Neighborhoods and Neurons: Study Finds Association between Neighborhood Disadvantage and Alzheimer’s Disease-related Brain Changes

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Show Notes

Read more about the study "Association of Neighborhood-Level Disadvantage with Alzheimer Disease Neuropathology," which was published in JAMA Network Open on June 11, 2020.

Visit the Neighborhood Atlas, an online interactive mapping tool that provides measures of U.S. neighborhood disadvantage in an easily accessible format that is free and open to everyone.

Transcript

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: Our guest on Dementia Matters is Dr. Ryan Powell, a health services research scientist at the University of Wisconsin School of Medicine and Public Health. Dr. Powell is interested in improving the ways in which research is developed, interpreted, and used to inform key healthcare decisions. In a recent study, Dr. Powell and his co-authors found people in the most disadvantaged neighborhoods may face greater odds of developing Alzheimer's disease-related brain changes. Welcome to Dementia Matters.

Dr. Ryan Powell: Thank you. Thank you so much for having me here! I love the show. I’m excited to be here.

Chin: Well I love that you said it and I didn't ask you to say it, so thank you. (laughs)

Powell: (laughs)

Chin: Now your recent publication, “Association of Neighborhood Level Disadvantage with Alzheimer's Disease Neuropathology,” is the first of its kind to link neighborhood disadvantage to brain tissue markers associated with Alzheimer's disease, so this is an incredible finding. Before we actually dive into what it means, let's start by explaining a few key concepts to our listeners. Neighborhood-level disadvantage addresses a concept called social determinants of health. To begin, what are social determinants of health?

Powell: Yeah that's a great question. It's kind of one of those buzzwords that's used in the research community. They're essentially just – they’re conditions in your daily life that impact your health. That's super broad but what we're talking about is the context here in which somebody lives. You can think about it for example - some examples would be economic stabilities, so conditions related to income or employment or even some cascading things related to it. If you think about access to affordable health care, talking about things related to education, for example, or if you just kind of take your daily life. Where do you live? What's your neighborhood look like? What's the safety around your neighborhood? Do you have access to healthy foods within the neighborhood? What's the transportation system look like around your neighborhood? Are you able to get to your doctor or do you have to walk, you know, a half mile and then take a train or take a bus or something? It's really all these conditions that are kind of going around in your whole life, so where you live, where you work, where you do things for fun – so you think about things related to fun would be like access to parks and green space, those types of things. It's a pretty broad term to really talk about the context in which people are living their lives.

Chin: I really like your answer because you're right about context. Really it's about explaining not just health because, I mean, that's what's misleading is social determinants of health. You just assume, “Oh this is about high blood pressure, cholesterol issues, things that might increase risk for cancer,” but it's more than that. It really encompasses all those other things that you mentioned that perhaps we take for granted and don't consider in our overall health. And so one of the other concepts that you use in this paper and in your research is this tool to measure neighborhood-level disadvantage and you call this tool the Area Deprivation Index. Now for our regular listeners – and I hope there's many out there - this was discussed in detail in a recent interview that we did with another Wisconsin scientist, one of your colleagues, who studies Alzheimer's disease. This is Dr. Jack Hunt. For those that didn't listen yet, will you explain to us this Area Deprivation Index?

Powell: Sure, yeah. It's just one way of capturing some of these social determinants of health at a neighborhood level. This measure – the Area Deprivation Index – reflects 17 factors and they're around income, education, employment, and housing at a very, very precise neighborhood level. We're talking – technically speaking – we're talking at the census block group level. To put it in contrast we're talking about, over the U.S., about seven million neighborhoods that we can look at contrasted to, if you think about where typically most of these geographic variations analyses look at are at the county level, county levels are about 3,000. You can kind of see the precision that it's getting at. It's a ranked index so it ranks from least disadvantaged to the most disadvantaged. The data that we use comes from the U.S. Census survey. For more recent years, it comes from the American Community Survey. Some other aspects would be that it's NIH-funded. Oh, this is a big one - it's freely available to anyone! We have it online. You guys, the listeners, can do a web search for it. You can check it out if you type in ‘University of Wisconsin Neighborhood Atlas,’ you can take a look at the features that it has. You can even use your phone. You can look up any neighborhood in the U.S. and it can tell you kind of the relative rankings of those neighborhoods and you can get an idea, if you look at your own neighborhood, to kind of understand the geographic precision that it's at. We use this tool in research. We've used it with, for example, to look at hippocampal volume in Dr. Jack Hunt's study and other types of brain health, but we've used it as well across a variety of different research topics, a lot around health care quality and outcomes. The tool can be applied beyond research. It can be really used by anybody in the community so it's freely available. You can download it for free. If you have a data set, you can link to it. If not, you can look at the maps and you can start thinking about, for example one area would be – you could use it to target outreach efforts to neighborhoods with the greatest need, for example.

