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In this episode, you will learn about dementia, cognitive decline, Alzheimer's, and "The End of Alzheimer's Program".

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About My Guest

My guest for this episode is Dr. Dale Bredesen.  An internationally recognized expert in the mechanisms of neurodegenerative diseases,  Dale Bredesen, MD'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.  Dr. Bredesen earned his MD from Duke University Medical Center and served as Chief Resident in Neurology at the University of California, San Francisco (UCSF), before joining Nobel laureate Stanley Prusiner’s laboratory at UCSF as an NIH Postdoctoral Fellow. He held faculty positions at UCSF, UCLA, and the University of California, San Diego. Dr. Bredesen directed the Program on Aging at the Burnham Institute before joining the Buck Institute in 1998 as founding President and CEO.  Dr. Bredesen’s research explores previously uncharted territory in explaining the physical mechanism behind the erosion of memory seen in Alzheimer’s disease, and has opened the door to new approaches to treatment.  This work has led to the identification of several new therapeutic processes that are showing remarkable early results. Dr. Bredesen is a prodigious innovator in medicine, with over thirty patents to his name. His book “The End of Alzheimer's Program: The First Protocol to Enhance Cognition and Reverse Decline at Any Age” is the follow-up to his earlier work “The End of Alzheimer's: The First Program to Prevent and Reverse Cognitive Decline”. 

Key Takeaways

  • What are the recent developments in the ReCode protocol?
  • Why is holism a more appropriate way to approach cognitive decline over reductionism?
  • What is the "unjection" needed for Alzheimer's disease?
  • How can one access a cognoscopy?
  • Can the amyloid precursor protein molecular switch be tested?
  • What are the key contributors to inflammation?
  • How might one approach insulin resistance?
  • Which nutrients, hormones, and tropic factors are most commonly deficient?
  • What is the impact of nocturnal hypoglycemia and oxygen deprivation on quality sleep?
  • How might EWOT be helpful in cognitive decline?
  • What are the new types that have been categorized since the first book?
  • What is the role of ketosis in reversing cognitive decline?
  • How is treatment of microbes and toxins contributing to Alzheimer's approached?
  • What is the role of the amygdala and limbic system in the ReCODE protocol?
  • How might one support the sinus biome?

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Interview Date

August 13, 2020 


Transcript Disclaimer: Transcripts are intended to provide optimized access to information contained in the podcast.  They are not a full replacement for the discussion.  Timestamps are provided to facilitate finding portions of the conversation.  Errors and omissions may be present as the transcript is not created by someone familiar with the topics being discussed.  Please Contact Me with any corrections.   

[00:00:01.18] Welcome to BetterHealthGuy Blogcasts, empowering your better health. And now, here's Scott, your Better Health Guy.

[00:00:13.28] The content of this show is for informational purposes only and is not intended to diagnose treat or cure any illness or medical condition. Nothing in today's discussion is meant to serve as medical advice, or as information to facilitate self-treatment. As always, please discuss any potential health-related decisions with your own personal medical authority.

[00:00:34.21] Scott: Hello everyone, and welcome to episode number 125 of the BetterHealthGuy Blogcasts series. Today's guest is Dr. Dale Bredesen, and the topic of the show is The End of Alzheimer’s Program. An internationally recognized expert in the mechanisms of neurodegenerative diseases, 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. Dr. Bredesen earned his MD from Duke University Medical Center and served as Chief Resident in Neurology at the University of California San Francisco, before joining Nobel laureate Stanley Prusiner's laboratory at UCSF as an NIH post-doctoral fellow. He held faculty positions at UCSF, UCLA, and the University of San Diego.

Dr. Bredesen directed the program on aging at the Burnham Institute before joining the Buck Institute in 1998 as a founding president and CEO. Dr. Bredesen's research explores previously uncharted territory, in explaining the physical mechanism behind the erosion of memory seen in Alzheimer’s disease, and has opened the door to new approaches to treatment. This work has led to the identification of several new therapeutic processes that are showing remarkable early results.

Dr. Bredesen is a prodigious innovator in medicine with over 30 patents to his name. His book, The End of Alzheimer’s Program: The First Protocol to Enhance Cognition and Reverse Decline at Any Age is the follow-up to his earlier work, The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline. And now, my interview with Dr. Dale Bredesen.

I was very excited to learn that Dr. Dale Bredesen now has a follow-up book to his End of Alzheimer’s, as that was one of my personal favorites in the past few years. His latest book, ''The End of Alzheimer’s Program'' has just been released.

I had a chance to read a preview copy, and it was so full of rich information to really help us maximize and improve our cognition throughout our lifetimes. If you've not heard our earlier discussion on episode 89, I recommend listening to that as well. Thank you so much for being here today, Dr. Bredesen.

[00:03:06.08] Dr. Bredesen: Great to be here, thanks so much for having me, appreciate it.

[00:03:08.21] Scott: Give us the state of the union in terms of the ReCODE protocol that you've put together to enhance cognition, to reverse cognitive decline at any age. How's the protocol working? What percentage of people can expect to see some observable benefits? And where do you see research going next?

[00:03:25.18] Dr. Bredesen: Yes, a lot of questions in there. So, this is now ReCODE 2.0, so we've learned a lot in the last several years. The first book came out in 2017 and was really conceptual, as you know. It was really about here for the first time; we think we have an understanding of what's driving this process. And it turns out, not to be one thing, this is a complex chronic illness, and we talked about 36 holes in the roof.

A drug is great for one hole, but you've got to now also patch the other ones. Over the last several years, we've had a number of developments that have come up, and so it's interesting. As we're going through, we're seeing that when you have a physician who is very good with this, and we've trained over 1500 physicians now, most of their patients will improve. And no surprise, the earlier, the better. So this is why we want people; we just urge people, please don't wait.

This is, as you know, dementia is something that sneaks up on people. The doctors often say, hey, there's nothing you can do now; just come back next year; you're not that bad yet. We hear this again and again, and then at some point, they say you've got Alzheimer’s, nothing we can do. So we recommend people please if you've had senior moments that anything, please get in. We used to talk about this as a disease of old age. You get Alzheimer’s 60s, 70s, 80s, and 90s. Now, as it's turned out that 20 years ahead of a diagnosis is when you're seeing the beginning of the pathophysiological changes. So we're really talking about a disease of the 40s, 50s, and 60s, which is diagnosed 20 years later.

So just to give you an example, a few of the things that have come up that we didn't know about before. One of the things that's turned out to be the one of the most common contributors to cognitive decline has turned out to be reduced oxygenation at night. So nocturnal oxygenation. Now people talk about this as sleep apnea, and they say oh no, I don't snore, I don't have sleep apnea. Well, yes, there are a few people have sleep apnea, and that's absolutely a contributor.

But there are many people who don't necessarily have a diagnosis of sleep apnea and, nonetheless, will decrease their oxygen saturation at night for numerous reasons. They can have upper airway resistance syndrome, for example. They can simply be sleeping on their backs, not getting good enough expansion, not getting good enough oxygenation, and other reasons.

And of course, we're also aware of oxygenation with COVID-19, it's been such a big issue, and of course, you can check your oxygen saturation on your iPhone if you like. And make sure you're doing well. While you're sleeping, you should be in the 96 to 98 percent oxygen saturation. Many people we see are dropping not only into the 80s; we have people even into the low 70s.

It turns out that there's a very nice research showing that if you look at the mean oxygenation for the night, this correlates very well with the size of various nuclei within your brain; including nuclei critical for Alzheimer’s disease. So you're really doing yourself a disservice if you are allowing yourself to drop your oxygen saturation at night, which so many of us are, and simply aren't checking. And in fact often when we go in to the physician and say hey, we're having memory problems, we're having cognitive issues, the physician doesn't do the critical tests that are needed to determine why you actually have this cognitive decline.

And so he or she often doesn't check for nocturnal oxygen saturation. If you have obvious sleep apnea, they may say okay, I’m going to send you for a sleep study, but it's not one that's routinely done. Another one that's come up in the last few years has been the importance of the oral microbiome. And we talked a little bit before about rhinosinal microbiome.

Yes, having chronic sinusitis is an issue, and so many people with mold exposures have this. But we didn't talk enough about the oral microbiome. And what is turning out, you can get this simply tested with a test called Oral DNA test. So many of us with suboptimal dentition have species that are critical. So P. gingivalis, T. denticola, F. nucleatum, Prevotella intermedia, and there are a few others as well. These are all pathogens.

And interestingly, when you look at the brains of patients with Alzheimer’s, what you find, this has been published repeatedly, you find these different species. You find oral bacteria; you find Herpes Simplex 1 from the lip. You find various mold species and fungal species and even yeast, so Candida things like that. And so the pathologists have been telling us for a while, there's something going on in the brains of patients with Alzheimer’s.

And of course, it has turned out that the amyloid that we produce, that we associate with Alzheimer’s disease is really an antimicrobial as Professor Robert Moyer and Rudy Tanzi from Harvard showed a number of years ago. So this is what we've been vilifying as oh if we could just get rid of that amyloid stuff, everything would be fine that's turned out to be wrong.

In fact, you want to first get rid of the insults; then, you want to get rid of the amyloid. So these are just some of the many things that we've discovered between the first book and second book. The first book was really conceptual, second book is really practical; it's the details that so many people ask for after the first book.

[00:08:51.15] Scott: Why is holism a more appropriate way to approach cognitive decline as compared to reductionism? And I think it's really interesting that your background really was not in holistic or integrative medicine, that was kind of an acquired taste.

Something that evolved for you as a part of your life's work, really. And so why should we look at the forest and not the trees? And what will it take to gain broader acceptance of these kinds of approaches in the allopathic community?

[00:09:19.10] Dr. Bredesen: You know this is such an important point because I was not a believer in integrative medicine, functional medicine any of that stuff. As a scientist, I just was interested in reductionism. We're going to find that one thing. In fact, I told my wife 25 years ago when she said whatever you guys find in the test tube, that's going to be driving the neurodegenerative process, which is what our laboratory work was for the whole 30 years. Could we understand the basic molecular mechanisms? Because this has been the area of greatest biomedical therapeutic failure. So let's figure out what the heck is this.

Why is Alzheimer’s so common? Why are so many people getting this? Why is it so hard to treat? And as we began to do that, my wife had said you're going to find things that have to do with holistic things like exercise and stress and diet, all these sorts of things as part of the overall concept. And of course, I said no, we're going to find one fold of one protein that's going to be the entire answer. We're going to design a drug that fits into that one fold, and we're going to wipe out Alzheimer’s.

And of course, I should have listened to my wife 25 years ago, she was right. It's very interesting to me because when you just go from the basics, you look at how do you get amyloid? Why does your brain make it? Where does it come from? And of course, there is a precursor to the amyloid that is associated with Alzheimer’s, and this is called amyloid precursor protein, APP. And when there are mutations in APP specific ones, you have familial Alzheimer’s.

