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In this episode, we discuss:

  • An update on Dr. Bredesen’s work
  • Why conventional medicine treatments for Alzheimer’s disease and cognitive decline don’t work
  • How finances and politics have interrupted progress
  • The Functional Medicine approach to Alzheimer’s disease
  • Why the name “Alzheimer’s” is used incorrectly
  • Hear other people’s stories: How to turn Alzheimer’s disease around
  • Bredesen’s ongoing research

Show notes:

Hey, everybody. Chris Kresser here. Welcome to another episode of Revolution Health Radio. Someone in the world develops dementia every three seconds with over 10 million new cases worldwide each year. There are over 50 million people around the world now living with dementia, and this number will almost double every 20 years, reaching 82 million in 2030 and 152 million in 2050.

This is one of the scariest pandemics of chronic disease that we’re facing today. The annual global cost of dementia is now above $1 trillion. But even this staggering number doesn’t reflect the true cost of the disease, which is the horrific toll that it takes on the affected individual and those they are close to. We know, for example, that caring for someone with dementia or Alzheimer’s [disease] is one of the most stressful situations we can experience, as evidenced by the fact that many research studies seeking to examine the impact of stress recruit caregivers of [patients with] Alzheimer’s as subjects. But despite the shocking impact of dementia on our lives and institutions, there are few if any effective treatments available, at least within the conventional medical paradigm. And that’s why I’m so excited to welcome Dr. Dale Bredesen back as a guest on the show.

Dr. Bredesen is internationally recognized as an expert in the mechanisms of neurodegenerative diseases like Alzheimer’s disease, and he’s also the author of the New York Times bestsellers The End of Alzheimer’s in 2017, and The End of Alzheimer’s Program in 2020. He’s held faculty positions at UCSF, UCLA, and the University of California San Diego, and he’s directed the program on aging at the Burnham Institute before coming back to the Buck Institute for Research on aging in 1998 as its founding president and CEO, and he’s currently a professor at UCLA. I had Dr. Bredesen on the show before to discuss his two books and his groundbreaking Functional Medicine approach to treating dementia and Alzheimer’s [disease], so I’m really looking forward to hearing the latest updates on this really important topic.

In this show, we’ll discuss the latest updates on Dr. Bredesen’s approach to preventing and reversing cognitive decline with Functional Medicine, recent research that validates the results of Dr. Bredesen’s protocol, why Dr. Bredesen decided to write a book featuring stories from patients who’ve gone through his ReCODE protocol, surprising insights and the key takeaways from patients [who] have done the ReCODE protocol, and what’s next for Dr. Bredesen’s research and the ReCODE protocol. We’ve used elements of Dr. Bredesen’s protocol in our clinic for many years with great success, so I’m eager to have this conversation with him so [he] can share his most recent insights with all of us. Let’s dive in.

Chris Kresser:  Dr. Bredesen, it’s such a pleasure to have you back on the show. I’ve really been looking forward to this.

Dale Bredesen:  Thanks so much, Chris. I love the work you’re doing. [I] always enjoy talking to you. It’s always enlightening. So thank you.

An Update on Dr. Bredesen’s Work

Chris Kresser:  I’d love to start with an update since you’ve been on the show before. We’ve talked about your groundbreaking work using a Functional Medicine approach to reverse cognitive decline. So I’d love to hear what’s new. I recently saw, I think, my sense of time is admittedly a little blurry these days. But it seems pretty recent that I saw a study that came out validating the ReCODE protocol or studying a certain aspect of it. I’d love to hear about that and any general updates with ReCODE and the protocol.

Dale Bredesen:  Yeah, thanks so much, Chris. Lots going on. So, as you know, back in 2011, we actually tried to do the very first comprehensive protocol for cognitive decline. We got turned down; it was multiple variables, [like] what’s wrong with us, we don’t know how to do a trial, all this sort of stuff. Then we did a bunch of anecdotes. We published 100 anecdotes with documented improvement [in] 2018. So we finally got it approved in 2019, we finished the trial December of 2020, [and] we’re still analyzing the data. [It’s] very exciting. So we just put on the med archive, the preprint server that a lot of COVID[-19] things and various things are on. So it’s now public information. Our first proof of concept trial [was with] 25 patients, [who] did spectacularly well. So it was really exciting to see this.

Eighty-four percent of them improved their [central nervous system] (CNS) vital sign scores, 76 percent improved their MoCA scores. We looked at five different things. We looked at their AQ change scores, which is basically partner generated. Because, as you know, with some of the drugs, you’ll find a minimal effect, but the partner can’t even see it. It was like, oh, I can’t tell. These people actually improved; it was great to see. Their [magnetic resonance imaging] (MRI) [scans] actually improved. So interestingly, as you know, just aging alone, you have a slight reduction of gray matter and hippocampal volume both over age, with Alzheimer’s [disease] or mild cognitive impairment [(MCI)]. You have an accelerated decline in this. And in this case, people actually did better than normal aging, even though they had MCI or Alzheimer’s disease. Their gray matter volume actually increased, which was striking, and their hippocampal volume very slightly declined, but less than normal controls. So [they were] very exciting results.

