A Comprehensive Plan For Alzheimer's - with Dr. Dale Bredesen | The Empowering Neurologist EP. 53

Hello everyone, I'm Dr. David Perlmutter. Welcome again to The Empowering Neurologist. You know, we in the field of neurology have pretty well accepted over the years that there really isn't anything that has any meaning in terms of being therapeutically effective in dealing with Alzheimer's disease. Even recognizing that certain medications are marketed to so-called treat Alzheimer's, the reality is that these medications that are sold and patients are taking do nothing to change the ultimate course of events that an Alzheimer's patient will experience. Having said that, we are so gratified to learn of the work of Dr. Dale Bredesen. Dr. Bredesen has been working to try to unravel this mystery of Alzheimer's disease, not from the perspective of trying to find a miracle cure. You know, we certainly have billions of dollars in pharmaceutical research that's dedicated to that, and I think that's great. That has come up empty-handed. Dr. Bredesen has looked upon the issue from a different perspective, and that is not by trying to find one magic bullet, but as Dr. Bredesen talks about, magic buckshot. And that is using multiple entry points to really come at this disease that has multiple factors involved with it in terms of what's causing it, to leverage those multiple inputs and bring about change. Having said that, Dr. Bredesen has published his work and has now been able To reverse Alzheimer's in a number of patients, which is unprecedented. It's monumental. Dr. Bredesen, let me tell you a little bit about him. He is internationally recognized as an expert in understanding and publishing information about the actual mechanisms of neurodegenerative conditions like Alzheimer's disease. He is a graduate of Caltech. Then earned his MD from Duke University Medical Center in Durham, North Carolina. He served as chief resident in neurology at the University of California in San Francisco before he joined the laboratory of Stanley Prusiner at UCSF, who was a Nobel Prize laureate and also was involved at the NIH as a postdoctoral fellow. Dr. Bredesen has held faculty positions at UCSF, remains at UCLA, as well as University of California, San Diego. He is the director of the Program on Aging at the Burnham Institute before he came to the Buck Institute in 1998 as its founding president and CEO. He is the chief medical officer of MPI Cognition. There is a very interesting interview that we'll probably put a link to, at the Buck Institute that Dr. Bredesen and I did a couple of years ago, at the time when his work was starting to get out there. Dr. Bredesen has a new book out called boldly The End of Alzheimer's: The First Program to Prevent and Reverse Cognitive Decline. It is a chronicle of his scientific discoveries as well as his clinical experiences in dealing with this incredibly pervasive and even becoming more pervasive disease. I wanted just to mention an interesting quote at the beginning, and it says that— let me get my glasses for this because it's really very important— You never change things by fighting the existing reality. To change something, build a new model that makes the existing model obsolete, and that's by Buckminster Fuller. That's what Dr. Dale Bredesen has done. He has certainly challenged the mainstream dogma of magic bullets and has really created a new reality looking at this problem, Alzheimer's disease and neurodegenerative conditions in general, from a very different perspective, and he's having phenomenal results. So, it's a great honor and pleasure to speak with Dr. Bredesen today. Let's jump right into the interview. So, Dr. Bredesen, it's certainly a delight to be with you today. Thanks for joining us.

Thank you very much, David. Great to be with you.

In the intro, I was talking about your phenomenal book, The End of Alzheimer's, a pretty bold title, but, you know, Lord knows you certainly are able to defend it in your work. You know, I think many would say, especially as I mentioned that quote in the introduction from Buckminster Fuller about really paradigm changing, that, you know, many would say that you are really challenging the mainstream. And, you know, how do you respond to that and why?

Well, David, you know, this is a really good point and it's part, as you know as well as anyone, this is a part of a much, much bigger picture. You know, the, The goal of the entire success of 20th century medicine, of course, was mainly about getting rid of a lot of the infectious illnesses, triumphing over the infectious illnesses with a combination of public health and antibiotics. The problem, of course, is that we are now all pretty much to a one dealing with complex chronic illnesses, whether you talk about Alzheimer's or other neurodegenerative diseases, cancer, cardiovascular disease, so forth and so on. And unfortunately, as you know, as a medical community, we have used a checker strategy for a chess match. We have continued to use the old idea of let's collect very tiny datasets, and let's try to get a monotherapy that impinges on this disease. And the problem is, it has not worked. So absolutely, we need much larger datasets. We need much more robust statistical analysis. Better computational algorithms for these illnesses. And really, functional medicine and integrative medicine have taken a critical first step, because they have allowed us to look at the very different contributors. And as you know, in Alzheimer's disease, you're talking about many, many different contributors. It's not one thing. So, monotherapy is not optimal. Fine to use it, as long as you use the rest of the program. Right. And