Chin: It's an incredible tool. I've gone on it just to play around and look at it. It's beautifully done and it's pretty easy to use for someone who's not in this technical field. How updated is the information, when you talk about the census? Like what was the year that you're using to create the atlas?

Powell: Right. Prior to I believe 2010, we were doing an update ever – we could do an update every ten years. That's what the census is based on, but now that the this type of information is moved to the American Community Survey we can do an update every year. So really our goal is to have a new update for each of the years.

Chin: Oh wow! That's quite a challenge but also really important because you're going to have really updated information for people.

Powell: That's right! That's right. The capabilities of having it be a ranked index is you can compare over time. You can kind of compare backwards and forwards so you can kind of look at exposures over time or changes over time. 

Chin: Okay, so now that we have those concepts explained, what exactly did your study look at using this Area Deprivation Index and Neighborhood Atlas?

Powell: To evaluate brain health, what we're really doing is we're evaluating Alzheimer's disease related brain changes and really the definitive way to measure that is that autopsy, so a neuropathologist really looking at tissue samples and kind of trying to understand the brain-related changes. The two hallmark brain-related changes are the tangles and the plaques. In this study we're really looking at just the presence of plaques. To evaluate brain health we looked at 447 brains from across these two centers from people who have donated their brains over a span of 25 years, which to me is – it kind of chokes me up. It's really amazing. I'm so grateful that we're able to make these new discoveries considering that some of these brains are donated from people that have donated over 25 years ago, which is just super. Really we were looking at that linkage between Alzheimer's disease and neighborhood deprivation, neighborhood disadvantage.

Chin: I think it's really important for our listeners to realize too, that so many of the studies that come out that are really important and pivotal are using surrogates or markers of Alzheimer's changes. These are CSF, or cerebrospinal fluid changes, and PET scans are advanced technology, but you guys actually looked at the brain tissue. You looked at the most definitive, or what we call the gold standard, of brain changes related to Alzheimer's disease and then you compared that or you studied that in the context of the Area Deprivation Index to see if there was a correlation or some sort of relationship. 

Powell: That's correct, yes.

Chin: And so what did you find?

Powell: Yeah, there's a couple of really interesting findings from here. First off, at the really basic level it's feasible to add this connection to the existing brain bank data. Really this could apply to any of the brain banks, any of the ADRCs that we have. They can start trying to consider context within their own research, which is a super exciting thought. Sort of, we've established the feasibility of adding this neighborhood-disadvantage connection to the existing brain bank data. Then number two is we found an association. As neighborhoods become disadvantaged, the odds of these brain-related changes of someone living in that context increases. And so when you compare the odds of somebody living in the least disadvantaged neighborhoods to the people that are living in the most disadvantaged neighborhoods, the odds of having these brain-related changes is about double.

Chin: Wow! Okay, so two times the increased risk of developing these actual Alzheimer's disease changes in the brain when you're living in the most disadvantaged neighborhood compared to the most advantaged neighborhood.

Powell: That's right, yeah. This is just kind of really just establishing an association. There's much more work to be done. We can talk about that, but this is just kind of the initial baby steps here. We're kind of just exploring associations and we can talk about some of the things that we can do in the future to kind of really understand what's driving this. At this point, we just can really try to understand the associations between the two.

