Meet the Scientist Connecting the Dots between Air Pollution and Dementia

HEALTH, 29 Feb 2016

Clayton Aldern, Grist – TRANSCEND Media Service

17 Feb 2016 – At first blush, you might not think air quality is related to brain health. But what if the two are connected? Air pollution continues to worsen in the developing world, especially in rapidly developing countries like China and India; at the same time, our global population is aging, and dementia rates are expected to rise accordingly. Increasingly, research suggests a link between air pollution exposure and the risk of diseases like Alzheimer’s and Parkinson’s. How might this relationship be possible, and what might it mean for what the world is — or isn’t — prepared to handle in the coming decades?

Aaron Reuben

Aaron Reuben is a science writer, recovering policy wonk, and neuropsychologist-in-training who’s exploring just these questions. A PhD student at Duke, Reuben’s journalistic endeavors include an eye-opening feature for Mother Jones (cross-posted at Grist) that draws attention to the connection between dementia and dirty air.

Driving Reuben’s work is the notion that the countries that will see the most aging in the coming years are the same countries that are going to have the most polluted air — and the same places that have some of the least developed infrastructure for diagnosing and treating brain disease. I caught up with Reuben to chat about the state of the science, the justice issues at stake, and the difficulties of communicating the invisible.

1. What do we know about the links between air pollution and dementia?
2. There are two branches of relevant science here. The first body of research studies people in older age brackets and maps their health outcomes onto possible air pollution exposures generated from regional pollution monitoring data. When you do that, you find that people who are exposed to more air pollution, particularly fine particles, show an increased risk for dementia and pre-dementia, called mild cognitive impairment. A study that came out of Taiwan, for example, drew on a cohort of nearly 100,000 people and showed that for every unit increase in exposure to particle pollution, the risk of developing Alzheimer’s went up by more than 100 percent.

Of course, before we can say that one causes the other, one of the things that needs to happen is data to arrive from longitudinal studies in which you follow people from day one, categorize their exposures, follow their outcomes, and control for things you’d like to control for, like exposures to other toxins like lead. But every month and every year, more and more studies are coming out, and the fact that they’re all finding the same thing is very compelling.

The other kinds of studies that are contributing to the evidence base are animal studies. You can’t sit someone down and expose them to air pollution and watch their brains degenerate in real time. But you can do that in mice. There are a lot of studies coming out now on changes in cell dynamics and epigenetics in mice exposed to air pollution, and you see that many of the changes are in the direction of Alzheimer’s disease and heavily related to dementia outcomes. Something that’s really sexy that hasn’t been published yet are studies using transgenic mice that have been engineered to develop Alzheimer’s-type pathology. If you expose generations of these mice to air pollution and that changes the development of pathology, then you can make a call that in this particular animal, the exposure to fine particles fostered the disease. So far the mouse studies are pointing in the same direction as the cohort studies.

1. So are we at smoking-causes-lung-cancer levels of evidence?
2. No, we’re not there yet. But when people ask me this, I also ask them how long it took to get there for lung cancer. How long did we think cigarettes caused cancer before we were finally willing to say ‘we know’? It took decades. I don’t think anyone thinks the evidence is going to start weighing against this trend. It’s a matter of how long new research needs to pile up before people are willing to make a bold statement.
3. And what do we know about how pollution might contribute to dementia?
4. There are a couple ways we think it works. One is by nature of the fact that some of the particles are very small. Your sense of smell is a very potent sense, and there is a direct connection from the nose to the brain via the nasal nerve. That means that once you get something in your nose, if it’s small enough, it can pass into the nerve and make its way all the way to the brain.

Keep in mind that pollution particles typically bring in a host of other nasty things with them, including heavy metals: things that can directly kill neurons. The end result is a disruption of the brain’s homegrown immune system. Microglia cells — which clear waste, trim away dead neurons, improve synaptic connections, and clear pathogens — end up performing an unsuccessful process. They continue to release oxidative chemicals that are designed to kill pathogens, but instead of killing anything, the chemicals just accumulate and disrupt neural activity. The damage this causes looks a lot like what you see in Alzheimer’s and Parkinson’s patients.

Another mechanism comes via the lungs. When pollution particles are inhaled into the lungs, they tend to be small enough to make it past the body’s defenses and end up in the deepest tissue, where they then pass into the bloodstream. When they do that, they trigger an immune reaction that circulates molecules related to inflammation, cytokines, in the bloodstream — the kind of thing that seems to cause chronic low-level inflammation wherever the particles go. We’re not sure if the particles can enter the brain through the blood directly or if the chemicals they trigger actually reach the brain, but there’s evidence that they interact with the blood-brain barrier and damage it somehow. It’s all about low-level inflammation that turns into long-term damage. Particles that enter through the nose will cause neuroinflammation directly, and particles that enter through the lungs will also cause neuroinflammation indirectly.

1. You’ve suggested we’re past the tipping point at which this theory is going to be wholly refuted, but you’ve also cited overly cautious scientists who are wary of overstating the evidence. Why do you think this hesitance exists?
2. I think in all of science there’s a tendency to be as precise as possible. It’s never unusual for scientists to hedge their bets. But the other thing I think is going on here is that there’s been a sort of history of jumping the gun on Alzheimer’s. We’ve been talking about one cause, but there are many ways to brain disease. The brain is uniquely susceptible to damage. Air pollution isn’t causing all the dementia we see around us. There’s pesticide exposure, there are concussions — there’s not just one way to get this disease. And it’s also a function of your cumulative exposures and your genetic predisposition.

