The narrow promise of lecanemab for Alzheimer disease

Lecanemab arrived in Canada in January 2026 as an anti-amyloid therapy meant to slow Alzheimer disease. A new practice article in CMAJ, "Lecanemab use for early Alzheimer disease in Canada," lays out key challenges with the drug including narrow eligibility, a modest effect that may not be clinically meaningful, and a resource-intensive path to treatment.

Dr. Sophie Weiss, a co-author of the article and a third-year internal medicine resident at the University of Toronto, walks through eligibility and effect size of this novel treatment. Qualifying is a multi-step process of confirmed amyloid on a PET scan or lumbar puncture, genetic testing and a baseline MRI. However, the Clarity AD trial slowed decline by 0.45 points on a standard dementia scale, short of the roughly 1-point difference considered clinically meaningful. Patients eligible and interested in pursuing the therapy, in spite of its modest benefit, will need to pay $35,000 to $40,000 a year which presents one more barrier to treatment.

Dr. Vivian Ewa, a care of the elderly physician in Calgary and a clinical associate professor at the University of Calgary, describes the drug's limited role in her practice. She is unable to prescribe it as this is restricted to a small number of specialized prescribers. She says biweekly infusions and urban-only diagnostics put it out of reach for rural and remote patients. For the many who will not qualify, she points to the 2024 Lancet Commission finding that 45% of dementia cases are potentially preventable by modifying 14 risk factors, through such interventions as physical activity, socialization, vascular risk management and hearing correction.

For some patients, lecanemab may offer hope for a devastating condition lacking effective disease-modifying treatments. Physicians should be clear about the potential barriers, modest effect size and significant cost. At the same time, primary care physicians should emphasize the impact of reducing identified risk factors.

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Transcript

Dr. Blair Bigham:

I'm Blair Bigham.

Dr. Mojola Omole:

I'm Mojola Omole. This is the CMAJ Podcast.

Dr. Blair Bigham:

So, Jola, we are talking about dementia today, and in particular a drug that is very, very expensive and maybe not as clinically impactful as people had hoped for.

Dr. Mojola Omole:

Yes, we're talking about lecanemab, 

Dr. Blair Bigham:

And in particular a practice article published in CMAJ titled, "Lecanemab use for early Alzheimer disease in Canada."

Now, you've probably seen lecanemab in the news. It was all over the media when it first had FDA approval, but the challenge is it's really, really expensive, and the data is, I don't know, how do I say it, lukewarm.

And Jola, I don't know about you, but like, we work in healthcare, we see people with Alzheimer's disease, and it's horrific, it's awful.

Dr. Mojola Omole:

And it's a—it's a hard disease, especially for not just the person who has Alzheimer's, but also their families and caretakers.

Dr. Blair Bigham:

Absolutely. And as with many diseases that don't have a clear path forward or are degenerative or predicted to get worse, I understand the desire that people want some good news. We want something that we can do to move the needle on this horrible disease.

Dr. Mojola Omole:

And this paper is addressing what was first thought to be a promising drug for Alzheimer's, and it's showing us that it might not be living up to all we wished it could be.

Dr. Blair Bigham:

Yeah, we're going to get into it with the authors here, but let's just say it's a complicated drug to sort out regardless of its cost.

And we're going to get into those details now to help people understand where does lecanemab fit into our healthcare system and into Alzheimer's care in general.

Dr. Mojola Omole:

After we review lecanemab and the data on it thus far, we're going to talk to a physician who takes care of the elderly population and talk about some other methods in terms of preventing and also managing Alzheimer's.

Dr. Blair Bigham:

That's coming up on the CMAJ Podcast.

Dr. Blair Bigham:

Dr. Sophie Weiss is a co-author on the article in CMAJ. She's also a third-year internal medicine resident at the University of Toronto. Sophie, thank you so much for joining us today.

Dr. Sophie Weiss:

Thank you for having me.

Dr. Blair Bigham:

Let's break this down. Tell me, what is this drug meant to do? How does it work?

Dr. Sophie Weiss:

Yeah, so lecanemab is an anti-amyloid therapy, and it's meant to target amyloid build-up in the brain and help promote the body removing it.