Chin: Yeah, I appreciate that you're being very clear with your words too because you're saying association and you're saying the odds are sort of a risk to these findings. You're not saying that one is causing the other but when we think about that, when we think about this relationship, clearly there are you know more granular or more specific things that could be causing it. I guess I'm wondering how you think the social factors that you're looking at with your Area Deprivation Index that you're measuring, how those could potentially interact with the actual brain changes in the human person and how you think that you know those could relate?

Powell: That's right, yeah. We're starting with these associations and the next step really would be to kind of, let's try to understand what would be driving the relationships kind of from neighborhoods to neurons really. What are the possible factors that could be causing this? We know from other studies looking at increases in amyloid that they're related to chronic stress, sleep disruption, lifestyle factors such as diet and exercise, pollution and cardiovascular disease risks like diabetes. So really the next series of steps will be to kind of really try to understand what are the pathways? There's probably multiple pathways really, but really trying to understand how it is that this association exists.

Chin: You and your co-authors, you looked at something else in the study. Through advanced mapping techniques, you discovered that 56 percent of Americans live within 100 miles of the National Institute on Aging-funded Alzheimer's Disease Research Centers like the one here in Madison, Wisconsin. For our listeners out there, there are 32 of these centers across the country. They are all funded through the National Institute for Health and they all conduct this longitudinal research on Alzheimer's disease and related dementias, where we have participants coming in and staying with us for years, even decades. Now they collect data in similar ways and they share this anonymous data with each other really so that we can work together on this true national strategy to research, understand Alzheimer's disease. Why is geographical access to Alzheimer's Disease Research Centers so important in Alzheimer's disease research? What is the significance of your findings of 56 percent of Americans – what does that mean for us?

Powell: Yeah that's a super question. Thank you for asking that! Yeah, the geosimulation really suggests that geographic access is difficult for about half of the country and it's particularly challenging and difficult, potentially, for those living in the most disadvantaged neighborhoods. This really mirrors what we found in our brain bank sample that we had, so we had most people living within 100 miles and we really overrepresented those living in the more affluent areas and really underrepresented those who are coming from the most disadvantaged areas. I can speak best from the research perspective. It's really important because it determines who's involved in our research studies. Down the line this could be really worrisome if you think about research eventually informing prevention strategies and treatment efforts. We really don't want to leave anybody out of that process, kind of the process from research to kind of these really tailored treatments. We want everybody to have a seat at the table so to speak. We want everybody to be represented. Otherwise any sort of treatments or prevention strategies that come out might be less effective for certain populations or certain groups. It really underscores the need for a continued effort to make diverse participation and geographic access to research centers a priority in our strategy moving forward. A lot of the geosimulation, the map, really was just for readers to understand and try to get an idea of maybe where efforts could really be diverted to think about where maybe some additional outreach can happen across the U.S. 

Chin: Yeah, your map is beautiful. We'll have a link to that in your article and for those that are interested, they should really take a look at it. I mean, we're very fortunate that the National Institute for Health has funded so many centers, but it does show that we need to change or adapt and modify our approach to recruit more people or to find ways of reaching people in these more disadvantaged areas. I think your study, as well as other studies coming from your group, is showing how we define ‘disadvantaged’ and ‘underserved.’ People usually think of an urban setting but it really is rural settings as well and it is areas away from cities that are going to need access to healthcare but also access to research. 

Powell: That's right, and there's a lot going on in the field, I should say, to try to address some of these things. Somebody that's really involved in the recruitment sciences could probably speak more to that, but there's really a lot going on. This is a known problem and there's a lot of people, smart people, really trying to tackle this.

Chin: Thank goodness for that. I will say, as a physician going through this COVID situation and trying to improve ways to access my patients, I think our research centers are doing the same thing considering how can we reach people virtually, how can we speak to them and work with them even if they're not physically in front of us. It's an exciting time but research like this really shows the importance of why we need to push forward. I guess in that line of thinking, what is the next step for your research and for your research team?

