EPA and California have argued that the fuel producers are arguing on the basis of outdated facts and a market that has shifted since the rule was first approved by the EPA in 2013.  The EPA needs to grant approval to California to issue such rules. The approval was revoked by the Trump administration and later reinstated in the Biden administration.  If the justices revive the currently dismissed case, lower courts would then have to decide whether to uphold the California rule — though the underlying case could eventually make its way to the high court as well.  Meanwhile, California has since passed subsequent standards that go even further — banning the sale of gas-powered cars in the state by 2035. That rule was approved by the Biden administration — though Congress may try to repeal it.

EPA fires or reassigns hundreds of staffers

The Environmental Protection Agency plans to fire or reassign more than 450 staffers working on environmental justice issues, it said Tuesday.Why it matters: The large-scale changes could effectively end much of the EPA's work tackling pollution in historically disadvantaged communities.It's part of the Trump administration's effort to vastly shrink the federal workforce. EPA has around 15,000 employees.Driving the news: EPA notified roughly 280 employees that they will be fired in a "reduction in force." Another 175 who perform "statutory functions" will be reassigned.The employees come from the Office of Environmental Justice and External Civil Rights, the Office of Inclusive Excellence, and EPA regional offices."EPA is taking the next step to terminate the Biden-Harris Administration's Diversity, Equity, and Inclusion and Environmental Justice arms of the agency," a spokesperson said.Between the lines: The firings will likely see challenges from congressional Democrats and the employees themselves.EPA had previously put many environmental justice staffers on administrative leave.Administrator Lee Zeldin, during a Monday news conference, defended the agency's broader efforts to cut environmental justice grant programs, arguing the money is ill-spent."The problem is that, in the name of environmental justice, a dollar will get secured and not get spent on remediating that environmental issue," he said.

The Environmental Protection Agency plans to fire or reassign more than 450 staffers working on environmental justice issues, it said Tuesday.Why it matters: The large-scale changes could effectively end much of the EPA's work tackling pollution in historically disadvantaged communities.It's part of the Trump administration's effort to vastly shrink the federal workforce. EPA has around 15,000 employees.Driving the news: EPA notified roughly 280 employees that they will be fired in a "reduction in force." Another 175 who perform "statutory functions" will be reassigned.The employees come from the Office of Environmental Justice and External Civil Rights, the Office of Inclusive Excellence, and EPA regional offices."EPA is taking the next step to terminate the Biden-Harris Administration's Diversity, Equity, and Inclusion and Environmental Justice arms of the agency," a spokesperson said.Between the lines: The firings will likely see challenges from congressional Democrats and the employees themselves.EPA had previously put many environmental justice staffers on administrative leave.Administrator Lee Zeldin, during a Monday news conference, defended the agency's broader efforts to cut environmental justice grant programs, arguing the money is ill-spent."The problem is that, in the name of environmental justice, a dollar will get secured and not get spent on remediating that environmental issue," he said.

EPA firing 280 staffers who fought pollution in overburdened neighborhoods

The Environmental Protection Agency (EPA) will fire 280 staffers who worked on tackling pollution in overburdened and underserved communities and will reassign another 175. These staffers worked in an area known as “environmental justice,” which helps communities that face a disproportionate amount of pollution exposure, especially minority or low-income communities.  The EPA has framed its...

The Environmental Protection Agency (EPA) will fire 280 staffers who worked on tackling pollution in overburdened and underserved communities and will reassign another 175. These staffers worked in an area known as “environmental justice,” which helps communities that face a disproportionate amount of pollution exposure, especially minority or low-income communities.  The EPA has framed its efforts to cut these programs — including its previous closure of environmental justice offices — as part of a push to end diversity programming in the government. Supporters of the agency's environmental justice work have pointed out that Black communities face particularly high pollution levels and that the programs also help white Americans, especially if they are poor.  “EPA is taking the next step to terminate the Biden-Harris Administration’s Diversity, Equity, and Inclusion and Environmental Justice arms of the agency,” an EPA spokesperson said in a written statement.   “Today, EPA notified diversity, equity, and inclusion and environmental justice employees that EPA will be conducting a Reduction in Force,” the spokesperson said. “The agency also notified certain statutory and mission essential employees that they are being reassigned to other offices through the ‘transfer of function’ procedure also outlined in [the Office of Personnel Management’s] Handbook and federal regulations” The firings will be effective July 31, according to E&E News, which first reported that they were occurring. The news comes as the Trump administration has broadly sought to cut the federal workforce. The administration has previously indicated that it planned to cut 65 percent of the EPA’s overall budget. It’s not clear how much of this will be staff, though according to a plan reviewed by Democrat House staff, the EPA is considering the termination of as many as about 1,100 employees from its scientific research arm.  Meanwhile, as part of their reductions in force, other agencies including the Department of Health and Human Services and the Department of Veterans Affairs have fired tens of thousands of staffers. The EPA is smaller than these agencies, with a total of more than 15,000 employees as of January.  Nearly 170 environmental justice staffers were previously placed on paid leave while the agency was “in the process of evaluating new structure and organization.”

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