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In this episode of Minding Memory, Matt & Donovan speak with Dr. Lisa Barnes, the Alla V. and Solomon Jesmer Professor of Gerontology and Geriatric Medicine, Department of Neurological Sciences and Associate-Director of the Rush Alzheimer’s Disease Center at Rush University. Dr. Barnes talks with Matt & Donovan about racial disparities in Alzheimer’s disease dementia and several obstacles that have impeded our understanding of race and dementia. 

More resources

Faculty Profile: https://www.rushu.rush.edu/faculty/lisa-barnes-phd  

RADC Resource Sharing Hub: https://www.radc.rush.edu/  

Article Referenced in Podcast:   

Barnes LL. Alzheimer disease in African American individuals: increased incidence or not enough data? Nat Rev Neurol. 2022 Jan;18(1):56-62. doi: 10.1038/s41582-021-00589-3. Epub 2021 Dec 6. PMID: 34873310; PMCID: PMC8647782. 

Transcript

Matt Davis:

Alzheimer's disease affects one in eight older Americans and costs the US economy billions of dollars each year. Due to shifts in demographics, the number of older adults living with Alzheimer's disease is projected to increase significantly in the United States. Mounting evidence though, has shown that older African-American individuals bear a disproportionate burden of Alzheimer's dementia. Specifically, studies have found that the risk of Alzheimer's dementia is twice as high among African-American individuals compared to other racial ethnic groups. Despite the high risk among this population, African-American individuals are underrepresented in studies, and this creates an obstacle in disentangling the relationship between race and Alzheimer's disease. I'm Matt Davis.

Donovan Maust:

I'm Donovan Maust.

Matt Davis:

You're listening to Minding Memory. Our guest today is Dr. Lisa Barnes. Dr. Barnes is the Alla V. and Solomon Jesmer Professor of Gerontology and Geriatric Medicine, and a cognitive neuropsychologist within the Rush Alzheimer's Disease Center at Rush University Medical Center. She's also the associate director of the Rush Alzheimer's Disease Research Center. Dr. Barnes is internationally recognized for her contributions to minority aging and health. Her research interests include disparities in chronic diseases of aging, cognitive decline and risk factors for Alzheimer's disease. She's here today to speak with us about issues regarding research on racial differences in Alzheimer's disease dementia. Lisa, welcome to the podcast.

Lisa Barnes:

Thank you for having me.

Matt Davis:

Our discussion today is based on a perspective piece that Dr. Barnes wrote titled Alzheimer's Disease and African-American Individuals: Increased Incidents or Not Enough Data? That was published in Nature Review's Neurology. The paper discusses several obstacles in understanding racial differences in Alzheimer's disease. We'll include a link to the article, make sure to check it out. So to start things off, as someone who's thought a lot about race and health, and also to make sure that we're all on the same page regarding our definitions, simply how would you define race and differentiated from ethnicity?

Lisa Barnes:

That's a great question. Race is a socially defined construct and it has very little basis in genetics. And in the United States in particular, it's a construct that is used to group people who are similar in ancestral backgrounds. So they come from similar regions, and/or they share phenotypic features like skin color. And importantly, race shapes access to power and socioeconomic resources. Ethnicity, on the other hand, has historically referred to a person's cultural identity. For example, language, customs, values, religion, et cetera. And ethnicity is regardless of racial classification. So you might have someone from Latin America who would be considered a Latino or Latina, Latinx regardless, but they could still be considered a white person or African-American. So ethnicity relies more on cultural identity and race is sort of socially defined about how you look, basically.

Donovan Maust:

So we think, we assume most of the people who are listening to this podcast are people who think about or are interested in research related to dementia. They may not necessarily regularly think about that through a lens of race or racial differences. So for people who are learning more about dementia, why is it important to consider race as part of their understanding of the syndrome and the illness?

Lisa Barnes:

Well, there are a couple of main reasons. So the first reason I think is that our nation is becoming much more diverse. So if you look right now at our population, it predominantly consists of predominantly white people, but in maybe 20 or 30 years, that's going to change dramatically. And racial and ethnic minorities will become the majority in number. And this is also true for older adults who are at risk of Alzheimer's disease. So it's critical that researchers, clinicians, practitioners and policymakers really, that we are all able to meet the needs of this growing diverse older population in the United States. So that's the first reason, changing demographics.