So when amyloid builds up, this is what we're thinking is contributing to some of the features that we see in Alzheimer's disease and cognitive slowing.

So when the medication then binds to the amyloid and removes it, we're hoping to see slowing down of those symptoms associated with Alzheimer's disease.

Dr. Blair Bigham:

Now, the eligibility criteria or who's a candidate for this drug has been a little bit controversial. Break down the eligibility for me. Who can this drug actually help?

Dr. Sophie Weiss:

First of all, it needs to be a clinical diagnosis to start of early Alzheimer's disease or mild cognitive impairment thought to be due to Alzheimer's. So typically, this might be more seen in the primary care setting before the Alzheimer's disease has progressed and become more advanced.

And once an individual is thought to be potentially eligible from a clinical perspective, we need to actually confirm that there is amyloid present. So the individual either needs to go for a PET amyloid scan or have a lumbar puncture done, and then the cerebrospinal fluid will be sent for analysis to confirm amyloid.

So one of those two ways needs to confirm that that is in fact present for the medication to be effective.

Dr. Blair Bigham:

Do you have to have imaging or spinal fluid showing amyloid, or could anybody who has mild cognitive impairment qualify?

Dr. Sophie Weiss:

So you would have to have amyloid positivity, so either through the imaging or through the cerebrospinal fluid analysis, but there must be a presence of amyloid for the medication to be effective and for the patient to be eligible.

Dr. Blair Bigham:

So it's not like everybody with cognitive impairment is eligible. You have to have some sort of proof that you do have too much amyloid in the brain.

Dr. Sophie Weiss:

Yes, exactly. And I think that that is really key for family physicians to know and also for patients to understand is that the presence of amyloid is crucial for individuals to be eligible.

And then there's a few other factors that will also need to be confirmed before a patient can proceed with treatment. The next steps would be doing some genetic testing. So due to the trial that was done that then led to the approval of lecanemab, it was found that those with that were homozygotes for the APOE4 gene were more at risk of adverse events, and so they're actually ineligible for lecanemab. So that would be something that the patient needs to undergo, those genetic tests.

And they also need to undergo a baseline MRI.

Dr. Blair Bigham:

Oh, so would there ever be a time—I mean, a spinal tap's like a bit of a to-do—would there ever be a time where you need a spinal tap to find amyloid, or is any MRI good enough to show that you would both qualify for having amyloid and also have that baseline MRI?

Dr. Sophie Weiss:

So the baseline MRI is more so to look for any pre-existing microhemorrhages that would also make that patient ineligible to proceed with treatment—

Dr. Blair Bigham:

Gotcha.

Dr. Sophie Weiss:

—whereas the cerebrospinal fluid would be to look for amyloid specifically.

Dr. Blair Bigham:

Okay. So I'm just walking us through this. So number one, cognitive impairment. Number two, amyloid either on a PET scan or on an LP. Number three, we have to make sure you don't have this genetic predisposition to having more adverse events, so there's something that would disqualify you. And then number four, again to make sure you're not disqualified, we need to make sure you don't have microhemorrhages on an MRI.

Dr. Sophie Weiss:

Yeah, that's absolutely correct, you're following along.

Dr. Blair Bigham:

All right, I'm picking this up. Anything else we need to work into our algorithm here?

Dr. Sophie Weiss:

The other things to consider would be of course if the patient has poorly controlled comorbidities that would make them not suitable, or if they're on anticoagulation for another comorbidity, then that could increase their risk of adverse events. So those are things that both primary care providers and the specialist would take into consideration as well.

Dr. Blair Bigham:

Gotcha, okay. So if you're on a blood thinner, you're probably not getting lecanemab, is that fair?

Dr. Sophie Weiss:

Yeah, I would say that the DOACs are not recommended. Believe that single antiplatelet therapy is okay, but typically anything more than that would not be appropriate.

Dr. Blair Bigham:

Okay. So I think I'm clear on how to get to the point where I'm ready to write a script for somebody. But what does access look like? If I've gone through all that work, I mean that's going to take a couple of months and a whole bunch of appointments, we've gotten to the point where we're ready to go: how much does it cost? How do people actually get a prescription and get that drug into their house?

