Getting Back to Life

[00:00:02] Speaker A: Bottom line is infusions are a piece of cake. You know, sometimes I'm in there and they can't get. They have to dig. I'm not as happy then, you know, and I tell the people, look, I'm about ready to punch you, but that's sarcastic. I'm thrilled when I walk into the infusion area and I sit in the waiting room. I'm seeing people that have a lot of serious issues. And I understand, you know, there's all kinds of ailments, you know, they're being treated for. But, you know, I'm thinking, this isn't this bad and it really isn't. [00:00:48] Speaker B: Welcome to the Age of Aging, a show about living well with an aging brain. Produced by the Penn Memory center and the Michael Nadoff Communications Hub. I'm Terence Casey. Almost a year and a half, we released our first episode of our second season titled In Sickness and in Health in which we explored the new anti amyloid therapies Lecanemab and Donanemab. With the commercial names Leqembi and Kasunla respectively. These drugs are reshaping how clinicians treat and patients and caregivers live with Alzheimer's disease. If you're interested in learning how these treatments work and how they're being prescribed at the Penn Memory center, we'll share a link in the show notes. But for today's show, we wanted to see how those therapies have impacted both patients and clinicians. And for that, I'm joined by my Age of Aging colleagues, Jake Johnson and Jason Karlewish. Thanks for being here, Jake. [00:01:38] Speaker C: Great to be here. [00:01:38] Speaker B: And thanks, Jason. [00:01:40] Speaker D: Great to be here, Terry. [00:01:41] Speaker B: Jake's going to have reporting on this episode and then he and I will be joined after by Jason to discuss his personal experience with anti amyloid therapies. But first, a word from our sponsor. [00:01:53] Speaker D: Caring for an aging loved one isn't easy, but you don't have to do it alone. At Rothkoff Law Group, we guide families throughout New Jersey and Pennsylvania along every stage of your aging journey. Our team of elder care attorneys, care coordinators, public benefit specialists and elder care advocates ensure your loved one's well being and your peace of mind. Rothkof Law Group, your partner in elder care advocacy and senior care planning every step of the way. Visit rothkofflaw.com for more information. That's R-O-T-H-K-O-F-F-L-A-W.com [00:02:29] Speaker E: we were at our club having lunch with some dear, dear, dear friends that we've known forever. And I went to introduce the woman and I couldn't remember her name. [00:02:40] Speaker C: A few years ago, Evelyn found herself going down a path very similar to ones we hear again and again at the Penn Memory Center. Moments of lapsed memory that at the time just seemed strange, but looking back, unfortunately makes so much sense. [00:02:56] Speaker E: And then all of a sudden, my husband, her husband, they popped in. But that was the first clue that something wasn't right. When I was a little girl, we used to have these birds that if you put a glass of water in front of this fake plastic bird, it would dip in and dip out, dip in, dip out. And that's kind of how I felt like I was that bird, dipping in and dipping out. And then my husband started to notice some things. And it's downhill from there. [00:03:28] Speaker C: After many doctor's appointments and a misdiagnosis of long Covid, Evelyn and her husband Dave, who asked that we not use their last names, ended up at the Penn Memory Center. And after a series of tests, Evelyn was diagnosed with Alzheimer's disease. [00:03:43] Speaker F: We were hoping it was going to be something more treatable, easier, simpler, curable, whatever. But, you know, reality sets in and we were glad that we finally had a diagnosis and it was from people we trusted. [00:03:54] Speaker C: However, unlike every person who has received an Alzheimer's diagnosis up until three years ago, Evelyn could choose whether or not she wanted to treat her disease. [00:04:04] Speaker F: They told us there was some risk, but that didn't matter. [00:04:07] Speaker E: What choices did I have? And that's the way I looked at it. Everything is a crapshoot and this could be that too. And I just. If I didn't take a chance, I'd never know. [00:04:19] Speaker C: According to anthropologist Dr. Justin Clapp, Evelyn's sentiment of why not was common among people who chose to start treatment of one of the anti amyloid therapies. Clapp is currently conducting a study for the Penn Memory center, which interviews couples, or dyads, as they're called in the study, first when they were considering starting the therapies and then later reflecting on their experience and the effectiveness of the [00:04:43] Speaker G: drugs with people who do undergo the infusions. The sense seems to be that, like, there's this urge to do something to combat the disease and this is like potentially the only avenue that's perceived as being able to exert some control, to have some hope. [00:05:02] Speaker C: Dr. Kira O' Brien is a neurologist at the Penn Memory Center. She said that despite the potential but unlikely side effect these drugs pose of microscopic bleeds in the brain called aria, she still had many patients who felt they were worth