We also did brain HQ, and all of them did better on brain HQ. So by all of those five parameters, people improved. And I think it’s important that we talk about the semantics of success. As you know, aducanumab was just approved on June 7th, and it doesn’t make you better and it doesn’t even stabilize you. In one trial, at one dose only, it slowed the decline by 22 percent. In our trial, you actually get better; you don’t just slow your decline. So it’s strikingly different.

Chris Kresser:  Yeah, to me, it speaks to the fundamental difference in the paradigm and the approach. In one paradigm, you’re basically just trying to slow the progression of the disease using drugs that suppress symptoms, rather than really looking at what are the root causes of this ongoing cognitive decline and how can we identify and address them so that the patient can not only slow the progression, but even stop and reverse the progression?

Dale Bredesen:  Exactly.

Why Conventional Medicine Treatments for Alzheimer’s Disease and Cognitive Decline Don’t Work

Chris Kresser:  So you used one example, but I want to highlight this for folks that are maybe less familiar with the conventional medicine options for Alzheimer’s [disease] and cognitive decline. How did the results of your trial compare with the currently available conventional treatments?

Dale Bredesen:  Yeah, very good point. There are three different treatments that are now available. One is a cholinesterase inhibitor like Aricept. That will give you a slight bump, but you go right back to declining. And, in fact, if you look down the road in the long run, people actually do worse if they took that drug than if they didn’t. That’s the scary part. Furthermore, if you cold turkey the drug, you drop down dramatically and typically do much worse. The second one is memantine, which has a minimal effect. The families couldn’t tell who was on it in the trials and who wasn’t on it. So a very, very minimal effect, although again, just a barely significant effect with slight improvement. And again, you go right back to declining.

And then the third one, which are these monoclonal antibodies. So the drugs, these are anti-amyloid antibodies, have not worked, and multiple have failed. And in fact, we’ve seen a number of patients who clearly got worse, which, actually, if you think about it, makes a lot of sense. Your amyloid is there as protection. It is a response to these Functional Medicine insults that we talk about all the time. Various pathogens and toxins and [a] decrease in metabolism, all these sorts of things. And so you give these, and [they remove], it’s a little bit like getting rid of the president of your country. Well, you might be able to get away with some things that you couldn’t get away with for a short period of time, but your country is going downhill.

Chris Kresser:  Right.

Dale Bredesen:  And this is the same sort of thing you see with strokes, you actually see people get worse. So, unfortunately, pharmaceuticals for Alzheimer’s [disease] currently, at least alone, do not work.

Chris Kresser:  Well, that approach reminds me somewhat of the conventional approach to certain autoimmune conditions and the use of biologic response modifiers, like Imuran and Remicade, where yes, they’re very effective at suppressing the immune system, but they’re non-selective in what they’re suppressing. They’re globally suppressing the immune system, and then you get a situation where, oh, wait, I actually need my immune system to fight infections and not get sepsis. And so you see on the black box warnings of those medications that there’s a potential for those very serious side effects and complications. Because instead of asking the question, what is aggravating the immune system and causing immune dysregulation in the first place, and let’s look at that, it’s just like, oh, a part of the immune system is overactive; let’s just globally suppress the whole thing. It’s very strange to me that we’re in 2021 and that’s still the thought process behind approaching chronic diseases like this.

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How Money and Politics Have Interrupted Progress

Chris Kresser:  Why is it taking us so long to learn? I mean, you’ve been involved in this, you started out in the conventional paradigm and with drug discovery if I’m not mistaken, and looking at these drug treatments, you saw that that was not going to be a fruitful path after as many years as you were in it. But it seems to me that the conventional approach is still very much designed around this silver bullet idea. And I love the term you use, and we need silver buckshot. But maybe you could talk a little bit about that, from the inside perspective, having been involved in that world and now developing your own functional approach. Why do you think it’s taking so long for your progress to be made here?

Dale Bredesen:  It’s such a good point, Chris, and this is one that comes up all the time. I was recently invited to a major national show to talk about our work. And then I was literally uninvited the day that they had someone from the Alzheimer’s Association on the show. It was like, “No, we don’t want to hear about the way it actually works. We want to push the drug.” And unfortunately, the Alzheimer’s Association was paid by [the company] Biogen, to talk about how good this new drug is, which doesn’t work. So it’s very unethical, and it’s unfortunate, actually.

The problem here is that finances and politics outweigh [the] truth. That’s the bottom line. [It’s] sad to say, but we need to deal with the truth, the data, which is why I think it’s critical to get these clinical trials out, to get the truth out about what actually works. And as you indicated, we need to be asking why. Why do you actually have this problem? There’s one drug I’m sure you’ve seen. All it does is it kills your eosinophils. So basically, “Oh, you got eosinophils? Oh, let’s kill them.” I mean, it’s such a silly and naive approach. Let’s ask why you have these eosinophils there. Let’s not just kill them before we know why they’re there. So you’re right. This is happening everywhere. And these complex chronic illnesses, which are the major causes of morbidity and mortality in our country currently, and in the Western world currently, are not being approached by the kind of medicine that we were taught 30 or 40 years ago. And certainly, that’s true for me and for all of us. So we do need to come into the 21st century and ask why.