Dr. Sophie Weiss:

So it's a very costly medication. The drug itself costs around $35,000 to $40,000, and that's annually per patient just for the medication itself.

Dr. Blair Bigham:

Has anyone decided to cover it?

Dr. Sophie Weiss:

I don't believe so so far.

Dr. Blair Bigham:

Okay, but a couple have explicitly said no.

Dr. Sophie Weiss:

So Quebec was the first to say that they are not covering the medication, and so this means that patients will be paying either out of pocket or looking to see if they have private coverage if they would cover a proportion of that cost, but that might also not be the case and it may all have to be out of pocket.

And that cost does not include the actual infusion clinics or include the genetic testing, so there are a few other costs that are not even included in that 35 to 40,000 per year per patient quote.

Dr. Blair Bigham:

I think there's a fair question—it's certainly been reported in the press quite a lot—around whether or not this drug is worth it at all, especially with the hassle of making sure you're eligible, and then making sure you stay eligible, and then making sure you don't have an adverse event. Tell us, what is the effect size if you take this drug? How helpful is it for somebody who is terrified of losing their memory?

Dr. Sophie Weiss:

So the Clarity AD trial that was done looked at the difference in a score over the 18 months, and the score is called the Clinical Dementia Rating - Sum of Boxes score.

So over 18 months, they saw that the individuals on lecanemab's final score did not worsen as much as the individuals on the placebo, so there was about a 0.45 difference. However, that does not reach what we consider to be clinically meaningful, which is a difference of 1.

And this is an average, so every patient may have different impact from the medication, so we can't with certainty say that an individual patient would not experience a clinically meaningful benefit; however, the average suggests that they would not. And so it's important for them to know that it would be modest, if at best the impact would be modest.

Dr. Blair Bigham:

I want to just touch on the difference between the statistical significance and the clinical significance. Make it real for me: like, what does 0.45 or 1 mean in terms of things that I would relate to if I'm thinking about my parents?

Dr. Sophie Weiss:

Yeah, and I think that's where it's challenging because what the score looks at is cognitive functional outcomes, and again that 0.45 isn't so clinically meaningful, that small change. Maybe somebody doesn't see much of a difference at all.

Dr. Blair Bigham:

I see. So it may be imperceptible, is that fair to say?

Dr. Sophie Weiss:

That is what is currently being thought of with the fact that the score was under the 1 in terms of the change.

Dr. Blair Bigham:

So 1 is sort of the minimum threshold at which a neurologist might say, "Oh, this is actually improving your life."

Dr. Sophie Weiss:

Yeah, I would say that that is a good way to phrase it. But what is important to think about is there was still a slowing, so the medication is doing what it proposes to do. And again, every patient is different, and so each individual will have to make that ultimate decision for themselves. But yes, I think you have the right idea.

Dr. Blair Bigham:

At the end of the day, you know, I mean I think most physicians have said something along the lines of "I never want to end up like this person who seems to be a shell of what they used to be." So if, you know, I'm a physician, I make good coin, if I'm, you know, 78 and I'm starting to be like, "Oh, I don't know, I'm getting forgetful," and I'm flush with cash, like is there a reason not to try it if I've gone through this process? Like, and if I decide to try it, like how many months or years or weeks, like how long does it take before I can say "This isn't really helping, I'm going to cut my losses and save money," or do you kind of just have to be on it for years and hope that cumulatively it's just done its little bit to spare your memory?

Dr. Sophie Weiss:

Yeah, these are great questions. When it comes to reasons to not give it a try when it comes to benefits, the main things would be risks. So every patient should know that there are risks associated with lecanemab. Specifically, it's the ARIA, so it stands for amyloid-related imaging abnormalities. So seen on MRI typically will be these microhemorrhages or edema that's caused from the amyloid being cleared.

And so the trial done shows that the majority were asymptomatic, so 85% were asymptomatic. And then those that did have symptomatic ARIA were typically on the more mild side, and so it would be things like dizziness or some mild headache. And the more severe cases were much less common. I think really serious ARIA were only actually 0.7% of those events. So much lower, but it is still a risk.

