In Good Health: The Alzheimer’s Research Revolution

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0:22A diagnosis of Alzheimer's disease for you and your family is a turning point. What the future will hold, what symptoms will happen, and when. It's something about 7.5 million people in the U.S. currently are dealing with. And every year, around half a million more receive a diagnosis of Alzheimer's disease or another less common form of dementia. As the population gets older, with more baby boomers aging into their 70s and beyond, we expect that figure will rise to around 1 million Americans diagnosed every year. Yes, I said 1 million new diagnoses per year. For decades, researchers have struggled to understand these brain diseases, what causes them and how to treat them.

1:07There's still a lot to learn. But when it comes to testing and treatment, particularly for Alzheimer's, there have been significant advances in the past few years. Taken together, they start to look like a revolution in dementia care. Could this moment be an inflection point for how we treat dementia and improve the quality of life for patients and their families? and how close are we to stopping these devastating diseases in their tracks? I'm Naila Boodoo, in for Jen White, and you're listening to the 1A podcast. We get into all of that for this installment of our series, In Good Health, where we put your questions to the experts.

1:43That's right after this.

1:48This message comes from Mattress Firm. Sleeping hot can ruin your night. Mattress Firm's sleep experts can match you with a temper breeze designed to deliver cooling comfort for hot sleepers. Visit Mattress Firm and upgrade today. Restrictions apply. See store for details. This message comes from Mint Mobile. If you're tired of spending hundreds on big wireless bills, bogus fees, and free perks, Mint Mobile is for you. Shop plans at mintmobile.com slash switch. Taxes and fees extra. See Mint Mobile for details. The last time Antonio Mays Sr. heard from his son, It was in a note the 16-year-old left in the family's garage.

2:29He told me he was going to make me proud. Antonio Jr. left home to join a protest in Seattle. A week later, he was shot and killed there. I need some arrest made, justice for my son. Listen to We Keep Us Safe on the Embedded podcast from NPR. Let's get started by meeting our experts. Joining us from New York City is Pam Bellick. She's a health and science reporter for The New York Times who covers neurological disorders. Pam, welcome back to 1A. Oh, thank you so much, Nyla. And joining us from the Alzheimer's Association International Conference in London is Dr. Jason Karlawish. He's a physician, author, and co-director of the University of Pennsylvania's Penn Memory Center.

3:10He also writes the column Neurotransmissions for Stat News. Dr. Karlawish, welcome back to you as well. It's a pleasure. Great to be here. One important reminder as we get started here, As with all installments of Ingun Health, this discussion is not a replacement for a diagnosis or discussion with your doctor or other medical professionals. Dr. Karlois, if we can start here with just a reminder of the terms, because sometimes the popular understanding of dementia can gloss over some important details. Can we start with what the difference is between Alzheimer's disease and other forms of dementia?

3:47Sure. Dementia describes disabling cognitive impairments, typically early on troubles with daily activities like managing money, medications, putting together a meal. A variety of different diseases cause dementia. One of those diseases is Alzheimer's, but it is not the only one. Another common cause is Lewy body disease, frontal temporal lobar degeneration, vascular disease, a newly described disease called late. All distinct pathologies, although have the common clinical manifestation of causing, in a word, dementia or disabling cognitive impairments. You also use the phrase cognitive impairment.

4:26What does cognitive impairment mean, and how is the diagnosis of, say, mild cognitive impairment different from a dementia diagnosis? Sure. As I say, dementia describes disabling cognitive impairments. A person needs help doing something else. Excuse me. Needs help doing something they used to do on their own, if you will. Now someone else or some other device has to step in, whether it's a caregiver or a better smartphone. In contrast, mild cognitive impairment describes cognitive impairments that are causing inefficiencies in daily life. It takes longer. You're making mistakes. You catch them.

5:03Maybe you need a little bit of help here and there. Oftentimes, persons with MCI are showing the earliest signs of the disease, like Alzheimer's or Lewy body disease. When we say cognitive impairment, what we're simply describing is the assembly of the different behaviors our brain does, memorizing new information, following a route, thinking and deciding. I should emphasize, of course, that dementia just doesn't simply cause memory problems, problems with cognition, but also troubles with emotion, mood, social cognition, and perception. Pam, I mentioned the idea that we might expect soon one million Americans per year to be diagnosed with dementia, what do we know about how likely it is for us in the U.S.

5:46to develop a form of dementia in our lifetimes? Yeah, so like a lot of things in this space, you're going to find varying estimates. The overall consensus is that there will be significantly more cases of dementia in the coming years, even if the percentage of new cases per year might be decreasing, And I can explain that. The estimates of kind of the number of cases increasing vary from something like going from about 7 million, which we have now, to about 14 million in 2060, so doubling by 2060. But there are some people who estimate that that's a bit too high and that it's going to be more like, let's say, 10 million.

