Alzheimer’s Research Controversy with Dr. Dale Bredesen: Rational Wellness Podcast 271
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Dr. Dale Bredesen discusses Alzheimer’s Disease Research Controversies with Dr. Ben Weitz.
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0:35 Alzheimer’s disease is the most common form of dementia and it’s the most common neurodegenerative disease, and numbers are increasing. Conventional medical research has not produced any successful drugs or treatments. Last year a controversial drug–Aduhelm (aducanumab) was approved for the treatment of Alzheimer’s disease, but it actually failed 3 of the 4 clinical trials that were conducted and while it reduces amyloid plaques in the brain, patients with Alzheimer’s disease do not actually improve but only get worse at a slower pace. And 35% of patients get painful brain swelling and some also get bleeding in the brain.
1:45 On July 21st in Science, an article was published that blew the lid off of the Alzheimer’s disease research. It was revealed that images were likely falsified that were included in the landmark study published in 2006 by Dr. Sylvain Lesne, Karen Ashe, and others that was supposedly the first to proved that beta amyloid is actually the cause of Alzheimer’s disease. This study was referenced in over 2000 other studies and is the basis of hundreds of millions of dollars of NIH and drug company research. Therefore, this is perhaps the largest scandal in the medical research field and appears to me to call into question the 30-year-old beta amyloid Alzheimer’s disease hypothesis.
2:40 Another important paper, with Dr. Dale Bredesen as the senior author, was also published online in July in the Journal of Alzheimer’s Disease that demonstrates for the first time that a precision medicine approach, (a Functional Medicine approach) can actually reverse Alzheimer’s disease. [Precision Medicine Approach to Alzheimer’s Disease: Successful Pilot Project. Toups, Kat et al.]
4:03 I asked Dr. Bredesen what the significance of this science article that alleges fraud that appears to have been committed by Dr. Lesne and possibly others? His answer is “The Titanic that is mainstream medicine is sinking right before all of our eyes, having crashed into the iceberg that is chronic illness and that is the problem.” Alzheimer’s Disease, like diabetes and lupus and heart disease and cancer, is a chronic disease that is not going to be properly addressed by simply prescribing a drug. Alzheimer’s disease researchers have developed many drugs to remove amyloid–bapineuzumab, solanezumab, gantenerumab, crenezumab, aducanumab, donanemab–but they don’t reverse the condition and at most slow down the progression a bit. While Western medicine can effectively treat many types of infections, it is not effective for complex chronic illnesses like Alzheimer’s disease.
6:27 Dr. Bredesen used the following analogy to explain why the reductionist approach of conventional medicine fails when dealing with complex, chronic diseases: “imagine that you took your jets from all the different jets that are flying, from all the different groups, from Delta, United, American and so forth and so on, and you took them in for servicing, but you said you can only limit it to one prescription. You give one thing, you can either fill it up with gas or you can fix the oil, or you can look at the engine, but you can only do one thing. These jets would be crashing left and right.” If you see a patient with hypertension and instead of asking why that patient has hypertension and all you do is write a prescription that prevents your body from doing what it’s trying to do. This is an outdated way to practice.
7:27 To be fair to Dr. Lesne and Dr. Ashe and the other researchers involved in this scandal, it should be pointed out that this started with an investigation into a drug being developed by Cassava Sciences, and Martin Schragg, the neuroscientist who discovered the falsified images, was being paid by a financial firm that was shorting the stock to make millions of dollars, so this is quite questionable and likely illegal.
9:01 One of the issues with Alzheimer’s research is that while we know that amyloid has something to do with the condition, it is not the root cause, which is why drugs that reduce amyloid do not make patients better. Amyloid is more a mediator than a cause. As Professor Rudy Tanzi has shown, amyloid is an antimicrobial peptide that results from infections in the brain among other insults. What Dr. Bredesen’s research has shown is that there is often a network insufficiency, so you may need more energetics, more mitochondrial function, blood flow, oxygenation, and keytones. You need growth factors like NGF and BDNF, hormones like estradiol and testosterone and nutrients like vitamin D. On the negative side are various toxins like mycotoxins, inorganics, organics, air pollution, inflammation… etc.
15:03 The pandemic created conditions likely to increase the risk of Alzheimer’s disease over time. Citizens are ordered to stay in their homes and everybody is very stressed out. Many people ate poorly and did not exercise since gyms were closed and the average person gained 29 lbs. And we have a virus ravaging the country that we know penetrates the brain. Many patients after COVID end up with brain fog as a part of long COVID. We don’t know, but in some cases this may be one of the earliest stage of Alzheimer’s and there have been several people who have developed Parkinson’s disease from COVID. The first period you’re asymptomatic but you can pick up changes on PET scans and spinal fluid. Then you have Subjective Cognitive Impairment (SCI), which lasts about 10 years. During this stage, you know something is wrong but you may score normal on standard cognitive testing. The third stage is Mild Cognitive Impairment (MCI), which is actually a relatively late stage of the disease. And then the fourth and final stage where you’ve now begun to lose activities of daily living is, of course, what we call Alzheimer’s.
17:38 Dr. Bredesen just published a paper online in the Journal of Alzheimer’s Disease and it will be published in print this month (August): and just basically showing that with a proof of concept trial, we made 84% of the people actually better: [Precision Medicine Approach to Alzheimer’s Disease: Successful Pilot Project. Toups, Kat et al.] 84% of patients got better and had improved cognitive scores and their gray matter in their brains got larger on mri. This trial uses a functional medicine approach looking at inflammatory markers, various metabolic pathways, pathogens, toxins, nutrient levels, etc..
