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Episode 167
The Doctor's Farmacy

Is Alzheimer’s Reversible? Getting to the Root Causes

Open the Podcasts app and search for The Doctor’s Farmacy. If you’re viewing this site on your phone, you can just tap on the

Tap the subscribe button and new shows will be added to your library.

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Alzheimer’s doesn’t just happen overnight; it’s the severe end of a spectrum, that comes after decades of changes have already been occurring in the brain. 

So why is it that we’ve grown accustomed to dreading this diagnosis, instead of doing what we can to proactively stop it in its tracks? For one, we’ve long been told that once the brain starts downsizing we can’t reverse the process. Now, we know that’s not the case. It’s possible to avoid brain degradation and actually even rebuild it.

Today’s guest on The Doctor’s Farmacy has been a pioneering detective for Alzheimer’s and other neurological issues.

Dr. Dale Bredesen and I talk about the many factors that lead to inflammation in the brain, cognitive decline, and eventually Alzheimer’s. Exposure to toxins like mercury and mold, nutrient deficiencies, hormonal imbalances, and an overload of sugar are some of the most common contributors. Genetics play a part, too—Dr. Bredesen breaks down the different ways the ApoE4 gene increases Alzheimer’s risk and how it impacts the general population.

We also talk about the relationship between insulin resistance and the spectrum of brain disorders and why limiting sugar is such an essential piece when treating the brain.

Cognitive decline stems from an insufficiency in the network that mediates plasticity—the ability to change and mold the brain, to add new thoughts and memories. Insults, like sugar, damage our synapses and stop information from being transmitted effectively, taking us from plasticity to rigidity. When we look at those insults we begin getting to the root cause of brain damage.

We talk about all this and more on this episode. I hope you’ll tune in to hear about the groundbreaking program for preventing and treating Alzheimer’s that Dr. Bredesen has created. 

This episode is brought to you by BiOptimizers, Thrive Market, and TrueDark.

Right now, BiOptimizers is offering my community 10% off their CogniBiotics. Just go to cognibiotics.com/hyman and use code hyman10 at checkout.

Thrive Market is offering all Doctor’s Farmacy listeners an extra 25% off your first purchase and a free gift when you sign up for Thrive Market. Just head over to thrivemarket.com/Hyman

Right now, TrueDark is offering podcast listeners 15% with code DRHYMAN15. Just go to truedark.com/hyman.

I hope you enjoyed this conversation as much as I did. Wishing you health and happiness,
Mark Hyman, MD
Mark Hyman, MD

In this episode, you will learn:

  1. Addressing the root causes of dementia, cognitive decline, and Alzheimer's disease
    (3:49 / 8:02)
  2. How a ketogenic diet and metabolic flexibility can support brain function
    (7:39 / 11:52)
  3. The way your brain responds to inflammation, and how inflammation drives cognitive decline and Alzehimer’s disease
    (11:33 / 15:46)
  4. What is a cognoscopy and how can you get one?
    (21:48 / 26:01)
  5. Your brain can grow and improve, even after an Alzheimer’s diagnosis
    (26:28 / 31:10)
  6. The gut-brain connection
    (28:36 / 33:18)
  7. Heavy metals and their effects on the brain
    (31:49 / 36:31)
  8. Hormonal dysfunction and risk of Alzheimer’s disease
    (36:46 / 41:28)
  9. How nutrient deficiencies drive cognitive decline and the diet that is best for your brain
    (40:19 / 45:01)
  10. Is it possible to reverse Alzheimer’s disease, and if so, to what degree?
    (53:48 / 58:30)

Guest

 
Mark Hyman, MD

Mark Hyman, MD is the Founder and Director of The UltraWellness Center, the Head of Strategy and Innovation of Cleveland Clinic's Center for Functional Medicine, and a 13-time New York Times Bestselling author.

If you are looking for personalized medical support, we highly recommend contacting Dr. Hyman’s UltraWellness Center in Lenox, Massachusetts today.

 
Dr. Dale Bredesen

Dr. Dale Bredesen is internationally recognized as an expert in the mechanisms of neurodegenerative diseases and the author of the New York Times bestseller, The End of Alzheimer’s. His latest book, The End of Alzheimer’s Program, goes into greater detail on the protocol he uses with his patients and how it can be tailored to anyone’s needs, at any age. Dale held faculty positions at UCSF, UCLA, and the University of California, San Diego, and directed the Program on Aging at the Burnham Institute before coming to the Buck Institute in 1998 as its founding president and CEO. He is currently a professor at UCLA and the Chief Science Officer at Apollo Health.

Show Notes

  1. Get his book, The End of Alzheimer’s Program: The First Protocol to Enhance Cognition and Reverse Decline at Any Age

Transcript

Dr. Dale Bredesen:
Calling someone Alzheimer’s is like saying late stage cancer, metastatic cancer, because it’s a very late stage of this process that’s been going on typically for 20 years.

Dr. Mark Hyman:
Welcome to The Doctor’s Farmacy. I’m Dr. Mark Hyman. That’s Farmacy with an F, F-A-R-M-A-C-Y, a place for conversations that matter. If you have a brain, you better listen to this podcast because it’s going to matter to you, because it’s about, “How do we prevent and even reverse the worst condition that afflicts humanity, which is Alzheimer’s and dementia and neurodegenerative disease?” In other words, our brains are facing an onslaught of insults that are treatable, that can literally reverse and even prevent diseases like Alzheimer’s and Parkinson’s, which sounds crazy because everything we’ve done hasn’t worked.

Dr. Mark Hyman:
Today, our guest is an extraordinary doctor, a friend of mine, pioneer in the field of neurodegeneration, whose broken ground that few have traded on. It’s none other than Dr. Dale Bredesen, who you may remember from our previous podcast, where we discussed his book, The End of Alzheimer’s. His latest book is called The End of Alzheimer’s Program, which is a much more robust programmatic insight into how to actually use the protocol that he uses with his patients that I use and how we can tailor it to anybody at any age and any part of the journey along protecting your brain or fixing your brain.

Dr. Mark Hyman:
He’s been on the faculty of UCSF, UCLA, University of California, San Diego. He’s directed the program on aging at the Burnham Institute before coming to the Buck Institute in 1998 as its Founding President and CEO. He’s currently a professor at UCLA and the Chief Science Officer at Apollo Health, which is a great online platform for addressing neuro degeneracy. So, welcome, Dale.

Dr. Dale Bredesen:
Thanks so much for having me on, Mark. I really appreciate it.

Dr. Mark Hyman:
Okay. So, let’s get into this, because most people worry about heart disease or obesity or diabetes, but it doesn’t take away who you are. Alzheimer’s takes away who you are. Neuro degeneracy takes away your soul in a sense, your memory, which is really what we’re made of is memories. I think that it’s a terrifying disease for so many. It’s growing in scope. It’s affecting millions and millions of Americans. I think about 5 million now, projected to be about 14 million in a few years. The caregiver burden is enormous that goes along with this. The costs are even more than taking care of a patient with cancer or heart disease. This is an epidemic really. Globally, literally, hundreds of millions of people are going to be affected by this.

Dr. Mark Hyman:
Now, you’ve been on the forefront of Alzheimer’s research. You’ve seen amazing results in helping people prevent dementia through various protocols that are based on functional medicine. Your wife is a functional medicine doctor and introduced to you this many years ago. You often tell the story of how you came across my book, The UltraMind Solution, which I wrote about 12 years ago that mapped out how we can start to think about treating the system not just the brain itself. You created the Bredesen Protocol that fundamentally changes how we think about cognitive decline.

Dr. Mark Hyman:
So, tell us about how you came to understand what you’ve learned as a neurologist and as a researcher around Alzheimer’s corresponded with these emerging ideas around functional medicine and how that led to you developed the Bredesen Protocol.

Dr. Dale Bredesen:
Yeah. Thank goodness there was functional medicine or we would still be figuring out, “How do we put all this together?” So, we were interested for 30 years in the laboratory. We’re simply going, and as you said, people have been unable to treat these diseases, Alzheimer’s, frontotemporal dementia, ALS. Neurodegenerative disease has been the area of greatest biomedical therapeutic failure. So, we were trying to study, “What are the molecular drivers of this process?”

