Bonus: Dr. Dale Bredesen | How to Make Alzheimer’s Just a Bad Memory

Transcript for Dr. Dale Bredesen | How to Make Alzheimer’s Just a Bad (Bonus Episode)

Jordan Harbinger: [00:00:00] Welcome to the show. I'm Jordan Harbinger. As always, I'm here with my producer, Jason DeFillippo. In today's conversation, we're talking with Dr. Dale Bredesen. He's an expert in the mechanisms of neurodegenerative diseases such as Alzheimer's disease. We cannot escape the news about this disease. I have aging parents. Every time they forget something, I'm like, “Oh my gosh!” Right? This is the only disease in the top 10 causes of death here in America with no real treatment whatsoever. On the Jordan Harbinger Show, we spend a lot of time teaching you how to improve your brain, your cognition, the way you think, making you smarter, more efficient. Today, we're talking about cognitive decline. We'll discover what causes cognitive decline. It's now what you think, and Alzheimer's is actually three different syndromes with 40 plus different contributors, some of which you're exposing yourself to right now. It's not audio, relax.

[00:00:49] We'll also uncover some of the symptoms of cognitive decline. Why and when you should be worried about them, especially if you're pushing 40, listen up to this part of the show. And we'll explore how cognitive decline can be slowed and even reversed and know it doesn't require some magic pill or supplement. In fact, you might be surprised to find out what the best means to attack this set of contributors to cognitive decline actually is or are. There's a lot here on this show. It may sound a bit complicated at first. We'll do our best to make it digestible here, and don't forget we have worksheets for today's episode so you can make sure that you solidify your understanding of the key takeaways from Dr. Bredesen here. That link is in the show notes at jordanharbinger.com/podcast.

[00:01:32] Now, here's Dr. Dale Bredesen. I don't think there's anyone that hasn't been touched by Alzheimer's in some way. You can't escape the news about this disease. I have aging parents every time they forget anything now I'm like, “Oh no! Oh my gosh.” You know, and my mom will say, “Oh, this is how it begins.” And she's kind of not joking, and it's a little scary, and there's further -- you mentioned in the book as well, there's no new Alzheimer's drugs since 2003, and this is the only disease in the top 10 causes of death with no real treatment whatsoever. And that's terrifying for people like me, 38 pushing 40. This disease takes down the rich and the poor, the educated in the on educated. No one's immune, no one's privileged. This is like -- this is one of those terrible equalizers.

Dr. Dale Bredesen: [00:02:17] That's exactly right. And the thing is, it is something that concerns us as we age. And as you know, it is now the number one cause of aging Americans, it has past cancer as the concern. So everybody's concerned what's going to happen to my cognition. And the reality is we have a situation where everything needs to change.

[00:02:38] Number one, we should be checking, get a quote, what I call a cognoscopy. Everybody knows you get a colonoscopy when you're 50, you know if you're 45 or older or if you've got parents who have dementia, you should think seriously about a cognoscopy. It's not a difficult thing to do. You get some blood and urine tests, you get an online cognitive assessment and you can determine where you stand and what your risk factors. No different than 40 years ago people said, “Oh, I need to check my cholesterol.” “Oh, okay,” so same idea. And so you know, this is an important to have.

[00:03:09] And then the second thing is you need to be working on it actively. So yeah, if your parents are concerned or if you are concerned, do some brain training, get on the right diet, exercise, sleep, stress. That's why we generated this computer program that looks at what is a subtype or subtypes that you are at risk for, or already beginning to show. And then here are the things that you can do optimally to address this. I mean, it's amazing how many of these things have kind of elephants in the room.

[00:03:38] One of the big ones is you go in to see a physician and you say, “I'm having some problems with cognition.” He or she doesn't ask what's causing it. You say, well, they say, “Oh, you have an early Alzheimer's.” Okay, “What's causing it?” “Well, it's early Alzheimer's.” “Well, wait a minute, I need to know what are all the things.” This is very much like taking your car in, mechanic says to you, “Oh, we yet we recognize this, “this is Car Not Working Syndrome.” And you say, “Well, wait a minute. I mean, what's causing it?” “Well, the Car Not Working Syndrome, we don't know what causes it and there's no cure.” And older cars tend to get it. And you'll say, “Well wait a minute, aren't you going to check some, -- get to check the gas, the oil, et cetera?” They has going to say, “No, those aren't reimbursed.” And that's exactly what's happening right now. We go in and we're told it's early Alzheimer's, nothing to do. Well. In fact, if you look at larger datasets, which is part of 21st century medicine, you can ask, “What is the status? Do I have insulin resistance? Do I have the chronic activation of my innate immune system? If so, what's causing it?”

[00:04:38] And so the whole idea here is you need to look at all of the contributors and we described in the book that there were 36 we initially identified. It's going to be end up being closer to 50, but it's not thousands. You know, there's a finite, there's dozens of things that contribute to cognitive decline and you can measure them and you can address them and you can prevent the problem and you can reverse it, the earlier, the better. Though later, you can still get some times and sometimes you don't. But looking at the critical causes, all of the root cause contributors is absolutely crucial and not being done at the major centers.

Jordan Harbinger: [00:05:18] When you say not reimbursed, is that what you're talking about is doctors in hospitals won't necessarily check for cognitive impairment because early Alzheimer's is considered kind of the end of the story. And then they say, “Look, I could run a bunch of tests, but insurance isn't going to pay for it. And since we have collectively kind of given up on treating this with drugs, we're not going to look for alternative ways to deal with this. You're just going to have to suffer and live with this for the next 30, 20 years, whatever, until you die this sort of sad Alzheimer's death.” And that seems terrible, especially because if we know that cognitive decline can be reversed and that not all is lost and later on in the show we'll discuss some steps we can take now if we see that. It seems kind of unfair, and what I took from the book was if you are dealing with some cognitive decline, you shouldn't go, “Well, this is what it means getting older, no problem there.” It's kind of like you get a wound on your leg and it's bleeding. You don't go, “Yeah, I guess that's just going to bleed forever until I'm dead.” Right? You put a bandage on it, you try to figure it out. If there's other things you can do, but with Alzheimer's it's just like, “Oh well, I guess that's in your brain, and unless they come up with a brand new drug, which again they haven't for the last 15 years now, you're screwed!” And that's not good news for anybody.

Dr. Dale Bredesen: [00:06:35] And this is exactly the issue, the very tests that you need to determine what is causing your cognitive decline are the very tests that are not reimbursed. How ridiculous is that? So for example, you can get a reimbursed MRI and that can tell you, “Oh yeah, you've got some atrophy in your hippocampus.” Okay, but that doesn't tell you what's causing, and you say, “Look, I want to know if I have insulin resistance. I want to know if there are various pathogens that are causing this response.” And as I mentioned in the book, there’s a big surprises Alzheimer's disease is actually a protective response to multiple different insults. That's the big surprise.

[00:07:15] So getting rid of the protection is not the right way to go. You want to understand what caused the problem and then yeah, it's fine to get rid of the amyloid after you've got rid of what's causing you to make it. Amyloid is a little bit like napalm. You're putting it down because you have been invaded. So you want to know what pathogens are there. You want to know if your innate immune system is activated. You want to know specific toxins -- organic toxins, metalotoxins, biotoxins.

You want to know about specific nutrient deficiencies and responses to those. Methylation defects, these things are all contributors to this thing that ultimately ends up as Alzheimer's and as you know by the time you get a diagnosis of full blown Alzheimer's, the underlying process has been going on typically for 20 years or so. And so yes, you need to know what causes and preferably you look at it when you're in your 40s or early 50s, for example, and say, “Okay, here are the things that are putting me at high risk for Alzheimer's.” I can address them now literally, and this is not a joke, this disease should be a rare disease. It should mostly end with this generation. If everybody looks, if everybody gets on the appropriate prevention and early reversal program, this should be a rare, rare disease.

Jordan Harbinger: [00:08:38] That's really good news. The other good news, or I guess news, it might just be general here, but that everyone over 40, you'd said in the book is starting to hit some cognitive decline. So everyone 40 and up are close like me, especially in their 50s, needs to be paying to this. And I guess the good news part of this is that it can be addressed now and that we can slow and reverse it. And we found some ways to do that. We had no hand in this view, and then other doctors and researchers have found ways to deal with this.

[00:09:09] First though, let's talk about what is and what is not Alzheimer's. Because I think first of all, most of us, including myself, had no idea and have no idea what this actually is. It's not like a cancer where cells aren't doing what they're supposed to do. This is something completely different, right?

Dr. Dale Bredesen: [00:09:25] Absolutely. So as I mentioned, so there is a molecule in your brain, you know, and it's one of your -- it comes from one of your 20,000 genes, which is called amyloid precursor protein, and we discovered that this thing actually works like a molecular switch. So this thing sits in your membranes and it can be cleaved, it can be cut by molecular scissors in two different ways. And that depends on where you stand, whether you need the protection or not. So it's a little bit like a CEO. If everything's good, you've got the appropriate support and you know, think about a CEO sitting in the company saying, “Do we have the support of the board? Do we have the support of the community? Do we have enough cash flowing in? Do we want to build another building? Do we have new products on and on and on?” It’s looking at all those things and saying, “Can we go forward?” If that's the case in your brain you have the appropriate nutrients, you don't have any major pathogens, you don't have ongoing inflammation, you have appropriate trophic factors and sex hormones and all these things. Then this molecule APP is cleaved, is cut at a single site, which is essentially like the CEO sending out two memos. So you get cut at one site, you got two peptides. One memo is for public consumption and one of them is for internal consumption. It's telling itself and it's also telling the community times are good. We're going to be able to grow forth, make new synapses, make new memories. All is good. That's called the alpha site. APP is cleaved at the alpha site. That doesn't produce any of the amyloid.

[00:11:08] Now on the other hand, if things are bad. You have ongoing inflammation. You're low on your vitamin D, your testosterone, you have pathogens about, you have toxins you've been exposed to. Then it's like the CEO saying, “Hey, wait a minute. Times are bad. I've got to downsize.” So it's then cleaved at three alternative sites, which are the beta site, the gamma site, and the caspase site. Now you can imagine if you cleave something at three sites, you end up with four pieces, you know the head, the tail, and the two in between. Those four pieces are four memos. Two of them that go out to the public and two of them that come into the cell, and they are saying, “Things are not good, we need to downsize.” And by the way, one of those four memos is, guess what? Amyloid beta. It's the stuff that is made in the brains of Alzheimer's patients.

[00:12:02] So when we see someone with Alzheimer's, we're talking about someone who's been on the bad side of that integration. In other words, the CEO has been saying, “Downsize, downsize, downsize.” So our job is to say, “Okay, why is this downsizing signal coming? From what are you protecting yourself?” And then you have to look at a larger data dive, right? You need to know your homocysteine and your insulin, your fasting insulin and your mercury level and your copper zinc ratio, and on and on and on. You need to look at the things that are driving this system in the direction of making the amyloid. Now one of the interesting things, as I said, making the amyloid is a protective mechanism. You're literally, it's like bringing out the napalm, if you have your borders breached, then you say, “Okay, I've got to kill the invaders.” And in fact, some beautiful work by Professor Rudy Tanzi and Robert Moir from Harvard showed that the amyloid beta is an antimicrobial.

[00:13:05] So you're trying to kill the microbes which are present in the brains of so many patients with Alzheimer's disease. But again, that's not the only contributor. So you're making this stuff. You put down the napalm, you kill the invaders. But guess what? You're now living in a smaller country. So you are literally downsizing your arable soil. You're living in a smaller country, literally living with a downsized neural network. And the remarkable success of this as a protection is shown that this goes on for 20 years before you have full blown Alzheimer's. It shows how well you can do. You can still drive a car for many of those years. You can still play tennis, interact with your friends, read, write, calculate. It's amazing how much you can do.