22:18 Dr. Bredesen’s approach is not being well received by the conventional neurology community because they have been trained to practice 20th century medicine and they are reluctant to give up that approach. We need to teach 21st century medicine (precision medicine, functional medicine, integrative medicine, P4 medicine) in medical school. Instead of just asking what is it and then writing a prescription, we need to ask why is it? What are all the things that contributed to the current state of affairs? We need larger data sets and we need to look at how we can address all of the different contributors to neurodegeneration.
23:48 Two Contrasting Studies. We need to get the word out about these 2 contrasting studies. One study with aducanumab, where they are trying to argue for efficacy, when it’s clear that this drug did not really have a significant impact, and the other study using a precision medicine/Functional Medicine approach where it’s clear that there were more improvements. To do justice to a Functional Medicine approach we need a new model for scientific studies. According to Dr. Bredesen, “So we’ve got to find a better way to do our trials. And again, we have to match up the way we do with trials with what the science is telling us. The science is telling us this is not a single variable problem. This is a network insufficiency. And to get best outcomes, we’re going to need to address different parts of that network.”
29:03 The best benefit for patients with Alzheimer’s and other chronic diseases is to intervene as early as possible. For Alzheimer’s disease the early signs break down into an amnestic and a non-amnestic presentation. Amnestic patients typically have problems with short term memory like remembering where they left their keys or what they had for breakfast. The other, non-amnestic presentation patients will have problems with executive function and will have problems with planning. They also have trouble with word finding, what’s called primary progressive aphasia or it’s trouble with recognizing shapes and faces, what’s called posterior cortical atrophy. They can have trouble with calculations, another parietal lobe problem. Dr. Bredesen said that when he sees patients with a non-amnestic presentation, especially if they’re relatively young, they’re in their fifties, for example, they are strong candidates for toxin associated cognitive decline, often related to biotoxins such as mycotoxins.
31:48 Cognoscopy. Dr. Bredesen recommends that everybody who is 45 years or older get a cognoscopy, which includes very detailed lab testing much beyond the limited labs included in a typical annual exam, a simple online cognitive assessment, then if you have symptoms or score poorly on the cognitive exam, an MRI with volumetrics, such as a Neuroquant. If this is the case, then you want to get on active prevention. There is a tendency for neurologists to see mild forms of cognitive dysfunction as part of normal aging and to just wait until things get bad and then you take a drug that doesn’t help much. The goal is to keep everyone sharp until 100.
33:47 Conventional neurologists also do not recommend that patients check their APOE status, which is the most common gene association with Alzheimer’s. If you have no copies of AOE4 your lifetime risk of Alzheimer’s is 9%. If you have a single copy of APOE4, it’s about 30%. And if you have two copies, it’s way over 50%, so most likely, you will get Alzheimer’s. You should check your APOE status early and get on appropriate treatment and prevent yourself from getting Alzheimer’s disease. A cognoscopy will look at many sources of inflammation, including leaky gut and even the oral microbiome, since these pathogens can get into your brain. And if pathogens do get into the brain, it coats them with amyloid to kill them and bar them from getting to the rest of the brain. Some people are lowering their oxygen to their brain due to sleep apnea. For some people, it’s more vascular, so it’s important to know what and why your risk is.
36:22 Nutrient status. Mainstream medical doctors will tell you that supplements are not a cure for Alzheimer’s and of course, they are not, but as part of a program that involves diet, exercise, and lifestyle changes, appropriately chosen nutritional supplements can play a positive role. Part of preventing Alzheimer’s is to eliminate network insufficiency. Take vitamin D, which interacts with so many receptors around the body. It enters the nucleus of the cells and affects hundreds of genes so that it changes your immune system, your response to COVID, your heart disease related problems, your calcium metabolism, and your cognition. Vitamin B12 deficiency has been associated with cognitive decline and we need not to just have enough to get to normal limits. You can have normal levels and die from having too little B12. You need to get your B12 levels at least 500 and 300 is not optimal. Omega 3 is important, as are resolvins, their cousins. Magnesium is essential. Studies are showing nutritional levels of lithium are important both for behavioral problems and for cognition. And poor diet can contribute to Alzheimer’s, though diet alone will not cure Alzheimer’s. Dr. Bredesen recommends a plant rich, mildly ketogenic diet and he likes to see people have a 1.0-4.0 millimolar betaydroxybutyrate on a blood test and 10-40 for acetone on a breathalyzer test.
40:25 Dr. Bredesen’s favorite neurocognitive assessment tests are CNS Vital Signs, which is best for SCI (subjective cognitive impairment) and MoCA (Montreal Cognitive Assessment), which is best for MCI (mild cognitive impairment).
Dr. Dale Bredesen is a neurologist and an internationally recognized expert in the mechanisms of neurodegenerative diseases like Alzheimer’s Disease and the Chief Science Officer at Apollo Health. He is the author of the best selling books, The End of Alzheimer’s, The End of Alzheimer’s Program, and The First Survivors of Alzheimer’s. Dr. Dale Bredesen’s career has been guided by a simple idea: that Alzheimer’s as we know it is not just preventable, but reversible. Thanks to a dedicated pursuit of finding the science that makes this a reality, this idea has placed Dr. Bredesen at the vanguard of neurological research and led to the discoveries that today underlie the ReCODE Report. Dr. Bredesen offers training for doctors and practitioners in his ReCODE system at his website at ApolloHealthco.com.
Dr. Ben Weitz is available for Functional Nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss and also athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.
Dr. Weitz: Hey, this is Dr. Ben Weitz, host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting edge health information. Subscribe to the rational wellness podcast for weekly updates and to learn more, check out my website, drweitz.com. Thanks for joining me and let’s jump into the podcast.
