An Alzheimer's breakthrough?

The past few months have been full of Alzheimer's optimism: new ideas that could prevent the disease from taking hold, medications that seem to slow it down, and an experimental surgery that might even be able to reverse its progression. It's a lot of hype. Should we believe it? Guest: ⁠⁠Dylan Scott⁠⁠, senior correspondent at Vox To watch this episode on video, find us on ⁠⁠⁠Netflix⁠⁠⁠! For show transcripts, go to ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠vox.com/unxtranscripts ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠For more, go to ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠vox.com/unexplainable ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠And please email us! ⁠⁠⁠⁠[email protected]⁠⁠⁠⁠We read every email. Support Unexplainable (and get ad-free episodes) by becoming a Vox Member today: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠vox.com/members Learn more about your ad choices. Visit podcastchoices.com/adchoices

• 0:01Speaker 00

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• 1:23Speaker 01

  There are these almost surreal videos coming out of China.

• 1:27Speaker 02

  This is a gentleman, 76-year-old, who was diagnosed with late-stage Alzheimer's disease.

• 1:34Speaker 01

  Alzheimer's patients who had trouble even communicating. They're getting this experimental surgery and they're answering questions.

• 1:44Speaker 02

  Observe how he will be sitting down unassisted.

• 1:48Speaker 01

  They're talking like they used to.

• 1:51Speaker 02

  He now had coherent speech.

• 1:54Speaker 01

  They're recognizing family members again.

• 1:57Speaker 02

  And in the second video, he was singing, and singing required higher brain function than just talking.

• 2:05Speaker 01

  These videos are getting so much attention because for a long time, there's barely been any progress in Alzheimer's research. There have been false starts, there have been dead ends. And Alzheimer's is this disease that doesn't just attack your body or your health. It doesn't just kill you. It steals your identity. But recently, it seems like things are starting to shift. So I called up Dylan Scott. He's a senior correspondent at Vox, and he's been covering Alzheimer's for years. I wanted to ask him about these kind of shocking videos. And I also wanted to take stock of where we are right now on Alzheimer's research.

• 2:50Speaker 01

  Turns out, there's actually good news. After years of stalling, we're starting to make real progress. But today, on Unexplainable, what does all this progress actually mean for people living with Alzheimer's? And are we any closer to a real cure?

• 3:29Speaker 01

  Dylan Scott, welcome to the show.

• 3:30Speaker 03

  Thanks for having me.

• 3:32Speaker 01

  So we're talking about Alzheimer's today, and you've been reporting on it for years. When did you first start digging in deep here?

• 3:42Speaker 03

  So my first big story on Alzheimer's was about five years ago. And what was happening then, it was a really dark time for Alzheimer's science. It'd been decades since a new treatment had been approved for the drug. We didn't have anything that could actually like slow the disease down or even stop it or reverse it. The only treatments we had basically gave you a couple of months of relief from your symptoms, but then after that wore off, it's like you were right back to your initial trajectory. And then about five years ago, there was this drug that was approved by the FDA, but it was really controversial. The FDA's scientific advisors had actually said it shouldn't be approved because the

• 4:27Speaker 03

  evidence of its effectiveness was not very strong and the evidence of serious side effects was pretty high. But the FDA went ahead and approved it anyway, and immediately it was like a mess. And it was, it was really a harrowing moment for, for the community because it was like this emotional whiplash of like, at first it seems like, oh, we've got what we've been waiting for, something that can slow down Alzheimer's disease. And then almost immediately, it was like it was yanked away from these people. And this all happened in a context of like, you know, it'd been decades. We hadn't really made any, seemingly any progress. And at that time, scientists were really questioning like, do we have Alzheimer's disease completely wrong?

• 5:09Speaker 01

  Okay, but you just wrote this piece where you said, believe the hype about the latest Alzheimer's breakthroughs. What, what are the breakthroughs? What's the hype?

• 5:17Speaker 03

  Yeah, trust me, I was as surprised as anybody to be writing that story. So there were a couple of things that happened in the years between 2021 and a couple of weeks ago when I wrote this story. We did have some new treatments that like you can be prescribed tomorrow if you get diagnosed. We have exciting new ideas to prevent Alzheimer's disease from ever taking hold in the first place. And, you know, who knows? We've also got this experimental surgery that's now, you know, upended our understanding of what might be possible in terms of treating this disease. So it's like, we haven't cured it. We're not there yet. But there's, I think, yeah, a real belief now that maybe five, 10, 15 years down the road, that Alzheimer's could be a, a treatable disease like many others, rather than this,

• 6:01Speaker 03

  you know, boogeyman that's like, it's coming for you. When you get it, you're going to totally lose your sense of identity and eventually it's going to kill you. That has been the paradigm for decades. And now it seems like there's a real possibility that we could break that and make Alzheimer's a treatable disease.