so, you know, for our viewers, people are generally used to the fact that there is a magic pill, a silver bullet to treat the blood pressure or the elevated blood sugar or whatever it may be. And, you know, that has failed miserably as it relates to Alzheimer's. So suddenly Dale Bredesen shows up and says, you know, this isn't working. Here's another way. And What you've decided was that we didn't get into Alzheimer's by one door, and we're not going to get out of there by one door. So, you have actually put together your program of 36 different entry points, most of which have to be leveraged in order to turn this thing around. And if you could, tell us about what that means to actually turn Alzheimer's around.

Right. So, as you know, we spent 30 years in the lab looking at what actually drives this process. And so, we're coming specifically from from a test tube to say what actually drives— when you get neurodegeneration that we call Alzheimer's, it's really a protective response. That's a big surprise. It's a protective response to 3 fundamentally different things, as you know, anything with chronic inflammation, anything with trophic loss, and anything with toxic binding. The amyloid is there as a protection. It's a little bit like thinking of it as a mobile electric fence, so that you're essentially, okay, I'm going to pull back, but I'm going to guard what I And so, when you go about turning that around, the most important thing is you want to know what are all the contributors, and then you want to document this for each person, because of course, they are different for each person. And then you want to set about addressing each one. And as you know well, you can address some by things like a ketogenic diet. You can address some like BDNF with increased exercise, or with things like whole coffee fruit extract, which you introduced me to. You can change some things with specialized pro-resolving mediators. You want to get to the root cause. And the problem with trying to go around the cause and say, let's just give a medicine and trick nature, it just hasn't worked. And I think nowhere is that better shown than in Alzheimer's disease.

Well, you mentioned something, and I don't want it to get lost in passing, about this amyloid, the beta amyloid that has been the so-called hallmark that we all learned about in the Alzheimer's brain. After the fact, you look in the brain of the Alzheimer's patient, and you see this accumulation of a protein called beta amyloid. And even now, in vivo, in patients or individuals, there are scans that are available that can measure the load of beta amyloid. And as you explained, there's been dedication of huge sums of money in an attempt to rid the brain of this beta amyloid. Right. All of which have failed in terms of developing a drug to do that. And beyond that, you are challenging this notion that this beta amyloid that we all learned about was the cause of Alzheimer's is really the cause. I mean, what you've talked about in the book and what others have talked about over the years, myself included, is that really beta amyloid— you know, they say the enemy of my enemy is my friend. And so, it's really a different way of looking upon beta amyloid. You talk about that. How is mainstream neuroscience accepting that view?

Mainstream neuroscience has not accepted it yet, as you know, but what's becoming very clear is that removing the amyloid without removing the inducers of the amyloid is failing time and time and time again. And it's now running into the billions of dollars, as you said, spent on this without any significant success. So people keep saying, well, let's try to go earlier, earlier, earlier. Well, what we really need to do is to understand why it's there. And, you know, President Obama said you can't have perfect security and perfect freedom. So, the reality is when you are dealing with these various threats, these various terrorists, you are essentially calling out the amyloid, which is like a police force. Yeah, there are going to be some— there's going to be some downsizing. Things are going to be tougher, but you are protected. And so, the point is, that beta amyloid is absolutely part of the innate immune system. This comes up again, and again, and again. It's very clear. So, as long as you have chronic stimulation of your innate immune system, which, as you know, has to do with your genetics, has to do with your mold exposure, has to do with chronic inflammogens, and on, and on, and on, as long as that's activated, you are producing amyloid, and you are at risk for Alzheimer's disease.