Hello, Rational Wellness podcasters. Today, we’re going to be talking about a controversy in Alzheimer’s disease research. Alzheimer’s disease is the most common form of dementia and it’s the most common neurodegenerative disease, and numbers are increasing. It’s crucial that we make some progress on preventing and treating this horrific condition, but conventional research has not been all that fruitful and has centered on the role of beta amyloid protein plaques that are found in the brains of most patients with Alzheimer’s disease. No successful drugs or treatments have been developed based on this amyloid theory of Alzheimer’s prior to the approval of Biogen’s Aduhelm last year. But this drug was approved with much controversy. Since it failed three of the four phase three clinical trials conducted by Biogen and three of the scientists on the FDA advisory board resigned in protest over this drug being approved. While at Aduhelm does reduce amyloid plaques in a brain, none of the patients get better, but only get worse at a slower pace. And 35% of patients get painful brain swelling and some also get bleeding in the brain.
And then on July 21st in Science, an article was published that blew the lid off of the Alzheimer’s disease research. It was discovered after a six month investigation by Science Journal, that the results were falsified. In the landmark study published in 2006 by Dr. Sylvain Lesne, Karen Ashe and others that supposedly was the first to prove that beta amyloid protein was actually the cause of Alzheimer’s disease. This is perhaps the largest scandal in the medical research field and appears to me to call into question the 30-year-old beta amyloid Alzheimer’s disease hypothesis. Since this study was referenced in over 2000 other studies and is the basis of hundreds of millions of dollars of NIH and drug company research.
On the other hand, another important paper on Alzheimer’s disease was also published in July, this in the Journal of Alzheimer’s Disease, the paper that demonstrates for the first time that a precision medicine approach, what I would describe as a functional medicine approach can reverse Alzheimer’s disease. Though, interestingly, it got much less attention than the other article that I just mentioned. No presidential medal of freedom, no noble peace prize nomination. The principal author of this study is Dr. Dale Bredesen, who’s joining us today. Dr. Bredesen was the chief resident in neurology at the University of California, San Francisco and he’s the founding president and CEO of the Buck Institute Program on Aging. Dr. Bredesen has published over 200 scientific papers and he’s written a number of books, including The End of Alzheimer’s, The End of Alzheimer’s Program and The First Survivors of Alzheimer’s. Most importantly, he has developed this precision medicine program that he calls to ReCODE protocol that he’s teaching other doctors and practitioners that is the only treatment that has ever been shown to reverse Alzheimer’s disease. Dr. Bredesen, thank you so much for joining us today.
Dr. Bredesen: Great to talk to you, Ben. Thanks for having me.
Dr. Weitz: Excellent. So what do you think is the significance of this science article that demonstrates that this alleged fraud was committed by Dr. Lesne and possibly by others that he worked with?
Dr. Bredesen: Yeah. Great point. And you know, let’s pull back to the most important point here that you touched on a minute ago. The Titanic that is mainstream medicine is sinking right before all of our eyes, having crashed into the iceberg that is chronic illness and that is the problem. Whether you talk about Alzheimer’s, frontotemporal dementia, Louie body disease, ALS, autism spectrum disorder, late stage cancers, lupus, just go right down the list. We as physicians have been very successful at simple illnesses, pneumococcal pneumonia, TB, even HIV, which took three drugs, instead of one. These are the sorts of things we’ve been very successful with. We have not been successful, as you know, over 40 billion has now been put into Alzheimer’s research and drug development with nothing that really moves the needle. And so what happens is people keep going back to the idea, okay, can we remove the amyloid? Is that going to make you better? And the answer time, after time, after time, bapineuzumab, solanezumab, gantenerumab, crenezumab, aducanumab, donanemab. Oh my gosh. But because there are hundreds of billions of dollars in the offing, if you can just get past the bar and the bar is very low, it’s not even make people better, it’s not even keep people steady, it’s can you slow the decline? And in the case, as you mentioned, in aducanumab in one trial at one dose, it slowed the decline by 22%. That’s it. And that was set to make hundreds of billions of dollars, but the problem is that unlike these simple illnesses where we know what causes COVID 19, we know what causes pneumococcal pneumonia, and in those cases, as long as we get after that main pathogen, we do pretty well. Unfortunately, Alzheimer’s is not that simple. It is a complex chronic illness.
It’s so interesting to me it’s as if imagine that you took your jets from all the different jets that are flying, from all the different groups, from Delta, United, American and so forth and so on, and you took them in for servicing, but you said you can only limit it to one prescription. You give one thing, you can either fill it up with gas or you can fix the oil, or you can look at the engine, but you can only do one thing. These jets would be crashing left and right. And it’s time for all of us to recognize that human beings are complex organisms. So this old fashioned idea that, oh, you have hypertension, we’re not going to ask why you have hypertension. We’re just going to write you a prescription that prevents your body from doing what it’s trying to do. And this is really barbaric and it’s really outdated and this is just the latest. We’re watching that next piece of the Titanic going down mainstream medicine. So we need to look at larger data sets.
And so to be fair to Dr. Lesne and Dr. Ash and I’ve known Dr. Ashe personally for almost 40 years now. She is a brilliant neuroscientist and neurologist, MD, PhD from Harvard. I have no doubt that she was doing the right thing. I don’t know about the postdoc. I don’t know him personally. And there have been some questions about other data that he has published as well, so the jury is still out. As you know, this actually came from looking into a company that had used their data to go the next step and this was to create a drug. This was Cassava Sciences to create a drug called simufilam. And the idea was it looked as if some of their blocks were questionable. And so there was a question raised about data coming out from both of those groups. And as you probably know, the Department of Justice is actually now looking into the Cassava Sciences situation. Now you can argue about whether it’s appropriate to criticize a study when you own the stock and you’ve shorted it purposefully to make many, many millions of dollars. It seems like that probably should be illegal. It’s a little bit like insider trading. You’re going to go short the stock, and then you’re going to go complain about the company and make lots of money, so that’s a separate issue, I think. It’s more of an ethical issue and legal issue, but there’s no question. And of course, others have been interviewed on this very topic.
