The Megyn Kelly Show - A Deep Dive Into Alzheimer's and Disturbing New Scientific Findings, with Dr. Dale Bredesen, Dr. Matthew Schrag, and Charles Piller | Ep. 373

Episode Date: August 15, 2022

Meygn Kelly takes a deep dive into Alzheimer's with Dr. Dale Bredesen, Dr. Matthew Schrag, and investigative journalist Charles Piller, to talk about the history of the disease, disturbing scientific findings regarding Alzheimer's drugs and treatments, how research that advanced certain hypotheses has been called into question, the revelation about falsified images, how scientists in question are attempting to explain what happened, the investigative journalism that exposed this story and brought the doctored images in the Alzheimer's research to the public, the lack of NIH action after the news came to light, how the NIH is involved in funding this questionable scientific research, what we know about the scientists in question, conflicts of interest in the scientific community, the era of mainstream medicine failing us, what's really the cause of Alzheimer's, how to help improve brain health and stave off Alzheimer's, memory tests we can do to help ourselves, and more.Follow The Megyn Kelly Show on all social platforms:YouTube: https://www.youtube.com/MegynKellyTwitter: http://Twitter.com/MegynKellyShowInstagram:http://Instagram.com/MegynKellyShowFacebook:http://Facebook.com/MegynKellyShow Find out more information at:https://www.devilmaycaremedia.com/megynkellyshow

Welcome to The Megyn Kelly Show, your home for open, honest, and provocative conversations. Hey everyone, I'm Megyn Kelly. Welcome to The Megyn Kelly Show. Tomorrow, we're going to tackle the latest developments on this FBI search of former President Donald Trump's Mar-a-Lago home, and there is a lot to go over. A lot's happened since I was last on the air on Thursday, and I've got a lot to say about it. But today, we've got an amazing show for you on a different subject, and I'm really excited about this program. We've got the first in-depth broadcast interview with a whistleblower who discovered that one of the most influential studies in Alzheimer's research, may have been a fraud. It is not an understatement to say that Dr. Matthew Schrag's discovery has caused headlines

around the world. Every major media outlet has covered this. And if that turns out to be true, it means about a billion dollars in U.S. taxpayer money used for Alzheimer's research over the past 16 years may have been for nothing, not to mention if you know a loved one dealing with Alzheimer's, you know that it's a nightmare disease and we have no time to waste. So for 16 plus years, we may have been focusing our energy in the wrong direction if this seminal article and study was fraudulent. This disease affects roughly 6 million Americans, a number that's expected to double in the next 25 years, double. And there is no treatment that cures it. So what Dr. Schrag discovered about this seminal study is a very, very big deal.

He will walk us through what he discovered, what it means for Alzheimer's research, the pushback he's received, and whether he now fears for his career. Then we will be joined by an investigative journalist for Science Magazine who took a close look at the doctors who authored this controversial study, the funding they received, and what happened after Dr. Schrag, the whistleblower, notified the National Institute of Health of his troubling discovery. And then we will welcome back renowned brain health expert, Dr. Dale Bredesen. He has thoughts on all of this, what it means about medicine, and also specific steps that you can take today

if you would like to help boost brain memory. All hope is not lost if you become a sufferer of dementia. There are certainly forms of Alzheimer's that there's very little you can do about, but there are forms of dementia that you can help stave off and improve if you happen to become subject to them. But we begin today with Dr. Matthew Schrag. He's a neuroscientist at Vanderbilt University, and it's our pleasure to welcome him here to the program. Welcome, Dr. Schrag. Great to have you.

Hi, Megan. Thanks for the invitation. I'm looking forward to our conversation. Schrag. Great to have you. Hi, Megan. Thanks for the invitation. I'm looking forward to our conversation. Me too. And may I just say, I admire your courage and your willingness to just say what's real based on your own independent scientific findings, as opposed to what you know is going to go over well and what people want to hear. Yeah, I appreciate that.

I'm a physician and I see patients suffering with this disease day in and day out. And there really is no judgment call here. You have to speak the truth. So you are a very accomplished man in terms of your own medical history and your resume, neurology residency and fellowship at Yale, vascular neurology fellowship at Vanderbilt, board-certified vascular neurologist, assistant professor of neurology at Vanderbilt University Medical Center. And your research focuses on how cerebral amyloid angiopathy contributes to cognitive impairment in Alzheimer's disease. You're an expert in Alzheimer's. What causes it, what's likely to cause it, and so on. you're there at at Vanderbilt doing your thing in medicine, teaching, researching. And this all got started because, as I understand it, you got a call to take a look at this and see whether this is actually likely to help people

because it's been approved by the FDA? And a bunch of scientists were like, we don't we're not sure we don't we're not sure we like this drug. We're not sure this should have been approved. What do you think so far? Do I have my facts right? Well, I, along with quite a lot of other scientists, expressed some concerns about atcanumab over a year ago now. And I think that as a community of scientists, we're very committed to making sure that drugs that we offer to our patients deliver on the promise, especially if they're dangerous and especially if they're expensive. So that was my first exposure to national media was simply speaking out along with quite a lot of other scientists about concerns about Biogen's aducanumab. And that led to-

Okay, and that's also known as Adjuhelm? Correct. The trade name is Adjuhelm. Okay. So let me just, we're going to go through it in baby steps so people can follow. And fear not audience, because I have done the deep dive as a lay person so that we can i can walk us through this in a way i think everybody's going to get okay so um there was a july 2021 new york times article on adjahelm this drug it was approved by the fda and this thing attacks amyloids and there was there's just briefly explain what's an amyloid so 115 years ago when dr alz. Alzheimer's defined what Alzheimer's disease is, he saw two things happening in the brain.

One is the accumulation of huge numbers of what he called plaques, which we now know is formed of this little tiny peptide called beta amyloid, which is sticky and has formed giant clumps in the brain. And the second thing he discovered were tangles within the neurons that caused them to not be able to fire properly anymore. And so amyloid, the plaques, have been proposed to be the problem that starts off this disease. And the drug tried to remove those plaques. So just to stop you there, so what they found in the brain was amyloids or plaques and tangles.

And we knew that they were associated with Alzheimer's disease, that they were characteristic of Alzheimer's, but we did not know that whether they were a cause. That's the next step. Do the plaques that we find in the brains of deceased Alzheimer's patients actually cause Alzheimer's?

And that's a much bigger leap. And even right at this moment, we don't know the answer, but that's where our story's going. That's right. So in the early 90s, during the genetic revolution, when we started understanding the genetics of some rare forms of Alzheimer's disease, this became a leading theory that the plaques themselves were the driver, the thing that starts the process of neurodegeneration and Alzheimer's disease. Okay, so this drug, Adjahelm, which was by Biogen, the drug maker, was supposed to address these plaques. And yet a bunch of doctors, including yourself, were very critical

of this, saying the proof is not there that it does that. And the proof is not there that the costs are outweighed by the benefits. Now, as I understand it from the New York Times article, the FDA approved this drug despite a council of senior agency officials resoundingly agreeing two months earlier at the FDA, there was not enough evidence that this drug worked. And they wanted another clinical trial. They said otherwise people could be harmed. But then on June 7th of 21,

FDA greenlit the drug anyway, scathing rebuke from Alzheimer's disease experts like you, calls for an investigation into how that thing got approved. It cost $56,000 a year, this drug. And the FDA just defended itself saying, we didn't lower our standards. Look, we subjected it to what's called accelerated approval, where serious disease is faced with very few treatment options. It's basically like, you know, the long shot, the Hail Mary, and the drug flopped. Okay, so you were one of the scientists pulled in on there and you, again, spoke honestly and said, serious questions, serious questions.

And then a different group of scientists, I think, or maybe it's the same, came back to you about a different drug made by Cassava Sciences. Is that how you pronounce it? Correct. Cassava Sciences. This one's called Samufilum. Samufilum. Yeah called Samophilum. Samophilum, yeah.