[00:13:56] And somebody asked me one time, “Well, why does memory goes so earlier? That's such a bad thing.” “Well, yes, it's a bad thing.” But if I asked you, “Okay Jordan, you want to wake up tomorrow morning, you either want to forget how to read, how to write, how to do your job, how to calculate, how to interact with other people, or you forget the Friends rerun from tonight, which would you choose?”

Jordan Harbinger: [00:14:18] Yeah.

Dr. Dale Bredesen: [00:14:19] And that's exactly, that's an easy choice. So, in fact, you can do a tremendous amount with what you've learned so far. Your brain has kept only the most important things throughout your life. And so this is telling you, this is the canary in the mind when you're having trouble learning new things and that's why you want to jump on this, get yourself checked out and get on inappropriate program.

[00:14:43] One of the common things we hear is, “Wow! I can remember phone numbers again. I can remember, my appointments again.” And one of the other common things is the spouses will often tell me, “Oh yeah, there's so much more engaged.” I interact with them and they're just so much more present than they were before. So yeah, they're hitting on all cylinders again.

Jordan Harbinger: [00:15:02] So again, this isn't like a cancer where cells are going completely off the rails and they're doing something crazy. Alzheimer's sounds like a normal quote unquote brain housekeeping slash defense process. That's natural, but just very advanced. So like you said, it's better for the brain to go, “Hey, you can't remember where you put your car keys.” But you do have all of the things you need to do to survive. You kind of remember how to do basic things in your life. And then of course, as years and years and years go by where you become less and less functional. But in fact, that's actually amazing that the brain can go, “Look, we've been downsizing for 20 years. There's not much left to cut that isn't completely integral to survival.” Then you've got, “Oh, well look, your grandfather has Alzheimer's.” “Well, no kidding.” But this process that's defending the brain against, like you said, inflammation, nutritional issues, toxic exposure, et cetera. This stuff all started years and years ago attacking the brain, and it just shows up later on. And the idea that this is a protective response to inflammation or low nutrition and toxic exposure that leads to these three different types of Alzheimer's. So Alzheimer's isn't just -- this is this thing that causes this and you get this one disease, this is a process in the brain that's caused by multiple contributors.

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[00:17:21] Also everybody, don't forget about the LevelOne course that I created for you. I should say we, but look, I sat there and did a lot of this, all right? Took forever! LevelOne, what this is, is everything I wish I knew about networking, relationship development, well I shouldn't say everything. A lot of the things I wish I knew about networking and relationship development over the last 10, 15 years, and I created a bunch of drills and exercises for you based on that. And one of them, for example, is every morning in the coffee line or over your coffee, if you're making your coffee at home, scroll all the way down to the bottom of your text messages and text the last five people. You know the ones where it's like, “Oh, I sent this in February of 2016,” and I've got scripts for you and I've got ways to make sure that people respond engaging old and weak and dormant ties in your network and strengthening those relationships. And I just have a dozen plus drills like that that have really moved the needle for me. But don't take more than a few minutes per day, even a few minutes per week. And that is the LevelOne course. It is free. A lot of people are like, “Oh, I didn't know it was free.” It is free, of course, that's the whole idea. I'm trying to get you guys to get off your duffs and move the needle and see that you can actually do the networking and relationship development thing. It's at advancedhumandynamics.com/levelone, advancedhumandynamics.com/levelone.

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[00:19:37] Are there different types of Alzheimer's itself?

Dr. Dale Bredesen: [00:19:41] Yeah, and of course, that hadn't been said previously and what we did found is that we published this back in 2015, what we found is that when we started looking at people and we looked at the things that were actually causing their amyloid precursor protein to go in the quote wrong direction. And of course, things like phosphorylation of tau, and we talk about the importance of tau in the downsizing, that's critical. Absolutely. And that's downstream from the production of the amyloid. So we started looking at that and ask, “Why did these people have this? What is ongoing here?” Then we found that yes, these people actually will subset -- will fragment, so you can look at the different subsets. We can look at people and say, “Oh, okay, here's a person who has what we call sub type one or type one Alzheimer’s, which is inflammatory or hot Alzheimer's,” and that's people who have chronic activation of NF kappa B, for example, which is one of the inflammatory mediators.

[00:20:40] So you know, again, you expose yourself to things, whether it's pathogens or whether in fact you have a terrible, too much things like trans fats and things like that. You caused this chronic inflammation. If you have metabolic syndrome, which is very common, has hypertension, dyslipidemia and inflammation, and abnormalities in insulin resistance, you have a chronic inflammatory state. So that's type one, then there's type two. It's very different. It's cold. It is atrophic. It is due to a reduction. So if you think about it, think about it like a seesaw. You can be on the wrong side either because someone's pushing down on the wrong side or someone's pushing up on the other side. Either one of those will get you to the same place on the teeter-totter. Same idea here.

[00:21:34] You can have it because you've got too much inflammation. You're pushing out this amyloid because you're trying to fight something, or you can do it because you just don't have the support to build new synapses. You don't have the support to push yourself. So you've got to downsize, not because someone's invading you, you're downsizing because you have no soup and bread for everybody. So you've got a downside because you literally cannot support your system. And that includes everything from estradiol to vitamin D to testosterone, pregnenolone, thyroid, nerve growth factor, brain-derived neurotrophic factor, on and on and on. The trophic molecules that support your synapses are into short of supply. Well guess what? We can measure those. We can improve their supply so that you can now tip the balance in the right direction. So that is type two or cold Alzheimer's.

[00:22:30] And then there's actually a type 1.5 which has some of both, and that is glycotoxic or sweet. And this is when you've got too much sugar over years. And in fact, yes, that does contribute to cognitive decline, and that's certainly been shown repeatedly. So you have the combination of the inflammation or the type one from the fact that you've got glycated proteins. Of course, we measure it as hemoglobin A1C, but of course, it's glucose will stick on to many other proteins just like remoras on a shark. So you stick on there and your body then recognizes, “Hey wait, this protein is not quite normal.” You get inflammation so you get some type one, but you also get some type two because you now have insulin resistance. You've had to ramp up your insulin for so long that in fact you've turned down your response to insulin, and insulin doesn't just deal with glucose. It's also a very important trophic factor for your brain cells.

[00:23:35] So now you're not responding to insulin as well, and so you are again downsizing. So you have both hot and cold. You have glycotoxic or type 1.5 or sweet Alzheimer's. And then type three, the other major type is a toxic type. So if you are exposed to mercury or high doses of copper or biotoxins like mycotoxins that are produced by molds, you in fact make this goo that sticks to them. Amyloid actually is a very good binder for divalent metals like copper or like iron, for example, or mercury. And so if you've got very high levels, you will make some of this amyloid again as a protective measure.

[00:24:23] So for all of these reasons, you can make the amyloid and undergo this downsizing event. So we need to determine what subtype you have and no surprise, a lot of people will have subtypes, you know, one and two or one and three, for example, and that's why we wrote the program. This'll show you, for example, you have 70 percent type one and 20 percent type two and 10 percent type three and 0 percent type 1.5 as an example. Many people will have some combinations.

Jordan Harbinger: [00:24:54] So amyloid plaque, this binder gets between the synopsis and does the downsizing. We know that the symptoms are invisible for 15 to 20 years. Explain it like, I've never heard of this before. What do those symptoms start to look like? Because I think a lot of people go, “Oh, well, you know the symptoms don't show up till you're 75,” and it's like, “Well, not really though.” Right?

Dr. Dale Bredesen: [00:25:17] Right, exactly. Well, first of all, I should clarify. It's not the amyloid plaque that's the problem. The problem is when you make this stuff, you make all the oligomers, so imagine this, you've got, it's a little bit like Legos. You can have one Lego by itself. You can have two or three or four. You can have six or 12, et cetera, stuck together. In general, what's been found and each of these has a different function. When you look at a plaque, you're looking at millions stuck together. That's not so much the toxic problem. Now it's got its own issues, you essentially now have a little lake there and you will bring in inflammatory cells to begin to get rid of that. But here's the problem. The problem is when you have what's called the oligomers, so small groups together, those are the fighting units. Those are the ones that are antibacterial and those are the ones that are also synaptotoxic, single ones by themselves, not so much of a problem. Huge lakes, not so much of a problem. We've come to think of these big lakes as essentially forced.

[00:26:27] Imagine that you've got soldiers and they're really damaging when they're in their units, you've got groups of six or eight or 10, they're the ones that are going out and doing the damage, you know, one by himself who's often doesn't have his rifle with them walking around in town, getting a drink or something, not a problem. A big fort full of them, not damaging the community around, when you open the fort, when you let them out, when you let the oligomers out to fight the bacteria, the fungi, the viruses, the spirochetes, all those things. That's when they are active and that's when they are doing this damage. And unfortunately, it's not a perfect war. Yes, just like if you have a war in your town, there are going to be some innocents who are going to be killed. And so again, the idea of looking at it and seeing the killing and saying, “Okay, get rid of all the fighters.” You know that might sound good, but in fact what you really want to get rid of is why the war broke out to begin with.

Jordan Harbinger: [00:27:27] Right. Of course, addressing the cause always makes sense. What symptoms are we going to see initially? The earliest ones to the ones that that happen later on, right?

Dr. Dale Bredesen: [00:27:34] Yeah. Great point.

Jordan Harbinger: [00:27:35] Because of course when we see advanced, we look at like, “Oh well this person can't remember anything. They don't remember how to drive. They can't sleep.”

Dr. Dale Bredesen: [00:27:44] It's exactly right.

Jordan Harbinger: [00:27:45] What else were we looking at?

Dr. Dale Bredesen: [00:27:46] You know, that's exactly right. So as a very general rule, there are two kinds of presentations amnestic and non-amnestic. In other words, memory losing and non-memory losing. The more common one is the memory losing amnestic. That's the typical person we think of. And so people will notice early on things like, “I just can't remember phone numbers the way I used to.” Or “I'm forgetting my keys.” Now again, here's where everything has been so backwards. In the past because there's nothing you can do about that. You just say, “Oh, it's probably not Alzheimer's.” “Well, yeah, it probably isn't for some people,” but it could be the earliest manifestations, so get on it now. So in the past everything was about delay, delay, delay, because there's nothing we can do about it anyway. And I can't tell you how many people that have come in. So like they've been told by their doctors, “Yeah, you're not that bad.” Come in in a year, “Ah! It’s not Alzheimer's yet.” Come in in a year and then, “Oh, it's Alzheimer's.” Yeah, now there's nothing we can do about it. That doesn't help. We want to be proactive.

[00:28:49] So the earliest changes are either memory issues, and one of the common ones, by the way, is memory for space. So commonly people will say, “ I was driving down the street, I pulled up to a stop sign, totally my neighborhood. Place where I feel very comfortable, and suddenly I had no idea which way to turn.” So spatial memory is a common one. People will say, “Oh, my spouse asked me the same question three times at dinner.” Declarative memory, very common problem. Or they can have memory for other things as well -- facial recognition, another common one. So they'll say, “Oh, I went to my reunion. I knew, I knew this person, but I just didn't remember the name. I didn't remember much about how I had interacted. Did I really know them for sure?” These are all very presentations, and I go over, you know, each of these things in the book.

