Air pollution and brain damage: what the science says Now researchers are trying to determine how pollutants do their damage, and how much harm they cause

Epidemiological studies have linked dirty air to dementia and other brain disorders

In 2012, Deborah Cory-Slechta at the University of Rochester, New York, received a “bucket of brains”. A colleague had been studying how air pollution around the university harms the hearts and lungs of mice, and had asked Cory-Slechta to check the animals’ brains for damage. As a specialist in the neurotoxicity of lead, Cory-Slechta remembers thinking: ‘Air pollution? How bad could this be?’ But what she saw in those brains was so “astounding”, she says, that it shifted her entire research focus.

Focusing on how air pollution harms the brain¹ landed Cory-Slechta in lonely territory. It’s well established that air pollution, in the form of particulate matter, ozone or other toxic gases, contributes to asthma, lung cancer and other respiratory illnesses, and that particulate matter especially contributes to heart disease². But back then, she says, few people studying air pollution were interested in the brain — and even fewer neuroscientists were interested in air pollution. Her presentations got so little attention at neuroscience conferences that she stopped attending the meetings.

Now, this area of research is getting more notice and prompting concern around the globe³. Study after study has shown that higher levels of air pollution are correlated with increased risks of dementia, as well as higher rates of depression, anxiety and psychosis⁴. Researchers have also found links to neurodevelopmental conditions, such as autism, and cognitive deficits in children⁵.

In 2020, the influential Lancet Commission on dementia recognized air pollution as a risk factor for the condition⁶, and in its follow-up report last year⁷ it stated that exposure to airborne particulate matter “is now of intense concern and interest”. Meanwhile, a 2022 report⁸ from the UK government’s Committee on the Medical Effects of Air Pollutants called for more research on air pollution’s links to dementia. Likewise, the 2021 global air-quality guidelines from the World Health Organization (WHO) emphasized the importance of studying air pollution’s neurological effects on young and old people⁹.

The WHO estimates that 99% of the world’s population is exposed to pollution above recommended levels, with many cities in low- and middle-income countries having particularly bad air quality. But it’s not just megacities, such as Mexico City and Delhi, where people face risks. “Even low-level exposure that people think is safe enough for public health is doing something at the brain level,” says Megan Herting, a neuroscientist at the University of Southern California in Los Angeles.

Researchers must now try to tease out the mechanisms behind these problems to take steps to mitigate such issues, says Ian Mudway, an environmental toxicologist at Imperial College London and a co-author of the 2022 UK report. For Mudway, the million-dollar question is: “What is it in air pollution which is driving these effects?”

Making the links

Studies of the brains of children and dogs in Mexico City in the late 2000s and early 2010s were among the first to raise alarms about air pollution’s neurotoxicity. Neuroimaging revealed that many more children living in the highly polluted city had lesions in the white-matter tracts that connect brain regions than did children in less-polluted areas, with the prefrontal cortex seeming particularly vulnerable. And city children, with no other risk factors for brain disorders, performed comparatively poorly on cognitive tasks¹⁰ (see ‘Problematic proteins’ for more findings).

Source: L. Calderón-Garcidueñas *et al.* *Int. J. Environ. Res. Public Health* 3, 11568 (2021)/(CC-BY-4.0)

Pollution is a hugely complex mix of gaseous and particulate components that differ depending on the source. Vehicle exhaust and industrial manufacturing are major sources of particles of various sizes, and cooking stoves, wildfires and desert dust also contribute. Fuel combustion and other sources release nitrogen and sulfur oxides, carbon monoxide and ozone. Studies in multiple countries, including in those where regulations have drastically improved air quality in recent decades, have found associations between pollution and specific brain disorders.

A 2023 analysis of more than 389,000 participants in the UK Biobank showed that long-term exposure to airborne particulate matter, nitric oxide and nitrogen dioxide correlated with higher levels of depression and anxiety¹¹. Lead author Guoxing Li, an environmental toxicologist at Peking University in China, emphasizes that even very low exposure levels increased the risk of these conditions.