Let me say for our viewers, because Dr. Bredesen and I oftentimes, we get into the science a little bit, and it may seem compelling, but one of the things I want people to be certain of is that in this book, you're going to understand the technicalities of what we're talking about right now. We enjoy getting into the depths of this, but what is so wonderful about The End of Alzheimer's— what a bold title, but you substantiated totally, is that this information is understandable, but beyond that, it's leverageable. There's a take-home message here in terms of what each and every one of you can do day to day. Back to our story. You had mentioned in passing one of the factors that's important, and that is fasting and ketosis. I say a factor because they're very much related. Can you take us through why that really relates to brain health?

Yeah, very good point. And let me just back up for one moment, because you mentioned the book. So absolutely, it is written to be read by everyone. It is written to be a manual that can be used by caretakers, by patients, by physicians, scientists. So I actually put scientific proof of the— of why we're doing what we're doing, but also tried to make it so that everybody could see what are the actionable items here. And with respect to ketosis that you mentioned, absolutely. Absolutely. What has turned out is, as you know, you can look at PET scans and show specifically that there is poor glucose utilization in the temporal and parietal regions. Literally, it looks like 2 L's in the temporal and parietal regions in someone not only with Alzheimer's, but with pre-Alzheimer's as well. And it turns out that ketones are utilized better, and especially in those particular patients. So we want to create A mild ketosis, 0.5 millimolar to 4 millimolar beta-hydroxybutyrate, so one of the ketone bodies. And certainly you can measure this very easily and inexpensively with a ketone meter. So you want to drive this, and certainly many people are seeing the same thing, as you know, whether you use coconut oil or whether you use MCT oil, exercise, fasting, low carbohydrate diets, all of these things. good fats, as you've emphasized so many times in your research and your books. These are things that have been shown again and again to be positive for support and to be anti-Alzheimer's.

And there was a very good point that you just made, and that is whether you utilize exercise or low carbohydrate or healthy fats or adding in MCT oil or fasting, and I think the The beauty of your program is it's not or, it's and. It's really bringing these factors and hormone correction, vitamin B12 status, normalizing vitamin D levels, normalizing homocysteine, you name it, bringing as many factors to bear and in line as possible because it's a compelling adversary that you're up against.

No question. One of the points here, as you well know, this is a terminal illness, so if you don't get at it completely— and so my argument is we're dealing with something that is an emergency, literally. You need to do everything possible, and the earlier the better. And I should say along those lines, you know, this is a biochemical problem that you can measure systemically, that has central nervous system manifestations, but it's really largely a systemic problem. So you want to manage it systemically. And the most important outcome of everything we've found so far is that when you see the improvement, It is sustained. We have not had a single person— there are now over 1,000 people on this— we've not had a single person who got the improvement, stayed on the protocol, and then went downhill. So unlike with all the other therapeutics, where you get a bump and then you go right back to decline, you see an improvement that is sustained because you are getting at the root cause of the problem.

And that is so important because, you know, clearly, these so-called Alzheimer's drugs, as if they really were, are not getting at the problem. Drugs designed to increase the availability of a chemical called acetylcholine, which was found to be depleted in the Alzheimer's brain, in these cholinesterase inhibitor drugs that are still sold, that's not the cause. That's multiple steps down the line. Right. When the brain is starting to contract and lose its functionality, or a term that you've used, which is downsizing. I'd like to— you've talked many times in scientific venues about this balance between the formation of brain cell connections called synapses and the degrading or the loss of these brain cell connections called synapses. You call it synaptopathy. Yeah. Synaptoblastic activity. And I think, you know, when we break that down, it's kind of an interesting way for individuals to understand where your program really does its magic.

That's exactly right. So, what we found— so, we, as you know, we were studying the basic molecular mechanisms underlying neurodegeneration. And what we found is that amyloid precursor protein, APP, could literally be cleaved to Signal in 2 different directions. It could either make neurites and make synapses, so synaptoblastic activity, or it could literally mediate pulling back and ultimately killing the cell, inducing apoptosis, so literally synaptoclastic activity. And then if you look at all the things that feed into that, that's where the 36 things came from. They feed into this beautiful balance. And then what's interesting is— This balance will actually accentuate itself, which is where you— which is where we believe prions come from. So the idea here is you have like a snowball rolling downhill effect. Either you're going to be making this, the synaptoblastic activity, or synaptoclastic activity. So we are altering that balance in these people, and of course, providing the appropriate constituents that it takes for the synaptoblastic activity. Right.