But those are the rare cases. The mutations in APP represent less than one percent of all Alzheimer’s cases. And in fact, the familial ones represent in total APP Presenilin-1 and Presenilin-2 represent less than five percent. So the vast majority of us, the 95 plus percent of us who get Alzheimer’s disease, get it as a sporadic Alzheimer’s.

And if you follow how this APP is cleaved, in fact, it's a beautiful story. APP functions as a molecular switch; so that it is literally integrating, looking at what are your hormone levels? What are your vitamin levels? What are your various toxin levels and things like that, metal, it's a very metal responsive gene among other things. So when things are positive, when you have abundant hormones, nutrients, trophic factors.

You don't have an inflammatory status; you don't have insulin resistance. You don't have lots of toxins around, things like that. Your APP actually senses that, and it is signaled by being cleaved by alpha secretase, which cleaves in the APP to produce two fragments. One is actually extracellular; one's intracellular. And this is very similar to the head of your company saying okay, things are good, we're going to go, we're going to grow.

We're going to now make new interactions, and this is what your brain does, it makes new connections and supports those connections. And that allows us to make new memories and do all the things that we do each day. On the other hand, the same APP molecule when things are bad when you have insulin resistance. When you have low hormone levels when you have ongoing toxicity or inflammation, various pathogens, poor vascular support, any of these things.

Your body senses this now, and it cleaves the same APP, which sits in the membranes of the neurons and in other cells as well, but more in the neurons. Then it cleaves it at three sites beta, gamma, and caspase sites. Thereby producing four fragments, two that are essentially external and two internal. And these now signal wait a minute, we are under attack, we're going to pull back. And you know we've seen such an analogy here with COVID-19, what happened with COVID-19?

We recognize we're under attack by SARS-CoV-2, and it's spreading, so what do we do? Everyone says okay because the administration tells us. Okay, we're going to have to now pull back, we're going to have to have social distancing, we're going to have to shelter in place. But in so doing, we are decreasing the network. We are now in a recession due to this. So this is a protective downsizing response that we have had to COVID-19.

And Alzheimer’s disease is also a protective downsizing response that your brain undergoes when it is under attack from these various things we've been talking about the pathogens etc. So it knows hey, something's going wrong here, and literally, it's producing things that are trying to kill the various organisms that are trying to bind the various toxins. But unfortunately, in so doing, you are downsizing.

Now, if you find what's causing the downsizing and remove it and then support the brain, you can actually reverse the process, which is what we've been doing now for over eight years. However, of course, in most people and in the standard of care, you don't recognize what's causing the problem, so you just have a continued downsize.

It's as if you just had COVID-19 increasing, and people just got to the point where they're sitting there by themselves in a corner not doing anything. Hopefully, we'll get past that with COVID-19, and hopefully, we'll get past that with Alzheimer’s. But that's been the problem with the standard of care in Alzheimer’s disease.

[00:14:52.23] Scott: So this amyloid precursor protein that really is the switch that leads to either blastic or clastic activity that moves us in an anti-Alzheimer’s or a pro-Alzheimer’s direction. Is there a way to test to see how that's expressing in a particular person?

[00:15:09.21] Dr. Bredesen: Yes, you know that's a great point. And I really wish we had a simple lab test that would say aha, your APP is 92% blastic making more synapses, and 8% clastic pulling back; you're in good shape, let's see you next year. Unfortunately, there is no simple way today; there's no clinical test to say what is your APP doing.

So, therefore, we look upstream, which, of course, is the way functional integrative medicine works. We're looking at all the things that are driving this, so we can infer from the different things. But we can look at each of these things because each one is a potential contributor. If you're walking around with an hsCRP of 10 as so many people are if you're walking around with a vitamin D of 18 or 20. If you're walking around with a C4a of 10,000, these things are all contributors.

They're telling you things are sub-optimal, and therefore your APP is likely to be signaling synaptoclastic activity. Now you bring up a good point, some people, of course, trigger that much more easily. So if you have ApoE4, you have a more pro-inflammatory genome. Which is great if you are a Tsimane' Indian, and you're full of parasites, you're going to do better, if you have ApoE4.

But if you are not in a third world country, and you're trying to avoid cardiovascular disease and Alzheimer’s disease, then, in fact, you want to know, if you're ApoE4, you're going to do a little extra on the anti-inflammatory side.

So you've got to kind of know where is your set point, but looking at all of these different contributors is what tells us these are the things that are your risk factors. And we're actually just starting something called PreCODE; ReCODE is the reversal of cognitive decline that we've been using. We've now set up PreCODE, which is a simpler approach just for prevention. For people who are truly asymptomatic.

[00:17:10.19] Scott: Beautiful. In the book, you talk about the needed vaccine for Alzheimer’s. It's not an injection, but an unjection. Tell us what you mean by an unjection.

[00:17:22.29] Dr. Bredesen: Yes, and of course, I recognize that term unjection has been trademarked by Pfizer. I was simply using it as a way to say hey, it's interesting, this whole study of complex chronic illnesses the Alzheimer’s, Parkinson’s, cancer, cardiovascular disease this is really changing medicine. The medicine I learned in the 20th century was about what it is, get a diagnosis, write a prescription, move to the next patient.

That's not the way medicine is optimally practiced. 21st-century medicine is about why is it? Why did you get this problem? Because, as you know, prescription medicine has not helped Alzheimer’s. So, therefore, the point is we had global programs for things like Polio and Smallpox, where we're now looking at vaccinating people.

And so my point in the book is we now need the same sort of program. So we now need the same sort of program for Alzheimer’s disease. There should be global programs to prevent and reverse cognitive decline. But the point is, it doesn't work to just take an injection. This is really about looking at a set of things; this is now about more of an integrative approach to ask okay, what is driving this? What is driving your risk in each person?

So this is why I said we need to have a global program. And the ''vaccine'' for Alzheimer’s disease, to prevent Alzheimer’s disease. And by the way, I should say, as you know, there was an attempt at a vaccine years ago and actually killed a number of people, unfortunately. Because when you try to vaccinate someone, a true vaccination against amyloid, of course, many people's brains are making amyloid anyway; it's a protective molecule.

So now you're trying to vaccinate against something that's there already, that's what we call autoimmunity. You're now responding to a normal part of your body. So that did not work, unfortunately. Instead, what we need to do is take a completely different approach. It's not about an injection; it's about a protocol that is personalized to you.

If you, as I said earlier, if you're walking around with a Vitamin D of 18 or 20 or you're walking around with a Vitamin B12 of 250. Or you're walking around with a red blood cell magnesium of 4.1. You are at risk. If you're walking around with no Estradiol or low testosterone, low pregnenolone, you can go on and on and on. So many of us are exposed to these various things. And by the way, you can add things like mycotoxins, and we simply don't know about it. This has been both the good side and the bad side of chronic illness.

On the bad side, we're developing these diseases, and we don't know we have them until very late in the process. And as you know, that's true for renal failure, hepatic failure, heart failure, just go on and on. Cancers, and of course, neurodegenerative diseases. When we diagnose, it is relatively late in the process.

So please get an early, get what we call a Cognoscopy, check things out if you're 45 years of age or older. And make it so that we can make the global burden of dementia very modest, so you want to get in early. Now the good side of chronic illnesses is that if you know what to look for, you can see them coming for years ahead of time. So you can see people who are at risk for cognitive decline if you just bother to look.

[00:20:54.07] Scott: Similar to a colonoscopy, you mentioned a Cognoscopy to really look at the various factors that can provide you with insights about the direction that someone's cognitive function is heading to help avoid cognitive decline. How easy is it for doctors to order a Cognoscopy as a single panel through some lab? Is there a one-stop Cognoscopy shop?

[00:21:16.02] Dr. Bredesen: Yes, in fact, you don't even have to go to your doctor, you can get Cognoscopy online. Just go to MyCognoscopy.com. You can get the tests there, and actually, you can get them at reduced rates on that particular site. We interact with the laboratory to reduce their rates so that many people could get Cognoscopies.

And I think this is a really important point to mention. We all know when we turn 50; we're supposed to get a colonoscopy. And that helps we can reduce the risk for getting significant colorectal cancers, that could limit our lifespans. In fact, my wife and I decided this was such a pain; we really don't want to do this. Okay, so we ended up having his and hers colonoscopies on Valentine’s Day. We thought okay, this is just get past this, let's make sure that we're both okay.

But we don't talk about, just like we talk about carcinogens but not dementogens. We talk about colonoscopy, but we forget to talk about Cognoscopies. And it's a silly word Cognoscopy, but it's easy to remember. So you want to know, and I talk about this in the book. It's three things, number one is a set of blood and urine tests easy to do, and again you can do it at MyCognoscopy.com. Look at that, that's a set of tests to get. 

And you want to know all the things we've been talking about; we want to know if you've got a burden of different toxins. You want to know if you have vascular risk factors that's turned out to be one of the surprising things. We used to talk about vascular dementia and Alzheimer’s; well, in fact, they are much more intimately linked than people used to believe.

So that's the first thing is the testing, number two is the part of the Cognoscopy is looking at your current cognitive status. And the good news it used to be hours and hours of tests, you can do this in 30 minutes online, it's an easy thing to do. Whether you use CNS Vital Signs, whether you do a MoCA test, MMSE, Cog State, there are a lot of ways to go.

And we're agnostic, whatever works best, that's what we're interested in using. And so that's the second piece, you want to know where you stand. That's particularly important because you've had a number of people who have come in for prevention. But because this sneaks up on you, and I’ll give you an example. I talked about this in the book, a woman who was at risk with multiple family members with Alzheimer’s.

She said I think I’m doing pretty well; she's actually in her late 40s. And when we tested her, MoCA score was only 23 out of 30. So she was already well into MCI and just didn't realize it. And by the way, it's now 30; she's doing absolutely great. She wrote me a beautiful email talking about how well she's doing. Because we got in there, even though it wasn't quite prevention, it was early reversal. And for prevention and early reversal, this is successful virtually always if you do the right things.

If you optimize your biochemistry, that's the idea. Then the third part of the Cognoscopy is actually optional. If you have no symptoms, you don't have to have an MRI with volumetrics. But if you do have symptoms, or if you're scoring poorly on cognitive tests, we recommend that people then get MRI with volumetrics.

So that you can see you want to know is your hippocampal volume reduced, for example, is your cerebral cortical gray, for example, reduced. So these things are critical to know if you are symptomatic, they are important prognostic indicators. And of course, also they'll tell you whether, in fact, your cognitive changes are due to something else.

If it happens to be multiple strokes, you want to know that. If it happens to be a brain tumor, you want to know that. Of course, in the vast majority of cases, it's the thing that ultimately really leads to what we would call Alzheimer’s 20 years later. But again, you want to get in as early as possible. So that's all the Cognoscopy is those three things.