Dr. Blair Bigham:

So it's not just a coin toss and a waste of money and let's just see what happens. There are a sizable list of problems that could occur from giving it a go, but most of those problems are mild. It seems like the benefits are mild, the problems are mild. It's a really tough call. Let me go back to another objective measure here. Is there any evidence that this drug actually reduces the amyloid in someone's brain?

Dr. Sophie Weiss:

Yes, so the Clarity AD trial did have some secondary outcomes, and one of them was looking at the PET amyloid scan pre-treatment and post-treatment, and it did see that there was amyloid clearance. So the medication is doing what it sets out to do. The question is more around the clinical outcome of that amyloid removal from the individual receiving treatment.

Dr. Blair Bigham:

Does this raise a question about the role of amyloid in Alzheimer's?

Dr. Sophie Weiss:

So, yes, I think that Alzheimer's is seen now more as multifactorial. Amyloid is thought to be a contributing part of the disease and its progression, so the amyloid hypothesis, and it is seen now through this trial that removing amyloid is slowing down the cognitive decline, so it must be contributing to some extent.

However, there are other theories on what contributes to Alzheimer's, so other proteins, tau is a well-known one that can contribute to Alzheimer's disease, and associated things such as inflammation, there's also other comorbidities that can be associated, so vascular disease that can cause similar cognitive decline.

So it's really multifactorial, and I think that amyloid is part of the problem, but not the entire problem, and by fixing the amyloid or removing amyloid, it doesn't cure the disease.

Dr. Blair Bigham:

If I'm a family doctor and I've listened to this podcast, off the top of my head I don't think I'm bringing up lecanemab to a lot of people, but if a patient brings it up and I walk them through this and we end up at this stage where I'm like, "Oh, you've gone through my algorithm, you meet criteria, you've got the money," how do I get them access to it? Do I send them to a neurologist and say, "Hey, I've done the workup, go for it"? Should I send them to a neurologist as soon as they ask the question? How do we execute on this?

Dr. Sophie Weiss:

I think that initiating a referral to a cognitive neurologist or geriatrician that has formulated their practice around neurodegenerative disease as early as possible is the most ideal when individuals have been identified as likely eligible clinically and are interested in the medication.

The family physician can initiate some of the workup, but ultimately this will differ depending on province and different practice. It's not clear the exact pathway. We suspect that specialists will be doing the majority of the eligibility confirmation and also will be the ones to prescribe the medication, and then do the monitoring throughout administration of the treatment course. So once they're set up with the specialist, then they can take over in starting that.

I did want to also just mention that for, like you had a great point, you said if patients bring up these questions, then maybe the family physicians will have a bit more information to share, but I think that this also raises an important question about what does Alzheimer's look like early on, and are family physicians able to pick that out? And so it's a good thing for them to be thinking about. So Alzheimer's is a bit more on the short-term memory, and there's also typically a family history. So if family physicians are noticing these things, then that might also increase their suspicion and cause them to consider lecanemab for their patients if they're interested.

Dr. Blair Bigham:

Fantastic tip. Sophie, thank you so much for joining us today.

Dr. Sophie Weiss:

Thank you. Thanks for having me.

Dr. Blair Bigham:

Dr. Sophie Weiss: is a co-author on the article in CMAJ. She's a third-year internal medicine resident at U of T.

Dr. Mojola Omole:

So, that's the research. But what does lecanemab look like in the clinic? And if its impact really is underwhelming, what else do we have for treating Alzheimer's?

Dr. Vivian Ewa: is a care of the elderly physician in Calgary, and a clinical associate professor in the Department of Family Medicine at the University of Calgary.  She's also co-author on the paper. Thank you for joining us today.

Dr. Mojola Omole:

So, this medication was initially touted as this breakthrough drug for Alzheimer's patients. From your perspective, is it living up to that?

Dr. Vivian Ewa:

Well, we haven't had a lot of experience in clinical practice with this drug. As you know, it was approved late last year, and only in January was it approved for use in Canada. So there's not a lot of experience with using it in clinical practice, especially in primary care.

Dr. Mojola Omole:

And when the studies say that you gain a year for every three, what does that actually look like for a patient? Can you describe that?

Dr. Vivian Ewa:

That's a—that's a very good question. And I think, how do we describe that when you're having that shared decision-making conversation with patients and their families? How do you talk about an extra year for every three years?

