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Hello everyone and welcome to this educational presentation presented by Medall. Medall is committed to uh open access and free health education for all healthcare professionals. They're a great group to work with. I'm very excited to work with them on this important presentation entitled Amyloid Related Imaging Abnormalities Aligning Decisions Across the Alzheimer's Care Pathway. My name is Doctor Chuck Vega. I'm a clinical professor of family medicine here at the University of. California Irvine and delighted to be here with you today, but our target audience is pretty broad because AA is, if you're not familiar with it, uh, can affect a lot of different practices from radiology to emergency medicine to neurology to primary care. And so we're gonna cover all those bases and you can read our learning objectives here. I have an outstanding group of faculty that I'm presenting with. So, uh, again, we're just gonna get things started today. Here are disclosures. Here's the accreditation statement for this activity. Some, some more busy work to, to get through. And now let's, I'm gonna talk about shared decision making. Uh, when it comes to folks with Alzheimer's disease or mild cognitive impairment who are considering amyloid targeted therapies or ATT, uh, because these therapies are disease-modifying. They're the first disease-modifying agents we have for Alzheimer's disease, but they do come with this rate, this risk of brain edema or even brain hemorrhage. And so we wanna put that in context. So, our pathway today is we're gonna learn how to have this conversation. How to initiate using a case. Um, we certainly wanna make sure that patients' neuroimaging is done. And this is something I do at the outset. Uh, so this is called tier one testing. When I, I have a strong suspicion somebody has cognitive impairment. Um, at this point, I'm not sure if it's Alzheimer's disease or another type of, uh, cognitive disease. Um, I'm going to image them. So I'm gonna get a baseline MRI. That's very important for considering, uh, the risk of amyloid-related. Imaging abnormalities or ARIA. I'm just gonna say ARIA from now on. Um, but, and, and, and you'll see that this, uh, these imaging abnormalities are not uncommon. They can happen during treatment with ATT. And so, therefore, uh, we wanna keep that in mind. We want to continue to monitor patients. And, uh, and then we wanna make sure everybody's on the same page with what to do if we, uh, if we detect a case of ARIA. So let's start with the case. Margaret is 74 years old. She's a former teacher. And she has early symptomatic Alzheimer's disease. So say mild disease, that puts her in the category, uh, ATT or for patients with MCI or mild Alzheimer's disease. Um, we confirmed amyloid pathology, so that's very important to do. That, that's, that means she's set up for ATT. She's an APE 4 heterozygote and APE 4 is important for these patients. This is one time when I have a symptomatic patient with cognitive impairment. I will check APE 4. If we're gonna think about ATT, the more copies of that APE 4 allele you have, the higher risk of aria. Um, and so what we did a good job of talking about what matters to her, not that unusual for, uh, for our patients, wants to be independent as possible, stay involved in activities, but concerned about this possibility of brain bleeding or brain edema, those sound really scary. Um, also, it's a fairly rigorous schedule in terms of getting, um, IV infusions, um, particularly, uh, and, and then also getting follow-up MRIs. The 1st 6 months in particular are very busy. So I always wanna check with patients as part of my counseling, hey, you're gonna have a lot of healthcare visits. Is this something you think you can do? So let's start with the polling question. Margaret asked, if treatment can cause swelling or bleeding in my brain, why would I consider it? Good question. Um, which response best opens an informed patient-centered discussion? Is it A, let's first establish whether treatment is clinically appropriate before discussing possible adverse events. Uh, B, let's compare. Likely benefit, RA risk and what matters to most of you personally. C, the specialist can explain RA once the rest of the eligibility assessment is complete. D, the treatment is approved, so it's expected benefits usually justify the monitoring burden, or E, let's arrange the first monitoring MRI before deciding whether the treatment is acceptable. And I think the best answer here is B. And we'll talk about why. You know, so, um, we wanna practice shared decision making. This is a really important one. It's a, it's a big decision. You're, you're having some serious balance of benefits versus risk. There's also a burden on patients and often their loved ones who are bringing them into visits. And, and it really comes down to what are the patient's goals? What are their values? What do they wanna achieve with this treatment? And we know that clinicians can have a very different approach to this process. We're gonna try to standardize it. Of course, you have your own take and you're going to individualize this discussion. But that said, uh, I think it's a very important discussion to have and giving you a little bit of a framework