[00:25:03.28] Scott: I’m excited to hear that we now have the MyCognoscopy.com, I think that's new since our last conversation. Many listeners of this show are dealing with chronic Lyme disease, in chronic Lyme disease parasites and other infections are very common.

You mentioned that in ApoE4, which is potentially a contributor to Alzheimer’s that it can also be protective of parasites and protective of chronic infections. So does that suggest that ApoE4 is less likely or less common in those people with chronic infections or parasitisms?

[00:25:38.20] Dr. Bredesen: So that's a very good point, so here's the thing. There are two parts to this, and this has been just published by the way in COVID-19. So people with ApoE4 have done more poorly with COVID-19, and that is likely to be because they have a more brisk inflammatory response. But theoretically and for everything we know about how ApoE4 actually works, you have this more brisk response.

So theoretically, you should actually be protected from getting the disease in the first place. But once you get it, you have a more brisk inflammatory response, and therefore you may do more poorly. So you have to think about this in two phases. Phase one, yes, having that brisk inflammatory response, good thing. You're likely to be more resistant to getting these things.

On the other hand, once you get them, you're going to have to be careful. As dexamethasone has come out as being something helpful in COVID-19 because you're dialing down that severe cytokine storm that can kill people with COVID-19.

And the same story happens with Alzheimer’s; we want to be careful about that inflammation. So again you've got one thing that's pro, one thing that's con, and it depends on where you end up with those.

[00:26:56.05] Scott: You talk about the common contributors that we need to explore and evaluate in terms of our risk ongoing inflammation that you just mentioned. That may not present with obvious signs and symptoms, but it can still be an underlying or smoldering inflammation. What are some of the key contributors to inflammation? And what do you recommend in terms of mitigating those inflammatory contributors?

[00:27:20.01] Dr. Bredesen: Yes, that's a very good point. And in fact, the problem is, is that many of us are giving ourselves Alzheimer’s disease or being exposed to things without our knowledge that are contributing to our cognitive decline. So this is the problem we've got these ongoing things for years, and then we end up finally hey, something's wrong.

So let's begin with you want to know your ApoE status, and we've been told in the past don't bother to check it, because there's nothing you can do about it. It's absolutely wrong. There's a tremendous amount you can do about it. And in general, the armamentarium for the cognitive decline of Alzheimer’s we've been told is zero. It is huge; there are all sorts of things as we talk about in the book that are absolutely crucial.

So you want to start by knowing your genetic status, then you want to know as you said your inflammatory status. And you can get that with things like hsCRP, and the various pathogens that are contributing to this. You want to know that. And these are things that if you've got a poor dentition, important to know. You can use things like Dentalcidin mouthwash, and Dentalcidin toothpaste, which actually improves your oral microbiome.

We've heard so much about the gut microbiome and its critical relationship to disease states such as Parkinson’s and Alzheimer’s and cardiovascular disease and autism. All these sorts of things and inflammatory bowel disease, you can go on and on and on, so many of these things related to the gut microbiome and leaky gut.

People have begun to talk about gingivitis and periodontitis as leaky gums. It's the same idea. You've got a change in the microbiome that is associated with damage to critical barriers. And so you want to know whether you have exposure to these different pathogens as we talked about earlier. And so we'd like to know your hsCRP and exposure to various pathogens and things that increase inflammation. Be it from the gut, be it from chronic sinusitis, be it from Lyme disease.

And Lyme disease is an important one because it's so incredibly common. And what does it do? It sets up a chronic infection, chronic inflammation with a systemic effect. And what happens then? You increase your risk for Alzheimer’s disease. And people have talked about wait a minute, is it Alzheimer’s? Is it Lyme disease? No. In fact, you have to understand Alzheimer’s is a name we give to a pathology that is a protective response to all these different things, including, by the way, Lyme disease. And a number of the people we see with cognitive decline have the Borrelia of Lyme disease.

But also, as you know, more than half the people who are Borrelia positive will be positive for other tick-borne infections. And great example of a woman who had done well and was starting to decline again and it turned out that look, we've got to look further, she ended up having Babesia, and she's done very well with the treatment for Babesia.

So people, as you know, may have Ehrlichia, may have Bartonella, may have Anaplasma as other tick-borne infections, and you've got to identify those and treat those as well so that you can remove that systemic contribution to cognitive decline. And then probably the most common thing of all is insulin resistance.

So many of us, of course, I grew up like everyone from my era, loving popsicles and sweets and all these sorts of things. And eating the wrong food, and loving cheeseburgers and fries and cokes and things like this. This was the world when I grew up. I remember when McDonald’s first appeared, and everyone thought, wow, here's a cool new place to go. Well, it turns out, of course, that these things have created a pandemic as Jeff Bland has said COVID-19 is simply a pandemic within the pandemic.

We're already in the pandemic of metabolic disease, which increases our risk for Alzheimer’s, and Alzheimer’s is on the increase dramatically. And so in fact, over a hundred million Americans have some degree of insulin resistance, as you know. Of course, some have type 2 diabetes or pre-diabetes, but many of us have the insulin resistance that is heading us in that direction, which is why it's so critical for us to know our fasting insulin status.

And to know whether, in fact, we are insulin resistant. Again, you go into an Alzheimer’s center; they typically don't measure your fasting insulin. They say well, that's about metabolism, we're talking about your brain. But these are, of course, related. And insulin is a critical growth factor for your neurons. When we grow neurons in a petri dish in the lab, we have to add insulin to keep them supported.

So no big surprise as you now have insulin resistance, and you can actually see that as a change in the phosphorylation of IRS1, a signaling molecule that is downstream from the insulin receptor. You can actually measure the insulin resistance that you've developed. Then you actually begin to see that there is a lesser activity of your insulin. There is less tyrosine phosphorylation and more of the serine and threonine phosphorylations that are associated with insulin resistance. This is a critical contributor to cognitive decline, and of course, if you progress to type 2 diabetes, you've more than doubled your risk for developing Alzheimer’s disease.

So here's something we can all treat very simply with a mildly ketogenic diet, with some exercise, with some reduction of stress. Make sure that you don't have sleep apnea and things. These are things that will actually give you back your insulin sensitivity, and make you metabolically flexible once again. So that's a very common one to know.

And again, we talk about the various trophic factors, hormones again, which most people don't check and then toxins. So we are being exposed to this incredible pro-Alzheimer’s … it's everywhere. And no surprise, 15% of our populations are dying of Alzheimer’s. So the currently living Americans, we're always told that five and a half million Americans have Alzheimer’s. Well, yes, that's the ones that have it now.

But we're talking about let's look at the entire country. Of all of us who are currently living, how many of us will die of Alzheimer’s disease? And the answer is about 45 million Americans; about 15 percent of the population will get it.

And so we have a chance now to reduce this drastically. Alzheimer’s should be a rare disease as we talk about in the book because it's something that we can see coming, and we can look at all the factors that are contributing to it. And prevent it or reverse it early on especially. We do see people in the late stages who improve, but it's much easier to do it in the early stages, so please don't wait.

[00:34:31.26] Scott: A lack of various nutrients and hormones and trophic factors can impact our methylation; it can impact our metabolism, such as our thyroid, it can impact our brain function. What are the nutrients or hormones or trophic factors that you most commonly see that need to be supported in people with cognitive decline?

[00:34:51.04] Dr. Bredesen: Yes, that's a great point because, again, so many of us are not looking at this. One of the things that I’ve been doing during COVID-19 is following myself on Cronometer, just to see where do I stand with various nutrients. And it does a very nice job of looking at all the different things. And so one of the things I ran into is that I’m just like so many other Americans, I’m not getting enough choline in my diet.

That is one of the most important things, you should be getting about 550 milligrams of choline per day, and most of us don't. And in fact, what is choline important for? It is what you need to make acetylcholine, which is the most important transmitter in cognitive decline. When you are forming memories, you need to have enough acetylcholine.

And in fact, if you give an anticholinergic, you increase your risk for Alzheimer’s disease, and that's been one of the problems. So many people, the medications have contributed to their risk for cognitive decline. So choline is critical.

So, in addition to choline, vitamin D, huge player. Of course, we've heard about it a lot with COVID-19, so many of us are deficient in that. Zinc, over a billion people globally, are deficient in zinc. Incredibly common, important for your immune system.

Important in diabetes, important in cognitive decline, important to reduce the likelihood of a poor outcome in COVID-19, incredibly important, and common. Vitamin E is another one, it was actually years ago there was a monotherapy, and monotherapies haven't been successful in Alzheimer’s. But these minimal changes that people have found, one of the few things that actually just barely reached statistical significance was vitamin E.

So, in fact, that's another one that's important. Vitamin C, glutathione, these are all critical players in cognitive decline, all critical nutrients. B12, another big one. B12 reductions associated with dementia have been around for years, but the assumption was always that all these other things are ''treatable'' sources of cognitive decline; they're separate from Alzheimer’s.

No, they're much more related than people realize. These things can all contribute. Then you move from the nutrients to the hormones as you said. And our hormones also support our neural connections: estradiol, progesterone, testosterone, pregnenolone, DHEA sulfate. We measure as DHEA sulfate, the DHEA, and then thyroid, huge issue.

As you know, so many people have sub-optimal thyroid function, and this contributes to brain fog and can contribute ultimately as one of the contributors to cognitive decline. And typically, we find when we look carefully at people between 10 and 25 different contributors for anyone who is suffering cognitive decline. Human beings and their brains are complicated; this is typically not one thing that you were exposed to that, boom that was the thing that gave you, if we just fixed that, everything's okay. It's typically a suite of factors. And then you mentioned trophic factors, growth factors for the brain, and they are absolutely critical.

I look forward to the day when there's more intranasal administration of things like ADNP and NGF and BDNF and things like this. For now, these are critical players, and you can increase your BDNF in a number of ways, and that has a direct anti-Alzheimer’s effect. And so you can do this with exercise, it turns out exercise increases your BDNF.

Ketosis increases your BDNF interestingly. And whole coffee fruit extract is another one that actually increases your BDNF. So a number of ways that can be used to increase your brain-derived neurotrophic factor. There are also a number of things that increase; nerve growth factor is another one. Nerve growth factor supports cholinergic synapses, which are critical ones for memory in your brain. ALCAR, acetyl L-carnitine is one of the things that actually increase nerve growth factor.

Another one is horizon erinaceus, which is a mushroom. And in fact, that mushroom alone is in trials for Alzheimer’s disease. So there are ways that you can get at all these things. The goal here is to change your chemistry from synaptoclastic downsizing to synaptoblastic. Now you're upsizing; now you're making and keeping critical synapses within your brain. And so as you can see, the armamentarium to do this is huge.