Samophilum, okay. Now this one, once again, these scientists are concerned. It's got similar problems in that the early results seemed a little suspect. The FDA approved it to go forward to be tested in human beings, and these scientists were concerned that people were going to be harmed. This drug company was worth nearly five billion bucks last summer. So they were doing pretty darn well. And they wanted someone like you to take a hard look at that drug and see if in fact it should be used to treat Alzheimer's. So that's where our story really starts to begin. So tell us what happened of note while you were taking a look at

that drug. So this is outside of my work with Vanderbilt University. I was contracted by an attorney representing a number of scientists who had concerns that the data that was used to justify moving this drug into clinical trials had a pattern of artifacts in it that was concerning. And then one raised concerns that perhaps there was some manipulation of the data or research misconduct. And I was asked to come in and independently look at their concerns and to look at the papers more broadly and give another independent voice regarding what the basic science data looked like. And what we found was a pervasive pattern of these red flags. There's some limitations about what you can say just from published information. And so, it's very hard

to conclusively state that there's a fraud or that there's misconduct there, but certainly there is a pervasive pattern of things you wouldn't expect in the data. And I think journalists and photographers look at a lot of the visual images the same way we do. The data that this company was producing ends with a photograph of an experiment, and the photographs just didn't look natural. And that was the starting point for us to say perhaps this needed a closer look and that some regulatory bodies should make a priority to review this, especially with patients being exposed to the drug. So how does a doctor named Sylvain Lesny appear in your world in this time?

Well, it's almost happenstance. At the time, I was looking at ways of doing a forensic analysis on these images. And I encountered his paper, partly because it was a prominent paper, but some people who do research integrity work had flagged a couple of his other lower profile papers. And it just caught my eye that the images in his paper look similar to the ones I had been investigating. And just, like I said previously, didn't look natural. They sort of had the kinds of things that look like Photoshop type changes in them. And that prompted me to take a closer look, especially because as I reviewed his body of work, a number of his works were enormously influential. So his name, again, Sylvain, I don't know how you pronounce it, to be honest, Lesney, L-E-S-N-E, French guy, neuroscientist, associate professor at the

University of Minnesota. And he had sort of the mentorship of a very important doctor named Dr. Karen Ash, who's also a neuroscience scientist and professor at the University of Minnesota. She's a full professor. So this guy, Dr. Lesney, the French guy, but he's here in America, you start to see some of the images that he's been using in papers that he's been putting out over the past couple of decades. And they look, as my 11-year-old daughter would say, sus. They look sussy baka, as she might explain. And you start to dig a little deeper. And this guy, along with his

mentor, Dr. Karen Ash at the University of Minnesota, are the authors of the seminal study from 2006 on Alzheimer's and what causes it. And in particular, you know, we'll get it to exactly what their theory was. But basically, that paper that they wrote in 2006 has been like the genesis of studies on what causes Alzheimer's and how we should treat Alzheimer's ever since. And they've gotten billions of dollars in funding to pursue this line of research and so on. And what you basically said was this 2006 study they did together has got equally problematic images to the ones I found Dr. Lesney using in virtually every study he's been attached to ever since. Yeah, that's right. The 2006 was an interesting moment for the amyloid hypothesis because

it was one of the times when it was coming under the hardest scrutiny because the first clinical trials had started to fail. And so, the hypothesis was starting to be reformulated to focus on something called an oligomer. Instead of saying that the whole clump of sticky beta amyloid protein was the problem. They assumed that before you had a giant clump, you must have had a very small clump that grew together to form these plaques. And these very small clumps we call oligomers have become the focus of a lot of Alzheimer's research because they think this is what's actually conferring the toxicity that's damaging the neurons. And this study was very influential at advancing that hypothesis.

Okay. So what they did together at the University of Minnesota back then, 2006, as I understand it, is she, Dr. Karen Ash, who again was, and I assume right now remains well-respected, had these mice that she developed. And they basically took these mice and they took something out. They were like purified mice. And they took something out of these mice and injected it into rats. And those rats who had been perfectly able to find the treat in the maze by going through door two suddenly could no longer remember how to find door two and get the treat. They'd been fine on Monday, then she injected this stuff in them. And then on Tuesday, they couldn't find the treat. Is that pedestrian explanation about right?

No, that's perfectly okay. They isolated these oligomers, in this case, a very specific one, which was a clump of 12 strands of this little tiny beta amyloid protein that they thought was the silver bullet. And they found that when they put it into mice or to rats, rather, that they could no longer remember as well as they had before. And so they were like, this is the aha moment that proves, to go back to our original, the opening of our discussion, the plaques cause Alzheimer's. It certainly was an important part of showing that the oligomers contributed to the toxicity. And importantly, which had never been shown at least robustly before, they showed that the plaque caused memory problems. In the past, it had always been a problem with the amyloid hypothesis is that

the plaques don't correlate very strongly with memory. By the time patients have memory problems, they have a massive amount of plaques in their brain. And that was the real problem for the hypothesis that this paper started to unravel. Because all along, Alzheimer's researchers, if you zoom out to the 30,000 foot level, have been debating, well, you know, do the plaques cause memory problems? What actually causes Alzheimer's? Is it the plaques? Is it something else? There are other theories out there besides the plaques being sort of at the center.

And, you know, Dr. Ash and Dr. Lesney were in the plaques do cause it and do cause memory problems lane. But there have been other scientists in these other lanes saying, you're wrong. We can't replicate your results, and we would like more funding in our lanes for research on these other potential causes. Yeah, it had been a huge problem trying to get funding to alternate theories. The amyloid hypothesis, particularly in the mid-2000s, was so dominant and continued to be dominant that a lot of very respected researchers, but that the oligomers are in the lane of the plaques cause Alzheimer's. And we're advancing that theory with this study. That's essentially what they said they proved.

That's right. And there were obviously quite a number of other scientists that were also in that lane. And so the entire hypothesis certainly doesn't hinge on this one paper, but it was a hugely influential paper and a core piece of the foundation of this oligomer hypothesis going forward. And it created a lot of momentum for the hypothesis. And created, as I understand it, the NIH funding for that type of research was, according to our research, zero. And then now it's up to $287 million a year, a year. So it was important. It definitely had a role in increasing funding on, you know, pursuing this line.

Again, Dr. Karen Ash, very well respected. Lesney, less known. So you figure out, oh, my God. I mean, you must have just as a personal matter, you must have had sort of an holy cow moment when you realized this study had what you believe to be falsified images in it. Yeah, I think, you know, we tend to respect our colleagues implicitly in this business. And I think that scientists on a whole pride ourselves on being very trustworthy. So it's sort of hard to believe at first blush. And I think, you know, I went back to it over and over again, trying to understand how this might have happened. And, you know,

I think got to the point where the concerns were strong enough that something had to be said about it. You know, and I understand because I've looked at the images now and there's all sorts of questions about these pictures and what they show and have they been manipulated. And it seems to be kind of generally accepted right now that they were manipulated by this guy Lesney. But one of my questions was, you know, just because, let's assume that the photographs submitted were doctored.

How does that undermine the study? She's still got rats who couldn't find the treats. So that wouldn't be in the picture. Right. Well, so there's only certain components of a study that you can subject to forensic analysis. So it's very hard to look at charts that show the response time and the behaviors of mice and rats and conduct a forensic analysis on that without a team who has access to the original data. But photographs, in this case, are the original data. They're a sampling of the

original data. It's not all of it. And one has to worry that if the components that we're being shown have problems in them, it's possible that it's the tip of the iceberg and that other elements of the study that can't be as easily analyzed also have problems. And that's why it's so important for regulatory bodies to take these red flags seriously when we see them, because there may be other issues that are harder to see in the studies as well. I understand that you use something called the Western blot, widely used lab imaging technique, and it helps one see protein bands. Now, when you were looking at them, I saw some of them and you could see some had just been, they look like obvious copies from a different study. Is that what you believe this guy Lesney did? He just kind of said, here's one that shows what we're looking for, you know, and what is like, what are these blobs that we're seeing on the screen showing us? So this is one of the ways that we study proteins. We separate them out in a gelatin so that the

larger ones separate from the smaller ones. And how big that black blot is in each one of those little marks, we can measure how black that is. And that tells us how much is in the sample. And it helps us to understand if the amount of the protein is changing with the disease state. It helps us understand how big the protein is. So when it's clumping together, we can measure the size of the protein using this technique. So it's a very excellent technique for understanding the behavior

of a protein within, in this case, the brain. But the end result is a photograph. And just like, you know, you can Photoshop a photograph and make it look different than the original one was, the same thing can happen with the end result of this Western blot, which is just a photograph. And in the old days, we used film. And now, of course, we use digital images and process them with Photoshop. Is it a photograph of the protein found in the rats' brains after they were injected by Dr. Ash? So in this case, they're showing you the purification steps. They're verifying the purification of the protein that they're injecting into the mice, or to the rats, rather. So this comes from her mouse model, most of these images. And the two of them are showing you the range of proteins that are being identified, different forms of beta amyloid that are being identified within this mouse's brain. And then I put it through a series of isolation steps to purify out the one that they're looking for. So if the protein that's purified is not what they say it is, then it's very hard to interpret the rat's behavior.

