Researchers at the University of California, San Francisco found that among older adults with cognitive impairment, the greater the air pollution in their neighborhood, the higher the likelihood of the presence of amyloid plaques in their brain. Lead researcher Leonardo Iaccarino, PhD, details his work examining air pollution and brain health outcomes and discusses possible ways individuals and society can lower the impact of air pollution on Alzheimer’s disease risk.
Guest: Leonardo Iaccarino, PhD, University of California San Francisco Memory and Aging Center
- What sparked your interest in neuroscience and Alzheimer's disease research? 1:06
- Why is your research so pivotal? 2:21
- What was the IDEAS Study? 4:12
- What kinds of air pollution are you referring to? 6:09
- What can generate PM2.5? 7:45
- Are cars or factories potential sources? 8:50
- How does air pollution increase risk for Alzheimer's disease? 9:15
- Is there a further increased risk after long exposure? 11:00
- Why is it important that there was no link to ground-level ozone? 12:04
- Did you look into the APOE4 genetic risk from air pollution? 14:32
- What should people do with this information? 16:19
- Is there a way to find your own neighborhood value of PM2.5? 18:44
- Do you see any policy or system changes in the future from your findings? 19:55
- Do you believe there might be other environmental factors that increase risk? 21:03
- What do you do in your life to decrease risk for neurodegeneration? 21:57
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Dr. Leonardo Iaccarino's paper "Association Between Ambient Air Pollution and Amyloid Positron Emission Tomography Positivity in Older Adults With Cognitive Impairment" was published online at JAMA Neurology on November 30, 2020.
Read some of the news coverage about the paper:
- "Forest Fires, Cars, Power Plants Join List of Risk Factors for Alzheimer's Disease" University of California, San Francisco (UCSF) News, November 30, 2020
- "Could Dirty Air Help Speed Alzheimer's?" Health Day, December 1, 2020
- "Air Pollution May Lead to a Key Alzheimer's Biomarker in the Brain" Being Patient, December 10, 2020
Intro: I'm Dr. Nathaniel Chin, and you're listening to Dementia Matters, a podcast about Alzheimer's Disease. Dementia Matters is a production of the Wisconsin Alzheimer's Disease Research center. Our goal is to educate listeners on the latest news in Alzheimer's Disease research and caregiver strategies. Thanks for joining us.
Dr. Nathaniel Chin: My guest today is Dr. Leonardo Iaccarino, a neuroscientist and assistant professional researcher at the University of California, San Francisco Memory and Aging Center. Dr. Iaccarino was first author on a recent study published in November 2020 in JAMA Neurology that found an association between air pollution and Alzheimer's disease related brain changes. Dr. Iaccarino, thank you for taking some time to join me on Dementia Matters.
Dr. Leonardo Iaccarino: Hi Nate, and thank you really for having me here. It's really an honor and I'm super excited about this.
Chin: Well great! So then we'll just jump right into it. Before we talk about your actual research, tell our audience how you got involved in neuroscience and what sparked your interest in studying Alzheimer's disease and air pollution?
Iaccarino: I originally trained as a psychology undergrad in Naples, Italy, where I was born and raised. Really into that, I very soon felt like neuroscience, and actually particularly clinical neuroscience, was my calling. This really led me to a journey to first Milan, in Italy, and then to San Francisco, where I am now, for the last three years. I've been working since on neuroimaging techniques and biomarkers for Alzheimer's disease, and really air pollution actually was a more recent interest for me. About halfway into my postdoc, I started to be more and more interested in these modifiable risk factors. Air pollution really struck me as something that is interesting, is important for public health, and is something that we can act on in terms of policies. The interest was also related to our access to a very important database, which is the IDEAS study database. This is a database that I used and we used for my study in JAMA Neurology.
Chin: A growing body of evidence shows air pollution can be added to the list of risk factors for Alzheimer's disease, so tell us about your research and why it’s so pivotal – and this is the one again that was published in November 2020 in JAMA Neurology.
Iaccarino: Yeah, so there's been more and more evidence that exposure to different types of pollutants, airborne pollutants, is associated with a number of poor brain health outcomes. These include increased incidences of dementia, acceleratity of cognitive decline, and so on. Really, the leading hypothesis is that these brain health outcomes are associated, or let's say mediated, by actually cardiovascular and respiratory conditions that are really strongly associated and triggered by exposure to air pollution. However, our study kind of provides some evidence that even if these mechanisms are important, actually exposure to air pollution may contribute to brain health outcomes also through other pathways and mechanisms, in particular perhaps contributing to the accumulation of this brain pathology, which is amyloid plaques pathology. This is the idea essentially that kind of our study was aiming at and provide an alternative theory behind the poor brain health outcomes associated with air pollution. Really the take-home from our study is that if you keep a number of medical, clinical, family, history characteristics that we included in our models constant – so persons with, individuals with exactly the same characteristics but these individuals would be living in different areas in the US with different pollution levels – they would actually have a different probability of having this buildup of amyloid in their brains. That’s really the take-home of the study.
