Scott Webb (Host): I'm Scott Webb. And today, we're discussing anti-amyloid agents in Alzheimer's and how these newer medications are helping patients to slow the progression of dementia. I'm joined today by Dr. Allison Hennigan. She's a neurology specialist with Carle.

Doctor, its so nice to have you here today. We're going to talk about anti-amyloid agents in Alzheimer's. And I can say those words, but I'm not sure what they all mean. So, great to have you here, great to have your expertise. I want to have you start by discussing the non-pharmacologic treatments for the different forms of dementia.

Dr. Allison Hennigan: Yeah. Absolutely. Thank you so much. It's great to be here. Dementia is a chronic illness. It is going to continue. There is nothing we can do to stop it. These anti-amyloid agents do not stop the dementia. And really, the key to therapy, the beginning of therapy, no matter what level of memory problems that you have is lifestyle modifications. So, this involves physical, mental, social, spiritual, nutritional activity. So, physical activity is one that has the best evidence for it. A hundred and fifty minutes a week of moderate exercise, which means if you're walking, great. You can still have a conversation, but you can't sing a song. So if you're walking and you can still carry a tune, then you're not walking fast enough. Mental activity, of course, learning something new: games, puzzles. Social activity can just be having a conversation with your spouse or a friend over dinner. We learned with COVID that social isolation can definitely cause dementia, any type of dementia to progress more quickly. Spiritual activity is just connecting to the greater creation around you. It doesn't have to be a faith tradition. It can be gardening or fishing. And then, nutritional activity, we recommend the MIND diet, which is a combination of the Mediterranean and the DASH diet.

Host: I like that, the MIND diet. That'd be a separate podcast. But yeah, I see what you mean, like, you know, lifestyle behavior on a variety of different levels, lots of things that folks can do to make life a little easier, a little better, but it's not going to cure dementia per se. So then, I want to have you compare and contrast the pharmacologic treatments for the different forms of dementia.

Dr. Allison Hennigan: So, non-pharmacologic are easy to do, they're cheap, and they have very few side effects, very few negative side effects. Most of the side effects are beneficial. Medications, not so much. So, medications that we use are—there are many, some of the medications that we use are symptomatic. And I won't get into those.

But the medications that we use actually for the memory problems have most of their evidence, if not all of their evidence in Alzheimer's disease. Now, Alzheimer's is the most common form of dementia, but it's not the only one. So, we use it off-label for other types of memory disorders as well. So, this would involve one type of medication that's called an acetylcholine esterase inhibitor.

So, that would be things like donepezil, rivastigmine, galantamine. I'll usually use donepezil more frequently unless the person is already on escitalopram, in which case that can prolong the QT interval, or there are QT prolongation issues anyway, and then I'll preferentially use the rivastigmine. Rivastigmine comes in a patch. The pill is dosed twice a day. Donepezil is dosed once a day, which is why I usually prefer it.  Galantamine, I just don't use all that often. As far as the other prescription medication that we've been using for a long time, mementine is what it's called. It is a glutamate antagonist. And we're not quite sure how that works, but it does seem to slow down the progression.

So, all of these medicines have been on the market long enough that they have generics available and should be relatively inexpensive. If the insurance is telling you that you need to pay $50 a month for them, then go to a different pharmacy.

Host: I see what you mean. Yeah. And it does seem to me, you know, having hosted these for a few years and had other, you know, Carle guests on and experts on, you know, that the science is just moving so fast—science, medicine moving so fast. And just wondering, maybe you can give us a sense at least, like what's the science behind these new medications for Alzheimer's disease?

Dr. Allison Hennigan: Those two classes that I mentioned are the old ones. The new ones are quite fascinating. They're called anti-amyloid agents. I call them amyloid scrubbers. But the idea is with Alzheimer's disease specifically. Now, these are medicines that are approved for Alzheimer's disease that we do not anticipate to work in other disorders.

So with Alzheimer's disease, there's a whole cascade of events that happens in the brain. , That cascade begins with the deposition of abnormal amyloid proteins in the brain. And so what happens is the, that amyloid deposition happens long before any cognitive symptoms show up. And then, it continues while cognitive symptoms start to develop, and then atrophy and tau deposition and all of those things kind of progress. So early stages, the theory is that if we clean out the amyloid at early stages, we can help slow down some of that process that is going to destroy the brain tissue. It does not stop the process that destroys the brain tissue, but it can help slow it down by about 30%.