Dr. Dale Bredesen:
What we could see with the research was that there is a central switch, APP, which is literally integrating over all these signals. So, the big surprise was that everybody who was talking about Alzheimer’s had the wrong idea. They’ve told you it’s misfolded proteins, it’s reactive oxygen species, it’s prions, it’s tau.

Dr. Mark Hyman:
Amyloid.

Dr. Dale Bredesen:
Amyloid, all this stuff, but the reality is when you look at it, at the heart of Alzheimer’s is an insufficiency. You have an insufficiency of signaling, which is picked up by this molecule APP, which then is protecting your brain for downsizing. It’s very much, by the way, what’s happened with COVID-19. We have an insult, SARS-CoV-2. Of course, we’re supposed to be sheltering in place, social distancing. But what’s happened with that with less interaction, we have a recession. This is exactly what goes on in the brain of an Alzheimer’s patient. You have insults. These are everything from herpes simplex type 1, P. gingivalis from your mouth, various molds from your sinuses, leaky gut, as you know, on and on and on, dozens and dozens of these things.

Dr. Dale Bredesen:
These insults trigger your brain to say, “Okay, I need to downsize. I need to shelter in place literally.” It produces something that is an anti-microbial, which is the amyloid. So, as long as you don’t find those things and correct them, you’re going to keep downsizing, downsizing until you can’t dress yourself, you can’t speak. Unfortunately, when you go into see some doctor, an expert in Alzheimer’s, they don’t look for those things. This is a critical piece. So, what we studied was, “What is the fundamental nature of this problem and the nature of it?” It is an insufficiency in the network that mediates plasticity. So, what happens? You lose that plasticity and you start downsizing just as you see with COVID-19.

Dr. Mark Hyman:
What is plasticity?

Dr. Dale Bredesen:
So, plasticity is the ability to change from plastikós in the Greek, something that is moldable. So, the ability to mold your brain, to add new thoughts, to add new memories, this is exactly what is lost in this disease, because that is the network that is now downsizing. It’s basically saying, “Okay, Mark, can you live with fewer synapses so that we can fight these things?” You’re going to use your resources now to fight the various pathogens or toxins or changes in insulin sensitivity and things like that, but you’re going to have to live with a smaller function basically, just as we’re stuck with a recession here in the United States right now.

Dr. Mark Hyman:
Yeah. So, plasticity is essentially all the networks that tie everything together in your brain, all the connections between the cells, all the messaging, all the new wiring that helps you learn and grow. That diminishes with all these insults that cause your brain, as you say, downsize.

Dr. Dale Bredesen:
Yeah, it is protecting itself.

Dr. Mark Hyman:
What we’ve always learned is that once you go down, you’re not going back up. Once you lose your memory, it isn’t coming back. The best we can do is maybe slow it down. The best research and we’re talking about billions of dollars, hundreds of studies over many decades haven’t really come up with a big fat zero when it comes to any meaningful result to write stop, to slow, or to treat Alzheimer’s or dementia. We’ve spent so much money and got so little, because we’ve been focusing on the wrong thing.

Dr. Mark Hyman:
So, in your program, The End of Alzheimer’s Program, you talk about what we actually should be focusing on. You talk about these metabolic factors that can literally trigger this downsizing. So, what are those factors? How do we rebalance them, so we don’t end up having this decline in brain function?

Dr. Dale Bredesen:
Yeah, that’s a great point. So, we could actually see people improve just as you described in your 2007 book. So, this shows that there is a set of things that are synaptoblastic, making connections and keeping connections and a set of things that are synaptoclastic, pulling back. When you’re young, there’s this beautiful balance. You’re actively forgetting the seventh song that played on the radio in the work yesterday and stuff, that thing. But then what happens with everybody with Alzheimer’s, too high on the synaptoclastic, too low on the synaptoblastic side. So, what are the things that are synaptoblastic? Well, step one, there is an energy gap. This turns out to be one of the most important parts about the Alzheimer’s brain.

Dr. Dale Bredesen:
As you know, if you just look at a PET scan, an FDG PET scan, you see that there is a decrease in the utilization of glucose by your temporal lobe and your parietal lobe. That is the hallmark, the signature of Alzheimer’s disease. It’s present for about 10 years before a diagnosis. So, you have a critical energy gap that you need to change. You need to address that gap. The best way to do it, of course, is with ketosis. Stephen Kinnane showed years ago. You can ramp those ketones up to one, two, three millimolar beta-hydroxybutyrate. You can address that energy gap. That’s the first thing. The second thing is when we used to grow the neuron-

Dr. Mark Hyman:
So, basically, using a ketogenic diet, you can increase-

Dr. Dale Bredesen:
Absolutely.

Dr. Mark Hyman:
… the way the brain uses energy and makes it basically have more energy by feeding it fat instead of sugar and carbs.

Dr. Dale Bredesen:
Exactly. There are two problems there. One is that you’ve lost the flexibility. You’ve lost the ability. Everyone’s stuck on the glucose side. They’re not able to use the ketone side. You have to have the flexibility. And then the second is that they have the insulin resistance, so that even though they’re trying to use the glucose, which is what they’ve used for years and years and years because of this Standard American Diet, they’re now unable to do that, because you literally have changes in the ability of insulin to signal. You change your insulin signaling, IRS-1 molecule from tyrosine phosphorylation, which is active to serine and threonine phosphorylation, which is inactive. You literally shut it down. When we used to grow neurons in a dish in the lab-

Dr. Mark Hyman:
So, basically, what you’re saying is that sugar screws up your brain’s ability to metabolize energy. Is that what you’re saying?

Dr. Dale Bredesen:
That’s exactly right.

Dr. Mark Hyman:
Okay, because I won’t be able to know what tyrosine and serine is. I think that’s a basic take home point is that when you eat sugar, your brain doesn’t like it and starts to shut down. It leads to Alzheimer’s.

Dr. Dale Bredesen:
It becomes resistant to it, exactly right, resistant to the insulin effects, which are so critical for keeping your neurons alive. So, the beautiful thing here is that what we saw in the lab reflected beautifully what you and David Perlmutter and Jeffrey Bland were saying clinically. So, that if we hadn’t had all the great work you did, we would have been stuck, saying, “Okay, what’s the next step we take now from the lab?” But here’s this beautiful functional medicine already to plug in the underlying science of Alzheimer’s disease. So, in that sense, very helpful.

Dr. Dale Bredesen:
As you said, sugar damages your ability to support your synapses. So, you got to address with ketones. You got to address the energy. You’ve got to adjust the insulin sensitivity. You got to get insulin sensitive, instead of insulin resistant, which virtually everybody with Alzheimer’s is. And then you have to reduce any inflammation. Your brain responds to inflammation by saying, “I am being attacked. There’s some organism out there. So, I’m going to make this amyloid which kills these microorganisms, but in so doing, again, I’m downsizing.”

Dr. Dale Bredesen:
So, you’ve got to get rid of that inflammation, not just get rid of the inflammation, resolve it, but you also have to find out what’s causing it and address that. So, those are the first three things. And then you’ve got to have the support. You’ve got to have hormones and trophic factors and nutrients that are critical for rebuilding those synapses. Fortunately, before you actually lose the neurons, you first lose the efficiency of the synapses. The synapses don’t work well, but they’re still in place thankfully. So, when we do the right things, this starts working well again.

Dr. Mark Hyman:
Yeah, it’s interesting, I remember reading this article, because what you’re talking about is multiple different factors that explain the phenomena we see as dementia, but that it’s not one disease. It’s many diseases and many dysfunctions manifesting as a particular set of symptoms that are common among people, but it doesn’t tell you why. So, everybody you look at who’s got cognitive decline or Alzheimer’s, you have to be a detective and find out, “What is their particular issue? Is it more insulin resistance? Is it more of an infection? Is it a mold? Is it a toxin? Is it some other nutritional deficiency or hormonal lack?”

Dr. Mark Hyman:
Too much of something, not enough of something else. What’s really striking is that the inflammation is this common theme in all brain dysfunction. Whether it’s depression or ADD or autism or Alzheimer’s or Parkinson’s or whatever, it’s inflammation in the brain. So, a lot of your work has really been in understanding what is driving that inflammation, because the amyloid, like you said, is not the problem. It’s actually your body’s attempt to fix the problem.