• 6:18Speaker 01

  Okay, so before we get into all this new, exciting research, can you just give me like a basic explanation of how Alzheimer's works in the brain or how we think it probably works in the brain?

• 6:31Speaker 03

  Well, and I think it's important to emphasize how we think it probably works.

• 6:35Speaker 01

  Okay, like there's a lot we don't know, I imagine?

• 6:37Speaker 03

  There's still a lot we don't know.

• 6:39Speaker 01

  Yeah.

• 6:39Speaker 03

  But the short version of it is, as you get older, you'll start to accumulate in your brain something called beta amyloid plaque, which is basically this peptide that your brain and your body has naturally that does perform important functions. But it starts to like congeal and stick together and form these like clumps of plaque that then start to disrupt your brain's function. At the same time, you develop these tangles of these tau proteins, which is another thing that like, again, your body does need and uses in a productive way when you're younger. But it starts to create these tangles that likewise start to further compromise your cognitive function.

• 7:20Speaker 03

  This all may be supercharged by inflammation and like vascular deterioration inside of your brain. But it seems like basically as you get older, these stuff starts to accumulate in your brain that starts to disrupt your brain signals and therefore you start to experience the symptoms of Alzheimer's.

• 7:38Speaker 01

  And I imagine a lot of this is still unknown because we're still so far from curing this, right? If we had a better

• 7:44Speaker 03

  Very much.

• 7:45Speaker 01

  clear explanation of exactly how this works, we would be able to have better treatments or better interventions.

• 7:52Speaker 03

  Right, it would be simple.

• 7:53Speaker 01

  Okay, so, so let's talk about some of the recent breakthroughs, the, the good news here. Tell me about what we've learned recently about preventing Alzheimer's from happening in the first place.

• 8:02Speaker 03

  Yeah, I think there's, there's a few different elements to this story. On the one hand, like if we think about those risk factors, you know, it's age, genes, but then it's like lifestyle and behavior. And so I think we're learning more and more that the better you take care of yourself early in your life, especially when it comes to like your cardiovascular health, the more likely that might be to pay off in either delaying or ultimately preventing the onset of Alzheimer's disease.

• 8:29Speaker 01

  Exercise is good.

• 8:31Speaker 03

  Exercising, eating well, stuff like that. On top of that, we're also identifying some frankly surprising treatments or therapeutics that might actually also be effective in preventing Alzheimer's disease. The one that I've written about and that's gotten some, a fair bit of attention is there seems to be an association between getting the shingles vaccine.

• 8:54Speaker 01

  The shingles vaccine?

• 8:55Speaker 03

  The shingles vaccine.

• 8:57Speaker 01

  Is related to Alzheimer's?

• 8:58Speaker 03

  We don't exactly understand how, which again, goes back to this idea of like, we're trying to solve a disease that we don't totally understand. But you had like one generation of people who did not get the shingles vaccine. And then you had, you know, even people who were just a day older or a year older did get the shingles vaccine. And they found it actually does look like if you get that vaccine, it reduces your chances of developing Alzheimer's. Now, why that might be?

• 9:25Speaker 01

  Yeah.

• 9:25Speaker 03

  I talked to scientists about it. They're not totally sure. There's a few different possible mechanisms. It may be that getting that vaccine, especially later in your life, helps to like reduce some chronic inflammation. It could be just in general that the shingles vaccine like invigorates your immune system at this period in your life where it's generally declining.

• 9:45Speaker 01

  Just invigorates you.

• 9:46Speaker 03

  Yeah, so maybe that's why. We're not totally sure. You know, I do think there's still some question about like how strong the effect actually is, but it's at least like evidence of something like a really commonly used vaccine that like for our generation of people who got chickenpox and don't want to get shingles, you should probably get the vaccine anyway because shingles seems horrible. But it may also have this secondary benefit of reducing your risk of Alzheimer's disease.

• 10:16Speaker 01

  Tell me about some of the treatments we have. Like, if you already have Alzheimer's, what have we gotten in the last few years that can help you?

