Brain maps show how exposure to fine particulate matter (PM2.5) and nitrogen dioxide (NO₂) was associated with cortical thickness in two groups of older adults. Warmer colors indicate regions where greater exposure was linked to a thinner cortex (in WHIMS), while cooler colors indicate regions where greater exposure was linked to a thicker cortex (in VETSA).
Photo Credit: Stevens INI
Scientific Frontline: Extended "At a Glance" Summary: Air Pollution and Brain Cortex Changes
The Core Concept: Exposure to common outdoor air pollutants, specifically fine particulate matter (PM2.5) and nitrogen dioxide (NO₂), is associated with structural changes in regions of the brain's cortex that are highly vulnerable to Alzheimer's disease.
Key Distinction/Mechanism: The study revealed a complex, non-linear relationship where older women exposed to these pollutants showed cortical thinning (often associated with neurodegeneration), while a younger group of men exhibited cortical thickening, suggesting a potential early, temporary biological response before later damage occurs.
Origin/History: The findings, published in August 2026 by researchers at the USC Mark and Mary Stevens Neuroimaging and Informatics Institute, draw on MRI brain scans and residential air pollution data from two independent cohorts: the Vietnam Era Twin Study of Aging and the Women's Health Initiative Memory Study.
Major Frameworks/Components:
- Pollutant Exposure Analysis: Estimation of individuals' exposure to PM2.5 and NO₂ over the three years preceding their brain scans, utilizing residential histories.
- Cortical Thickness Measurement: Assessment of the cortex, focusing on four areas particularly vulnerable to Alzheimer's: the entorhinal, fusiform, inferior temporal, and middle temporal cortices.
- Non-linear Aging Response Hypothesis: The theory that initial brain responses to pollution might present as tissue thickening (potentially due to inflammation or early amyloid accumulation) before shifting to tissue thinning as neurodegeneration progresses with age.
Branch of Science: Neuroscience, Neurotoxicology, Environmental Epidemiology, and Gerontology.
Future Application: The research highlights the need for longitudinal studies tracking both sexes over time, incorporating Alzheimer's biomarkers (like amyloid and tau) and inflammation measures, to definitively link specific pollution exposure levels to distinct stages of brain injury and subsequent dementia risk.
Why It Matters: Because air pollution is a pervasive environmental factor, understanding its precise mechanistic impact on brain structure provides critical insight into modifiable risk factors for Alzheimer's disease, potentially guiding public health strategies and early intervention approaches before clinical dementia symptoms manifest.
USC researchers found that exposure to common air pollutants was associated with different patterns of cortical thickness in two groups of older adults, pointing to a potentially complex relationship between pollution, aging, and brain health.
Exposure to common forms of outdoor air pollution may be linked to structural changes in brain regions that are especially vulnerable to Alzheimer’s disease, according to a new study led by researchers from the USC Mark and Mary Stevens Neuroimaging and Informatics Institute (Stevens INI) at the Keck School of Medicine of USC.
The study, published in NeuroToxicology, examined brain scans and residential air pollution estimates from 1,484 adults without dementia or a history of stroke. In a group of older women, greater exposure to fine particulate matter and nitrogen dioxide was associated with a thinner cortex, the brain’s outer layer, in regions important for memory and commonly affected by Alzheimer’s disease.
The researchers found an unexpectedly different pattern among a separate group of younger men: Greater pollution exposure was associated with a thicker cortex in the same Alzheimer’s-vulnerable regions. That association weakened with age and reversed around age sixty-five, although the later negative association was not statistically significant.
The divergent findings may reflect different phases of a complex biological response to pollution, but the researchers caution that the study cannot determine whether age, sex, or other differences between the two groups account for the results.
“Air pollution did not correspond to one uniform pattern of brain structure across all participants,” said Lauren Salminen, PhD, lead author of the study and assistant professor of research neurology. “The contrasting findings suggest that the brain’s response to pollution may change across the aging process. Following people over time will be essential for determining what these patterns mean for Alzheimer’s risk.”
Measuring Pollution’s Imprint on the Brain
The researchers studied two independent groups: 387 men from the Vietnam Era Twin Study of Aging, who were about sixty-two years old on average, and 1,097 women from the Women’s Health Initiative Memory Study, whose average age was approximately seventy-eight.
Using participants’ residential histories, the team estimated exposure during the three years before each person’s MRI scan to two widespread outdoor air pollutants: fine particulate matter, known as PM2.5, and nitrogen dioxide, or NO₂.
