Episode Transcript
[00:00:12] Speaker A: Hi everyone. Happy New Year and welcome to a special bonus episode of the Age of Aging. We wrapped up season two in early December of last year, and when we were thinking about ways to end the season, one of the ideas we tossed around was a look back at dementia care and research in 2024, as well as developments in the field in 2025. It has been a particularly revolutionary year in the Alzheimer's and dementia space. So we sat down with three major figures here at Penn and in the field in general to hear their reflections. What you'll hear is a discussion between Dr. Jason Carlos, who if you've been listening for a while, you know has been on a few episodes of the age of Aging, Dr. David Wolk, and Dr. Eddie Lee. I found this to be a very insightful conversation. Few people know as much about the latest in dementia care and research as so we'll announce more about the next season of the Age of Aging soon, but I hope this holds you over until then.
[00:01:14] Speaker B: I'm Jason Carlos. I'm a professor at the Perelman School of Medicine at the University of Pennsylvania. I co direct the Penn Memory center along with David Walt and I'm one of the associate directors of our Alzheimer's Disease Research center and I also lead the center as outreach, recruitment and engagement core.
[00:01:31] Speaker C: Hi, I'm David Wall. I am a cognitive neurologist, a professor of neurology here at Penn. I am co director of the Memory center with Jason Karlewish. I direct our Alzheimer's Disease Research center and I co direct the Institute on Aging with Eddie Lee.
[00:01:51] Speaker D: I'm Eddie Lee. I'm a neuropathologist here at Penn and the Department of Pathology. I co directed Institute on Aging with Dave Wolk and I'm also an associate director of our ADRC where I am also leader of the Neuropathology corps, meaning I direct our brain bank looking at neurodegenerative disease tissues.
[00:02:11] Speaker B: One of the things I did in 2024 was I undiagnosed a patient with Alzheimer's disease. So I had this elderly patient with dementia mild stage who I had diagnosed with Alzheimer's maybe three or four years ago. And in 2024, after running a series of biomarker tests, I removed that label and applied a different diagnostic label, namely the label of what I call TDP 43 disease. But the reason why it's a shout out in particular to Dave and Eddie was because of the advances that they are leaders in, which is the discovery of this other cause of dementia, particularly in the oldest old, namely TDP 43 disease. And what's exciting about it is, you know, I was using biomarker tests that are now almost routinely available to test for the markers of Alzheimer's. I don't have a marker for tdp, but I have pretty good inferential data from MRI interpretation work that Dave led. But I thought that was just unbelievable. I mean, the idea, I just kind of tremor at the thought, like in years past, it was definitive Alzheimer's, really, you know, given everything. And. And I'll never forget her daughter said to me, you don't know how important this is. And I said, well, you know, it's. Your mother still has dementia. I mean, it doesn't change the clinical picture. And she said, no. Every time I would talk to her, I would think that this is the last conversation we're ever going to have because, you know, she's slipping into the oblivion of Alzheimer's. And the more I learn about this other disease, it's not necessarily going to be that way. And it just recast her whole experience of living with the diagnostic label and living with her mother's dementia. So that was one, I think, big event of 2024 for me.
[00:03:49] Speaker C: Yeah, thank you for. For bringing that up. You know, I think it's kind of amazing that this late in, you know, what we know about these diseases, that we're still sort of discovering new things and things that we, you know, sort of recognized one way in the past that now we're thinking about differently. You know, the TDP 43 was discovered in part here at Penn, and Eddie probably can fill in more details about that. But as something that causes late life cognitive decline, it really wasn't recognized until the teens that it was at least associated with some of the cognitive symptoms people have and then basically was defined pathologically about four or five years ago. And over the last year, we realized we can start to recognize these cases and that they're a mimic of Alzheimer's. But there are features that allow us to say someone has this condition, this TDP 43 condition versus Alzheimer's disease. And so this year, we developed clinical criteria in collaboration with Eddie and many others across the country and outside the country to allow clinicians using biomarkers inferentially to say whether someone's more likely to have late versus Alzheimer's disease, whereas in the past, we would have just been them together. But, Eddie, maybe you want to talk a little bit more about the history of TDP 43.