[00:39:39.13] Scott: You mentioned zinc deficiency, is it more common that you see copper deficiency or copper toxicity in your patients? And if the answer is toxicity, is that connected then to the zinc deficiency? How do you balance that zinc-copper ratio and resolve copper toxicity when it's present?

[00:39:59.24] Dr. Bredesen: You know that's a great point. And Professor George Brewer at the University of Michigan spent his career looking at copper and zinc. As he pointed out in general, of course, we know that most of us are going to be deficient in zinc, often deficient in magnesium, often deficient in iodine, and often deficient in a few other things like choline as I mentioned. So as you said, copper and zinc actually have some antagonism.

So if you've got too much copper, you're not absorbing your zinc well enough. If you take too much zinc, in fact, you can drive your copper down. So we want that ratio to be about one to one, as we mentioned in the book. And most of the people, as Dr. Brewer pointed out over the years, most of us have an excess of copper and too little zinc. So we want to rebalance.

On the other hand, some people are too aggressive. They may take 50 milligrams of zinc and no copper, and after a while, they're now deficient in copper. So you want to be careful and make sure we typically want people to be more in the kind of 20-25 milligrams of zinc. So we do see this, and by the way, we see it, especially in type 3 Alzheimer’s disease, which is the toxin associated disease that we see these high copper-zinc ratios.

Papers from years ago show that people who have ratios above 1.3:1 are at greater risk for cognitive decline. So we like to see a more like 1:1, we see these with people who have toxicity 1.5, 1.82 we've seen people with 3:1 ratio of copper to zinc.

So we'd like to see it more like 1:1. Now we do see in cases sometimes with ALS; you'll see an increased zinc to copper ratio. But in general, with cognitive decline, we see the other way around high copper to zinc ratios.

[00:41:52.21] Scott: I want to talk a little bit about optimizing sleep; that's been a big area of focus for me over the last couple of years. I sleep in a silver-lined faraday cage to avoid EMFs. I turn off the circuit breakers to the bedroom at night to kind of create a sleep sanctuary.

You've talked about the potential for nocturnal hypoglycemia; you've also talked about the potential for low oxygen levels during sleep. What are some of the tools that you use in looking at nocturnal hypoglycemia? And also the low oxygen potential.

[00:42:24.25] Dr. Bredesen: Great point. You know sleep is one of the most underappreciated contributors to cognitive decline and an incredibly common one. Patient zero that I wrote about in the first book came in back in 2012; she was sleeping four and a half to five hours per night. And part of the improvement and she by the way just emailed me this morning just by chance; she's doing absolutely great.

She's now over eight years into this, and she's sustained fantastic improvement and is actually now working as a brain health coach and doing a great job. So sleep is a huge issue. And as you indicated, the first thing is what is your status with respect to oxygenation at night; we really need to know that do you and do you have sleep apnea?

The second thing, as you indicated, is sleep hygiene. And so many of us are trying to sleep where number one, we're waiting till really late to go to sleep. You want to be able to go to sleep earlier if possible, and I know I’m a horrible offender. I’m having come through internship and residency where I wasn't sleeping for days at a time, that's really been a problem.

So you want to have good sleep hygiene wind down at night, you don't want to have a bright blue light, that's, of course, driving you. So you want to have red light associated, you want to power down your computer, or you want to have a screen so that you don't have that blue light. You can put on some blue blockers at night, very helpful.

Some people like things like lemon balm, some people like things like various aromas that actually will be relaxing and supportive like lavender sheets and things like that. You want to turn off your Wi-Fi, as you mentioned, that is continuing to stimulate you throughout the night. So that's another huge thing. You want to be in a place that has no sound.

Boy, you know when I travel to places like New York City. Boy, you know you're hearing stuff going on all night, you've got thing trash cans banging, and you've got sirens going throughout the night that is really harming your brain. And so you want to minimize that. And then, of course, I like to wear shades, especially as the sun's starting to come up.

Now again, of course, ancestrally, we're going to go to bed with the sun, we're going to wake up with the sun. But typically, that's not the way we're conditioned in our current society. So okay, if you're going to be going to bed later than the sun, which almost all of us do, then be aware that when it's starting to rise in the morning, you might want to put on a blindfold.

So that you're not getting it. Of course, as soon as you've got light, that is shutting down your melatonin production very effectively. So that's another thing, make sure that your melatonin is enough. For many of us, our melatonin will start to go down. One of the ways to get rid of your melatonin and hurt yourself is to eat late at night and make sure to include some carbs.

So there's again another thing that you can help to give yourself cognitive decline by not doing the right thing, by eating late at night, by having carbs, so that your insulin is continuing at night and you're not making the melatonin that you were meant to make. So all of these are critical features, really good sleep is an art and it's something that we can learn to do better.

And we can use to our great advantage, and helps us to reduce cognitive decline for so many people who are out there getting four or five hours of sleep at night; they're really hurting themselves. Now the caveat is, and you probably saw the recent research, genetically there are a few people that do not need as much sleep as the rest of us, and there's an ongoing effort to look at what are the genetics of this and who are these people.

But for the vast majority, and especially when you're thinking about cognitive decline, make sure to get seven or eight hours of sleep per night, this is critical. Now there's also an association as you know, people are sleeping 10 hours a night. They're typically people who have hypothyroidism or other problems. They have exhaustion; they have adrenal insufficiency. Yes, they're also at increased risk for cognitive decline, you want to be at that sweet spot.

But you want to be at that sweet spot because you are making sure that your adrenals are supported, that your thyroid is appropriate. You're getting good sleep hygiene. These are all things that can contribute to better. And I should add it's not just about preventing cognitive decline, it's also about better day-to-day cognition. Most of us who have normal cognition would actually be better if we were doing all the right things.

[00:47:00.23] Scott: You know one of the things when I was exploring my own sleep issues was using a continuous glucose monitor to explore the potential for nocturnal hypoglycemia. Turned out, that was not an issue.

But coming back to your point about not eating carbs close to sleep time, in those cases with nocturnal hypoglycemia potentially having some protein, can be helpful in terms of keeping the blood sugar more stable. Are there other things that you do in terms of helping to balance that blood sugar while people are sleeping?

[00:47:29.28] Dr. Bredesen: Huge issue. And I think that the CGMs, these continuous glucose monitors, that have come out last several years have been one of the most important developments. We should all know the two weeks of monitoring that a typical CGM gives you. Because as you indicated, you actually see a couple of different things that you otherwise wouldn't know. Number one, you see when you're spiking.

We've had people say oh my gosh, I never realized that that healthy stuff that I thought I was eating is spiking my glucose and that's increasing your risk for cognitive decline. Then secondly, as you said, people then go to sleep, and because they haven't had enough good fats or good protein during the day, they're now dealing mostly with carbs. So they've got the spike, and now you go to bed, and now it's coming down.

One woman was waking up between 2 and 3am almost every night, and wondering what the heck is going on? Why am I waking up? And it turned out she was waking up because her glucose was dropping into the 40s at night. And so to smooth that out, you want to get something that's got a longer, smoother curve which are good fats, increase your fiber.

And it's interesting to me that there's kind of an anti-fiber group out there, fiber is one of the most important things. It is helpful for detox; it is helpful for your lipid profile. It's helpful for your glycemic load and glycemic profile; it's helpful for your gut microbiome. It's incredibly important. So the idea is that most of us our forebears a thousand years ago, we're probably getting something around 100 grams of total fiber per day.

We try to get people up to get 30 grams of fiber per day; it's still less than our ancestors, but better than most of us. Most people are walking around 5, 10, 15 grams of fiber a day, that's simply not optimal. So check out see where you stand, you might want to add some organic psyllium husk, you might want to add some Konjac root, but of course, the key thing is you want to get fibrous foods and things like that in addition to your probiotics and prebiotics.

Get that microbiome working for you, so all of these things are absolutely crucial. And as you indicate, you can get hypoglycemic at night. If you're doing that, have yourself a fat bomb. Have more of a ketogenic diet, have more fiber in your diet, and you'll smooth out that glycemic index.

[00:50:02.05] Scott: Another thing that I explored for the oxygenation piece, which is very simple, was actually doing mouth taping at night, so that you're breathing through your nose. And so I’m curious on that oxygenation concept more broadly for cognitive health. Is exercise with oxygen therapy or EWOT, is that something that you found helpful? 

[00:50:22.08] Dr. Bredesen: You know this is really interesting. EWOT is turning out, I think, to be highly important. And I was a skeptic at the beginning. So when I’ve actually heard about this from a person that we were dealing with someone with macular degeneration, and they've done very well on EWOT because, in macular degeneration, the overall chemistry is slightly different than it is with cognitive decline.

But it's the same idea; you have a subsystem of the brain essentially, that has got a more of a demand than it is supplying. So you've got to balance that just like we have synaptoblastic and synaptoclastic; in that case, it's maculoblastic and maculoclastic. And you're now with a different chemistry supporting the same thing.

So the idea here is with many people with cognitive decline, they are not reaching the far reaches of their neurons, their brain architecture with enough blood flow, with enough oxygenation and with enough nutrients. And basically, combustible material, in this case, ketones or glucose. And of course, when you look at a PET scan of someone with Alzheimer’s or pre-Alzheimer’s, what do you see? You see decreased glucose utilization in the temporal and parietal regions.

These are critical regions for Alzheimer’s disease. And we know therefore you have an energy gap. So part of what we are treating in people with cognitive decline is to bridge that energy gap, and we do that with ketosis. But we also do it by improving blood flow by improving oxygenation, and that's where EWOT is huge. And in fact, a good example is, and I don't push any products, I’m agnostic, whatever works.

But I did have an interesting talk with the group that developed Live02 the other day, and a little background on you why they developed it, etc. And so what they developed for training is actually a great idea for people who have cognitive decline or at risk for cognitive decline, because again now we are getting appropriate blood flow, and we are getting appropriate oxygenation. And by the way, it also helps with detox.

So some of the most important things for cognitive decline are being addressed with EWOT. So I have great hope for EWOT both for macular degeneration as part of the overall program for that, and as part of the overall program for cognitive decline. And presumably, some other neurodegenerative diseases and vascular diseases as well. 

[00:53:01.07] Scott: Okay. It's been on my wish list for a while; I think you've convinced me. In fact, I was looking at Live02 recently, so maybe that's the sign from the universe that it's time to pull the trigger on that one.

You talk about injecting pathogens or microbes, is it the pathogen that causes the damage? Or is it the host response to the pathogen? Meaning the immune system being hyperactive or autoimmune that's creating inflammation. So is the goal to eradicate these populations? To minimize them? Or do we also need to think about immune modulation to really quell the inflammation?