Is there any way she had no idea? I mean, I don't understand because he's gotten all the flack, this guy Lesney, and she's still sort of sitting there at the University of Minnesota, and apparently he's gone underground. He hasn't spoken to anybody. She's given four different statements that are getting increasingly defensive. But is there any way she would not have known? I don't know. You know, I don't know her personally, but I've known her work for a very long time. And she's a highly respected scientist. And I'll tell you that I did analyze a number of her studies that did not involve Dr. Lesney. And I did not find the same

pervasive pattern of changes there. They seem to segregate with the studies that she co-authored with Dr. Lesney. The degree to which she was aware of this or should have been aware of this, I simply don't know. She originally told NBC News her wish is that the study be retracted in its entirety. She said, quote, having worked for decades to understand the cause of Alzheimer's disease so that better treatments can be found for patients, it is devastating to discover that a coworker may have misled me and the scientific community through the doctoring of images. What she said to us today, Dr. Schrag, is very different. She said to us in a statement we just got this morning, quote, I have absolute confidence in the scientific accuracy of our A-beta-star-56 research, despite recent media reports focused on images included in a research paper from 2006. While the editing of select images should not have occurred, the adjustments are non-material,

inconsequential, and have no bearing on the research findings themselves. Your reaction to that? Well, I think that I would encourage them to cooperate with the regulators and not only the regulators, but also with the scientific community. They say that daylight is the best disinfectant. And I think sharing those images with the wider scientific community so that our confidence can be improved would really help us to understand exactly what happened. I will say there was quite a number of papers that were implicated in this. And one of them, prior to the article that broke this news, they issued a correction for it, an article in a prominent journal called Brain. And then they said the

same thing, that the changes should not have occurred. They were inappropriate changes to those images, but they didn't change the results at all. And when I analyzed the new images that they released, I found quite the opposite. It looked to me like quite a number of the results were very substantially different with the new unadjusted images that they released. And so I think I certainly accept that Dr. Ash believes the results of these studies, but I think without sharing the results, we're just not going to have confidence in them. I think that they should make the original material available for closer scrutiny.

She does not seem to be even trying to push back on the fact that the images were manipulated. I mean, she says that in her study, I mean, in her statement. But to say that the, quote, adjustments are non-material, inconsequential, and have no bearing on the research findings is a different leap. I mean, inconsequential, what, really, are they? Quite simply, one has to ask, why were they done? You know, I don't think that if, think that if the fact that they were done speaks for themselves. If they were inappropriately manipulated, then the data is simply not trustworthy. And despite her opinion, which she's, of course, very much entitled to,

if the images were manipulated, the article must be retracted. What does this mean? And it hasn't been yet, correct? Yeah, I think, of course, they're entitled to due process. And again, as I said, the material we have access to is much smaller than the whole sum of the data. And so I understand these processes take time and they must be fair. What does this mean for scientific research when it comes to Alzheimer's causes for the past, since 2006? Yeah. Well, so as I mentioned earlier, there are other studies in this vein from totally independent researchers. So this is not the only foundation of the oligomer hypothesis, but it's an important piece of it. And I think that it has to be factored into the way we interpret all of the failed clinical

trials that have been targeting beta amyloid and different versions of beta amyloid, that there are problems with the data and the clinical trials are consistently showing us that this approach has not been successful. It is certainly appropriate to look at this pathway very, very carefully. But I think the field as a whole needs to invest in alternative ideas. Yeah, we started off the discussion by talking about two drugs that got FDA approval that a bunch of Alzheimer's researchers like yourself said, what are we doing? These cause more harm than good, and they're not actually helping patients. And now we can sort of see how we got so far down this lane. Studies like this one that have red flags all over them, that form the basis for development of drugs, that have red flags all over them. And here we are 16 years later without a

cure and maybe having wasted a bunch of time and money. Yeah. Well, semifilm is not FDA approved yet, but it has been greenlit for clinical trials. And I think it is just so critical that when we ask patients to take the risk of participating in an experiment where we don't completely understand the risks and benefits, we owe them the highest degree of candor and the highest degree of scientific integrity for the beginning data. We have an important ethical partnership with patients as physicians and scientists. And we have to be able to say, you know, when there are problems, we have to be able to say, you know, when there are problems, we have to be able to say that out loud. What kind of pushback, if any, have you gotten, Dr. Schrag, for doing all of this? Well, I think that the field as a whole seems to be willing to

consider these concerns. You know, I think that we're at a moment where we have the backdrop of a lot of failed clinical trials, and there's a lot of introspection at this moment. And I think that's been helpful, that many of my colleagues are willing to candidly look at this, most of them, and even people who are firmly in the camp believing that amyloid is a major driver of the disease have been willing to candidly look at these concerns. And I've been impressed and encouraged by that. Do you worry at all about, you know, the NIH controls everything.

It controls funding to basically every university, every scientist. And so far, all they're saying is credible complaints will go to the Department of Health and Human Services Office of Research Integrity for review. That agency could then instruct grantee universities to investigate prior to. In other words, it's going to take years. They say if it's deemed credible, we'll investigate, but we may make the university investigate first, which could take years and might not become public unless it results in an official misconduct finding. To me, it just seems like push it, push it down the road.

And the NIH could control your future as a researcher in the grants and so on you get. Well, I think the NIH certainly follows their procedures, but this is part of why it's so important to have this conversation in the light of day with all of the stakeholders. You know, when things reach a certain magnitude and patients are being exposed to drugs, they deserve to have all of the facts. And I absolutely appreciate that the NIH has to conduct a complete and full investigation and that that takes time. But patients are being exposed to these things today. And I think that's why we have to be able to speak candidly about these issues. The Science Magazine article, which broke this and we're going to have the journalist on next, has a great quote from you that reads as follows.

You can cheat to get a paper. You can cheat to get a degree. You can cheat to get a grant. You can't cheat to cure a disease. Biology doesn't care. 16 years post the publication of that paper, has biology told us not to believe it? I think so. I think a lot of my colleagues have reached out both before and after this became public to say that they could not reproduce that data. And that is the ultimate test. So I think that we're learning. And in any complex human endeavor, there's going to be some margin of error. And in science, we try very hard to correct it.

And frankly, there's going to be some margin of mischief in any complex human endeavor. It doesn't mean the system is broken. It means we need to be able to speak candidly and get back on track as soon as possible to limit the damage. Right on. Right on. Dr. Schrag, thank you. So great to have you here. I really appreciate all of it. It's my pleasure to be with you. All right. We're going to be right back with one of the journalists who broke this story, what he found when he had other doctors look into Dr. Schrag turned when he knew he needed to get this information out to the public. Charles, thanks so much for being here. Thank you, Megyn. I have to say my brother-in-law, Ken, brought it to me. He was at our house and had just flown in when this broke. He said, have you seen this?

And I said, what are you talking about? No, this is crazy. That's crazy talk, what you're saying. He's like, no, read the whole thing. And that day I sent it to my team saying, let's get these guys on. This is incredible. So great work to you. And I'm sure your jaw dropped when you first spoke to Dr. Schrag.