[00:05:14] Speaker D: Yeah. So as director of the brain bank, we have thousands of postmortem brain tissues that we've collected since the mid-1980s, actually. And so several years ago, it was John Trujanowski, Virginia Lee we were able to look at these brains where they had some kind of protein that's accumulating, but we didn't know what it was. And they were able to identify TDP 43. It was specifically in diseases called frontotemporal dementia or ALS. Amyotrophic lateral sclerosis. And after that landmark discovery, people started looking at other tissues and they realized, hey, there's a subset of Alzheimer's disease patients who also have this protein aggregate building up in their brain, and it seems to affect their cognitive function. And also in the very old individuals where this is driving the disease in those cases. And so those were firmly grounded here at Penn. I'll say. The other big thing, of course, is the anti amyloid immunotherapies, which now are being used in actual patients. There was a lot of work. I didn't do any of the work. It was Dave and Jason and others to implement this. But to be able to offer something that can affect the disease on a biological basis, I mean, that's remarkable.
[00:06:29] Speaker B: Yeah, it is. And you know how I can tell you how remarkable it is? We had nine applicants for our fellowship program, which is multiples above what our usual applicant pool was. And it's a. It's a great group, too. And in general, you see this. The one reflection of the impact of these therapies is just a recognition within medicine of Alzheimer's and as a disease that you can diagnose and treat. And that all unfolded in 2024. Our first patient was infused in November 2023. Not much happened after that for a while. But now, how many are we up to? Dave?
[00:07:10] Speaker C: I think we're in mid-160s at this point. 160 patients and many on the wait list to get started on therapy.
[00:07:19] Speaker B: Yeah. And it's just stunning how that all unfolded slowly over decades in some sense, and then all at once last year, the ability to diagnose and deliver those therapies.
[00:07:31] Speaker C: Yeah, I mean, I'll add. And, you know, I think maybe this ties into the first conversation about TDP and lead is that one of the side effects, a good side effect of the implementation of these medicines is it really has pushed us to begin to translate biomarkers that tell us a lot about the underlying biology into our clinical practice. And actually, part of why I think CDP 43 is so important is for actually two reasons. One is because many of the people who come in with a diagnosis of possible Alzheimer's disease, who we work up to see whether we're going to give one of these therapies, end up not having Alzheimer's disease. And people want to know what they have. And so recognizing TDP43 pathology as a major cause of those symptoms is going to occur more and more and is going to help our patients with understanding that condition as well as hopefully lead to defining a group of people. We can apply interventions for them. But the other is one of the things that I think our field has come to think a lot about, particularly now in this last year, and really face is the idea that oftentimes patients have more than one pathology. And so TDP 43 often occurs with Alzheimer's disease, as Eddie said earlier, as do some other pathologies. And so really starting to try to decompose in every patient, what are the things that are driving their symptoms, is going to become important for us to see who's most likely to benefit from these therapies. And all of this gets sort of pushed forward once there is a therapy in practice for us to kind of. It's now game time in terms of actually applying these things as opposed to research.
[00:09:19] Speaker B: It is interesting how in American medicine, treatment drive medicine, the practice of medicine. It's fascinating. Having said that, Eddie, in a typical brain, you autopsy, is it typically more than one disease you're seeing?
[00:09:33] Speaker D: Almost always, I would say so somebody who had a history of Alzheimer's disease. If you consider everything else so vascular disease and strokes, or TDP43 or another protein. We didn't discuss alpha synuclein.
It's less than a quarter of them only have Alzheimer's disease.
There's tremendous heterogeneity. The other thing with heterogeneity, and we were talking about this the other day, is it's not just biological heterogeneity. There's also, you know, socioeconomic diversity and race and ethnicity. And we're just beginning to learn what that means in terms of how that. You had that paper? Yeah, so we had one where we were able to look at the neighborhood that you lived in and relate that to your cognitive function. So the more deprived your neighborhood, the worse your cognitive scores. And people have seen this many times. What we did, what was unique, is we were able to look at their brains because we have their autopsy tissue, and show that it actually is not Alzheimer's disease that's causing this cognitive decline. The amount of pathology they had in the brain, if anything was a little bit lower. So it's something about the stressors of living in challenging environments that's affecting your brain. And it makes sense. But now we're finally at the stage where we have these cohorts that we've been recruiting to better study these issues.