What was interesting to me, I had a lot of interaction with my neurological colleagues who were already kind of presupposing, okay, we’re going to get a drug, [and] it’s going to be a monophasic sort of thing. We’re going to give you one drug, same for everything, uniform, having nothing to do with what causes the disease, and we’re going to find one that makes you better. It’s a little bit like saying, we’re going to find an arrow that shoots to the moon. You can try all the arrows, keep pulling that bow back, oh, maybe this arrow, maybe that arrow, maybe this arrow. But you have to get the fundamental concept that no, that’s not the way this works. You’re actually going to have to build a rocket to get there. So our research, as you said, showed over the years that you can actually trace the molecular pathways. You can see how [nuclear factor kappa B] (NF kappa-B) turns on specific genes, including the beta and gamma secretases. You can see why your aPP has shifted from a growth in maintenance mode into a protective downsizing mode. This is analogous to what’s happened to all of us with COVID-19, where we were told to [use] social distance, isolation, etc. And what happens, we go into a recession.

And so the same thing is happening with your brain. You are protecting yourself; you’re going into a protective downsizing mode. And until you’re able to determine why that is and address those very things, and there can be dozens and dozens of them, you’re going to continue in this downsizing mode. I do think in the long run, Chris, bringing these together, having specific targeted drugs, with precision medicine protocols, is going to be the best way to go.

Chris Kresser:  Yeah. Well, I hope we get there sooner rather than later because as I was remarking in the introduction, the numbers are pretty staggering. [In] some estimates I’ve seen, there’ll be 150 million people with dementia by 2050, and maybe that’s even conservative; it might be more than that. And I don’t know anyone who wants to die, period. But most people, I think, if you ask them how they want to die, it’s maybe a heart attack in bed, or something like that. It’s not dementia and Alzheimer’s [disease]. That’s pretty much one of the most scary ways to spend the later years of your life. And so it’s a really, really urgent pressing problem in all chronic diseases, arguably. But this seems to be at the top of the list in terms of how important it is that we get a handle on this.

Check out this week’s episode of RHR where I talk with Dr. Dale Bredesen about his work treating and reversing Alzheimer’s disease with Functional Medicine. His new book, The First Survivors of Alzheimer’s, features inspiring stories from patients who have reversed cognitive decline naturally using his protocol. #functionalmedicine #chriskresser

The Functional Medicine Approach to Alzheimer’s Disease

Chris Kresser:  I want to go back to something that we were both alluding to, [which] is a fundamental difference in Functional Medicine versus conventional medicine. And then I want to segue into asking you about how you approach Alzheimer’s [disease]. In the conventional model, it’s one disease, one treatment, right?

Dale Bredesen:  Right.

Chris Kresser:  So it’s like, [if] you have [irritable bowel syndrome] (IBS), you take this drug.

Dale Bredesen:  Right.

Chris Kresser:  It doesn’t matter what kind of IBS you have or how you got your IBS; you take that drug. If you have diabetes, you take this drug. It doesn’t matter what the underlying causes were. And that’s how Alzheimer’s [disease] is being approached, as you mentioned. But in the functional model, you could have someone with the same disease, 10 people with the same disease, but 10 different profiles of how that got caused. For example, [in] 10 people with Crohn’s disease, one person maybe has post-infectious Crohn’s disease because they got an infection, like a parasite infection, and that evolved into Crohn’s disease. Maybe somebody else was exposed to high levels of mercury or lead, and that dysregulated their immune system, and they develop[ed] Crohn’s disease that way. And you can go on down the list.

And the thing is, the treatment will be different for each of those people. And you might use some things that are the same, but there are other things that will be different. And that’s, to me, one of the things that stands out the most about ReCODE and your approach to Alzheimer’s [disease] is you’re acknowledging the different types of the disease, and those different types usually [have] different causes. So, for the folks who didn’t hear the first podcast with you, can you talk a little bit about what those types are and what kind of insight they provide into the treatment protocol?

Dale Bredesen:  This is a great point, Chris. And yeah, we’ve talked about this before. As you indicated, there are different things that all contributed. Ultimately, what we found is that what we call Alzheimer’s disease is fundamentally an insufficiency. There is a supply and a demand, and when the supply is constantly, is chronically exceeded by the demand and it’s multiple different things as we’ll talk about. But let me just preface this by saying for the first time from the work you’re doing, from the work we’re doing, from the work others are doing, virtually nobody needs to get Alzheimer’s. It really is now optional. I know that sounds crazy, but it is an optional disease. If everybody gets on appropriate prevention, and we recommend when people hit [age] 45 get a cognoscopy or appropriate early reversal, please don’t wait, then virtually no one needs to get this disease.

