Putting Lecanemab into Practice: A Clinician’s Perspective on the New Alzheimer’s Treatment

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Headshot of Dr. Bob Pryzbelski
Robert Przybelski, MD, MS

On July 6, 2023, the U.S. Food and Drug Administration (FDA) granted full approval for the Alzheimer’s disease drug Leqembi (lecanemab-irmb), the first medicine shown to delay the course of the disease. Having gone through a rigorous approval process, the medication exemplifies a critical advancement in the ongoing battle to treat Alzheimer’s disease. Having already prescribed the treatment to real-life patients, Dr. Robert Przybelski joins the podcast to discuss his experience prescribing and administering lecanemab, what clinicians and patients should discuss when considering these treatments, and what is needed to integrate these treatments into the healthcare system.

Guest: Robert Przybelski, MD, MS, director, Geriatric Memory Clinics, UW Health, professor, Division of Geriatrics and Gerontology, University of Wisconsin School of Medicine and Public Health

Show Notes

Read more about Lecanemab’s Appropriate Use Guidelines on our website.

Read the FDA’s press release, “FDA Converts Novel Alzheimer’s Disease Treatment to Traditional Approval.”

Listen to previous Dementia Matters episodes on lecanemab, “Introducing Lecanemab, The Latest Alzheimer’s Disease Drug to Receive FDA Accelerated Approval,” and “A Closer Look at the Lecanemab Clinical Trials,” on our website and all major podcast platforms.

Listen to Dr. Przybelski’s previous episode of Dementia Matters, “Vitamin Deficiency And Its Impact On Brain Health,” on our website, Spotify, Apple Podcasts, Podbean, and all major podcast platforms.

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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. Today I'm joined by Dr. Robert Przybelski, a professor in the Division of Geriatrics and Gerontology at the University of Wisconsin and the director of the Geriatric Memory Clinics at UW Health. One of the goals of Dementia Matters is to bring listeners the latest in Alzheimer's disease news, and today Dr. Przybelski joins us in light of the U.S. Food and Drug Administration's decision on July 6th, 2023, to grant full approval to the Alzheimer's drug Leqembi, the first medicine shown to delay the course of the disease. Dr. Przybelski is a physician who has already prescribed Leqembi to patients, and I've asked him to share his perspective on the process of prescribing and administering these types of drugs. Dr. Przybelski, welcome back to Dementia Matters.

Dr. Robert Przybelski: Hi Nate. It's good to be back. I've been looking forward to talking to you again and meeting with your audience once again. Yeah, it's such an exciting time. In fact, as you indicated, it was just approved yesterday for full approval, which means that we will actually have it for more general clinical use and, probably equally importantly, Medicare should be paying for it and insurance companies should be paying for it. Up until now I've only been able to get it through the companies.

Chin: And so Bob, before we get into the drug itself, I'd really like to start the podcast by having you walk us through your memory care experience. I'm hoping you can touch on how long you've worked in the memory clinic, some of the changes that you've seen over the past years, and some of the key milestones you've been a part of during your tenure.

Przybelski: Okay, yeah thanks. I started my memory work back in 1988-89. I did a fellowship at Walter Reed at that time, mostly working at lab-based, research-based. I came to the University of Wisconsin in 1993, ostensibly to set up memory clinics and actually had a couple clinics in Northern Wisconsin while we got things set up here. Basically the biggest advantage back then was actually having the multidisciplinary clinics that University of Wisconsin set up involving a neuropsychologist or psychologist, a physician, and a social worker, which is a unique model that we still have in Wisconsin called the Wisconsin Alzheimer's Institute. What exciting – I guess exciting milestones over that period is when I was coming out of my residency, we had the first drug that actually treated Alzheimer's disease symptoms. In other words, it would help the memory. It was called tacrine. Just to put it in perspective as you and I talk more about lecanemab, tacrine was a drug like donepezil and basically it helped memory work better. What was interesting is at that time, being a new drug and being the first drug, we would use the product even when it caused serious liver problems. In fact, we were told when liver enzymes became five times abnormal, then we'd stop and let the liver cool down and reuse it again. I mean, that's how toxic it was and yet that's the only thing we had. After that, of course, the medications like donepezil and others came along that we are using currently, and memantine, that we've been using for the last thirty years waiting for something like lecanemab. Over that time – and this is where I should kind of throw things in as far as how exciting this is – is when I was in my fellowship, coming out of my fellowship, the drug AZT, which was the first drug we had for AIDS came along. Suddenly we had a drug that would actually change the course of AIDS. That too was very, very toxic, as far as a lot of people had liver damage and other things. In fact, when I was working in the hospital we'd have patients who come in and actually die from the medications more so than the AIDS, so it was a long course for that disease. Meanwhile, I say finally after one hundred years of looking at Alzheimer's disease and similar diseases, we have a product that's going to change things finally in lecanemab.