Dr. Dale Bredesen:
Yeah, exactly.

Dr. Mark Hyman:
It’s the band-aid that the body uses to deal with the inflammation and the microbial factors, which often can come from gut and other factors. So, talk to us about how we need to rethink this, because I remember reading this article years ago in JAMA, which was called shifting in thinking about dementia. There was a great line in there that says, “We combine categorical misclassification with etiologic imprecision.” What that means in English is that we categorize people according to symptoms, not causes. We are not really good at finding the etiology or the cause, right? So, we’re just throwing spaghetti at the wall trying to see what works.

Dr. Mark Hyman:
What you’ve done with the Bredesen Protocol and The End of Alzheimer’s Program is to really map out systematically, the ways in which you can identify those factors that are harming your brain, right? You call them dementigens. What are those factors that we need to provide the body to optimize enhance brain function?

Dr. Dale Bredesen:
Exactly. So, what happens in COVID-19, again, is cytokines? So, cytokines are killing people as you know. This cytokine storm is the problem. Well, part of the inflammatory cascade, part of your innate immune system activation is amyloid. So, we have to quit thinking of amyloid as the cause of Alzheimer’s. Amyloid is just like cytokine storm except it’s longer. Of course, COVID-19 has compressed all the things that go wrong in Alzheimer’s into two weeks instead of 20 years, but it’s the same idea. As long as you have something that is saying, “Hey, something’s wrong with your brain,” you are going to continue to make that amyloid. That’s part of the response.

Dr. Dale Bredesen:
So, you’re absolutely right. You have to determine what these factors are. There are often biotoxins or organic toxins or metallic toxins. Air pollution, of course, has turned out to be a big one. So, all of these critical things and then various pathogens. There are several of these chronic pathogens from the Babesia to Bartonella to Borrelia to various mold species to herpes simplex type 1 to HHV-A. These are all chronic pathogens. Typically, as you know, we don’t know that we have them. So, as you said, this is interesting to me that we used to talk about people dying of fever.

Dr. Dale Bredesen:
In the 1600s, people died of fever all the time. So, now, people talk about people dying of Alzheimer’s. It’s no different than fever. You shouldn’t have a period after fever, fever due to what? You shouldn’t put a period after Alzheimer’s, Alzheimer’s due to what? That’s the critical piece. So, the doctors have always put the period. They say, “You have Alzheimer’s,” but we need to know why for each person. It’s not one thing. It’s not like tuberculosis. It’s always the tubercle bacillus. It’s all these different things. So, it is a systems disease. That’s the point.

Dr. Mark Hyman:
Yeah, that’s so true. I think in neurology, there’s a famous joke that you see the doctor and it’s basically diagnosed and adios. Here’s the name for the condition you have, and there’s not much we can do about it. Goodbye. Get your life in order. That makes me crazy, because over 25 years of doing this and working with people’s brains, I wrote about this 12 years ago. I’ve seen more and more since then, of how we can really impact these patients. I mean, I saw a patient who had dementia. She had Lewy body dementia, which is a combo of Alzheimer’s and Parkinson’s. She couldn’t walk. She was in a wheelchair. She had real cognitive issues. She was trying to run her business. She couldn’t function anymore.

Dr. Mark Hyman:
We essentially did this detective work that you’re talking about using the approach that’s described in The End of Alzheimer’s Program, in the Bredesen Protocol. We found she had tremendous gut issues, tremendous overgrowth of bacteria in her gut, massive nutritional deficiencies. She was diabetic, poorly controlled. Her thyroid wasn’t working. She was postmenopausal and all these various issues. We simply corrected those things that we found.

Dr. Mark Hyman:
She came back incredibly. Her energy came back. Her cognitive function came back. She was able to be in her business again. She was a relatively famous person. She was able to record another album, writing songs and write a book, where she’d been totally dysfunctional and non-functional before and was able to even get up out of her wheelchair and start walking.

Dr. Mark Hyman:
So, it’s quite remarkable. This was even over 80 years old. So, no matter where you are in the spectrum, we see these remarkable changes that people just don’t think are possible. When you talk to traditional doctors about it, they dismiss it. There has been research on this.

Dr. Mark Hyman:
You published a number of papers, looking at these case studies, but one of our colleagues, Richard Isaacson did an incredible study that looked at similar personalized interventions, not even the full protocol. He saw that he could not only stop, but he could slow it. He could also reverse some of the symptoms of cognitive decline. So, can you talk a little bit more about what approaches you do to looking at the factors that are going on and maybe list some of the key factors that you’re finding that are common among these patients?

Dr. Dale Bredesen:
Yeah. I think the best way to do that is to talk about the subtypes. So, what we published back in 2015 is when you start to look at these to do the very evaluation that you just talked about, then in fact, what you find is that although there are multiple contributors, people tend to have specific subtypes. So, type one, inflammatory. These are people who have exposure. They may have leaky gut. They may have periodontitis. They may have metabolic syndrome, lots of reasons that they have inflammation. That’s the critical driver. You can literally follow the molecular pathway from NF-kappaB activation, part of the inflammatory pathway to where it’s producing the amyloid, which as I mentioned, is part of the inflammatory pathway.

Dr. Dale Bredesen:
So, that’s the type one. In those people, you need to look for things like hsCRP, TNF-alpha, things like that. And then you need to use resolvins to improve these and then you need to identify where this is coming from and attack that. So, again, upstream is critical. Then there’s type two, which is atrophic. These are the people where they have low vitamin D, pregnenolone, progesterone, estradiol, testosterone, on and on. The critical supports for this, nerve growth factor, brain-derived neurotrophic factor, B12, all these things.

Dr. Dale Bredesen:
As you know, it takes a lot to keep a brain functional. You have over 500 trillion synapses in your head. You’ve got an amazing supercomputer inside your skull. So, you’ve got to keep that supported and prevent it from downsizing. Again, this is a disease of insufficiency. By the way, one of the most common things we’re seeing now, nocturnal hypoxia. People don’t realize it. The doctors don’t check it. They say, “Oh, I don’t snore. I don’t need to look at this.” It turns out that when you actually look at it, you see that the oxygen has crept down during the night into the 80s, even into the 70s. We see people in the low 70s, who don’t realize that they have problems with oxygenation.

Dr. Mark Hyman:
Sleep apnea, you mean, sleep apnea.

Dr. Dale Bredesen:
Without sleep, that’s the key. Sleep apnea is the tip of the iceberg, but there’s upper airway resistance syndrome as another one of these. There are people who just don’t get enough oxygen at night, even though they don’t have full blown sleep apnea. So, that’s critical to check. And then of course, we talked about the ketones earlier. Then there’s the type 1.5, which is glycotoxic. This is the people where they’ve got both inflammatory changes, because of glycation of hundreds of proteins. They’ve also got the atrophic effect, because they now have resistance to the insulin. So, type 1.5 are glycotoxic. Those are the factors. You got to look at their hemoglobin A1c, their HOMA-IR, stuff like that.

Dr. Mark Hyman:
Glycotoxic means sugar being toxic to the brain that it forms this cross, like crème brûlée on the top of your brain. So, it can’t really work properly. You talked about atrophic, which means lack of things to help the brain grow. Atrophic factors are essentially the fuel and the food or the ingredients that the brain needs to function, including hormones and the right nutrients and vitamins and fish oil, all kinds of stuff that the brain actually needs to function. So, you talked about the way you identify this. I thought this was brilliant the first time I heard about it.

Dr. Mark Hyman:
Now, everybody knows they should get a colonoscopy to check their colon, but you come up with this term called a cognoscopy, which I love, which is essentially, “How do you do a deep dive into your brain and all the things that affect your brain that cause risk of cognitive issues?” By the way, all the things that you measure with a cognoscopy are all the things we measure for any chronic illness to look at. Some are more prevalent, different illnesses. But with Alzheimer’s, you really come up with a model of a cognoscopy. So, can you talk about what is a cognoscopy? What should we be looking for? How do we get it? Can we get it with a regular doctor, or is it something that you really need specialized care for?