[00:10:55] Speaker B: Yeah.
[00:10:55] Speaker C: And I think, you know, more and more what we're learning and work like what Eddie shows is that, you know, that a lot of what drives people's symptoms, again, is not just, you know, plaques and tangles, which are the main two pathologies of Alzheimer's disease, but a variety of other factors. And so I think while we've developed more and more tools to measure some aspects of brain changes associated with aging, you know, I think a real drive in the coming years as to how can we decompose different pieces or parcel at different aspects of what's driving cognitive symptoms in individuals to know what to best target. And to me, while I think we're at the very early stages of this, I think this reflects a real shift in our field towards, you know, what in the cancer world is referred to as precision medicine, which is where we're really trying to understand all the factors that drive any individual's presentation, their symptoms, and what are the things that, you know, we can do to ameliorate those types of issues in a very directed way.
[00:12:06] Speaker B: I would just like to say that you just used the word parsley, which I'm not sure is a. Is an actual word, but I love.
[00:12:12] Speaker C: We use that in imaging all the time. You parcel the brain.
[00:12:16] Speaker B: It's beautiful. But I will say that the oncology world's idea of precision medicine in general is very, very biological, with no objection offered. But I think our world, apropos what Eddie showed and others is the importance of the environment. And I do think the other big event in 2024, which you could have knocked me over with a feather when medicare did it. It hasn't fully rolled out yet. Is the guide program. I can't remember what it stands for, but it's an acronym for a medicare benefit. It's not actually a benefit. It's offered through cmmi, which means it's a demonstration program to deliver caregiver education and training and support for caregivers of people with dementia. The emphasis is dementia, not disease specific causes, but dementia. And if you don't have a caregiver, they'll still deliver you the services to the person with dementia, which is fascinating, but you get. But the health system that offers it will get paid. In other words, there's a business model behind it. If you do guide right, it plausibly will pay for the staff you need to deliver this. And that got rolled out last year. We're a site Kir O'Brien here is going to lead up, is leading our efforts to roll it out. We have a year to get the infrastructure in place and then the next year we'll start it. And my understanding is across the health systems of the United States, many of them have taken this up. And if you had asked me again, much like the diagnostics and therapeutics two, three years ago, if you had described this world of there'll be these diagnostics, therapeutics and a Medicare program to support education and training for caregivers, I would have said, are you kidding me? And all that's coming is coming in place. Now I will say that the guide program is not a benefit of Medicare. It's, it's actually offered as a demonstration project, which technically means it could go away because all demonstration projects have a time span unless they're renewed or incorporated the benefit. But this is, it's for eight years. And in America, eight years is like, it's a long time.
[00:14:09] Speaker C: I mean, you know, to your point, I mean, I, I think it's somewhat unexpected given, you know, some of the sort of focus on medicinal therapeutic interventions, that this happened in parallel with, you know, the rollout of what's a very advanced and complicated and expensive therapy that kind of gives you a little, little bit of, of faith in, in our system to try to, you know, improve the lives of patients dementia. Because I think that's a, even a more shocking development in many ways than a therapy being rolled out in practice. It's a care program being.
[00:14:49] Speaker B: No, I agree, I agree. I would not have expected it and it'd be great to see it last as well. You know, in some sense it made sense because for every. I'm going to make up the numbers. But for every 10 people you work up for an anti amyloid therapy, only a fraction are going to be able to get the therapy. But what you've done is labeled a bunch of people along the way who still need care and that's where programs like GUIDE step in. So I think that's really encouraging. I think there's a lot of wins in 2024 and we'll see what 2025 if they hold up.