Chin: And it's such an important take-home, but I also want our audience to understand what you meant by such a rich and important data set. You mentioned the IDEAS study. Can you explain to us what IDEAS study is or was, and what you looked at specifically within that study?
Iaccarino: Yes, so the IDEAS study. IDEAS stands for the Imaging Dementia–Evidence for Amyloid Scanning study. It was a countrywide study led by my PI, Gil Rabinovici, in the US and enrolled actually more than 18,000 older US individuals with kind of impairment, either a mild cognitive impairment or dementia meeting appropriate use criteria for amyloid PET. The primary aim of this study was to assess the impact of amyloid PET results on patient management and care. What we did for this study on the association of air pollution was essentially accessing the data originally collected in the IDEAS study and then using the patient's residence zip codes to sort of merge the data acquired in the IDEAS study with the EPA Air Quality Data and, you know, test our hypothesis.
Chin: And fortunately, there are participants from all across the country in the IDEAS study. Is that right?
Iaccarino: Yes, they – actually, the density, let's say, the geographical distribution of individuals in the IDEAS study largely reflects the population density in the US. That is also very important. Actually, this is a very important point is that the IDEAS population, first, is very large. It's a uniquely large cohort to study such an association. Second, it's really geographically dispersed in the US, which allows – for us, at least, allowed to look at the entire range of PM 2.5 and ground level ozone concentrations in the US.
Chin: And in your study you talk about air pollution. What kinds of air pollution are you referring to?
Iaccarino: We consider two different pollutants; either particulate matter 2.5 and or ground level ozone. As for particulate matter 2.5, this is – particulate matter itself is a mixture of solid and liquid droplets. These are suspended in the air and so they can be inhaled. Depending on their size, they may have different effects on our health after being inhaled. When you see PM 2.5, this really is the first two concentrational particles that have a 2.5 micrometer diameter or less. You know, just to give you an idea of this size, the largest PM 2.5 particle is about 30 times thinner than an average human hair. So really, the idea is that these particles are so small, when they are nailed they can deposit in different places in your airways and they can also even enter your bloodstream or reach the central nervous system. PM 2.5 is one of the most studied pollutants because it seems to be particularly bad for us when inhaled. The other pollutant we looked at was the ground level ozone, which is a gas and can be, also has been associated also with poor brain – sorry, poor brain health outcomes. In our study, however, as you know we only found an association with PM 2.5.
Chin: And so what kinds of things can generate PM, these particulate matter 2.5 microns or less?
Iaccarino: Yeah. So first of all, PM 2.5 could be also naturally present in the aerosol. You know, it can be associated with, for instance, sea salt, dust, but then can also be secondary, let's say, so it can actually be produced in different ways, also by human-made activity, of course. Actually in the cities, in like very densely populated areas, most of the PM 2.5 is actually secondary. You know, PM 2.5 could be either directly emitted – so it can be actually emitted directly from activities like constructions or can also be produced by natural events like wildfires, for instance, in California where we are very worried about this – or it can actually result from chemical processes actually happening in the air, so other particles and gasses can react together and sort of clamp together and kind of result in these particles.
Chin: And for those in more densely populated areas, do cars, for instance, generate particulate matter 2.5 or being near a factory? Are those potential sources?
Iaccarino: Yes, so emissions – these types of emissions can be definitely associated with, ultimately, with the concentration of PM 2.5 in a given area, so yes.
Chin: How does air pollution increase the risk for Alzheimer's Disease, or why do you think there was this increased biomarker of amyloid in people with this risk?
Iaccarino: Yeah, so this is an excellent question. You know, it's also one of the, in part, an aspect of this study that we have been thinking about a lot, about the interpretation of the findings. The leading hypothesis – and, you know, we are not the first ones to show such an association. There have been previous studies in animal models and in cellular studies actually showing very similar findings, but we kind of take this concept and we tested this hypothesis on a very large human population in vivo. The leading hypothesis is that anyway inhaling these particles and breathing them in somehow triggers an inflammation response, a systemic inflammation response. This inflammation response can also result in inflammatory responses in our brain that in turn may lead to accumulation of amyloid plaques. The idea really is that we have a physiological system to sort of clear up amyloid plaques or clear up amyloid and also have a physiological system that's kind of taking under control the production of amyloid peptides and proteins. The idea is that when we have these inflammatory responses and when these inflammatory responses can become chronic, these physiological systems are altered, can be impaired. This is one of the hypotheses behind the association between exposure to air pollution and in increased amyloid pathology, we have observed.