PM2.5 consists of particles less than 2.5 micrometers wide—small enough to travel deep into the lungs and potentially enter the bloodstream. It can come from vehicle exhaust, power plants, wildfires, and other sources of combustion. NO₂ is a gas produced largely by burning fossil fuels and is commonly associated with traffic.
The researchers then measured cortical thickness across the brain. The cortex is the folded outer layer involved in memory, language, decision-making, and many other essential functions. It generally becomes thinner with age, and accelerated thinning in certain regions can be a sign of neurodegeneration.
The team focused first on four areas that are particularly vulnerable to Alzheimer’s disease: the entorhinal, fusiform, inferior temporal, and middle temporal cortices. Together, these regions formed a combined measure of cortical thickness.
Among the older women, higher exposure to both pollutants was associated with a thinner cortex in this Alzheimer’s-vulnerable group of regions. For each additional microgram per cubic meter of PM2.5 exposure, the estimated difference in cortical thickness was comparable to about thirteen months of aging. For each additional part per billion of NO₂, the difference was comparable to roughly three months of aging.
The pattern also extended well beyond regions associated with Alzheimer’s. Higher PM2.5 exposure was linked to a thinner cortex in twenty-three of the thirty-four brain regions examined, spanning all four lobes of the brain.
Why a Thicker Cortex May Not Always Mean a Healthier Brain
In the younger group of men, higher pollution exposure was associated with a thicker cortex in regions vulnerable to Alzheimer’s disease. Although thickness is often interpreted as a sign of healthier tissue, emerging research suggests that the cortex may temporarily thicken during the earliest stages of some disease processes before becoming thinner as neurodegeneration advances.
Possible explanations include inflammation, swelling or enlargement of brain cells, or early changes associated with the accumulation of amyloid, a protein involved in Alzheimer’s disease. The new study did not measure amyloid, tau, or inflammation, however, so it cannot confirm whether any of these processes explain the findings.
The age-related pattern among the men offers a clue: The association between PM2.5 and greater cortical thickness gradually diminished between ages fifty-five and sixty-four and became negative after approximately age sixty-five.
“Our findings raise the possibility that pollution-related brain changes are not linear,” Salminen said. “A thicker cortex at one point in life could represent an early biological response, while thinning later in life could reflect accumulated damage. This is an important hypothesis, but it must be tested in studies that track the same people as they age and include Alzheimer’s biomarkers.”
Because the two study groups differed in both age and sex, the researchers cannot determine which factor—or combination of factors—explains the contrasting results. The analysis also provides a snapshot at one point in time, meaning it cannot establish that air pollution caused the observed brain differences.
Still, the findings add to evidence that environmental exposures may play a meaningful role in brain aging and dementia risk.
“Air pollution is a widespread and potentially modifiable risk factor that affects people across entire communities,” said Arthur W. Toga, PhD, director of the Stevens INI. “Advanced brain imaging gives us a powerful way to investigate how these exposures may influence the brain long before dementia symptoms appear. Understanding when these changes begin and how they evolve could ultimately help guide more effective approaches to protecting brain health.”
Future research will need to follow men and women from the same study over time while measuring inflammation, amyloid, tau, and cognitive change. That could help researchers determine whether the contrasting cortical patterns represent different stages of pollution-related brain injury and whether they predict a greater risk of Alzheimer’s disease.
Funding: The research was supported by the National Institutes of Health, including the National Institute on Aging, the National Institute of Environmental Health Sciences, and the National Heart, Lung, and Blood Institute; the Southern California Environmental Health Sciences Center; the Alzheimer’s Disease Research Center at USC; the Wake Forest Alzheimer’s Disease Research Center; the NIH Intramural Research Program; and US Environmental Protection Agency research assistance agreements supporting the air pollution models.
Published in journal: NeuroToxicology
Authors: Lauren E. Salminen, Xinhui Wang, Andrew J. Petkus, Christine Fennema-Notestine, Jeremy A. Elman, Donald J. Hagler Jr., Joel D. Kaufman, Joshua Millstein, Meredith N. Braskie, Joshua Liu, Hyung Jin Cho, Deydeep Kothapalli, Paul M. Thompson, Daniel P. Beavers, Mark A. Espeland, Margaret Gatz, Susan M. Resnick, Ira Frahmand, Stephen R. Rapp, Caleb E. Finch, Jiu-Chiuan Chen, William S. Kremen, and Carol E. Franz
Source/Credit: Keck School of Medicine of USC | Sidney Taiko Sheehan
Edited by: Scientific Frontline
Reference Number: ns081826_02