The second reason I would say is that Alzheimer's is a huge health disparity. As was mentioned in the introduction, we know that Alzheimer's disease disproportionately affects African-Americans. They're thought to be at greater risk of the disease, yet most of the research in this area has focused on older white adults. And so I think understanding racial differences might help us learn new information about Alzheimer's disease overall, including information that could improve diagnosis and prognosis and even open the door for further scientific discovery.

Matt Davis:

I have to say the times have changed so much. I think Donovan and I have talked about this as well, like 10, 15 years ago, we would just put race and ethnicity in as a variable in control for stuff. And now it's kind of nice to see people sort of pausing before they do that and kind of rethinking the degree to which we explore differences and understand them rather than just control differences away. I don't know if that's something you've experienced at all in your career, but that's something I've sort of observed.

Lisa Barnes:

Yeah, absolutely. I mean, 15, 20 years ago, race was considered a nuisance variable, and now we are really trying to unpackage and learn much more about it. So yeah, I completely agree with that.

Matt Davis:

So you mentioned how studies out there that have looked at different risk factors for Alzheimer's dementia, a lot of the data are predominantly from white individuals. I'm just curious to what degree do you think the findings from these studies translate or perhaps don't translate well to the African-American population?

Lisa Barnes:

Yeah, that's a great question. I do most of my research actually. I think some of the risk factors like age, which is the biggest risk factor actually, those kinds of risk factors, they do translate fine. So as you get older, your risk increases regardless of your racial background. And then there's some, I guess, vascular related risk factors like hypertension, diabetes, those seem to translate as well. But then there's these other risk factors that are more, I would say I would call them maybe psychosocial in nature. We know that they influence dementia in African-Americans, but because African-Americans have not been included to the extent that white Americans have been, we know less about.

So things like experiences of discrimination, early life disadvantage, neighborhood factors like segregation, access to healthy resources or educational quality, those kinds of things we know are important. But because we don't have as much data, we don't have as much information about those risk factors. So I would say of the risk factors that are well established, age and some medical comorbidities, those seem to translate. But then you have a host of other psychosocial risk factors that either don't translate well or haven't really been explored.

Matt Davis:

I went back when we were talking about this interview and thinking about all the things we wanted to ask you, and I went back and looked at the Lancet report that goes over modifiable risk factors, and I ran a quick search to see just how many times it mentioned race. It only comes up a few times in that.

Lisa Barnes:

Really? That's interesting.

Matt Davis:

Yeah, I didn't know what to make of it. And I guess it gets back to are these risk factors different in these subpopulations or is it more than that? But to some level it was a little surprising to me there wasn't sort of a whole separate section to get into some of the differences by race.

Lisa Barnes:

Yeah. And I think part of that is just that we don't have the data in a lot of cases. Some of those risk factors, there's just not much going on when we look at race. So that's an area of growth that we really need.

Donovan Maust:

You wonder too, that's maybe a little bit of a segue into the next question. So the Lancet is based in the UK, and you wonder the extent to which that really speaks to the fact that race is a social construct. And so the way we maybe talk and think about race in the US may or may not have similarities with how race operates in other countries in the UK and Europe. And so I'll try to have this be less of a comment and more of a question, but I just want to make sure while Dr. Barnes is here with us. So I think medicine sometimes has gotten in trouble because people use race to stand in for something biological.

And so you use correct formulas, you... "Correct", people listening can't see my air quotes, you sort of correct renal kidney function for race, all these places where things are modified or adjusted based on race. And what you're really telling us, and we hope listeners are understanding, is that race is not a biological thing. It's something that society has created. And so it operates through non-biological mechanisms and pathways to influence the experience of the person who has been labeled with that race. And so is that a reasonable summary of how to be thinking about race?

Lisa Barnes:

Absolutely. You said that so elegantly and thank you for that. That's exactly what I had hoped to get across in my article. I think in the past a lot of research really tried to look at these disparities that we're seeing and attributed the group differences to genetics, culture or behavior. And when you do that, you really are biologizing these disparities. And I think the attempts to link risk factors to biology or cultural practices rather than the social forces that we know influence race differences, poverty, unemployment, structural racism, those things get us in trouble if we continue to focus on genetics, the race and genetics, kind of making those synonymous in effect. And so I think it's going to be really important for research to try to identify those structural and social drivers of these differences. And that's what I tried to get set forth in the article.

