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What Is Anti-Amyloid Antibody Therapy and Can It Help Slow Alzheimer's Disease?

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What Is Anti-Amyloid Antibody Therapy and Can It Help Slow Alzheimer's Disease?

Oct 18, 2023

Managing Alzheimer’s disease requires an intricate understanding of available treatments. Michelle Sorweid, DO, MPH, sheds light on anti-amyloid antibody therapy, how it works, and what patients are good candidates. While not a cure, this therapy can decelerate disease progression for certain patients. Learn who might be eligible and why timely intervention could be key to optimizing potential benefits without exacerbating the condition.

Episode Transcript

Interviewer: You've heard of anti-amyloid antibody therapy for Alzheimer's and you're trying to determine if it would be useful for yourself or a loved one.

Dr. Michelle Sorweid is the Medical Director of the University of Utah Aging Brain Care Program, which offers evaluation, diagnosis, and ongoing management of cognitive complaints and disorders. And today, Dr. Sorweid is going to walk us through how she counsels patients on these promising new therapies for Alzheimer's.

Criteria for Anti-Amyloid Antibody Therapy 

Dr. Sorweid, first of all, I think the beginning of this conversation, from what I understand, really is about who is a good candidate for these therapies because it's kind of a limited number of people if I understand correctly, and it doesn't matter how great the therapies work if you're not a good candidate. Would that be an accurate assessment?

Dr. Sorweid: Exactly. So there are quite a number of restrictions for this therapy, and those are mostly based on the clinical trials that were used to study this drug. So, for example, these types of medications are typically only prescribed and indicated for patients with mild Alzheimer's disease, so that's mild cognitive impairment or mild dementia due to Alzheimer's disease.

Complexity of Mild Alzheimer's Diagnosis

Interviewer: All right. And how does one exactly determine what is mild?

Dr. Sorweid: So a clinical evaluation is necessary in order to determine the stage or the degree of impairment.

Interviewer: All right. And are you pretty good, are doctors in general pretty good at being fairly accurate when you do this evaluation? If you tell somebody that they have a mild case, it generally tends to be the case.

Dr. Sorweid: So I would say just a general conversation, a visit itself is not going to be enough to determine the degree of severity. Just having that conversation with a patient can be very misleading. We need objective data in order to determine not only the severity or mildness of the disease but also whether or not someone indeed has Alzheimer's disease as the cause of their symptoms as well.

Interviewer: Oh, okay. All right. So yeah, that's something you need to make sure for it to work it's Alzheimer's disease, and then it needs to be in that mild category. And these tools are pretty good at figuring out if somebody would fall within that mild category.

Dr. Sorweid: Right. So we just do objective cognitive screening, for example. It may include additional testing, such as brain imaging, physical exams, lab work, etc. But just to determine the exact cause of their symptoms.

Effectiveness and Limitations of Anti-Amyloid Therapy

Interviewer: And if they fall within this mild category, what kind of results could a person expect with this type of therapy?

Dr. Sorweid: So in the clinical trials, patients did still get worse on Lecanemab, but not as much of a decline as those on placebo. So this is a treatment for Alzheimer's disease, but it does not completely prevent decline over time.

Interviewer: And it generally doesn't reverse it. It just mainly kind of slows down the progression. Is that correct?

Dr. Sorweid: Exactly.

How Does Anti-Amyloid Therapy Work?

Interviewer: I'd like to get into briefly how these therapies work. What's going on in the brain? What are they doing in the brain that's actually helping to slow the decline for eligible patients?

Dr. Sorweid: Sure. So one of the parts of the evaluation would include testing in order to determine the presence of amyloid plaque in the brain. Amyloid plaque is one of the many causes of Alzheimer's disease. Accumulation of a protein called amyloid, and essentially this protein is misbehaving in the brain and causing these sticky chewing gum wad-like plaques microscopically in the brain. So not something we can see on a normal MRI or CAT scan of the brain. So this, again, is just one of the many causes, which is why these medications aren't a cure and are just a treatment to clear the amyloid plaque from the brain.

Interviewer: And from what I understand, they adhere to the amyloid plaque and then somehow carry them out of the brain. Is that correct? Is that a good visualization or not?

Dr. Sorweid: So they are very specific for . . . Well, this particular drug, Lecanemab, which is the one that's usable and FDA approved, specifically adheres to the amyloid-beta protofibrils. And so it tends to be pretty toxic towards those amyloid protofibrils.

Decision-Making and Considerations for Anti-Amyloid Therapy

Interviewer: So then by adhering to them, they're able to clear those plaques out of the brain, which then helps slow down the progression of Alzheimer's disease. So how do you counsel patients when deciding whether or not to move forward with this type of treatment? Let's say that, you know, they do meet the requirements. You know, they're a mild form of Alzheimer's. They have amyloids. What kind of conversations do you have at that point?

Dr. Sorweid: Right, so I would say about 15% of patients I've seen do qualify based on just disease severity. And then there's quite a long list of other criteria that have to be met. One of the more common reasons that patients won't qualify is if they are already on a medication called a blood thinner, specifically medications for conditions like heart arrhythmias or COTS, a blood thinner that can increase the risk of side effects when using this drug. There are other criteria. There's, again, quite a long list, including active cancer, where patients won't qualify. But essentially it's just counseling them on whether or not they qualify based on their clinical criteria.