Dr. Dale Bredesen:
Yeah, that’s a great point. People have told me don’t use that term cognoscopy. It sounds so horrible.

Dr. Mark Hyman:
I love it. I love it.

Dr. Dale Bredesen:
But it’s simple. It’s easy to remember. We all know we should get a colonoscopy when we turn 50. So, we recommend everybody 45 or older, get a cognoscopy. As you said, it is things related to chronic illness, but the key is to prioritize. I mean, that’s the key. The people who are getting the best results, as you know, are the ones who are prioritizing the things that are the most important drivers. It’s different for each person. For some person, it’s going to be getting at that Borrelia. For the other person, it’s going to be getting at that mycotoxin. For another person, it’s going to be the glycotoxicity. So, today, it’s very simple to get cognoscopy.

Dr. Mark Hyman:
One might be mold. One might be Lyme. One might be sugar.

Dr. Dale Bredesen:
One might be sugar, yeah.

Dr. Mark Hyman:
One might be mercury, right?

Dr. Dale Bredesen:
It might be vascular. A common one is people just don’t have the vascular support for their brain. This is why they are downsizing. So, if we return that support, we return the oxygenation of the blood flow, they do better.

Dr. Mark Hyman:
Hey, everybody. It’s Dr. Hyman. Thanks for tuning in to The Doctor’s Farmacy. I hope you’re loving this podcast. It’s one of my favorite things to do and introduce you to all the experts that I know and I love and that I’ve learned so much from. I want to tell you about something else I’m doing, which is called Mark’s Picks. It’s my weekly newsletter. In it, I share my favorite stuff. From foods to supplements to gadgets to tools to enhance your health, it’s all the cool stuff that I use and that my team uses to optimize and enhance our health.

Dr. Mark Hyman:
I’d love you to sign up for the weekly newsletter. I’ll only send it to you once a week on Fridays, nothing else I promise. All you do is go to drhyman.com/picks to sign up. That’s drhyman.com/picks, P-I-C-K-S. Sign up for the newsletter and I’ll share with you my favorite stuff that I use to enhance my health and get healthier and better and live younger, longer. Now, back to this week’s episode.

Dr. Dale Bredesen:
So, the way you can get a cognoscopy is three things. It is number one, a set of blood and urine tests, easy to do. Number two, it is a simple online cognitive assessment. If you’re completely asymptomatic and doing great and you’re just in for prevention, you can stop there, just those two things. If you have any symptoms or you’re not scoring well on the cognitive tests, you want to include number three, which is an MRI with volumetrics. You want to know the volume of your hippocampus. You want to know the volumes of your frontal lobes and your parietal lobes and things like that.

Dr. Mark Hyman:
Hippocampus is that little memory center in the brain. It tends to shrink. I’ve heard you present some cases that when you’ve done these cognoscopies, you start these interventions that are in The End of Alzheimer’s Program, your new book, which everybody should get. You map out the changes over time when you implement the Bredesen Protocol. I remember the story you told of the neuroradiologist to look at the scans and was like, “This was before. This is after. This doesn’t make any sense. I’ve never seen this in my entire life to go from 20% of what it should be to 70 or 80 or 90% of what it should be.” Can you explain how that happens?

Dr. Dale Bredesen:
Absolutely. We see this again and again and again. We’re actually just publishing another paper showing not only increase in hippocampal volume, but also improvement in PET scans, where you go from a PET scan that shows Alzheimer’s to a PET scan that doesn’t show Alzheimer’s. We also see improvements in electrophysiology. So, improvements in EEG, improvements in evoked responses, and of course, improvements repeatedly in cognitive scoring and testing.

Dr. Dale Bredesen:
So, this is happening, because you are putting the things in that actually support the brain. You’re getting hormones and trophic factors that are critical. So, the brain is now making the synapses once again. Now, we don’t know yet, “Is it making more neurons? Is it making just more synapses? Is it changing in terms of its astrogliosis?” We don’t yet know what’s happening at the cellular level, but we do know that that atrophy is improving in many of these people.

Dr. Mark Hyman:
So, you said two things there that struck me. One is that your brain can grow. You can rebuild brain tissue that’s been damaged by the insults and literally grow your memory center, which correlates with improved cognitive function on the brain cognitive testing. Second, you said you can do a brain scan that you can see Alzheimer’s on. You can repeat the brain scan and the Alzheimer’s markers on the brain scan are gone. That’s like, “What?” Stop the presses, headline news, why isn’t this on the cover of New England Journal, JAMA, cover of New York Times, Wall Street Journal? What’s going on here?

Dr. Dale Bredesen:
Yeah, well, partly because of course, the standard is do 1,000 people and then do the whole study. So, at the beginning, you have to start somewhere. We’re just getting the airplane off the ground. You got to start somewhere. So, we’re looking, as you said, at these various cases. We are in the midst, I should say, of the first trial in history in which we look at all the different contributors for each person and address all these different things. We will be finished with that in December.

Dr. Dale Bredesen:
So, we’re very enthusiastic about that trial. But yes, we do see in these anecdotes that we’re now looking at, we see improvements in PET scanning and electrophysiology and hippocampal volume and all these things when you are getting these people to improve and to do the right things. You’re literally just restoring a synaptoblastic neurochemistry.

Dr. Mark Hyman:
What that means is you’re creating a brain that likes to build new brain cells.

Dr. Dale Bredesen:
That is capable. Almost 30 years ago, it was discovered. Of course, I was taught years and years ago that the brain doesn’t make new neurons. You get the ones you have, and that’s it. And then about 30 years ago, it became clear that hey, there are neural stem cells and you actually do make new neurons throughout life. so, it’s a question of, “Which ones do you keep? Do you have them interact with other neurons? Do they become part of the functional network?” So, it turns out, you do make more of them. If you do the right things, you can keep them and you can keep their interactions.

Dr. Mark Hyman:
Now, one of the big topics that you cover is the microbiome, leaky gut, inflammation in Alzheimer’s. So, most neurologists aren’t saying, “Well, let me look at your digestive system. Let me look at your gut and see if there’s inflammation there.” How does that connect to the brain? We talked to a colleague of ours, Rudy Tanzi, who’s been pioneering some of the work around finding microbes in the brain. We thought the brain was sterile. We thought the brain had a blood brain barrier that prevented anything bad from getting in.

Dr. Mark Hyman:
Well, it turns out that barrier is only semipermeable and that things can get in. They can be even microbes. So, can you talk about this amazing research on the gut and the brain and the microbiome and how that impacts what we have to do with patients with Alzheimer’s. By the way, that patient that I had, who really had brain dysfunction, her main issue was her gut. We fixed it up after decades of being constipated, needing enemas to go to the bathroom and laxatives and tons of bad bugs growing in there. It was just amazing what happened. We fixed all that.

Dr. Dale Bredesen:
Absolutely. I think that when a neurologist makes a diagnosis of Alzheimer’s or pre-Alzheimer’s, best thing the neurologist can do is refer the patient to a functional medicine doctor to deal with all the things that are driving this problem. But of course, the neurologists will feel like, “Oh, this is our province. We have to give the drug and watch you go downhill,” which is really unfortunate. I think that’s going to change. So, absolutely, the gut is a driver.

Dr. Dale Bredesen:
I think one of the most interesting studies that was done in the last couple of years was they were actually studying rodents, but what they were doing was injecting Candida. They wanted to see, “How long does the blood brain barrier keep the Candida?” They injected it into the blood vessels and asked, “Okay, what happens when it goes by the brain? How long can the brain keep it out?” The answer was it went in immediately.

Dr. Mark Hyman:
Wow.

Dr. Dale Bredesen:
This is in a normal animal. So, the fact of the matter is just as you pointed out and as Rudy has been pointing out, there is much more communication between the brain and the periphery than anyone thought possible. What have the pathologists shown us when they looked in the brains of patients with Alzheimer’s? What do they see? Herpes simplex in the brain. They see Candida in the brain. They see Borrelia in the brain. They see P. gingivalis from your dentition in the brain.

Dr. Mark Hyman:
Gum disease.