I'd like to say to our viewers that, again, we're having a bit of a science talk here, but this book, The End of Alzheimer's, was recently the number one book in all the books available on Amazon in America. That includes all the nonfiction, every book sold on Amazon. This was the number one book, so there are a lot of people that are getting this message. And what's been the response now that you've had this incredible success with this book?

Yeah, thanks, David. So we've had a lot of, a lot of interesting emails, as you can imagine. And you're right, we went to the number 1 book of the 8 million plus books on Amazon for a day. We've remained on New York Times bestseller list for 5 weeks now and counting. So very happy to see that people are looking at this and reading it. We're getting a lot of responses. Interestingly, some of them are saying, we've been doing this sort of thing for a while and have had good results with it. I'm always happy to see that. Others are saying, we're going to jump on this and start this immediately, or, how can we find a physician who practices this? And we've now trained over 600 practitioners from 7 different countries and all around the United States. So, my hope is that many, many more people will be practicing the sort of medicine that you've been practicing for years and the sort of medicine that we've been discussing. Of course, we've had the occasional person who will say, I simply don't believe this. And so, my argument usually is, look, line up the people that you've made better with another program, and we'll line up the people that are better on this program, and let's talk to these people. Let's ask them what's actually happened. And we've, as you know, published papers showing changes with hippocampal volume, showing changes with quantitative neuropsych assessment. So, clearly, we need to have larger and larger trials. This is easier Easier said than done, as you know, because IRBs like monovariable trials, and we're talking now about a program, but that's the way of the future.

To our viewers, Dr. Bredesen was recently telling us a story about how you demonstrated improvement, increase in the size of the brain's memory center called the hippocampus, in a patient who was on your program, and how the neuroradiologist looked at the brain scans and totally denied that that could happen. Was it he thought that there was an error, or it just wasn't real? How did that play out?

Yeah, I have to say, it's very interesting. People are not ready to see certain things. He said that they'd done over 70,000 scans at that particular hospital. They had never seen this before. He said— he just basically said straight out, it's impossible. I said, well, do you have the scans in front of you? He said, yeah. Are you seeing it? He said, yeah. I said, well, can I get a copy so I'll take it to another computer-based algorithm, which we did. And actually, it confirmed exactly what was seen. What was interesting, though, he was in the middle of changing the report to the patient. So instead of going from 17th percentile to 75th percentile, it was going to read that it went from 35th to 35th. And I said, well, how would you come up with 35th? And he said, well, you know, we would just kind of make that up so that we'd be clear that, you know, nothing— no rules of nature Nature had been broken. It's a crazy time because we're seeing things that have not been seen before.

Wow. I have to take that in. On the list, I wanted to ask you about vitamin D. We're hearing so much about vitamin D. Well, it's good to make your bones strong. It might have a role in inflammatory bowel disease, maybe in diabetes, but there is certainly a fundamental role for vitamin D, with vitamin D receptors being seen throughout the brain. You've added that in as one of your important points. What have you found with vitamin D, and why?

This is a really good point, David. You know, my argument is, if you, if you live indoors or you wear clothes, then you're likely to be vitamin D deficient or suboptimal, at least. And so What you see, and as you alluded to, the vitamin D receptor has specific mutations in some people with Alzheimer's. So it is a risk factor for Alzheimer's, the vitamin D receptor SNPs. And then if you look at vitamin D level, lower vitamin D level is associated with cognitive decline and Alzheimer's disease, as you mentioned.

And Parkinson's and multiple sclerosis and autism.

And as you noted, in the multiple sclerosis trial, you really had to get above 50 nanograms per mL to see an improvement with the MS. So the old idea that 20 or 25 is good enough is simply not correct. And so we typically try to drive people to between 50 and 80. And the suggestion has been, again, and we see many people coming in with cognitive decline with vitamin Ds in the teens or low 20s who do better. Now, Do we change that alone? Of course not. This is a concert. We change everything in parallel, but we certainly include vitamin D. Again, all of the epidemiological and biochemical work would suggest that it's one of the many important players.