[00:29:44] On the other hand, there is a different approach, where different presentation, which is non-amnestic, and these are people who typically have problems with so-called executive function. People who have problems with, for example, putting things together. I often remember, I often ask people, “Hey, if you have to get out of town in an hour, can you really throw everything together?” “Oh, you know, I can't do that anymore. I just can't organize.” We interacted with one woman, for example, who said, “I was the person in the office who organized everything, and then I got to the point, I just could not organize these things anymore.”

[00:30:27] So organization, that's a common non-amnestic presentation. And then calculations, one person came in, first thing that happened, she could not figure out how to calculate a tip, and that's a relatively common thing to do. And then the visual perception problems, and this comes up commonly what's with what's called PCA or posterior cortical atrophy. So things that are typically by parietal. So you know, you have your parietal lobes that are in between your occipital lobes and your frontal lobes and also between occipital and temporal. So they're essentially the gateway. And these things are important for dressing. They are important for things called agnosia. So knowing how to do things, knowing specific not only tasks but also specific knowledge, recognition, things like this. And so you can think of it in a simple way, the ones who present with amnestic problems, this is largely a temporal lobe problem. And the ones that present with difficulties, with facial recognition and calculation and things like that. This is typically more of a parietal problem.

[00:31:51] But ultimately as you indicated, you get to both of those, but typically people will present with one or other. But here's the interesting thing. Virtually everybody who presents with the non-amnestic presentations turns out to have toxin exposures. So we need to know what are the toxin exposures, what's actually driving this, and we see it again and again. And interestingly, this is -- this kind of Alzheimer's which we call type three or toxic Alzheimer's is unusual and it's actually more closely related to Lewy body disease than it is related to the other kinds of Alzheimer's, and infected Lewy body disease, you also have toxin exposures. These people tend to look different from the amnestic ones, they tend to start earlier. Often these people will start in their 40s, and come in with significant Alzheimer's by the time they're in their late 40s, or up to mid-50s. And we do see some people who are older, but often it's in the late 40s, and early to mid-50s. They will often have some depression. So they often have some so-called HPA axis dysfunction, hypothalamus and pituitary and adrenal axis dysfunction.

[00:33:08] They will often have this non-amnestic presentation and they'll often be exquisitely sensitive to stress. So they stay up all night one night and they get much worse. They'll often be very sensitive to hormones. So if you give them bioidentical hormone replacement, they tend to improve. So these people tend to look different than the amnestic presenters. So you can imagine early on, you begin to get some of these things and yes, it should make you think, “Hey, I should get on it now. Let's check my cognition now. Let's get a cognoscopy, and let's make sure that I don't get Alzheimer's disease in the future.”

Jordan Harbinger: [00:33:50] I know a lot of this is genetic. And I know that you had said that cognitive decline is, is possible when it comes to this. What if we have the two or four copies of the ApoE4 gene, is it reversal of cognitive decline still possible with these people?

Dr. Dale Bredesen: [00:34:06] Oh, absolutely. In fact, so first of all, ApoE4, you get one from your mother and one from your father, so you either have zero, one or two copies. So for example, I checked myself, I’m an ApoE33, which is the most common one, that's kind of the generic. And ApoE4 is incredibly interesting. So this is Apolipoprotein E, which carries around lipid. It is a fat carrier. It's kind of like your butcher. It carries the fat around. And in fact, when we were a Samians between five and 7 million years ago, as you know, what happened is that the appearance of hominids occurred and in fact, at that time with the appearance of hominids came the appearance of ApoE4.

[00:34:55] So it was the primordial one, and in fact this comes in three flavors, three alleles, two, three and four. Each person has one copy of one, either a two or three or four from the mother and a two or three or four from the father. Now, about 25 percent of the population, about 75 million Americans have a single copy of ApoE4, and about 7 million Americans have two copies of ApoE4. If you have zero copies, your chance of getting Alzheimer's during your lifetime is about 9 percent, one in 11. If you have one copy, it's about 30 percent, if you have two copies is over 50 percent, so most likely you will get it during your lifetime.

[00:35:49] A program that we've developed actually works quite well. In fact, if anything, it works a little better for people who have ApoE4 for from people who don't have ApoE4. And we believe that that's because the people who have ApoE4 tend to have more inflammation and the ones who have ApoE3 tend to do more poorly with toxins and the toxin type, the type three is more difficult to treat. So what happened when the hominins appeared between 5 and 7 million years ago. There was a small number of changes that occurred in our genome as you indicated, and surprisingly a large number of these changes turned out to be related to proinflammatory changes among them ApoE4.

[00:36:33] So how does this work? That's something that's your butcher, that's carrying around the fat actually has something to do with your inflammation and Professor Tuck Finch from USC had suggested years ago that when you come down out of the trees, what are you doing? You're walking along the Savannah, you're stepping on dung, you're puncturing your feet, you're fighting with your brethren for food. You're fighting with your food as well. You're getting punctured, you're eating meat that is uncooked, and you're getting pathogens in your gut. For all of these things ApoE4 is an advantage because it produces a proinflammatory state that helps you. And in fact, if you are living under squalid third world conditions, you will survive a better as an ApoE4 than as an ApoE3.

[00:37:25] Now, just 4 percent of the time we've lived on Earth as hominids. We've had ApoE3, so only 220,000 years ago, ApoE3 appeared and then 80,000 years ago ApoE2 appeared. But ApoE3 is now the dominant one, it’s the most common one. So as I told my wife, if you look at my entire genome, it's actually more similar to a male chimp genome than it is to yours. And she said, “well, duh! You like ESPN, the chimp likes ESPN, that sort of thing.” So in fact, there aren't that many differences between a chimp genome and a human genome. And one of the critical ones is this ApoE.

[00:38:08] So what we found in the lab over the years is that when you look at what ApoE does, it actually enters the cell and goes into the nucleus, which hadn't been appreciated before. It interacts with 1700 different promoters, and for example, this SIRT1, which is so important for longevity and so important for Alzheimer's actually. And when it interacts with these things, it literally changes the programs in yourself. So the surprise was, not only as ApoE your butcher, it is also your Senator. It is also participating in changing the laws of the land. And so when you're reprogramming yourself, one of the things that occurs is a more proinflammatory state. And if you look at the list of these 1700 genes that are impacted by ApoE4, the list includes all of the things that you would imagine for Alzheimer's. It includes things related to inflammation, it includes things related to glucose toxicity and glucose handling and insulin resistance. It includes things related to response to hormones. So the surprises thing has a widespread effect and in fact it makes perfect sense why having one or two copies of ApoE4 would put you at increased risk for Alzheimer's disease.

Jordan Harbinger: [00:39:38] Interesting to see that the gene -- like everything in our body actually serves a purpose. Because one of my questions for you was, “Well, thanks a lot, we have this gene that gives us this stinking disorder. What is it good for?” There's always an answer to that if we look hard enough, right?

Dr. Dale Bredesen: [00:39:55] Absolutely.

Jordan Harbinger: [00:39:56] I find that pretty fascinating from just an evolutionary psychology or biology standpoint that, “Yeah, if you grow up and you're not drinking clean water and you're eating animals that eat other things because you don't have a choice and you can't cook things very well because of where you live, this is helping you out.” And “Yeah, in 30, 40 years, you pay the price, but you're not going to live that long anyway. Look where you live, you live in a dump. You're going to die before this catches up to you.” But now we live a long time, but we still eat crap. So explain to me like I'm five here. How does my brain get Alzheimer's? How do I give myself Alzheimer's? How does half of the Western world end up giving ourselves Alzheimer's?

Dr. Dale Bredesen: [00:40:36] Right. So this is the important, important point here, as you indicated. People keep saying, “Well, it's genetics.” So look, “My genetics, I'm going to get Alzheimer's. I have ApoE4.” “No, that's absolutely wrong.” What ApoE4 does is give you risk, you give yourself Alzheimer's by what you're exposed to, by the way you live in. In chapter four, I went into all these issues. Here's how you can give yourself Alzheimer's, and I wrote that specifically so that people could see how many of the things that are pro-Alzheimer's that they do. So the bottom line is “Yes, we have a major ability to impact our likelihood of getting it and to impact whether we can actually reverse the cognitive decline.” So look, Jordan, you want to wake up tomorrow and say, “Look, my goal for the rest of my life, I'm giving myself Alzheimer's.”

[00:41:25] Here's what you do. You stay up all night, you don't get any sleep. You don't allow your brain to clear out the damaged proteins. You don't allow it to get of the amyloid. You damage the synopsis. You increase the reactive oxygen species, so forth and so on. You don't induce autophagy, you get under constant and chronic stress. We were made to handle short bursts of stresses as of course, Professor Robert Sapolsky has shown so beautifully with his studies over the years. That's what we were made for. Short bursts of stress and then periods of non-stress. The way we live is the opposite. We have chronic mild stress and sometimes more than mild, that damages your hippocampus, that increases your cortisol, which in and of itself decreases the volume of your hippocampus. The area that's so critical in Alzheimer's, so critical for storing memories.

[00:42:13] You have a horrible diet. So you go out, get a bunch of trans fats, eat plenty of sugar, make sure that you have a fasting insulin that's off the charts. You should have a fasting insulin that's five or lower. And we see people who have fasting insulins of you know, 20, 30, 40. This is insulin resistance. You go out and you run up your lipids, you get your high LDL particle number, a low HDL. You make sure that you don't exercise. You make sure that you have a leaky gut. As you know, leaky gut was something not even recognized when I was in medical school, and it turns out to be very common and very important, important for Alzheimer's, important for Parkinson's, important for IBS, I mean on and on. This is a critical contributor. You damage your microbiome, you take a bunch of sodas and things like that. You expose yourself to toxins. We've all got -- already got copper in our pipes so you don't, you know, you don't worry about that. You don't eat green leafy vegetables, which turn out again to be, is helpful to do that. You avoid those, you get exposed to mycotoxins, and these are toxins that are produced by mold. Who new molds are, can actually contribute to cognitive decline. They absolutely do. Others have reported this as well. We first reported this back in 2016, and we see it all the time. You have poor dentition, so what happens is you get exposed to things like Percent gingivalis, which is a bacterium from poor dentition. Fusobacterium nucleatum, another one.

Jordan Harbinger: [00:43:56] Poor dentition, meaning like you don't brush your teeth?

Dr. Dale Bredesen: [00:43:58] Yeah. And so by the way, a lot of people like now to do the oil pulling, which is actually helpful as well.

Jordan Harbinger: [00:44:05] What is oil pulling?

Dr. Dale Bredesen: [00:44:07] Oil pulling is something that was actually done by the ayurvedic of thousands of years ago. And the idea, you take some coconut oil and you swish it into your teeth for about five minutes. Again, many people do this. It actually improves dentition, and so again, the idea of having bad teeth turns out to be a bad thing for systemic inflammation. So whether your systemic inflammation is because of a horrible diet, because of pathogen exposure, because of a leaky gut, because of poor dentition, because of chronic wounds that are poorly healed, whatever it is, this is contributing to your requirement to protect yourself, in which case you will produce some of the amyloid and you will begin the downsizing process. So all of those things are critical and yes, diet, exercise, sleep stress and brain training, all of those are critical. If you fail on those, you are contributing. So in fact, again, just as we monitor ourselves over the years for our cholesterol, we monitor ourselves for obesity and for our weight. Those are things we think about every day. We should do the same for our cognition and we can have a huge impact if we do so.