Chin: And you're getting on my next question which is really – your history is helpful to me because I really want to get a sense for our listeners, particularly those that are not clinicians, how significant it is for the Centers for Medicare and Medicaid Services, known as CMS, to cover this disease-modifying therapy called lecanemab or Leqembi, and its full approval by the FDA, which just happened July 6th. How big of a deal is this in the scheme of your time in a memory clinic program?

Przybelski: Yeah, it's just amazing in terms of what this can do for us clinically. Again, it's a big deal for Medicare because it's going to be very expensive for covering a lot of people. On the other hand, I should also throw in, Nate, I meant to mention this in your last question – what really propelled the field in this whole area of treatment is actually the tools that we've developed in terms of identifying the disease and marking the disease with the biomarkers. In the last five to ten years, we have techniques of imaging, looking at the brain, that can find those proteins – the amyloid and tau – and quite clearly diagnose the disease like we've never been able to do before. In essence, it's been showing us where the target is, what the target is and how to approach the target, which is the amyloid for lecanemab. It also is, I think, eventually going to show us whether or not we're effective in our treatment. Getting back to Medicare, so Medicare did approve the original or the earliest imaging called glucose PET scans, which again shows us whether the disease is in the brain. Soon it's going to, I think, approve also the amyloid scans which are necessary to prove that the amyloid is in the brain, that the Leqembi  actually removes. So, again, there's a lot moving forward, a lot of exciting things. In the next six months, Medicare, I believe, is going to cover completely the treatment, diagnosis, and so forth, and all the ancillary procedures and efforts that are done associated with it.

Chin: Well it seems like if a drug is designed to remove a protein in the brain, you'd have to be able to have a test that can identify the protein to begin with. I mean, that will be one of the main criteria for who's appropriate for the therapy. It seems to me though – and you mentioned the history of tacrine and then donepezil – there's a lot of excitement, of course, from a clinical perspective of a drug that's a new drug for Alzheimer's disease. Does this feel similar to you to when donepezil first became approved or does this have a different atmosphere for you?

Przybelski: Yeah, it's a totally different atmosphere. Donepezil was exciting in that it was a safer drug like the one before, the tacrine. We knew that it would change – it would help people function better. It kept people out of nursing homes for up to six months longer. Donepezil was an improvement over the previous; it was finally something to treat this. This is different totally in that – I liken what you and I do in our Alzheimer's treatment like being an oncologist, like being a cancer doctor. I imagine back to the 1950s and 1960s when the first drugs were approved for cancer, when no longer did you have to say, ‘I'm sorry, you have cancer, you're going to die. There’s nothing I can do.’ Now we can look at an Alzheimer's patient and say, I'm very sorry you have Alzheimer's disease but there is something we can do. It's not the silver bullet. It's not going to end the disease per se, but we believe that it's probably going to change the course of the disease. In the next five to ten years when we get other treatments that could potentially actually stop the disease, we're actually buying time. So it's a very exciting time and much much more exciting even than when Aricept came along.