But you spent months trying to make sure Dr. Schrag had it right. Talk to us just a little bit about your investigatory process to make sure you didn't go too far out on a limb that wasn't stable. Sure. And thank you so much for your comments, Megan. So I handled this story as I would any of my investigations, which is to say that one must validate the claims of a whistleblower. And in this case, it required a very high degree of validation because the claims were so important to the field of Alzheimer's research involving, as you said in the earlier segment, a seminal paper that has had a lot of influence in the field. And so, the way I went about it is that I wanted to investigate the veracity of his concerns based on his analysis of actually turned out to be

well over 170 images in two categories. One involving the Cassava Sciences experiments and related experiments from scientists who are affiliated with that company in some way. And the other involving Sylvain Lesny and Karen Ash's work and independent work by Sylvain Lesny. And so what I did is I wanted to look at two categories of validation. One is image forensic analysts who are experts in understanding how these images could possibly be doctored and how that might have been done. And the second category were experts in the field of Alzheimer's research. And in that latter category, I really wanted to make sure that I was not just going to critics of the amyloid hypothesis. I wanted to go to a range of

people who understood the technology well, understood the science deeply, and would have no reason to be critical or supportive one way or the other. And I was able to give each of these scientists and forensic analysts the full Schrag dossiers on both the Simufilam case and also the Lesney work. And what I found is that every single scientist who evaluated these images and the forensic image analysts all agreed that his work was credible. It was well supported and it suggested the you and in your lap in the first place the good doctor was very smart because he understood as a whistleblower he needed to bring this to the nih but he well understood how slow those wheels of justice could move and so tell us Tell us what else he did. Sure. So I had been talking with Matthew Schrag beginning in December of last year. And this was a point at which he was largely through with the analytic work that he had

done on the Cassava Sciences issues. But he was, as any, I think, expert would be doing, trying to refine his skills further. And in so doing, he stumbled on, you might say, the Lesney issues, the issues related to this very important amyloid beta protein that was dubbed star 56 by Sylvain Lesny and Karen Ash. And it was really around the time I started talking to Schrag that he started to see this happening with Lesny. And I was talking with him. I remember quite distinctly as he started to describe it to me, in a sense, both of our jaws dropped at that moment. We both realized that this was

something of some great significance, in some ways, much more important scientifically than the Cassava Sciences issues because of the wide influence that the Sylvain Lesny and Karen Ash study had had and their other work in the same realm. So, he came to me for a couple of reasons. One is that, as you say, he wanted to see it get a wider audience. He also wanted to work through a venue that would have the scientific backdrop and expertise to do a close examination of this. Science Magazine, of course, is a scholarly journal, but also our journalistic portion of the magazine. We have access to a lot of good expertise and a lot of ability to delve deeply into these kinds of technical matters. Yeah. With all due respect to People,

there's a reason he didn't go to People magazine. He wanted somebody who could really fact check him and not just rubber stamp what he was saying. He seems like a true seeker of truth. So he comes to you, he went to the NIH, and it sounds to me like the NIH is not doing much so far. Am I correct about that, Charles? It seems like it's basically saying we'll take a look at it if we deem this complaint

credible. Yeah, I mean, I think the NIH is pretty opaque about what they do. I think we can read the tea leaves. It looks like they referred it to something called the Office of Research Integrity, which is part of the Health and Human Services Department, kind of a sister agency to NIH. This is a pretty small outfit within the federal government that takes another look at it. So, what you're talking about is an initial look, and then a second look by a second federal agency. And then if they deem the concerns raised by Schrag to be potentially credible, then they might refer it to the University of Minnesota in this case,

where Sylvain Lesney and Karen Ash work. And it appears that that's what happened, but we don't know for sure. But we do know that the University of Minnesota is doing their own close look at this, or so they say. What about Dr. Lesney? Where is he? Well, so in the course of my reporting, naturally, I made very, very serious and repeated efforts to engage Dr. Lesney, his voice would have been critical to understand the significance of what we were looking at in the Schrag dossier associated with his work, and also with the additional reporting that I had done. And unfortunately, he did not agree to talk with me, nor did Professor Ash agree to talk with me, although she did email me a cryptic statement before the story ran.

I think that the issue with approaching these scientists, to me, was one of me being as straightforward and complete as I could in helping them understand what I was up to, what I was seeing, what I was finding, and why their view on it would be so critical to give the fuller picture to our readers. And consequently, I emailed them not just the full dossier created by Matt Schrag, but I also sent them a detailed list of questions so that there were no surprises. They knew exactly what I had from the very beginning. She originally told you she found your reporting sobering, right? Then she says to NBC, she wants the study to be retracted in its entirety, saying this is devastating to discover that a coworker may have misled me

and the scientific community through the doctoring of images. Then to us today, I have absolute confidence in the scientific accuracy of our A-beta star 56 research, despite recent media reports focused on images included in this research paper from 06. While the editing of select images should not have occurred, so she's not disputing that they were manipulated, the adjustments are non-material, inconsequential, and have no bearing on the research findings themselves. She's having quite an evolution. I mean, you and I know as journalists, she's having quite an evolution on her response. Sobering, pull the study, devastating to absolute confidence, non-material, inconsequential,

no bearing on my research. What do you make of it? Well, I think I would just go back and say, just as I felt that I needed to be skeptical of Dr. Schrag's work in order to validate it so that it had more credibility for our readers, I would just kind of apply the same kind of skepticism to Dr. Atkins. Let me just say that in her comments to you and others, she has tried to minimize the influence of these changes, these apparently improper changes to images in her work. And it's not just this one study. It's five studies that she did with Lesney and another 15 or 16 studies that Lesney did independent of Ash. And so consequently, we're talking about paper after paper, image after image, 10 total papers involving this very important so-called A-beta-star-56 protein that is at the heart of their understanding

of what might be a cause and effect relationship for Alzheimer's disease. So what I guess I would say to that is, if she's so confident, then let's see the full complete record of these experiments, put it in the hands of people who know how to evaluate it. And, you know, I guess perhaps at this point, it would be important to say that I have asked, and I think a lot of experts in research review have raised the question about whether the university where Ash and Lesney work is the appropriate institution to actually do this full and complete review. I mean, let's face it, their employer has the least to win and the most to lose from doing a thorough investigation that actually finds fault with the work being done in their own labs. So I guess I would just say I would find

that suspect. I think it would be important to have an independent kind of set of eyes that go over that work and try to assess whether her claims associated with that research hold any water. The way I see it, just to sort of, you know, dumb it down, is the amyloid hypothesis, you know, that there's this sort of protein that these plaques cause Alzheimer's, was one possibility that scientists have been considering for many years. But there are other lanes of possibilities. And so let's say the amyloid hypothesis is like an apple. Some people say that an apple, apples cause Alzheimer's. But other lanes are saying, no, it's oranges. And other lanes are saying, no, it's plums. And her team was like, it's definitely

apples. And not only is it apples, it's green apples. We're advancing it even more. We know specifically what kind of apple is causing it. And then Lesney put up photos showing the green apple doing damage. And everybody said, oh, there it is. We've got it. This is the closest we've had to proof of causation. It's the green apple. And now she seems to be sitting back saying, okay, he may have manipulated the photos. I get it. But I still have a bunch of rats who ate green apple, who were fine the day before and the day after had serious memory problems. So I'm good. I don't really care what Lesney did with his little photos of my apples. I saw the rats. I knew that they had clean brains that could find the treats on day one. I fed them the green apples. And the day after that,

they had memory problems. Like, why isn't that an okay defense? Well, let me put it in these terms. So if you're a reasonable person trying to understand the truthfulness and the believability of a complex scientific experiment, wouldn't it be good to take a comprehensive look at the entire body of work in order to understand it better? So let me start with this 2006 study. So in her comments to other media, Dr. Ash has said that it was only an image or two that were potentially altered by Lesney. And actually, if you look at Schrag's body of work

associated with that paper, it's six or seven images. So, first of all, you're seeing a situation in which she appears to be minimizing the extent of the apparent problem. Second, if you have a study where six or seven of the most important representations of data in the study are deeply suspect, and I don't think there's much dispute that they are deeply suspect, are you going to believe that they have no effect? I think any reasonable person would at least ask the question, we can't just take her word for it. We need to have this looked at much more carefully by a wider range of experts who have the knowledge, the expertise, and the empowerment to do a closer look. What's crazy in this story, among other things, and we have a lot more to get to, is what happened to Lesney after Dr. Schrag blew the whistle and the money that he's been getting. So he may have gone underground in terms of the press, but he's still out there. And we're going to pick it up there right after this very quick break. Don't go away. Charles is staying with us.

And remember, folks, you can find The Megyn Kelly Show live on Sirius XM Triumph Channel 111 every weekday at noon east in the full video show and clips by subscribing to our YouTube channel, youtube.com slash Megyn Kelly. If you prefer an audio podcast you can follow us and download on apple spotify pandora stitcher or wherever you get your podcast for free and there you will find our full archives with more than 370 shows now so charles one of the things that you did was to find out, go to other experts and say, take a look at Dr. Schrag's conclusions about the images in this paper. And you went to some real experts in the field. What did they say?