[00:15:21] Speaker D: The other thing I noticed that you just reminded me about is this debate that's been raging this year about what is Alzheimer's disease and how we define it as we Work up these patients and if they have, and we call them Alzheimer's disease versus at risk for Alzheimer's disease, and, you know, how much do we appreciate the heterogeneity or the environment they're in and trying to distill this diagnosis down to a single biological construct. I don't think that debate has gone away. So we'll see that next year as well.
[00:15:51] Speaker B: No, it's definitely heated up. There's an article in Alzheimer's and Dementia by several Alzheimer's researchers in the clinical trial space in particular, and they make the argument that amyloid lowering should be used for regular approval of a drug as a sole endpoint to constitute enough data to say this drug is approved, not for accelerated approval, meaning contingent on further data, but amyloid lowering alone should get a drug approved. That just came out. And I will say, because I'm working on a piece, I think will come out on it. I'm in the camp that says someday, but not yet as a surrogate. I don't think we are. It's ready to be rolled out like that. I would hope someday it will be, but I don't think so. I think that'll be a big debate in 2025. I think we'll be arguing about the definition, and rather than this being an academic argument, it has tremendous policy and clinical implications.
Should we do a round robin amyloid alone? Is that good enough to call it Alzheimer's? I say no, not yet. What do you think, Eddie?
[00:16:52] Speaker D: Oh, I have to go second. I say no because I think Alzheimer's is more complicated than that.
[00:16:58] Speaker C: Yeah, I would say that. I think it depends on what we mean by the term Alzheimer's and what the intuition is about that term. So I think it means there is the pathology of Alzheimer's disease present in the brain. I think that's a very different construct than the idea that Alzheimer's disease is causing symptoms for you or might ever cause symptoms for you, depending on how long you live. And so I think, you know, it is, you know, a pathologist would refer to Alzheimer's disease as having plaques and having at least, you know, some degree of tangles. Many patients with plaques that are picked up by the time you see them with amyloid PET do have what pathologists in the past at least would say is intermediate stage Alzheimer's disease without yet having symptoms. But many of them might not. And. And so I. I don't. I guess my larger argument is I don't believe it's particularly useful, or I. I think it's you know, only useful to use those termin that terminology if we all know what we're talking about. And I think part of the problem is when you define Alzheimer's based on amyloid, a lot of people still think of, well, if you have Alzheimer's, that means you have a disease that's causing symptoms for you or that is definitely will cause symptoms for you. And I think that that's not necessarily the case. And so that's where the problem lies.
[00:18:36] Speaker D: Well, I guess that part of the angst is we don't want to tell patients that you have this diagnosis that might be incurable and, and fatalistic. I think it'll be interesting how opinions change if treating people with amyloid without symptoms, if that really prevents the onset of later dementia, I think might be changing how we view these things.
[00:19:02] Speaker B: I totally agree. I mean, that's why I said not yet is my view though. I mean, if I think it's what Trailblazer 3 or 4 and the AHEAD study, which are testing Donanemab and lecinumab, respectively, in people who have elevated amyloid, if they show that that changes the time to event, where the event is onset of dementia, that would be compelling data. And I specifically geeked out and said time to event because what I dread is the conclusion that change on a cognitive test score would be good enough to say we should use the drugs. I'm sure there will people make that argument. I can understand why they would. I'm empathetic to it. But from a cultural perspective, you'd just like to show definitively that people were less likely to develop dementia or at least mci. So you really know you're getting the benefit that matters to people rather than, you know, change on a composite measure of cognition that, you know, you extrapolate will have a long term effect. Because I just. This disease is so hard for. As you one time said, Dave, there's so much nuance in Alzheimer's and if you don't live, it becomes extremely confusing. Indeed, one feels almost symptomatic the more they learn about it. And I just hope for clear data that shows that. I really hope. And those trials will read out, I think in a year too. 2026, I think, is potentially the earliest.
[00:20:29] Speaker C: Yeah, I mean, the challenge. And I think this is the balance. And I'm kind of with you, Jason, with regard to I don't think we're quite ready for amyloid as a surrogate marker to determine full FDA approval, which is a somewhat different question than does amyloid define you know, Alzheimer's disease.