Well, it's interesting that vitamin D segues back to our beta amyloid discussion in terms of acting as an antimicrobial peptide or activating cathelicidin, as an antimicrobial peptide, getting us to a place of maybe considering that there may be some involvement of some as-yet stealth infectious agent that may be involved in what you call downsizing the brain. Where are we on an understanding of the possible role of herpes simplex virus type 1, or chlamydia, or mold, et cetera, and their influences upon the brain? Yeah.

Yeah, David, this is one of the most interesting and most important areas. It is absolutely clear, and the more we look, the more we see it. You've done all this wonderful work on the microbiome, the gut microbiome. We're finding more and more that there is probably going to turn out to be a normal brain microbiome. I always was taught that the brain should be absolutely a sterile organ. That may not turn out to be the case. Certainly, the rhinocinal microbiome, is turning out to be absolutely critical. And as you indicated, when you look in the brain of a patient with Alzheimer's, what has been reported? Fungi, spirochetes, oral bacteria, molds, the, you know, herpes simplex, as you mentioned. So this is turning out to be a veritable zoo of organisms. And in fact, what is your amyloid doing there? It is a beautiful antimicrobial agent, as Rudy Tanzi and Robert Moyer from Harvard have shown beautifully over the last few years. So absolutely, if you want a brain to make amyloid, expose it to some biofilms and some chronic pathogens. And initially, we identified what we call type 3 Alzheimer's, where we frequently saw exposure to mycotoxins and molds. What we're finding now is that although that type 3 represents about 20% of all people with Alzheimer's, if you look at the contributions So, in other words, how many of these people have chronic pathogens? It's the majority. So, most people with Alzheimer's disease or pre-Alzheimer's have exposure to chronic pathogens, and either we need to eradicate those— and one of the big questions is, should we be doing it by things like educating the immune system the way we are now doing to tumors? Do we need to do that for Alzheimer's as well? Do we need to change the microbiome in the brain, the sinuses, and the gut? Yeah.

Recently, a publication came out that demonstrated that individuals with the so-called Alzheimer's gene are carrying the APOE4 allele, which we have all believed conferred significant increased risk, as it does in Western cultures, was actually protective in concert with high parasitic load in a certain indigenous group of individuals living in South America. In other words, These are people who had preserved cognitive function, carried the so-called Alzheimer's gene, and had a much higher, what we call eosinophil count, so a surrogate marker for high level of parasites. Kind of runs in the face of our notion about the APOE4 gene and Alzheimer's, but on the other hand, I think it sort of, again, reinforces the interplay. Yeah. between infectious agents and our genomes that has been going on an awful long time. So, I mean, I think your comments about organisms and the brain are certainly well taken. Exercise is a really critical part of your program. How did that enter into it?

Yeah, and not only from the— from looking at the APP, you know, the inputs to APP biochemically, but actually from direct observation of patients. So we've had some people where literally The spouse can tell whether the person has exercised that day. We have one person who, for example, when she exercises, she's clearly better for several hours after that. When she misses her exercise, she's clearly worse. Of course, theoretically, as you know, it is an important inducer of ketosis. So, and as well as other things, PGC-1 alpha effects, you know, oxygenation to the brain, on and on. of course, improved insulin sensitivity. So by multiple mechanisms, exercise, you could argue, is one of the most important of all of the dozens of things that are critical for your cognition and for an anti-Alzheimer effect.

And how about sleep?

Sleep is, I think, one of the most underappreciated things. And so many people, as you know, 70% of people who have sleep apnea go undiagnosed during their lifetimes. So it is absolutely critical. Sleep apnea is an important contributor. Again, it impacts on the same signaling. It impacts because of the hypoxia. It impacts because essentially having a toxic effect, the increase in carbon dioxide, etc. And of course, the increase in adrenaline. You're now jolting yourself back awake. Repeatedly. So it absolutely impacts, and we recommend that everybody get evaluated, anyone with cognitive decline get evaluated for their sleep status. And beyond, of course, beyond sleep apnea, there's also upper airway resistance syndrome, so-called UARS, which can also be important.

And self-arousal with periodic leg movements, a variety of things that can interrupt restorative sleep. You know, as you know, I have a very strong family history of Alzheimer's. And as such, I went ahead and had a sleep study and have made some modifications based upon that. In moving forward, there's a beautiful movie that I'm told about, a really exciting movie. Can you tell us about that?