Well, basically, each one of them agreed that the concerns raised by Dr. Schrag were credible. They were well supported by his work and raised serious questions about the validity of an entire body of research associated with Dr. Lesney, including this, as you mentioned, seminal paper, as well as others associated with this protein they found that seemed to suggest a cause and effect relationship with a kind of dementia associated with Alzheimer's. This is from your article because you did a six-month investigation prior to publishing this. A leading independent image analyst and several top Alzheimer's researchers, including George Perry of the University of Texas, San Antonio, John Forsyth of the University of California, San Francisco, reviewed most of Schrag's findings.

They concurred with his overall conclusions, which cast out on hundreds of images, including more than 70 in Lesney's papers. Some look like shockingly blatant examples of image tampering, says Donna Wilcox, an Alzheimer's expert at the University of Kentucky. The authors, quote, appeared to have composed figures by piecing together parts of photos from different experiments, says Elizabeth Fick, a molecular biologist and well-known forensic image consultant. Quote, the obtained experimental results might not have been the desired results, and that data might have been changed to better fit a hypothesis. Let's talk about why this hypothesis was out there and being researched to begin with, because I know that one of the things I found interesting about your paper was back to my apple, orange, pear, plum, whatever my third fruit was. Example, there are other lanes of study as the cause of Alzheimer's. And one of the things you talked about was these other lanes

have been sidelined. They've been effectively sidelined for a long time now because we've been so focused on the apple and the green apple. In other words, this amyloid hypothesis. Yes, let me put it a little bit into the context of what was happening at that time. So in 2006, we had already begun to see failure after failure after failure of drugs targeting amyloid proteins. Failure in the sense that they did not seem to improve cognition, nor did they seem to prevent the disease. Consequently, that idea, the so-called amyloid hypothesis, was under some strain. Some skepticism was increasing. And then this important study entered the breach. This was the 2006 study in Nature, which, as many listeners may know, is one of the most important scientific journals. And this study by Lesney and Ash seemed to show

a cause and effect relationship showing neurocognitive impacts, memory problems in rats associated with their star 56 protein. And so for the first time, there was a substance that seemed to directly cause effects in an animal that mimicked Alzheimer's disease and gave a lot of credence and hope to people who had been believing all along that this discovery would be made and that the amyloid hypothesis would be proved out in a very practical way that would present new targets for drugs that would be able to cure the disease eventually. So that was the contribution it made. It made a contribution of great importance to the field at a moment when the amyloid hypothesis was meeting with more skepticism. Yeah, the people were starting to get a little wobbly on whether they had it right. And then along comes, boom, this 2006 study, this gift shoring up their lane.

This is from your article. Scientists who advance other potential Alzheimer's causes, such as immune dysfunction or inflammation, complain they've been sidelined by the amyloid mafia. Forsyth, the doctor I mentioned a second ago, says the amyloid, I mean, hypothesis became the scientific equivalent of basically the model of the solar system in which the sun and planets rotate around the earth. And people had started wondering by 2006 whether the field needed a reset. No worries. Enter Dr. Karen Ash with her trusty protege, this French guy who come out with this study. And what do we know about this French guy, Dr. Lesney? Because he's not speaking and his fingerprints are all over this and many other studies,

but he's still an associate professor at the University of Minnesota. I mean, how underground can he go? Well, so yes, I think in fairness to Lesney, he does deserve an opportunity to defend his work during an investigation being conducted by the university. I hope that will be a rapid and thorough investigation. universities and other entities with vested interests in a particular outcome is that it won't be thorough and fast. But I think we need to hold out the possibility that the university will get to the bottom of this. So I think Lesney deserves his opportunity to defend himself, and I presume he is doing so in the university's look. But let's take it a step back to the evolution of Lesney himself as a scientist. So I was very curious about this idea that he was the guy who was responsible for all this, as Karen Ash now seems to be implying, or in some cases, almost openly saying. And I think what I wanted to do was to ask myself the question, how far back did these

concerns with Lesney's work go? And Matt Schrag had looked at papers that go back a couple of decades and others, including Elizabeth Vick, who reviewed some of Lesney's even earlier work, found additional problems. So we had more than 20 papers going back a couple of decades where it seemed that there were anomaly after anomaly, question after question. And that sort of a history certainly does raise eyebrows. But to me, the acid test was talking to one of his mentors at the University of Cannes in Normandy, France, where he did his PhD training. And this particular professor, he said that he was doing a joint paper with Lesney back in his PhD days, 2002 approximately, and he found images that Lesney had been producing in service of that paper that he regarded as suspect, untrustworthy. He tried to have those images repeated by other

graduate students. They could not get the same result. So finally, this professor pulled the paper, which was about to be published in a prestigious journal. And he pulled it because he feared that would affect his own scientific integrity as the senior author of the paper. So I guess what I'm saying is that there had been a history of suspicion, a history of concern. And in the field, he became known as someone who had the ability to get things done in the lab that some others weren't able to do. He was a brilliant bench scientist, they call it, who was able to complete experiments in ways that others found very difficult to do or could not accomplish. And when you have that combination of history of difficult to prove images that appear to have been doctored and suspicion from his own mentor in France, and this idea that he

had kind of the ability to get things done in the lab that others could not accomplish. And then you have image after image and paper after paper that is suspect. Well, that paints a picture of someone who, you know, maybe has been engaging in possible misconduct for a long time. I think people have looked at this sort of activity in science or really in other fields is that it rarely occurs just once in one image. It's usually a pattern. No, if this is true, he loves to doctor images. He's the Kim Kardashian of science. I mean, he just loves he's got the same little perfect 365 app on his phone, except he's putting scientific data in there instead of noses and butts and legs. Sorry,

Charles, that's my level of trying to bring the story to the viewers. But seriously, if this is true, this guy's got a massive problem and he's got a lot to answer for, but seems to be going the other way. According to your piece, not only did he become the leader of the University of Minnesota's neuroscience graduate program prior to this,

this is two years ago, but he's leading their neuroscience graduate program. It's a respected program, respected university. If this guy did all this, that should end. Tell us what happened in May 2022, four months after Dr. Schrag delivered his concerns to the NIH. Yes, that is a kind of a befuddling aspect to this whole strange story. And in May of this year, he received what is called an R01 grant.

So this is a prestigious, important grant from the university, very competitive to get these grants. It can give him up to five years of funding for his work. And this was, as you say, months after the agency knew that his work was under a cloud, that years and years of his studies were being suspected for possible manipulation and scientific misconduct. So that's question number one about the NIH's action. I would add that there's another strange twist to this NIH grant story, which is that the grant administrator for Dr. Lesney for his new grant is a guy by the name of Austin Yang, who is himself a respected scientist and was a co-author of the 2006

study in nature, this very important influential study that is now under a cloud. That is not okay. These conflicts of interest are all over the place. By the way, what, if any, connection does Francis Collins at the NIH have to this story? None whatsoever that I know of. Okay. I'm just wondering, because his name obviously has been in the news so much. What about that? Because there are a lot of people in the country who have a lot less faith in institutions like the NIH in the wake of all the covid madness than they used to. And, you know, this is not going to help. This this story is not going to help. What are people to make of our lead medical institutions within the government and the faith that we should

be placing in them? Well, let me say that the NIH is so enormously important to our country, so enormously important to curing diseases and to understanding more fundamentally the nature of the bioscience behind many of the dread illnesses that are being explored by physicians and scientists all over the world. So I have nothing but praise for much of the work that NIH does. Now, as an investigative reporter, I have looked at federal agencies, including the Food and Drug Administration and the National Institutes of Health, when

there are possible lapses or concerns associated with how they administer their programs. And so like any big bureaucracy, like any human endeavor, there's going to be questions. There's going to be lapses in judgment at times. There's going to be doubts. There's going to be conflicts of interest. And I think it doesn't invalidate the enormously important body of work that the agency has, in a sense, what some scientists might call captive to certain interests. Again, it's been described as the amyloid mafia in this case. I'm not saying that the amyloid hypothesis is useless or is somehow disproved. What I'm saying is that when you have a situation where year after year, drug after drug has failed when targeting amyloid plaques, that it's worth asking, on the amyloid hypothesis and on enormous billions

of dollars of pharma company drug development efforts are focused on that. It's worth asking the question, should there be a shift in priorities or at least a broadening of interest in this, especially in light of what we've seen with the Lesney-Ash situation, where some of the key research supporting that hypothesis has been found to be deeply suspect. Well, I mean, and that's the thing. I mean, these poor families out there suffering with Alzheimer's, now waiting for the next drug to come through the pipeline, the disappointment of Adjahelm, the drug we talked about earlier that did get FDA approval, but at $57,000 a year, $56,000 a year flopped because it doesn't appear that it was doing what they had said it would do.