the risk with these drugs. [00:05:18] Speaker H: There's a side effect called ARIA or amyloid related imaging abnormalities. And these are areas of small bleeds or swelling in the brain tissue. I had one family member say to me, and this is actually a patient who had numerous bleeds already in their brain, so wasn't a candidate. And the family member said, well, facing a future of them declining further with the dementia versus having a catastrophic brain bleed, I would rather have the brain bleed. And I was like, that's, I mean, you know, not a common perspective. But I think she vocalized maybe what a lot of people might feel, which is that, you know, the caregiving responsibilities as someone progresses through later stages of dementia can be quite intense and may not be, you know, the quality of life that the patient themselves has expressed wanting. [00:06:09] Speaker C: According to Dr. Clapp and Dr. O', Brien, this wasn't everyone's perspective. Many who chose to either not start treatment or stop midway through usually cited two main concerns. The first was this potential side effect of aria. [00:06:23] Speaker H: So a lot of people tell me, you know, they see stories in the news about people who died of brain bleeds and, and, you know, if there's any risk of brain bleeds, they don't want to do it. And even when I explain, like, most people don't have symptoms from these and they're actually very small and we have this intense monitoring plan that they still don't want to take any risk. [00:06:43] Speaker C: The other main concern that played into couples decision making, Dr. Clapp and Dr. O' Brien said, was the logistics of getting treatment and what that might mean for the quality of life of the patient and the caregiver. Both drugs require patients to come into the hospital for an infusion, meaning an injection in the arm that takes a total of around one hour. For lecanemab, patients come in every two weeks for 18 months. And for Donanemab, patients come in once a month for 18 months. But if their amyloid is cleared after a year, they can decide to come off of treatment. On top of this, patients must get a 40 minute baseline MRI and then three more 10 minute MRIs throughout the course of their infusions to monitor their brain for ARIA risk. And before any patient can even qualify for treatment, there must be proof of amyloid in the brain, which is tested through either a lumbar puncture or PET scan. [00:07:37] Speaker H: Sometimes, you know, they'll say, oh, like anything medical makes the patient anxious and I don't want to put them through that. And there's There just seems to be this subtext of, like, this is going to add a lot to what I have to do, and I don't think I'm willing to do that. [00:07:52] Speaker C: Even just getting to the appointments can be difficult, as Dave and Evelyn expressed. [00:07:56] Speaker F: I mean, it takes four hours for us to leave our house, drive into Philly, you know, valet park, do the infusions and get home. And so every two weeks, right. It's a. It's a huge commitment, but we've done it, and we've done it religiously. [00:08:08] Speaker C: Dr. Justin Clapp explained that weighing these burdens and benefits of the infusions was the main difference between people who started treatment and those who didn't. [00:08:17] Speaker G: With people who haven't undergone the infusions, whether it's patients or caregivers, there's more of a sense of, like a sort of weighing of risk benefit. Right. And saying, okay, I think given the risks associated with these treatments, I think given the burdensomeness of getting these infusions, we don't think it's kind of ultimately going to be worth it. Which I think is a different way of approaching or developing a rationale for why you would get these infusions or not get these infusions. Right. One is very much this focus on. [00:08:52] Speaker B: On hope. [00:08:52] Speaker G: Whereas in accounts of people who haven't gotten the infusions, it's more of this weighing of like, okay, let's do this risk burden kind of calculation. [00:09:01] Speaker C: When it came to people who stopped infusions midway through, Dr. O' Brien said they were either forced to stop due to ARIA or they decide getting the infusions was just too difficult. [00:09:12] Speaker H: It did have to do with the logistics of getting them to infusions. You know, they don't like needles, so having to get an IV placed every single time is actually worsening their quality of life, if anything. Similar thing with the MRIs. They really hate MRI scans. They get anxious, they get claustrophobic. [00:09:30] Speaker C: Joanne and Bruce Thomas from Harrisburg, Pennsylvania, explained to me that while getting Bruce to the infusions can be a hassle, they've made it work. [00:09:38] Speaker D: I went with him the first six months, then he didn't want me to come. Like, I couldn't. [00:09:42] Speaker H: I couldn't go. [00:09:43] Speaker A: And he's been going all by himself on the train for big boy stuff. I do Sudoku. I do all kinds of crossword puzzles, all that stuff. Bottom line is, infusions are a piece of cake. You know, sometimes I'm in there and they can't get. They have to dig. I'M not as happy then, you know, and I tell the people, look, I'm about ready