• 10:23Speaker 03

  Yeah, so there have been two new drugs approved that are available to patients right now. Like, if they walk into a clinic and get diagnosed. Those drugs are called lecanumab and donanumab. And the way they work is they target those amyloid plaques in the brain. They also come with a reduced risk of those serious side effects, although there is still some risk of brain bleeds and a handful of people have died after taking these drugs. And, you know, even scientists will acknowledge to a layperson, it may not be that obvious that these drugs are working. Because you are, you're, you know, if you're the patient or if you have a loved one, like, they're still going to decline.

• 11:04Speaker 01

  So it seems like these are not making anyone better.

• 11:08Speaker 03

  Right.

• 11:08Speaker 01

  They are just making them get worse slower.

• 11:12Speaker 03

  Exactly.

• 11:13Speaker 01

  Which is not nothing.

• 11:14Speaker 03

  Which is not nothing. And again, the ultimate hope is like, OK, for somebody who's already started to experience symptoms of the disease, maybe the best we can do for them with these drugs is slow it down. But it's a starting point. And again, these are things that we never had before, that we never would have been able to offer something that we could say will slow down the disease. And now we can.

• 11:37Speaker 01

  What about this big, exciting Chinese surgery? Where these videos have been coming out that show patients actually getting better?

• 11:46Speaker 03

  Yeah, so we've seen some big reports in the last year from Science and Nature, you know, two of the leading scientific publications we've got, about this surgery. And the gist, as I understand it, is the surgery creates this drain in your brain that allows that amyloid plaque and those tau proteins to drain out, clear them out, which is the same thing that these drugs are trying to do. And there have been some experiments with this surgery, and they've been presented with these videos, these before and after videos that are super compelling.

• 12:19Speaker 04

  You live where?

• 12:20Speaker 05

  He's a little unhappy. He's not saying anything.

• 12:22Speaker 04

  He's not saying anything?

• 12:23Speaker 03

  One of the ones I've seen is a woman who, you know, somebody asked her what her name is. She doesn't know. She doesn't really talk at all. And then in the after portion of the video, she's talking, she recognizes her loved one, she's doing some household chores, helping her family prepare a meal. Like, she seems like a totally different person in the after video compared to the before video.

• 12:46Speaker 01

  Yeah, when you saw these videos, what were you thinking as someone who's reported on this for years with, like, barely any progress?

• 12:55Speaker 03

  It was weird. You watched the videos and you read the descriptions in these nature and science stories. And it was like, oh, my God, like, is this the thing? Like, this is what everybody's been waiting for. They've been waiting for my grandma can't even identify me to grandma knows my name and can take care of herself around the house.

• 13:14Speaker 01

  Yeah.

• 13:15Speaker 03

  I immediately went to like, can I trust this? Can I actually believe this? And not only because, like, you know, it hadn't been verified by any, you know, scientists in the United States or Europe or anything, but also just because we've been through this before, where it seemed like we had something really promising only for it to end up fizzling out. And I immediately wondered, like, is this for real?

• 13:39Speaker 01

  Yeah, are the videos real? I mean, are they verified? Is it possible that any of these are, like, faked?

• 13:46Speaker 03

  I don't know. And I do think that's the concern, because again, this is a field where there's been accusations of fraud in the past that has derailed research. It is obviously like, everybody wants to find the cure for Alzheimer's disease. So maybe that creates a temptation, you know, to present fabricated findings. I don't know. There's also been controversy within China about the scientist who pioneered this technique. He's under arrest. There's been some vague accusations of financial fraud.

• 14:15Speaker 01

  So he, wait, he's under arrest for fraud, not for something related to this surgery?

• 14:20Speaker 03

  Not related to the surgery, although there's also been reporting out of China that, like, Chinese authorities have tried to crack down on the surgery, whether that is like, because it hasn't been validated, whether that's for other, even like, political reasons. I mean, the fundamental problem here is there is a bit of like an iron curtain between like, Western and Chinese science. It's obviously hard to know, like, exactly what's going on within China, just because of the larger geopolitical situation. And so I think the scientific community in America and Europe has seen these videos and been like, well, this is at least superficially really compelling. The sort of underlying theory of the surgery makes some sense. And so what's happening now is researchers across the United States,

• 15:05Speaker 03

  and I mean, this is literally like, within the last year. So it's going to take a while before we find out what happens. But they are starting to set up their own studies to perform the same kind of surgery and see what they find.

• 15:17Speaker 01

  Like replicate it?

• 15:18Speaker 03

  Exactly, doing those replicative studies that are so important in the scientific method. So we'll see how that turns out. I know at least one of them is starting to recruit patients. But I mean, yeah, it's just, it's really intriguing. But it's sitting here today. It's really hard to know what to make of this experimental surgery. And the only good news is we should find out more soon as other scientists try to do the same thing.