Now, as you indicated, we want to understand why you get it, and it’s different for each person. So type one is inflammatory, and this can be from pathogens, it can be from metabolic syndrome, it can be from poor dentition, [and] so forth and so on. Type two is atrophic, and these are people who don’t have enough hormones or growth factors or nutrients. Type 1.5 because it’s got some of both of those, is glycol toxic. These are people who become insulin-resistant. So they have some of the type two because their insulin signaling doesn’t work. They also have some inflammation from the non-enzymatic glycation. Then there’s type three, which is toxic. And the toxins come in, as you know, three basic groups. It’s the inorganics, things like mercury, and also air pollution. We have [that] here, especially in California and people who were in the California fires, things like that.

Then it’s the organics, glyphosate, toluene, benzene, things like that, formaldehyde. And then the third group is the biotoxins. Very common. We see people all the time. [I] just heard about a patient a couple of minutes ago, whose, it turned out, their ductwork had major, major mold. And, of course, this person’s getting exposed to this every day. And then type four is vascular. Very common association with Alzheimer’s disease, and type five is traumatic. So those are the six different types that we see. And interestingly, we’ve now developed, you can actually look at an equation that says your probability of developing it is proportional to an integration over time. So you’re looking at all your exposure over time to basically four things, two things in the numerator, two things in the dominator. So anything that increases inflammation, as we talked about pathogens, etc., anything that increases toxins, and then on the denominator, anything that will reduce energy, and that’s mitochondrial function, cerebral blood flow, oxygenation, ketosis, all of those. And then anything that will reduce trophic influences. And that’s everything from vitamin D to estradiol to testosterone to nerve growth factor to [brain-derived neurotrophic factor] and those.

So, if you just look at those four groups, you can see why the person’s system, why their neural subnetwork is now involuting, which is what’s happening. And for each of these neurodegenerative diseases, they have their own unique neurochemistry. And so you’ve got to identify those issues; you’ve got to address those issues. And as you indicated, it’s different for each person. Absolutely.

Chris Kresser:  Right. Well, one thing that stands out is, it’s really hard to do that in a 10- to 12-minute appointment in the conventional model, or even a half-hour appointment, frankly. That’s a lot of information to be collecting and [diagnosing], and you’ve really systematized this in a big way with the ReCODE protocol and the software and all the tools that you offer to clinicians that you train. But what would you say to someone who says, “Geez, that’s a lot of work. That’s a lot of money to spend on testing and diagnosis. It’s so much easier and faster just to prescribe a drug.” How would you respond to that?

Dale Bredesen:  It’s such a great point, because [as] we pointed out in the publication on the trial, we can now show that it’s possible to do this and clearly show even a denominator, how often can we do it, etc. What we haven’t shown is that it’s practical. And you’re absolutely right. But here’s the problem: the average American spends $350,000 during their time with Alzheimer’s [disease], much of it, no surprise, on nursing homes. The new drug is $56,000 per year plus administration costs, plus MRI and [positron emission tomography] (PET) scan costs. So total, it’s about $100,000 per year for something that does not make you better. It might slow the decline a little bit, or it might make it worse, and we’ve seen that happen, as well. So in fact, even if you were simply investing for a portfolio or something, you will actually put far less money and do far better for far longer by doing the appropriate protocol. By looking at what’s causing it and then addressing the things that cause it.

I usually tell people, imagine that you’re going to spend something like a tenth of what you would spend for a typical [patient with] Alzheimer’s [disease]. We’re going to keep you out of the nursing home, keep you out of your decline. And one of the things that we’re doing now is putting together a program that will guarantee prevention. Because what we’re seeing is nobody who goes on prevention actually ends up declining. We don’t see people become demented if they are on appropriate prevention. Now, of course, if they don’t do it, if they are not compliant, they don’t do the right things, they ignore it, of course, they’re at risk. But for those who do the right things, we can pretty much prevent everyone from developing cognitive decline and, ultimately, Alzheimer’s [disease].

Chris Kresser:  That is just amazing. And that’s why I’m always so excited to talk to you because so many people interpret Alzheimer’s [disease] or even the early signs of dementia as a death sentence and as [if] there’s no way out. It’s just going to get worse and worse. And even just colloquially, if someone, I’m middle-aged.

Dale Bredesen:  A very healthy middle-aged.

Chris Kresser:  It’s funny to say that. I kind of like to say it just because it’s, but anyway, if I went into the doctor, which I don’t. I can’t even remember the last time I went to a doctor, conventional doctor, but if I did, and I said, “You know, I’m feeling a little bit more tired; I’m starting to forget things. I couldn’t find my keys the other day, or I have difficulty with recalling certain words,” they’d probably just pat me on the back and say “welcome to the human race” or something about “this is just normal for [your] age.” You should just expect to decline in significant ways as you age. And you’re saying that that’s not necessarily normal.