Jordan Harbinger: [00:45:25] Okay, so leaky gut, we've been hearing about this for a while. I don't want to get into that. It does, I will note, sound disgusting. But it's caused I know by a lot of things like gluten, et cetera. I didn't realize the human body isn't designed to process over 15 grams of sugar a day. And that doesn't just count sugary foods, but simple carbs like white bread and things like that, that causes insulin resistance. I mean, there are things that people drink that I certainly drank as a kid that had three times that in one glass.

Dr. Dale Bredesen: [00:45:52] Absolutely. And I drank them as a kid too, and I certainly drank them as an intern trying to stay up all night. So absolutely, and here's the problem. Our bodies, and this is a lot about complex chronic illness. As you know, in the 20th century, many people died from simple acute illnesses, especially in the first half of the 20th century -- pneumococcal pneumonia, tuberculosis, diphtheria, things like that. And of course, the great success of 20th century medicine was to combine public health policy with antibiotics to make these diseases an uncommon cause of death.

[00:46:31] Now the problem is we are dying of 21st century illnesses because we are still practicing 20th century medicine, which is you wait for symptoms, you write a prescription, you send them home. That's not the way these diseases work. 21st century diseases -- Alzheimer's, cancer, cardiovascular disease, type two diabetes, on and on. These are complex chronic illnesses that have many different things that contribute to them, and therefore, you need to look at these. The good news is you can see them coming for years ahead of time. And so yes, you need to include all these different things and the things we just talked about and things like your gut leak. And by the way, as you pointed out, that 15 grams of sugar, more than that, and here's the issue. We weren't made. So we are living in a way that our bodies were not produced to live.

[00:47:31] So here's an example. If you said, “Hey Dale, let's go out.” We decided there's a new fun thing we're all going to do and that's jumping out a third floor windows. Well, some people are going to survive that and some people are not. It's like, “Yeah, but it's fun. This is what we do every day.” Well, our bodies weren't made to do that. So a lot of 21st century illness is actually because we are living in a way that is evolutionarily inappropriate. We were not designed evolutionarily to eat a lot of sugar. We were not designed evolutionarily to stay up all night. The reality is we really weren't designed to have lights on at night. We were designed to have light dark cycles there with the sun, and so we're already pushing the envelope when we're sitting there at night. And I'm absolutely guilty of this myself, so we have to be careful, and so in fact, I'm dealing with some people who have macular degeneration. We need to look at how much blue light exposure. The diseases that we are talking about, these complex chronic and especially the neurodegenerative diseases of which there are many as you know in Parkinson's and Lewy body, macular degeneration, frontotemporal dementia, progressive supranuclear paralysis, corticobasal degeneration, on and on. These things are essentially mismatches between our supply and demand, and they occur because we are not living in the way we are designed to live and we are not exposed to the appropriate environment, and now many of us get away with it. But as you indicated, genetics will play a role.

[00:49:07] So these things are all written onto our genome, and when we have a sensitive genome to one thing or another, we have an increased risk to go down the Alzheimer's pathway or the Parkinson's pathway. So that's why the genetics are important, but they confer risk and they – the vast majority of cases do not confer absolute determinism, it is simply risk. So we want to know what we're at risk for and we want to get on it. As you know, when the first genome was sequenced from James Watson, he did not want to know one gene, which was a ApoE, because he said, “There's nothing you can do about it.” Well now, there's a lot you can do about it. And so there's a wonderful website started by a woman named Julie G, who started a website called ApoE4.info. There are over 3000 people on that website who are actively looking at their own status and what they can do, and in fact, the vast majority of them are on some version of the protocol that I described in the book, and they are actively preventing their own cognitive decline.

Jordan Harbinger: [00:50:17] So Dr. Bredesen, we need to address as many holes or as many contributors to Alzheimer's as we can. There's 36, you said now there's going to be like 50, which isn't a thousand, which is good news. So we address the root causes, like the cause of inflammation, not just the inflammation itself, the leaky gut, not just the leaky gut itself, the causes of leaky gut. So what we're trying to do from the sound of it is reached a tipping point where synapse creation eclipses synapse destruction by the protective mechanisms in the brain. And I know people are going, “But what about medication?” And it sounds like, “Yes, we'll use medication, but it's not even the first line of defense.” It's kind of like buttering the bread. You don't just start housing the butter. You've got to have something, and by the way, don't eat any bread. But if you were to use bread in an analogy for Alzheimer's, we need that, right?

[00:51:04] So we don't want, we don't want to have just a time where we're growing. All right, well they're going to figure out some pill to get rid of this, because the pill will just get rid of the protective mechanism, but it's not going to get rid of the mold in your house. It's not going to get rid of the stuff that you're eating that's causing the inflammation. It's not going to get rid of the other problems that are causing your brain to react. Because we don't want to turn off our defense mechanisms. It's kind of like saying, “Well, I'm so sick of getting cuts., I should just take all my skin off and then I won't have to worry about it anymore.” You'd never do that to your body, but we do it to our brain.

Dr. Dale Bredesen: [00:51:36] It’s a really good point actually. And so we tell people that, “Look, there are 36 holes in your roof. And if you've got certain things like a leaky gut or if you've got low vitamin D or you've got high homocysteine, those particular holes are open wide. On the other hand, let's say you have an optimum B12 and you have an optimum vitamin D or an optimum testosterone, or you have no pathogens that you're dealing with, then those holes are pretty much closed. So here's the thing, a drug is a very good patch, a tight, a wonderful patch for one hole. So my argument is, “Look, the drugs are going to be very, very important, but we've been asking them to do too much.” We've been asking the drugs to do about a hundred different things, that's too many things. So what we need to do is to combine, and think about even with something as simple as HIV, a little retro virus, it took three drugs to have a big impact, and that really changed the world.

[00:52:34] So with Alzheimer's, we need to have an entire program. So this is programmatics not monotherapeutics, we need to know which holes are open the widest and we need to know that we can cover all of them. So yes, it's relatively straightforward to get tested, to get a cognoscopy. You want to find out where you stand and we can break it down into the groups that go along with the subtypes. You want to know, “Do I have ongoing chronic systemic inflammation?” So what's my hsCRP? You might want to check your IL6, or TNF alpha, but hsCRP is a good one to start with. Do I have pathogens? Do I have chronic herpetic family viruses? Do I have chronic spirochetes? Do I have chronic fungi? Do I have chronic bacterial infections? Those are all important to know. So those are all related to type one, and in fact, do I have ongoing activation of my innate immune system? These are all things you can look at with blood and simple urine tests. Then type two, do I have suboptimal levels of specific trophic factors, hormones, nutrients? All the things that you need to support your synapses.

[00:53:57] So if you're walking around with a as so many people are with the vitamin D of 19 or 20 or 21, you want it to be more up in the 50 to 80 range. You want it to be optimal, and so you want to know what that is. And similarly, testosterone, estradiol, pregnenolone, progesterone, thyroid hormone, your cortisol, DHEA, all of these things are critical to know. What's your B12? What's your homocysteine level? What's your B6? What's your folate? These are all important as supports. And yes, you know, if you're living a perfect life, if you're doing things right, then you may not need to worry about these.

But for most of us who are living in Western societies, we need to know whether we have optimal levels of those things.

[00:54:47] Professor Clayton, by the way, from the UK as pointed out, in fact that our soils are so bad now, that our typical nutrition that we get from our meals is worse than it was during King Henry VII style. So in fact, we -- you know, a lot of us are malnourished and simply don't know it. That does contribute to multiple things such as suboptimal cognition. All right, let's go to type 1.5, so you want to know what your fasting insulin is. You want to know what your hemoglobin A1c is. So you want to know if you have insulin resistance. Critical, absolutely critical. By the way, the higher those are, the more you have an association with shrinkage of your hippocampus and you can literally go and put that on a line.

[00:55:34] Similarly, the higher your homocysteine on average, the smaller your hippocampus, the more rapidly it will begin to atrophy with age. Then you want to know for type three, do I have exposure to toxins? And this has been the tough one because toxins are ubiquitous as we know. So you want to know about metalotoxins. What about mercury? What about your copper zinc ratio? What's your level of ferritin? These sorts of things. Now, again, it's tricky. These metals are important things like copper and zinc and iron are important for your life as well. So no big surprise. You need some, you need not too much, and like everything else in biology.

[00:56:22] So now what about organic toxins? Dr. Joseph Pizzorno from Seattle has shown that in fact people with Alzheimer's do tend to have more exposure to things like DDE, so there are organic toxins.

Again, you are responding to these toxins, and then you need to know what about biotoxins? These are things made by organisms, so things like trichothecenes. And you can measure these easily in the urine, for example, if you're exposed to molds and there are specific ones, things like stachybotrys and penicillium and aspergillus and chaetomium. These are specific molds that produce specific toxins, which can be neurotoxic and immunotoxic and otherwise toxic genotoxic as well. So these things can contribute to cognitive decline. And as I said, these are the tough ones to treat because they often have multiple biotoxins and you've literally got to get rid of these things.

[00:57:28] And I should note, as I mentioned earlier, these things tend to give you presentation around the time of your 50s, menopause basically. And what's happening is you store these toxins, you sequester them in your bones among other places when you are younger, then as you get to menopause, you are beginning to release some things like mercury, go back up again. And so that's probably why you tend to get these problems at that time. So you want to know all those toxins. And then from that, you want to know what subtype am I at risk for? And then what is my optimal program that I could work on with my doctor and my health coach to prevent my cognitive decline, or if it's already started to reverse it. And by the way, we see this all the time. I had a woman for example, who came in and she said, “I want to prevent, she took the MoCA, her MoCA was 23, she already was well into MCI. And then of course, when she got on the program, her MoCA score went to 30, which is perfect. And she said, “ I didn't realize how much I'd lost until I got better.” And we hear this sort of thing all the time.

Jordan Harbinger: [00:58:32] So it's never too early to test for Alzheimer's. And of course, the genetic markers. We can link to 23andMe on the show notes, but where do I get the other tests that you'd mentioned? If I go to my doctor and I ask for all of these, aren't they just going to go, “Wait a minute, I'm not writing all these for you.” You might have to pay out of pocket for these, right? If it's from the sound of it.

Dr. Dale Bredesen: [00:58:50] You can go to the website, drbredesen.com. You can take a look at the book. There's a list, check chapter seven and eight. We go through the whole list and now we are actually just bringing out, so within the next few weeks you'll be able to get your direct to consumer, just like a 23andMe sort of thing, where you'll be able to get all the testing and a report.

Jordan Harbinger: [00:59:09] Great. Dr. Bredesen, thank you so much. This is a little scary but also enlightening and good to know that we can start to prevent what was previously thought inevitable, if we just do the right things and pay attention.

Dr. Dale Bredesen: [00:59:21] Actually that's so true. So let's all work together to reduce the global burden of dementia. It's something that's absolutely within our reach now.

Jordan Harbinger: [00:59:29] Great big thank you to Dr. Dale Bredesen. The book title is The End of Alzheimer's. If you enjoyed this one, don't forget to thank Dr. Bredesen on Twitter. Tweet at me your number one takeaway here from Dr. Bredesen. I'm @jordanharbinger on both Twitter and Instagram. And don't forget, if you want to learn how to apply everything you heard from Dr. Bredesen, make sure you go grab the worksheets also in the show notes on our website at jordanharbinger.com/podcast.

[00:59:56] This episode was produced and edited by Jason DeFillippo. Show notes by Robert Fogarty, booking back office and last minute miracles by Jen Harbinger, and I'm your host, Jordan harbinger. The fee for the show is that you share it with friends when you find something useful, which should hopefully be in every episode. So please share the show with those you love and even those you don't. We've got a lot more like this in the pipeline. We are very excited to bring it to you and in the meantime, do your best to apply what you hear on the show so you can live what you listen, and we'll see you next time.

imer's is actually three different syndromes with 40 plus different contributors, some of which you're exposing yourself to right now. It's not audio, relax.