Dr. Dale Bredesen:
Gum disease. So, the bottom line is our brains are communicating with the periphery much more than anyone thought before. As you said, we actually probably have a normal brain. As much as that blows my mind, we actually probably do have a normal brain microbiome. We’re going to have to have probiotics for our brain at some point.

Dr. Mark Hyman:
Cognobiotics, right?

Dr. Dale Bredesen:
Cognobiotics, yeah, there we go.

Dr. Mark Hyman:
Wow, that’s incredible. Well, the approach also that is needed is something we don’t do in traditional medicine, which is, “How do you restore a healthy microbiome?” This is what the focus-

Dr. Dale Bredesen:
Absolutely.

Dr. Mark Hyman:
… of functional medicine is. How do you take the symptoms that people have… They may not have any symptoms in the gut, but look at the environment in there and optimize it by taking out the bad stuff, putting in the good stuff, and using the functional medicine approach to really heal the gut. So, I think what you’re saying is that each patient is different. Some may have gut issues, some may have other issues. I mean, one of the other issues that it really affects people is heavy metals. There’s been a lot of talk in the past about aluminum and Alzheimer’s, but it was ignored. I remember a patient I had, one of the first patients that I was like, “I don’t know what I’m doing with Alzheimer’s. This patient is being diagnosed with Alzheimer’s dementia.

Dr. Mark Hyman:
I have no clue if anything I’m going to do is going to work, but I’m going to try my basic framework of functional medicine to see if we can just take out the bad stuff and put in the good stuff.” So, I did a cognoscopy of sorts, got rid of the dementigens. What was really striking about this guy was he was 70 years old. He was a CEO of his major family business, couldn’t function at all. So, he was in the corner, basically depressed and not functioning. Nobody wants to be around him. He had pretty significant dementia. But when I looked at his story, he grew up in Pittsburgh and he lived in Pittsburgh. There’s steel plants there.

Dr. Mark Hyman:
Almost every patient of mine from Pittsburgh is mercury toxic, because they put coal ash on the streets. They put it on the fields. It gets in the food. It’s in the air. He had a mouthful of fillings. Normally, when you do a challenge test for mercury with a patient in functional medicine, you see a level of 20 or 50. You worry about that. That’s high. I’ve had maybe 20 in my whole life of pay me 10,000, 20,000 tests. His was 350. I’ve never seen anything like that. I have one other patient. He got 400, but almost nobody like that. I got rid of his fillings. We detoxified him from the mercury.

Dr. Mark Hyman:
He also had all these genes, ApoE4. He had methylation gene problems. [inaudible 00:33:33] vitamins. He had genes that affect insulin resistance. He had years of gut issues. He had irritable bowel for decades and was on Stelazine for his gut. So, he had all these issues that we treated. So, we fixed his insulin and blood sugar. We fixed his gut. We fixed his B vitamins. We got rid of the mercury. The guy literally came back like Rip Van Winkle from the dead. It was the most striking thing I’ve ever seen in my life. I’m like, “Holy cow. I just cured Alzheimer’s.”

Dr. Dale Bredesen:
Yeah, how about that.

Dr. Mark Hyman:
This was probably 15 years ago. I’m like, “What?” That was really what began the process of me going, “Wait a minute. The brain is so fixable if we understand the insults,” which you’ve mapped out so well in The End of Alzheimer’s and if we understand how to actually repair and heal the system. So, talk about mercury and the metals and how these affect the brain, because this is not to say that everybody with Alzheimer’s has heavy metals. They don’t. But I’ve had a number of patients, it makes a huge difference when you deal with it.

Dr. Dale Bredesen:
Yeah, but as you said, a certain number of them, that is the key piece. Here’s the thing. I mentioned earlier, your brain makes amyloid when it is under attack by microbes, because it’s trying to kill the microbes. But interestingly, the gene itself that amyloid comes from, which is called amyloid precursor protein is a gene that is responsive to metals. So, there’s literally a metal binding region on the RNA, this piece that’s going to be making the protein. So, it responds to mercury. It responds to copper, zinc, iron. So, this thing is part of what’s binding up those metals. So, it actually binds up.

Dr. Dale Bredesen:
So, what happens is you can actually give mercury. As you indicated, mercury is literally a cause of Alzheimer’s, not in everybody, but in a small group of people, probably something like 3 to 5% of all Alzheimer’s patients, which still that’s a lot of them. There are going to be 45 million people with it, who are currently living Americans, 45 million of us will develop Alzheimer’s during our lifetimes.

Dr. Mark Hyman:
5% is a couple of million people who have metal issues.

Dr. Dale Bredesen:
Exactly. This is a big problem. So, this is why, as you said, you want to check this on everybody, because if that’s one of the contributors, you need to deal with it. When you do, they do better. It increases the production of the amyloid. Both interestingly, it induces the amyloid and it induces the tau as well. So, it is a great way. If you want to give yourself Alzheimer’s, take some mercury.

Dr. Mark Hyman:
Eat some sushi.

Dr. Dale Bredesen:
Exactly, some tuna sushi.

Dr. Mark Hyman:
But the funny thing is that not everybody accumulates the mercury. A lot has to do with genetic variation. I personally had mercury toxicity, and I have cognitive dysfunction. I felt like I had dementia. Really, I did. My level wasn’t 350. It was 187, which is bad enough.

Dr. Dale Bredesen:
Still. Yeah.

Dr. Mark Hyman:
Still bad. So, I understand from a personal point of view what this does. It’s one of the most potent toxins on the planet, probably second only to plutonium. It is the most potent neurotoxin. It’s unconscionable to me that we don’t as a profession really think about the role of toxins. We check the blood levels, but that doesn’t really reflect the total body burden of these metals. So, there are ways through functional medicine and the approach you’re talking about to really do this.

Dr. Mark Hyman:
Let’s talk about the next topic, which is hormones. I’ve seen some really interesting responses to hormones around thyroid, sex hormones. This is what we call a trophic factor. So, it’s not something that’s hurting you. It’s something that you’re lacking, that your brain needs to function. So, talk about some of the big hormonal findings and what you’re seeing with these patients.

Dr. Dale Bredesen:
Yeah. There’s some elegant work published out of the Mayo Clinic a number of years ago, where they simply looked at women who had oophorectomies for whatever reason.

Dr. Mark Hyman:
Take their ovaries out.

Dr. Dale Bredesen:
Remove the ovaries right at the age of 40 or younger, who did not get BHRT versus one did not get hormone replacement versus those who did get hormone replacement. Even though the hormone replacement has been imperfect for many of these, there was a striking difference. The ones who did not get the hormone replacement had more than doubling of the risk for developing Alzheimer’s, even though the Alzheimer’s wasn’t diagnosed until years later.

Dr. Mark Hyman:
Wow.

Dr. Dale Bredesen:
It goes perfectly with the science that we talked about earlier. This APP is looking for support. When it does not get that support, it’s flipping over to the synaptoclastic. It’s saying, “We can’t support this brain.” It goes beyond just estradiol to progesterone and pregnenolone and testosterone and vitamin D and all these things, thyroid hormone as well. These are all critical. So, repeatedly, people have come upon the fact that you’re getting this at the time often when you’re losing those hormones or down the road from this. We see a lot of people now, something I never saw when I was training, people who are in their 50s, women who are going through menopause or perimenopause, who have their first symptoms at that time.

Dr. Mark Hyman:
Wow.

Dr. Dale Bredesen:
So, for a number of reasons, it’s huge, not only the support side, but also as Dr. Chris Shade has pointed out, progesterone is one of the most critical parts for your detoxification apparatus. So, when you now get this relative lowering of so-called relative estradiol excess or estrogen access, this is because you’ve lost both, but you’ve lost the progesterone to a greater extent. You are at increased risk for toxin-related Alzheimer’s disease. You’re now getting this synaptoclastic burst. You are rereleasing these toxins, including mercury, that you have sequestered for so many years. So, by multiple mechanisms, having too low support from your hormones is a critical risk factor for cognitive decline.

Dr. Mark Hyman:
Yeah, there is controversy about hormone replacement, particularly around cancer. Do you worry about that?