to punch you, but that's sarcastic. I'm thrilled when I walk into the infusion area and I sit in the waiting room. I'm seeing people that have a lot of serious issues. And I understand, you know, there's all kinds of ailments, you know, they're being treated for. But, you know, I'm thinking this isn't this bad and it really isn't. [00:10:30] Speaker C: Although they haven't noticed any real changes from the treatment in Bruce, they said they're happy they made the decision to start the infusions. You don't feel like you've noticed any significant change? [00:10:42] Speaker A: No, I really don't. No, I don't think that I have. You know, I mean, as far as that goes, that's kind of a tough question to answer. [00:10:51] Speaker F: Yeah. [00:10:51] Speaker A: You know, because I think he sleeps [00:10:53] Speaker D: better, but he says he doesn't. [00:10:56] Speaker C: Dr. O' Brien explained that since these treatments work by removing existing amyloid plaques, patients can only expect them to slow down the progression of Alzheimer's symptoms. They shouldn't be able to bring back any lost abilities. However, she said she has seen a wide range of responses from patients. [00:11:14] Speaker H: I think something that has definitely been true is that people who are treated earlier in their disease course, so the mild cognitive impairment stage, seem to be progressing slower than those who are later on in the disease. Definitely had some folks who were borderline on the moderate dementia stage and really doesn't seem like the drug did anything for them. I've had a couple people in the early, early MCI stages who told me that their symptoms were better and indeed their cognitive test scores were better, and I don't know how to explain that. [00:11:51] Speaker C: One patient reported her memory lapses, stopping altogether, and Dr. O' Brien said she actually scored higher on her cognitive test scores than before she started treatment. However, this is the only case Dr. O' Brien has seen of this. Sandy Schulin from Yardley, Pennsylvania, said that after 18 months of treatment, her MRI showed her brain was free of amyloid and reported the return of a previously lost ability. [00:12:17] Speaker D: Look, it changed my life. I just can play Beethoven on the piano now like I used to. [00:12:24] Speaker C: So you couldn't. You couldn't play? [00:12:26] Speaker D: At a certain point, I just stumbled and it was upsetting to hear it, but now I'm fluent again. [00:12:48] Speaker C: Sandy Schulin playing Beethoven's Pathtique Sonata Schulin said that even though her treatment is done, she's continuing with at home infusions of lecanemab. Dr. O' Brien explained that whether or not patients should continue getting infusions after the prescribed period is still an unanswered question with these therapies. [00:13:09] Speaker H: So for the lecanemab study, they did not recheck amyloid status like during the course of the trial. Everyone got the drug for 18 months and then they showed some follow up data that people who came off the drug started to decline at a little bit of a faster rate compared to people who are still on the drug. But that was the evidence that they showed to support this idea of a maintenance therapy. With Donanemab, they took patients off after they cleared, so they checked for clearance at like six months, a year, 18 months, and then took them off. And they showed that patients continued to progress at a slow rate even once they were off the drug. We know that the amyloid protein, it does come back, it does reaccumulate into those plaques, but at a very, very slow rate. That argues sort of against a maintenance therapy. It also doesn't quite make sense that, you know, you can stop one drug and see continued benefit and stop another drug and not see that same benefit. So it's not only a debate, it's just an area of complete uncertainty. We have no data to answer that question. So I think often it just comes down to like patient and family preference in terms of whether to you on maintenance for lecanemab. [00:14:30] Speaker C: Despite the remaining questions and the variety of experiences people have had with these treatments, from talking to clinicians, researchers and patients, they seem to have brought a general sense of hope that was once absent in the world of Alzheimer's research and care. [00:14:45] Speaker H: Before I went into this field, a lot of people would say, why are you doing this? There's nothing you can do for your patients. And while I don't believe that to be true, and I didn't believe that to be true, even then, it still feels like a huge limitation, not having something that can really address the disease process. It feels like there's hope in the field and it's not false hope. I am very happy to have something to offer in addition to all the other supports and lifestyle management that is still very, very important. [00:15:19] Speaker C: Dr. O' Brien said that she believes anti amyloid therapies are just the beginning and that hopefully in the future we will have treatments that target multiple different aspects of Alzheimer's disease, like drugs that reduce brain inflammation, protect brain cells, or target another protein associated with Alzheimer's disease, called tau. Identifying