For years, the two patients had come to the Penn Memory Centre at the University of Pennsylvania, where doctors and researchers follow people with cognitive impairment as they age, as well as a group with normal cognition.
Both patients, a man and a woman, had agreed to donate their brains after they died for further research. "An amazing gift," said Dr Edward Lee, the neuropathologist who directs the brain bank at the university’s Perelman School of Medicine. "They were both very dedicated to helping us understand Alzheimer’s disease."
The man, who died at 83 with dementia, had lived in the Centre City neighbourhood of Philadelphia with hired caregivers. The autopsy showed large amounts of amyloid plaques and tau tangles, the proteins associated with Alzheimer's disease, spreading through his brain.
Researchers also found infarcts, small spots of damaged tissue, indicating that he had suffered several strokes.
By contrast, the woman, who was 84 when she died of brain cancer, "had barely any Alzheimer's pathology", Dr Lee said. "We had tested her year after year, and she had no cognitive issues at all."
The man had lived a few blocks from Interstate 676, which slices through downtown Philadelphia. The woman had lived a few kilometres away in the suburb of Gladwyne, Pennsylvania, surrounded by woods and a country club.
The amount of air pollution she was exposed to — specifically, the level of fine particulate matter called PM2.5 — was less than half that of his exposure. Was it a coincidence that he had developed severe Alzheimer's while she had remained cognitively normal?
With increasing evidence that chronic exposure to PM2.5, a neurotoxin, not only damages lungs and hearts but is also associated with dementia, probably not.
"The quality of the air you live in affects your cognition," said Dr Lee, the senior author of a recent article in JAMA Neurology, one of several large studies in the past few months to demonstrate an association between PM2.5 and dementia.
Scientists have been tracking the connection for at least a decade. In 2020, the influential Lancet Commission added air pollution to its list of modifiable risk factors for dementia, along with common problems like hearing loss, diabetes, smoking and high blood pressure.
Yet such findings are emerging when the federal government is dismantling efforts by previous administrations to continue reducing air pollution by shifting from fossil fuels to renewable energy sources.
"'Drill, baby, drill' is totally the wrong approach," said Dr John Balmes, a spokesman for the American Lung Association who researches the effects of air pollution on health at the University of California, San Francisco.
"All these actions are going to decrease air quality and lead to increasing mortality and illness, dementia being one of those outcomes," Dr Balmes said, referring to recent environmental moves by the White House.
Many factors contribute to dementia, of course. But the role of particulates — microscopic solids or droplets in the air — is drawing closer scrutiny.
Particulates arise from many sources: emissions from power plants and home heating, factory fumes, motor vehicle exhaust and, increasingly, wildfire smoke.
Of the several particulate sizes, PM2.5 "seems to be the most damaging to human health", Lee said, because it is among the smallest. Easily inhaled, the particles enter the bloodstream and circulate through the body; they can also travel directly from the nose to the brain.
The research at the University of Pennsylvania, the largest autopsy study to date of people with dementia, included more than 600 brains donated over two decades.
Previous research on pollution and dementia mostly relied on epidemiological studies to establish an association. Now, "we're linking what we actually see in the brain with exposure to pollutants", Lee said, adding, "We're able to do a deeper dive."
The study participants had undergone years of cognitive testing at Penn Memory. With an environmental database, the researchers were able to calculate their PM2.5 exposure based on their home addresses.
The scientists also devised a matrix to measure how severely Alzheimer's and other dementias had damaged donors’ brains.
Lee's team concluded that "the higher the exposure to PM2.5, the greater the extent of Alzheimer’s disease", he said. The odds of more severe Alzheimer's pathology at autopsy were almost 20 per cent greater among donors who had lived where PM2.5 levels were high.
New York Times News Service