Dr. Dale Bredesen:
I do, absolutely. So, I think it’s critical to have people see experts in this area, Dr. Anne Hathaway, Dr. Prudence Hall, and many people who are BHRT experts who look at, “When’s the best time to do this? What are the best doses?” Can you improve? If you get the better outcome, yeah, there is a worry about cancer. Although some of the studies have actually shown reduced with appropriate use of estrogen and progesterone, reduce likelihood of cancer. So, you really want to stack those against each other.

Dr. Mark Hyman:
There’s very personalized approaches to this depending on your genetics, your family history, what actually is going on with you, what your biology is. Actually, helping women to personalize the treatment using the biological hormone replacement, not-

Dr. Dale Bredesen:
Absolutely.

Dr. Mark Hyman:
… actually, the kind that comes from horse urine, which is studies were done. So, we don’t even have big studies on the good stuff. All right. Let’s talk about nutrition. We’re going to talk about diet a little bit, but I want to talk about the widespread nutritional deficiencies that you’re seeing and how those play a role in the brain and cognitive decline. What are the most important nutrients we need to be focusing on?

Dr. Dale Bredesen:
Yeah, it’s amazing to me, because we’ve got so many things working against us. Obviously, you’ve written probably more on this than anyone, looking at the critical nature of nutrients for your health, changing the world one bite at a time, and all these fantastic things you’ve done. Again, it just fits perfectly with the science that we’ve studied over the years. So, Paul Clayton from Oxford has pointed out that we don’t even have the nutrients in the soils that people had 100 years ago, 200 years ago. When we were thinking these people while they didn’t know what they were doing, they were doing much better than we are, because he’s pointing out that Henry the Eighth had better nutrition than we do. Of course, he ended up being obese and had problems with arthritis and things.

Dr. Dale Bredesen:
But the key is that they actually had better soil. So, we’ve got essentially a triple whammy. Number one, we have poor soils. Therefore, we have poor overall nutrition. Number two, we’re eating food that’s way too high in sugar obviously and way too high in processed foods and all these issues. So, we’re eating stuff that’s toxic. And then number three, we’re not getting nearly enough fiber, nearly enough phytonutrients. So, we have this system. It’s as if you took your car out and you’re trying to drive this car that needs appropriate fuel and you’re putting stuff in that is very low octane. It’s just sputtering. It’s spluttering. It’s having trouble getting out of the block. You might go a little way. That’s what we’re all dealing with every day.

Dr. Mark Hyman:
Crappy fuel.

Dr. Dale Bredesen:
Crappy fuel. You optimize those things. You get people into some ketosis. You get them appropriate fiber for detox and for their microbiome. You get them appropriate low carb diet. You get the appropriate phytonutrients. By the way, one of the most common deficiencies, choline. As you know, choline is needed to make acetylcholine, which is a critical neurotransmitter for memory. It’s reduced in people with Alzheimer’s. I’ve checked myself on chronometer and I realize I’m not getting enough choline in my diet. We should be getting around 550 milligrams or so of choline each day. Most of us aren’t.

Dr. Mark Hyman:
Which you get from eggs and sardines.

Dr. Dale Bredesen:
You get it from eggs and some sardines, from liver, obviously, organ meats, things like that, from oysters, things like that, a number of vegetables as well. If you’re not getting it from there, take some citicoline. This is why Professor Wurtman from MIT found that citicoline is so helpful for synapse formation. So, lots of ways to get choline, but please make sure that you get enough. So, all of these things are critical.

Dr. Mark Hyman:
What besides choline is so important for the brain? What nutrients?

Dr. Dale Bredesen:
Take flavonols. Flavonols and flavonoids, those alone, a study that just came out showing that over thousands of people, those who are in the highest quartile of flavonols had a much lower dementia risk than those who are in the lowest quartile of flavanols. So, things like strawberries and things like grapes and things like that are all helpful to give you the flavonols. And then the flavonoids, things like blueberries and things like that are all critical.

Dr. Mark Hyman:
So those are like 25,000 different phytochemicals in plant foods.

Dr. Dale Bredesen:
Exactly.

Dr. Mark Hyman:
Flavonols and flavonoids are part of those. So, eating a rainbow colored diet where half your plate is vegetables is a simple take home to protect your brain and pretty much everything else that can go wrong with you. So, we’ve got choline. We’ve got flavonoids and phytonutrients. What other major nutrients are an issue?

Dr. Dale Bredesen:
Well, minerals. So, the key ones that almost all of us are deficient as you know, zinc. Zinc has become a huge issue because of COVID-19. So many of the people who are deficient in zinc have an increased poor outcome, increased risk for having a poor outcome from COVID-19. So, zinc, magnesium, iodine, potassium, those are the big four that most of us are deficient in.

Dr. Dale Bredesen:
And then of course, vitamin D, as you know, the study that just came out about 10 days ago, showing if you take the people who are low in vitamin D, they have a much worse outcome in COVID-19 than the people who have sufficient vitamin D. Of course, Alzheimer’s is no different. The same thing you see, people who are low in vitamin D more likely to get Alzheimer’s, people who are sufficient vitamin D. Of course, same thing in multiple sclerosis, high vitamin D associated with better outcomes. So, as you said, it’s multiple diseases that all depend on these critical factors.

Dr. Mark Hyman:
Some of the most important things that I found are B vitamins. I once had a patient who was about 87 years old. She was on multiple boards, very successful woman who was noticing depression and really severe cognitive decline and been diagnosed with MCI or pre-dementia, was told to get her affairs in orders. She came to see me. I checked your levels and found she had really high level of something called methylmalonic acid and homocysteine, which are things that most doctors don’t check, but reflect your status of B12, methylmalonic acid and homocysteine, which is a folate and even B6.

Dr. Mark Hyman:
So, I basically gave her B12 shots, high doses of methylfolate, which is a particular kind, saw she had some genes that made her need a special folate. She called me back and was doing amazing. All of her symptoms have gone away. And then a few years later, maybe four or five years later, she called me up. I saw her on my schedule. I’m like, “Maybe she’s not doing well or she’s declining.” I’m worried about her a little bit. She’s like, “Dr. Hyman, I’m going trekking in Bhutan. I want to know what I should do to prepare and what I should be taking.” So, I was like, “Okay.”

Dr. Mark Hyman:
Sometimes it’s that simple, but it’s not always that simple. But I think understanding the role of nutrients and nutritional deficiencies is huge. It’s far more common than we think. You can’t get everything you need from food. I think a lot of the reason the studies on vitamins have failed in MARS trials, whether it’s for cancer or heart disease, is because they’re not dealing with the whole system. If you’re eating doughnuts all day, you can take all the fish oil or vitamin D you want, it’s not going to do anything to fix your risk of heart disease, right? So, you have to look at everything together.

Dr. Dale Bredesen:
Absolutely.

Dr. Mark Hyman:
So, let’s talk about this concept you talked about called KetoFlex. We’ve touched on it a number of times, but what is the diet that’s best for your brain? What is the diet that’s best for your brain if you actually have Alzheimer’s?

Dr. Dale Bredesen:
Yeah, great point. So, let me preface this by saying I know far less about nutrition than you do. So, I’m really talking to someone who’s an expert here. I’m looking at the neurochemistry. So, I’m interested in synapses, how they’re made, how you keep them. So, KetoFlex 12/3 is nothing more than what’s the thing we can use to drive your biochemistry toward an optimal biochemistry for making and keeping synapses.

Dr. Dale Bredesen:
So, what do you need? You need to have ketosis. You need to have all the nutrients we were just talking about for support. You need to have high fiber, because you need to help yourself detox. You need to improve your microbiome, all those sorts of things. You need to have appropriate probiotics to support your microbiome. You need to have fasting periods for autophagy, fasting periods for helping you to get into ketosis, fasting periods for all the great things that fasting does, even things like lowering your blood pressure. Hypertension is another big risk factor for Alzheimer’s.

Dr. Dale Bredesen:
So, if you put all that biochemistry together and you mix it up in a blender and you say, “What’s the diet?”, we named it KetoFlex 12/3. It’s ketonic. It’s mildly ketonic. It’s plant rich. This is not a bacon-related ketogenic diet. This is a plant rich, high good fats, intermediate proteins, low carb and no simple carbs. It is flexitarian. I realized flexitarian means you have to eat some meat and fish. It’s really more about flexibility. You want to be a vegetarian, no problem. Make sure to check your homocysteine and your vitamin D and things like that, but fine. If you want to have some meat, have some fish.