Powell: Yeah great question! Thanks for asking it. There's a lot going on, so again this is just sort of the first baby step. I think the first thing that's needed from other researchers out there is to kind of confirm the finding, as well as overcome some of the methodological limitations we had. Right now, again, we're just viewing associations at this point. We really don't know what could be driving the association. That's a way off. Again, the hope really would be that similar technology that we used here, the ADI, could be used to explore this pathway from neighborhoods to neurons or social context to basic biology, however you want to put it. For us, one of the next steps is we know that Alzheimer's disease is clearly a life course problem that's happening. For example, the neuropathologies – these changes are occurring over decades. Our next approach with neighborhood disadvantages is to try to take on this life course perspective. What we're doing is we're developing methods that can go trace through a person's whole entire life and try to understand to what extent they've lived in disadvantaged areas. You can think about a myriad of questions around it – are there critical or sensitive periods that are more important than others? Is it really about the cumulative effect over time? Hopefully this research can lead to kind of understanding when we really need to start providing really tailored treatments and prevention strategies. That's kind of the next first step is this life course perspective. Another one is we look to partner with additional brain banks to really start moving forward to uncovering this causal pathway from neighborhood disadvantage to brain-related changes. With our study that we just did, you could see that again the most disadvantaged neighborhoods are underrepresented. Hopefully with all of us kind of banding together, we can kind of have the ability to understand really the complex pathways that are happening within all these different populations. At this point from the research perspective it's sort of an issue of power, sort of how can we slice and dice the data and look at all these different really complex pathways. With this data that we have right now for the study that we just did, we weren't able to really do that. One of the reasons is the low number of people in the most disadvantaged group but, as well, we don't have additional characteristics that we need to kind of understand these pathways, so information around behavioral lifestyle kinds of things, diet and exercise. We don't have any information on cardiovascular risks, for example, or some of those types of measures to add that in there to really get a really well-rounded idea of what's going on here. Partnering with brain banks, with additional brain banks, to really start moving this research forward is another next step.

Chin: That makes a lot of sense, providing more data, more richness, to your data as you build the context of this human life course as it relates to Alzheimer's. I want to ask you – I want to end by asking you a tough question because I want you to think five, ten steps down the road for our listeners. I'm not gonna hold you to your answer and we're not gonna replay this when the time comes but I want to know, as a society where do we go from here? How can we make changes at the community level to help prevent or slow the development of Alzheimer's disease brain changes?

Powell: Wow, gosh that's such a great question! Unfortunately I don't have an answer for that. It's so – right now there's just so much we don't know. I wish we were farther along so it's really difficult to say at this point unfortunately. From a research perspective, we're just starting. Again, many of the underlying reasons that are driving these disparities are really unknown. And again, I want to reiterate how crucial it is to have this diverse representation in the research because that's really where any sort of community level strategies are going to be developed. Without that diverse participation, any prevention strategies or therapies are probably going to be less effective than they really could be. I'm sorry I don't have a good answer for that. I wish we were farther along, but hopefully working together with all the other ADRCs to really try to tackle this problem we can make some great progress in the next few years.

Chin: I can appreciate that answer. You did a nice job of not dodging it entirely but also you said we need participants right we need people from all backgrounds, all walks of life, all socioeconomic statuses, all neighborhoods –

Powell: That's right.

Chin: – to participate if they can. I think that's a good message. I appreciate that, Dr. Powell, and I'd like to thank you for joining me on Dementia Matters. We do hope to have you on with your future studies.

Powell: Oh thank you so much, Dr. Chin. I really had a lot of fun here. Thank you.

Chin: I'd like to end this episode with a commentary. To say this is an important finding is an understatement. What you, Dr. Powell, Dr. Amy Kind, and the rest of your team are showing that where we live and how we live has an effect, literally in our brains, decades and decades later, but this finding can only be shown by the generosity of people being willing to donate their brains to science. It is the ultimate gift to research and an incredible gesture to our future generations, so I'd like to take this moment to sincerely and wholeheartedly thank the participants signed up for brain donation and the family members of those that have donated their brains and other organs to science. Thank you. 

Outro: Please subscribe to Dementia Matters on Apple Podcasts, Spotify, Podbean, or wherever you get your podcasts. 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 dementiamatters@medicine.wisc.edu. Thanks for listening.