6:37But everybody agrees that there will be more cases. And the main reason for that is that we have many more people who are living longer. And we have, as you mentioned, the baby boom generation. So you have a bigger denominator. And age is the biggest risk factor for developing dementia. You mentioned the rates. Can I just ask you about that? Because we do know there's actually some good news on that front that today's 60, 70, and 80-year-olds have developed dementia at lower rates than past generations. Do we know why that is? Yeah. So this is what's referred to as the incidence of dementia. So new cases per year, say, per a certain population.

7:18And that has been declining in the U.S. and other Western countries. And the good news, and that's good news, obviously. And the reasons that have been given are that partly our cardiovascular health is much better. You know, we have better treatments for heart disease, for vascular disease, and also preventing those conditions. And those are very big risk factors for dementia. There are other reasons that people give. The sort of overall education level in the United States has risen. over the last several decades. And education is, low education is a risk factor for dementia. And so the more educated are you, the more you're using your brain, that's considered a bit protective.

8:11Dr. Karlois, what is the link between cardiovascular health and dementia? What else is your take on what's driving down this rate? Probably links is the better word. The connections between vascular disease and the brain are many and multiple. It's a very hot and emerging area. A lot of our knowledge comes from epidemiology, namely robust associations between cardiovascular problems like high lipids, hypertension, adjacent problems like obesity, diabetes, and the development of dementia. Mechanistically, it's still a work in progress, but there's some emerging encouraging data from what have been known as the finger and pointer studies that efforts to target cardiovascular disease and risk factors in persons who have them can improve their performance on cognitive testing.

9:11It doesn't show that it reduces the risk of developing dementia. That's an extremely important point. But those studies, which are randomized trials, so they have that robust inferential data that you can get from randomized trials, together with a host of many epidemiologic studies, all point to the same message, which is what's good for your heart is good for your brain. Nonetheless, as I say, we don't have a definitive what's the mechanism. There's some promising studies that were just announced here as in progress or to be put together that are going to further test some hypotheses related to cardiovascular risk reduction.

9:48And I'm sure we can talk more about it. The use of GLP-1 inhibitors, namely, of course, the iconic drug ozemphec, although that's not the drug that they're going to pick. I don't know what it'll be. But yeah, a very hot area, the interaction between vascular disease and neurodegenerative diseases. Let's go to some questions that you all are sending in. Here's Jeff in Chicago. Hi, my name is Jeff. I live in Chicago. I'm 70 years old, in good shape, but concerned about my risk for dementia. My father had frontal lobe dementia, and my mother developed full-blown dementia, both in their 90s. But my grandparents did not have those problems.

10:25How do I know if I'm at risk? We are going to get into some of the advancements in testing in a moment. But, Dr. Karloish, what options are available to someone like Jeff who walks into a neurology clinic today? Well, he just said the four-letter word, risk. Everyone wants to know that, and I understand why. That is one of our great goals, which is to develop for patients like Jeff in Chicago risk calculators that are as solid and robust as what we have for cardiovascular disease and osteoporosis. We're getting there, but we're not quite there yet. Having said that, what we're good at right now is if you've got cognitive complaints and we pick up cognitive impairment, mild though it may be, we've got additional tests, particularly biomarker tests is what we call them, that can indicate whether you have the disease, Alzheimer's disease, or we have biomarker tests also for some of the other neurogeneral diseases such as low-body disease.

11:23So we're good right now with diagnosis of symptomatic individuals whose symptoms do translate into show us that they have cognitive impairment. For someone who's asymptomatic, worried, etc., we're still working on identifying what are those tests we should do. Having said that, there are promising genetic tests that we can order right now, but those don't predict your risk in the next five years as well. It's the biomarker test we really want to hone in on for people like Bob. We've been hearing from you. One of you texted, my 67-year-old sister was recently diagnosed with dementia. How was the best way to support her and her husband?

11:59How do I make her days more meaningful? We get into that and more after a quick break.

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13:27Still at it. Listen to Fresh Air on the NPR app or wherever you get podcasts. Back to this installment of In Good Health. Today, Alzheimer's disease and other forms of dementia and how this field of research and treatment is changing rapidly. Pam, we were talking about rates of dementia before the break. Are we seeing rates declining evenly among all demographic groups? Um, no. And there are demographic groups that are considered more at risk, among them black Americans, partly because they are living longer than they used to, which is good news. But also because certain risk factors, like the ones we were talking about before, cardiovascular risk factors in particular appear to be higher.

