Dementia Matters Special Series: The National Strategy for Alzheimer's Disease Data and Research Part 1:
Kicking off our six-episode series on the National Alzheimer’s Coordinating Center and their Spring 2022 ADRC meeting, Dr. Walter Kukull joins the podcast. He explains what NACC is, what they do with the data they collect from the 42+ Alzheimer’s Disease Research Centers, the center’s biannual ADRC meetings and what he’s most excited about for the next five years of Alzheimer’s disease research.
Guest: Walter Kukull, PhD, director, National Alzheimer’s Coordinating Center, professor, University of Washington department of epidemiology
Learn more about the National Alzheimer’s Coordinating Center at their website.
View slides and video recordings of NACC’s Spring 2022 ADRC Meeting on the NACC website.
Register for NACC’s Fall 2022 ADRC Meeting on their website. Registration is free and open to the public. The fall meeting, which will focus on diversity, equity, and inclusion in Alzheimer’s research, will take place Thursday, October 20, and Friday, October 21, both virtually and in person in Chicago, IL.
Learn more about Dr. Kukull in his bio on the University of Washington’s Memory and Brain Wellness Center website.
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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: Welcome back to Dementia Matters. This week, Dementia Matters is kicking off a new six-part special series called The National Strategy for Alzheimer's Disease Data and Research, exploring the systems and processes being built to propel Alzheimer’s disease research forward. This series is a collaboration between Dementia Matters, the National Institute on Aging, or NIA, and the National Alzheimer’s Coordinating Center, known as NACC. Each week, we’ll be joined by a new scientific researcher from NACC’s Spring 2022 Alzheimer’s Disease Research Center Meeting sharing insights into their work in data harmonization, data security, and more. These episodes will lead up to the Hybrid Fall Alzheimer’s Disease Research Center Meeting happening online and in Chicago, IL, from October 20th to the 21st. The theme for this fall’s meeting is diversity, equity, and inclusion in Alzheimer’s disease research, and registration for this hybrid conference is free and open to the public. To learn more and listen to the talks at the fall ADRC Meeting, register at NACC’s website. You can find the link in the episode description. To kick off this series, I'm here with Dr. Walter Kukull, a professor of epidemiology at the University of Washington in Seattle. He studies neurodegenerative and vascular causes of dementia and since 1999 has served as the director and principal investigator of the National Alzheimer's Coordinating Center, also known as NACC. In this role, he works closely with the 42 Alzheimer's Disease Research Centers and Exploratory Centers funded by the National Institute on Aging. Dr. Kukull, welcome to Dementia Matters.
Dr. Walter Kukull: Thank you, thank you! I'm glad to be here.
Chin: My hope is for our listeners to learn about the system and the processes involved in conducting Alzheimer's disease research, starting with this annual spring ADC meeting. So to begin, Dr. Kukull, can you tell our listeners, what exactly is NACC and how has it evolved since 1999?
Kukull: Okay, well, NACC serves as a repository for clinical data that's collected at the Alzheimer's centers funded by the NIA, the National Institute on Aging. The Alzheimer's Disease Centers Program actually began in 1984. Between 1984 and about 1997 or so, no common data was collected and stored anywhere. Each of the centers, of course, had their own, but there wasn't anything going into a central repository. About 1998, the centers finally agreed with the NIA that they should have some kind of data sharing. So they started to put together a very brief minimum data set of about 55 data elements that they'd retrospectively gather from the centers to characterize cumulative enrollment across the center's program at that point. In about 1999, they issued an RFA for somebody to take over this activity. We were lucky enough to be funded at that point. So when we assumed control of this fledgling minimum data set, we began to contact the centers and see what we could provide to fill in the blanks because there were a lot of missing values and so on. We worked on the minimum data set, which we still have, to do this for about five years. During that time, because we thought it would be more useful for research and a lot of the center directors thought it would be useful for research, to start gathering a really detailed clinical standardized data set. We began talking with people at NIA and they appointed a clinical task force, which at that time was led by John Morris at Washington University and started to, in about 2002 or so, started to discuss how to create what we called a uniform data set, or UDS, which would be a longitudinal, very detailed clinical examination.
Chin: So in essence, I mean, good science is about good data and NACC is really the person – or the group, I should say – that collects and organizes and makes sure that the data that's going on at all these centers across the country on Alzheimer's disease is appropriate, clinically relevant, and valid.
Kukull: Yeah, we put a lot of effort into that. Working with the clinical task force to make it relevant to where the current science is is also really difficult, and then quality control of these things as we go. It's also probably important to note that each one of these 37, or however many centers there are, also a lot of other data that isn't specifically just this. So we're kind of this standardized core of data collection from the centers.
Chin: How have things changed for you since 1999 to now?
Kukull: I think the biggest change was coming up with that standardized data set, moving from just what was like retrospectively abstracted from records, which might have been collected in all sorts of ways, but we do have that minimum data set still available if people want to do things with it. It's valuable in its own right for some kinds of things. For the most part, we've moved on to the UDS, or the uniform data set, because it is longitudinal and we can track change over time that way.