Chin: And do you see a dose-dependent relationship – and for our audience members, what I mean is that if you are exposed to PM 2.5 more intensely than others, meaning it's more dense in your city, or if you're if you're seeing it over years instead of just a year – do you see that there is a further increase risk?
Iaccarino: This is another excellent question, Nate. In our study, we did not really have access to, let's say, this type of information. I think the leading hypothesis is that we should be worried about chronic exposure, even not particularly high concentrations but still like chronic and longstand, long-term exposure to these pollutants. Not really like single events, for instance. I think we should be worried about that as well, but in terms of brain health it seems like this long-term chronic exposure is what we should be particularly wary of.
Chin: You did not find that relationship with ground level ozone and then this amyloid in the brain. What does that finding mean for us, for the non-neuroscientists?
Iaccarino: Yeah, definitely. On one end, we kind of liked that there was a specificity, let's say, associated with the association with pollutants in our study. Meaning that we found something for PM 2.5 and not really for ozone, saying that we were looking at a specific mechanism rather less likely to be non-specific. As for the ozone, one thing actually that I want to bring up, also for PM 2.5, is that in the last years, the air quality in the US has improved a lot. You know, in the study we looked at the two different bienniums, as – like biennial – as time windows. One was in 2002-2003 and then a more recent biennium, 2015 to 2016. Really, in this fourteen years sort of range the air quality has improved a lot for PM 2.5. Also ozone has not changed a lot, but the levels are not worrying. Really, we could not find an association with ozone and compared to literature, when actually you can see these results, these findings, for instance between exposure to ground level ozone and increased incidence of dementia, usually these are done in places or areas that have a much higher concentration of ozone. Our take on this is that maybe the levels we have observed in our study were not high enough or perhaps – being ozone, a different pollutant compared to the PM 2.5 with different chemical and physical properties – the effect of ozone wasn't maybe associated with another type of,you know, brain health outcome that was not found or observed in our study and also maybe in different populations. We have looked at a population that is very specific with these older individuals that are already cognitively impaired, so either in a mild stage or in a more advanced clinical stage, but we had the not cognitively normal subjects in our cohort. Maybe, you know, looking at different populations may also provide further insight on this, let’s say, difference between the associations of PM 2.5 and ozone.
Chin: Well, it's good news to hear that our air quality has gone up over the past few years and more recently. Another thing about your study that I appreciated is that you had the control for a lot of other factors when doing your analysis, so things like medical conditions, lifestyle behaviors, and socioeconomic level. You even looked to see if gender had a role in your findings, and it seemed like the answer was no. I'm wondering if you were able to look at the ApoE4 genetic risk. Were certain people at higher risk of having this effect from air pollution versus others?
Iaccarino: Yeah, we controlled for a lot of other factors, as you are mentioning. This was also to kind of try to be as specific as possible in our statistical testing to understand whether there was an association between pollutants, exposure to pollutants, and likelihood of being a positive – I mean, having a positive amyloid PET scan, controlling for these other factors that we know are associated with either the amyloid PET positivity or also with actual exposure to air pollution like, for instance, cardiovascular and respiratory comorbidities. Yes, we indeed looked also for if gender had a role. This is because, in some of the literature, it’s been shown that there could be actually a role of gender in how you are vulnerable to exposure to air pollution, but we really could not see that in our study, in our data. And you're absolutely right thinking of ApoE genetic risk. We, unlikely, did not have access to ApoE info for the participants included in our study. That would have been absolutely important and interesting. There is already evidence that, you know, if you are a carrier on the ApoE4 allele, you may be more vulnerable to exposure to air pollution so that would have been very interesting.
Chin: And then taking what you found and trying to apply it to our listeners, to the US population in particular, there's an estimated 5.8 million people 65 and older that have Alzheimer's disease. When we look at that, this may mean that tens of thousands of cases of those with Alzheimer's could be partly at least attributed to air pollution. Knowing this and keeping this in mind – and not that I'm trying to rouse fear – but what should people do with the information that you have now found?
Iaccarino: Yeah, this is also an excellent question. Let me first maybe clarify, Nate, that what I'm thinking is that our study does not really demonstrate that air exposure to air pollution is like a cause of Alzheimer's disease. We show that it is associated with, let's say, an increased likelihood of having this specific pathology in the brain, which itself is, you know, a risk factor for developing Alzheimer's disease, dementia in your lifetime. Having a positive amyloid PET Scan does not really say that you have Alzheimer's disease itself or that you will have dementia in your life. There are also individuals that are perfectly cognitively normal who actually have an amyloid positive PET scan. The way we have to think about this is that it actually just increases the risk that you may have – in your lifetime, you may end up developing Alzheimer's disease, dementia, but it's not like a cause of it. We can definitely – I mean, air pollution is not a cause of Alzheimer's disease. It, indeed, looks like it's one of the possible risk factors, so like contributing to the risk overall. What should we do with this information? Well, I think we can be more mindful of our exposure to air pollution. We can do, actually, like very concrete actions we can take to limit our exposure. We can check, for instance, how is the air quality in our area. We can take actions like even wearing a mask. You know, it's something that we used to do also before the pandemic but during the wildfires to limit your breathing in these particles that are suspended in the air. You know, it's something that we should think of just in our lives, I think.