And then now we've got some eupholim, which we discussed with the doctor, very concerned about that one too. And I'm sure there's others that are being researched right now, maybe in part in the Green Apple Lane, you know, maybe in part based on this research. So what does this mean for families who are waiting for the breakthrough? according to experts with whom I've spoken, that really what we're talking about is opportunity costs. So if you're focusing so much of your effort and so much of your money on a particular scientific direction that has failed over and over, then to the neglect of other ideas that themselves could have some possible benefit and could be fruitful in leading to potential remedies for Alzheimer's disease. I think the patients and their loved ones have reason to be concerned and have reason to be angry that this occurred and that these suspect studies have proved to be so influential. Now, that said, I would say that to me,

one of the acid tests for me was talking to a really eminent scientist by the name of Dennis Selko, who's at Harvard University and is a progenitor of the amyloid hypothesis and someone who believes deeply in the importance of studying the amyloid oligomers that Dr. Schrag had mentioned in his segment, that these are the subtype of amyloid proteins that are thought to be toxic and to be perhaps instrumental in Alzheimer's disease. So Dr. Selko said to me that there are currently clinical trials of drugs that are attacking these oligomer types of amyloid proteins. And if they fail, the amyloid hypothesis is under some duress. Now, that was pretty interesting to me because this is a guy who is a total advocate for this hypothesis, believes deeply in its importance, and has spent a lot of his career studying how best to get at it. Yeah, the NIH spent about $1.6 billion

on projects that mention amyloids in this fiscal year. That's about half of its overall Alzheimer's funding. So we'll see whether this shakes that or opens up funding in the other lanes and leads to a realistic reassessment of this paper and others like it in which this guy Lesney has had any connection. Charles Pillar, I hope you win all sorts of awards for this article. It was brave and it was important, and I encourage the audience to read it because Charles actually does a great job of walking you through it. You know, amyloid this and all. It's complex, right? But

he takes the time to walk you through it in a way that makes sense. All the best to you. Thank you, Megan. Up next, one of the experts on Alzheimer's, Dr. Dale Bredesen and what he thinks of what you just heard. Don't go away. Welcome back to the Megan Kelly Show. My next guest is an expert in the field of brain health who has done some revolutionary work to treat Alzheimer's. He also happened to be Dr. Karen Ashe's chief resident when she was an intern. Dr. Dale Bredesen is a UCLA professor in the Department of Molecular and Medical Pharmacology and author of The End of Alzheimer's. Great to have you back, Doc. Thank you for being here. So what did you make of this article in Science Magazine and of our whistleblower's testimonial?

Yeah, thank you very much, Megan. And here's the problem. This is actually part of a much bigger problem. So we are all witnessing the Titanic, that is mainstream medicine, going down because it has rammed into the iceberg of chronic illnesses. And I'm talking about Alzheimer's, Lou Gehrig's disease, frontotemporal dementia, Lewy body disease, on and on, CBD, PSP, all these other ones, and including late stage cancers, including chronic renal failure. We are all in an era in which mainstream medicine is treating things the way we treated them in the 20th century, simple illnesses, viral illnesses, bacterial illnesses, things like that. And so we're ending up with things where the big problem here is really about what Alzheimer's is. And let me just for one moment say, yes, I've known Professor Ash for 40 years. She is a brilliant scientist, a brilliant neurologist, and she's absolutely committed to finding the mechanisms underlying Alzheimer's disease. And the work that

she did, you did a beautiful job with Charles Piller and with Dr. Schrag, but didn't mention that this is based on an analogy with Nobel Prize winning work. This was from Professor Stan Prusner that identified in the case of prion diseases, this is a different kind of neurodegenerative disease, looks a little like Alzheimer's, typically faster than Alzheimer's disease and much more rare. And he found one form of a protein that is normal and one form that's abnormal. And if you give the abnormal one, the person or the animal gets the disease. So this was an analogy here, which I think is one of the reasons that it was, you know, interesting to people at the beginning. Aha, we have the same story. Makes

sense. But as you've shown beautifully, this is much more complex. And I should add, you mentioned the green apples. In this case, this is a brew. This stuff interchanges. So you have green apples, red apples, and yellow apples, and they're changing into each other. You have larger apples, smaller apples. You have apples that are sticking to each other, just like heated gummy bears. So you've got this brew, and it's not simple. They're trying to say, is there one part of this brew that is actually causing the disease? And you mentioned Professor Selko was

really the first many, many years ago to argue that it was assemblies of small numbers of these amyloid molecules that were the critical players. But here's the problem. That doesn't explain the disease. And as Charles mentioned, the problem is that when you remove the amyloid, you don't get better. So we're left with this amazing paradox. For lots of reasons, amyloid looks like a bad actor. There it is sitting there in the brains of patients with Alzheimer's. There it is when you look and you see this stuff, you now drop it into cell culture, or you mentioned into Professor Ash's mouse brains, and absolutely, you get symptoms. There's no question, multiple forms of amyloid are toxic. But the paradox is when you now remove them with antibodies,

and Aduhelm was not the first. Bapineuzumab failed. Solanazumab failed. Cronazumab, Gantanarumab, just go right down the list. They have all failed. And so people keep saying, well, it's because of this. Well, it's because of that. Yes, when you put $40 billion into developing these things and trialing them, it's hard to say, you know, this has really failed. But the surprise was that the FDA actually approved this when, in fact, the trial proved just the opposite of what the reason that they approved this. They approved it because they said, well, it removes amyloid. So we expect it to have clinical benefit. What the reason that they approved this, they approved it because they said, well, it removes amyloid.

So we expect it to have clinical benefit. No, that's exactly what all of these trials showed is not the case. When you remove the amyloid, it does not give you clinical benefit. So we're left with we need a better understanding of this disease. It just it's so undermining of my own faith in places like the FDA, not to mention movies like Dope Sick. But there are all sorts of reasons to be skeptical of them and whether they're acting in our best interest. Let's not even get started on COVID and the vaccine and so on. I just think people see this sort of this rubber stamping of drugs that really might be hurting the sickest and most suffering amongst us. And we think, forget these guys. We can't trust the FDA. Can't trust the NIH. Why are they

giving this Dr. Lesney more money after this well-credentialed whistleblower went to them and said, here are all the images. This guy appears to have been doctoring, manipulating, editing, to use his boss's word, images in study after study, and they still give him money. It's a good point. You know, we're right back to cold fusion, aren't we? This is cold fusion in the brain. You know, does it work? Does it not work? Is this what's going on? And you really can't put the toothpaste back in the tube. Once you've given out millions and millions of dollars of grants for what is now a suspect result, are you going to ask for that the grants be returned? What are you going to do?

Now, in this case, again, there's some important nuances here. It may turn out, just as Professor Ash has suggested to you, it sounds like today, that this will all turn out to be supportive of her theory and supportive of the work they originally published, even though there are clear red flags about how this was presented, or it may turn out not to be the case. And so you're right, this is really concerning. And I think it just shows how complicated and how difficult research into human conditions is and the fact that humans are complicated organisms. And there's a lot going on here, far more than just amyloid. Multiple amyloid species clearly have toxic effects.

But the question is, is that the cause of Alzheimer's? It is likely to be a mediator, but not the upstream cause of what's going wrong in an Alzheimer's brain. What do you think is the cause? Talked about this a little bit the last time you were on. Yeah, we did. And actually, you know, we've had a tremendous amount of pushback and people just saying that, you know, this can't be. So what we're arguing is this, and I'm glad you asked. Thank you for asking that question. So here's the thing. There are lots of theories of Alzheimer's, as you know. It's herpes simplex, it's prions, it's amyloid, it's tau, it's type 3 diabetes, it's on and on and on. You know, it's reactive oxygen species, free radicals, all these ideas, none of them has led to

a successful treatment. So what our research over the last 30 years has suggested is that this is fundamentally a different type of disease. It's not a simple, it's amyloid or it's tau or it's something like that. This is a network insufficiency. So when you change, it really changes the way you think about this illness, and it fits much better with all the data. So the idea here is you have this beautiful plasticity in your brain. You're learning all sorts of wonderful things. You're remembering all sorts of wonderful things. You can make new synapses. You can support them and so forth and so on. And in fact, the big issue with Alzheimer's, as you know, is the loss of those synapses.