Last month, a 16-year study of more than 200,000 residents in Scotland found that higher cumulative nitrogen dioxide exposure was associated with increased hospital admissions for mental-health and behavioural disorders¹².

Meanwhile, studies in France, the United States and China have documented that in regions where air quality has improved, there are decreased rates of dementia, cognitive decline and depression in older populations⁷.

Observational studies have also linked air pollution to structural changes in the brain, such as reduced hippocampal volume, that are consistent with heightened dementia risk in older adults¹³. And Herting’s studies of neuroimaging data from the developing brains of thousands of young people across the United States suggest that air pollution disrupts the development of white-matter tracts. Last year, her team reported that an increase in exposure to air pollution seems to alter communication between brain regions¹⁴.

But such studies have yet to converge on a clear pattern of damage, Herting says. She suspects that the timing of exposure during development might shape vulnerability.

Despite all the evidence connecting air pollution with damage to the brain, researchers say that it is hard to pin down a clear cause using just observational studies. For example, people in poor communities, who often breathe the worst-quality air, are likely to have more risk factors for brain disorders, stress, lower educational attainment and obesity, compared with those in higher-income areas. And many existing studies estimate exposure on the basis of residential addresses, without accounting for how people’s professions and lifestyles shape their exposure.

The specific types of pollutant that people breathe almost certainly matter, researchers say. Standard air-quality measurements are based on levels of primary gaseous components and of particulate matter that have diameters smaller than 10 micrometres (PM₁₀) or 2.5 micrometres (PM_2.5). But airborne particles carry a range of chemicals, from simple salts to countless highly toxic compounds, that vary across locations. “All particles are treated as being equally toxic,” says Mudway, “yet they are a smorgasbord of every chemical — hundreds of thousands of chemicals — in the air.”

What’s more, ultrafine particles aren’t routinely monitored, notes Cory-Slechta. Yet, particles less than 100 nanometres across are the most chemically reactive airborne particles and the most likely to penetrate the body and brain, she says.

Even without this gap in monitoring data, Mudway says, observational studies of people breathing many pollutants cannot isolate the responsible chemicals to yield a mechanistic understanding. Cardiovascular disease is a known risk factor for dementia. So the damage that air pollution does to the heart and blood vessels is another confounding factor. “The only way to unravel it,” says Mudway, “is through experimentation.”

Into the lab

Lab studies can show, for example, that under controlled conditions, real-world cocktails of airborne pollutants harm the brain. This is what Cory-Slechta saw in 2012, when she compared the brains of mice that had breathed air from around the university with those that had breathed filtered air. Subsequent studies from her lab reported that mice exposed to ultrafine particles during development — including in the womb, from their mothers’ breathing — have enlarged white-matter tracts and brain ventricles¹⁵. Mice exposed during development went on to exhibit greater impulsivity and short-term memory deficits.

The physical brain changes partially overlap with those in people with neurodevelopmental conditions such as autism and schizophrenia. In older animals, air pollution seems to accelerate the deposition of the amyloid and tau proteins associated with Alzheimer’s disease. Other animal studies have found damage at the anatomical, cellular and molecular levels.

Brain scans show areas of reduced cortical thickness (coloured regions) in children exposed to higher levels of traffic pollution during their first year of life.Credit: T. Beckwith *et al./PLoS ONE* (**CC-BY-4.0**)

Although signs of damage vary from study to study, Caleb Finch, who researches ageing at the University of Southern California, says that there is one shared facet: “It’s an inflammatory response,” he says. Studies from his lab and others show that the genes that mediate inflammatory responses are switched on; messengers associated with inflammation become more abundant; there are signs of oxidative stress; and microglial cells that sense damage and protect neurons are activated. Every major class of brain cell is affected, says Finch.