Chin: And that's so important in a condition like Alzheimer's disease where changes happen decades in advance and we need to understand it over a person's lifetime. What are NACC’s goals? What specifically is NACC working towards or that could be separate from our ADRCs, but how do you anticipate NACC is going to expand as AD Research is expanding?
Kukull: We're trying to do as much as we can to connect different data sources, other resources that the National Institute on Aging has, like genomic data and specimen data and other kinds of things that are going on, so that people can come to us and not only get the uniform data set or our neuropathology data but they can easily connect to these other sources and link them to the same IDs that we have in our database. Although we don't hold all that other data we can, we can facilitate that interface.
Chin: And I think a lot of our research participants wonder, well what actually happens to the data that's collected at each site. What does NACC do with that data? And I presume they receive it electronically, but how does NACC handle that data?
Kukull: Well, we set it up in a database and we have a system where researchers from, actually, around the world can contact us on the web and apply to use the data. The data is free. We don't charge anything for that. People have to show that they're qualified users. We're not giving out to commercial companies and that sort of thing, but they basically make requests of data because they want to look at different things or maybe want to write a paper, something like that or just are curious about what data is collected. We get – oh I don't know – we've had probably over 4,000 data requests from different people. Those all haven't resulted in published papers or anything, but we do have about almost a thousand published papers at this point from the data. Most of those come from the uniform data set and the neuropathology data that goes with it.
Chin: And that's incredible. I mean 4,000 requests but almost 1,000 or over 1,000 actual shared publications so that other scientists and community people can see that. And I'm wondering, could you highlight for some of our listeners, in your opinion, some really important findings or publications that came out of the NACC data set?
Kukull: Let's see. One that I can remember, a few years ago we were looking at – within this set of people we have people who are normal cognition, others who are MCI or mild cognitive impairment, and others who have one form or another of dementia. Out of these 45,000 people that are in that bin, we have about almost 7,000 with autopsy data, detailed neuropathologic exams. From that group, we were able to look at people who didn't have any symptoms and yet had features of Alzheimer's disease – amyloid and tau and so on – or other kinds of neuropathology and also look at people with different characterized dementias. One of the important things that we were able to look at was – what were the characteristics of these people who had pathologic disease and how did they decline? Or how did they change over time in their clinical symptoms and how did that match up with people who we were following also, but came into this program already with clinical symptoms? So I think that that fit with a lot of the impetus from the centers at the same time trying to characterize, well because this pathology might start 20 years before, how can we describe how people are changing? Maybe they're changing in such subtle ways that it's not very noticeable. We began to look at it in that way. Maybe another one – just to bring up another one that's kind of in the news, and this is in conjunction with Julie Schneider from Rush and Pete Nelson from Kentucky, primarily. They were the prime movers on it. That's looking at something that's called late disease. I'll get all these things wrong. Limbic associated TDP encephalopathy is sort of a retinopathy of TDP-43 that accumulates late in a person's life, frequently along with Alzheimer's disease pathology. People who have both of these decline more steeply than people with just one of the pathologies. That's one of the big issues today is describing how multiple pathologies work together both to synergize their spread internally or pathologically, as well as to accelerate their kind of clinical syndrome.
Chin: And I think it's so important for people to recognize that we have to do studies like this, where we have to follow people for a long period of time so that we can contextualize all the various things that may be impacting our aging brains. Through the NACC data set we’re really able to do that. It's because of this uniform dataset or minimum dataset – whichever term we want to use – but that's really for those that are not involved in research. It's a standardized set of forms, some questionnaire-based, some observed data, collected data, cognitive testing data, but it's really all put together. It does represent sort of a health evaluation for someone, certainly a lot of research data points for our scientists. How are these forms actually determined? You mentioned the clinical task force. And then, how often are they updated, because the field is changing so quickly?
Kukull: The clinical task force is kind of responsible for that. They have come up with it based on what the current set of information that people usually use in a standard workup for one of these dementias, Alzheimer's disease, and so on. Then they expand out a bit to see how – as time has gone on, we've been more interested in trying to find the very earliest changes, the very earliest clinical changes. That's where mild cognitive impairment kind of came from. We keep pushing that envelope back a little further to try to look and see how we can identify people. In one of the more recent versions, we added things about biomarkers – being able to measure amyloid and tau for instance, first in CSF or in PET imaging and now more recently in some blood and plasma-based biomarkers for the same thing. If we can identify people who have the disease, we can then better characterize and better look for earliest clinical signs or earliest observable signs that they might be changing symptomatically. We review these things all the time. The clinical task force kind of turns over. NIA appoints people on a rotating basis – always seems like the leaders in the field from the centers. It turns – it's somewhere five to eight years in between and there's no set time. It's just when the critical mass views that it's time for a revision or the basic disease criteria have changed somewhat., like the addition of biomarkers or the idea of the biological start of the disease rather than the symptomatic disease. That was probably the last big change in thinking about the disease.
Chin: I think it's also important for our listeners to know that, while change is good and change is needed because we have to be able to adapt to new findings, it's also important to keep the old, or parts of the old, so we can compare our studies from ten years ago and 20 years ago. So it's a balance I'm sure that must be walked with NACC and our clinical task force.