The thing here is that the diagnosis of dementia is very devastating. And so when people hear you get an extra year for three years, it seems to speak to that hope in terms of the delay in the progression of the disease.

But in clinical practice, I mean, the trials have been going on, I think, upwards of 36 months in some cases. We don't yet know what the impact is on quality of life, on independence, and on caregiver burden. We don't know. But when it comes to that hope when you're facing a devastating disease, and you use that, you know, one year for every three years, it seems to give people hope. But what it means in clinical practice, we're yet to see.

Dr. Mojola Omole:

Wow. So, are you actually able to prescribe it? Like, who's prescribing it?

Dr. Vivian Ewa:

So, I'm a care of the elderly physician, so in other words, a family doctor who did additional training in care of the elderly medicine, and I can't prescribe it.

There are some in my jurisdiction, which is here in Alberta, we do have—we do have actually one care of the elderly physician that can prescribe it, and we do have a couple of geriatricians and cognitive neurologists that can prescribe it.

A lot of these people that can are people who were involved in the trials and have a lot of experience and clinical expertise in the use of the drug, in the monitoring, and also being able to respond in a timely manner to potential adverse effects with the drug. So, I can't prescribe it personally.

Dr. Mojola Omole:

So, what I'm hearing, that it feels like it's so narrow who can prescribe it, which then equals is there equity in actually people meeting being able to get the drug? So, why is there such this narrow window of people who can prescribe it?

Dr. Vivian Ewa:

And again, I think it speaks to the fact that we are still learning about this drug. The people who can prescribe it now are those who not only have the clinical expertise, but also have been involved in the research, so they've used the drug.

And given the fact that right now it's not even available for public reimbursement, so public formulary, I think it makes sense that the access to it is to the expertise that can deliver it, because it's quite expensive if you're paying out of pocket with all of the monitoring.

You made a good comment about equity and access, and that's certainly a concern because not only is it an expensive drug, but even access to it. So, you talk about people who are in rural and remote parts of the country—

Dr. Mojola Omole:

Yeah, that's what I was thinking.

Dr. Vivian Ewa:

—they can't access it, literally. I mean, just think about traveling every two weeks for the infusion, traveling to an urban center to get the diagnostic imaging and the diagnostic blood test or lumbar puncture that is required.

And so there is an equity concern here because you would have difficulty accessing it if you live in the rural and remote parts of the country.

Dr. Mojola Omole:

Yeah, that's exactly what I was thinking, I was just like, we're such a huge country, and when we start concentrating care, especially something like this which is already a burden on families managing elderly patients who have, or anybody who has, Alzheimer's and dementia, then we're just narrowing the window of who can actually equitably access even something that's on trial.

So, it sounds like it's the young, the healthy, the independent person who is going to be able to access this, and maybe add who lives very close to an urban center. So, how often is that who's sitting in front of you?

Dr. Vivian Ewa:

It's not often. And that's why we—when we look at the eligibility criteria, it's really that very early stage, you know, mild cognitive impairment. So, we're looking at people who in primary care who present to—so, they're knowledgeable about the changes in their cognition, and so they will present and then get the, you know, initial assessments. And so just the staging, it really has to be people who are well-informed.

Now, I have to say there is a silver lining to all of this. There's an opportunity here for us to say, okay, in primary care, how do we recognize those who are experiencing changes in cognition? How do we make the diagnosis of early Alzheimer's-type dementia? So, that's the opportunity to train physicians, nurse practitioners, and other healthcare providers who work in this space in primary care to be able to make that earlier diagnosis, and if yes, this person will meet the clinical eligibility criteria, then referring them onwards, and especially if they can—if based on the risk-benefit discussion, they can afford it, then referring them on.

So, I would say there is an opportunity here to provide education because when we look at mild cognitive impairment or early-stage Alzheimer's-type dementia, even if they're not going to be eligible for drug therapy or they can't afford it, there are definitely other things that we can do. So, we can manage vascular risk factors, we can treat hypertension, we can treat diabetes, we can optimize weight, encourage physical activity. If there's hearing impairment, advise people to have their hearing checked and have hearing aids.