Donovan Maust:

And so if my summary was good, it's because your article was good, and so people should make sure to read it at the link that'll be available along with the podcast.

Matt Davis:

If you wonder, has anybody thought about international comparisons? I mean, that have different social constructs in comparing similar groups of people?

Lisa Barnes:

A lot of that work's being done in low and middle income countries for sure, but some of the really elegant work that it's not happening currently because that study ended, but there's a researcher out of Indiana University named Hugh Hendry, and he had a great study where he looked at Nigerians and compared them to African-Americans in Indianapolis. I'm sorry, my phone never rings. I cannot believe this. And the concept was trying to see, you have these two populations that share ancestral background, but obviously have very different environments, Africa versus the US, Indiana. And he ran an epidemiologic study to compare risk factors in those two countries. And so there are smaller studies that are doing that currently, but that to me was one of the most elegant displays to really try to separate ancestral background from environment, social construction of race basically.

Matt Davis:

When we start thinking about and talking about how to conduct research in this space, it starts off obviously with accurately identifying people who may have mild cognitive impairment or dementia. And I recall in your article you talk a little about some of the issues when it comes to identification of people using conventional assessments, cognitive assessments, and how it differs by race. I was wondering, could you talk a little about that?

Lisa Barnes:

Yeah, I'm a neuropsychologist, so I'm not trying to put myself out of work, but I think it's important to recognize that at least in the field that we're in now, these neuropsychological measures that we're using, they were designed by and for white people because that was the population that was being studied. So they're really culturally bound to that population, the majority culture. And we know that African-Americans, especially older African-Americans, so people in the older age group now, they were born in the 1920s and 30s, with a very different educational experience. And we know that education is really tied to performance on these cognitive function tests. So I think it's important to understand that when we are trying to interpret these tests, we need to take that into account. It is not just years of education, but it's also quality of education that determines performance on these tests.

And then there are other parts of the exam that we give to make a determination of Alzheimer's. Like for instance, we have to determine if the person has a functional deficit and it's based on a study partner's report. A lot of older African Americans do not have study partners. They don't have anyone that will go with them to the doctor and be able to give information about these functional deficits. So some of these questions, again, are still really culturally bound. And I think all of these things make it more challenging to use cognitive tests by themselves as a way to document dementia.

Matt Davis:

So these tests that provide a score of some type?

Lisa Barnes:

Yes.

Matt Davis:

Why isn't just using a race-based norm a solution?

Lisa Barnes:

That is a really touchy situation. I think the most problematic part of using norms is that it makes a number of assumptions about biological construction race that we've already been talking about, and it might lead to some erroneous or potentially harmful interpretation of what the underlying racial difference is. And more importantly, when you use norms, it's almost impossible to understand why the differences exist in the first place because you are given a different set of normative values for one group compared to the other. So you can't understand why there are differences. So I mean, I think in some cases people who use norms in a clinical setting, that's all they have, and so they have to do that. But I think in research it becomes problematic because really it's sort of a crude proxy for lifelong social experience. It doesn't really capture everything we need to know. And so in my studies at least, I've tried to get away from that. And instead of using norms, I look at people over time longitudinally and compare them to themselves rather than to some normative value that can't really capture everything about a person's experience.

Donovan Maust:

One thing to just clarify, in the opening of your article, you talk about higher rates of dementia, higher prevalence of dementia among the African-American population. Just to be clear, I don't think that that's a function of the testing. So is the prevalence really truly is higher or is it that it's just like an artifact of the type of testing that we're using?

Lisa Barnes:

The prevalence seems to be higher, if you strictly look at prevalence, right? Because that's more of a function of starting level. So if you just look at performance on these tests and take into account the other factors that we use to make a diagnosis, it does appear their prevalence is higher. Now, incidents is the question. So if you follow people over time, do you see these same differences? There the data are much more mixed.

Matt Davis:

So in your article, you talk and review just the high points of the literature on race and cognitive outcomes. And you mentioned just how many of them are cross-sectional studies. In other words, studies that don't follow people over time. Could you talk a little about why this is an issue when it comes to understanding differences in Alzheimer's disease by race?