to work with, um, and keeping you in the evidence-based bounds of healthcare is really important as well. So, um, I do talk about the fact that leanimab and danumab, the two, drugs that are approved as ATT, um, really do have an effect. There's a disease-modifying effect. They don't, there's no cure. They're not curative. And they don't make your cognition better. What they do is they reduce the rate of slowing of, uh, your cognition. So, uh, and one thing I also mentioned is in clinical trials, they have been shown to delay slipping down in terms of, uh, more severe classes of dementia. So they, they keep you more time in that mild stage of dementia versus slipping into to moderate dementia, for example. But you wanna stay away from statements like, oh, it'll make you a lot better, uh, because they don't. They, they slow the rate of progress of Alzheimer's disease. That's what they do. And the risk of RA is quite real. In the main, uh, study of leanimab, you can see rates of RAH, which is hemorrhage, uh, 17%, RAE edema, about 13%, and even higher with, uh, denanimab, uh, RAH 19% and RAE 24%. Although with a modified dosing schedule with denanimab, especially the rates of RAE are significantly lower. Particularly, uh, for patients like Margaret with an APOB4 allele. So, um, so we want to think about patients' risk before we see them. Um, a lot of that comes down to the baseline MRI. So patients with, uh, cirrhosis, you know, evidence of previous bleeds or more than 4 microhemorrhages or existing edema or other, uh, say they have an aneurysm. Many times those patients will not qualify right off the bat, uh, for ATT. I mentioned AP 4 status. If you carry two copies, it's worse than one copy and one copy is worse than no copies in terms of the risk of RA. And there's not much in terms of modifiable risk factors we can, we can use. Uh, so for patients with anticoagulants, that, you know, that's a risk factor. But antiplatelet agents don't seem to be a major risk factor. In one, review analysis that they found was that, uh, uncontrolled hypertension was another risk factor. That's the one modifiable risk factor that I know of for RA. So we wanna pay attention and make sure BP is treating, uh, treated appropriately. And then, uh, it is going to be many visits, oh, especially in those 1st 6 months of therapy where we're not only, uh, getting infusions, um, and with, uh, leanumab there is the option for subcutaneous administration, so that's relatively new, uh, that can take away some of the burden, but still MRIs, we're, we're looking at multiple MRIs during that first month, so. Lots of clinic time. So we wanna make sure patients can actually achieve, uh, that schedule. And after the 1st 6 months, it's less rigorous and, and, uh, and much more doable. Um, but so this has a lot to do with the support around them, the travel that they have in them, and, and what they, what they want out of this short-term period for the longer term benefit, uh, with ATT over time. It's also important that patients understand the concept of what happens if during a monitoring MRI or if the patient develops symptoms, what is the plan of action. So symptoms, uh, things like headache or confusion or or other focal neurological deficits, um, are very concerning while on treatment. So, uh, if they are new and, uh, and persistent, then, uh, then definitely it's, it's, this could mean a visit to the emergency room. So I wanna make sure patients are aware of that, um. They might need urgent MRIs and they might get their treatment pause. Even on screening MRI, um, most patients are not symptomatic with RA. So that's, that's one thing to reassure patients. It's less than 5% of folks actually have symptoms. Um, most of these, uh, aria, uh, do resolve with time, but it may require a pause in treatment. Does not mean the treatment's not working. It just means that there's going to be a pause. Let's make sure that the aria either gets better or stabilizes, and then we can proceed with more treatment. So Margaret Valley, another question for you. Margaret values maintaining everyday function, that lives 2 hours from the MRI center. She's worries about that treatment pause would mean treatment had failed. What's the best next step? Is it a recommended against treatment until she can relocate monitoring to a center closer to home? B, proceed if her daughter agrees to provide transport for every scheduled MRI appointment. C, explore her priorities, explain treatment pauses, and agree whether monitoring can work in practice. D, ask the specialist to decide whether the travel burden makes treatment clinically unsuitable. E, delay the the risk discussion until a treatment has been selected and authorized. Uh, please mark your answers now. Um, I think, uh, C is the best answer. It's practical and takes her values, um, and her wishes into account. So we wanna offer a general explanation and explain the benefits and risks of some of the burden associated with ATT, um, and then we wanna personalize it to patients, uh, individual goals, explore any differences we have, check to make sure if we have a plan in place, and then, and then set that plan up. And so, uh, so I, I, these are some good, uh, examples of questions about, uh, getting larger goals. Some patients may wanna.