• 15:44Speaker 01

  So what are patients supposed to do when their options are get worse slower or wait around for an unverified experimental surgery that may or may not work? We'll get into all that in a minute.

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• 19:15Speaker 00

  One of the most influential studies in Alzheimer's research may have been the Unexplainable podcast.

• 19:22Speaker 01

  You know, we've done episodes on Alzheimer's on our show in the past. We've talked about how medications were approved and they didn't really help, or there were, you know, these researchers that took us down what seems like maybe the wrong road. Maybe there was fraud involved. Is there something about Alzheimer's, like just how horribly bad this disease is that makes people, family members, researchers act kind of desperately in these sort of, I don't know, maybe unethical or irresponsible or even fraudulent ways?

• 20:05Speaker 03

  I do think there's enormous pressure to deliver. I think that is true. And like, I don't want to get inside of the head of somebody who committed research fraud or something like that. But I think back to where we started with this drug that was approved by the FDA, but it was really controversial. The science seemed pretty clear that this is not a drug that by normal standards, we would approve. And yet, the FDA went ahead and did it anyway, because I think what's implied there is they want to offer people something. Like, again, this is a disease that's 100% fatal, even if there is a risk of serious side effects, like, you know, these may be people who feel like that risk is worth it, because the alternative is just, you're going to keep getting worse, and you're eventually going to die

• 20:48Speaker 03

  anyway. Some of these things are much more fraught with Alzheimer's compared to some other diseases, because of just the mysteries of the mind that complicate the scientific process here, the lack of progress for decades, and just the fact that like, it's become, it is becoming more and more common, because the population is growing, the older population is getting bigger.

• 21:10Speaker 01

  Yeah.

• 21:11Speaker 03

  Right now, sitting here today, there are 57 million people with some kind of dementia. Alzheimer's is the most common form of dementia across the world. That number is expected to triple by 2050. And so, again, I think that really adds to like, the pressure to try to get something done. Because it's like, not, you know, there's obviously like, the sort of human cost of those numbers. But those numbers also exact a really serious financial toll. Healthcare spending increases, obviously, when, when somebody gets diagnosed with Alzheimer's disease. Like, we have all of these reasons to want to try to figure this out. And I do think that may put pressure on researchers and scientists to convince the FDA to approve a drug that its

• 21:54Speaker 03

  scientific advisors told it to reject, for some of these researchers maybe to fudge things a little bit, just to try to move the story forward. I think this is such a unique disease space.

• 22:06Speaker 01

  Yeah.

• 22:07Speaker 03

  And that's part of the reason it's been so hard to crack. And that may explain some of the unsavory behavior that we've been talking about. But, you know, hopefully, a lot of that stuff is in the past. And we've now, we've now found a path, or multiple paths, to making things better.

• 22:24Speaker 01

  Yeah, it's interesting, because we talk so much about humility and responsible science on our show. And I try to imagine what it would be like to be a family member of someone with Alzheimer's. Like, I don't have anyone in my immediate family with Alzheimer's. I've had friends with family members with Alzheimer's. And I'm just imagining how desperate that would feel. And if someone is like, oh, there's no phase three trial of this drug, don't use it.

• 22:52Speaker 01

  And the person is like, well, what do I have to lose? Almost.

• 22:56Speaker 03

  Exactly.

• 22:57Speaker 01

  And I guess I wonder, I wonder if you've talked to any patients or family members of Alzheimer's patients who've expressed anything like that to you, of just what it is like to sit in this space of unknown, problematic data, controversial treatments? Like, what is it like to be in this world where there is no good option?

• 23:25Speaker 03

  Yeah, I mean, I think about, I talked to a woman named Randy Epstein, who described like, what her mom went through when her dad was diagnosed with Alzheimer's disease.

• 23:35Speaker 07

  I think a lot of people who have loved ones with Alzheimer's say they experienced two deaths. You know, you're, you're with someone who is a shell of the person that they used to be. And then, years later, you bury this physical person that you were with.

• 23:54Speaker 03

  You know, I keep repeating this idea of like, you know, you lose your identity. But it's like, imagine, like, in a marriage, especially a long term marriage, like, you kind of become one unit.

• 24:04Speaker 07

  My mother was the primary caregiver for my father. I mean, that's basically all she did in, in their retirement together, was she was by his side all the time and caring for him. I think it's really hard when you've been married to someone who's your equal, or been with someone or partnered, and, and you see their decline. How can you not try something?