Lisa Barnes:

Because Alzheimer's disease develops slowly over decades, and so cross-sectional studies can really only give you a snapshot of performance at one point in time. And we know because of the social determinants of health that African-Americans perform more poorly on these tests, as I've been talking about. And these are the same tests that we use to make a diagnosis. So if you want to understand differences in Alzheimer's disease by race, we really need to have studies of people who enroll without disease and then they're followed over time with longitudinal designs, right? Because those factors that we know are influencing performance in cross-sectional studies, you're going to hold those things constant in a longitudinal design where you are essentially comparing the person to themselves.

And so I think that that's a much stronger design, especially when you're comparing across race and ethnicity, because there's no way that you can control for everything that's different between different people from different backgrounds in the cross-sectional design, but the longitudinal design, at least you're going to hold some of those things constant. So I think we need to be able to move more towards longitudinal designs. It's more expensive, and I think that's probably why, and it takes longer. It's why people probably don't do it as much, but I think that is needed if you're going to really understand racial differences in Alzheimer's disease.

Donovan Maust:

In your article, you talked about a really fascinating study looking at early life experiences and how that can impact education and segregation for African in the US that I think really highlights talking about race is much more than talking about race and it's about the experience in society. Can you talk just a little bit about that very cool study?

Lisa Barnes:

Yeah, that was one of our studies in our cohort here at Rush in the Alzheimer's Center, so in our cohort, where we enroll people without dementia and then we follow them over time, we have this interview where we ask them questions about their early life experience. And we had a block of questions where we were asking about whether or not they attended a legally segregated school when they were coming up, when they were younger. So these people are all in their sixties, seventies, and eighties now. So we are measuring their cognition in late life, and we're asking about their early life experience. And so what we found was that there were two cool things. Well, first we found that people who reported being born in the South, because everyone lives in Chicago. At some point, they migrated to Chicago and they enrolled in our study.

So the people who reported being born in the South, they performed more poorly on the cognitive function tests than people who reported being born in the North. Now, there's all these differences, of course, between the South and the North that could influence the results. But one thing we know for sure is that there were really different educational experiences of people born in the South and the North, such that at least in the South, it was much more likely that you attended a segregated school. But in 1954 when they had Brown versus Board of Education, where they outruled that you could attend a legally segregated school, we had some people who reported that they went through that transition. And so we looked at that in our data and we found that people who were born in the south and reported attending a legally desegregated school, so they had to go to school with other white students, when we look at their cognition in seventies and eighties, they are performing much more poorly, even compared to their southern counterparts who were in segregated schools.

And so this was a little surprising to us because we thought that segregated schools would be worse because fewer resources, maybe the teachers had lower quality or credentials. But what we think is going on is that attending a legally desegregated school during that time was probably a toxic stressor for these young kids. Because you remember all the pictures you would see of people being escorted with security guards and parents on the sidelines screaming at them and throwing stuff. That's got to be a really terrible, traumatic experience. And maybe it's something that we can pick up years later when we're looking at their cognitive performance. And we've seen this in other research, like with the Holocaust survivors. So it's a plausible explanation, but it really was a powerful indication of social context and lived experience and how early life experience may impact late life cognitive function in older African-Americans.

Matt Davis:

We could have done an entire episode just on that study, to be honest. Really interesting.

Donovan Maust:

Amazing.

Lisa Barnes:

And you told me to be brief, I'm sorry, but it's hard to talk about that because there was so much involved.

Matt Davis:

Has this study and other things you've worked on and thought about changed how you think about early life and cumulative experiences?

Lisa Barnes:

Yeah, definitely. I mean, before that, I really was focusing much more heavily on what people were doing right now, but people don't just show up at age 65 with these disparities. It's a lifelong process. And so we have to really understand what has happened across the lifespan to affect these cognitive aging outcomes. So yeah, it really has changed how I think about it.

Donovan Maust:

You have to, I think, work to not be too sort of pessimistic about dementia prevention efforts. We've had episodes earlier where we talked about Lecanemab and these treatments that are, okay, well, it'll be mild dementia, and then it's going to be for MCI and then it's going to be for amyloid accumulating. But it's like, no, no, no. It's like your childhood, what your childhood looks like influences your risk. So you have to... It's remarkable, the time span over which you have to really think about dementia prevention and it really is a lifelong kind of thing.