Chin: Now for our listeners, I'm not going I'm not going to go into full details about lecanemab itself or discuss the findings from the clinical trials, which I know you know very well, Dr. Przybelski, but you can find those prior podcast episodes in the show notes. I've asked you, Dr. Przybelski, to be in the show because as a physician who's already prescribed this medication or the precursor, the one aducanumab, before that to real-life patients, I'm hoping to get a sense of what the actual process is like. I don't want you to have to share any patient-specific information or make any statements beyond your own experience, but I think it'd be helpful for our listeners to know what it actually looks like to go through an infusion process. So with that said can we start with how many patients in the past have you treated with monoclonal antibodies. Going forward I'll just call them ‘mabs.’ These ‘mab’ therapies are human-made infusion treatments that are antibodies, like your own immune system, directed towards the proteins in the brain. So I'm really curious to know what your overall experience with the process looks like.

Przybelski: Yeah that's good to bring that up, Nate, because I wish it was as simple as prescribing a pill or basically here’s a prescription, go to the infusion center and I'll see you back when you're cured kind of thing. Actually it's very involved. First of all, we got to make an accurate diagnosis. I would say 50% of the people that come to see you and me with their supposed Alzheimer's disease really don't have Alzheimer's disease. Of course, treating them with something that's going to take amyloid out of the brain is going to require knowing there's amyloid in the brain. Basically it goes – it starts with a very good evaluation, not only for looking for Alzheimer's disease but everything else besides Alzheimer's disease like strokes and Lewy body, other conditions, Parkinson's, et cetera, and treating those. Then when we make an accurate diagnosis, which includes the brain scans as I mentioned before like the PET scan and so forth, then we have to make sure the patient is appropriate for treatment. Appropriate means not on medications that could cause them harm during treatment, for example blood thinners of certain types can cause problems. We want them to be optimal for the treatment. In other words, I want them exercising. I want them to have a good diet. Doing all the things that's going to minimize their chance of having side effects but also optimize them for the treatment. Then after going through several visits with them to make sure not only that they are the right patient and prepared but also making sure that they know what the potential side effects are. There are. There are potential side effects. All of these products thus far – there's two that have been approved and one that's on its way, donanemab – do cause micro hemorrhages in the brain. These are small things that we see on scans typically that aren't symptoms – that don't cause symptoms, but then nonetheless they could be dangerous. They could cause large strokes and there have been deaths reported with these products. We have to be very careful that patients know that there's a definite risk in taking these medications and a presumed benefit. In other words, presumed in that we see changes on the clinical studies but we don't know what they mean five years from now. When I talk to a patient in the family – like you say, on multiple occasions before we go this route – I say, look what I really want for you is I want to be having a conversation like this with you five years from now. I don't know that it's going to make a big difference in your memory per se, but I want you to be very functional.

Chin: Thank you for going through that process, Bob. When you do the evaluation process or you think about that, are there important blood tests that providers, whether it's primary care specialists, should be getting?

Przybelski: Yeah. First of all, they're going to do the usual blood tests like for thyroid, vitamin deficiencies, that kind of thing to make sure they're treating everything. Also, of recent, we actually for the first time now have a blood test that's accurate for Alzheimer's disease. In fact, it basically is going to replace the spinal fluid and maybe even some of the imaging we do, so that's very exciting. In fact, I got to use the test for the first time yesterday. I know soon I think it’ll be in many hospital laboratories. But again it is a blood test for Alzheimer's disease and I think that's going to be a tremendous advantage to primary care doctors who to this point would do the best they could trying to understand somebody that has Alzheimer's and now actually have a physical blood test, a biomarker.

Chin: For looking at that amyloid protein in particular?

Przybelski: Yes, amyloid and actually it's tau also. You remember the other protein that's most important is the tau and these tests will do both.

Chin: Yeah, that's incredible. Is there any other blood tests that you think about?

Przybelski: Actually yes. In terms of not only for diagnosis – in fact, it's not really very good for diagnosis but it’s very important for treatment – and that is the gene testing or genetic testing. There's a gene that's associated with Alzheimer's that I think most people have heard about called the ApoE gene. I say it's not good for diagnosis because you can have those genes and not have Alzheimer's. On the other hand, when I'm telling people about their risk of having those microhemorrhages, the risk is much higher if you have two of those genes. In other words, having a blood test for the gene, which fortunately comes along actually with the new blood test for Alzheimer's, I can tell them, is your risk of having micro hemorrhage is five percent or is it twenty percent. So yes, gene testing is very important.