individuals for treatment even before they show Signs of cognitive impairment is another area she's hoping to see the field move towards. [00:15:47] Speaker H: I hope it's going to look like an oncology care model where we start to identify these patients much, much earlier in primary care and then immediately get them to a neurologist, a cognitive specialist on treatment and then hopefully, you know, monitor for many, many, many years after that. I think the hope that I feel is more so for the future of treatment that I think it's going to look very, very different even five years from now. [00:16:16] Speaker C: Dave and Evelyn said that while they would have done some things differently, like not trying to move houses while starting infusions, they're very happy with their decision and are starting to get back to life. [00:16:27] Speaker E: I wish I didn't have to go through any of this, but I feel as though I'm in good hands. I feel as though medical team is very supportive. I feel great. I feel great. Less confusion. I feel great. [00:16:43] Speaker F: We've decided to get back going in our life, right, because we took six months off of the move and getting injections started and not showing where life was going to be. And so we started to travel again and we started simple with three days at Cape May and then we took the grandkids to Disney World and we just booked London to go see Wimbledon tennis in July. And we do things differently than we used to do. But we decided that her health is good enough now. We can continue on and live our life and get back to living our life. Yeah. Together. [00:17:20] Speaker C: Welcome back. [00:17:21] Speaker B: I'm Terence Casey and I'm here with Jake Johnson and Jason Karlewish. Jake, thanks for your reporting. That was an excellent story. Really helpful insights into these anti amyloid therapies. [00:17:31] Speaker D: Yes, brilliant. Good job, Jake. [00:17:32] Speaker C: Thank you so much. [00:17:33] Speaker F: Yeah. [00:17:34] Speaker B: Jason, we haven't really gotten a chance to talk with you much so far. When you are not hosting the Age of Aging, you are a geriatrician and an Alzheimer's specialist. Specifically, you're headed to the clinic today right after this. So tell me a little bit about what your experience is with anti amyloid therapies. If you have a patient come in today with a diagnosis of Alzheimer's disease and they're interested in learning more about these treatments. [00:17:57] Speaker D: Yeah. [00:17:57] Speaker B: What's that like? [00:17:58] Speaker D: Well, in fact, today I do have just that I'm going to be seeing a patient who has Alzheimer's disease. He's got mild cognitive impairment, level of severity, he's got elevated amyloid and he certainly could take the therapy. So how am I going to introduce this to him? I think, you know, the opening, most important question is there is a drug that I can prescribe that can slow down the progressive declines that you're experiencing. And then I try to say back what the declines are that they've told me. They'll say to me, well, you know, I'm really bothered by. It takes me longer to. Or I struggle. So it can slow down those problems, the pace. Would you be interested in a therapy that could do that? And that's kind of the key crossroads, because if the answer is not really no, et cetera, even at that level, then there's, I would say there's, quote, no further discussion. And generally people want to hear more, but it frames what the issue is because you don't want to jump right into the particulars and get lost in those particulars. As Jake and the caregivers and patients who he interviewed spoke about are a lot of particulars. You know, the intensity of the infusions in terms of frequency, the MRIs, you know, it's a lot of work. And then the issues surrounding the risks of brain bleeds and swelling and whatnot. But the fundamental question is, are you at a stage right now with this disease where slowing down the pace of decline is something that you would value? [00:19:13] Speaker B: And when do they say no to that? [00:19:16] Speaker D: Well, rarely. It's interesting, I've had a few where that's just not something they're interested in. And it's pretty much cut off quickly. I recall once where the wife just moved her hand in a sort of cut off type way, like we're not thinking about that and. But generally people want to know more. And that's when I think the decision making unfolds and the want to know more are around matters related to. Tell me more about the specifics of the treatment. And in that knowledge gathering and processing, some people will drop off. I emphasize, clearly the goal of this visit is not to, quote, reach a decision, but rather to introduce you to the things you need to learn about to make it. Having said that, there's certainly a crowd, as Dr. Klapp pointed out, who pretty much from the get go, like, yeah, let's do this. And no amount of facts are going to change that. And I'm laughing because I think it suggests as he's getting at two very different, dare I say, mindsets. One is, yeah, let's slow this down. And the other is, I think, more complicated, like I do, but the more I learn about this, I don't. And then I think the other, and it's less Explicit