There are some red flags in the research coming from both of those. And one of the issues here is people have gone, as you mentioned, just gone after, hey, this is an amyloid disease. Let’s get rid of the amyloid and let’s make it better. Unfortunately, that still hasn’t happened. So we have to now update our thesis. Amyloid is clearly involved in some way, potentially as a mediator, but it is not the upstream cause. And when you get rid of it, it doesn’t make things better. And so the work we’ve done in the lab, as you mentioned, we published over 200 papers on this and what we see is that amyloid is indeed just as Professor Rudy Tanzi and Robert Moir said several years ago, it is a response to various insults. And as they showed, it is an antimicrobial peptide. So what our research showed over the years is that the fundamental nature of the disease that we call Alzheimer’s is actually a network insufficiency. So you have all these different factors and it’s basically four big groups. It’s energetics, you need enough energetics, mitochondrial function, blood flow, oxygenation, keytones all of those. You need enough trophic support and that’s growth factors like NGF and BDNF and that’s hormones like estradiol and testosterone and that’s nutrients like vitamin D. So those are the first two groups. And then the other groups which are on the negative side are the various toxins, so things like mycotoxins, inorganics, organics, of course, air pollution. A lot of this has been an issue with the air pollution and of course, the California fires. We are at increased risk. And then finally, anything produces inflammation and you can literally trace the molecular biology as NF-kappa B gets activated, for example, and changes your production of amyloid goes literally from a growth and maintenance mode, over to a protective downsizing mode.
And it really is a beautiful story. It’s very much like what we saw in our country that happened with the pandemic. We were all told shelter in place, socially distance, don’t go to work, do your meetings on zoom and what happened? We go into a recession. So that’s the same thing your brain is saying, okay, I’ve been exposed to various toxins, various pathogens, and I’m going to go into a protective downsizing mode. And the amyloid is part of that. Now, unfortunately, yes, amyloid causes you to lose synapses. And so there are multiple forms of amyloid and each one has its own effect, but ultimately these things impact your mitochondrial function. They impact your insulin signaling. And so Dr. Ashe, I believe, in her papers was going after is there one predominant form that is the toxic form and they did beautiful work. Now we’ll see if it holds up, but they did beautiful work to show that there’s something called a beta star 56, one particular form that seems to be quite toxic. Now my argument would be, yeah, it’s part of the downsizing and let’s face it, all the other ones have some degree of toxicity as well. Now, a number of other labs have tried to repeat that work. It’s not been clear. That hasn’t been held up as, yes, this is the obvious thing. This is the only thing that causes the problem. And again, I would argue that this is more of a mediator, just like tau is also a mediator. These are mediators rather than the upstream cause. And that’s important because when you go after them, if you’re just going to remove that, but you don’t remove the cause, you’re going to have long-term problems, of course. So there are all sorts of theories. It’s herpes, it’s type three diabetes. As you know, theory, after theory, after theory, none of them has led to an effective treatment for this disease.
Dr. Weitz: Right, because they’re using this stripped down analytical, there’s got to be one pathway with one drug. I want to make a couple of points. One, just to wrap up what we were saying about the study is one of the things to say is that the original researcher, this Schrag guy, he was working for a hedge fund that could solve a drug, but the data that’s been reported in science was Science Magazine took his data and then they did their own six month investigation without any sort of hedge fund involved or anything else and hired several doctors, several experts at imaging and took six months to really investigate this before they actually reported their findings. So I think we should be pretty confident that those findings are free from influence.
Dr. Bredesen: Absolutely.
Dr. Weitz: And then second of all, one of the points that you’re making is we always have to think about the human body and the wisdom of the body and if the body is laying down a protein in the brain that’s damaging us, we’ve got to ask ourselves what’s going on? Our body doesn’t just lay down proteins to cause damage, to harm us. There’s usually a reason why. The reason why the body’s laying down cholesterol in the arteries is not to cause us to die of heart disease, it’s to protect the arteries from inflammation. And so therefore, the point you’re making about the brain is that the amyloid is actually helping to protect the neurons from infections, Rudolph Tanzi found out for the first time that, actually, pathogens like bacteria and viruses, and maybe even fungi can penetrate the brain and then also heavy metals and other toxins and all these things can cause damage to neurons. And the amyloid is originally the body’s attempt to try to protect us.
Dr. Bredesen: All these things.
Dr. Weitz: Oh yeah. The other point about the pandemic. If we ever wanted to have a situation that’s liable to increase the risk of Alzheimer’s disease, let’s close all the gyms. Let’s cause everybody to stay inside. Let’s have them stressed out. Average person gained 30 pounds. And then on top of that, we have this virus ravaging the community, a virus that we know penetrates into the brain. All the conditions are there the last two years. It’s not going to surprise me if we have an increase in Alzheimer’s disease.
Dr. Bredesen: Yeah, no. And that’s been one of the big concerns. As you know, there are all sorts of factors that influence us and just for perspective, let’s point out that there have been over a million Americans who have died from COVID 19. Of the currently living Americans, about 45 million of us will die of Alzheimer’s, so it actually dwarfs the COVID 19 pandemic, unfortunately. It’s just that, of course, it goes more slowly. So yeah, absolutely, there is a concern. There’ve already been a couple of people who developed Parkinson’s, as you know, associated with COVID 19. Fortunately, it’s only been a very few, so time will tell whether that… And I think what’s happening so far is that we’re seeing much more brain fog, especially in the long COVIDs, where people just know something is not quite right. And this may be the earliest stages because I think it’s important to point out that you don’t get Alzheimer’s overnight. You really go through four phases.