There is an opportunity here for not only diagnosing early, but also helping patients get on that pathway to helping some of those modifiable risk factors for dementia.

Dr. Mojola Omole:

So, you've answered a lot of my questions, it's like, so what are some of the effective pharmaceutical options since it seems as if this drug is not for a lot of people?

Dr. Vivian Ewa:

Yes, yes, yes. Not for a lot of people. And you asked about how many of those people sitting in front of me would qualify, and so because I do a lot of that care of the elderly work in the population, I tend to see more of the frail patients who wouldn't qualify.

But to your question about what are some of the effective pharmacological therapies, I probably want to start with one of—with the non-pharmacological therapies, and I mentioned some of them. So, physical activity: get people up and active. It really doesn't matter—people ask, "Oh, should I do aerobic, anaerobic?" It really doesn't matter. Just move. And move at least a couple of times a week, whatever is comfortable with you.

Socialization: so, we talk about our older population, social isolation and loneliness, get involved in social groups, community groups, and just have opportunities to have conversations, to do some sort of mental activity, crochet, playing cards, woodwork, bingo, all of those kinds of things, a wellness diet, managing blood pressure, managing diabetes—and some of those people, they haven't been optimized with regards to their vascular risk factors—hearing assessment. That's big. Even in middle life, if you have hearing impairment and you can get that addressed by hearing aids, it does reduce your risk of dementia.

Dr. Mojola Omole:

How? Can you explain that to me?

Dr. Vivian Ewa:

So, if you can hear properly, then that affects your comprehension, that affects your conversation, that affects your socialization, you tend to withdraw, and that in itself increases your risk of having dementia.

Dr. Mojola Omole:

That's really cool. All of the things that you've mentioned, to be honest, I'm a surgeon, so everything is cool to me that's non-surgical. "Oh, that's so cool." So, do all of these things work to prevent or slow the progression of the disease? Does it fall in the same?

Dr. Vivian Ewa:

There was a Lancet Commission study that was released in 2024 that showed that almost half of dementia cases, so 45% of dementia cases, can be prevented—can potentially be prevented by modifying 14 risk factors.

And so we know that now. I mean, the commission showed that. And so, I think in primary care, that's where this opportunity is, to do a lot of that work. So, starting in early childhood is ensuring that people have as much education as they have. So, we know that people who have 12 or more years of formal education have lower risk for dementia. And then in middle life, I've talked about all the vascular risk factors, the hearing loss, and then as you get older, really paying attention to vision, social isolation and loneliness, and addressing those risk factors.

So, we know that from multiple studies and collation of all these studies, and so I think putting a lot of our resources into these potentially modifiable risk factors that can prevent or at least delay the onset of dementia.

Dr. Mojola Omole:

Okay, so there was this—some studies are showing shingles vaccine can protect against it. What are your—what's your kind of initial thoughts about that?

Dr. Vivian Ewa:

Oh, so my initial thoughts, is this a correlation versus an association? Cause—so, is it a cause-effect or it's just two things occurring at the same time? Very difficult to see that in clinical practice. So, I have to say that my perspective is—is we're yet to see if this is, you know, sort of a cause-effect.

Dr. Mojola Omole:

Okay. So, realistically, the first presentation will be to a primary care physician, nurse practitioner. What do you think the first recommendation should be when someone presents or their family is concerned about mild cognitive decline or, I guess, more?

Dr. Vivian Ewa:

Excellent. So, the—the first step will be, yes, confirm the diagnosis. And so in clinical practice, we will, or at least in primary care, we will do an initial assessment that will include cognitive screening, we'll ask about function. Yes, if there's cognitive changes and we see that in the cognitive test, then we support that with function. So, if the individual is completely independent, that will be your mild cognitive impairment if they do have cognitive deficits. And if they have mild changes, like, you know, we talk about the higher-order function, so probably some difficulty with managing finances, but they can still do it, they just need a lot more help, then we're thinking of that sort of early stage.

And then we have a conversation about, okay, what next? In some people, they really want to try the disease-modifying therapy, they've heard about it, and that's why they're presenting, and then we can engage in a conversation about, okay, yes, clinically they appear to be eligible, and then we will refer them on to a specialized center. So, I know across the country, different provinces are creating a navigation pathway so that it's very clear to primary care how we—how we can refer up to the specialist clinics where they can have the laboratory and the diagnostic imaging to confirm the diagnosis.