Kukull: We keep a harmonization or a link to the data that were gathered before so that people can actually do these broader longitudinal things. Of course, there are some things that we just didn't know about before so they start at some point, and other things that are dead-ended because maybe they were not so useful or the task force wanted to cut down on the patient burden or something like that. It's always a tension back and forth of how do we keep things up but have enough link to the legacy data that we can really use the full extent of what's been gathered and jump off from there to generate new hypotheses.
Chin: I think a good example of that is, I know that in the future we'll be studying COVID and its impact on aging brains and cognition. That's something that just came up and will be added to the subsequent forms.
Kukull: Yeah, that's true. We're working on that right now to try to add that in.
Chin: Well, so then, we're here to talk about the NACC Spring ADC – Alzheimer's Disease Center – so the next spring ADC meeting. Can you explain for our listeners what is this annual meeting? How long has it been happening?
Kukull: Oh gosh, I think these have been happening since the program started back in 1984. Actually, it used to be just the kind of the pool of directors. At first when the center started, it was about ten centers, and so they'd kind of get together and talk over what was going on and that sort of thing. That usually happened in the spring and in the fall. It's just continued but it's gotten bigger. In the distant past, it was just the directors kind of sitting around a big table and talking. As it's gone more, it involves more of the core leaders. Each center has different cores like a clinical core, neuropathology core, and so on. We brought in more people. In the last few years with COVID and so on, we've gone to virtual meetings. People didn't have to pay for travel anymore. Since we were in charge of setting up these meetings we also opened it up a little bit with NIA’s approval to other people at the centers so they could listen in and hear what Dr. Hodes, the director of the NIA, had to say about funding and so on, or listen to experts on the science. There's always good science talks at these meetings in addition to just other updates in what people are doing, what NACC is doing, what other groups are doing or studies they might be interested in. It made it much more broad, and his time was the first true hybrid meeting that we put on or that has been put on for the center's directors, so we had it in-person at the same time as the virtual meeting.
Chin: And it's an incredible opportunity for people to see what happens at that level of the centers and of the data collection. Looking at the agenda, what do you think are the goals for this year's spring meeting?
Kukull: The main things are, as always, to let people know what's on the – what's on the minds of the people running the various cores, biomarkers core, the imaging cores, the research and education core. What are their big initiatives and how are they moving forward? And NACC also presents what we're doing, how we're trying to move ourselves forward to help the program. Those are kind of the – oh I don't know – stock goals of this whole thing, just to begin to update everybody about where are you and where are you going. The dual purpose of these things is not only just to do this update, but usually to bring in some scientists who are doing the cutting edge work to be able to talk about the specific things and either open up new ideas to the listeners or the people who are there or bring everybody up to speed on what these people are doing and most interested in, how that fits with moving the field forward.
Chin: And in this miniseries, Dr. Kukull, I'll actually be interviewing some of those scientific presenters who are at this conference and highlighting the work they're doing but also the future directions of the science. I guess to end, I'm curious to know, as someone not directly involved in the ADRCs but someone very intimately involved in the AD field, what are you most excited about when you think of the next five years of Alzheimer's disease research?
Kukull: I think we're in a place right now where we're trying to think about and explain how multiple pathologies work together to cause symptoms of dementia. We're in this odd place where we have a lot of new information about the biology, the pathology of these disease-causing entities and how they maybe work together, but we aren't too sure about that end of it. Then we've kind of got a parallel set of interests about the phenomenology – the symptom patterns – and the public health end of it. How does that place a burden on the system, on the public health, on the caregivers, on everybody else? What can we do with people who have symptoms to make their lives better. We haven't been able to find much in the way of treatment, but that's kind of the promise and the hope that we have with all of these things – to try to do what we can to alleviate symptoms as well as, on the biology end if we can, prevent the disease etiology, proteinopathies, and so on, from causing symptoms. So we've kind of got two things going at the same time. There is some tension between the two because the people on the symptom-end are saying, ‘Why – you're wasting your time with all these biological markers’. We want to make the world better for the people who have the disease. I think everybody really wants both. It's just that it's kind of a new and exciting time that we're trying to find the best ways to make that jump and really really help people out.
Chin: Well with that, I'd like to thank you for being on Dementia Matters and we certainly hope to have you on in the future.
Kukull: Oh thank you. This has been fun.
Outro: Thank you for listening to Dementia Matters. Follow us on Apple Podcasts, Spotify, Google Podcasts, or wherever you listen or tell your smart speaker to play the Dementia Matters podcast. Please rate us on your favorite podcast app -- it helps other people find our show and lets us know how we are doing. Dementia Matters is brought to you by the Wisconsin Alzheimer's Disease Research Center at the University of Wisconsin--Madison. 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 of Dementia Matters was produced by Amy Lambright Murphy and edited by Caoilfhinn Rauwerdink. Our musical jingle is "Cases to Rest" by Blue Dot Sessions. To learn more about the Wisconsin Alzheimer's Disease Research Center and Dementia Matters, check out our website at adrc.wisc.edu, and follow us on Facebook and Twitter. If you have any questions or comments, email us at firstname.lastname@example.org. Thanks for listening.