Chin: And that's not something that's been commonly done in many primary care or memory clinics, so that too is a change in sort of our landscape. Frankly, everything you just said deals with the conversation and the visits prior to even writing the order for the medication and having the patient and family go to the infusion center. This seems like a lot of time I think, and I know this from talking to you outside of this podcast. How many visits does this take to have a good thorough conversation with a patient and family and how much time are you spending just in this pre-ordering phase of it?

Przybelski: I estimate between five and ten hours besides clinic time. In other words, not the diagnostic time, not the workup time per se, but more like talking to the patient, talking to the family, having multiple conversations, being on the phone with them again at some point. In fact, now I think we're getting better at using the time. For example, the first visit is often done virtually because I want to know what they know. I want to know that they've read about or have information. I want to know that they know that they get what they're getting into in terms of risk and benefit ratio. So yeah, it takes a lot of time. Fortunately, we're starting to get some support in terms of some nursing help and so forth. I have a wonderful, very small but really wonderful staff that's helping. Getting back to your early question about the numbers and the time and so forth, just from my own panel and our panel that you and I have had for a while – there's a good 200 to 500 patients out there that we could be starting to treat in the near term. Again, if you add up that five to ten hours per person you see, it's quite an investment to help people get started. I think you and I are going to need to train – as this podcast is doing – train other clinicians and other people to know how to do this.

Chin: One of the things you mentioned and highlighted earlier was first there's this process of identifying change – doing a thorough valuation, ruling out other conditions – and then, for the first time really ever, making Alzheimer's a diagnosis of inclusion – having a test or a series of tests that identify the protein. That itself takes quite a bit of time, and now you're describing five to ten hours of what I think of, in the research world, as good, proper informed consent, making sure they understand everything, that they're comfortable, and then getting them to the point where now you're ready to prescribe the medication. Can you lay out for us what does that look like? I mean, this is an infusion drug but some of our listeners might be confused as to what that means. What does that process look like?

Przybelski: Yeah that's – believe it or not, that's the easy part as you're basically alluding to. When I write a prescription, it's going to go to an infusion center, which, because we've been sort of pioneers in a sense using these clinically, it's been difficult the last two years getting that part of this system set up as far as most of the infusion centers are full of cancer patients and they have very few beds for a new drug. We've been able to find some initially in the Milwaukee area, now in the Madison area. Also in Northern Wisconsin fortunately because I get a lot of referrals from that area. Basically when you get the infusion center set up – and these people have been wonderful as far as excited about using the new medications – I write an order for the infusion for lecanemab. It's a twice-a-month infusion. The infusion lasts about an hour. In other words, an IV is put in the arm. They sit in a chair. People watch them closely. The nurses make sure nothing bad happens. After the infusion, they check them to make sure that there's no reaction to the infusion, which can happen. There can be allergic type reactions. Then people go home and then come back in a couple weeks and have it again. Again, that part is relatively easy. I've not had – knock on wood – I've not had any infusion problems so far. Then in between – this is another thing, in between about every three or four months we need to do another brain scan called an MRI to look for these microhemorrhages as I mentioned earlier because most of them are not going to be not going to cause symptoms even if they could be significant. About every three to four months we're doing another MRI, at least for about four times when we're monitoring. Again, I've been really, very fortunate. Patients have been fortunate. I've only had one case of a microhemorrhage and it was – I stopped the treatments, waited for three months like it was recommended, went back, microhemorrhage was gone, and we restarted the treatment and they did well. Anyway, so yeah, that's the relatively easy part. The problem are the numbers, as you said. If you and I would start two hundred patients on treatment, that's over seven thousand infusions. So the important thing is following folks and all making sure they're safe.

