What follows is a transcript for the podcast Ending Alzheimer’s: Lifestyle Changes to Prevent Neurodegenerative Diseases.
Sub-section topics within the interview include the following:
- State of Research on Cognitive Decline
- What is Beta-Amyloid?
- What Dr. Bredesen Has Learned Since He Published "The End of Alzheimer's" Book
- Ketosis and Diet Type for People with Alzheimer’s
- Insulin Resistance Doubles your Likelihood of Developing Azheimer’s
- Creating Apollo: Integrating Tech and Medicine
- Importance of Health Coaches in Helping People Get Better
- Assisted Living Facilities for People with Dementia
- How to Prevent Dementias and Slow Aging
- The ARK Project
- Acute Effects and Neurological Complications for People with COVID-19
- Next Steps for Making Alzheimer’s a Rare Disease
- Dr. Bredesen's New Book: The End of Alzheimer's Program
- Learn More About Apollo
Dr. Heather Sandison: Welcome to Collective Insights. I'm your host today, Dr. Heather Sandison, and I am so pleased to be joined by Dr. Dale Bredesen today. Thanks for being on the show.
Dr. Dale Bredesen: Thank you Heather. Thanks for having me.
Dr. Heather Sandison: So you and I both have some research going on in our perspective "labs" in my clinic and in your group. Why are these studies so important to the field of Alzheimer's and dementias?
Dr. Dale Bredesen: Well, as you know, this has been the area of greatest biomedical therapeutic failure. So as they say, everyone knows a cancer survivor. No one knows an Alzheimer's survivor, although now we have hundreds of them. But this has been the area where whether it's ALS, whether it's frontotemporal dementia, whether it's Lewy body disease, whether it's Alzheimer's disease, we just as a standard of care, a medical system, we have not had anything to offer people. It's really been hopeless and very depressing as you know, for people to come to these centers. And so we spent 30 years. I ran a laboratory for 30 years looking at what are the fundamental mechanisms that drive the neurodegenerative process with the idea that if we could understand these mechanisms, we could begin to get at how does this work so that we can do something about it and when do we have to intervene?
Is this something we can do late? Can we do early, in the middle? When do we have to do this? And it's really been an amazing journey to see that what these diseases are really boils down to a fundamental mismatch between the various supportive signaling, everything from trophic signaling to hormonal signaling to nutrient signaling to various inflammatory signaling, things like NF kappa B and things like that. And then on the other side of the equation is the issue of demand. What does it actually take to run the various neural subsystems of your brain? As a simple example, you look at your macula, obviously this is an extension of your brain, but you look at that, it is the highest area of metabolic activity in your body. So it has its own critical needs. And when you don't meet those needs, you get age related macular degeneration and 11 million Americans have that.
On the other hand, the Alzheimer subsystem, you're really looking at neuroplasticity has its own specific needs, things like specific trophic factors and specific lack of activation of innate immune system, NF kappa B and things like that. So again, there's a mismatch there. When that demand is not met, you end up with a degenerative condition that we call Alzheimer's. And you can do the same thing with some of the motor systems. And what's really interesting about the motor systems, whether you're talking about ALS or whether you're talking about Parkinson's for example, where it's really motor modulation, these are areas where in fact the mitochondria are critical. So it's a little bit as if you're driving around a Ferrari at 220 miles an hour for 16 hours a day or something like that. At some point, if you can't support that system, it begins to break down.
And that's what we see was if you inhibit mitochondrial function, in the case of Parkinson's, it's really mostly about complex one. But in the case of ALS, it's really about an activation of this system where you're essentially over driving it to clean up because you're not cleaning up the glutamate in the synapsis and things like that. So you would end up with this excitotoxic disease. So each of these has its own set of demands, and each one has its own set of supplies that's based on your genetics and based on your lifestyle, based on the food that you're eating, all the different things, the toxins you're exposed to, et cetera. When you mismatch those chronically or repeatedly, the system begins to downsize. And so the good news is we can measure so many of the different variables that are on both sides of the equation for each of these sub systems, and then we can optimize it.
So of course in people with cognitive decline, we look at, as you know, we look at all the synaptoclastic contributors and all of the synaptoblastic contributors, and then essentially we rebalance them. We increase the synaptoblastic contributors, we decrease the synaptoclastic contributors. So I think this is an exciting time because we're beginning to get insight into this and as you indicated, the research is showing us what are the critical variables. It's also showing us that standard medicine measures far too few of these variables and addresses far too few of them.