[00:53:37.03] Dr. Bredesen: Yes, that's a great point. And of course, this has come up so much in Lyme disease, and of course, we're seeing it again and again with COVID-19. You can survive the virus and die from your cytokine storm that you have created. So, unfortunately, it is complex because it is a mixture of what is the pathogen itself, what are the fragments of the pathogen that are now also, this happens, for example, with gut, you get the LPS is the standard, but of course, this happens with other things.

When you go into a water-damaged building as an example, as Dr. Shoemaker himself has pointed out. There are over 20 different things you're exposed to. And some of these are some of the fragments of the various pathogens, inflammagens, and ….

So again, it's a soup, and unfortunately, it's a dementogenic soup that these things are exposed to. And so it's not just the proliferating microbes. And then, of course, it's how often are you exposed to it, how much, again as we've heard with COVID-19. You get a smaller exposure; you're in better shape. You get a huge exposure, you're in much worse shape.

So and this is one of the concerns we have with cognitive decline. People who re-expose themselves every day to mycotoxins, for example, and to the very molds that carry and produce the mycotoxins, they're doing worse. So it's the organism, it's the various fragments, it's the toxins made by the organisms. And of course, bacteria make toxins; molds famously make toxins. The molds are in there saying hey, I’m a slower-growing organism than the bacteria that I co-habit within various places. And therefore, I am not going to survive because the bacteria are simply going to outgrow me.

So what I have to do is make antibacterial compounds, and of course, that's where penicillin came from. Unfortunately, when they make these protective compounds for them, they're trying to destroy the organisms around them. They are destroying us as well. So especially, and it's not all molds, but especially the big five.

The Stachybotrys, Penicillium, Aspergillus, Chaetomium, and Wallemia. Those are the big five, and they make things like Trichothecenes from the Stachybotrys, Ochratoxin A, all sorts of Zearalenone, and all these different toxins that show up in our bodies. And unfortunately, we can be exposed to for years without realizing. These things damage our immune systems; these things can increase our risk for cancer. These things unquestionably increase our risk for cognitive decline.

So these are major problems and things again that we need to get checked for. So then, as you pointed out, your immune system. And there's something very interesting in the immune system; we're experiencing this again and again and again. There's an interesting phenomenon in which, as you know, there's the innate immune system. That is the first order of business; when you're exposed to something, your innate immune system kicks in.

It recognizes these pathogen-associated molecular patterns, so-called PAMPs. And so it's recognizing these patterns which are typically these repeating patterns from these little microbes, and kicking through your toll-like receptors, kicking into gear this early, this is the evolutionarily older part of the immune system. And this is the part that is non-specific. So this is just like if you have someone invading your town, the first thing you do is say okay, everyone be on high alert.

Get inside, we don't have a picture of what this group looks like yet, but we know there's something bad out there. That's what your innate immune system does. Then it hands off to your adaptive; it triggers your adaptive. And interestingly, as your adaptive gets going, it can now turn off the innate. The problem is the adaptive is now specific; it's going after this bacterium, it's going after just like we're trying to get effective vaccines for COVID-19.

The problem is in Alzheimer’s disease and in other conditions as well, and it looks like this is an important thing in COVID as well. You have activation of the innate system without sufficient activation of the adaptive system. And in fact, you can look at people with Alzheimer’s disease; they often have poor phagocytosis.

How do you get poor phagocytosis? Lower your vitamin D, lower your Omega-3s; you will have poorer phagocytosis. And of course, there are genetic influences and things like that as well. Or, of course, just continue to be exposed to this stuff, where you just never catch up. In a perfect world, the innate system is triggered; it now gives you that brief bit of inflammation.

You hand off to the adaptive system, the cellular, the humoral, you clear it, you reset, now you're ready to go again. In Alzheimer’s disease, what happens is you have chronic activation of the innate immune system. And part of that chronic activation is amyloid beta; A beta is part of the innate immune system. So as long as you are triggering your innate immune system, you are not going to get rid of that amyloid. In fact, you're actually going to continue to make more.

So this where you've got poor activation of the adaptive system, you are really hurting yourself. You want to get that adaptive system, you want to get rid of that pathogen, and then you want to reset. And of course, resolvents have come in to be very important.

This wonderful work from Professor Charles Serhan at Harvard showing that you actually have to have a resolution phase. It's not just about anti-inflammatory, it's about resolving ongoing inflammation. And this is a critical part for resetting things and a critical part for making it. So you're not continuing to produce that amyloid over the years.

[00:59:42.26] Scott: So those would be things like SPM active from Metagenics, or MegaOmega from Microbiome Labs, for example, when we're talking about these resolvins. But one of the things that I loved probably five years or so ago when I first came across your work was how you were pulling in, and really kind of being a bridge for some of the ideas in the Lyme community, the mold community.

Where there's still not a lot of more conventional acceptance of those ideas. And so bringing those in in the context in which you've done, I think has really been a huge step forward. And talking about mold and mycotoxins, would you say that we've arrived at the place where we now view those as a significant contributor to dementia and cognitive decline?

[01:00:27.03] Dr. Bredesen: Absolutely. And so just to start, we came from the test tube. I did not come; if anything, I came with a bias against functional and integrative medicine, if anything. But we came from the test tube saying what is it that's driving this process? Why is it so incredibly common? Is there anything that we can do to prevent it or reverse the problem?

And the surprise to me was when we actually look at the molecular signaling of APP; you can't deny, you can literally trace a direct molecular pathway from estrogen to estrogen receptor, to changes in transcription to the change in the way you now cleave your APP to produce these synaptoblastic fragments. You can do the same thing with NF-kappa B, and show why you get the synaptoclastic fragments.

So it's been very clear that the test tube, the research fits much better with what we've thought about as integrative and functional medicine than it does with the classical standard of care medicine that I was trained in. So it's hard to ignore truth, now of course in politics, you can ignore truth very easily, truth is kind of irrelevant in politics.

But in medicine and in science, you can't ignore the truth. You can't ignore what actually is happening here. So this is what's driven us. Now when we started looking at the subtypes, we initially only knew about type 1 and type 2. And there was a group of patients way back in 2014-2015 where we didn't understand; these people look different, they act different. They still have Alzheimer’s, but it looks different.

They're often present in a non-amnestic way. They're often very young; these are people in their 40s and 50s which used to be unheard of for developing Alzheimer’s disease. These are people who often started with depression, who often started with difficulty with organizing things, things like that. So we started wondering what the heck is going on, and they weren't responding to the typical let's just get your inflammation down and things like that.

It turned out that these people were people who had exposure to toxins, and chief among them, the toxins really come in three groups. It's the metallotoxins like mercury, and other inorganic toxins, of course, air pollution, lots written about air pollution now, and the increase in Alzheimer’s cases with air pollution. Then second one is organics. Toluene, benzene, formaldehyde, glyphosate all these things. And then the third one is the biotoxins, things like the mycotoxins we just talked about.

And so there's no question, I wrote a paper on this, and others have written about the cognitive changes that occur. And Dr. Shoemaker has written about seeing increase in Parkinson's, as well as Alzheimer's. So there's little question. Now at the same time, what's happened? The medical community has basically said we don't recognize this as a cause of Alzheimer’s.

So they've gone back to the old idea that we don't know what causes Alzheimer’s, we have no idea, there's nothing you can do about it, and this is all 20th-century thinking. And my hope is that we will see more and more people testing for these things. Of course, the proof is when you actually reduce those toxins, and the people get better, and we see this again and again.

[01:03:48.15] Scott: Let's revisit the types. So when we talked about the various types in the first book, you have the type 1 inflammatory or what you call the hot type. Type 2 is the atrophic or cold type, related to the missing nutrients and hormones and trophic factors that we talked about.

You had already introduced the concept of type 3, which was the toxic or vile type where we talk about mold and mycotoxins and other toxins. That's kind of where we left off in the last discussion. And I think since then, you've added three more types. So tell us about the new types that have been added.

[01:04:23.25] Dr. Bredesen: Right. So again, as we go along, and as we're looking at these larger data sets, we're starting to look at okay, what's happening? What's likely to be driving this? And you can match these again with APP signaling. So what you see in the clinical lab tests mirrors what you see in the test tube.

And so what we found is yes, as you said type 1 hot or inflammatory, type 2 atrophic, type 3 toxic. Well then we also recognize look there is this very common problem of glycotoxicity, and we call that type 1.5 because it's really a combination of inflammatory and atrophic. Just kind of the worst of both worlds. So what happens is as you get exposure to high levels of glucose or other simple carbs, fructose, and things like that.

A couple of things happen, number one, you have non-enzymatic glycation of proteins, and there are hundreds of proteins that undergo this. This is just like remoras on a shark. So you are now impacting the shark, right? You're changing the shape of the shark, and you're also changing its function. You get enough remoras on there; the shark's not going to be able to swim as fast. It changes your protein function. And structure so first of all your body recognizes this as something different, and so you can get a response this.

You can get an inflammatory response; you're also changing some chemistry. You're developing advanced glycation end products. Glyoxals and things like that, so that gives you this inflammatory process. In addition, however, you are also, as we discussed earlier, now developing insulin resistance because you've got this chronically high insulin.

And of course, you use insulin-degrading enzyme to degrade your insulin; this also metabolizes A beta. If it's degrading your insulin, it's not going to be able to degrade you’re a beta. So this has been recognized for years. So you've now got this horrible combination of more inflammation and less trophic support. So type 1.5 glycotoxic.

Type 4 is vascular; we recognize that so many of these people have a vascular contribution to their Alzheimer’s. When I was training years ago, we listened to this thing called the Hachinski score; we learned to do the Hachinski score. If you have a high Hachinski score, it's going to be more likely vascular dementia. If you have a low Hachinski score, more likely Alzheimer’s. Well, guess what? It turns out that they contribute to each other.

And in fact, as it has been shown out of USC, Dr. Zlokovic has shown that, in fact, very early in the process that leads ultimately to Alzheimer’s disease, you have vascular abnormalities. And of course, on the other side, the vascular support. If you don't have good vascular support, you're not getting the trophic support that you need for your brain. And so in fact, vascular support is critical, and we talked about oxygenation, blood flow.

These are critical, so that's type 4. And of course, so many people have a degree of atherosclerosis. Incredibly common in our society, it's not only putting us at increased risk for strokes and heart attacks, but also for dementia, for Alzheimer’s disease. And then type 5 is traumatic, and of course, if you have a history of head trauma, you are at increased risk for cognitive decline.

Now, of course, we recognize CTE, chronic traumatic encephalopathy, as we all saw in the film Concussion with Will Smith. But in fact, that's a situation where you've had the trauma, and you're young, you're healthy, you cleaned out the amyloid, so you have the tauopathy left. But there's no question when you have head trauma; you undergo this increase in the production of amyloid.