So what our research suggested, and we've just published a successful clinical trial based on the implications of this, is that you have, this is a network. This is just like running a large company or running a country. There are many, many different contributors. And in the case of Alzheimer's, we initially identified 36 different contributors. There are a few more, but the good news is it's not thousands. There are dozens. And so insulin resistance is critical, ongoing inflammation, various pathogens, various toxins, all of these things can change that network function. And so the idea of just doing the same thing for each person, it's like taking every single car that comes into a garage not doing well and just filling it up

with gas. Yeah, a couple of the cars, that's going to be fine. But you need ultimately to treat these cars as complex mechanics and look at what's going on. And the same thing needs to be done for people with Alzheimer's, and it is not being done in mainstream medicine. We need to look at many, many different contributors. We need to have computer-based algorithms that will now look at these data and say, okay, in this particular person, it was mainly A, B, C, D, E. In this person, it was mainly F, G, H, I, J, et cetera. Let me ask you a question about that because I'm just looking at the specific factors got my brain moving.

So you could have a person who came in to see you who says, very outgoing, extroverted person who says, I've got tons of friends. I love to smoke and drink with them many nights a week. I know I shouldn't, but I do. And I've got high cholesterol and I've got some inflammation and I know it's not great, but I think I have some memory issues. That's patient A. Patient B comes to you and says, I'm an introvert. I exercise every day. I do it in my house by myself. I have a very, very stressful job, but I eat very well, but I don't like to see people. And I'm having some memory issues and I'm worried that I have dementia. You actually would treat them differently.

You would see different problems that lead to dementia in each one of those patients. Absolutely. We right now look at 150 different variables. So we're looking at, is this person insulin resistant? Do they have ongoing inflammation? Do they have different types of pathogens? Do they have a leaky gut? All of these things.

I mean, isn't it amazing though, Megan, when they have all of these theories, each one has a little bit of supportive evidence. Now, if this were something simple, one theory would have all the evidence and all the others would have none. Yeah, just stop smoking. You're good. That's not the case. But like some of the factors that did jump out at me was it's not great.

Smoking, of course, not great. Smoking is bad for everything. Smoking is not great. High cholesterol, not great. No socialization, low socialization, not great. No exercise, not great. A balance that doesn't have enough like folate in it. I saw you tweeting about that recently. You know, like I got some spinach in there and some kale and so on. So there are all sorts of different things that one person might be doing that could be bad for them. And somebody else might think that they're doing just fine because they're eating well and they're not drinking and they're not smoking, but they're not getting enough social interaction, which apparently is also not so great. And leaky gut. I mean, now in the past

few years, we've been talking about the microbiome and taking a probiotic. But like, how the hell do you know if you have a leaky gut and why should we be worried it's going to cause Alzheimer's? This is a great point. And we need to have more doctors understand this very point that you need to know if someone has a leaky gut. You need to know, by the way, not only about their gut microbiome, as you mentioned, but also about their oral and nasal and sinus microbiome. Where does that stand? That is a

contributor. And guess what? Sleep apnea, another big contributor. So there are many, many different contributors. And the idea that we're just going to find one thing is really not stacking up given all of the data. And so therefore, we end up with these things where, well, was this correct about the amyloid? Was this incorrect about the amyloid? It's a little bit like talking about a two-foot hole in the Titanic. Well, it was that big, that huge one that really sank it. Sure, the two-foot hole, I'm sure that that contributed a little bit, but it's that big one that sank it. So there are many different pieces we have to look at here. And I think this is where medicine is headed.

What is there? Is there a society on earth where they really don't get Alzheimer's or dementia? There are societies where there is less. But there, other than people dying young, it is all over the world. But yes, for example, it's been argued that people who, you know, who eat curcumin, for example, people in India, as you can imagine, part of the problem here is curcumin, yeah, turmeric, which happens to have a nice anti-inflammatory property. And this has been eaten for thousands of years. And yes, there seems to be a little bit less in that particular group. And of course, there are others,

some areas, for example, Okinawa, where people live long lives and have, in general, longer health spans. Of course, Dan Buettner's Blue Zones, so-called. But the answer is no, there's no place where people simply don't get it. This is a common problem. And in the United States of the currently living Americans, about 45 million of us will die from Alzheimer's. So it actually dwarfs the pandemic. And of course, the pandemic is now associated with brain fog. So I think, you know, these are important areas going forward to optimize brain

health. Let's not wait for that single therapy, that drug that may never come. That is the cure for Alzheimer's disease. A couple other quick questions. Is there a diet, you know, keto, paleo, intermittent fasting? What what would you say, you know, we should be doing if we want to prevent this? And again, it's part of the overall piece that you need to look at what's driving the problem. So for some people, it's going to be very important, some people not quite as important. But yes, the biochemistry that needs to be addressed by the diet is, number one, you need to get people into mild ketosis. That's one to four,

what they call millimolar beta-hydroxybutyrate. So a little bit of ketosis is helpful, and why? Because your brain runs on only two different types of energy, glucose, ketones. As we get older, we lose the ability to do both. And people with Alzheimer's tend to have lost both. They have the insulin resistance that means that they don't use glucose well. And by the way, the PET scans, that's exactly what they show, that the brains don't use glucose well, but they're also not keto adapted. They're

not making and using ketones. So that's the first piece. It should be plant rich, doesn't have to be just plants, but plant rich for all the phytonutrients, should be high fiber, and should be plant rich, doesn't have to be just plants, but plant rich for all the phytonutrients, should be high fiber and should be colorful and should be associated with a period of fasting that allows you to be metabolically flexible. And that means able to burn glucose, able to burn ketones. Most people, as I mentioned, who have Alzheimer's or pre-Alzheimer's are unable to burn either of those. Last time you were on, you mentioned coffee. My husband gave it up for, I don't know why, but he started to resume because of the brief conversation we had,

but coffee could be good. Absolutely. And some beautiful work out of University of Florida has shown that, in fact, coffee, it reduces your likelihood of developing Alzheimer's. So, yes, it's got some issues. You know, it can be stressful for your adrenals. It can interfere with your sleep, of course. But it does in terms of just epidemiology. It is associated with a lower likelihood of developing Alzheimer's disease. Women get it more often than men, at least in America. And I was sitting there getting my hair done before the show today. And I was thinking, I was breathing in all the toxins from the hair

spray and the other products that she uses. And I was like, this is why, this is why. And I was like, we should do a study to see whether news anchors or actresses or people have to get their hair done or women who work in hair salons get it more often than women just who have naturally gorgeous hair and don't need all that nonsense. I'm telling it's like the toxins. That's what I'm going for, the toxins. And also why the women? It's a great point. And as Maria Shriver has told us for years, this is a woman-centric disease. Almost two to one, about 65% of the patients are women and about 60% of the caregivers are women. So this

is a huge issue. And part of the reason may be because of the rapid hormonal change during menopause where you lose estradiol rapidly because estradiol does have a beautiful anti-Alzheimer effect. And as you indicated, exposure to toxins, we've been very surprised at how commonly toxins are one of the important contributors to cognitive decline that turns out to be associated with Alzheimer's disease. So yes, you may be right. Maybe time for you to write a paper on that. I mean, I'm just going to have to have flat hair. What about drinking? I mean, we always joke like, oh, I killed some more brain cells.