Lisa Barnes:

Exactly. And I think rather than being pessimistic, we can really think about, wow, what can we change now for people as they are aging? Now we're learning all these things, let's change policies to make education more equitable for everyone. So I think there's room for optimism, but yes, it's a lifelong disease. You're aging. We now know from our pathology studies that you're accumulating this pathology in your thirties and forties, I mean, long before you show any symptoms. So it's a long game.

Matt Davis:

It's too bad that so much of our work, those of us that have projects supported by the NIH and stuff, it's just so hard to... I mean, it ties back to things from so distant and I feel so disconnected from those types of things in terms of influencing our society and stuff.

Donovan Maust:

But I do actually just, not to put in a plug for the funder, but I do think NIA is actually interested in and appreciates this sort of life course perspective.

Lisa Barnes:

Oh, yeah.

Donovan Maust:

So they're not purely like, "What? The cutoff is 65." So they get the life course stuff.

Lisa Barnes:

Oh, absolutely. And they're even funding studies where the age range is much lower than 65 because they recognize this.

Matt Davis:

Yeah, I mean, so my comment was more based a little bit more on thinking about what your research could inform, you know what I mean? It is so much easier to say, oh, care in the hospital should be a little different or whatever, versus people should have better educational experiences and whatever. It's just too big of a concept. You know what I mean? How do you influence that? It's beyond the scope of an RO1, I suppose.

Lisa Barnes:

Right.

Matt Davis:

Okay. So just changing gears a little bit, one of the key things that you talk about in your article, you talk about this lack of enrollment of African-American individuals and how big of a problem it is when it comes to dementia research. I'm just curious, what factors do you think led to the underrepresentative nature of studies?

Lisa Barnes:

That could be an entire podcast itself as well. There's so many factors, I think. I'll just name a few of the big ones I think. So one is this reliance on passive recruitment strategies where you just basically recruit from your memory clinic, hang up a flyer. Well, we know that African-Americans have a fractured relationship with the healthcare system. They don't have access to a lot of these tertiary memory clinics, and so they're not going to be represented in your studies. So a lot of the recruitment science is still sort of not centered in communities of color. And so we lack community-based recruitment models. So that's one big one.

Another one is that oftentimes the eligibility criteria favor white participants because you have to have access to transportation, you have to have a few comorbidities. They screen out people who have hypertension and diabetes, which we know are very prevalent in African-American older adults. And then I think the third one I would say is not having diverse research teams or even creating a space where African-Americans feel welcome. You come to the clinic and you only see pictures of white people. You only see magazines of white people. So not really feeling like you belong in that research setting is a turnoff for older African-Americans. So I think those three things I would say are the biggest. There are lots of other ones we could talk about, but those really are the big ones.

Donovan Maust:

So who do you think is doing a good job in this space? And feel free to toot your own horn if you'd like.

Lisa Barnes:

I was going to say, can I toot my own horn? There are people out there doing a great job, but I would have to say that that's something that we do pride ourselves on here at the Rush Alzheimer's Disease Center. All of our studies are community-based. So we go to the community to find participants or recruit participants. We start out with really asking or not giving first before we ask anything. So I spent a few years in the field just giving presentations about healthy aging and memory loss and whatever they wanted to hear about so that they really felt like they were becoming more aware, getting educated about the issue before I just came in and said, "Hey, can you be in a research study?" So sort of building the trust and relationship. And then when it came time to actually do the study, I had all this buy-in because I had been in the community, I had built a relationship.

I built trust, me and the team. And so it was really easy to recruit people. And so we go to the people instead of having them come to us. The second thing we do is we do all of our testing in the person's home. So we never have them come to Rush and navigate a complicated maze of a medical center or have to have transportation. We just take our team to them. They're in the comfort of their own home and we can do all of our testing there. And I think those have been really great examples for us. And so because of that, my study has been going on for 20 years. Next year I'll be celebrating 20 years of following older African-Americans, which is really, really remarkable. And then there are others out there doing great work. But yeah, I'd have to say are I think we show that this is a really good model and it's shown in the high recruitment rates, the high retention rates, and then just the good, high quality research that comes out of it.

Matt Davis:

I was just thinking, considering the time it takes to invest into a community and kind of embed yourself and connect to them, I don't know, it makes me rethink, sort of. It argues for these longstanding projects like yours and others that sort of invest because it takes time. It's hard to do that in a single small research project to have that kind of resources.