This is a little bit like type 2, and in this case, it's not that you don't have enough of the factors, they're not able to get to the right places. So that is type 5 or traumatic. And so, therefore, we have a total of 6 different types. And it's important to know which ones you have, and often it's a combination to get best outcomes.

[01:08:32.09] Scott: And that was my next question, can someone potentially have all six types?

[01:08:37.08] Dr. Bredesen: Yes, you could. If you went out and you hit your head and then had metabolic syndrome and a few more things, absolutely you can. Typically, what we find is that there's more than one, and typically we find that there are two or three that are dominant for each person. And what's interesting, we start with this idea of 36 holes in the roof; we want to hit critical things, critical players to make your brain function.

As you start to improve, people will often plateau, and what happens is there's a rate-limiting step that's being missed. So then you've got to search for that rate-limiting step when you get that, there's one thing that's now preventing you from getting to that higher plateau. So as you address that, and it may be mycotoxins, that's a common one. It may be that you're not getting into ketosis, that's another common one.

It may be that you're not doing EWOT, and you're not getting that oxygenation; that's another common one. So as you're getting the vascular flow and the support and the trophic support and the energetics, you start increasing your plateau and then just say if you have a rate-limiting step, you're going to stop at that plateau. You want to keep going until you get to your optimal cognition.

[01:09:48.13] Scott: We know that the brain burns fat for fuel, and that's where we get into the whole conversation around ketosis. In the book, you talk about the KetoFlex 12/3 kind of approach. Where you don't eat for 12 hours a day, and you don't eat for three hours before bedtime. You talk about intermittent fasting.

Talk to us a little bit about the idea of MCT oil or exogenous ketones. If we're using tools like that, do we need to cycle in and out of this ketotic state for a long-term health perspective? And are there some people where a ketogenic diet or the introduction of these exogenous ketones might not be appropriate?

[01:10:27.24] Dr. Bredesen: Absolutely, and that's a really important point. So here's the critical piece, there are several things going on at once as you know. Immediately, we have to deal with the fact that there's this energy gap. Your mitochondria are not delivering what you need, and often it's because you have got this insulin resistance.

And so one way to get around the insulin resistance is ketosis. What we like for people to be in the long run is metabolically flexible. They can burn glucose at an appropriate time, they can burn ketones at an appropriate time, and they can switch back and forth. So many of us are not; we are insulin resistant. So we're doing a poor job of burning glucose, but on the other hand, we're also not delivering the ketones. So we have true energy failure, which you can literally see on a pet scan.

So what we say is look at the beginning, just go ahead and take the exogenous ketones, get that ketone level up. Over time, we want to make you insulin sensitive, and we want to make you able to produce endogenous ketones. That's the perfect scenario that is better for your inflammation, for example. So we want to give you we want to burn your own fat.

Most people, when they do this correctly, will lose some weight. Now, what about the people who are too thin already? All right, they're the ones you really want to make sure get those ketones up, and take some exogenous ketones. Now, as you indicated, there are two ways to take exogenous ketones. One of them is with oil, so MCT oil or coconut oil. MCT oil largely caprylic acid. The coconut oil has a longer carbon chain, a lot of it's C12, whereas the MCT is C8 typically.

But there are some of both in both. The problem with those is that they can increase your LDL particle number; they can give you a poor lipid profile, especially if you're ApoE4 positive. So we suggest to people if you're going to do those, fine, but make sure to check your lipid profile. Then, on the other hand, if your lipid profile is not so good or if you're concerned about ApoE4 or if you have known cardiovascular disease, simply take exogenous ketones: ketone salts or ketone esters.

And actually, there's a new one called KE1 that's a combination salt and ester that I happen to like. But there are others as well. Again, I’m agnostic; whatever works for you, get your ketone level up. What we found is people do the best when they're in the 1.0 to 4.0 millimolar beta-hydroxybutyrate range. Or if you're using a breathalyzer, and in the past, the breathalyzers I have to say haven't been so helpful. There is a new one that looks very promising called Biosense, and you want they score ACEs because that's for acetone. And you want to get your ACEs up above 7, and you'd like to be at some point in the day even up around 10 or so.

So these are kind of same idea for how much ketosis you need to have to get optimal cognition. So this is where ketone is helpful. In the long run, you're going to be generating these from your own fat by using some of this intermittent fasting, exercise, appropriate sleep; these things are all helpful to help get you into endogenous ketosis over time.

But remember that again if you're trying to do fasting and you're very thin, if you have a BMI of 17 or 18, you may hurt yourself by trying to get into these fasts and then you can do the exogenous ones. We typically recommend fast if you're ApoE4 negative 12 to 14 hours; if you're ApoE4 positive 14 to 16 or even 18 hours of fasting.

Again, this just helps your autophagy; it helps your ketosis, it helps your glymphatics all these sorts of things. And so it has multiple mechanisms to improve your metabolism. And by the way, it also helps to lower your blood pressure, improving your blood pressure. We've had so many people who, as they get on the right things, they find that they don't need their anti-diabetic medication.

They don't need their anti-hypertensive medication, and they don't need their statin as well as they're doing the right things. These are all there because we've been doing the wrong things; we've been exposed to these horrible things over the years that are giving us metabolic syndrome.

[01:14:51.22] Scott: Let's talk a little bit more about fats. I was a huge fan of coconut oil. I’m a little conflicted now, given some of the research from Kiran Krishnan and presentations from Dr. Jill Carnahan talking about coconut oil potentially increasing LPS and endotoxemia. In the book, you talk about extra virgin olive oil.

I personally like some of the blends, like the Balance oil from Body Bio, the Udo's oil, Panaseeda. What are some of the oils that you commonly would use in patients? Or do you like to stick with the single oils as opposed to some of the blends?

[01:15:27.08] Dr. Bredesen: Yes, that's a great point. And so this comes back to the issue of good fats, how do you do good fats? And so interestingly we talked before about look saturated fats, which have been vilified over the years and can definitely be harmful, especially in the presence what we call the Berfuda triangle.

You got the saturated fats; you've got the no fiber, and you've got the simple carbs, that is a horrible triad as Dr. Mark Hyman pointed out years ago, that's a horrible combination. But these things can help, you need to be able to burn the fats. So we typically start with people and either use those or, as I said earlier, use ketone salts or esters.

Giving yourself something to burn. Now over time, you're going to hopefully generate your own. As far as oils, nuts, seeds these are giving you as you know a lot of monounsaturates. And then for the polyunsaturates, yes, there are different ways to go, but we do like extra virgin olive oil. And you're right as Steven Gundry and Jill Carnahan and others have pointed out, these things if you've got the wrong situation, if you've got an unhealed gut and you've got a poor microbiome, you are helping to ferry this stuff across.

So again, it's a concert all playing; you got to get everything playing in the right way. And part of that is, and we talk about this in the book, is healing your gut and getting an optimal microbiome in which case it's not an issue about ferrying the LPS across.

And your LPS levels should be quite low. When you're doing a lot of things wrong, and that's one of the points we made in the book as well. Be careful, you start to do one thing, but you're doing everything else wrong, you can hurt yourself.

And a good example is giving yourself MCT oil, which can potentially hurt you if you're still high in your simple carbs. You're really hurting yourself; you're going to drive up your triglyceride to HDL ratio, which is an important contributor, an important indicator of your risk for cardiovascular disease.

So as far as oils, yes, we do like EVOO, but others as well depending; we talk in the book about when to use avocado oil. Again, the polyunsaturates, you have to remember these things are not all good, all bad. We so commonly here this is bad, this is good, these things have positives and negatives. As you go to more polyunsaturates, of course, they have double bonds that allow them to become rancid much more easily. They also often have a lower smoke point.

So if you're going to cook with these things, you got to be very careful and just keep it very quick and low. Things that will allow you to are things that are less unsaturated like avocado oil and things like that. So there are others, you can use it again, depends on what scents are you cooking, are you using this on salads as Julie G. has pointed out. And she was a big, an important contributor to the handbook part of this new book, that this is really.

EVOO oil is more about being a finishing oil. And I want to take one moment just to thank Julie G. and my wife, Dr Aida Lasheen Bredesen because the three of us wrote the handbook together. And Julie really wrote a lot of this based on her own experience. So I wanted to do something different. The first book was to say was conceptual; it's from science; here's what we found in the test tube.

Everybody said yes, but we want more day-to-day details, where do we go, what do we look up, what do we buy, what are the workarounds, all these things. So I linked up, so we have a scientist, we have a clinician, and we have a user who's been highly successful. And this gives us a really unique view of here are the things, yes. Here's the concept, how it works.

Here's what happens in the clinic, but here's what happens when you do it at home. Here are the things that are working for someone who's doing exceedingly well, and Julie is now over eight years doing this and doing exceedingly well.

[01:19:36.17] Scott: I should point out that the oils that I mentioned, those are not oils that I cook with, those are oils that I put into my smoothie. So there is a difference in terms of oil selection if you're cooking with them, versus just taking them cold or at room temperature. One of the things that I liked with your co-author Julie, I think she provides a lot of hope.

Because if I remember correctly, she was an Apoe44 that has actually recovered. And so sometimes I think we get so caught up in the idea that because of our genetic potential, maybe not even expression that we're somehow broken and cannot recover. And so I think it's beautiful that we see somebody in Julie’s case that had the genetic card stacked against her, and yet recovered.

So that message of hope is so important. When we look at infections, this could probably be a whole different podcast. And so maybe just at a very high level. We know that many of us have thousands of different types, or all of us have thousands of different types of microbes in us and on us. More microbes than human cells.

We know that in terms of Alzheimer’s, there are lots of pathogens that you've identified that can be contributors to dementia and cognitive decline. Are there a few key microbial support interventions that kind of come to the top of your list of things that work fairly commonly well for people with cognitive decline in terms of managing the microbial burden?

[01:21:08.11] Dr. Bredesen: Yes, it's a good point. And let me go back for one moment to your earlier point of hope, because I think this is so critical. We've had a number of people who said hey, you guys can't have anything important, because if it were important if this really actually helped anybody, it would be on the front page of every newspaper across the country.

Which is very interesting to me, and my response is talk to Julie, talk to the hundreds of other people who have improved. Read the papers we've published, we published peer-reviewed papers 2014, 2016, 2018 look at the papers, evaluate this for yourself.

There is clearly a; there's a standard of care that is pushing back very hard against this because they're looking for the next drug. And my argument to that is hey, this is like telling the Wright brothers that they didn't stay up in the air long enough. Yes, we're now in the midst of the first clinical trial in history in which instead of predetermining a treatment, which, if you think about it, makes no sense.

You say okay, we're going to treat all the people who come in with cognitive decline with one thing and let's see if it helps. Well, that's not the way cognitive decline works. So we're actually looking at over 150 different variables for each of these people, and this will be finished in December and published next year. But coming back to your point about the pathogens, very interesting because, of course, I learned in medical school, you're either infected, or you're not infected.