Why the Name “Alzheimer’s Disease” Is Used Incorrectly

Dale Bredesen:  And that’s such a good point. And you know, Chris, this really brings up one of the most important points, and the reason that we’ve had so much Alzheimer’s [disease] in our society. And this is because people have actually named it incorrectly. Here’s what I mean by that. There are four stages of this problem. Stage one is you don’t feel anything; you’re asymptomatic, but you already have the underlying biochemistry that’s been shown very nicely by PET scans, spinal fluid, etc. So you have a period there where you’re in a pre-symptomatic stage. Then you go into subjective cognitive impairment (SCI). You know there’s something wrong, your spouse may know it, [and] some of your co-workers may know it, but you’re still testing in the normal range. And that is called [SCI]. But what it should be called [is] early Alzheimer’s disease. Virtually every one of those people we can improve, get them back to normal. That can last 10 years, and it typically does last about a decade. Then you go into what’s called MCI.

Now, as you can see, that’s the third of four stages. Doctors will say to you, “Ah, it’s a little bit of age. It’s mild cognitive impairment.” This is like telling someone they have mildly metastatic cancer. This should be called advanced stage Alzheimer’s disease because it’s a relatively late stage. You’ve already had more than 10 years of the underlying biochemistry by the time you get to MCI. But as you indicated, most doctors just tell you, “Ah, Chris, you’re getting a little older; don’t worry about it.” They should be jumping on this with all four feet jumping on and making sure that everything works; let’s see what’s causing this. And then what we call Alzheimer’s [disease] where you actually have to lose activities of daily living should be called final stage Alzheimer’s [disease], because that is a very, very late stage of the underlying pathophysiological process. So all of us should be getting evaluated as we get older, and should be optimizing things and [making] sure that we do not get Alzheimer’s disease.

Chris Kresser:  Yeah, this drives me crazy, and I talked about it in my second book Unconventional Medicine. I used the example of diabetes where it costs $15,000 a year for a healthcare system to treat a patient with type 2 diabetes. Relatively affordable compared to Alzheimer’s [disease] or dementia. But still, let’s say somebody gets diagnosed when they’re 40 and they live another 40 years, that’s 600 grand right there. And it doesn’t take a genius, you don’t have to be a genius investor to think, “Hey, maybe if we spent $5,000 upfront on earlier testing before they’ve reached full-fledged type 2 diabetes, when they’re in the pre-diabetic stage, or even in the high normal stage,” which we know will often progress. And we could do it for less than $5,000. We just do a few thousand dollars for testing, setting them up with a health coach, getting them on a solid nutrition and exercise plan, they would then avoid ever developing type 2 diabetes, and that saves the healthcare system $595,000 over the course of that disease. And that’s all from just earlier detection and earlier intervention. And it sounds like you’re saying that’s exactly what we need to be doing in the case of dementia. Not waiting until the person has reached that fourth and final stage but intervening at the earliest stages where I imagine, I know from our many conversations and using your protocol, it’s far easier to prevent a disease or to catch one at an earlier stage than it is to slow or halt or reverse it at the late final stage.

Dale Bredesen:  Absolutely. And we now know many of these critical factors that are actually driving this as you indicated, type 2 diabetes and insulin resistance, and even pre-diabetes, looking at various pathogens and things that are causing inflammation. We know specific viruses that tend to be associated with Alzheimer’s [disease] and viruses that tend not to be associated with Alzheimer’s disease. New biochemistry, things like plasmalogens, where we can look at, okay, is this going to be one of the things that’s driving this process? So there’s a tremendous amount we can do. What we’re doing right now in practice is saying to someone, “You’ve got a new car. Just keep driving it until it just stops. When this car stops, then give us a call, and we’ll see if we can fix it.”

Chris Kresser:  And even like, “There [are] four warning lights on the dashboard, but what you need to do is just put some tape over them because then if you don’t see them, they’re not there anymore.” Right?

Dale Bredesen:  Yeah, those warning lights are what we see with car aging. So just ignore them. It’s crazy.

Chris Kresser:  Just put tape over it, exactly, yeah.

Dale Bredesen:  It makes no sense.

Hear Other People’s Stories: How To Turn Alzheimer’s Disease Around

Chris Kresser:  It makes no sense and yet that’s what we’ve got so far. I want to talk about your new book. We talked about your first two books, which again, were absolutely groundbreaking, The End of Alzheimer’s and The End of Alzheimer’s Program. And this latest book, which is out on August 17th, right?

Dale Bredesen:  Right.

Chris Kresser:  Is The First Survivors of Alzheimer’s: How Patients Recovered Life and Hope in Their Own Words. And I’m excited about this, because your first two books were so thorough and comprehensive by necessity, because you’re introducing a new paradigm for how to treat Alzheimer’s [disease]. And most of my patients just ate them up and devoured them, but my patients are, let’s say they’re highly motivated, highly educated about all of this stuff. And they’re the ones who go to the summits and read the blog posts and listen to the podcast. But human beings primarily learn through stories, and narrative and story is just part of our DNA. That’s how information was passed down for millennia before we developed the kinds of tools that we have now and even written language.

And so I’m a big believer, like when I write my emails or when I write blog posts, or when I speak in public, I always use case studies because I find that people can relate to that so well, and it just goes in their brain and sticks in a way that it doesn’t. If you could just tell them about the results of a study, great; that’s helpful. But it’s not the same as hearing about somebody who’s life was transformed [by] this approach. So I imagine that has something to do with why you decided to write this book. But tell us what was the impetus for this?