Dr. Mark Hyman:
It’s hard to be, I think, keto if you’re not eating animal protein. I mean, you can do it as a vegan or vegetarian, but it’s harder because-

Dr. Dale Bredesen:
It’s harder.

Dr. Mark Hyman:
… you reduce the carbohydrate load, because you need the protein from beans and grains and things like that. So, how do you do that with those patients?

Dr. Dale Bredesen:
Yeah, that’s a great point. So, again, because getting into ketosis is so critical for supporting brain energetics, we tell them just start by taking some exogenous ketones. Do it for a couple of months, no problem, because we need to get that energy up.

Dr. Mark Hyman:
So, taking as a supplement.

Dr. Dale Bredesen:
Exactly. Then you can get yourself into endogenous ketosis. We do that by increasing the fat consumption, all the appropriate oils and the nuts and the seeds and all the things you’ve written about that are excellent sources of good dietary fats. And then if they can’t get into enough ketosis, okay, we can supplement that a little bit to get them where they need to be. So, that’s the flex part. And then 12/3 is 12 hours as a minimum.

Dr. Dale Bredesen:
If you’re ApoE4 positive, you should really make it 14 to 16 hours of a fast between when you finish your dinner, when you start your breakfast, brunch or lunch. And then the three is for three hours before you go to bed. You don’t want to be eating right before bed, because it will spike your insulin, reduce your growth hormone and your melatonin and so forth and so on. So, this is why KetoFlex 12/3 is essentially our attempt to take the neurochemistry of synaptogenesis and to put it into a diet.

Dr. Mark Hyman:
That’s so incredible. So, you’re saying you don’t have to be keto if you’re not having Alzheimer’s for prevention. This is more for treating a patient, right?

Dr. Dale Bredesen:
It’s a great point. This is one of the things that we’ve been arguing about lately. If you’re just there for prevention, do you want to get yourself into ketosis? It depends on how concerned you are. If you are really concerned about prevention, then you probably want to do at least part time getting yourself into some mild ketosis. But you’re right, you don’t have to. For someone who’s trying to reverse, absolutely, it doesn’t reverse well if you don’t get into ketosis, because you’re missing out and energy gap.

Dr. Mark Hyman:
Yeah, I’ve seen that with my patients when I put them on ketosis if they’re struggling, because often people get better without it. They’re on a low glycemic diet, but then you really want to push that envelope. They seem to do a lot better.

Dr. Dale Bredesen:
Absolutely.

Dr. Mark Hyman:
What about ApoE4? Because this is a common gene that increases your risk and you have one or two copies. There may be some interesting data that I’d love to explore with you, because historically, there was concern that these patients should not eat saturated fat, that they may have more problems with cardiovascular disease and dementia. What is the current status of the data on these ApoE4 patients? Which are a lot, I mean, they’re about 45 million or something in America.

Dr. Dale Bredesen:
Yes, 75 million.

Dr. Mark Hyman:
Seventy-five million.

Dr. Dale Bredesen:
So, here’s the thing. Three-quarters of the population is ApoE4 negative, and one-quarter of the population is ApoE4 positive. So, it’s incredibly common. There are some advantages you have to being ApoE4 positive. So, in third world countries, it actually gives you a big advantage, because you have a more pro-inflammatory state. You’re better at fighting off pathogens. You’re actually better if you have a starvation diet. If you’re starving, you want to be ApoE4 positive, because you are better fat absorber.

Dr. Dale Bredesen:
So, 75 million Americans have one copy. They are at 30% lifetime risk for Alzheimer’s. If you’re negative, about 9% lifetime risk. One copy, 30%, two copies, well over 50%, most likely you will develop Alzheimer’s. That’s seven million Americans. So, critical for all of these people to be on prevention. Absolutely.

Dr. Dale Bredesen:
As far as the fats, it’s a good point. This is a controversial area still. Some arguments would say, “Yes, a limited amount of saturated fat is okay.” I think most people who are ApoE4 positive would like to stick with the monounsaturates and polyunsaturates and stay away. So, typically, we don’t recommend, for example, coconut oil, MCT oil. We recommend if you want to get into ketosis exogenously, just take some exogenous ketone. Take ketone salts, take ketone esters, those sorts of things. You can do that a couple of times a day and get nice spikes in your ketone levels. And then ultimately, again, you want to get into it endogenously.

Dr. Dale Bredesen:
So, if I had to say one way or the other today, I would say the preponderance of the evidence today is on the notion that you would want to stay away from saturated fats. Having said that, there are people who do have some saturated fats in their diet and have beautiful lipid profiles, despite the fact that they are ApoE4 positive.

Dr. Mark Hyman:
So, you want to check your bloodwork and see how it’s responding to your diet, not just guess, right?

Dr. Dale Bredesen:
Absolutely, check your LDL particle number. Try to keep that between 800 and 1,200. Or if you want, check your calcium score, makes sure that you don’t have any cardiovascular disease, but of course, there’s an increased risk for cardiovascular disease as well with people who are ApoE4 positive. So, as you said, check to see where you stand to make sure you’re doing well.

Dr. Mark Hyman:
Now, a lot of people listening and if there are medical professionals listening, they’d probably think it’s heresy to say that we can reverse Alzheimer’s, that it’s providing false hope, that we don’t have the science behind it. It’s really not possible, but you and I both seen that it is possible. It’s not always 100%. But the question is really, to what degree in your experience is this reversible? How far along can you be before you can be confident that’s it’s going to be reversed? Otherwise, is there a time when it’s too late? So, can you talk about what that is? Maybe a case or two that explains really how this works in practice.

Dr. Dale Bredesen:
Absolutely. So, we can think of this in four phases. Phase one is where people are asymptomatic, but they already have the pathophysiology ongoing. Those people are the ones for prevention. They do very well. Let me ask you a question. Have you ever had a person who came to you for Alzheimer’s prevention who then develop Alzheimer’s while on your program?

Dr. Mark Hyman:
I think I’ve had people progress slowly over 10 years. I’ve kept them good for 10 years. If they slip off the program, that’s when they get into trouble.

Dr. Dale Bredesen:
Well, exactly, slipping off the program. So, I asked this to many functional doctors. Typically, very few people have seen this. When you’re on prevention and you start when you’re asymptomatic, you do very well. Then the next phase is SCI, subjective cognitive impairment, which actually lasts about 10 years, where you know there’s something wrong. Often, your spouse does, but you’re still scoring well on the testing. Those people, virtually, all of them get better, because these are still early stages. Then the next stage is mild cognitive impairment. These are people who are scoring 23, 24, 25 on the MoCA Scores or 26. This is Montreal Cognitive Assessment Scores out of 30.

Dr. Mark Hyman:
The memory test, right?

Dr. Dale Bredesen:
Yeah. So, they clearly have significant early Alzheimer’s, but we call it mild cognitive impairment at that point. The majority of those people will increase their scores. We wrote a paper on this with 100 documented improvements and published it in 2018 with 15 different laboratories. The average improvement in score was 4.9. So, if you came in at 22, you ended up around 27 typically. So, that’s clearly improving. They typically sustain it. Then the ones who then are all the way to Alzheimer’s, they’re now losing activities of daily living. Calling someone Alzheimer’s is like saying late stage cancer, metastatic cancer, because it’s a very late stage of this process that’s been going on typically for 20 years. Some of those people improve.

Dr. Dale Bredesen:
We’ve had people with MoCA Scores of zero improve, but when they improve, they go from zero to five. They dress themselves again. They speak again. They interact with their families again. They can even do emails again, but they’re not normal. So, we’re not so far not able to take someone from 0 to 30. That’s one of the big research questions right now. What is missing? They come to a next plateau. What do we need to get them to a higher plateau? Is there a rate limiting step that’s preventing, or is it just the massive loss of synapses? Do we need to then think about stem cells, intranasal trophic factors, methylene blue, all these sorts of things that are coming?