This was all pre-microbiome era. And now we know it's not about infected, uninfected it's about the mix of the various organisms that you have in your gut. And in fact, again, Professor Rudy Tanzi's looking at the normal microbiome of the brain. Is there a microbiome that is normal in the brain? Jury is still out, we'll see. I was always taught that should be a sterile organ, but we'll see.

Certainly no question in pathology, you see these organisms in the brains of patients with Alzheimer’s, you don't typically see them in the brains of the non-Alzheimer’s patients. But more and more, we recognize that there is this give and take. So it tends to be in cognitive decline, organisms that are able to set up chronic infections without a massive acute response at the beginning. So it's not the pneumococcal pneumonia, it's typically the…. And I think I’ve said it in the past, in the first book, to some extent Alzheimer’s is the neuroSyphilis of the 21st century.

We used to worry about the Syphilis organism before penicillin because it could set up something that would live in your brain for 20 plus years and you could get all sorts of syndromes like so-called Lewy’s and meningoencephalitis, in general paresis and these Syphilis-associated brain degenerations. This is the same idea, except that instead of one organism, Treponema pallidum, it's many organisms that all have a similar response.

So we respond to these organisms, and they are typically as I mentioned earlier, it's Herpes simplex 1. It's HHV-6A, which often will come in through your sinuses. It is molds, that again through the sinuses. It is the oral bacteria, and then it is some systemic things like Bartonella, Babesia; the tick-borne organisms. Those are the major ones we run into.

Although, I should add Candida has also been found. And there was a really interesting experiment done in rodents, where they simply injected Candida in the bloodstream. Look, everybody's exposed to Candida, it's incredibly common. And they assumed that it would take a while. They wanted to see how long would it take this thing to get into the brain; guess what? It went in immediately; despite the blood-brain barrier.

And the initial response protecting the brain against it looked exactly like the earliest changes in Alzheimer’s disease. So again, it comes back to we are protecting ourselves, and there are all sorts of things you can do. A great study out of Taiwan showing that treating lip blisters from Herpes simplex 1, versus the people who didn't treat them. The ones who did treat them had a lower risk for Alzheimer’s, quite substantially lower.

And so good idea to treat those. Second thing, keeping your immune system sharp. So having appropriate zinc, having appropriate vitamins C and D, having appropriate glutathione. I actually like to take it; I’ve been taking during COVID AHCC, which supports, it's a mushroom extract that happens to support your cellular immune system. For viruses, the cellular immune system is actually even more important than the humoral immune system.

So that again, as Jeffrey Bland would say that pandemic within the pandemic, keeping your metabolism optimized. And then, of course, curcumin has been something that's been used for years, and people who are using turmeric, or curcumin, do have a lower risk. You can actually interestingly see that the curcumin interacts directly with the amyloid itself and with the tau; some beautiful work from Professor Greg Cole and his wife, Professor Sally Frautschy out of UCLA. They've studied curcumin for years and done elegant work on curcumin and its effects on the brain and on neuropathology and Alzheimer’s disease.

And, of course, Omega-3s, another critical support. Omega-3s support phagocytosis, which is often defective in Alzheimer’s disease. And then, of course, I like Dentalcidin toothpaste and mouthwash, these things, again these are Biocidin related. They are supporting the positive side of the oral microbiome. And then also prebiotics and probiotics, not only for the gut, but there are now, of course, pre and probiotics for dentition.

So things like Revitin, I think, is one of the toothpaste that's come out that actually has probiotic. So again, it's not about getting rid of infection; it's about getting the right mix of the right organisms. These organisms, as you indicate, they're all over. But we want to have the right ones; we want to stay away from the pathogens. So all of these things are critical for giving yourself the optimal support for preventing yourself from having cognitive decline due to exposure of these different pathogens.

[01:27:39.22] Scott: As we get into maybe our last 10 or 15 minutes together, I wanted to next get your thoughts on some of the top detoxification strategies that you're finding helpful for people. Are we primarily looking at things that we're taking like glutathione, or are we using things like saunas, for example, or other tools that are helping to minimize the toxic burden?

[01:28:01.24] Dr. Bredesen: Yes, that's a great point. And for so many of these things, when you just sit and look at it for two minutes, you can see well, okay, it's obvious. Of course, if you think about this as something that is, that you've been dealing with for years. Your body's sequestering these things, these toxins. We are all living in quite a toxic world.

And I went into this in the new book where it's the food you're eating; it's the air you're breathing, it's the water you're drinking. It's the various perfumes; it's the products that you're using. Bruce Ames gave us such a wonderful gift when he gave us the Ames test for carcinogens. But we haven't had a standard test for dementogens, and yet we are being exposed left, right, and center of these things.

And a good example, one of the people who came with cognitive decline was a woman who had been exposed to the World Trade Center, and that was massive exposure in a very short time. So again, taking many years of exposure and crunching this down to just a few days. And she then, unfortunately, developed cognitive decline, and you could see the signature in her blood from the various toxins that were associated with the World Trade Center.

Same sort of story with another woman who'd been exposed to years and years and years of paraffin candle burning. Paraffin candles are relatively toxic, if you're going to be burning candles a lot, please look at beeswax and please keep it to a minimum. So these are absolutely toxins. So it's a combination of number one, you want to minimize your exposure, and every excellent physician who deals with these toxins such as Dr. Jill Carnahan will all say the same thing.

I can't make people better until they remove the exposure. If you're living in a home with big-time mycotoxins, you've got to get rid of those, get out of that home. Again, we're finding the same as with COVID, outdoors better than indoors. However, as you indicated, there's also the issue of air pollution. If you're living with air pollution, that's an issue, of course.

The California fires that means we're going to have increased dementia down the road because of the poor quality during those fires. And so many of us were exposed to those particulates, unfortunately. And even these tiny particles that are absolutely critical in dementia risk. So you've got to remove the exposure and identify those things, and then you want to increase the detoxification. And as you indicated, yes, sweating is part of this, absolutely.

But so every method possible, so you want to have urination, you want to have clean water, filtered water, absolutely crucial. And we use one called BioTrue use whatever you like; it doesn't really matter. Get yourself a good system for removing the toxins in your water. And get up there, I don't know what you typically recommend, but most people will say you want to get up above one liter a day into the two liters.

And some people, Dr. Pizzorno, would say get to two to four liters a day. Whatever you like, make sure that you are now flushing this stuff through, it's huge. And then the same thing with getting this through your GI system. And so again high fiber diets are huge and getting a healed gut and getting appropriate probiotics and prebiotics. These are absolutely crucial.

Try to get at least above 30 grams if not more per day of fiber. So now you're excreting this stuff, what happens is there's a dynamic balance, and most of us are on the wrong side of that balance. So over the years, we're accumulating this stuff, and we're doing, we're using our cytochrome P450s to deal with it, and we're sticking it, we're trapping it into our bones, we're sequestering it. We're trying to deal with our liver. Unfortunately, we're putting some of it in our brains, in our other organs.

We're trying to excrete it; we're overwhelmed with this stuff. And at the end, unfortunately, we end up developing dementia, or we develop osteoporosis, or we develop type 2 diabetes, or we develop cancers from these things. One of the things that was so surprising when we first started looking at the type 3s, almost all of these people were presenting right around the age of 52, plus or minus.

Some would be 49, some would be up to 55, but it was right around the time of menopause? Why is this? And two interesting things came out of looking at this. Number one, as Chris Shade has pointed out, as your progesterone goes down, your detox system is not working as well. Progesterone is an important push for your detoxification system.

But the second thing is what's been called the osteoclastic burst. You have about a seven-year period there, where you're now going from osteoblastic nice balance to now more of an osteoclastic surge. You don't necessarily have osteoporosis, although you may get it in the future, but you're now removing these. And guess what's in there, you have sequestered some of these toxins, and you see that for example with mercury, but there are others as well.

So you really have a very risky time in your late 40s and early 50s. And that's a time when you want to make sure especially and even in preparation for that, to be on an appropriate detox regimen. And you indicated sweating; absolutely, you can do this with exercise. You can do this with sauna, don't forget after that to use a non-toxic soap like castile soap, help wash away some of these. Of course, Stephen Genuis has done such a beautiful job looking at what toxins come out in sweat.

And as he pointed out, cadmium is one that's massively higher in sweat than in blood, for example, but there are all sorts of toxins that can come out and sweat. So with all these different pieces, and then, of course, don't forget the biochemical piece. Increase your glutathione. Many people are walking around with suboptimal glutathione, use sulforaphane.

Get your crucifers into your diet; these are critical. So with this combination of these three things, lesser exposure, removing those increased metabolism and excretion, and then optimizing your biochemistry for detox. This is a very positive combination. Now there are then specific things beyond that; there are books on this. Neil Nathan has a great book called a toxic heal your body, which is mostly about bio-toxins.

Dr. Joe Pizzorno has a wonderful book called The Toxin Solution, which is mostly about chemotoxins. These are critical to look at, and of course, Dr. Shoemaker has some wonderful books on mycotoxins. So all important.

[01:35:00.25] Scott: Yes. I think your idea or comment on autointoxication from the lead and other toxins in the bones is one that we often don't think about. And as many in this realm say, the solution to pollution is dilution, right?

So drinking plenty of water. One of the things that you mentioned in the handbook that I liked, sometimes we get tired of just taking supplements and handfuls of pills. And so you talked about the benefit of various spices and teas that we can incorporate into our daily routine. What are Dr. Dale Bredesen's favorite spices and teas?

[01:35:35.19] Dr. Bredesen: Yes, a great point. There are a number of these things I think that are wonderful. And so again, I would start with turmeric because it actually does bind the amyloid; it helps it to be removed. It actually is a nice study just published showing that curcumin actually has an antiviral effect. So that's certainly a really nice one. And then there are things like mint, that's also very helpful for detox as well.0

And then there are things like; the things like well, the crucifers obviously, you wouldn't really call that a spice. But things that are things like cinnamon, which I think are just fantastic. Cinnamon, of course, is one of the best ways to improve your insulin sensitivity. So for those people who have metabolic syndrome or who are pre-diabetic, cinnamon wonderful way to go.

And you mentioned, let's look at what we can do other than supplements; the supplements are supplementary; we made a big point of this in the book. Supplements are supplementary, just combining an optimal diet, optimal exercise, optimal sleep, optimal stress levels, brain training, and then some added things like CGM, EWOT a few things like this.

You can do a tremendous amount without taking supplements. Now supplements do provide that next level, it's true. For certain things, they're extremely helpful from the ketone, from the exogenous ketones to appropriate magnesium levels to appropriate B12 and methyl folate levels; all these things are critical. But there's a tremendous amount you can do long before this.