14:21Women seem to be more at risk than men, although the reasons for that are a bit unclear. One main reason people suggest is that women do tend to live longer than men, but there are some studies trying to explore whether there's something biologically different about women as well that increases their risk. And then one thing we didn't mention too much yet is genetic risk. So, you know, there's one particular genetic variant called APOE4 that is, you know, present in, you know, some percentage of Americans. And that does greatly increase your risk, particularly if you have two copies, which is rare.

15:14But I think it's about 10 or 15 percent who have one copy. You can correct me if I'm wrong on that, Jason. But so, you know, risk is not evenly distributed. Jason, was there anything you wanted to add on that, Dr. Karloish? Yeah, the APOE gene has been well described as a genetic risk for developing late onset Alzheimer's disease to be contrasted from early onset age under about 60, 65, where there are a variety of different genes that have been described. That's a much less common manifest cause of Alzheimer's disease compared to the late onset form. About 60 % of persons with Alzheimer's have an E4 gene.

15:57So not everyone with an E4A develops Alzheimer's, and B, not all persons with Alzheimer's are E4 gene carriers. So not all genetic. We get this email from Rich. I'm a 68-year-old male that was diagnosed with early onset of Alzheimer's last fall. I just recently began receiving the infusion drug Laquembe on a biweekly basis. Please talk about the research and effectiveness of the infusion drugs. Dr. Karlois, it's a great time to turn to treatments. There are two drugs, not just Laquembe, that have specifically been FDA approved in the past few years. Can you remind us what Lequembe and the other drug does, how they work, how expensive they tend to be?

16:41Sure. Yeah. Lequembe or lecanumab targets beta-amyloid, one of the two pathologies that cause cell death and dysfunction seen in persons with Alzheimer's. The other pathology is tangles of tau protein. And Lequembe and denanimab or consula is the other drug. So both target amyloid in the brain using an antibody-type mechanism that literally binds to the amyloid, different ways of binding between two drugs, and removes amyloid. And for both drugs, there's one well-done phase three trial that got them, earned FDA approval as treatments for Alzheimer's disease in either the stage of mild cognitive impairment or mild stage dementia.

17:29what we're seeing in clinical practice and the data that I'm seeing here presented in London is that the effects seen in the clinical trial pan out in clinical practice namely a change in the rate of decline so people progress slower than had they not been on drug and generally well tolerated with respect to their risks particularly risks of microscopic bleeds in the brain and some of in some cases those bleeds leading to angioedema or swelling They are disease-modifying, meaning they're targeting the disease and changing the rate of progression. We have not had drugs like that until both those drugs were available.

18:07And in that sense, I would say the word revolution is quite appropriate to describe them. Pam, there are a lot of studies being done on Alzheimer's. We were just hearing Dr. Karlawish talk about these two drugs in particular. There's more than 150 drug candidates in the pipeline that researchers are studying. What is the broad goal here? Where are you seeing from your reporting where researchers in this field want to get to in the next few years? Yeah, well, I think the overwhelming goal, and this is probably not achievable in the next few years, but it is potentially on the horizon, is for Alzheimer's to become a disease like heart disease or diabetes, where you can assess people's risk before they have symptoms, and ideally give them some kind of treatment before they develop symptoms to either delay or ideally prevent the onset of cognitive decline.

19:19So that is the holy grail. There are trials going on right now, which we actually expect to see results from in the next, one of them probably in the next year, the other one probably in a couple of years. which could get us closer to that goal. And those are trials of the two anti-amyloid drugs that Dr. Karloish mentioned in people who do not yet have symptoms of cognitive decline. So if those drugs show that they're effective in slowing or delaying the onset of symptoms in people who don't yet have symptoms, then that would be very, very significant because all of a sudden there is something to do for people who are at risk but don't yet have cognitive decline.

20:09And I think, you know, the widespread consensus is that with Alzheimer's, as with many other diseases, the earlier you can intervene with something effective, the better. So that's going to be something that I'm going to be watching. Dr. Karloch, what about, to Pam's point, the earliest you can intervene, the better, But what about for people who are currently not early stage? What are the treatments looking like in terms of medicine that's available for them? You mean persons in, say, the moderate to severe stages of disease? Correct, yeah. Yeah. So the two treatments that we discussed, licanumab and denanimab, are prescribed for persons with either mild cognitive impairment or mild stage dementia, which means when I see someone at the memory center, if they have moderate or severe stage dementia caused by Alzheimer's, verified by a biomarker, which I can now do.

21:01Unfortunately, you're right. I can't prescribe those treatments for them. They're not effective. And unfortunately, I don't have an equivalent treatment for those individuals to slow their disease. Not yet. There was a release yesterday, a very promising study of treatment to help address some of the more problematic symptoms that persons in those advanced stages experience, in particular persons in the severe stage, even close to the stage of being terminal, have agitation. And it can be a devastating symptom. And the study tested a well-formulated, meticulously formulated, I should say, combination of CBD and THC components of what we often refer to as medical marijuana, although it wasn't medical marijuana proper.