Host: It just stands to reason then—not being an expert here—but it stands to reason, Doctor, that early diagnosis would be key, right? And maybe you can give us a of, like, as you say what happens to the brain happens long before perhaps the symptoms. So, how do we know to come in? Is it family history, genetics? Like, give us a sense of how we would know to be checked or diagnosed.

Dr. Allison Hennigan: Unfortunately, the medication is not approved for anybody who does not have symptoms, And so, really, if you have a family history if you start to notice things, if you start to notice that you're asking the same questions or telling the same stories, or you're having a conversation with your kid and she looks at you funny and says, "You know, we talked about that yesterday, right?"

Host: "We just talked about that, Dad."

Dr. Allison Hennigan: "We just talked about that." So, the little things, I would say the most important thing is to pay attention to the little things we as humans have a tendency to deny unless it is really negatively affecting our lives. And so, in this condition, it's really more important to say, you know, I need to at least ask the question. Because the sooner people come in, the more effective the medication is going to be for getting the amyloid out.

Scott Webb: Right. As you say, none of this is a cure per se for dementia, Alzheimer's, but it can slow it down. And we will take that, right? We'll take that for the win, at least where we are here, right, in 2026.

Dr. Allison Hennigan: Exactly. It's like it is the beginning. We're never going to cure Alzheimer's disease with a single event, never say never. But this is the beginning of a new realm of Alzheimer's treatment. That's really exciting.

Host: It is for sure. I feel like we're just scratching the surface here today, but I want to give you a chance here, Doctor, at the end. Any risks or benefits that folks should be aware of about these anti-amyloid agents?

Dr. Allison Hennigan: There are definitely risks. The biggest side effects to watch for are something called ARIA, amyloid-related imaging abnormalities. And the reason they're imaging abnormalities is because when you are on these medications, you have to get MRIs regularly to catch them early. If you catch them late, then that can be a huge problem.

So, ARIA. I call them amyloid scrubbers, right? And so, they're really cleaning the amyloid out of the brain. But if you've ever used COMET, cleaning with COMET, if you're clean the wrong surfaces with a COMET-like substance, then it can scratch it up and ruin the surface of the thing that you're cleaning. Same thing happens with the blood vessels of the brain.

And so we have to be very sure that the blood vessels aren't already damaged. And we have to be very sure that they're not likely to be damaged by our medications. And so, the way that we do that is we do an MRI of the brain beforehand, looking for any evidence of bleeding, significant evidence of vascular disease that would indicate that they're at higher risk of the bleeding and bruising in the brain that we see with ARIA. That MRI usually is done in a particular protocol so that we can take that MRI. And every MRI that happens after it gets compared to that first MRI. Preferably, it's on the same scanner, definitely in the same facility. So, the same people are looking at it and comparing apples to apples. So, that is how we discover it. Usually, it's asymptomatic. And we discover it with this cadence of MRIs that we have to do. So, that initial MRI is really very important.

 Another thing that we have to do is we have to prove that there's amyloid there. You can do that with a spinal tap or with an amyloid PET scan. But that's another thing that's required.

The final thing is APOE testing. So, APOE is a genetic variation that everybody has APOE, it's just a matter of which type of APOE you have. And there's 2, 3, and 4. And they're associated with Alzheimer's disease. But the more copies of 4 you have, the higher your risk of this ARIA response, the bleeding and bruising.

Right now, at Carle, we are not infusing people who have APOE4, two copies of APOE4, because that is an increased risk that we don't think is worth the benefit. Risk can be up to 40% in those patients, and the benefit is only about 30% of slowing down. But really, regular MRIs letting your doctor know, or letting the doctor know about any abnormal neurologic symptoms that you might have that might trigger an additional MRI. And also, if there are stroke-like symptoms, people who are on these medications absolutely cannot get any blood thinners. If they're already on blood thinners, they cannot get these medications because the risk of bleeding is too high.

Host: Okay. Like I said, I feel like we're just scratching the surface. It's great to have you on. Great to benefit from your expertise. I think I followed you all the way along.

Dr. Allison Hennigan: Oh, good.

Host: Yeah. I would love to stay on with you, but you've got things to do and, you know, folks can only listen for so long. But really, appreciate your time, your expertise. As you used the word earlier, you said amazing. And it is amazing. And I can't wait to see where things go. It's the beginning of something. These anti-amyloid agents. Great stuff. Thank you so much.

Dr. Allison Hennigan: Absolutely. Thank you.

Host: For more information and to get connected with one of our providers, please visit carle.org. And that wraps up this episode of Expert Insights with the Carle Foundation Hospital. I'm Scott Webb. Stay well.