is I kind of don't want to slow it down. And yeah, and they don't say that. They just kind of point to, well, you know, the risks, etc. And they just sort of phase from subsequent conversations. The epic messages aren't followed up, you know, so, you know, following up, no reply back. But it's just sort of faded off. That's what I've gotten. Having said that, I'll tell you one story which I thought was really interesting. Was a gentleman who was on therapy and was his past tense, because I remember a conversation with his daughter and he was getting worse. And the framing of the decision was very much around some of the hassle issues, but really it was around, he's getting worse. This just isn't worth it. And you know, the thought experiment, which I didn't challenge her with was, well, what if it was just a once a day pill, et cetera, you know, would you still want to stop it? And I'm not saying that I think she would have, but I sense that a lot of the motivation was this almost unstated. We've crossed a point. In his progressive declines and experiential and agentive abilities, his mind has gotten to the point that swelling the style just isn't what we need to focus on. [00:21:36] Speaker B: Yeah, because I think there's a lot of optimism in this episode. [00:21:38] Speaker D: And the caregivers, and there should be, [00:21:40] Speaker B: but ultimately these are treatments that slow down what remains a progressive decline. [00:21:45] Speaker D: Correct. Which is not a paradigm that I think is unusual for many different diseases. I mean, when I was an internist, I treated people with heart failure. And there's no question the drugs we were giving were slowing down the pace of their heart failure. But yet over time, their heart failure did progress. It just didn't progress as fast. And you can look to that in other diseases, such as multiple sclerosis, with the therapies that are available for that, for example. [00:22:07] Speaker B: Yeah. And one of those moments of optimism that really stood out to me was the caregiver who focused on playing Beethoven. But how do you balance that, that optimism? These sort of stories that can seem miraculous to some people with the realities of a drug that just slows down decline. How do you navigate those discussions with a patient and caregiver? [00:22:27] Speaker D: You know, people feel what they feel, and I respect those feelings. And to be frank, there's this concept of stereotype threat. There's also like stereotyped optimism. Namely, if I tell you some really good things and put you in a frame of mind, you may do Better on things. In contrast, if I give you very negative feedback and whatnot, you might do worse on. Anyway, I'm not saying it's quote all in their head, but, you know, I think we're still learning about these drugs. Yes, the data show curves that are about slowing, not about improvement. And yet those are curves that reflect the response of aggregated data from hundreds of people. Drug versus placebo. You know, I think we'll begin to understand perhaps that maybe in some individuals, if you slow down the disease process and limit its damage to certain regions of the brain, given compensation, given other neural networks, people actually improve. I think this sort of divide behavior, you either get better because of the treatment improves you, or you just don't get worse, is a divide, that epistemic divide that we've created. I think there's still more to learn there. So I'll take her story as legitimate that courtesy of the treatment, whatever happened in her brain, whether it happened in the world around her, made her get back things that she thought she was no longer able to do. Yeah. [00:23:42] Speaker B: Great. Now I want to take it out of the patient perspective for a minute and talk about the big picture here because for years I've heard you talk about the business model that the Alzheimer's disease needs, a business model to really change. [00:23:55] Speaker D: A disease in America doesn't fully exist until it has a business model is what I'm on record saying. [00:24:00] Speaker B: And so, so now we have treatments, we have a business model which we're billing. Is this the business model or is there more that we need? [00:24:07] Speaker D: We're getting there. I think we've probably crossed that moment. I think we have a business model. It's not uniform across health systems in America, but I think at Penn we've figured out how to do this. And yeah, what's happening now is. And a lot of this work is led by my friend and colleague who was interviewed in the piece by Jake Kira o' Brien's work. How can we transform the Penn health system to deliver accurate on time diagnostics? And for some, these therapies, not just for those few that can get to the memory center, which does remain a challenge given resources, but how across the health system which takes care of hundreds of thousands of people, can this be transformed? And I do think we've probably arrived at the point where we can say in some period of time in the future there will be the kinds of centers set up that rival cardiovascular and cancer centers in terms of the access to diagnostics and therapeutics that are available quite widely now. [00:25:03] Speaker C: In the