Are you actually killing brain cells? I mean, are you killing the things that help memory and, you know, that you'll need to stave off dementia? Yeah. And so as with so many other things, there's a positive and a negative. Yes. No question. Ethanol is a neurotoxin. So unfortunately, when we drink, yes, we can damage some neurons and as well as other things. But it would also in general,

when people are drinking, it's relaxing them. Lower stress is better. People who are drinking tend to have a little better, a cleaner vasculature. So there's, you know, there's both sides here, but overall, yes, you don't want to be drinking to the extent that it impairs your cognition. How do you find out if you're somebody who has inflammation, right? I think most of us, especially all my women friends, we all feel inflamed at the end of the day. You know, you look good in the morning. You're like, I'll go to the beach now. If somebody told you how to go to the beach at 11 PM, you'd be like, hell no, right? So does that mean we have inflammation or is that

just being a human? Great point. So we all know when you turn 50, what do you do? You go get a colonoscopy. So if you're 45 or over, you should get a cognoscopy. Blood tests, simple online cognitive tests. And then if you have symptoms, you want to include an MRI with volumetrics to look at the various regions of your brain. But if you're asymptomatic and just for prevention, don't need to do that third part. Everyone should do this. When you do this, you look at blood tests. Unfortunately, many of these not being done by doctors who are treating Alzheimer's patients, but they tell you if you have inflammation or if you have insulin resistance. And as an example, there are multiple ways to look at inflammation.

HSCRP is the one you want. It's the simplest, quickest. This is high sensitivity C-reactive protein. It's made in your liver and it is something that responds to inflammation. I'm writing that down right now. HSCRP blood test. Okay. I don't know whether I've ever had that done, but I did take the cognitive test on your website. Is it your website? Yeah, I think it's yours this morning. Apollo, that's you, right? Yeah, I'm a consultant for Apollo. That's correct. Okay. So I took your cognitive test this morning and it's actually kind of fun. I recommend people go there and do it. It took, you know, 10 minutes and you're basically just pressing shift or enter and like sort of saying yes or no to the questions. But so I came out average, which I was like, OK, I'll take average. I definitely did not think I was above average when it came to my memory, which is but long ago memories? Yes. But my whole life I have, you know, I mean, I didn't have that many long ago when I was 25, but I've never been good at remembering the specifics of stories from long ago. I just have always had a bad memory. So what does that tell me? And being average at 51, what does that tell me? Yeah, well, of course, first of all, you wouldn't be able to do what you're doing without being very sharp. But each of us has different, as we all know, we all have different challenges, and we all have different strengths. And what you're describing is common. You're saying that

memory has not been your strong suit since you were younger. And so that's a very important point, because what we're looking for, which is, again, why everyone should have a baseline if they're 45 or over, is that we want to know change. And so we've had an example for one example where a guy who was the math champion of his entire state began to have very significant dementia. And his wife took him in to see a neuropsychologist who said, oh, great news. You're scoring in the 50th percentile. So you have no problems. And his wife said, are you kidding this guy? It was a genius.

He has fallen so far from where he was. So you want to know, have things changed? And this is unfortunately what when the first test you ever take, you won't know that you need to go, you know, you need to go several times over time to know whether things have changed. But by the way, there are things you can do to strengthen your memory. Part of this is about performance. This is not just about decline. It's also about having all of us perform better. What can you do? Because let's say I get the blood test. I mean, does that blood test? That's not the one that tells you whether you have a gene that's going to give you Alzheimer's. That's knowable too. And that's the one I was talking about in the tease where most people are like,

I don't want it. You know, it's interesting. The establishment has told us, don't bother to check this because there's nothing you can do and nothing could be further from the truth. There's a tremendous amount that can be done. And so, yes, the gene you're referring to is ApoE4. It's one of dozens of genes associated with increased risk for Alzheimer's disease. But it is not your fate. Now, we have zero copies, one copy or two copies. So you may have one from your mother or your father or both or neither. And so when you get this test, three quarters of us are ApoE4 negative. Our

lifetime risk is about 9%, not zero, but it's not too high. 75 million Americans have a single copy, 30% chance during their lifetime that they will develop Alzheimer's disease. So great to get on active prevention. There's an entire group on the internet, for example, ApoE4.info. Check it out. Over 3,000 people who all are ApoE4 positive doing things to prevent their own cognitive decline. And then 7 million Americans have two copies. Their chance of developing Alzheimer's during their lifetime, well over 50%. So in all likelihood, they will, there's a very good chance that they will develop it. Again, please get on active prevention so that we really can make Alzheimer's a much less common disease. That's so crazy. Like, truly, that is so uplifting

because I'm one of those people who's like, I'm afraid, I'm afraid to find out. I did not have any testing. I did have the colonoscopy at 50. I had a bone scan, which actually did find some issues, which I've addressed. And now I'm perfect in the bones. But I never had this done. And now I'm already worried that I waited too long. I waited six years after 45. It's not too late though, right? I can still get it done and get the blood test done. You can do it at 75. I mean, it's just that you want to do it as you hit 45, you want to be thinking about it. When you get Alzheimer's, as you know, you go through these four phases, pre-symptomatic, where you can already pick it up on a PET scan, but you don't have symptoms. SCI, subjective cognitive impairment, which lasts about 10 years,

where you know something's wrong, but you're still able to score in the normal range on testing. MCI, mild cognitive impairment, which is pre-Alzheimer's, but that's the third of four stages. And then, of course, dementia, the fourth Alzheimer's disease, where you're now losing your activities of daily living. If we could get everybody to get on prevention or earliest reversals, we could make this disease much less common. So I think you're at a perfect age to do this. And I think it's a good idea. We mentioned the APOE4, but it will look at other things. It'll look at your homocysteine, which is a measurement of several things,

but including inflammation, also your methylation, your ability to detoxify, things like that. And it'll look at things like, do you have specific pathogens? Do you have specific toxins you're exposed to? Do you have underlying vascular disease? These are all potential contributors to cognitive decline that can ultimately manifest as Alzheimer's disease. When you say APOE, I just want the audience to know it's A-P-O-E-4. And the website is.info, right?.info? Yes,.info. That's correct. And that is an apolipoprotein. So it's a protein that carries around fat. So this thing is like your butcher. It's the guy that carries around the fat. And it had been unclear why it is that that thing actually is so associated with Alzheimer's. Well, it turns out

this impacts many of these factors that we talked about. For one thing, it is a pro-inflammatory gene. And it is something, by the way, the one that's associated with Alzheimer's was the primordial one. So the initial hominids five to seven million years ago walking along the African savannah were all ApoE4. It helps them to survive because it's pro-inflammatory. For example, you can eat raw meat more and better and with more impunity if you are ApoE4 positive. In third world countries, you survive better and do better if you're ApoE four positive. So something we should all know, we should all know this whole set of things so that we know what our risk factor is. So final takeaway for the audience members

who are sitting there is everybody thinks they have Alzheimer's. I mean, you know that, right? You're a professor. Everybody's like, I've got it. I know I've got it. For the people sitting there saying, I got it. I know I got it. What are the two or three action items they need to do today? Yeah. So, you know, this is such an important point because you're right. We are all at risk and about 15% of our population dies of Alzheimer's disease. And we can do something about it for so many years. So if we can just get people to come in earlier, better. So the first thing, the most important thing to do is find out your risk factors, find out where you're, you know, what your blood tests actually show.

But then beyond that, there are seven basics. And we talked about some of these before, and they are diet, exercise, sleep, stress, brain training, detoxification, and some targeted supplements. And people say, well, supplements aren't a cure for Alzheimer's. Of course they aren't. But the idea of optimizing your brain chemistry so that you reduce your risk is excellent. And so we talked about the type of diet, exercise. There are some wonderful things coming up, things like Katsu bands, which were used by some of the Olympians, and what's called EWOT, exercise with oxygen therapy. Beautiful study out of Israel recently showed how important hyperbaric oxygen was in some people with cognitive decline.

Not for everyone, but for some people. Sleep. There's a whole huge, as you know, beautiful works from Arianna Huffington on sleep and also from Professor Matthew Walker from UC Berkeley. It's a huge, huge part of all this. Stress, another one. Brain training. Professor Mike Merzenich was the pioneer in brain training. So all of these things are absolutely critical.

And then targeted supplementation and detox. We are all exposed, just as you indicated earlier, to these various beauty products and things, as well as food, as well as air pollution and things. So yes, there's a tremendous amount that we can all do. Okay. And the one-stop shopping, I know your book is The End of Alzheimer's, but like if they want to go to one website to find this information, what is it? You can go to drbredesen.com. That's probably the easiest way to do it. You can go to- That's B-R-E-D-E-S-E-N.

Doctor, I love talking to you. Please come back often. This has been so illuminating. There's so much to be done. Thank you, Megan. All the best. Thanks for listening to The Megyn Kelly Show. No BS, no agenda, and no fear.