Chin: And so everything you just said, Bob, I imagine you say to patients and families too. Can you highlight, for some of our providers that may be listening, what are some key aspects that you feel really have to be covered when talking to patients and families about potentially being on this drug.

Przybelski: First of all, I think the clinicians should and would appreciate that we have to have the right patient and the right diagnosis and, again, have to be optimized for these treatments. In other words, they've got to be exercising. They've got to be on the right medications and off the wrong medications. They have to be – the vitamin deficiencies have to be treated, other things. Just sending them to our memory clinics and saying ‘Please treat these people,’ just is not going to work for the numbers and so forth. Also telling the folks honestly that we don't know exactly what's going to happen with treatment down the road. We think – based on the clinical data and the research data, we think there's going to be an improvement or at least over not being treated. We can tell them that much. Then also, the last thing we want is somebody coming in thinking that their memory is going to improve just by getting treated. It's going to be just like any other treatment – cancer treatment or anything else. There's going to be a lot involved and there's going to be a lot of work even afterwards. If we can change the course of the disease, as we expect, it's still going to take a lot of work for them to get back to the best they can be.

Chin: For our listeners that are healthcare providers, are there guidelines that are already published that can help direct them as to what this evaluation process looks like and the things that should be discussed with patients and caregivers?

Przybelski: Yeah, and thanks for bringing it up, Nate. I think that's really important and it's easy to access. It's called Appropriate Use Guidelines. Appropriate Use Guidelines. Cummings – C U M M I N G S – is the senior author. Basically what it is, it's a paper identifying who's appropriate to get these products and what type of things that exclude them, in terms of their level of memory problems at the time but also other conditions. It would be very, very helpful if the primary care doctors or the referring physicians would look through those articles or that article. There's some – there are very nice tables. In fact, I have the tables put up around my desk, which basically show the inclusion, exclusion, what's appropriate, what's not off and they have to be followed, that kind of thing. So yes, that'd be really, really helpful. It's called Appropriate Use Guidelines for Lecanemab or Leqembi. And again Cummings is the article I usually go to.

Chin: All right, well thank you. I'll make sure we put that in our show notes too. Are there questions or common scenarios that have come up in your process, things that families consistently ask you that, as clinicians who have not yet prescribed, we should be prepared to answer?

Przybelski: Yeah, I think the most common question is, is my memory going to get better? And, again, I'm very cautious in that regard. What I say is, your memories – I expect your memory is going to be better than if you didn't get treated. Then I said, a lot of that after that is going to depend on you. Are you going to do the brain puzzles? Are you going to do the exercise? Are you going to work hard? Do you continue to be sociale? Bcause the brain, as we know, is very resilient. All you have to do – an example I like to use, I say to the patient, I said, have you known anybody who's had a stroke and they couldn't walk? Most people do. I said, when you saw them six months ago could they walk? Well, yeah. Six months later, could they walk, could they do things they couldn't do before? Could they talk? They couldn't talk before. A lot of times they – yeah they did. They did pretty well with their rehab. I said, that's what we hope is that if we can change the course of the disease or even potentially put you into a remission, so to speak, you're going to be able to build the brain back up because, when you and I did our imaging studies, we see that you know a lot of times half the brain is perfectly normal and the other half is riddled with Alzheimer's disease. Theoretically, we can make that healthy half do more.

Chin: And so do people come to you asking what does slowed decline mean? I use that expression intentionally because I see that in the news all the time – slowing of decline, slowing progression. Is there confusion in the clinic room about what that actually means to a patient and family?

Przybelski: I think one of the things that we have dealt with – you and I in particular – and in doing a lot of Alzheimer's treatment over the last ten, fifteen years, whatever, is this whole idea that everybody goes through seven stages. Everybody looks the same, everybody ends up in a nursing home in five years. We know from our thousands and thousands of patients that everyone is a snowflake, that I can't tell. I tell them this. I say, look, nobody on earth – including me – can tell you where you're gonna be in two years, five years, ten years. This whole idea of slowing decline, does that mean that they're not going to be in a nursing home? Well, hopefully, and hopefully even better than that. So yeah, that's kind of a misconception that we've been dealing with for quite a while. That's one of the things that I really enjoy when I show them their brain scans, their PET scans. I can show them how much of the brain is involved and how much isn't. Also there's this whole concept that the more reserve people have when they start their disease, the more they're going–  the better they're going to do longer. There's so many variables and that's what I try to impress upon them.