Now, for those who are clearly not eligible, and this could be for many things—people on anticoagulant therapy, people who are a little bit more advanced in their dementia—will still have—encourage the conversation on risk factor modification. I always say that to promote cognitive and functional resilience, there's a lot that we can do. Things like engaging in physical activity, engaging in socialization, addressing those modifiable risk factors we talked about can still delay the progression of cognitive impairment and promote functional resilience. So, and that's why I said this is an opportunity because you may not qualify for lecanemab, but we can talk a lot about some of these non-pharmacological interventions that we can do.

And you asked the question about therapy, and so if this is that mild to moderate stage of Alzheimer's-type dementia, especially that moderate stage, and they don't qualify for lecanemab, and they do have some affective mood symptoms, we do have the cholinesterase inhibitors that we can talk about. And so again, if there are no—there are no contraindications, so significant heart disease or bradycardia, we can consider putting people on cholinesterase inhibitors, which has been shown to have some symptomatic benefit, because it helps with those affective symptoms like apathy, anhedonia, anxiety. Some of the symptoms that we see in mild to moderate stages of Alzheimer's-type dementia can respond to cholinesterase inhibitors.

Dr. Mojola Omole:

Thank you so very much for joining us today.

Dr. Vivian Ewa:

Thank you for having me. Okay.

Dr. Mojola Omole:

Dr. Vivian Ewa is a care of the elderly physician based in Calgary, and she is a clinical associate professor in the Department of Family Medicine at U of Calgary.

Dr. Blair Bigham:

So, Jola, how do we take the fear and the emotional desire to do something about Alzheimer's away and focus on the data here? Because I'm getting the impression that the data for lecanemab isn't that strong, the safety profile is a little bit hazardous, and the cost is pretty prohibitive.

When you package all of that together, I don't know, I think Vivian has some good points that we should direct our efforts elsewhere in preventing and treating Alzheimer's.

Dr. Mojola Omole:

I would say that maybe what it's showing us is that we're still at the beginning stage in terms of coming up with therapeutics for it. That doesn't mean that 5, 10, 15 years from now this will be a different conversation.

But now, what we should focus on is what Vivian talked about, are the preventative strategies and some of the management strategies of those who are living with dementia.

Dr. Blair Bigham:

Yeah, and maybe even more than that, getting back to the foundations and the basic science around Alzheimer's. I was so curious that although amyloid levels did drop with lecanemab, the benefit just wasn't there in the numbers, right, in terms of a clinically significant difference, it seems.

What else is going on with Alzheimer's? Maybe there's still underlying mechanisms that we don't understand, or maybe we just have to get to it way sooner before it's clinically apparent.

Dr. Mojola Omole:

Well, it seems that to even use the drug, it's such a narrow window of those who are eligible for it, being early, and also just having to be like the perfect candidate. So it might just be that we need more development in terms of this drug.

Obviously, neither one of us are part of the care of the elderly, but I still have hope that something can come out, because families and people who are living with Alzheimer's really want something to not just prolong life, but improve the quality of life of those who are living with dementia.

Dr. Blair Bigham:

Maybe this is sort of like 7 or 10 years ago with checkpoint inhibitors and immunotherapy for cancer where it was new and yes, there was a little benefit, but people were wondering if it was worth the cost and the hassle and the side effects. And now—I mean, now look at how cancer care is, revolutionized everything.

Dr. Mojola Omole:

100%, yeah.

Dr. Blair Bigham:

Maybe Alzheimer's is next for a revamp and a bright outlook.

Dr. Mojola Omole:

I cannot agree with you more. 

Dr. Blair Bigham:

That's it for this episode of the CMAJ Podcast. Thank you so much for listening. Please like, share, comment, rate, and download our podcast so that we can get the message out.

The podcast is produced by Podcraft Productions. Neil Morrison is our producer. Catherine Varner is a deputy editor at CMAJ and senior editor of the podcast. I'm Blair Bigham.

Dr. Mojola Omole:

I'm Mojola Omole. Until next time, be well.