State of Research on Cognitive Decline
Dr. Heather Sandison: So what is the state of the research?
Dr. Dale Bredesen: With respect to a cognitive decline or with respect to neurodegeneration or what?
Dr. Heather Sandison: Well, for instance, you published case studies in both 2014 and then in was it 2017 the hundred person case study report came out?
Dr. Dale Bredesen: 2018.
Dr. Heather Sandison: 2018. And so those are all looking backwards and saying, okay, here's people who have done well with this. Here's a hundred of them. This is possible. It sort of establishes that there's this potential. But it doesn't tell us the answers to one of the most common questions I get in my practice, which is if I have my loved one do this, how likely is it that they'll benefit? So I think we are both involved in doing prospective studies. And so where are you in that?
Dr. Dale Bredesen: Right. Yeah, that's a very good point. So several things going on and we are writing up a few additional patients that we think are very instructive where we have very good documentation, PET scanning and volume metrics and things like that. And meanwhile, we are in the midst of the first clinical trial in history in which instead of predetermining a treatment, as you know, all previous clinical trials they say, "Okay, here's what we're going to do to treat these people." And then you start the trial. Well, that actually is backwards from what we should be doing. Right? So what we should be saying is, "With the trial, we're going to evaluate the many, many different variables." We typically look at about 150 different variables, but of course that's a very tiny number. We need to look at millions to look at what are all the things that could potentially be contributing to any person A or person B's cognitive decline.
And then we want to address those things. And so in this particular trial, which we'll finish in December, it's been going on for a little over a year and it will finish in December and it should be published next year, we look at all these different variables and then say what's driving the decline and then address these things. And so I'm very excited to see how that all comes out. In addition, we've just completed a study. It's actually done by a different group, but with some input from me on looking at an abbreviated version, which we think of as pre-code. So this is instead of reversal of cognitive decline, this is prevention of cognitive decline. And interestingly, that looks very exciting. The data have just come back in and people have done very, very well. So excited about that. That has yet to be published.
I look forward to that and it really shows that you can take people who have "normal cognition." And as you know, most of us who have normal cognition that's kind of like saying normal health. There are so many more things we could do to improve things. And indeed you see that when you take people and you use a pre-code approach. Not only do you get some resilience that's going to protect you for the future, but in fact you have better performance after just a few months. And I think that comes as no surprise to many people.
Dr. Heather Sandison: Right. It sounds like neurohacking essentially.
Dr. Dale Bredesen: Exactly right. So these people were neuro hacked and they're doing very, very well. And then in addition to those, we have, so the protocol of the ongoing trial will really give us a denominator for the first time. And then of course we're writing up other things that are specific to essentially to the mechanisms. So what are the things that are actually driving the process because we want to understand the fundamental nature of these diseases. The better we can get accurate models. And as you know, it kind of goes, model, prediction and then either the prediction is right or wrong with the research and then that changes your model. So you continue that way to look forward. And we're finding new things.
As you know, we started out not knowing about type three, the toxic one. And that was a group of people that looked different than the other people, that didn't respond as well to the metabolic changes, the hormonal changes. And these people have ended up doing much better. Of course, when you address their toxicity, of course, at the same time, those are the toughest ones to make better when they've got a lot of toxicity. Unfortunately, as you know, by the time you get Alzheimer's disease, you often have many, many years of decline. So again, we suggest to people, please, please get in as early as possible because it's so much easier and so much more complete to do this earlier. That's why I think neurohacking is such a good idea. So that's all going on. I think we're going to, we will know a lot more as this thing finishes up later this year.
What is Beta-Amyloid?
Dr. Heather Sandison: So you talked about this scientific process where you have a hypothesis and you test the hypothesis and you change your model based on the response that you get based on the data and the information you get from that process. Now outside of your group, conventional medicine is still hammering away with this beta-amyloid model. And that if we can just get rid of the beta-amyloid using a medication, then we can cure Alzheimer's. So why has that not worked despite the billions of dollars and decades of time that very bright individuals have put into this?
Dr. Dale Bredesen: Yeah, so that's a great question. And if you, again, this is why we were so interested in the research over the last 30 years. If you actually step back and ask what is driving the phenomenon, there should be internal consistency. What you see in the clinic, what you see in the laboratory, what you see with your transgenic mice, what you see for people's own cognitive decline, how they respond to various drugs, et cetera. These should all be one. They should all make sense. And so if you look at what amyloid is, that's the problem. It actually doesn't make sense. So what happens, you have a molecular switch as I mentioned in the book, APP. And that's again, the kind of the simplest way to look at this. Amyloid precursor protein turns out to be a type of receptor that we discovered in the lab and described first in 19 way back in 1993.