• 24:30Speaker 03

  You are saddled with the burden of trying to take care of this person who is, you know, doesn't recognize you as much anymore, doesn't remember the, maybe some of the, these important moments in your life over time, who eventually, like, can't take care of themselves. You know, I even think about my grandma. And it's like, I remember her before the dementia really set in. And she didn't have Alzheimer's, as far as we know, to be clear, but she had just dementia from aging. But like, the last five years of her life was, again, this sort of like, will she, won't she remember me, or my family and stuff. And it's just like, that's what kind of lodges in my brain when I think about her, as much as I hate that. But if it's a parent, or a partner, somebody who you've really lived your whole

• 25:13Speaker 03

  life with them, like, always having it together, you depended on them for things, to suddenly have that taken away. I mean, I don't, I just don't think there's anything like it. And that's certainly been my experience in my own life, and the experiences of patients that I have talked to. And so that's why I try, you know, I keep returning to the topic. And while I admit that, like, I want to feel optimism, because I don't want anybody to be put in that kind of situation.

• 25:40Speaker 01

  Yeah, I mean, that just makes me think about the problem of false hope. Like, given that this is so horrible, and people are so desperate. You know, you wrote this article years ago, saying, like, don't believe the hype. And now you're saying, believe the hype. It feels, I don't know, do you feel like things have really changed?

• 26:03Speaker 03

  I take optimism from a few different places. Like I said, we've got actual drugs now that are more effective and safer. You know, I called this one doctor at Penn, who five years ago was not optimistic. And sitting here today is like, the difference between then and now is revolutionary. Like, patients come in to the clinic now, and there is real hope and optimism that didn't exist before.

• 26:25Speaker 01

  Wow.

• 26:26Speaker 03

  But you want to be clear about, like, where we've been, and where we're at, and where we might be going, and all the things that could go wrong along the way. That's why you've heard me say, multiple times in our conversation, like, with these drugs that we do have available right now, a layperson might not really notice, you know, the slowing of their loved ones' cognitive decline. With these, the stuff that's in development, like, it's exciting. There's been promising preliminary results. But like, the, the default of any drug development is, most candidates are going to fail. So a lot of these things that people are optimistic right now, like, a lot of them probably aren't going to work. But if some of them do, then that's still going to represent real progress. And both of those things can be true at the same time.

• 27:11Speaker 03

  And likewise, you know, again, with like, the experimental surgery, you know, it's exciting, it's really intriguing. But I want people to understand that, like, it's going to be a long path to figuring out whether that thing really works or not, because we have to do all this replicative work. It's hard, like, in our current information ecosystem, to deliver that kind of nuance. But I do think that we are in a meaningfully different place today than we were five, 10 years ago.

• 27:38Speaker 01

  It sounds like you're saying that there's good news. Caveat, caveat, caveat. There's a lot of reasons it might not be so good. But what you really need to understand is just how horrible this is, and how little progress we've made. So even if we have these little bits of good news, they're just so incredible relative to how hard it's been.

• 28:01Speaker 03

  Exactly. Like I said, five years ago, it was like, nobody was even sure we even understood the basics of Alzheimer's disease. And I don't think that's true anymore. I think there is a little, there's more widespread agreement that it's this multifaceted disease that has these different elements contributing to it. And that alone is a stronger foundation for the future of Alzheimer's science and research than we had five, 10 years ago. And so that, even just that, is, I think, a reason to be more optimistic today than we were previously.

• 28:37Speaker 01

  All right. Dylan Scott, thanks so much for, for taking the time to chat.

• 28:41Speaker 03

  Thanks for having me.

• 28:47Speaker 01

  If you want to see this episode on video, check us out on Netflix. This episode was produced by Valerie Schenckman and me, Noam Hassenfeld. It was edited by Joanna Solotaroff. Our video editor is Jacob Reynolds. Our animator is Kareem Karia. Our fact checker is Melissa Hirsch. And Meredith Hadnath runs the show. Mixing and sound design from Christian Ayala, music from me. And Bird Pinkerton woke up with a start. The beep beeper was going crazy. She looked toward the end of the subway car, and she saw the door rattling. The door burst open. And she saw a giant wing.

• 29:28Speaker 01

  Thanks, as always, to Brian Resnick for co-creating the show with me and Bird. If you have thoughts about the show, we would love to hear from you. Please email us at [email protected]. Or if you'd like to support the show, you can join Vox, become a member. Just go to vox.com/members. And if you signed up because of us, let us know. We'd love to hear it. Unexplainable is part of the Vox Media Podcast Network, and we'll see you right back here next time.