21:46Anyway, the study nicely showed notable reductions in measures of agitation in that population without sedation, which I think is really key. So that was encouraging to address one of the more problematic and devastating symptoms that patients and, frankly, families experience at the late stages of the disease. Could I go back to talk about the prevention space too, by the way? Absolutely. Yeah. So the two drugs that are now currently prescribed for persons with MCI and mild stage dementia are being tested, as Pam said, in persons who have a biomarker-based risk of developing dementia, meaning they test positive on a blood test that detects the pathology of Alzheimer's.

22:33And the goal is, of course, to see if giving these drugs that currently are used for persons with MCI or dementia will slow down the pace with which they would go on to develop MCI. That's incredibly promising. I think if they work, and as Pamela mentioned, we should hear about one of them within about 6 to 12 months. The next step will be to come up with criteria to define who is at risk. Certainly that blood test will be part of that, but I would predict we'll also be looking at other criteria like age, perhaps the APOE test that was discussed earlier, maybe some other additional testing and or characteristics such as your gender.

23:12And so we must imagine not terribly far away, potentially a future where you at certain ages, based on other characteristics, the results of this biomarker test, you are eligible for therapy. That's, again, the word revolution should be used if we achieve that. And that's not that far away, at least to find out the results of those trials. We'll see. Sharon asks, why get tested and diagnosed with Alzheimer's when the treatments today offer very limited benefits, delaying the progression of the disease by only a few months? Pam, do you want to start with answering that? Yeah, sure. I mean, it's a great question.

23:51And I think the answer is that it really is up to the individual. I have talked to people who do not want to get tested for the reasons that the question seems to suggest. There's not much you can do. It's obviously a very stressful and devastating diagnosis. But I've also talked to many people who would like to know. and their reasons are it might help them plan their lives, change what they're doing, perhaps make a change in their work, retire sooner, it might help them discuss things with their family. And then in terms of what can be done, I mean, these are things that people probably should do anyway without being tested or not, But we were talking a bit about lifestyle factors, you know, things like diet, exercise, social stimulation, cognitive stimulation.

24:59There's, you know, better and better studies that are showing that lifestyle factors can help. They're not going to, you know, prevent decline completely. they're not going to, you know, be a cure-all, but they can help, you know, stave off the pace of decline. And also they can help with some of the symptoms that we were mentioning earlier, things like mood and agitation. You know, those kinds of things are part of the composite of, you know, the picture of dementia. And they can be very upsetting, not only for the patient, but for the family. So if you can, you know, somebody I think earlier was asking a question about how to support the, you know, a relative, you know, who just got diagnosed.

25:58And I thought that was such a great question because it recognizes that, you know, support is needed. And one of the ways I would answer that is try to provide opportunities to engage with that person, make their situation less isolating, less lonely, provide a little bit of respite for the spouse. All of those things, these are kind of small and maybe nuanced kind of steps, but they can help the real-world experience of both the patient and the family members. We heard from one researcher about the work he's leading looking at new ways to treat Alzheimer's disease. Dr. Adam Boxer is a professor in memory and aging at the University of California, San Francisco.

26:46He also directs their Neurosciences Clinical Research Unit, and he's one of the principal investigators leading a new five-year study funded by the NIH that will look at treatments that target tau proteins, which we've been talking about. Those are different from the amyloid plaques that are currently approved drugs target. His work, his study is now in the process of recruiting participants, and we are going to get into Alzheimer's funding later, but first, here's Dr. Boxer. We now have new approved treatments that work for patients with mild Alzheimer's disease that target the protein amyloid in the brain.

27:20Amyloid is an important part of Alzheimer's disease, but some people, in fact most people, can have amyloid in their brains for 10 years or more but have no symptoms of disease until another protein called tau starts to accumulate in the form of neurofibrillary tangles. We now have new therapies that look very promising that can also target the tau protein and might reduce the neurofibrillary tangles, which are really strongly correlated with the symptoms of Alzheimer's disease. This means that maybe if we added the tau therapies to the amyloid therapies, we would have the best of both worlds, and we might see a really large effect for patients with Alzheimer's disease.

28:13And maybe we could really either slow or completely stop their disease. Tau also can cause other types of dementia like frontotemporal dementia and progressive supranuclear palsy. So if we find a successful tau therapy that works for Alzheimer's disease, we might also be able to treat other forms of dementia with the same drug. Dr. Karlawish, you mentioned you're at this conference. I wonder if you can just briefly tell us before the break other things you're excited about looking at in terms of treatment. Yeah, well, following up on Dr. Boxer's remarks there, yesterday results of a study of a drug called D-R-N-A-S-R-N was represented, which targets tau.