Highlights from the 2023 Alzheimer’s Association International Conference

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: Welcome back to Dementia Matters. From July 16 to the 20, Alzheimer's disease researchers gathered in Amsterdam for the 2023 Alzheimer's Association International Conference, known as AAIC. The conference is the world's largest forum for dementia research bringing together researchers, scientists, students, people living with dementia and their care partners and many more. Returning to the podcast to talk about this year's conference and its highlights is Dr Percy Griffin, director of scientific engagement at the Alzheimer's Association. He holds his doctorate in molecular cell biology and previously worked on protein degradation and neuroimmunology in Alzheimer's disease and Parkinson's disease. Dr Griffin gave a wonderful summary of AAIC 2022 on August 10th, 2022, which you can listen to after this one. Percy, welcome back to Dementia Matters.

Griffin: Thanks for having me back, Nate. Glad to be back.

Chin: I'm excited to have this conversation. We had a good time last year and I'm assuming the same for today. Let me start with what made the Alzheimer's Association decide on the city of Amsterdam as a destination for this year's conference, and in that answer, were you able to see any of the sightseeing there as well?

Griffin: Yeah, so actually this was our third try to get to Amsterdam. We were trying to get to Amsterdam early on and then the pandemic happened. Then we wanted to go after things kind of eased up a little bit, but that didn't work out. Third time’s the charm, as they say. As you said in your introduction, the Alzheimer's Association International Conference is a global conference, and a global conference requires a global presence to get global perspectives. Alzheimer's is a truly global problem and to combat it we need these global perspectives, so we try to have our conferences in different places. We have them in the US for a couple of years, and then we go somewhere else. This year we finally made it to Amsterdam, and wow, what a fantastic city to see. The food was amazing – a little bit spicier than I had expected. We took a canal ride. I got to see the city. The architecture was quite fascinating. I got to see a mix of old buildings and new buildings with very interesting architectural structures; that was super cool. The bike culture was also quite interesting there. The bikes were there on the streets with us people. It was fascinating. How was your experience, Nate?

Chin: I want to echo what you said. I had a wonderful time at the conference. Of course fascinating presentations, which we'll talk about in a second, but the city was amazing. I'd never been there before, so I really took advantage. On one particular day I logged over 30,000 steps, and that is because the city is so walkable. I mean there were – you have an opportunity to bike, which I didn't unfortunately get to do, but it's a beautiful place. I agree, there's so many people from all walks of life from all over the world. It was really nice to see. I would say I enjoyed the museums a great deal. I enjoyed the canals. I, too, got to take a canal ride. There's just a great energy. Of course you know this Percy, I'm from the Midwest. I love being in the Midwest but that was quite a location. I'm really excited that – or I'm really grateful that AAIC held it there. I'm wondering too, because it's such an amazing place and because AAIC is still doing virtual presentations and attendance, what kind of turnout did you have this year?

Griffin: Yeah, well it was quite the conference. This was our largest in-person conference ever with 7,509 people joining us there in Amsterdam. These researchers from around the globe came together with us in Amsterdam. We are still – as you said, Nate – we’re still committed to providing access to people who may not be able to travel for whatever reason. In addition to the over 7,500 who were there in person, we also had another 3,752 people who joined us virtually for a total of over 11,000 participants. We had – as I said it is a global conference – we had participants from 104 countries. 59 percent of which were female. 35 percent were under the age of 35, these earlier career researchers who may not have had the chance to travel in the past few years because of the pandemic. Also 16 percent were from low and middle income countries. There was a breadth of scientific content that was presented at the conference. We had more than 5,500 submitted abstracts, which led to over 600 podium presentations and over 3,400 poster presentations. It was rich in scientific content.

Chin: I could tell, and I would say it's overwhelming with how much is there. The great, great discussion, the great presentations that are there. It's truly a place to network and learn. I know that through some of the great work of Sarah Walter that there were actual people living with this disease or living with symptoms that were able to attend, that were able to see the great work that scientists are conducting. It really is this ideal spot or ideal conference for everyone to be able to learn and see something. I would say the posters – I'm not so shocked by the number that you said. I was getting dizzy how often I was walking around looking at the posters, which kind of leads to my next question though. It is overwhelming, so what would you say are some of the key themes that this year really produced?

