#399 ‒ The evolution of Alzheimer's disease and dementia care: how early detection, personalized treatment, new therapies, and a multimodal approach are changing the landscape | Gayatri Devi, M.D.

“as are the two other drugs subsequently approved, Lecanemab, Leqembi, and Donanemab, Kisunla. All these three drugs reduce and eventually eliminate brain levels of tau. So that when you, the person's been on the medication for some time, there's no longer any plaque in the brain.”

“And one of the things that I unfortunately have discovered is the insurance companies, especially with Lecanemab, which starts at 10 milligram dosing right away, 10 milligram per kilogram, they will not reimburse patients if we start them at a lower dose and titrate them up.”

“But unfortunately, we haven't been able to do that with Lecanemab because it just starts at 10 milligram per kilogram. Yeah. Yeah. So we've had patients, Peter, who are 4-4 patients, who've had severe ARIA on just three milligrams of Lecanemab, three milligrams per kilogram, as opposed to the 10.”

“Alternatively, also, you know, for example, one of my younger patients who's on it for prevention, she's 51 or 2, and she's developed significant ARIA-E on both sides of her brain on 3 milligrams per kilogram of Lecanemab.”

“This young woman who's got 4-4 and three Lecanemab, three milligrams of Lecanemab, who has ARIA-E, which seems fairly refractory, I treat her with steroids as you would somebody who has cerebral amyloid angiopathy with the inflammation.”

“So Aducanumab, I can tell you exactly when. Aducanumab was approved in July of 2021. Oh, wow. It was post-COVID. Yeah. Yeah. Yeah. For some reason, I thought it was pre-COVID. But it was a very controversial approval in the scheme of things, because there was an advisory board to the FDA that recommended against approval.”

“There was a lot of brouhaha around it, but it was approved. And I actually was one of the first adopters of Aducanumab, because I thought that despite the controversy, I felt that if we could move the needle a little bit for patients with Alzheimer's, it was worth trying. So I started using it, and because the drug had a greater than 40% incidence of abnormal brain bleeding and brain swelling”

“What is the annual cost of Lacanumab and Aducanumab? They cost? The drugs themselves cost about $26,000, but then there's the administration fees, which can range, you know, sometimes in institutional settings, they can be as high as $10,000 just to infuse the drug, versus you go into an infusion center, it could be $400.”

“And this was one of, he was on Aducanumab. He was a 4-4 patient. He was in his early 60s. And he had been on Aducanumab, a slow titration, and he had gone up to eight milligrams per kilogram, and at month 19 or 18, he developed, on MRI, significant ARIA-E.”

“Donanemab, Kisunla. All these three drugs reduce and eventually eliminate brain levels of tau so that when you, the person's been on the medication for some time, there's no longer any plaque in the brain.”

“We titrate patients up very slowly. And in fact, recently for the drug Donanemab, which is a third drug in this group, they have the FDA has approved a slightly slower titration protocol than initially used because they too have noticed that a slower protocol is helpful in drastically reducing risk of side effects.”

“This is a very small change. And in fact, in the early data on Donanemab, there was really no change on the CDR sum of box scores between patients on drug versus patients not on drug. But I do believe that many of these patients had moderate to severe disease.”

“I have a pair of identical twins, and I take care of one of the two. And the one, she just, you know, she was on a monoclonal antibody, initially on Aducanumab, and then on Donanemab. And she did much better than her identical twin, who was in a facility. And my patient actually also had heart disease.”

“She went on GLP-1. but she also went on a monoclonal antibody”

“It's hard to imagine. So, tell me, what's on the horizon as far as the monoclonal antibodies? Like, where do you see, you know, with every drug, whether it be GLP-1s or statins or any drug, they always get better with subsequent generations. So, where do you see them going next? I think we're going to have drugs that are monoclonals that are able to, like, ameliorate”

“I believe so. I think the GLP-1s offer an advantage. And even the older drugs like metformin, you know, may offer benefit in this area. And so I do use it in my patients where I think it's necessary.”

“the other thing, too, is obesity is finally coming down in the United States, you know, thanks to GLP-1s. And I'd be very curious to see what happens as a result of that with so many diseases associated with the brain.”

“And if it's a large enough disruption, then you can actually have a massive brain bleed, and there are cases of death in such patients, particularly if they're on a blood thinner. We have patients who could be on a blood thinner for atrial fibrillation or something like that.”

“another condition who then have Alzheimer's disease and therefore are precluded from going on a monoclonal antibody because of the blood thinner, I recommend them getting a procedure like a watchman so then they can go off the anticoagulant and then get on the monoclonal.”

“and to this day I still have patients on a combination of a cholinesterase inhibitor, such as Donepezil, Galantamine, et cetera”

“we actually, years and years ago, did a double-blind placebo-controlled trial of Donepezil versus placebo in women going through menopause with cognitive impairment, and found a trend in 21 patients”

“And in the cases where you're managing the hormone, do you prefer a transdermal estrogen to an oral one given the other changes with the increase in SHBG and binding capacity and things like that?”

“I mean, I actually prefer transdermal in either a gel or a patch because, yeah, you have lower risk in my, for me, the big consideration is lower risk of strokes and venous clots.”

“You can also, in such women, use drugs like cholinesterase inhibitors, because the underlying mechanism of cognitive impairment is ultimately loss of acylcholine”

“and she had an artificial heart, And she was on Coumadin. And we still decided to put her on a monoclonal and watch her like a hawk,”

“kind of a heart problem that is the cause of the strokes. Right. I recommend a watchman so that they can then go off the anticoagulant medication, Eliquis, Xarelto, et cetera because many of these patients are at higher risk for falls just from their vascular pathology.”

“I still have patients on a combination of a cholinesterase inhibitor, such as Donepezil, galantamine, et cetera”

“She had, despite a negative DAT scan, she had been put on levodopa carbidopa, three, three tablets, three times a day of 25-100 at an academic institution for treatment, and she was eating presumable Parkinson's disease despite her negative DAT scan.”

“I know you and I have spoken about Obicetrapib and the profound impact it's having, at least in a pilot study, when you look at the biomarkers.”

“of Alzheimer's with just the blood tests alone. I mean, there are certain blood tests. The LumiPulse blood test, the Precivity blood test, the Quest AD blood test, the C2N assays. But all these are generally, all the blood tests are standardized against, for the most part,”

“stronger for the management of varicella zoster through the use of a shingles vaccine in individuals who have been previously infected, which of course, at this point, by the time you're 50, is virtually everybody.”