[00:00:49] We'll also uncover some of the symptoms of cognitive decline. Why and when you should be worried about them, especially if you're pushing 40, listen up to this part of the show. And we'll explore how cognitive decline can be slowed and even reversed and know it doesn't require some magic pill or supplement. In fact, you might be surprised to find out what the best means to attack this set of contributors to cognitive decline actually is or are. There's a lot here on this show. It may sound a bit complicated at first. We'll do our best to make it digestible here, and don't forget we have worksheets for today's episode so you can make sure that you solidify your understanding of the key takeaways from Dr. Bredesen here. That link is in the show notes at jordanharbinger.com/podcast.

[00:01:32] Now, here's Dr. Dale Bredesen. I don't think there's anyone that hasn't been touched by Alzheimer's in some way. You can't escape the news about this disease. I have aging parents every time they forget anything now I'm like, “Oh no! Oh my gosh.” You know, and my mom will say, “Oh, this is how it begins.” And she's kind of not joking, and it's a little scary, and there's further -- you mentioned in the book as well, there's no new Alzheimer's drugs since 2003, and this is the only disease in the top 10 causes of death with no real treatment whatsoever. And that's terrifying for people like me, 38 pushing 40. This disease takes down the rich and the poor, the educated in the on educated. No one's immune, no one's privileged. This is like -- this is one of those terrible equalizers.

Dr. Dale Bredesen: [00:02:17] That's exactly right. And the thing is, it is something that concerns us as we age. And as you know, it is now the number one cause of aging Americans, it has past cancer as the concern. So everybody's concerned what's going to happen to my cognition. And the reality is we have a situation where everything needs to change.

[00:02:38] Number one, we should be checking, get a quote, what I call a cognoscopy. Everybody knows you get a colonoscopy when you're 50, you know if you're 45 or older or if you've got parents who have dementia, you should think seriously about a cognoscopy. It's not a difficult thing to do. You get some blood and urine tests, you get an online cognitive assessment and you can determine where you stand and what your risk factors. No different than 40 years ago people said, “Oh, I need to check my cholesterol.” “Oh, okay,” so same idea. And so you know, this is an important to have.

[00:03:09] And then the second thing is you need to be working on it actively. So yeah, if your parents are concerned or if you are concerned, do some brain training, get on the right diet, exercise, sleep, stress. That's why we generated this computer program that looks at what is a subtype or subtypes that you are at risk for, or already beginning to show. And then here are the things that you can do optimally to address this. I mean, it's amazing how many of these things have kind of elephants in the room.

[00:03:38] One of the big ones is you go in to see a physician and you say, “I'm having some problems with cognition.” He or she doesn't ask what's causing it. You say, well, they say, “Oh, you have an early Alzheimer's.” Okay, “What's causing it?” “Well, it's early Alzheimer's.” “Well, wait a minute, I need to know what are all the things.” This is very much like taking your car in, mechanic says to you, “Oh, we yet we recognize this, “this is Car Not Working Syndrome.” And you say, “Well, wait a minute. I mean, what's causing it?” “Well, the Car Not Working Syndrome, we don't know what causes it and there's no cure.” And older cars tend to get it. And you'll say, “Well wait a minute, aren't you going to check some, -- get to check the gas, the oil, et cetera?” They has going to say, “No, those aren't reimbursed.” And that's exactly what's happening right now. We go in and we're told it's early Alzheimer's, nothing to do. Well. In fact, if you look at larger datasets, which is part of 21st century medicine, you can ask, “What is the status? Do I have insulin resistance? Do I have the chronic activation of my innate immune system? If so, what's causing it?”

[00:04:38] And so the whole idea here is you need to look at all of the contributors and we described in the book that there were 36 we initially identified. It's going to be end up being closer to 50, but it's not thousands. You know, there's a finite, there's dozens of things that contribute to cognitive decline and you can measure them and you can address them and you can prevent the problem and you can reverse it, the earlier, the better. Though later, you can still get some times and sometimes you don't. But looking at the critical causes, all of the root cause contributors is absolutely crucial and not being done at the major centers.

Jordan Harbinger: [00:05:18] When you say not reimbursed, is that what you're talking about is doctors in hospitals won't necessarily check for cognitive impairment because early Alzheimer's is considered kind of the end of the story. And then they say, “Look, I could run a bunch of tests, but insurance isn't going to pay for it. And since we have collectively kind of given up on treating this with drugs, we're not going to look for alternative ways to deal with this. You're just going to have to suffer and live with this for the next 30, 20 years, whatever, until you die this sort of sad Alzheimer's death.” And that seems terrible, especially because if we know that cognitive decline can be reversed and that not all is lost and later on in the show we'll discuss some steps we can take now if we see that. It seems kind of unfair, and what I took from the book was if you are dealing with some cognitive decline, you shouldn't go, “Well, this is what it means getting older, no problem there.” It's kind of like you get a wound on your leg and it's bleeding. You don't go, “Yeah, I guess that's just going to bleed forever until I'm dead.” Right? You put a bandage on it, you try to figure it out. If there's other things you can do, but with Alzheimer's it's just like, “Oh well, I guess that's in your brain, and unless they come up with a brand new drug, which again they haven't for the last 15 years now, you're screwed!” And that's not good news for anybody.

Dr. Dale Bredesen: [00:06:35] And this is exactly the issue, the very tests that you need to determine what is causing your cognitive decline are the very tests that are not reimbursed. How ridiculous is that? So for example, you can get a reimbursed MRI and that can tell you, “Oh yeah, you've got some atrophy in your hippocampus.” Okay, but that doesn't tell you what's causing, and you say, “Look, I want to know if I have insulin resistance. I want to know if there are various pathogens that are causing this response.” And as I mentioned in the book, there’s a big surprises Alzheimer's disease is actually a protective response to multiple different insults. That's the big surprise.

[00:07:15] So getting rid of the protection is not the right way to go. You want to understand what caused the problem and then yeah, it's fine to get rid of the amyloid after you've got rid of what's causing you to make it. Amyloid is a little bit like napalm. You're putting it down because you have been invaded. So you want to know what pathogens are there. You want to know if your innate immune system is activated. You want to know specific toxins -- organic toxins, metalotoxins, biotoxins.

You want to know about specific nutrient deficiencies and responses to those. Methylation defects, these things are all contributors to this thing that ultimately ends up as Alzheimer's and as you know by the time you get a diagnosis of full blown Alzheimer's, the underlying process has been going on typically for 20 years or so. And so yes, you need to know what causes and preferably you look at it when you're in your 40s or early 50s, for example, and say, “Okay, here are the things that are putting me at high risk for Alzheimer's.” I can address them now literally, and this is not a joke, this disease should be a rare disease. It should mostly end with this generation. If everybody looks, if everybody gets on the appropriate prevention and early reversal program, this should be a rare, rare disease.

Jordan Harbinger: [00:08:38] That's really good news. The other good news, or I guess news, it might just be general here, but that everyone over 40, you'd said in the book is starting to hit some cognitive decline. So everyone 40 and up are close like me, especially in their 50s, needs to be paying to this. And I guess the good news part of this is that it can be addressed now and that we can slow and reverse it. And we found some ways to do that. We had no hand in this view, and then other doctors and researchers have found ways to deal with this.

[00:09:09] First though, let's talk about what is and what is not Alzheimer's. Because I think first of all, most of us, including myself, had no idea and have no idea what this actually is. It's not like a cancer where cells aren't doing what they're supposed to do. This is something completely different, right?

Dr. Dale Bredesen: [00:09:25] Absolutely. So as I mentioned, so there is a molecule in your brain, you know, and it's one of your -- it comes from one of your 20,000 genes, which is called amyloid precursor protein, and we discovered that this thing actually works like a molecular switch. So this thing sits in your membranes and it can be cleaved, it can be cut by molecular scissors in two different ways. And that depends on where you stand, whether you need the protection or not. So it's a little bit like a CEO. If everything's good, you've got the appropriate support and you know, think about a CEO sitting in the company saying, “Do we have the support of the board? Do we have the support of the community? Do we have enough cash flowing in? Do we want to build another building? Do we have new products on and on and on?” It’s looking at all those things and saying, “Can we go forward?” If that's the case in your brain you have the appropriate nutrients, you don't have any major pathogens, you don't have ongoing inflammation, you have appropriate trophic factors and sex hormones and all these things. Then this molecule APP is cleaved, is cut at a single site, which is essentially like the CEO sending out two memos. So you get cut at one site, you got two peptides. One memo is for public consumption and one of them is for internal consumption. It's telling itself and it's also telling the community times are good. We're going to be able to grow forth, make new synapses, make new memories. All is good. That's called the alpha site. APP is cleaved at the alpha site. That doesn't produce any of the amyloid.

[00:11:08] Now on the other hand, if things are bad. You have ongoing inflammation. You're low on your vitamin D, your testosterone, you have pathogens about, you have toxins you've been exposed to. Then it's like the CEO saying, “Hey, wait a minute. Times are bad. I've got to downsize.” So it's then cleaved at three alternative sites, which are the beta site, the gamma site, and the caspase site. Now you can imagine if you cleave something at three sites, you end up with four pieces, you know the head, the tail, and the two in between. Those four pieces are four memos. Two of them that go out to the public and two of them that come into the cell, and they are saying, “Things are not good, we need to downsize.” And by the way, one of those four memos is, guess what? Amyloid beta. It's the stuff that is made in the brains of Alzheimer's patients.

[00:12:02] So when we see someone with Alzheimer's, we're talking about someone who's been on the bad side of that integration. In other words, the CEO has been saying, “Downsize, downsize, downsize.” So our job is to say, “Okay, why is this downsizing signal coming? From what are you protecting yourself?” And then you have to look at a larger data dive, right? You need to know your homocysteine and your insulin, your fasting insulin and your mercury level and your copper zinc ratio, and on and on and on. You need to look at the things that are driving this system in the direction of making the amyloid. Now one of the interesting things, as I said, making the amyloid is a protective mechanism. You're literally, it's like bringing out the napalm, if you have your borders breached, then you say, “Okay, I've got to kill the invaders.” And in fact, some beautiful work by Professor Rudy Tanzi and Robert Moir from Harvard showed that the amyloid beta is an antimicrobial.

[00:13:05] So you're trying to kill the microbes which are present in the brains of so many patients with Alzheimer's disease. But again, that's not the only contributor. So you're making this stuff. You put down the napalm, you kill the invaders. But guess what? You're now living in a smaller country. So you are literally downsizing your arable soil. You're living in a smaller country, literally living with a downsized neural network. And the remarkable success of this as a protection is shown that this goes on for 20 years before you have full blown Alzheimer's. It shows how well you can do. You can still drive a car for many of those years. You can still play tennis, interact with your friends, read, write, calculate. It's amazing how much you can do.

[00:13:56] And somebody asked me one time, “Well, why does memory goes so earlier? That's such a bad thing.” “Well, yes, it's a bad thing.” But if I asked you, “Okay Jordan, you want to wake up tomorrow morning, you either want to forget how to read, how to write, how to do your job, how to calculate, how to interact with other people, or you forget the Friends rerun from tonight, which would you choose?”

Jordan Harbinger: [00:14:18] Yeah.