And what we call Alzheimer’s is literally the fourth and final phase. So you have a period where you’re asymptomatic, as you know, but you can already pick up changes on PET scans and spinal fluid. Then you go through SCI, subjective cognitive impairment, which actually lasts about 10 years, surprisingly, where you’re still able to score normally on standard cognitive testing, but you know there’s something wrong. And then the third of four stages is called MCI, mild cognitive impairment. That’s an unfortunate name because it’s a relatively late stage of the disease. It’s like telling someone don’t worry, you only have mildly metastatic cancer, very unfortunate term. And then the fourth and final stage where you’ve now begun to lose activities of daily living is, of course, what we call Alzheimer’s. So if everybody would come in the first two stages, prevention or early reversal, instead of the last two stages MCI or Alzheimer’s, which is the typical story, then we really could make this a rare disease, which is what it should be.
Now, you mentioned the paper we just published and it’s actually coming out in print this month, but it came out online in July in the Journal of Alzheimer’s Disease and just basically showing that with a proof of concept trial, we made 84% of the people actually better. They improved their cognitive scores, didn’t just slow their decline, improved their scores. And it was, of course, a functional medicine approach, going after what’s causing the problem, looking at their inflammatory markers, their various metabolic pathways, pathogens, toxins, all these sorts of things. And we showed in that paper that, in fact, we improved the metabolic profiles of these patients. And in association with that, now we don’t know if it’s causal, but in association with that, not only did they improve their cognitive scores, improve their partner’s assessment of, oh, how well are they doing day-to-day? So there’s really real world improvement. But in fact, we actually improved their MRIs as well, so that their gray matter actually got larger. So just striking effects on these people. And we’re using those data to start a larger randomized controlled trial.
Dr. Weitz: That’s great. How many people are going to be in that trial?
Dr. Bredesen: This new trial, actually, we proposed initially a hundred, the statisticians came back to us and said, no, you’re having such big impacts on these people, you don’t need a hundred. The reason for these 1500 person trials that the drug companies are doing is because the effect is so small. You can’t get a statistically significant difference unless you do thousands of people. So for the effects we’re getting, we only need to do 72. We’ll have 48 of these in the treatment group initially. And then 24 in the control group that will get standard of care. Then after nine months, the control group, if they would like to, will then have six months of free treatment with the approach that we’re taking, the precision medicine approach. So everybody will ultimately be treated, but of course, it’s important to compare it to standard of care.
Dr. Weitz: That’ll be really interesting to see a group that gets standard of care and then does get some of the care, but a shorter period of time and then the other group.
Dr. Bredesen: Absolutely. And I should say, I’m really honored to be working with three absolutely outstanding physicians in the first paper and now six outstanding physicians for the second paper. We have Dr. Kat Toups from the East Bay here near San Francisco. We have Dr. Ann Hathaway, who’s right here in Marin County. We have Dr. Kristine Burke, who’s from Sacramento, Dr. David Haase from Nashville, Dr. Craig Tanio from Miami and Dr. Nate Bergman from Cleveland. So really excited to be working with six now absolutely outstanding physicians. We had three for the first group, and I should mention Deborah Gordon as well, who is in the first study, but is actually just retiring now.
Dr. Weitz: That’s great. That’s awesome.
Dr. Weitz: We’re having a great discussion, but I’d like to interrupt our talk for a few minutes to tell you about our sponsor for this podcast episode, Integrative Therapeutics. This is one of the few professional brands of nutritional supplements that I carry in my office. I’d like to highlight some research with Integrative’s highly bioavailable and absorbable form of curcumin called Theracurmin. A study was conducted at UCLA for 18 months with elderly men with memory decline, though not Alzheimer’s disease. And the study showed that this regular dose of Theracurmin, which is two capsules a day, resulted in significant improvements in memory and in mood. They also did PET scans of 67% of the subjects in the study and noted a significant decrease in amyloid tangles and Tau proteins in the Theracurmin group. A second study was completed in 2021 and published in current Alzheimer’s Research using Theracurmin and they looked at Alzheimer’s patients in this study with mild cognitive impairment, and they gave them Theracurmin for six months, the typical dosage of two capsules a day. And while they did not see a reversal of impairment, they did observe that the Alzheimer’s disease stabilized and cognitive decline was completely halted, which is an awesome result, much better than any of the leading Alzheimer’s drugs. And now back to our discussion.
Dr. Weitz: How well is your information being received by the conventional neurology community?
Dr. Bredesen: That’s a great point, not well at all. And so this is the problem. What we’re saying is guys, you’re all sitting on the Titanic, writing in prescriptions as it’s going down because of the chronic illnesses. You need to change course. You need to do something completely different. The problem is when your whole medical school experience, when your whole career has been about 20th century medicine, you’re very reluctant to give that up and to say, okay, this is actually going in the wrong direction. It’s very hard for people to admit, hey, this is going in the wrong direction.
So I do think in the long run, we need to teach in medical school more modern medicine, more 21st century medicine, more precision medicine, functional medicine, integrative medicine, P4 medicine, whatever you like to call it, where instead of asking the question, what is it? Is it lupus? Is it RA? What is it? And write a prescription, we need to ask, why is it? What are all the things that contributed to the current state of affairs? Human beings are complex organisms. There’s no question about it, especially when you’re trying to treat their brains. And so we need to have these larger data sets and we need to look at how we can address all of the different contributors to neurodegeneration.