And of course, these things have been done for years and years and years, and the point has been made that many of these herbs and spices are incredibly effective. And much more so on a molar ratio than many of the supplements.

[01:37:47.16] Scott: You share a number of things in the book that can damage the gut. Things like antibiotics and aspirin or ibuprofen, proton pump inhibitors, Zantac, Pepcid, antacids, and then antihistamines, including Benadryl and Zyrtec.

And so lots of people in the Lyme and mold community, and I would think that in the Alzheimer’s community potentially too, this idea of mast cell activation syndrome and histamine intolerance. So what are your thoughts on Benadryl and Zyrtec, for example, if you're working with mast cell activation.

Are we better to opt for more natural agents? So that we're not creating more gastrointestinal damage over a longer period of time?

[01:38:29.12] Dr. Bredesen: Yes, it's a good point. And in fact, Julie went through this very thing where she had very severe mast cell activation for years. And interestingly, being on the appropriate protocol and continuing to optimize things for her cognition has really damped down her MCAS dramatically, so that she really doesn't have problems with it anymore.

But to come back to what you said earlier, medications and some of the supplements people take are absolute contributors. And some recent work showing that a relatively common contributor to cognitive decline is the things that we take. And you mentioned PPIs absolutely, all the various anticholinergic medications that people take.

They are bad actors because, in fact, acetylcholine is so critical for memory for the formation of new memories. And you also mentioned the antihistamines, they also, unfortunately, things like Benadryl; over the years can contribute to cognitive decline and we see this again and again. Most people with who have been on PPIs for a while, you can pick it out because they have extremely low zinc levels. They often will have low B12 levels, and they are written at risk for cognitive decline.

As you know, it is critical to have appropriate acidification in your stomach when you are now using these enzymes, and some people will need to add enzymes to make it so that you've got appropriate function. And of course, as Dr. Jonathan Wright pointed out years ago, having poor stomach acid is one of the risks for macular degeneration as well.

So this is critical for getting appropriate nutrients, and if you've got GERD, you want to do the opposite. You want to make sure you've got enough acid there. You may need to eat, I noticed by the way I used to have years ago I would have occasional GERD; I thought what the heck is this all about. When I switched over to more of a plant-based diet, never had it.

Then interestingly, I went out about a week ago, and I had a bunch of meat, which I rarely do for a meal. But I had plenty of protein, got a bunch of meat, and actually woke up that night, first time I had GERD in years. Like oh, wait a minute, okay I’m an older guy, I’m approaching 70, and I did not take any enzymes at the time. And I went out and had a big meat load, a big protein load.

And these enzymes that are trying to break these proteins down, function only as enzymes in an acidic environment. And so if you don't have that acid there, they cannot do their function. You are not getting the appropriate nutrients that you need, so these are critical. Now you mentioned sometimes you need the antihistamines, absolutely yes.

So it's just like antibiotics, sometimes you need them just to live, to survive. Go ahead, go through the antibiotics you need, and then you're going to make sure your gut is healed, you're going to repopulate your gut. You're going to have appropriate prebiotics, appropriate probiotics. These things are all very helpful. And I think that you're going to see a lot of people have less MCAS as they do the appropriate things. 

[01:41:38.07] Scott: Another area that you get into in the book that I loved was the idea of the amygdala and the limbic system, and how it activates the fight-or-flight mechanism. You talk about one of my favorite tools, which is the Dynamic Neural Retraining System or DNRS.

Have you seen focus on the amygdala and the limbic system helpful in the ReCODE protocol? And what are some of the tools that you recommend for calming the nervous system to facilitate healing?

[01:42:06.03] Dr. Bredesen: That is a great point. And I recommend to anybody who's interested in stress and the amygdala and what it does to the brain. Please take a look at some really nice work from Dr. D.R. Claussen, who is a real neurospecialist who came from the rehab world; was actually an excellent football player in college.

And this guy really understands stress and what it does to your brain. And he's pointed out the importance of the amygdala, and kind of resetting. This is a part of what we are calling Alzheimer’s disease, is a response to threat.

We've talked earlier about the response to physical threat to biological threat. Response to things like bacteria, like spirochetes, like molds, like viruses. As he's pointed out, this is also a response to psychological threats. Stress that's going on in your life, whether you're being chased by a tiger or whether you're being chased by your boss.

This is something that gives you stress. And if you want to shrink a human brain, ramp up the cortisol, and you will see the brain shrink. And in fact, interestingly, one of the things that has come out of our studies over the years, looking at good targets for pharmaceuticals for Alzheimer’s, is the fact that, in fact, cortisol C are the receptor for cortisol releasing factor, corticotrophin-releasing factor 1.

It turns out to be a very effective way to decrease the amount of amyloid and tau. So as long as we are under these threats, as long as we are stressed out, we are going to continue to be protecting ourselves. And part of that protection is the amyloid that is associated with Alzheimer’s disease.

So as Dr. Neil Nathan and others have pointed out, you really need to reset, you need to dial down, and DNRS is one way to go. And again whatever works for you, for some people they use Neural Agility, for some people it's meditation, for some people it's music all sorts of different ways. But you really do need to reset that stress and threat level, that contributes to cognitive decline and downsizing. 

[01:44:27.02] Scott: My last question before we have a couple of wrap-up comments is, you talk in the book about the sinus biome, you mentioned that earlier in this conversation as well and the use of nasal probiotics as part of a protocol. How do we access nasal probiotics? Are there products on the market in that realm at this point?

[01:44:46.01] Dr. Bredesen: Yes, there are actually. And these are basically, the nasal and oral mix basically. So these are oral-nasal typically probiotics. And there's a Probio ENT was one of the ones people had used, a Lactobacillus sakei, that was available, that was looking at one that seems to be helpful.

So there are a few out there, people are now recognizing that oral probiotics are important as well. I mentioned earlier there's actually a toothpaste out there that is a probiotic toothpaste, called Revitin. And so there are a number of ways now that you can affect your oral, it's really an oronasal and orosinal microbiome.

[01:45:32.00] Scott: So they're not sprays necessarily, but they are still affecting the sinus microbiome being taken orally. Yes, the Revitin I think that's Dr. Gerry Curatola, that's a great tool as well. Five or ten years from now, how do you think the world will view Alzheimer’s disease, and how do you anticipate your approach might evolve over the next several years?

[01:45:52.27] Dr. Bredesen: Yes, very good point. And I think that ten years from now, five, ten years from now we will see begin to see a global reduction in the burden of dementia. People will start to look at yes, you can actually have the likelihood of preventing yourself, high likelihood of preventing yourself from cognitive decline. I think people more and more will get Cognoscopies and get on to these prevention programs.

And also they will be because they now realize there's something to do about it, they'll be getting in earlier and earlier. And therefore, we will see a, just as we saw a decrease in the 20th-century illnesses with things like antibiotics. As I said in the book, the 21st century will see the dramatic reduction in these complex chronic illnesses.

Alzheimer’s, Parkinson’s, Lupus, Rheumatoid Arthritis, autism, on and on and on. These things you're going to see lower and lower in the 21st century as we're changing the way we practice medicine from a in and out prescription pad approach to a much more of a systems biology, precision medicine approach. You're going to see much less of this kind of disease.

[01:47:07.04] Scott: If you haven't read Dr. Bredesen's first book, ''The End of Alzheimer’s,'' I highly recommend it. The follow-on book ''The End of Alzheimer’s Program'' lots of practical information. We didn't get into even the tip of the iceberg in this conversation.

So it's really a great book that you can take and learn to change your habits, the things that you do, the things that you eat and so on to improve your cognition over the duration of your lifetime. Really encourage people to get that book; it's a fantastic resource. And my last question, which is the same for every guest, is what are some of the top things that you do on a daily basis in support of your own health?

[01:47:43.25] Dr. Bredesen: Yes, that's a great question. And I guess the answer is probably not enough. But what I have, my wife and I talked about this, we've changed a lot of our habits over the years. Again, when I was training, it was all about pizza and soft drinks and things like that. If you want someone to come to a conference, you serve pizza.

And so of course, we've gotten off all that stuff. So number one, to make sure to have a plant-rich, we follow the KetoFlex 12/3 approach. And plant-rich mildly ketogenic diet. The second thing is I try to make sure to get eight hours of sleep at night, and I tend to be a night time, a night owl we're working on things that we're doing. And that's a problem I’m trying to move that to a little bit earlier. One of the things I think is most helpful quantified self, this is becoming critical. You ask ten years down the road; I think everyone's doing more of that.

So I’ve started to look at my blood pressure more often. I’ve started to look at my heart rate variability, started to look at my oxygenation at night. There are more and more now that we have all available to all of us. You can get an oximeter; stick it on your finger. Look at whether you are desaturating at night, these sorts of things. I try to make sure to get both some aerobic exercise and some strength training exercises. I try to keep the stress levels down.

All of these things are critical. I tried to obviously switched over to much more of an organic diet. When I found that I was eating too little choline, I’ve started to do more on the pastured eggs. To make sure I take some omega-3s, to make sure that I get an appropriate omega-3 ratio. I actually like organic psyllium husk to improve my overall fiber.

I use a sauna for detox; try to get in some swimming or jogging. So all of these things again to try to optimize my own particular microbiome and my own particular approach to life. So that I can minimize my likelihood of developing cognitive decline and other chronic illnesses in the future.

[01:50:00.18] Scott: I think it's clear that it's working; I don't see any evidence of cognitive decline. Your brain is kind of unbelievable how well it works. You are a hero of mine; you're a hero of so many peoples. You're changing lives; you're changing the world.

I have so much respect and admiration for the work you do, and I just want to thank you for generously spending your time to share with all of us today and appreciate you so much.

[01:50:27.02] Dr. Bredesen: Thank you so much. Thanks for being such an expert in this stuff, you know this stuff backward and forwards, I’m really impressed.

And let's all work together to reduce the global burden of dementia, it would make a huge impact on so many people, so many families that have been torn apart by dementia. So let's all work to end it with this generation.

[01:50:46.14] Scott: Thank you, Dr. Bredesen. To learn more about today's guest, visit ApolloHealthCo.com, that's ApolloHealthCo.com, ApolloHealthCo.com.

[01:50:59.01] Thanks for listening to today's episode. If you're enjoying the show, please leave a positive rating or review, as doing so will help the show reach a broader audience. To follow me on Facebook, Instagram, or Twitter, you can find me there as better health guy. If you'd like to support the show, please visit BetterHealthGuy.com/donate. And to be added to my newsletter, visit BetterHealthGuy.com/newsletters. This and other shows can be found on YouTube, iTunes, Google Play, Stitcher, and Spotify.

[01:51:34.04] Thanks for listening to this BetterHealthGuy Blogcast, with Scott, your Better Health Guy. To check out additional shows and learn more about Scott's personal journey to better health, please visit BetterHealthGuy.com.


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