[00:20:50] Speaker B: Right.
[00:20:51] Speaker C: But there is a balance, right? So I think this is the challenge in our field for preclinical trials is, you know, it's, there's very little signal because of the fact people can have amyloid and not develop symptoms for many years. And again, many people with amyloid just based on actuarial data will never develop Alzheimer's disease because they'll pass away from something else. So it does make it hard for trials to really be designed well and follow people for long enough to have the ability to detect a prevention of an event like dementia or even mci, just given the lower number of people who cross that threshold. And so I think we as a field have to live with this idea of if we're seeing signal, what's enough signal for us to say we want to prevent people from developing symptoms and you know, versus, you know, we want to wait longer and then potentially people who will develop symptoms, we wouldn't have gotten the drug in them early enough to do it. And I don't know the right balance.
[00:21:57] Speaker B: But I think it's funny, in this disease, in this disease, the middle is the extremes are really hard and the extremes are end stage dementia and how to care for that and whatnot, live with it. And the other extreme is the very beginning. And when does it begin and when would you intervene?
Not just because of some of the issues of economics where I'm handing out a drug to millions of people that doesn't work or they don't need, but labeling, stigma, et cetera. And that's why I just would really hope we have always going to have to extrapolate from who's in a trial to say who works in the general population, what works in the general population. But boy, you'd like some really good solid evidence to make that leap because of the impact of the label on people. You know what always bugs me and Eddie? You may. So, you know, hemoglobin A1C is a very powerful marker for diabetes. I mean, it's, you know, everyone gets one when you turn whatever, 30 and whatnot. But often that's used as the sort of analogous thing for lowering amyloid and. But hemoglobin A1c was intimately linked to a glucose intolerance test. In other words, they validated the hemoglobin A1C's cut points based on the. When a glucose tolerance test would become abnormal. And a glucose tolerance test, I know, sounds fairly geeky, but it's basically showing that your body's not handling Glucose. Well, it's the disease of diabetes beginning to unfold in a way that's disturbing. And before you can't see your kidneys fail and you have a heart attack and all the other things that diabetes causes. And I just don't see the data for amyloid lowering having the same link to the pathophysiology, you know, and this is where I'm out of my league, maybe. But, like, what cut point really is like, yeah, that's where amyloid's really causing tau to take off. But maybe we're there. But that's what I'd like to see, you know?
[00:23:43] Speaker D: Well, I. I think it's because amyloid is kind of like once removed. Right. So amyloid without tau really doesn't do anything on its own. And so if it's two, three steps ahead, the leak is not as strong, and it takes years, if ever.
[00:23:59] Speaker B: Yeah. So, Dave, why aren't we having tau scans routinely? Isn't that what we really want?
[00:24:05] Speaker C: I think if. I mean, it obviously depends on your goal, right. In terms of what you're trying to unpack. I think in the context of these new therapies, I think having taupet in symptomatic patients is really, really a useful test, because tau PET tends to really link with where there's downstream injury to the brain and whether or not people have symptoms of the disease and also has some prognostic value as well. And so in the symptomatic world and the patients we see, we are often, you know, left with, okay, they have amyloid, but is that really what's driving their symptoms? And if it isn't driving their symptoms, do we want to give them a drug to lower amyloid when, I don't know, let's say they're 85 years old and have other medical issues. Maybe you don't want to, like, put them at the risk of putting them on a amyloid therapy if that's not the primary driver of their symptoms. And so I think for disentangling, again, getting back to our prior discussion, what is really driving someone's symptoms? Tau PET is a very, very useful measure. You know, from our consensus conference, we're constantly saying, you know, oh, the thing here that would really help is if we had a tau PET scan. And right now, you know, that's not well covered. My hope is, again, as we learn a little bit more about these drugs and maybe who is more or less likely to respond, Taupet will be an important feature to measure in our patients. It also has implications in preclinical disease, because as we've been talking about, you know, amyloid levels, they do relate to your risk in preclinical phases of disease. So the higher your amyloid is, the more likely you are to develop. But tau is an even better measure. And it's not until people really in the preclinical phase before they have