Chin: And that's one of the the takeaways that I'm getting from talking with you, Bob, is that part of this conversation is about what's happening in the brain, the disease process itself, this medication, but the other, equally important part of the brain is this idea of resilience and how can we improve the connection of brain cells and make sure your brain is optimized. It seems to me that, in these visits, you're addressing both of them and making sure that both are spoken about, and that while there is a drug that's only a part of this care process. The other part are the things that we, right now, can do – the things, the exercise, the sleep, the foods, the activity. It seems to me that that's an important part of your process so far.

Przybelski: Yeah, and that kind of takes us a step further is, what are we going to do in five or ten years, or maybe even sooner, when we can actually put people into remission? The whole idea is stopping the disease, not curing the disease. It's going to be more like cancer or AIDS or whatever, where people are functioning quite normally with the treatments that may be ongoing. What's going to happen then? That's where I really get excited, is thinking about rehabilitation. Right now, I don't think we have a good system at all for rehabilitating people with Alzheimer's or keeping them functional in terms of sending them to somebody, getting cognitive rehabilitation, that type of thing. I think in the next few years we need to develop that system. What's also exciting is I just came back from a conference in Denver looking at psychoactive medications or psychedelic medications that actually stimulate nerve growth. I mean, if we can find compounds, healthy compounds, that actually help the brain to recover and form those connections that currently take a very long time to form, I mean theoretically we can rebuild the brain to some degree and recover functions. So there's so many exciting things coming now because of lecanemab, because of where we are.

Chin: Yeah, the research is going to pivot or at least expand to other areas of the brain, but certainly what you just said, too, about the importance of that interdisciplinary, multidisciplinary team – having certain therapists and experts who can help with cognition, cognitive symptoms. I know that in our own program we call upon physical therapy, occupational therapy and speech therapy frequently to build sort of a system. I phrase it that way so that – I have a question for you in a second about infrastructure but before I get to that – I think one last question I had related to the medications, these ‘mab’ therapies themselves, is this idea of ARIA, the Amyloid-Related Imaging Abnormalities, because this, too, has made it into the news and is something that I know people who are interested in the drug are still worried about. What would you like our listeners to know about that conversation? You know, ARIA is something that should be talked about in this whole process with the patient and family. How do you approach it and what are some key things that should be said, just to make sure that everyone is aware of the potential side effect?

Przybelski: Yeah. First of all, I wouldn't downplay the fact that there are microhemorrhages because there are. Depending on the medication, the first one that came through, Aduhelm, had somewhere between twenty and forty percent of patients at some point during the eighteen months will have ARIA. The more recent one, lecanemab, it's somewhere between five and twenty percent depending on what group you're in. They are definitely observable on their brain scans. Most of the time they are asymptomatic. In other words, they don't cause symptoms but, nonetheless, it can be associated with strokes. Overall the serious side effects, like stroke and death, is less than one percent but nonetheless they're serious. Now on the other hand – and again I don't mean to minimize – ARIA occurs in patients with Alzheimer's disease with or without these products because the brain is – again the tissue, that's damaged. There's an immune reaction to it. You're gonna have a certain amount of ARIA at baseline anyway, which can be between five and ten percent of the patients. That's, I think, very, very important. The other thing, again, when I alluded previously to AZT for AIDS, or the original product for Alzheimer's disease, the cancer therapies, there are always going to be side effects to medications. In fact, when I was doing – I used to do a lot of research in Europe as well as the US. Some investigator once when I was talking to him about a product said, ‘Well, you know, the stronger the medication, the more side effects. It's just a rule of thumb.” These are strong medications. These are going to have side effects. The important thing is to be honest about the risk and the benefits.

