Air pollution linked to more severe Alzheimer’s disease, Penn study finds

The air you breathe doesn’t just affect your lungs. It could be toxic to your brain.

A study by University of Pennsylvania researchers linked increased exposure to air pollution to worse cases of Alzheimer’s disease. They specifically looked at the smallest category of pollutants: particles with a diameter of 2.5 micrometers or less. That’s at least 30 times smaller than the average strand of human hair.

Pollutants of this size are considered particularly hazardous and come from a variety of sources, including combustion, car exhaust, and wildfire smoke.

“These particles are small enough that if you inhale them, they pass readily into your bloodstream. Some of it could probably get directly into your brain,” said Edward Lee, the senior author of the study published Sept. 8 in the medical journal JAMA Neurology.

Reports from other groups have linked them to decreased cognitive function and increased risk of dementia.

Lee’s study added to that growing body of research, with his finding that the risk of more severe Alzheimer’s disease increased by 19% with every 1 microgram per cubic meter increase in the concentration of these particles. That was based on there being worse buildup of amyloid and tau, two proteins that accumulate in the brain as the disease progresses.

For context, concentrations of these pollutants ranged from 5 to 17 micrograms per cubic meter in the study cohort, and the Environmental Protection Agency’s limit is 9 micrograms per cubic meter.

Higher exposure was also linked to greater cognitive and functional impairment. Still, Lee does not think such pollutants cause Alzheimer’s disease and stressed that people should not panic.

These findings were based on a sample of 602 patients with dementia — the umbrella term for conditions causing cognitive decline that includes Alzheimer’s disease — who had donated their brains to Penn’s Brain Bank, a repository of donated brain tissue used for research.

The team estimated each person’s exposure to pollution based on their home address and compared it to the individual’s clinical records and autopsied brain sample. The vast majority of cases came from Philadelphia and neighboring regions.

While there are likely multiple environmental factors that together could affect Alzheimer’s disease progression, this study aimed to assess, to the extent possible, just one of them.

The study is what’s known as an observational study, a method of research where an outcome is observed without intervening with or influencing the variables. It can be used to determine correlation but not causality, unlike randomized controlled trials, the gold standard for establishing a cause-and-effect relationship.

The Inquirer spoke with Lee, who is a pathologist and co-director of Penn’s Institute of Aging, to learn more about what air pollution might do to the brain.

The following conversation has been edited for length and clarity.

What caught my interest were studies saying that the incidence of dementia is actually decreasing decade over decade in developed countries, such as the U.S. and Sweden. That means there has to be a nongenetic factor that’s affecting dementia rates. Air pollution was one of those that’s been suggested.

In the U.S., air pollution rates, and specifically, levels of particulate matter 2.5 micrometers or smaller in size, have been steadily decreasing over the last 15, 20 years, even in the cases that we studied in this study. That potentially could be part of the reason why dementia rates are decreasing.

There are other things that we know affect cognitive function, like education and the neighborhood you live in. So there are likely a lot of different things that are helping dementia rates.

There have been several larger-scale studies that looked at the effect of pollution on cognition or dementia diagnoses, but there have been very few studies that have tried to study this relationship using autopsy, which is the gold standard. It’s how you ultimately are able to look into the brain and see what’s really going on. Our cohort had a very solid effect of air pollution on Alzheimer’s disease.

Air pollution seems to be exacerbating Alzheimer’s disease. I don’t think it causes Alzheimer’s disease. I don’t think we have any proof of that. But perhaps pollution is making it worse.

The risk for developing Alzheimer’s disease is very complicated. There’s genetics, air pollution, heart health, and all these things that are all adding to or taking away from your risk. So we think the data suggests that the more air pollution you have, the more exacerbated your Alzheimer’s disease pathology is. But I don’t want it to cause panic and hysteria.

One theory is that air pollution interferes with maintenance of the brain. Because air pollution seems to be associated with accumulation of more amyloid and tau, this shows that the brain is less able to maintain its normal state. Normally you don’t have these proteins accumulating in the brain.

There’s some thought that maybe these air pollutants might trigger inflammation in the brain, and perhaps that’s one way that it could exacerbate the buildup of these proteins. But I don’t think we really understand how air pollution is doing this. The study suggests that we should study it more to try to better understand what’s going on.

I hesitate going too far with clinical recommendations at this point. We need better, more solid evidence before we start changing how we treat patients.

The way we estimated people’s air pollution exposure was based on their home address, but that’s not a perfect measure of somebody’s air pollution exposure. For example, if you’re living indoors and your house is more ventilated or less ventilated, you might have different exposure risk. If your significant other smokes or doesn’t, your personal exposure risk is different. I think there are ways to follow up on this study to validate our findings, and I think that’s an important step before we start intervening or telling people how to change their lives.

We have to understand more about both our genetic and environmental risk for Alzheimer’s disease in order to better personalize diagnosis and better personalize treatments for Alzheimer’s disease.

This last year or two has been kind of a watershed moment in the field of Alzheimer’s disease, because now we have therapies that seem to be affecting the underlying disease biology, and seem to have some clinical benefit. So as we move into the therapeutic era for dementia, I think understanding all the risks that an individual person has experienced and how that affects Alzheimer’s disease is important.