any symptoms. It's not really until they develop tau, at least in their medial temporal lobes, that you can see on a scan. Now maybe they have some tau there. They almost certainly do if any looked at their brain. But you need to have enough load of tau to see it on a, on a tau PET scan before you start seeing signal where people begin to progress to things like MCA mild cognitive impairment over the next couple years. And so that has important implications for better predicting who you'd want to be more or less aggressive about a therapy. I would add one other reflection which is just this is also the year of plasma measures that certainly from a research perspective, but now starting to get integrated into practice. And that is really an unbelievable achievement that we can do a blood test for Alzheimer's. When people talked about a blood test for Alzheimer's three or four years ago, it seemed very, very far fetched. And now we have blood tests that can tell us a lot about what a spinal fluid study or even an amyloid PET scan could tell us in the past. And actually the technology is improving to the point where there's, you know, even some potential ability for like dry spotting blood to measure with pretty close precision these markers of Alzheimer's disease that really allows for research, but hopefully clinical care to move well beyond just tertiary care centers. And so ultimately the hope is that it'll have some democratizing value in terms of who can get diagnosed effectively and hopefully then treated certain conditions like Alzheimer's disease. And that I think as a segue into 2025, I think will be only more used in clinical practice and implemented in the years ahead.
[00:27:53] Speaker D: It just dawned on me that it's not an accident that significant strides in biomarkers and diagnostics often coincide with the development of therapies because they really feed off of each other. You need one in order to develop therapies and vice versa. Switching to 2025. I'm excited here at Penn because we have several groups here. We're funding, trying to develop novel therapies. And so it's amazing that we have these anti amyloid therapies, but we're working on RNA therapies and cellular therapies, gene therapies and small molecules because for, for a variety of reasons. One of the existing drugs have clinical benefit, but it's not enough. And there is a side effect profile. They're not, you know, a certain percentage, a small percentage of individuals have symptoms to this. So we need more. And I'm actually very hopeful that maybe not in 2025, over the next two, three years, we'll be able to develop something here at Penn and push it forward.
[00:28:48] Speaker B: Yeah, I, I agree. It's all about the future is going to be bloody in a good way and it's exciting. The tests, I think the therapies we have are a start that'll push us forward into other therapies. I think there's a lot of excitement around the longer acting antibodies. In other words, give it once and go back six months later, give it again. And different targets as well. In my world, the thing that has my group really excited is steady advances in two areas. One is recognizing this vast middle between having full capacity versus lacking it, mainly having marginal capacity, and the need to recognize for what we call supported decision making, which sounds nice on paper, like, you know, who wouldn't like it. But the more you probe it, it really changes clinical practice. In other words, what we're pushing is the moment you're diagnosed with this disease, who's going to support you and when are they going to come to the next clinic visit? Even if right now you seem to be doing okay, I think that's going to really change adult medicine. And then, you know, I just had a patient recently who is being treated for Alzheimer's and he needs to be treated for cancer. And we're going to try to figure out if we can do both at once. And you know, I could quibble with these terms. I have problem with the term quality of life. But you know, his oncologist said we have a real quantity, quality trade off here of, you know, how long to live and how well to live given these two diseases, one which goes after the body and the other which is going to go after his mind. I'd rather be in those spaces having those difficult conversations than not. But they are difficult conversations. So the moral amplitude of what we deal with is getting more intense in ways that I find very exciting. So 2025 is going to be an interesting year, I think.
[00:30:31] Speaker D: Can I ask you what is the state now in terms of decision making and your patience?
What happens right now in terms of these people in the middle zone that you're.
[00:30:43] Speaker B: Yeah, well, at the memory center? Kind of have a Culture of you have to come in with someone else.
[00:30:48] Speaker D: Okay.
[00:30:49] Speaker B: And that comes out of the dementia origins. But if you go out to like a general practice that didn't come out of a memory center origin, the idea of coming with someone else is not baked into the practice to sort of extend that.