Chin: Thank you for saying that, Bob. Now we have spoken briefly about this, but there is a lot of uncertainty still about what happens after this treatment course is over, the clinical trials and those eighteen months. So questions that already have come up: how do you monitor post-treatment? Do you give another course of treatment and, if so, for how long? How do you actually measure success in this process? So what future issue should we be considering really is something that I think is on the mind of many administrators and healthcare clinicians. I'm not expecting you to answer those, but what would you say to healthcare systems that are planning to implement this drug? What type of infrastructure – staff, testing, policies – do you see as beneficial and important based on your experience already?

Przybelski: Yeah. I think it gets back to the last question, what's the worst that can happen in terms of safety? So when I talk to groups, especially rural groups that are not in big cities and so forth, I say, as much as you'd want to use these medications, you’ve got to have a safe system. In other words, you’ve got to have radiology that can do the scans. These patients have to be monitored and that type of thing. I think that's the start. If you're going to prescribe these medications, make sure you have radiologists that know how to look for these microhemorrhages and so forth, which they should. An emergency room that knows when these people come in with – if they come in with headaches or other symptoms, they should be evaluated for strokes because that's a possibility. Again, safety is number one. Number two, from a standpoint of personnel. I think – I honestly believe, Nate, that primary care physicians can use these treatments, if they accurately diagnose the patients and have social workers and other people like we have to actually support these patients and their families. It's going to have to be at that level, with the five million people we have in the United States with Alzheimer's disease, where it's going to have to be at the primary care level eventually where these treatments are done. Again, if you have five or ten patients – let's say a physician has five or ten patients in their practice that they are treating for Alzheimer's disease is probably doable if you have your nursing staff and your others who can be trained by us and learn what to do. I think that's very important. Down the road – and this is where, again, it gets exciting to me – I honestly think that the cancer model is the way to go. In other words, when we get these patients into remission – which I think is going to happen in the next two to five years when we have other treatments that can actually stop the disease or even perhaps just looking at the amyloid – what I would want, what I expect to do eventually, is that when their course of treatment or eighteen months is done, or maybe even at twelve months, maybe even before eighteen months, repeat the brain scan to look for the amyloid. If the amyloid is gone, stop the treatment. Why keep exposing them to a medicine they don't need? Then perhaps at one year, two years, five years, take another picture, which we can do very easily, and see whether the amyloid is back. If the amyloid is back, treat them again. I mean, that's what I would expect at some point, is we're going to be more diligent and more conscious, let's say, of the fact that we have to follow these people.

Chin: And so to end, Bob, some of our listeners are clinicians or part of clinical staff. Some of our listeners are community members who are interested in the space or might have their own memory concerns. Can you summarize for us where are we in the whole scheme of things and what you think is important for any listener to just know before moving forward with these types of drugs?

Przybelski: First of all, make sure if you're worried about yourself or your memory or your family member or loved one, get an accurate diagnosis. Because, for example, when people come in and say, oh my dad had Alzheimer's, or, I was told I have Alzheimer's, what I hear is: there's a serious memory problem. That's all I hear until we work them up. Coming in saying, I want this lecanemab because I have Alzheimer's – well that's a long way away from getting the lecanemab because we have to be worked up. So don't throw in a towel. I guess I should say that – don't throw in the towel. Really get worked up. Lot of memory problems are reversible. They're due to stress. They're due to malnutrition. They're due to other conditions that are not adequately treated like thyroid problems. Get a good workup. Ask your primary doctor to do a very, very thorough workup before anybody labels you with Alzheimer's disease. Then if you do have Alzheimer's disease, come in early, be treated because these medications are only prescribed for people at certain levels.

Chin: Well with that, thank you Dr. Przybelski for being on Dementia Matters and sharing your experience with this whole process. I know for those of us that haven't done it yet we are looking to individuals like you who can give us words of wisdom and some guidance.

Przybelski: Oh thank you, and a very exciting time and very timely with the approval yesterday of lecanemab. So again, thank you, Nate. I enjoyed being with you.

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 dementiamatters@medicine.wisc.edu. Thanks for listening.