Dale Bredesen:  This is such a great point. When the first person contacted me, actually patient zero, a guy contacted me after about four months and said, “You know, I’m so much better and here’s what’s going on. And my memory is better than it’s been in 20 years.” I was so excited to hear that. And of course, it validated all the science we had done in the lab over the years. It validated the overall approach. But it was also heartwarming for people to say, “You know, I had given up.” One of the guys who wrote one of these seven stories in the book we had, [which] are all first-person stories, said, “I’ve allowed myself to talk to my grandchildren about the future once again.”

Chris Kresser:  Wow.

Dale Bredesen:  It’s such a heartwarming thing to hear. [For] a lot of people, there’ll be a tear that comes to their eyes reading these stories of people who were hopeless. As you know, Julie, one of the seven people in there, went to a neurologist who is a specialist in Alzheimer’s [disease] and said, “I’m an ApoE 4/4; I’m clearly declining. Could you do anything just to even keep me where I am?” And the guy looked at her and said, “Good luck with that.” Basically offering no hope whatsoever because that’s what the literature had suggested.

She’s now nine and a half years into this [and is] doing absolutely great. She’s gone from [the] 35th percentile to 98th percentile on her cognitive testing. She, interestingly, worked with your team. It turned out she had ended up having an undiagnosed Babesia, which turned out to be diagnosed by your team. Thank you very much for that and fantastic care for her. And that turned out to be one of the things that was, she was kind of stuck on a plateau. So now she’s done even better. So all of these stories are heartwarming, they’re articulate, [and] they really come from the horses’ mouths themselves. This is what it was like. So I wanted to give people some hope to say, “Hey, I can do this myself.” I also wanted the people to put down here’s what I do every day. I wanted them to offer real-world experience.

I can say as a physician, well, I think you should correct your homocysteine or something like that. But that doesn’t tell you here’s what I do. Here’s the website I go to, here’s the store I go [to], [and] here’s how I cook my food. Here’s what I do each day and how it’s worked and what hasn’t worked for me and what the workarounds are, etc. [I’m] so excited about The First Survivors of Alzheimer’s. And also, [I] updated the protocol, [and I] have a chapter there about enhancing normal cognition because so many of us have suboptimal cognition. We think of it as normal, but we can actually do so much better. So [I’m] very excited about this. And just to see these people get better, that’s still the thing that gets me the most excited is hearing about someone who had a terminal illness with cognitive decline improve.

Chris Kresser:  Yeah, it’s a miracle and it’s not, right? On the one [hand], it depends which lens you’re looking through. If you’re looking through the conventional lens, it’s like some kind of magic voodoo miracle because none of the drugs can do it. But when you understand the whole system’s approach to looking at chronic disease, it’s not a miracle; it’s just good medicine. It’s the way that medicine should be practiced with not just dementia and Alzheimer’s [disease], but all chronic disease. And we have to have this approach or we’re not going to make it through as a species. It’s just that the numbers are absolutely shocking.

Dale Bredesen:  Absolutely.

Chris Kresser:  I imagine, I know from my own clinical experience that I learn as much or more from my patients as I do from others, seminars, and continuing education and all, going to conferences and all of that stuff. I always say my patients have been my greatest teachers, and that’s absolutely true.

Dale Bredesen:  Yeah.

Chris Kresser:  What have your patients taught you? What are some of the more surprising insights or things that maybe you didn’t expect, or lessons that you took away? Because I imagine as you wrote this book, you were combing through lots and lots of different stories. So that must have been an incredible learning experience for you.

Dale Bredesen:  This is such a great point. And as we know with social networking, we’re now seeing thousands instead of hundreds. So we’re hearing more and more. And of course, with a trial, we’re looking very carefully at each thing. But we’ve also started something called the ARC project, where we look very deeply at one or two people who have each of the neurodegenerative diseases. So we’ve started with macular degeneration; we’re now going on to Parkinson’s [disease], Lewy body [dementia], and things like that. So we’ll learn more from each of these. But you’re absolutely right, tremendous lessons. One of the ones I learned first, which is now eight years ago, we started seeing people who weren’t responding. These were the ones that turned out to have mycotoxin exposure. So that’s what we didn’t know about that.

Initially, we just had type one and type two; we didn’t know about type three. And so we had to reorient and say, “Why do these people actually look different?” As you know, they tend to present differently. They tend to be younger; they tend to have a more non-amnestic presentation, more executive dysfunction, dyscalculia, primary progressive aphasia, posterior cortical atrophy, [and] things like that. They often will have stress as a big inducer of cognitive decline. You have to treat them differently; you have to recognize the problem and jump in. You kind of see new concepts and you say, wait a minute, am I missing something here? One of the things that we’re looking at right now, is the phenomenon, I call it AI2, but it’s basically auto-activated innate immunity. In other words, as you know, we have an autoantibody, an autoimmunity for things like what you had talked about earlier, things like IBD, and things like that.