Dr. Weitz: Yeah. I think what we just said about these two contrasting studies, that’s got to be common knowledge that conventional medical model is just not working for chronic diseases that are the main problem that we’re facing in medicine today. And just finding the one cause and the one drug is just not going to work for any of these conditions without addressing lifestyle and diet and exercise and sleep and exposure to toxins and nutrient status and all the other things that affect our bodies.
Dr. Bredesen: Yeah. I mean, you mentioned before, really, people have tried to ignore the fact that we just published, hey, for the first time, here’s something you can do about this disease. It’s not just anecdotes. And these clinical trials, they have a CTAD, which is clinical trials and Alzheimer’s disease meeting. This is a tale of two CTs. So two clinical trials, one with aducanumab where they’re trying to argue for efficacy, when it’s clear to anyone that they didn’t have an impact. And then here’s one where we’re using much more of a precision medicine approach where it’s clear that there were improvements. Now, one of the, I think, fair criticisms is you need to do a larger study and you need to do a control, where we used historical controls, in part, because when we first went to the IRB with this, they would not allow us. They said, look, this isn’t standard of care yet. So you got to start with an observational trial. If that works, then okay, now you go through more of a standard randomized controlled trial. Okay. Fair enough. So we’ll get there, but at the same time, we know what happens to patients with Alzheimer’s and MCI. They don’t typically get better. Yes, a few people with MCI may see an improvement, but I think to me, one of the best meters for comparison here is that we worked with a trial expert, Dr. Kat Toups, and she did dozens and dozens of trials during her career. And she never saw improvement. So she was part of this trial that we just published. In fact, she was the lead author on the trial and she has never seen results like this before, so that gives you someone who did lots of trials with standard of care. And now is doing a trial with a functional medicine approach and can see the much better outcomes.
Dr. Weitz: I’m sure one of the criticisms is going to be that what’s the acceptable model for study is that you just change one variable. Everything has to stay the same in both groups and one group gets one thing different and that’s because that’s the way you study drugs and anything else is not considered state-of-the-art research.
Dr. Bredesen: Exactly. Yeah. So we’ve got to find a better way to do our trials. And again, we have to match up the way we do with trials with what the science is telling us. The science is telling us this is not a single variable problem. This is a network insufficiency. And to get best outcomes, we’re going to need to address different parts of that network.
Dr. Weitz: Eventually, the whole medical model needs to change if we’re truly going to have a 21st century medicine that’s addressing the chronic diseases of today. This idea that the insurance companies are controlling the healthcare system and doctors are limited to this very short office visit where they can go in, figure out what the diagnosis is, write a prescription for a drug and that’s the end of the visit is just not going to work for these chronic diseases like autoimmune diseases, like Alzheimer’s, like diabetes, et cetera, cetera, that require a systemic of functional medicine or broader approach that involves changing diet, lifestyle, et cetera. So somehow the medical model has to change.
Dr. Bredesen: I couldn’t agree more. We as a society must decide if healthcare is ultimately about incomes or outcomes. The problem is it’s all been about incomes. How do they make more for this drug company? How do they make more for the healthcare model? And that’s why things are falling apart. We have to look more at outcomes. Can we get people to improve from these various diseases? Then we figure out how best to get them the appropriate protocol and what healthcare system will offer this. Those are the sorts of things, but we’ve gone down this blind alley and we’re now stuck at the end of it. Not to mix too many metaphors here, but we’re stuck at the end of this blind alley and it’s just not working. As everybody knows, medicine is broken. And you look at people who are practicing functional medicine. Oh my gosh, they’re getting better outcomes with cognition. They’re getting better outcomes with things like autism. They’re getting better outcomes with things like autoimmune diseases and you just go right down the list. And so we really need to be looking at how do we change medicine for the advantage of the patients instead of the companies.
Dr. Weitz: So the best benefit for patients with Alzheimer’s, just like it is for all these other chronic diseases, these autoimmune diseases, that there’s this long, long, slow progression towards disease. And how do we intervene as early as possible? So what are some of the most important early warning signs that somebody’s brain is going the wrong direction?
Dr. Bredesen: That is a great point. As you know, you can basically break it down into two groups, about two-thirds of people that are starting to have cognitive decline and ultimately down the road will have Alzheimer’s disease will start with what we call an amnestic presentation. So they’ll have problems with memory. And it’s typically short-term memory, it’s consolidation. It’s basically remembering what you had this morning for breakfast, remembering where you left your keys. And, of course, so commonly people say, well, I can’t remember this or I can’t remember that. And of course everything is backward because there hasn’t been a good treatment. So people will say, “Don’t worry, it’s probably not Alzheimer’s.” Well, that doesn’t help. What you want to do is fix whatever it is and make sure that you don’t get Alzheimer’s. Then the other one-third about of people will come in with a non-amnestic presentation and that is executive function, so planning problems.
I always ask people if you had to get a bunch of stuff together, throw it in a suitcase and get out the door in one hour, could you do that? And they’ll say, “Oh no, I can’t do that anymore.” They’ll have trouble at their jobs because they just can’t organize things the way they used to or it’s trouble with word finding, what’s called primary progressive aphasia or it’s trouble with recognizing shapes and faces, what’s called posterior cortical atrophy. Things like that, problems with calculations, another parietal lobe problem. So those are the non-amnestic presentations. And what we’ve found is that in general, as a general rule, when you have someone that has a non-amnestic presentation, especially if they’re relatively young, they’re in their fifties, for example, we see this now all the time, they are strong candidates for toxin associated cognitive decline, often biotoxins. So please look carefully at the mycotoxins. If someone is coming in in the fifties, they’ve got a non-amnestic presentation, especially if they’ve had some depression in association with it. This is something that I did not see way back in the eighties when I was a resident in neurology. And now it’s one of the more common presentations. And as you indicated, this is going on for years.