Dr. Dale Bredesen: [00:14:19] And that's exactly, that's an easy choice. So, in fact, you can do a tremendous amount with what you've learned so far. Your brain has kept only the most important things throughout your life. And so this is telling you, this is the canary in the mind when you're having trouble learning new things and that's why you want to jump on this, get yourself checked out and get on inappropriate program.

[00:14:43] One of the common things we hear is, “Wow! I can remember phone numbers again. I can remember, my appointments again.” And one of the other common things is the spouses will often tell me, “Oh yeah, there's so much more engaged.” I interact with them and they're just so much more present than they were before. So yeah, they're hitting on all cylinders again.

Jordan Harbinger: [00:15:02] So again, this isn't like a cancer where cells are going completely off the rails and they're doing something crazy. Alzheimer's sounds like a normal quote unquote brain housekeeping slash defense process. That's natural, but just very advanced. So like you said, it's better for the brain to go, “Hey, you can't remember where you put your car keys.” But you do have all of the things you need to do to survive. You kind of remember how to do basic things in your life. And then of course, as years and years and years go by where you become less and less functional. But in fact, that's actually amazing that the brain can go, “Look, we've been downsizing for 20 years. There's not much left to cut that isn't completely integral to survival.” Then you've got, “Oh, well look, your grandfather has Alzheimer's.” “Well, no kidding.” But this process that's defending the brain against, like you said, inflammation, nutritional issues, toxic exposure, et cetera. This stuff all started years and years ago attacking the brain, and it just shows up later on. And the idea that this is a protective response to inflammation or low nutrition and toxic exposure that leads to these three different types of Alzheimer's. So Alzheimer's isn't just -- this is this thing that causes this and you get this one disease, this is a process in the brain that's caused by multiple contributors.

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[00:17:21] Also everybody, don't forget about the LevelOne course that I created for you. I should say we, but look, I sat there and did a lot of this, all right? Took forever! LevelOne, what this is, is everything I wish I knew about networking, relationship development, well I shouldn't say everything. A lot of the things I wish I knew about networking and relationship development over the last 10, 15 years, and I created a bunch of drills and exercises for you based on that. And one of them, for example, is every morning in the coffee line or over your coffee, if you're making your coffee at home, scroll all the way down to the bottom of your text messages and text the last five people. You know the ones where it's like, “Oh, I sent this in February of 2016,” and I've got scripts for you and I've got ways to make sure that people respond engaging old and weak and dormant ties in your network and strengthening those relationships. And I just have a dozen plus drills like that that have really moved the needle for me. But don't take more than a few minutes per day, even a few minutes per week. And that is the LevelOne course. It is free. A lot of people are like, “Oh, I didn't know it was free.” It is free, of course, that's the whole idea. I'm trying to get you guys to get off your duffs and move the needle and see that you can actually do the networking and relationship development thing. It's at advancedhumandynamics.com/levelone, advancedhumandynamics.com/levelone.

[00:18:43] And this is the stuff that -- one thing I want to mention, a lot of people go, “Well you know I don't have time right now because I'm doing another online course.” You cannot make up for lost time when it comes to networking and relationship development. A lot of small business people, even people we know, Jason, are learning that the hard way right now. You can't just take over someone's Rolodex. You can't just go, “Oh it's been so long, but now I'm launching a product. I got to reengage my network.” It doesn't work like that. That is suboptimal. The idea, it's like fitness, right? Getting into shape, hard. Staying in shape, that's reasonable after you've done it for a long time, not nearly as hard because this is about habit change. So don't try to get it all down when you need it. It's too late to dig the well when you're thirsty. Advancedhumandynamics.com/levelone is where that's at. And I'd love feedback on this because I'm busy making LevelTwo right now as well.

[00:19:37] Are there different types of Alzheimer's itself?

Dr. Dale Bredesen: [00:19:41] Yeah, and of course, that hadn't been said previously and what we did found is that we published this back in 2015, what we found is that when we started looking at people and we looked at the things that were actually causing their amyloid precursor protein to go in the quote wrong direction. And of course, things like phosphorylation of tau, and we talk about the importance of tau in the downsizing, that's critical. Absolutely. And that's downstream from the production of the amyloid. So we started looking at that and ask, “Why did these people have this? What is ongoing here?” Then we found that yes, these people actually will subset -- will fragment, so you can look at the different subsets. We can look at people and say, “Oh, okay, here's a person who has what we call sub type one or type one Alzheimer’s, which is inflammatory or hot Alzheimer's,” and that's people who have chronic activation of NF kappa B, for example, which is one of the inflammatory mediators.

[00:20:40] So you know, again, you expose yourself to things, whether it's pathogens or whether in fact you have a terrible, too much things like trans fats and things like that. You caused this chronic inflammation. If you have metabolic syndrome, which is very common, has hypertension, dyslipidemia and inflammation, and abnormalities in insulin resistance, you have a chronic inflammatory state. So that's type one, then there's type two. It's very different. It's cold. It is atrophic. It is due to a reduction. So if you think about it, think about it like a seesaw. You can be on the wrong side either because someone's pushing down on the wrong side or someone's pushing up on the other side. Either one of those will get you to the same place on the teeter-totter. Same idea here.

[00:21:34] You can have it because you've got too much inflammation. You're pushing out this amyloid because you're trying to fight something, or you can do it because you just don't have the support to build new synapses. You don't have the support to push yourself. So you've got to downsize, not because someone's invading you, you're downsizing because you have no soup and bread for everybody. So you've got a downside because you literally cannot support your system. And that includes everything from estradiol to vitamin D to testosterone, pregnenolone, thyroid, nerve growth factor, brain-derived neurotrophic factor, on and on and on. The trophic molecules that support your synapses are into short of supply. Well guess what? We can measure those. We can improve their supply so that you can now tip the balance in the right direction. So that is type two or cold Alzheimer's.

[00:22:30] And then there's actually a type 1.5 which has some of both, and that is glycotoxic or sweet. And this is when you've got too much sugar over years. And in fact, yes, that does contribute to cognitive decline, and that's certainly been shown repeatedly. So you have the combination of the inflammation or the type one from the fact that you've got glycated proteins. Of course, we measure it as hemoglobin A1C, but of course, it's glucose will stick on to many other proteins just like remoras on a shark. So you stick on there and your body then recognizes, “Hey wait, this protein is not quite normal.” You get inflammation so you get some type one, but you also get some type two because you now have insulin resistance. You've had to ramp up your insulin for so long that in fact you've turned down your response to insulin, and insulin doesn't just deal with glucose. It's also a very important trophic factor for your brain cells.

[00:23:35] So now you're not responding to insulin as well, and so you are again downsizing. So you have both hot and cold. You have glycotoxic or type 1.5 or sweet Alzheimer's. And then type three, the other major type is a toxic type. So if you are exposed to mercury or high doses of copper or biotoxins like mycotoxins that are produced by molds, you in fact make this goo that sticks to them. Amyloid actually is a very good binder for divalent metals like copper or like iron, for example, or mercury. And so if you've got very high levels, you will make some of this amyloid again as a protective measure.

[00:24:23] So for all of these reasons, you can make the amyloid and undergo this downsizing event. So we need to determine what subtype you have and no surprise, a lot of people will have subtypes, you know, one and two or one and three, for example, and that's why we wrote the program. This'll show you, for example, you have 70 percent type one and 20 percent type two and 10 percent type three and 0 percent type 1.5 as an example. Many people will have some combinations.

Jordan Harbinger: [00:24:54] So amyloid plaque, this binder gets between the synopsis and does the downsizing. We know that the symptoms are invisible for 15 to 20 years. Explain it like, I've never heard of this before. What do those symptoms start to look like? Because I think a lot of people go, “Oh, well, you know the symptoms don't show up till you're 75,” and it's like, “Well, not really though.” Right?

Dr. Dale Bredesen: [00:25:17] Right, exactly. Well, first of all, I should clarify. It's not the amyloid plaque that's the problem. The problem is when you make this stuff, you make all the oligomers, so imagine this, you've got, it's a little bit like Legos. You can have one Lego by itself. You can have two or three or four. You can have six or 12, et cetera, stuck together. In general, what's been found and each of these has a different function. When you look at a plaque, you're looking at millions stuck together. That's not so much the toxic problem. Now it's got its own issues, you essentially now have a little lake there and you will bring in inflammatory cells to begin to get rid of that. But here's the problem. The problem is when you have what's called the oligomers, so small groups together, those are the fighting units. Those are the ones that are antibacterial and those are the ones that are also synaptotoxic, single ones by themselves, not so much of a problem. Huge lakes, not so much of a problem. We've come to think of these big lakes as essentially forced.

[00:26:27] Imagine that you've got soldiers and they're really damaging when they're in their units, you've got groups of six or eight or 10, they're the ones that are going out and doing the damage, you know, one by himself who's often doesn't have his rifle with them walking around in town, getting a drink or something, not a problem. A big fort full of them, not damaging the community around, when you open the fort, when you let them out, when you let the oligomers out to fight the bacteria, the fungi, the viruses, the spirochetes, all those things. That's when they are active and that's when they are doing this damage. And unfortunately, it's not a perfect war. Yes, just like if you have a war in your town, there are going to be some innocents who are going to be killed. And so again, the idea of looking at it and seeing the killing and saying, “Okay, get rid of all the fighters.” You know that might sound good, but in fact what you really want to get rid of is why the war broke out to begin with.

Jordan Harbinger: [00:27:27] Right. Of course, addressing the cause always makes sense. What symptoms are we going to see initially? The earliest ones to the ones that that happen later on, right?

Dr. Dale Bredesen: [00:27:34] Yeah. Great point.

Jordan Harbinger: [00:27:35] Because of course when we see advanced, we look at like, “Oh well this person can't remember anything. They don't remember how to drive. They can't sleep.”

Dr. Dale Bredesen: [00:27:44] It's exactly right.

Jordan Harbinger: [00:27:45] What else were we looking at?

Dr. Dale Bredesen: [00:27:46] You know, that's exactly right. So as a very general rule, there are two kinds of presentations amnestic and non-amnestic. In other words, memory losing and non-memory losing. The more common one is the memory losing amnestic. That's the typical person we think of. And so people will notice early on things like, “I just can't remember phone numbers the way I used to.” Or “I'm forgetting my keys.” Now again, here's where everything has been so backwards. In the past because there's nothing you can do about that. You just say, “Oh, it's probably not Alzheimer's.” “Well, yeah, it probably isn't for some people,” but it could be the earliest manifestations, so get on it now. So in the past everything was about delay, delay, delay, because there's nothing we can do about it anyway. And I can't tell you how many people that have come in. So like they've been told by their doctors, “Yeah, you're not that bad.” Come in in a year, “Ah! It’s not Alzheimer's yet.” Come in in a year and then, “Oh, it's Alzheimer's.” Yeah, now there's nothing we can do about it. That doesn't help. We want to be proactive.

[00:28:49] So the earliest changes are either memory issues, and one of the common ones, by the way, is memory for space. So commonly people will say, “ I was driving down the street, I pulled up to a stop sign, totally my neighborhood. Place where I feel very comfortable, and suddenly I had no idea which way to turn.” So spatial memory is a common one. People will say, “Oh, my spouse asked me the same question three times at dinner.” Declarative memory, very common problem. Or they can have memory for other things as well -- facial recognition, another common one. So they'll say, “Oh, I went to my reunion. I knew, I knew this person, but I just didn't remember the name. I didn't remember much about how I had interacted. Did I really know them for sure?” These are all very presentations, and I go over, you know, each of these things in the book.