And so you have a situation where you start by responding against a foreign pathogen. You start with [pathogen-associated molecular patterns] (PAMPs) and [damage-associated molecular patterns] (DAMPs) and things like that. You progress to your adaptive immune system, but if it’s too wide, you start making antibodies or cytotoxic T cells against your own antigen. So you now have autoimmunity. What we’re getting the suspicion of is that there is something that is analogous to that, but at the innate level, where in other words, someone starts with ongoing inflammation. You can bring that down, the inflammation is to a pathogen. But because of your own auto activation of this, so DAMPs, like A-beta, which functions essentially, as a DAMP, you’re essentially auto-activating a chronic inflammatory state. So it’s not good enough just to get rid of the pathogen; you have to kind of reset the system, which is where things like LDN (low-dose naltrexone) and things like that can come in. So we’re starting to see people where things went right, but they’ve really plateaued and even started to backslide a little and yet, there’s nothing. They’ve said, “Well, we’ve done everything right. There’s no pathogen there. There’s nothing that’s doing this.” But we’re now realizing they probably have an intrinsic activation, which we now need to work hard to reset.

Chris Kresser:  Yeah. That’s really fascinating because, actually, just this month, a day before your book comes out, we’re launching our first workshop on treating autoimmune disease naturally from a Functional Medicine perspective, so this is all very much on my mind, but the autoimmune nature of many diseases that weren’t considered to be autoimmune previously. For example, I just saw a paper, I don’t know if you saw this, on fibromyalgia. And they found a lot of antibodies in these patients’ muscle tissue, not surprisingly. And so now, they’re reclassifying fibromyalgia as an autoimmune disease. There was a paper on ME/CFS (that’s [myalgic encephalomyelitis]/chronic fatigue syndrome, for the listeners that are not familiar with that). And they found antibodies to the hypothalamus and the pituitary. And that then resulted in lower levels of cortisol and growth hormone production.

Dale Bredesen:  Interesting.

Chris Kresser:  So now there’s a thought that, at least in some people, chronic fatigue syndrome may be autoimmune. And then, [as] I mentioned before, postinfectious Crohn’s disease [is] an autoimmune disease that often starts with an infection. We know that viruses are often triggers for autoimmunity, like long COVID, and many people believe [it] is autoimmune in nature, and it’s triggered by the SARS-CoV-2 virus. And this concept, I’m always explaining it to patients, so I’m really glad you just brought it up, where the idea that if there’s a trigger for a disease, if you remove the trigger, then the body automatically just goes back to normal. So often, and maybe more often than not, that’s not the case.

Dale Bredesen:  Exactly.

Chris Kresser:  Because the immune system tends to get on kind of a track, right? So the trigger dysregulates the immune system, and then the immune system just kind of stays dysregulated even when that trigger is gone. And so we have to take steps to balance and regulate the immune system or restore that normal function. And I’ve come to believe that it’s quite, I mean, the statistics on autoimmune disease, the official ones even say, one in five Americans now. I think, if you could include fibromyalgia, chronic fatigue syndrome, and these kinds, and then maybe even dementia having an autoimmune element, it could be as high as one in three, or one in four. So it seems like it’s a really crucial thing for us all to be aware of.

Dale Bredesen:  Absolutely. And imagine a scenario in which you never get far enough; your adaptive system is not doing well enough to generate those antibodies. You’re stuck in a state where your innate system is on and your adaptive system has just never quite gotten there. That’s what we see as this AI2 idea that there’s this constant. So you essentially have an endogenous inflammation. And one of the things that had been pointed out years ago in [patients with] Alzheimer’s [disease] [is] they are not particularly good with phagocytosis and presenting of antigen. Their adaptive systems tend to be slow, whereas their innate systems tend to be on. You’d never get that nice turning off of the innate system by adaptive activation. So it’s almost like a precursor to auto antibodies.

Chris Kresser:  Yeah, that comes up for me or came up; it was puzzling for me earlier in my career when I would see patients that I was virtually convinced [had] Hashimoto’s [disease], for example, and yet they never tested positive for the antibodies.

Dale Bredesen:  Yeah, exactly.

Chris Kresser:  We could do 10 tests, and they wouldn’t be positive. And yet, they exhibit every other sign and symptom of it, and then if you send them for a thyroid ultrasound, they’ve got diverse multinodular goiter or some other evidence of Hashimoto’s [disease], but they never show up with antibodies. So that’s the same thing that you’re talking about in this subset. And this is how we initially connected, I think, Dale, was around mold and biotoxins. And, as you know, I’ve talked so much about this and written so much about it over the years, but I find that the awareness around it is still so low. And there [are] so many people who are spending a lot of time in water-damaged buildings, and even when they become aware of it, if they try to bring it up to the building manager if it’s their workplace, for example, or try to get help at home, it’s so difficult because it feels like we’re kind of living in the Stone Age when it comes to awareness of building science and indoor air quality.