Chin: Such an important clarification, and thank you for making that. Also a very interesting point about wearing face masks prior to our pandemic. Thinking about how people should really consider their risk and make informed decisions, is there a way for a person to know what their own neighborhood value is of this PM 2.5 or is this only something that researchers and scientists have access to?
Iaccarino: Well, so the data we use in our study are like specific sort of more complicated data to deal with, published by the EPA. Actually, there are also way more approachable data on our air quality in your neighborhood and yes, you can actually – there are like a lot of resources to check your own air quality. For instance, there is the AirNow website, which is a US government website where you can literally just enter your zip code, your residence zip code or I mean any zip code, then you will have, instantly, the air quality with a number of different parameters associated with it. It actually is pretty straightforward.
Chin: Well, that's great to know and good for our audience to know that they actually could take a look in their own neighborhood. I also think of your findings as potentially something that may have an impact on policy. Do you see some sort of future conversation about potential system changes and not just individual ones?
Iaccarino: Yes, this is actually our conclusion in the studies that, you know, policymakers should consider these findings and not – really not only our study. In the same months, there was also another study providing complementary findings and, you know, very convergent findings. I think now there is a very coherent story coming up from literature. Yes, I think policymakers should consider this because, as also this other study I was mentioning, we do see these associations even in ranges of values that are considered normal or like not problematic, let's say, considering the standard, the current standard. So, you know, like even trying to lower the standard more or thinking of other actions at the policy level to increase the air quality, I think they could go a long way.
Chin: And do you believe there might be other environmental factors that could be these modifiable risk factors such as water quality or sound pollution you hear about, or even things like pesticides and herbicides?
Iaccarino: Definitely. I think there is evidence for all the ones, all the factors you have listed. Usually with air pollution then you also think of environmental noise. It's another factor that has been determinant or factor that has been now been like – it's being now more and more studied. All these elements together, they sort of go to this larger umbrella category which is these social determinants of health. These are now becoming more and more important, and I think they deserve a lot of attention by future studies.
Chin: I'm so glad you're working on this because there is such a great overlap here, between these social determinants and Alzheimer's disease and the environment, so I look forward to more of your studies coming out. I always like to end an interview with a more personal question. What do you do in your own life to reduce your risk for Alzheimer's disease?
Iaccarino: Yes, this can be a difficult question, I guess. You know, I've been taking some actions in general. The way I approach this is that really anything you can think of that is associated with your general health is actually also associated and is very likely to be also a modifiable risk factor for Alzheimer's disease or dementia. This includes, you know, like looking at your blood pressure, having your physical exercise. One other important aspect that has been becoming more and more important is also watching your sleep quality. All these elements that actually just contribute to our general health in the longer run have been associated with Alzheimer's disease. Right now, personally, I'm working on my physical exercise and, you know, other lifestyle changes like that. I'm not a smoker, but smoking would be another important element to think of. These are the steps that we can take. I'm like slowly – maybe perhaps a bit lazy, in a lazy way, but I'm trying to take action myself.
Chin: (laughs) Well thank you for being honest –
Iaccarino: (laughs) Yes.
Chin: – and answering that question. Again, I’d like to thank you for being on Dementia Matters and I hope to have you back when you have more results.
Iaccarino: Thanks, Nate! This was awesome. Thanks.
Outro: Please subscribe to Dementia Matters on Apple Podcasts, Spotify, Podbean, or wherever you get your podcast. And rate us on your favorite podcast app; it helps other people find our show and lets us know how we're doing. Dementia Matters is brought to you by the Wisconsin Alzheimer's Disease Research Center. The Wisconsin Alzheimer's Disease Research Center combines academic, clinical, and research expertise from the University of Wisconsin School of Medicine and Public Health and the Geriatric Research Education and Clinical Center of the William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin. It receives funding from private university, state, and national sources, including a grant from the National Institutes of Health for Alzheimer's Disease Centers. This episode was produced by Rebecca Wasieleski and edited by Bashir Aden. Our musical jingle is "Cases to Rest" by Blue Dot Sessions. Check out our website at adrc.wisc.edu. You can also follow us on Twitter and Facebook. If you have any questions or comments email us at firstname.lastname@example.org. Thanks for listening.