episode, there's this question of the aria, this side effect that can happen with these drugs. I'm wondering how you as a clinician balance the kind of moral weight of somebody like in the episode saying, if I could choose between dementia and a catastrophic brain bleed, I would choose the brain bleed. How do you make that decision and communicate that information to families? [00:25:28] Speaker D: A couple things. First of all, I don't use the term aria. I find it to be missing. The point of the brisk is small microscopic bleeds in your brain which if left undetected can lead to swelling because ARIA is amyloid related imaging abnormalities. That's only the problem. There's something wrong with the imaging. You know, it's hurting the imaging, it's damaging the imaging and I really think it's a distraction. Those remarks all the more amplify the importance of having solid data about efficacy. You know, yes, there's a risk, but I'm confident this drug does benefit people in general. You know, these drugs were both developed with one adequate, well designed, randomized placebo controlled trial. And FDA more and more is moving towards having one, not two, as the standard. I think we have to think carefully about that. I'm not saying there was anything wrong with these trials design, but it all the more emphasizes that this rush to surrogate endpoints and whatnot gives us data that isn't as solid as say this helps you. Especially if you're talking about risks like small leaves in the brain and swelling. I'll wrap up though with one point. What we found at the memory center now where we're up to several hundred patients on these drugs, is that if you have an organized system for their delivery and monitoring and also a very good system prior to decide is this drug right for this individual. Our experience has been these are manageable risks in terms of their detection and if they occur, their management. We have had patients who have had to stop treatment and who have had small brain bleeds and swelling, but it's been, it's been manageable. [00:26:57] Speaker B: But what is, what is the risk of a brain bleed itself? [00:27:00] Speaker D: The short term risk is that left undetected, some of them can then go on and lead to this leakage of fluid, the swelling, the edema, and if that's left undetected over time can in some rare cases is actually caused death. We don't know the real long term implications of if you've developed microscopic brain bleeds, you know, what do they do to your long term brain health and whatnot. That's definitely a work in progress of understanding. Back to my original point. All the more reason why having adequate, well designed trials that show in a blinded randomized design, those who got the drug despite having more brain bleeds and swelling than those who didn't overall did better on measures of clinical benefit. That really helps you say at least overall people are going to do well. I'll wrap up with, you know, one of the projects we're doing here at the memory center that my colleague Chris Brown leads is to better understand in people getting the drugs as they experience these brain bleeds what is the damage done to brain and what are the clinical outcomes. And so we're studying that just about everyone who's on therapy is in a cloud observational study to better understand those kinds of outcomes. [00:28:07] Speaker C: Another question in the episode was kind of this uncertainty about whether to continue treatment after amyloid is clear. What do you tell patients that have amyloid cleared in their brain and they're [00:28:18] Speaker D: saying what, what happens now? Yeah, well it depends on which drug they're on. If they're on lecanumab, you know, Lecumab is labeled for continued maintenance therapy at a different set of dosage and whatnot. And I think we're back to the same topic I mentioned at the beginning of our conversation which is do you continue to value slowing down the pace of this disease the way things are now, something you'd like to try to extend and that invites just that reflection of well yeah, it is. Okay, well then on Lecainamab there's this option for maintenance therapy. Donanemab was studied that therapy stops and so at that point therapy does stop. Where things get complicated and uncertain is they've been on Donovab and they haven't cleared their amyloid. So a couple more rounds of Danamab, switch over lecanemab, etc. That is a work in progress. Both drugs have data to show that long term benefits of their therapies, both Dunamab, if you just stop it after clearing analyte and the cannabis, if you continue maintenance therapy. And David, what could I. When we chatted with you guys, you earlier, Terry, you know, I don't think we'll ever see the head to head comparison study that could help sort that one. Sure. [00:29:19] Speaker B: In this episode, a couple that Jake had spoken to, Dave and Evelyn, they talked about sort of the barrier to receiving these treatments. The four hour commitments minimum to come in, have the infusions go through our parking system here at Penn, which lovely. What are some of the other ways that this might be delivered in the future that could help avoid some of these barriers. [00:29:39] Speaker D: Yeah, well, Lecaneb