So we recommend everybody who is 45 years or older, please get a cognoscopy, just like we know you get a colonoscopy when you turn 50. And my wife and I had his and hers colonoscopies on Valentine’s Day when we were in our fifties. So we’re like, look, let’s get this over with and then we can relax a little. So everyone, please get a cognoscopy if you’re 45 or over, that’s some blood tests that look at these various things and things looking at the stuff that your doctor typically isn’t looking at. Second part of a cognoscopy is a simple online cognitive assessment. Everyone should have one of those to know where you stand because this can sneak up on you. And then the third part, if you have symptoms or if you score poorly on the cognitive exam, please also get an MRI with volumetrics, but if you did well and you’re just there for prevention, don’t need the MRI. And then, get on active prevention or the very earliest reversal I just had a group that contacted me the other day, husband and wife actually where they’re both physicians and the wife said, “Well, my husband is having problems and we took him to the neurologist and he said, oh yeah, this is just normal aging.” This guy had gone past phase one, past phase two, past phase three and now was in early stage of dementia, but he was told by his doctor, his neurologist, that this was just normal aging. And actually this guy turned out to have hydrocephalus.
So, oh my gosh, this should never be missed. Please, please get in early. The reality is Alzheimer’s should be a rare disease. We should keep our cognition. The goal is to keep everyone sharp to a hundred. And this idea that the current standard of care, you just wait for things to get really bad. And then you go in and get a drug that doesn’t help much. That is barbaric.
Dr. Weitz: So how did this neurologist miss that? Did he not give him a cognitive assessment test?
Dr. Bredesen: No. Well, what he did was he said, “This is just normal aging, so I don’t need to do anything more.” The other thing is, the foundations are hurting us, because one of their recommendations is you don’t need to check your APOE status. This is the most common gene in association with Alzheimer’s because there’s “nothing you can do about it” don’t bother to check it. Now, three quarters of the population is APOE4-negative. Typically, it’s a APOE33, which is the most common or APOE23, which is relatively resistant. Now, if you have no copies of APOE4, your chance of Alzheimer’s during your lifetime is about 9%, not too high, but it’s not zero. If you have a single copy of APOE4, it’s about 30%. And if you have two copies, it’s way over 50%, so most likely, you will get Alzheimer’s. Now the reality is none of these people should be getting it, check it early, get on appropriate treatment and prevent yourself from getting Alzheimer’s disease.
Dr. Weitz: Yeah, a similar situation exists with lipoprotein (a), LP little a, for cardiovascular disease because there’s no drug that’s presently approved to reduce it. Doctors don’t want to do the test. The insurance companies don’t want to pay for it. And of course, they’re working on a drug in a couple of years and once that drug’s available, then they’ll do the test, but the reality is, we need to know if this person has this atherosclerotic risk and there are things we can do naturally to reduce the risk.
Dr. Bredesen: Yes, exactly. So many things. And, again, if you get a cognoscopy, then you can actually get a report that looks at different pieces of this and says, here are your major risks. And so that people can know, ah, because some people it’s more about inflammation. It’s about specific pathogens or it’s about leaky gut. Of course, oral microbiome, as you indicated, these pathogens can get into your brain. And of course, what does your brain do in response? It coats them with amyloid to kill them and to bar them from getting to the rest of the brain, to cordon them off. That’s what amyloid does. And so you can get these things and you can look also some people it’s more atrophic. They don’t have enough support for their brain. Some people they’re lowering their oxygen. It’s more energetic. They lower their oxygen at night, for example. Some people it’s more vascular, so it’s important to know what your risk is and why your risk is.
Dr. Weitz: Can you just talk for a minute about how certain nutrients like vitamin D or omega-3s or some of these other nutrients, some of the B vitamins are crucial for brain health because you hear from a lot of the conventional primary care doctors that all the studies show that there’s no benefit to taking nutritional supplements.
Dr. Bredesen: Yeah. It’s so silly. It depends, of course, on how you couch the question, if you say, okay and what’s typically said is by the mainstream doctors, supplements are not a cure for Alzheimer’s. Of course, they’re not, nobody’s saying they are. And yes, to be fair, there are silly commercials that make claims where they haven’t supported them, when you’ve actually had a trial that gives you some support for, yeah, this actually helps. So you need to do that. But when you look at improving your neurochemistry and again, this is about a network insufficiency, so you got to find out what’s being insufficient. Is it because you’re asking too much because you got a lot of inflammation? Is it because you have low nutrient? And of course, poor nutrition is everywhere. We see it all the time with things like metabolic syndrome.
And of course, NASH, non-alcoholic liver disease, NAFLD, all this stuff. So, this is an issue and yes, as you indicated, vitamin D is a great example, one among many. Vitamin D, of course, interacts with its receptors. It enters the nucleus and affects hundreds and hundreds of genes so that it changes your immune system, changes your response to COVID changes your heart disease related problems, of course your calcium metabolism, but also your cognition. So that’s an important one. Of course, B12. B12 deficiency was shown and has been shown four years to be associated with cognitive decline. And it would always amaze me that, in what we call within normal limits, at the low end of that, you could literally die from B12 deficiency, but it was still being called within normal limits. You could be normal and die from having too little B12.