Griffin:We had a lot of abstracts that were submitted on biomarkers. Biomarkers are very, very hot these days. We know that early detection and accurate diagnosis are critical to make sure that people can benefit from emerging treatments, and we'll talk about that later on. We need to have the appropriate tools to enable that early detection and accurate diagnosis, but also to enable the use of these biomarkers to ensure that people have a response to the different therapies that are coming out or even lifestyle intervention changes. The abstracts reflected that. We also saw kind of a resurgence in the basic science and pathogenesis abstracts. A lot of work is surrounding amyloid and tau, but there are several aspects that change in the body when someone has Alzheimer's or a related dementia. We need to understand all of those biological changes that happen, so it's great to see that things are being studied from the molecular level all the way to the organismal level in the earlier stages of the disease. Half of the abstracts in the conference were looking at the combination of inflammation in the brain, also the fact there that leads to the death of the brain cells themselves, as well as tau. Then it's interesting to see how these themes have grown over the years because, back when I was a young whippersnapper back in grad school ,people did not believe that inflammation even happened in the brain. Now it's accepted as dogma. It's cool to see the growth of the field in that way.

Chin: For those that haven't attended virtually or in person AAIC, one of the things that I've appreciated is this idea of pathways. Percy, you're speaking to the molecular level. There’s the clinical research, there’s the biomarker aspect, there's clinical trials. There's also a care pathway or there's a care series for those clinicians that are interested. I think that really allows for those key themes to emerge, but also just for people to get a sense of the different angles at which the community is approaching Alzheimer's disease. I completely agree. There are so many key themes there and I'm glad, Percy, you're able to summarize that. My next question might be a little bit harder, which is, what were some of these emerging topics that came up that maybe you weren't prepared for or that you thought the writing was on the wall? Just as an example, last year when we spoke there were some very interesting things about ultra-processed foods, the impact of racism on cognition and these biomarkers of Alzheimer's, COVID-19 came up and even pre-eclampsia. It's very wide open. Did you see any of these more novel or emerging topics this year?

Griffin: One of the first ones that was kind of interesting to me – and as you said in the introduction I was trained as a molecular biologist, so this one piqued my interest – was the use of CRISPR technology for Alzheimer's disease. Now for the listeners at home, CRISPR is Nobel Prize-winning technology. I think it won in 2020. They're kind of like molecular scissors that allow you to precisely edit the DNA to affect different diseases. It's been applied in rare diseases. Now these ideas are being tested in Alzheimer's disease as well. It's pretty great to see. We also had for the first time ever county-level prevalence on Alzheimer's dementia. This validated something that we've said in our Facts and Figures Report for several years of the disproportionate effect of Alzheimer's and other dementia on underrepresented populations. It also allows us to more directly target public health interventions to some of these local spaces. I know in Wisconsin you have Amy Kind who has the Area Deprivation Index, so it would be kind of interesting to see the overlay of those two. We had a clinical trial readout on the ACHIEVE study that was looking at hearing aid interventions. Although the overall study was negative, there was some positive signal in individuals who had higher risk for atherosclerotic disease, now pointing to the importance of thinking of multifactorial lifestyle interventions versus targeting one thing at a time. Also we had work that was looking at the gut health. There's this connection with the bacteria that's in your gut and how that may affect your risk of developing dementia. We also had a closely related study on opioid use and mortality among older adults. Now we also had a pretty cool story – and this was more on the expected side but I still want to mention it – a pretty cool story looking at a proof of concept for a simple finger prick blood test and how that may be applied in Alzheimer's disease. Closely related to that is how we move forward with the implementation of this new blood test in the clinic. You know it Nate, I know it, we keep talking about these blood tests and people keep asking, “Can I get it from my doctor's office tomorrow?” Now the question is how do we get to the point where it gets to the doctor's office and it works for all people from all communities.

ADRC Announcement by Caoilfhinn Rauwerdink: We interrupt today’s episode with a word from the Wisconsin Alzheimer's Disease Research Center. Over the past year there have been numerous developments surrounding Alzheimer's disease treatments, but what options are really out there? Join the Wisconsin Alzheimer's Disease Research Center for the annual Fall Community Conversation happening Thursday, September 21st, 2023, from 4:30 to 7:30 pm Central Time at the Middleton Performing Arts Center in Middleton, WI, and livestreaming on our Youtube page. Focused on breaking down advancements in Alzheimer's treatments, the Fall Community Conversation will feature a healthy aging fair cosponsored by Dementia Friendly Middleton, talks led by University of Wisconsin faculty, and a Q&A with the evening’s presenters. To learn more about the Fall Community Conversation and how to attend go to adrc.wisc.edu/fcc2023 or find the link in the episode description. Thanks, and we hope to see you at the 2023 Fall Community Conversation. Now, back to today’s episode.

Chin: Percy, you did a great job of providing some of those key highlights from the conference. I would like for you now to tell me about one or two presentations that you were not anticipating attending, or were really surprised by the finding – something that just struck you as your own independent scientist.