[00:29:44] On the other hand, there is a different approach, where different presentation, which is non-amnestic, and these are people who typically have problems with so-called executive function. People who have problems with, for example, putting things together. I often remember, I often ask people, “Hey, if you have to get out of town in an hour, can you really throw everything together?” “Oh, you know, I can't do that anymore. I just can't organize.” We interacted with one woman, for example, who said, “I was the person in the office who organized everything, and then I got to the point, I just could not organize these things anymore.”

[00:30:27] So organization, that's a common non-amnestic presentation. And then calculations, one person came in, first thing that happened, she could not figure out how to calculate a tip, and that's a relatively common thing to do. And then the visual perception problems, and this comes up commonly what's with what's called PCA or posterior cortical atrophy. So things that are typically by parietal. So you know, you have your parietal lobes that are in between your occipital lobes and your frontal lobes and also between occipital and temporal. So they're essentially the gateway. And these things are important for dressing. They are important for things called agnosia. So knowing how to do things, knowing specific not only tasks but also specific knowledge, recognition, things like this. And so you can think of it in a simple way, the ones who present with amnestic problems, this is largely a temporal lobe problem. And the ones that present with difficulties, with facial recognition and calculation and things like that. This is typically more of a parietal problem.

[00:31:51] But ultimately as you indicated, you get to both of those, but typically people will present with one or other. But here's the interesting thing. Virtually everybody who presents with the non-amnestic presentations turns out to have toxin exposures. So we need to know what are the toxin exposures, what's actually driving this, and we see it again and again. And interestingly, this is -- this kind of Alzheimer's which we call type three or toxic Alzheimer's is unusual and it's actually more closely related to Lewy body disease than it is related to the other kinds of Alzheimer's, and infected Lewy body disease, you also have toxin exposures. These people tend to look different from the amnestic ones, they tend to start earlier. Often these people will start in their 40s, and come in with significant Alzheimer's by the time they're in their late 40s, or up to mid-50s. And we do see some people who are older, but often it's in the late 40s, and early to mid-50s. They will often have some depression. So they often have some so-called HPA axis dysfunction, hypothalamus and pituitary and adrenal axis dysfunction.

[00:33:08] They will often have this non-amnestic presentation and they'll often be exquisitely sensitive to stress. So they stay up all night one night and they get much worse. They'll often be very sensitive to hormones. So if you give them bioidentical hormone replacement, they tend to improve. So these people tend to look different than the amnestic presenters. So you can imagine early on, you begin to get some of these things and yes, it should make you think, “Hey, I should get on it now. Let's check my cognition now. Let's get a cognoscopy, and let's make sure that I don't get Alzheimer's disease in the future.”

Jordan Harbinger: [00:33:50] I know a lot of this is genetic. And I know that you had said that cognitive decline is, is possible when it comes to this. What if we have the two or four copies of the ApoE4 gene, is it reversal of cognitive decline still possible with these people?

Dr. Dale Bredesen: [00:34:06] Oh, absolutely. In fact, so first of all, ApoE4, you get one from your mother and one from your father, so you either have zero, one or two copies. So for example, I checked myself, I’m an ApoE33, which is the most common one, that's kind of the generic. And ApoE4 is incredibly interesting. So this is Apolipoprotein E, which carries around lipid. It is a fat carrier. It's kind of like your butcher. It carries the fat around. And in fact, when we were a Samians between five and 7 million years ago, as you know, what happened is that the appearance of hominids occurred and in fact, at that time with the appearance of hominids came the appearance of ApoE4.

[00:34:55] So it was the primordial one, and in fact this comes in three flavors, three alleles, two, three and four. Each person has one copy of one, either a two or three or four from the mother and a two or three or four from the father. Now, about 25 percent of the population, about 75 million Americans have a single copy of ApoE4, and about 7 million Americans have two copies of ApoE4. If you have zero copies, your chance of getting Alzheimer's during your lifetime is about 9 percent, one in 11. If you have one copy, it's about 30 percent, if you have two copies is over 50 percent, so most likely you will get it during your lifetime.

[00:35:49] A program that we've developed actually works quite well. In fact, if anything, it works a little better for people who have ApoE4 for from people who don't have ApoE4. And we believe that that's because the people who have ApoE4 tend to have more inflammation and the ones who have ApoE3 tend to do more poorly with toxins and the toxin type, the type three is more difficult to treat. So what happened when the hominins appeared between 5 and 7 million years ago. There was a small number of changes that occurred in our genome as you indicated, and surprisingly a large number of these changes turned out to be related to proinflammatory changes among them ApoE4.

[00:36:33] So how does this work? That's something that's your butcher, that's carrying around the fat actually has something to do with your inflammation and Professor Tuck Finch from USC had suggested years ago that when you come down out of the trees, what are you doing? You're walking along the Savannah, you're stepping on dung, you're puncturing your feet, you're fighting with your brethren for food. You're fighting with your food as well. You're getting punctured, you're eating meat that is uncooked, and you're getting pathogens in your gut. For all of these things ApoE4 is an advantage because it produces a proinflammatory state that helps you. And in fact, if you are living under squalid third world conditions, you will survive a better as an ApoE4 than as an ApoE3.

[00:37:25] Now, just 4 percent of the time we've lived on Earth as hominids. We've had ApoE3, so only 220,000 years ago, ApoE3 appeared and then 80,000 years ago ApoE2 appeared. But ApoE3 is now the dominant one, it’s the most common one. So as I told my wife, if you look at my entire genome, it's actually more similar to a male chimp genome than it is to yours. And she said, “well, duh! You like ESPN, the chimp likes ESPN, that sort of thing.” So in fact, there aren't that many differences between a chimp genome and a human genome. And one of the critical ones is this ApoE.

[00:38:08] So what we found in the lab over the years is that when you look at what ApoE does, it actually enters the cell and goes into the nucleus, which hadn't been appreciated before. It interacts with 1700 different promoters, and for example, this SIRT1, which is so important for longevity and so important for Alzheimer's actually. And when it interacts with these things, it literally changes the programs in yourself. So the surprise was, not only as ApoE your butcher, it is also your Senator. It is also participating in changing the laws of the land. And so when you're reprogramming yourself, one of the things that occurs is a more proinflammatory state. And if you look at the list of these 1700 genes that are impacted by ApoE4, the list includes all of the things that you would imagine for Alzheimer's. It includes things related to inflammation, it includes things related to glucose toxicity and glucose handling and insulin resistance. It includes things related to response to hormones. So the surprises thing has a widespread effect and in fact it makes perfect sense why having one or two copies of ApoE4 would put you at increased risk for Alzheimer's disease.

Jordan Harbinger: [00:39:38] Interesting to see that the gene -- like everything in our body actually serves a purpose. Because one of my questions for you was, “Well, thanks a lot, we have this gene that gives us this stinking disorder. What is it good for?” There's always an answer to that if we look hard enough, right?

Dr. Dale Bredesen: [00:39:55] Absolutely.

Jordan Harbinger: [00:39:56] I find that pretty fascinating from just an evolutionary psychology or biology standpoint that, “Yeah, if you grow up and you're not drinking clean water and you're eating animals that eat other things because you don't have a choice and you can't cook things very well because of where you live, this is helping you out.” And “Yeah, in 30, 40 years, you pay the price, but you're not going to live that long anyway. Look where you live, you live in a dump. You're going to die before this catches up to you.” But now we live a long time, but we still eat crap. So explain to me like I'm five here. How does my brain get Alzheimer's? How do I give myself Alzheimer's? How does half of the Western world end up giving ourselves Alzheimer's?

Dr. Dale Bredesen: [00:40:36] Right. So this is the important, important point here, as you indicated. People keep saying, “Well, it's genetics.” So look, “My genetics, I'm going to get Alzheimer's. I have ApoE4.” “No, that's absolutely wrong.” What ApoE4 does is give you risk, you give yourself Alzheimer's by what you're exposed to, by the way you live in. In chapter four, I went into all these issues. Here's how you can give yourself Alzheimer's, and I wrote that specifically so that people could see how many of the things that are pro-Alzheimer's that they do. So the bottom line is “Yes, we have a major ability to impact our likelihood of getting it and to impact whether we can actually reverse the cognitive decline.” So look, Jordan, you want to wake up tomorrow and say, “Look, my goal for the rest of my life, I'm giving myself Alzheimer's.”

[00:41:25] Here's what you do. You stay up all night, you don't get any sleep. You don't allow your brain to clear out the damaged proteins. You don't allow it to get of the amyloid. You damage the synopsis. You increase the reactive oxygen species, so forth and so on. You don't induce autophagy, you get under constant and chronic stress. We were made to handle short bursts of stresses as of course, Professor Robert Sapolsky has shown so beautifully with his studies over the years. That's what we were made for. Short bursts of stress and then periods of non-stress. The way we live is the opposite. We have chronic mild stress and sometimes more than mild, that damages your hippocampus, that increases your cortisol, which in and of itself decreases the volume of your hippocampus. The area that's so critical in Alzheimer's, so critical for storing memories.

[00:42:13] You have a horrible diet. So you go out, get a bunch of trans fats, eat plenty of sugar, make sure that you have a fasting insulin that's off the charts. You should have a fasting insulin that's five or lower. And we see people who have fasting insulins of you know, 20, 30, 40. This is insulin resistance. You go out and you run up your lipids, you get your high LDL particle number, a low HDL. You make sure that you don't exercise. You make sure that you have a leaky gut. As you know, leaky gut was something not even recognized when I was in medical school, and it turns out to be very common and very important, important for Alzheimer's, important for Parkinson's, important for IBS, I mean on and on. This is a critical contributor. You damage your microbiome, you take a bunch of sodas and things like that. You expose yourself to toxins. We've all got -- already got copper in our pipes so you don't, you know, you don't worry about that. You don't eat green leafy vegetables, which turn out again to be, is helpful to do that. You avoid those, you get exposed to mycotoxins, and these are toxins that are produced by mold. Who new molds are, can actually contribute to cognitive decline. They absolutely do. Others have reported this as well. We first reported this back in 2016, and we see it all the time. You have poor dentition, so what happens is you get exposed to things like Percent gingivalis, which is a bacterium from poor dentition. Fusobacterium nucleatum, another one.

Jordan Harbinger: [00:43:56] Poor dentition, meaning like you don't brush your teeth?

Dr. Dale Bredesen: [00:43:58] Yeah. And so by the way, a lot of people like now to do the oil pulling, which is actually helpful as well.

Jordan Harbinger: [00:44:05] What is oil pulling?

Dr. Dale Bredesen: [00:44:07] Oil pulling is something that was actually done by the ayurvedic of thousands of years ago. And the idea, you take some coconut oil and you swish it into your teeth for about five minutes. Again, many people do this. It actually improves dentition, and so again, the idea of having bad teeth turns out to be a bad thing for systemic inflammation. So whether your systemic inflammation is because of a horrible diet, because of pathogen exposure, because of a leaky gut, because of poor dentition, because of chronic wounds that are poorly healed, whatever it is, this is contributing to your requirement to protect yourself, in which case you will produce some of the amyloid and you will begin the downsizing process. So all of those things are critical and yes, diet, exercise, sleep stress and brain training, all of those are critical. If you fail on those, you are contributing. So in fact, again, just as we monitor ourselves over the years for our cholesterol, we monitor ourselves for obesity and for our weight. Those are things we think about every day. We should do the same for our cognition and we can have a huge impact if we do so.

Jordan Harbinger: [00:45:25] Okay, so leaky gut, we've been hearing about this for a while. I don't want to get into that. It does, I will note, sound disgusting. But it's caused I know by a lot of things like gluten, et cetera. I didn't realize the human body isn't designed to process over 15 grams of sugar a day. And that doesn't just count sugary foods, but simple carbs like white bread and things like that, that causes insulin resistance. I mean, there are things that people drink that I certainly drank as a kid that had three times that in one glass.