So there is a documentary film that will be coming out, should be coming out in the spring. There's still follow-up on some of the patients, and basically following people through to look at, you know, what were the problems? How did these impact their families and their lives? And then what happened when they actually went on the program? And as they improved, how did that change their lives? Because, as you know, this is something that impacts so many people. Just about everybody knows somebody with Alzheimer's or has had some interaction with someone with Alzheimer's. And yet, as you know, it's always said, everybody knows a cancer survivor, no one knows an Alzheimer's survivor. Of course, We're all seeing the first ones now. We're actually just putting a paper together from a number of different physicians documenting another 50 people who all had marked improvements.

Let me ask you then, you had mentioned earlier about training physicians around the world to implement the protocol that you've developed. How would a person get involved in that? What are people to do to learn about this information.

Yeah, that's a great point, David. And I just received a very interesting email from a whole group of physicians in Switzerland that are very interested in this and want to know how can they put together something. So we're doing 2 things. Number one is that we are interacting with the Institute for Functional Medicine to provide training. We've had a few already. There was one just recently in Dallas. There's one December 2nd and 3rd in Miami. There should be one in April in London. There will be 4 in 2018 in the U.S. and probably 1 outside the U.S. So, we are continuing with those training, not only physicians, but also other practitioners, health coaches, as you know, so important, neuropsychologists, nurse practitioners, nutritional therapists, and on and on. And so now there is also a new coaching training that IFM is also working with. Secondly, we are, as you know, working with a group, a group that initially you introduced me to, to establish the first institute, the very thing that you and I have talked about over the last few years, the need for an institute where people can come specifically for reversal of neurodegenerative illnesses, not only Alzheimer's, but other neurodegenerative illnesses, using computational approaches, using neural exosomes, using everything that is at the cutting edge to induce, to look at all the different contributors and to induce the first people who are actually showing improvements. So we're very excited about that.

So for our viewers, we're going to put— it'll probably appear right now on your screen— information about how you can learn more about Dr. Bredesen's work and how you could get involved for yourself or for a family member. That's available. It's amazing work. As I said on your book, it's monumental, and I think it's It's iconoclastic in a very, very good way. It is— you've really brought a level of recognition to this narrative that has been needed for so very long. My hope is that this approach will transcend just the neurological neurodegenerative conditions, and we'll begin to look at things like cancer, and heart disease, and diabetes, for example, from this more encompassing idea of prevention, of the role of lifestyle management, of epigenetics, how our lifestyle choices influence our genetic expression, the interplay between the microbiome and these various body systems. So, it's really very, very exciting to watch this evolve, and to see a guy like you at the forefront, making it all happen. So, you're doing amazing stuff. Congratulations. Thank you.

Thank you very much, David. And as you know, all of us working together should be able to make dementia, and beyond that, complex chronic illnesses rare. And this is the beginning that we're all in. We are in a part of history where we are now able to attack these complex chronic illnesses successfully for the first time. So thank you very much for having me.

Pleasure. Well, thanks for being here, and I hope we get a chance to talk soon.

Thank you, David.

Okay. Bye for now.

Okay. Bye-bye.

Well, as I mentioned at the— in the introduction, an honor and a pleasure. An honor to speak to such a pioneer, a revolutionary who is clearly bucking the mainstream in terms of the dogma of hoping for a magic Magic bullet to treat a problem with one modality. And, you know, as you heard Dr. Bredesen mention, it's not that he's against medication. Medication is a part of his program, but it's not the central piece. It's just a player in the orchestra. Dr. Bredesen, as you heard, is having results, positive results, in treating a disease for which we had thought there was no treatment whatsoever. So this is really revolutionary. As I stated on the COVID of his book, that this is clearly a monumental work. And what an honor to know Dr. Bredesen. What an honor to be living at a time when a guy like Dr. Bredesen is out there challenging the mainstream and having incredible success. So we wish him and his efforts All the best, and I certainly can tell you that he's going to continue to make great advances in neurodegenerative conditions. So I hope you enjoyed today's interview, a very exciting, revolutionary type of experience we're learning about. Thank you so much for joining me. I'm Dr. David Perlmutter. Thank you.