already is available as an injectable form for the maintenance therapy, meaning a subcutaneous injection. And I've had. We have a few people who have started that, and certainly that removes the hassle of coming for an infusion. And the manufacturer of that drug is pursuing efforts to have the subcutaneous be the initial way of delivering the drug in the first place. So we'll see. It'll be interesting to see how that innovation and delivery changes people's willingness to be on that drug versus Donanemab, et cetera. I think looking forward, though, some of the exciting treatments that are in the works are treatments that, because of what's known as the shuttle mechanism, will require lower dosages and lower frequency of dosing. That will both make it easier and more convenient to receive the drug, but also, if the data hold up, reduce the risk of the microscopic bleeds and swelling. So I think these drugs that we're currently prescribing are a start, not an end for treatment with this form of anti amyloid therapy. [00:30:33] Speaker B: And just logistically for the business of Penn Medicine, which is enormous. But when we have these infusions, they're down the street here for many of our patients. That's right. [00:30:43] Speaker D: For now, although we're moving over to Pennsylvania Hospital and there's plans potentially to move out to suburban locations. [00:30:49] Speaker B: Yeah, great. [00:30:49] Speaker D: It's not a question of whether, but when, I think for these. [00:30:53] Speaker C: So at the end of the. Of the segment, Dave, of Dave and Evelyn, he mentions how they're trying to get back to life. They're booking trips, trying to live with Evelyn's impairment. Now, how much do you think the change is the therapies and how much do you think it is a kind of psychological shift to re engaging with the world that changes people's outlook and the way that they feel about the dise. [00:31:21] Speaker D: Yeah, I think it's 63. I think it's a bit of both or perhaps something else. You know, I really mean that. I think we're in early days of understanding how therapies that manipulate the pathologies that cause Alzheimer's someday, maybe the pathology that cause Levi disease. How they change the way the brain works, meaning how they change the mind. We're good at measuring what they do to cognition. Memorize a paragraph, say it back to me, all kinds of other tests of cognition. We're pretty decent at measuring function, you know, fill out these various forms. But I think, you know, where we're still Barely figuring out is how do they change what it's like to be you? And I think that's the next wave in measurement. Could I could imagine a future where, courtesy of some of the more real time devices we have that monitor our lives. You know, I think I have mine here with me close at hand. Jason holds his cell phone. Love it. [00:32:18] Speaker C: Great. [00:32:18] Speaker D: You know, maybe that will begin to tell us, you know, what's going on with individuals. So they get these therapies and their caregivers, too. Yeah, absolutely. Look, there's ample data in our episode on, you know, the Miracle Kitchen shows this that if you manipulate the world around a person, you change how they function, you change their mind, alter their mind. And that's with humans who don't have a neurodegenerative disease. I think what persons with neurodegenerative disease show us is a brain that's quite vulnerable is even more susceptible to manipulations in their environment, both for the good and for the bad, if you will. Yeah. [00:32:52] Speaker B: So we know now we have these treatments. We've talked about other ones coming down the pipeline in previous episodes, but I think a primary takeaway is that having this optimism, having a way to reframe your life, rethink about your approach to the world, can oftentimes play as important [00:33:10] Speaker D: of a role as some of the [00:33:11] Speaker B: treatment that you're receiving in clinic. Well, I think that's a great note to end on. Jake, thank you so much for reporting on this and, Jason, for your perspective from the clinic. [00:33:19] Speaker D: You're welcome. [00:33:20] Speaker B: This has been a great episode. [00:33:21] Speaker C: Yeah. Thanks so much. In lieu of our usual closing theme, here's Sandy Schulin again. Thanks for listening to this episode of the Age of Aging. The show is made possible by generous support from the Michael Nadoff Communications Hub Fund and our sponsor, Rothkoff Law Group. The Age of Aging is a Penn Memory center production hosted by myself and co host Terrence Casey. Contributors include Dalielle Said, Jason Carloish, Emily Largent, and Allison Lynn. Thanks to my co hosts this episode, Jason Carlos and Terence Casey, and our guests, Dave and Evelyn, Justin Clapp, Keira o', Brien, Joanne and Bruce Thomas, and Sandy Schulin. If you enjoyed this episode, please consider subscribing to the podcast, leaving us a review or giving us a like. These types of things really help others find the show. And if you know someone who might be interested in these conversations, share this episode with them. We also love hearing from our listeners. If you'd like to reach out, our contact information is in the show. [00:34:30] Speaker D: Notes.