Dale Bredesen:  This is the biomedical equivalent of Surfside. So instead of waiting for your building to crumble, you’re waiting, basically, for your immune system to crumble. You’re waiting for your nervous system to crumble. Don’t wait. There’s actually so much that can be done ahead of time. And I think this is a new era because of Surfside. People are thinking more like, hey, let’s look early. And I wish the medical community would listen to that more.

Chris Kresser:  Yeah, the interesting parallel there is, if anything, if there is some, I think there are probably several silver linings of COVID[-19]. I’ve experienced them myself, and several others have. But from the perspective of what we’re talking about now, I’ve never seen more articles in the popular media about indoor air quality and filtration and changes of air permitted. These [are] things that you and I [have] been thinking about a lot for a long time, and now they are finally starting to get on the radar, and you hear about schools installing air filters or people bringing more air filtration in their home, primarily because of concern about COVID[-19]. But hopefully, that can have a positive impact on reducing other comorbidities that can come from exposure to bad indoor air.

Dale Bredesen:  Absolutely. And I think we’ve gotten away with, as health practitioners for thousands of years, with doing things that are very simple. And the reality is, we’re now understanding a lot more about human physiology. It’s not so simple, and we need to identify when you actually see what’s driving the problem. And as you indicated, getting it early on [is] huge.

Chris Kresser:  Yeah. So [it’s] always a pleasure to speak with you, Dale, and I’m so grateful for the work that you’re doing. It’s the gift of hope to these people. It means more than anything. Just having hope that there’s some other path in a steady decline, and painful, not just for them, but for the people around them, decline for the rest of their life. And it’s just, as a clinician myself, to be able to use the elements of your protocol or refer someone to you if they’re in that situation, it’s a tremendous gift. So I appreciate that.

Dale Bredesen:  Thanks so much, Chris. My wife Aida and I are huge fans of yours and fans of your fantastic work. So thanks so much. [It’s] always great to talk to you.

Dr. Bredesen’s Ongoing Research

Chris Kresser:  Before we finish up, I want to ask you what’s next. I always like to do that because you always have a lot of interesting stuff planned and going on. And then I want to tell people where they can get the book and find out more about the ReCODE protocol and your work, and both for people who are experiencing cognitive decline or dementia or concerned about that in themselves, but also for professionals. Because as I do, you train professionals. So we’d love to send them to the right resources, as well.

Dale Bredesen:  Yeah, thanks so much. And we’ve trained over 2,000 practitioners from 10 different countries and all over the [United States], so thank you so much. So what’s next? Step one, we’re doing a larger randomized controlled clinical trial that will start in January, [which] will have 100 patients, and [we’ll be] looking again at all the different parameters, their MRIs, their MoCA scores, and their CNS vital sign scores. And [we’ll] also [be] looking at can we now add other views. Do we need to [add] other[s]? Do we need to be looking more carefully at plasmalogens? Do we need to be looking? We actually use Intellicus DNA from, as you know, Dr. Sharon Hausman-Cohen, for this last trial and looking at, okay, are there specific genetic predeterminants that we need to address, as well? So the next trial.

[The] second thing is that we have the ARC project that I mentioned. So we’re looking at small numbers of people with deep dives to see what’s absolutely critical. And then the third thing, as I mentioned, [is] we’re developing a large-scale prevention program. The idea is can we actually move the needle on global cognitive decline? This is a trillion dollar global problem and growing, as you know. It’s a huge issue. There may be some increase because of post-COVID-19. There’s a lot of brain fog, as you know, associated with COVID-19, so we may even see a bump. And what we’d like to do is look at something, which would essentially be hierarchical. You can get most people with just prevention; they won’t have problems. A few of them will bleed through, so you now want to do those, and so forth and so on. Until there’ll be one or two that actually need to be in patients, and you need to look at everything. With that, it could be an efficient way to reduce the global burden of dementia. I really believe that, as I said, this is now an optional disease.

Chris Kresser:  All right, so where can people find your book or find out more about your book? And where can people find out more about the ReCODE protocol if they or a family member or friend is dealing with this cognitive decline? And where can people who might want to, professionals, doctors, coaches, etc., find out about training?

Dale Bredesen:  Yeah, great point. You can find the book on Amazon, Barnes & Noble, any of those. You can look at DrBredesen.com to get further information. You can also go to ApolloHealthCo.com because part of the future is writing code, getting more intense algorithms, more defined algorithms so that you can look at larger data sets. So that’ll be one way to go. And for training, absolutely. You just go on to DrBredesen.com and look at ReCODE training, ReCODE 2.0 training. And all those are currently available.

Chris Kresser:  That’s fantastic, Dale. [It’s] always a pleasure to speak to you. [I] look forward to having you on, probably in a couple of years, to get the updates, the [randomized controlled trial] and everything else that you’re working on. [I] can’t wait to hear more.

Dale Bredesen:  Thanks so much, Chris. Again, thanks for having me on. Thanks for the great work you’re doing.

Chris Kresser:  All right, everyone, thanks for listening. Keep sending your questions to ChrisKresser.com/podcastquestion. We’ll see you next time.