Lisa Barnes:

And that's a really great point because what I hope to do, or what I've been trying to do is to really build a resource that people can use. So because I know it takes so long and everybody can't do this kind of work, I try to make the experience of the study so pleasant that we're able to add different things. So researchers will come to me and say, "Hey, I want to do a study on hearing loss, or I want to do imaging," I have the infrastructure now to be able to introduce those things. And so people don't have to do that, the busy work of building the cohort. If they have a good research question and they're thoughtful and they really want to make a difference, they can partner with me and introduce their studies into my cohort. So I mean, that's another reason to have this longstanding 20 year, which I hope will be funded for another 20 years, to really be a resource for the scientific community.

Matt Davis:

Many of our listeners are kind of new to the ADRD space. So what's the process like for people that might want to use the data from your cohort?

Lisa Barnes:

Well, first they have to contact me, but we actually share our data really widely. We have a data sharing hub, so if you go to www.radc.rush.edu. So www.radc.rush.edu. On there, you'll find a data sharing hub that lists all of our cohort studies and all of the variables we collect. And so it's really easy to get data from us. Now, if you want to introduce something new, then that's when you have to contact me for my cohorts in particular, because we have to think about burden and all of that. But the data that have been collected already? That is freely available for anybody who wants to use it for papers or to write grants or whatever. So I encourage the listeners to go and check that out.

Matt Davis:

I think previous guests on our podcast have used it for really-

Lisa Barnes:

Oh, cool. Yes, I love that.

Matt Davis:

So in terms of the thinking about the field and what's next, you've given us a lot to think about, but from your perspective, what should the field focus on next when it comes to race and Alzheimer's disease?

Lisa Barnes:

Yeah, I think one is pretty obvious based on our conversation. I think we need to have better characterization of the socio-exposome, we're calling it now. Just basically the broader social context in which people are embedded, whether that's the neighborhood or a complete lifespan study. We really need to start thinking more about that and how to measure those types of variables. There's a lot of information out there now, but we can go much further in how we develop those measures. Another area that's gaining traction I think we need a lot more data on are the biomarkers to understand disease. Instead of waiting now until people die and get their brains, which is still really, really impactful and important, as we do that too at Rush. But now you can see the disease in vivo where people are still living. And so there's this huge growth in biomarkers like fluid biomarkers, which are much more accessible than a PET scan or a lumbar puncture, the traditional ways that we have used to see disease in people while they're living.

Now you can take blood and measure these biomarkers, but we have very little information about this in diverse populations. So we need more data in that space to really understand how these biomarkers function in diverse populations, but also how these risk factors of interest may influence the biomarkers. I think another area that I would like to see grow is more sensitive measures of cognitive performance. Instead of just relying on the traditional pen and paper tests, there's all these digital measures that might look at different metrics, like maybe they look at speed over accuracy or just other ways to conceptualize metrics of success. There's people in that space doing some really great work, and we need to have more diversity in that space as well.

I think the last thing I would say I would love to see is maybe more emphasis on resilience markers. Not everyone's going to get Alzheimer's disease. There are some people who are living to their 80s, 90s, 100s who never get the disease. How can we understand what they're doing, what their lifestyle is or what's in their body to help keep them protected? So more of a focus on resilience markers and diverse populations would be really, really awesome.

Matt Davis:

I think you've given our listeners half a dozen different incredible research ideas there.

Lisa Barnes:

That's good.

Matt Davis:

It sounds like it'll take a village. This has been great. Lisa, thanks so much for joining us.

Lisa Barnes:

Thank you for having me.

Matt Davis:

If you enjoyed our discussion today, please consider subscribing to our podcast. Other episodes can be found on Apple Podcasts, Spotify, and SoundCloud, as well as directly from us at capra.med.umich.edu, where a full transcript of this episode is also available. On our website, you'll also find links to our seminar series and data products we've created for dementia research. Music and engineering for this podcast was provided by Dan Langa. More information available at www.danlanga.com.

Minding Memory is part of the Michigan Medicine Podcast Network. Find more shows at UofMhealth.org/podcast. Support for this podcast comes from the National Institute on Aging at the National Institutes of Health, as well as the Institute for Healthcare Policy and Innovation at the University of Michigan. The views expressed in this podcast do not necessarily represent the views of the NIH or the University of Michigan. Thanks for joining us, and we'll be back soon.