There’s a lot to fear when it comes to dementia. It comes out of nowhere, there’s no cure, it erases everything about you. If you can point to something that’s causing it, people are going to take you seriously. That’s what happened with the aluminum scare in the 1980s, which led to sensationalist headlines and people worrying about their pans and the things they were drinking. The studies that found unusually large aluminum deposits in the brains of Alzheimer’s patients were real, but that didn’t mean that your personal exposure to aluminum actually influenced your dementia risk. The field of gerontology remembers this and is going to be slow to embrace air pollution. Especially because it’s something that everyone is exposed to, unlike, say, a concussion.

1. I’m interested in what you just said about air pollution being something that everyone is exposed to. There are obviously inherent justice questions at stake here given the inequities of air pollution exposure. How does environmental justice enter the conversation for you?
2. I think there are two things going on, and neither of them are good. The same communities that are reliably exposed to the most air pollution are the same communities that have the fewest resources to defend themselves or compensate for the effects.

Something you see time and again is that high-income, high-resourced individuals not only can buffer themselves against exposure to air pollution — they live in the nice parts of town, they don’t live by busy roads, they live by a lot of greenery, which we know can reduce pollution levels — but they also have the resources to respond to the kinds of cognitive impairments that we’re predicting. Researchers at the University of Southern California have found that air pollution levels are linked to developmental disorders. We know that if your child has a developmental disorder, there are plenty of services and activities you can do to improve their cognitive abilities. These are the kinds of things that aren’t always available to low-income communities, who are also at greater risk.

Another thing that people are talking about are the synergistic stressors at play. It’s not just that you’re living in a neighborhood that has higher levels of air pollution, it’s that there might also be more violence in your social environment. You might have an incarcerated family member. These are many forms of adversity that, on their own, modify the way the brain develops and modify a slew of risk factors. When you put them all together, these effects may be magnified.

1. What if I buy your story about air pollution and dementia but can’t move out of my heavily polluted neighborhood? What are my options?
2. Something we used to study in my old lab was called cognitive reserve. The basic idea is that there are some things you can do that appear to make you more resilient against showing symptoms of disease or brain injury. It’s based on old evidence of people who had died and, once an autopsy of their brain was done, appeared to have had Alzheimer’s-like pathology — but there was no evidence they had Alzheimer’s when they were alive. And it seems to be the case that they were compensating somehow to the brain damage.

There are certain things we know lead to good cognitive reserve. Yes, a lot of them are associated with your socioeconomic status, but some of them aren’t. If you have a higher IQ, it seems you’re buffered a bit against insults to your brain. For every year of education you get, your risk of presenting Alzheimer’s goes down — not because you’re immune to the disease, but because if you start to get early damage, you’re more able to deal with the damage in a way that maintains your cognitive function. More physical activity is another one.

With respect to age, young people and old people are the most vulnerable. Young people’s brains are still developing; old people have brains that are less likely to bounce back and repair themselves after injury. As a society, we can choose to design better communities around some of this knowledge. In California, there’s a law that says you can’t put an elementary school on a busy road.

But no, we can’t all move. In Beijing, if you wanted to move, you’d have to change your whole life. You can’t escape the pollution.

1. I feel like there’s a certain paradox here when you mention a place like Beijing. We’re building these factories in the name of progress, but for whom? If people’s brains are atrophying because of exposure to air pollution, there’s a pretty abysmal vicious circle going on.
2. It’s not just that we’re going to die younger or age more poorly. There’s lots of evidence that you’re stopping people at the start of their lives. Studies have found that kids drop IQ points for every unit of air pollution exposure. Or look at what’s happening in Flint. There’s a whole generation of kids getting set at a disadvantage from day one. We’re doing the damage to ourselves.
3. Something like climate change is already so slow and abstract. Something like air quality isn’t always something you can see. When you combine these kinds of things with mental health or brain health — which are already siloed off from the rest of the health spectrum — there’s a lot of abstraction going on in one place. That must make these effects particularly difficult to communicate. Does this ever leave you frustrated?
4. This actually reminds me of something I’m working on now, which is trying to look at the long-term effects of exposure to positive things like parks and green spaces — improved environments. I think of it as the flipside of these stressors. Almost everyone you talk to can speak at a personal level to the benefit of green spaces. Trying to find that effect in data and trying to make that data compelling is hard. There are a lot of things that are going to contribute to how well or how poorly you live. Something like your environment is just one of them. Trying to pull out the influence of that one factor is really hard, both scientifically and with respect to communication.

But we do know the places where people are getting older. In a lot of those places, we can reliably say there are going to be greater rates of dementia than there should be. A lot of those places don’t have infrastructure yet for diagnosing or treating these things, and I think it’s time we started thinking about the resources that need to be put into place in the areas where the air is bad. At some point we’re going to have to start paving the way to dealing with the brain health crisis that’s coming. Of course, it’d be great to clean up the air in these places, and we know how to clean up the air, but we’re not going to be able to do it right away. In the meantime, we know who the people are at risk, and we know pretty well what’s going to happen. Can we start getting ready for that in a real way?

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