Dr. Dale Bredesen:
EWOT, that’s another thing we’ve been interested in, exercise with oxygen therapy, all the things that we can bring to bear. So, the bottom line is the farther along, the harder it is and the less complete the improvement. But if you catch people early or even in mid-stage, you can do a lot just as you’ve indicated.

Dr. Mark Hyman:
Absolutely, I’ve seen that. So, can you share maybe a story or two of the patients you treated, what you found and what things you did and how they improved?

Dr. Dale Bredesen:
Yeah. Oh, absolutely. There are hundreds and hundreds like this. So, simple example of a woman, amazing lady, who’s a psychiatrist, who was having major problems. In fact, her husband said to her, he said, “Your memory is disastrous.” So, she got to the point where she just couldn’t remember anything. She’s 73 years old. Actually, she contacted me in my email a few years ago and we started going back and forth. She started checking all the various things. She initially had a lot of a type two, reduced estradiol, progesterone, no surprise, she was 73, reduced vitamin D, poor thyroid, all those. So, all of those were addressed. She then improved. So, she was at the 9th percentile on her initial cognitive scores. She’s now at the 97th percentile-

Dr. Mark Hyman:
Wow.

Dr. Dale Bredesen:
… on her cognitive scores. As you’ve seen yourself, people get into this. She started doing this game called Elevate, as well as BrainHQ. These are brain training programs. She just got into this stuff and started working it. She started dealing with all these-

Dr. Mark Hyman:
Brain exercises,

Dr. Dale Bredesen:
… brain exercises. And then interestingly, she optimized her various nutrients. and then it turned out, I said, “Wait a minute. We haven’t checked all the pathogens here.” She ended up having ehrlichia. She was from the New York area. She ended up having exposure because of a tick bite. When that was treated, she continued to improve and she’s just done well. Now, interestingly, she had not only improvement in her MRI hippocampal volume, she also had a PET scan. Her first PET scan was diagnosed as looks like early Alzheimer’s. Her latest PET scan looks like no Alzheimer’s.

Dr. Mark Hyman:
Wow.

Dr. Dale Bredesen:
So, she actually improved her PET scan, improved her MRI, improved her cognitive scores. As she said, her significant other said to her, “You went from disastrous to just plain lousy and then from just playing lousy to normal.” So, she goes out and plays golf with her friends. They can’t cheat her.

Dr. Mark Hyman:
Incredible.

Dr. Dale Bredesen:
They can’t cheat her anymore. She knows how many strokes they’ve taken.

Dr. Mark Hyman:
Incredible. What did her neurologists say?

Dr. Dale Bredesen:
Yeah, interestingly, her neurologist said… She said to me that she went in there and there were all these people. She said it was a very depressing, typical neurologist’s office. Everything’s bad. She said, “He came out and he was so excited,” because he saw how much better she was doing. He started saying, “What have you been doing this? This is incredible.” We hear this a lot. People will come out and say, “Whatever you’re doing, keep doing it, because something is working here.”

Dr. Mark Hyman:
Well, this is really exciting. What is on the horizon in terms of the research you’re doing? Because clearly, you and I have had experiences. We’re seeing this over and over. Our colleagues who are doing this in functional medicine are seeing these results, but it’s still pretty much dismissed by most traditional neurologists and Alzheimer’s researchers. Even all the Alzheimer’s funding isn’t going towards this.

Dr. Dale Bredesen:
Absolutely.

Dr. Mark Hyman:
So, what is on the horizon that gives you hope around the research that we can show the data and begin to change the conversation?

Dr. Dale Bredesen:
This is a great point, because we really do have the opportunity now to reduce the global burden of dementia dramatically. People wiped out things like polio and smallpox with vaccines. Global programs, we need to have a global program to reduce the burden of dementia around the world by doing these correct things. This is not magic. This is our complex organism that we’re dealing with. You have to look at the right things and do the right things to do that.

Dr. Dale Bredesen:
Where the research is going is to take these same principles… What we’re finding, of course, is that the supply is being exceeded by the demand in all of these diseases. So, we have to increase the supply, reduce the demand. There’s a unique chemistry for each of these, for macular degeneration, for frontotemporal dementia, for ALS, for Lewy body disease and on and on and adjusting this approach to each of these. We should be able for the first time to make improvements in all of these different neurodegenerative diseases.

Dr. Mark Hyman:
Yeah, I think that’s true. I’m excited. We really are at this forefront of an era when our rethinking of disease is going to provide the key that unlocked so many of our dilemmas and health, everything from these neurodegenerative diseases to mood disorders to ADD and autism and of course, even all the other chronic diseases. So, the approach of functional medicine provides a roadmap to really look at what’s going on with any patient. So, you talked about a cognoscopy. It’s the same approach to look at whatever is going on with somebody. What are the dementigens? They’re the same and similar things that cause all diseases.

Dr. Mark Hyman:
So, it’s not like there’s 4,000 causes of the disease. This is a short list of things that cause problems and a short list of things a body needs to actually heal and repair. What you’ve done is lay that out so beautifully in The End of Alzheimer’s Program. It’s called The First Protocol to Enhance Cognition and Reverse Decline at Any Age. I really believe that people get this book and they look at it carefully. It’s going to provide insights not just into the brain, because you’re a neurologist, your focus is on the brain, but I see this from the context of chronic disease in general to help really understand what’s going on.

Dr. Mark Hyman:
You really mapped out one of these dementigens. It’s things like our diet that’s full of starch and sugar. It’s our widespread nutritional deficiencies. It’s things like heavy metals. It’s infections like tick infections. It’s toxins like mold toxins. It’s microbiome issues in our gut. It’s our oral health. It’s all of these things that are driving these problems that are causing inflammation. And then at the same time, what are all those components that we need to be healthy? The right diet, ketones and nutrients and hormones and probiotics and all the things we need to actually add to the body to create health. If you do this with any patient, their health is going to improve. You particularly deal with a patient with cognitive issues in any age spectrum.

Dr. Mark Hyman:
I wrote an article years ago, which I was very proud of, it was way before anybody was talking about this. But I think Alzheimer’s and autism are often very similar diseases at different ends of the age spectrum. If you look at the biology of what’s going on with these patients, the amyloid and stuff is different, but their brains are both inflamed. They often have the same causes of the inflammation. Fixing them is often very similar. So, I think this is really the most exciting here. I think you should get the Nobel Prize for what you’re doing. I really do. I think you’re way ahead of your time. I think we really need to think about getting in the research phase.

Dr. Mark Hyman:
If anybody’s listening to this who has Alzheimer’s, who know someone who’s Alzheimer’s, who cares about this issue, I think we need to fund some big studies to look at this and get this done rigorously. I think it’s a really exciting moment where we can begin to do this, because we know enough about the brain. We have the big data analytics, the artificial intelligence, and the science of functional medicine and system biology to really put it all together. So, Dale, I can’t thank you enough for your work and what you’re doing to advance these ideas in medicine and to give people hope where there really was none.

Dr. Dale Bredesen:
Thanks so much, Mark. Thanks for having me. As you know, you and I are both on the same panel with Maria Shriver and a number of others to change the way we think about this. The problem, of course, is there’s going to be pushback. So, over time, I think we need to get people to understand that yes, there really is something to do, especially in the prevention and early reversal area. We really can reduce the global burden of dementia. So, thanks so much for the great work you’re doing. Thanks so much for having me on. I really appreciate it. Stay safe.

Dr. Mark Hyman:
Of course. Everybody should check out The End of Alzheimer’s Program: The First Protocol to Enhance Cognition and Reverse Decline at Any Age. If you go to apollohealthco.com, apollohealthco.com, you can learn more about the book, learn more about his program, learn about what you need to learn for your health and your family. It’s just an incredible resource and I hope everybody takes advantage of it. If you love this podcast, please share it with your friends and family on social media. Leave a comment. Tell us about your story of how you’ve identified ways to help enhance your brain. Subscribe wherever you get your podcasts. We’ll see you next time on the Doctor’s Farmacy.

If you are looking for personalized medical support, we highly recommend contacting Dr. Hyman’s UltraWellness Center in Lenox, Massachusetts today.

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