Again, we urge everyone get to that midpoint or above there. You want to be more in the 500 to a thousand range. You don’t want to be at the 300 or the 280 or any of that sort of stuff. And then there are others, as well. As you indicated, omega-3, resolvins, which are cousins of the omega-3s. Of course important, when you get inflammation to resolve that. As professor Charles Sirhan from Harvard showed a number of years ago, and you can just go again, on and on down the list. Magnesium, of course, there are studies suggesting lithium is also important, especially for behavioral things, but also important for cognition. And so yes, having appropriate nutrition and that starts with getting an appropriate diet. And again, I get it. Diet is not a cure for Alzheimer’s, nobody’s saying it is, but poor diet is certainly a contributor to cognitive decline. There’s no question about that. And we see it all the time.
So what we recommend is a plant rich, it doesn’t have to be exclusively plants, but a plant rich, mildly ketogenic diet. We’d like to see people 1.0 to 4.0 millimolar beta hydroxybutyrate if you do a blood test. If you want to blow in to a breathalyzer, like a Biosense, that sort of thing, then you want to be 10 to 40 on their “ACEs scale” for your acetone, so, yeah, sometime during the day. So plant rich, mildly ketogenic diet with appropriate periods of fasting, 12 to 16 hours, because critical things happen there with reducing inflammation and with cleaning your brain, appropriate autophagy. So phytonutrients are key. Appropriate fiber is key. All of these things are helpful for your cognition.
Dr. Weitz: That’s great. What’s your favorite neurocognitive assessment test?
Dr. Bredesen: Yeah, there are a number of these. I tend to like to use CNS Vital Signs because it tests various things, and we use that in our trial with MoCA scores. MoCA is great because it’s very quick, SLUMS, same idea. These are both zero to 30 point scales. MMSE is another one with a zero to 30. The only issue with MMSE, it’s more for people who have dementia. It’s not so good for picking up the earlier ones. So MoCA is good for MCI, which is, by the way, why it was developed. MMSE good for dementia, and then CNS Vital Signs good for SCI. Those two together give you a nice dynamic range. And we’re interested, by the way, in looking at people who have very low scores. I would call this the “Sarah trial,” severe Alzheimer’s reversal attempt and we’re looking at that down the line, but right now we’re focused on this RCT that I mentioned earlier.
So I like CNS Vital Signs, but, of course, there’s Cambridge. There’s a group out of University of Texas that has another very good one. So different people like different ones, but whatever you use, you want to have something. First of all, don’t take people four to six hours. Some of these older ones are just horribly long and very stressful. Stress is not good for these people, especially the ones who have toxin associated cognitive decline. So make it easy on them and use something that can be done online and fairly quickly and that tests various areas of the brain. You want to look at the verbal memory. You want to look at the spacial memory. You want to look at the executive function. You want to look at spatial recognition, things like that.
Dr. Weitz: And should we be considering using an MRI that looks at the volume of the brain as a screening tool as well? Maybe that would be something that everybody who’s really into longevity and prevention should get.
Dr. Bredesen: And as you know, people have done total body scans as part of the longevity studies. I think it’s fine. My only point is if you want to keep it simple, you don’t have to do that if you truly are for prevention, but if you prefer to do that, absolutely. And certainly if you are there and you’ve already got symptoms, you absolutely should do an MRI with volumetrics and the volumetrics add a lot because you’re looking at what is the hippocampal volume? What is the gray matter volume? What is the parietal lobe volume? Temporal lobe volume? Do you potentially have some normal pressure hydrocephalus? Is there in fact, a chronic non-malignant brain tumor, like a meningoma or a minimally malignant one that might have been missed. So all of these things are very helpful to know.
Dr. Weitz: Is the MRI with volumetrics NeuroQuant? Is that an example of that? Or that’s-
Dr. Bredesen: So there are two different groups, NeuroQuant and Neuroreader, they both work very well.
Dr. Weitz: Okay. Excellent, excellent. Good, good. Always a pleasure to talk to you, Dr. Bredesen, excellent information. I’m very excited for more people to learn about your work and for practitioners to start figuring out how we can really reverse Alzheimer’s disease by taking this systems approach.
Dr. Bredesen: Thanks so much, Ben, for having me on and I appreciate the fact that when you do your various interviews, you don’t have any fraud. You don’t fix the interviews, you don’t change the words coming out of the mouth, you don’t to have Science Magazine go after you and say there’s no cure from Alzheimer’s and you change their words, [crosstalk 00:44:15] And the here’s the problem. We appreciate that.
Dr. Weitz: Don’t give me any ideas. So can you tell people how especially, I guess, practitioners about your training programs?
Dr. Bredesen: Yeah. Great point. So we have a training program. We’ve trained now over 2000 physicians in 10 different countries and all over the US. This is so called ReCODE 2.0 training and it’s also available for health coaches, for neuropsychologists, for nurse practitioners, in all of those groups as well and hopefully to get them, to look at the right things and to have a strategy that will help to get the best outcomes. And you can look at ReCODE 2.0 training. You can look at Apollo Health. We set this up with Apollo Health Co. And so any of these to give you more information, also have a Facebook Dr. Dale Bredesen, so you can follow there or on Twitter or on Instagram.
Dr. Weitz: Awesome. Thank you, Dr. Bredesen.
Dr. Bredesen: Yeah. Thanks so much, Ben. Great to talk to you.
Dr. Weitz: Thank you for making it all the way through this episode of the Rational Wellness Podcast. And if you enjoyed this podcast, please go to Apple podcast and give us a five star ratings and review. That way more people will be able to find this Rational Wellness Podcast when they’re searching for health podcasts. And I wanted to let everybody know that I do now have a few openings for new nutritional consultations for patients at my Santa Monica White Sports Chiropractic and Nutrition Clinic. So if you’re interested, please call my office (310) 395-3111 and sign up for one of the few remaining slots for a comprehensive nutritional consultation with Dr. Ben Weitz. Thank you and see you next week.
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