Griffin: One presentation that I found very very interesting was by the Alzheimer's Association and National Institute on Aging. They had a presentation on the revised criteria for Alzheimer's. It's criteria on the biological underpinnings of the disease and how we define the disease. That was such a fascinating conversation, because this work group was convened by the Alzheimer's Association and consists of thought leaders from around the world. How we're thinking about the disease is to ensure that the disease is defined biologically and not symptomatically. Now this is important because, during that presentation, one thing that Dr. Cliff Jack, who leads the work group, said that really resonated with me is that someone has diabetes when they have the changes to their blood sugar levels and whatnot. They don't have diabetes when they get to the point of renal failure and all of the symptoms, so why should we think about Alzheimer's differently? That was such an important thing to hear is that the disease is the biology and not the symptoms. That really resonated with me, and it's something that I kept in my back pocket and have taken with me after the conference now until today.

Chin: I'm laughing as you're talking about this, not because your answer isn't wonderful, Percy, but because this has been a point of discussion ever since that presentation. It certainly has raised a lot of eyebrows and led to great discussion on what is Alzheimer's disease. How do we define it? What do we do with what we're learning? I think that presentation really has stimulated a great debate in the field. I know they have asked for people's commentary. For those that are listening, there is a website that you can go to and offer your thoughts. I know, as a geriatrician, the American Geriatric Society has released their own comments. We'll have a separate episode on that alone, Percy, because of how critical it is. I do appreciate everything you've said and I think biology really matters. I would counter that we care about biology in the context of caring about people and symptoms.

Griffin: Yep, yep.

Chin: It always has to be about the person and I think that's what we're getting to. I think we're getting closer to that unity. I, too, was fascinated by that discussion and it was a great opportunity for people to come together and debate, and truly debate what we are going to do. Part of the conference is also clinical trials. Were there any particular findings or readouts that you were struck by when in the clinical trial space?

Griffin: Yeah. I think the big one on everyone's mind was the deep dive on a drug called donanemab. AAIC 2023 was the first time that we had a deep dive on the TRAILBLAZER-ALZ 2 study, it was called. Now about half of the participants met the threshold to stop taking donanemab at 12 months. Now this is an important piece because people always ask the question with these emerging treatments, “That's how I get amyloid in the brain. When will people stop taking these treatments?”. It was such a pivotal moment for the field, but also something that cannot be overstated was the importance of the results on early detection and accurate diagnosis. In that presentation, they kind of separated the groups by people with low to medium tau – and tau is associated with the death of the brain cells – or the higher levels of tau, and they found that the people who had the low to medium tau had a greater benefit from treatment. Again, pointing to the – we've said it for a long time that early detection and accurate diagnosis are important, but this was clear evidence that points to need for early detection and accurate diagnosis. Of course we're not going to be taking our foot off the gas there. Not even close, because in the future treatment for Alzheimer's will likely be similar to what it’s like for other chronic diseases. We're going to be targeting these several different aspects of biology that I talked about earlier in our interview, that is being studied with all those abstracts and basic science and pathogenesis, and we're going to be treating them in a precision medicine way. If you don't have these changes, you should not be taking medications for these changes. We want to target inflammation and metabolic changes and even the changes to the blood vessels around the brain to make sure that people get the most benefit from these treatments.

Chin: That was incredibly exciting to see those results, and you're absolutely right. We are really getting – we're moving towards precision medicine and understanding all the complexities of Alzheimer's disease and all thinking changes. I agree with you, Percy. To end our talk today I'd like to hear from you, based on this year's group of presentations, where do you think the field is moving in the next year? What do you think AAIC 2024 is going to look like?

Griffin: I just want to say that – going back to AAIC 2023 for a second – I think the future is very hopeful for the field. With some of these therapies that target the underlying biology of the disease there are options for people living with early Alzheimer's disease, but we need options across the continuum of the disease, not just in the early stages. We have efforts for early detection and accurate diagnosis, but we need therapies that are targeting the underlying biology of the disease for the later stages. Also as you importantly pointed, Nate, we also need therapies that target some of these symptoms, these changes to sleep, changes to anxiety and depression. All of those are also important, but I want to summarize and say this: there is hope in this time of progress, and that's where the field is and that's where the field is going.

Chin: Well that's a wonderful way to end, Percy. I want to thank you, Dr. Percy Griffin, director of scientific engagement at the Alzheimer's Association, for being on Dementia Matters yet again. I would anticipate you will be coming on after 2024 too, but until then thanks so much, Percy. 

Griffin: Thanks for having me. 

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 on Aging for Alzheimer's Disease Research Centers. This episode of Dementia Matters was produced by Amy Lambright Murphy and Caoilfhinn Rauwerdink and edited by Haoming Meng. Our musical jingle is "Cases to Rest" by Blue Dot Sessions. To learn more about the Wisconsin Alzheimer's Disease Research Center, 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 dementiamatters@medicine.wisc.edu. Thanks for listening.