[00:31:03] Speaker C: What do you think about or what's the strategy or the model in the future for people who don't have a family member or, you know, partner that can serve that role?
[00:31:13] Speaker B: It's interesting. Is it a professional role? Is it. But I, I do think there's this emerging role of, you know, I've labeled you with a neurodegenerative disease, I've got you on treatment. You know, we almost like walk ourselves into, like, we have to figure out someone who's there for you and who that will be. And maybe is it, you can almost argue it, it ought to be someone whose job is to do that because it creates a fiduciary obligation, excuse my language, highfalutin legal language, but, you know, it creates a sort of, my job is to watch over you and make sure, you know, as mistakes develop, they're corrected, and that you're not a victim of fraud, abuse or neglect. And you can see a role there for a profession we have yet to name. You know, it's sort of like, sort of like the ultimate caregiver, you know.
[00:31:56] Speaker D: Interesting, because financial advisors, we don't, we don't think twice as normal out there. Yeah, but, but somebody in that role for, for healthcare.
[00:32:05] Speaker B: Yeah. Yeah. I mean, you know, in some sense, it's like a financial advisor that covers all life. Problem with financial advisors is, you know, a, their scope is very narrow and B, you know, issues of secrecy, confidentiality, fortunately, are incredibly intense.
Where I think it's got to come out of the healthcare professions broadly construed, social work, nursing, et cetera. Boy, you could really imagine the role of a certified nurses assistant finally recast to truly do what they do, which is support someone from the beginning to the end, you know.
[00:32:33] Speaker D: Yeah.
[00:32:33] Speaker C: I mean, I think thinking about someone in that space makes a lot of sense to me. And you think about like care managers as being kind of in, in that realm. But you could also imagine that there are some individuals who maybe only have adult children, don't have a spouse that would actually rather have a care manager as opposed to their, you know, children necessarily being the decision makers for all sorts of, you know, reasons based on those relationships. And so it, it seems to be a, an important gap to figure out a way to fill so that we can, you know, better reach, you know, many individuals that, that don't have that kind of support system.
[00:33:10] Speaker B: The more we tame these diseases, the more we need people who can run the corrals.
[00:33:15] Speaker C: I'll. I'll just add for my 2025 that, you know, I really am excited about the idea that, you know, our field really is trying to tackle many different pathways within the degenerative disease space. And some of that includes, you know, pathways that are more related to environmental types of effects as well, and lifestyle types of effects. But I think, you know, Eddie mentioned a variety of different threads of research that are being done here at Penn that are really, really exciting with regard to trying to tackle these diseases from, you know, a genetic all the way to a cellular level. The other thing I think just that I'm encouraged by data that I've seen in 2024 and a little in 2023 that I think we will see more of in 2025 and beyond is is more tau specific therapies as well. I think that tau is much more linked to the symptoms of the disease and there have been a couple of different mechanisms of trying to slow down tau spread that may be effective. It may actually, you know, help even more in symptomatic stages of disease to sort of stall the progression. And so I think that's one example where I think we're getting closer to another pathway beyond amyloid and perhaps even, you know, the combination of the two will be even more successful. So it's a really exciting time. I think, as Eddie had said earlier, you know, there's these parallel biomarker and therapeutics occurring that they both feed off of each other. I've been impressed by, when I go to conferences these days, how often phase two and earlier phase results are very, very encouraging based on improvements in the design of the trials as well as in terms of the mechanisms that they're proposing. Whereas I think five, ten years ago, you had to come a squint to believe there was anything worth moving on for earlier phase trials. So I think that's really exciting.
[00:35:24] Speaker A: Thanks for listening to this episode of the Age of Aging. The Age of Aging podcast is supported by the Penn Memory center, the University of Pennsylvania Alzheimer's Disease Research center, the Institute on Aging, and the Penn FTD Center. Contributors include myself and Terence Casey, as well as Nicola Kelsey Alcovecchia, Dalia El Said, Marie Engineeri, Jason Karlewish, Emily Largen, Meg McCarthy and Megan Sharp. More information on the stories you heard today can be found in our show notes and on our website, penn memorycenter.org.