Anti-Amyloid Therapy Treatment Procedure and Commitment

Interviewer: And if somebody, you know, passes all these qualifications, I understand that the drug is quite a commitment in order to get the treatment. Could you explain what that looks like?

Dr. Sorweid: So this medication specifically is an infusion every two weeks. The infusion itself can last for an hour, plus all of the checklist of things that have to be done associated with that infusion visit. On top of that includes extra visits for MRIs in order to monitor for side effects. One of the more important and unique side effects of these anti-amyloid therapies is tiny microbleeds and tiny areas of swelling in the brain. It was a common side effect in the clinical trials, even up to 25% of patients, though only about 3.5% were symptomatic.

Cost and Medicare Coverage for Anti-Amyloid Therapy

Interviewer: And I understand the drug is fairly expensive too. Is that correct?

Dr. Sorweid: So, currently, Medicare has approved the use of Lecanemab, unlike some of the other anti-amyloid therapies so far. And so it is covered by Medicare.

Interviewer: Oh, okay.

Dr. Sorweid: If someone is currently on Medicare, we can get it covered by their insurance.

Genetic Considerations for Anti-Amyloid Therapy

Interviewer: Yeah. But it sounds like, while it does slow down the progression of Alzheimer's in the correct cases, there are some downsides. Especially, you know, having to go in every couple weeks and some of the potential side effects, do you have patients that in the end decide that the benefits aren't worth the cost? And like what do those discussions look like? How do they arrive there?

Dr. Sorweid: Sure. So there's quite a complicated process in even determining whether someone has amyloid plaque in the brain. Once we get there, we do have to do or it's recommended that we do genetic testing for something called apolipoprotein E. Those patients in the clinical trial who had two copies of apolipoprotein E4, so we all have one of each, one from mom and dad, for those who were what we call homozygous, so had two copies of apolipoprotein E4, there was an increased risk of side effects, specifically these amyloid-related imaging abnormalities that I mentioned, so the microbleeds and areas of swelling.

Interviewer: Do you have patients that ultimately after they hear about the treatment decide not to have the treatment and what goes into those decisions?

Dr. Sorweid: Yes. So, for example, someone who is homozygous for apolipoprotein E4, who might also just not be the most ideal candidate, for example, doesn't have a family member or a friend that's committed to helping them navigate these complex appointments and regimen, watching for side effects, for example, that might not be the person who considers that drug for themselves. And so that's, you know, usually a pretty in-depth conversation that we have with our patients beforehand once they've done all the testing or even before obtaining some of the amyloid testing that's required.

The way we determine whether someone has an amyloid plaque in the brain can include an invasive procedure called a lumbar puncture as well. So because amyloid PET imaging, a brain scan looking for amyloid plaque in the brain isn't currently covered by Medicare, those patients who haven't already participated in a research study to determine whether amyloid plaque is present end up doing that lumbar puncture or spinal tap to determine whether they have amyloid plaque.

Interviewer: It sounds like quite a journey. This doesn't sound like you just take a pill and it helps to stop the progression of Alzheimer's. It's a very, very involved treatment it sounds like.

Dr. Sorweid: It's fairly complex. And for the moment, only dementia specialists at the University of Utah have prescribing capabilities, though that could change down the line.

Upcoming Anti-Amyloid Therapies

Interviewer: As of right now, the anti-amyloid antibody therapy that has been approved by the FDA, there's just one of them. But there are a couple of other ones that are on the horizon. Could you talk about those treatments, and do they kind of get around some of the things that we've discussed in this conversation or are they going to have some similar restrictions?

Dr. Sorweid: So one is Donanemab, which has data coming out towards the end of this year, 2023 versus early next year. So we should know more about it, but it does look promising and as far as being clinically usable may not be quite as burdensome. But for now, the process for monitoring for side effects and increased appointments with their provider is still quite burdensome for all of these drugs.

Resources and Continued Learning

Interviewer: If somebody is looking to follow along with the development of these treatments, are there any resources that you could recommend that somebody utilize to keep on top of kind of these promising developments in treatment, although burdensome right now?

Dr. Sorweid: I think the most helpful article that I can refer to as far, as the clinical criteria, is the "Best Use Recommendations or Appropriate Use Recommendations" by Jeffrey Cummings, which came out shortly after the Clarity AD trial, so that's the clinical trial publication for Lecanemab specifically. So the appropriate use recommendations are what we use as clinicians in order to determine whether a person is a good candidate for the drug and what seems to make the most sense clinically as far as criteria that we use. As far as layperson resources, I think the Alzheimer's Association is appropriate and Mayo Clinic.

Alzheimer's Prevention Strategies

Interviewer: At the end of this conversation, what would you want somebody to take away from what we just discussed, if this is, you know, a treatment that they are interested in for themselves or for a loved one?

Dr. Sorweid: I think the biggest take home is that these anti-amyloid therapies are for patients with mild disease. And so if you have a loved one with a severe disease, these medications would only increase problems rather than help. And then just, again, keep in mind that this is not a cure, though this is a great first step in establishing a treatment for Alzheimer's disease. We have a long way to go and probably are looking at multimodality therapies in the future.

So the most important thing for individuals and a thing that is well evidenced is staying physically active. Especially for patients who are maybe looking at an older loved one who might be in their midlife, who are caring for possibly an older adult parent with Alzheimer's disease or related dementia, the most important thing for them to be doing is not to be a smoker, don't get diabetes, and be physically active, So controlling risk factors and addressing risk factors that we know increases the risk of developing Alzheimer's disease.