Dr. Dale Bredesen: [00:45:52] Absolutely. And I drank them as a kid too, and I certainly drank them as an intern trying to stay up all night. So absolutely, and here's the problem. Our bodies, and this is a lot about complex chronic illness. As you know, in the 20th century, many people died from simple acute illnesses, especially in the first half of the 20th century -- pneumococcal pneumonia, tuberculosis, diphtheria, things like that. And of course, the great success of 20th century medicine was to combine public health policy with antibiotics to make these diseases an uncommon cause of death.

[00:46:31] Now the problem is we are dying of 21st century illnesses because we are still practicing 20th century medicine, which is you wait for symptoms, you write a prescription, you send them home. That's not the way these diseases work. 21st century diseases -- Alzheimer's, cancer, cardiovascular disease, type two diabetes, on and on. These are complex chronic illnesses that have many different things that contribute to them, and therefore, you need to look at these. The good news is you can see them coming for years ahead of time. And so yes, you need to include all these different things and the things we just talked about and things like your gut leak. And by the way, as you pointed out, that 15 grams of sugar, more than that, and here's the issue. We weren't made. So we are living in a way that our bodies were not produced to live.

[00:47:31] So here's an example. If you said, “Hey Dale, let's go out.” We decided there's a new fun thing we're all going to do and that's jumping out a third floor windows. Well, some people are going to survive that and some people are not. It's like, “Yeah, but it's fun. This is what we do every day.” Well, our bodies weren't made to do that. So a lot of 21st century illness is actually because we are living in a way that is evolutionarily inappropriate. We were not designed evolutionarily to eat a lot of sugar. We were not designed evolutionarily to stay up all night. The reality is we really weren't designed to have lights on at night. We were designed to have light dark cycles there with the sun, and so we're already pushing the envelope when we're sitting there at night. And I'm absolutely guilty of this myself, so we have to be careful, and so in fact, I'm dealing with some people who have macular degeneration. We need to look at how much blue light exposure. The diseases that we are talking about, these complex chronic and especially the neurodegenerative diseases of which there are many as you know in Parkinson's and Lewy body, macular degeneration, frontotemporal dementia, progressive supranuclear paralysis, corticobasal degeneration, on and on. These things are essentially mismatches between our supply and demand, and they occur because we are not living in the way we are designed to live and we are not exposed to the appropriate environment, and now many of us get away with it. But as you indicated, genetics will play a role.

[00:49:07] So these things are all written onto our genome, and when we have a sensitive genome to one thing or another, we have an increased risk to go down the Alzheimer's pathway or the Parkinson's pathway. So that's why the genetics are important, but they confer risk and they – the vast majority of cases do not confer absolute determinism, it is simply risk. So we want to know what we're at risk for and we want to get on it. As you know, when the first genome was sequenced from James Watson, he did not want to know one gene, which was a ApoE, because he said, “There's nothing you can do about it.” Well now, there's a lot you can do about it. And so there's a wonderful website started by a woman named Julie G, who started a website called ApoE4.info. There are over 3000 people on that website who are actively looking at their own status and what they can do, and in fact, the vast majority of them are on some version of the protocol that I described in the book, and they are actively preventing their own cognitive decline.

Jordan Harbinger: [00:50:17] So Dr. Bredesen, we need to address as many holes or as many contributors to Alzheimer's as we can. There's 36, you said now there's going to be like 50, which isn't a thousand, which is good news. So we address the root causes, like the cause of inflammation, not just the inflammation itself, the leaky gut, not just the leaky gut itself, the causes of leaky gut. So what we're trying to do from the sound of it is reached a tipping point where synapse creation eclipses synapse destruction by the protective mechanisms in the brain. And I know people are going, “But what about medication?” And it sounds like, “Yes, we'll use medication, but it's not even the first line of defense.” It's kind of like buttering the bread. You don't just start housing the butter. You've got to have something, and by the way, don't eat any bread. But if you were to use bread in an analogy for Alzheimer's, we need that, right?

[00:51:04] So we don't want, we don't want to have just a time where we're growing. All right, well they're going to figure out some pill to get rid of this, because the pill will just get rid of the protective mechanism, but it's not going to get rid of the mold in your house. It's not going to get rid of the stuff that you're eating that's causing the inflammation. It's not going to get rid of the other problems that are causing your brain to react. Because we don't want to turn off our defense mechanisms. It's kind of like saying, “Well, I'm so sick of getting cuts., I should just take all my skin off and then I won't have to worry about it anymore.” You'd never do that to your body, but we do it to our brain.

Dr. Dale Bredesen: [00:51:36] It’s a really good point actually. And so we tell people that, “Look, there are 36 holes in your roof. And if you've got certain things like a leaky gut or if you've got low vitamin D or you've got high homocysteine, those particular holes are open wide. On the other hand, let's say you have an optimum B12 and you have an optimum vitamin D or an optimum testosterone, or you have no pathogens that you're dealing with, then those holes are pretty much closed. So here's the thing, a drug is a very good patch, a tight, a wonderful patch for one hole. So my argument is, “Look, the drugs are going to be very, very important, but we've been asking them to do too much.” We've been asking the drugs to do about a hundred different things, that's too many things. So what we need to do is to combine, and think about even with something as simple as HIV, a little retro virus, it took three drugs to have a big impact, and that really changed the world.

[00:52:34] So with Alzheimer's, we need to have an entire program. So this is programmatics not monotherapeutics, we need to know which holes are open the widest and we need to know that we can cover all of them. So yes, it's relatively straightforward to get tested, to get a cognoscopy. You want to find out where you stand and we can break it down into the groups that go along with the subtypes. You want to know, “Do I have ongoing chronic systemic inflammation?” So what's my hsCRP? You might want to check your IL6, or TNF alpha, but hsCRP is a good one to start with. Do I have pathogens? Do I have chronic herpetic family viruses? Do I have chronic spirochetes? Do I have chronic fungi? Do I have chronic bacterial infections? Those are all important to know. So those are all related to type one, and in fact, do I have ongoing activation of my innate immune system? These are all things you can look at with blood and simple urine tests. Then type two, do I have suboptimal levels of specific trophic factors, hormones, nutrients? All the things that you need to support your synapses.

[00:53:57] So if you're walking around with a as so many people are with the vitamin D of 19 or 20 or 21, you want it to be more up in the 50 to 80 range. You want it to be optimal, and so you want to know what that is. And similarly, testosterone, estradiol, pregnenolone, progesterone, thyroid hormone, your cortisol, DHEA, all of these things are critical to know. What's your B12? What's your homocysteine level? What's your B6? What's your folate? These are all important as supports. And yes, you know, if you're living a perfect life, if you're doing things right, then you may not need to worry about these.

But for most of us who are living in Western societies, we need to know whether we have optimal levels of those things.

[00:54:47] Professor Clayton, by the way, from the UK as pointed out, in fact that our soils are so bad now, that our typical nutrition that we get from our meals is worse than it was during King Henry VII style. So in fact, we -- you know, a lot of us are malnourished and simply don't know it. That does contribute to multiple things such as suboptimal cognition. All right, let's go to type 1.5, so you want to know what your fasting insulin is. You want to know what your hemoglobin A1c is. So you want to know if you have insulin resistance. Critical, absolutely critical. By the way, the higher those are, the more you have an association with shrinkage of your hippocampus and you can literally go and put that on a line.

[00:55:34] Similarly, the higher your homocysteine on average, the smaller your hippocampus, the more rapidly it will begin to atrophy with age. Then you want to know for type three, do I have exposure to toxins? And this has been the tough one because toxins are ubiquitous as we know. So you want to know about metalotoxins. What about mercury? What about your copper zinc ratio? What's your level of ferritin? These sorts of things. Now, again, it's tricky. These metals are important things like copper and zinc and iron are important for your life as well. So no big surprise. You need some, you need not too much, and like everything else in biology.

[00:56:22] So now what about organic toxins? Dr. Joseph Pizzorno from Seattle has shown that in fact people with Alzheimer's do tend to have more exposure to things like DDE, so there are organic toxins.

Again, you are responding to these toxins, and then you need to know what about biotoxins? These are things made by organisms, so things like trichothecenes. And you can measure these easily in the urine, for example, if you're exposed to molds and there are specific ones, things like stachybotrys and penicillium and aspergillus and chaetomium. These are specific molds that produce specific toxins, which can be neurotoxic and immunotoxic and otherwise toxic genotoxic as well. So these things can contribute to cognitive decline. And as I said, these are the tough ones to treat because they often have multiple biotoxins and you've literally got to get rid of these things.

[00:57:28] And I should note, as I mentioned earlier, these things tend to give you presentation around the time of your 50s, menopause basically. And what's happening is you store these toxins, you sequester them in your bones among other places when you are younger, then as you get to menopause, you are beginning to release some things like mercury, go back up again. And so that's probably why you tend to get these problems at that time. So you want to know all those toxins. And then from that, you want to know what subtype am I at risk for? And then what is my optimal program that I could work on with my doctor and my health coach to prevent my cognitive decline, or if it's already started to reverse it. And by the way, we see this all the time. I had a woman for example, who came in and she said, “I want to prevent, she took the MoCA, her MoCA was 23, she already was well into MCI. And then of course, when she got on the program, her MoCA score went to 30, which is perfect. And she said, “ I didn't realize how much I'd lost until I got better.” And we hear this sort of thing all the time.

Jordan Harbinger: [00:58:32] So it's never too early to test for Alzheimer's. And of course, the genetic markers. We can link to 23andMe on the show notes, but where do I get the other tests that you'd mentioned? If I go to my doctor and I ask for all of these, aren't they just going to go, “Wait a minute, I'm not writing all these for you.” You might have to pay out of pocket for these, right? If it's from the sound of it.

Dr. Dale Bredesen: [00:58:50] You can go to the website, drbredesen.com. You can take a look at the book. There's a list, check chapter seven and eight. We go through the whole list and now we are actually just bringing out, so within the next few weeks you'll be able to get your direct to consumer, just like a 23andMe sort of thing, where you'll be able to get all the testing and a report.

Jordan Harbinger: [00:59:09] Great. Dr. Bredesen, thank you so much. This is a little scary but also enlightening and good to know that we can start to prevent what was previously thought inevitable, if we just do the right things and pay attention.

Dr. Dale Bredesen: [00:59:21] Actually that's so true. So let's all work together to reduce the global burden of dementia. It's something that's absolutely within our reach now.

Jordan Harbinger: [00:59:29] Great big thank you to Dr. Dale Bredesen. The book title is The End of Alzheimer's. If you enjoyed this one, don't forget to thank Dr. Bredesen on Twitter. Tweet at me your number one takeaway here from Dr. Bredesen. I'm @jordanharbinger on both Twitter and Instagram. And don't forget, if you want to learn how to apply everything you heard from Dr. Bredesen, make sure you go grab the worksheets also in the show notes on our website at jordanharbinger.com/podcast.

[00:59:56] This episode was produced and edited by Jason DeFillippo. Show notes by Robert Fogarty, booking back office and last minute miracles by Jen Harbinger, and I'm your host, Jordan harbinger. The fee for the show is that you share it with friends when you find something useful, which should hopefully be in every episode. So please share the show with those you love and even those you don't. We've got a lot more like this in the pipeline. We are very excited to bring it to you and in the meantime, do your best to apply what you hear on the show so you can live what you listen, and we'll see you next time.