And this thing essentially will be cleaved and give you two different types of signaling depending on what the input is. So it turns out that for APP, it's a really interesting sensor and integrator. So when things are good, you have enough nutrients, you have enough hormones, you enough trophic factors, you don't have too much inflammation, all of that stuff. Then your APP is actually cleaved at a single site, which is the alpha site by SAP, well, to produce sAPP-alpha and alpha-CTF. It's cleaved by the alpha-secretase, which in most cases is atom 10, but there are some other enzymes that can do it as well. So it's really saying things are pretty good. Let's go ahead and build synapsis and maintain synapsis. And this is a little bit like if you were the ... oops, sorry. If you were the president of my brainastan and you've got ... things are good.
You don't have a lot of pollution, you don't have people, other countries invading you. You don't have a lot of inflation and overall things are going well. You're going to say, "Okay, it's time to build. It's time to make new relationships. It's time for our country to grow." And that's exactly what your brain does. On the other hand, when things are on the bad side and you ... So in the case of your brain, you're now talking about ongoing inflammation, pathogens, toxins, low trophic levels, low hormonal levels, low nutrient levels, all the things that you are hacking with neurohacking. These various parameters, then no surprise, your brain needs to go into a protective mode. You are doing something very different. And in fact, your APP recognizes that. You can literally trace the molecular pathways to APP cleavage. And here's an example.
When you have ongoing inflammation, NF kappa B activated, that turns on a whole set of genes. And among those is the beta-secretase and the gamma-secretase that make a beta, the amyloid that we associate with Alzheimer's disease. So the problem is that amyloid, yes, when you pour amyloid all over neurons, no surprise they don't do well. But you have to look at why is your brain making the amyloid? Well, it's making it because of the ongoing signaling, because it's been invaded, because it's been insulted. So the idea that you would just say, "Well, we're going to take away the stuff that responds to the insults without taking away the insults," is absurdly simplistic. And no surprise when you take it away, many people actually get worse because you're now taking away a protectant. This stuff is anti-microbial, as Rudy Tanzi has shown in the past. And his colleagues, Robert Moyer and their colleagues have published repeatedly, this stuff is actually anti-microbial.
As Ashley Bush has published, it also binds metals. So this thing is there. Yes, it is downsizing. It's a little bit like again, like if you have a president who says, "We're going to have to downsize things. We're going to have to tighten our belts." And so what do you do? You say, "I don't want to tighten my belt. I'm going to kill the president." That really doesn't help you. You're still going to have to tighten your belt at some point. And so that's what's happening with APP signaling. So we want to go upstream, we want to look back and look at the big picture. What is all timers? It is a response to all of these different insults. We need to identify them, identify the ongoing pathophysiology and address that instead of trying to get rid of a mediator, be it tau, be it amyloid, be it a reactive oxygen species, be it iron, be it ... People have tried to get rid of all these different things.
Why don't antioxidants, isn't that the way to treat Alzheimer's? And then of course, recently people say, "Well, it's all about herpes." Well, yes, in some cases it is. Or it's all about mercury. Well, in some cases it is. But these things all are contributors and they're going to be a little different for each person. So you need to identify them and address them. And as you know, when you do that, that's when you get the best outcomes. Now, the most interesting things to me are the people who respond extremely well, where it just, everything just melts away and they do great. And on the other hand, the people where you do everything right and somehow they don't respond. And we need ... Those are the ones that there's something missing. We need to understand, do these people need stem cells? Have they lost too many synapses? Do they have ongoing inflammation? Is there something genetically?
One of the interesting things that's coming up right now, interestingly, it's related to COVID-19 in that as you know with COVID-19, young people are having strokes. They're getting occlusions of major vessels. There is a thrombotic state, a hypercoagulable state as part of overall inflammation, but of course this is screaming inflammation. COVID-19 has literally taken all the risk factors for Alzheimer's over 20 years and crunched them down into two weeks. So it's really telling people, it's really getting people to think more about resilience and about the future of resilience. I think we're going to come away in a different world.
So in Alzheimer's, it's turning out that the same things happen. Not only are we talking about inflammation and pathogens and toxins and trophic loss, but it looks as if there is a situation in which the a-beta, the amyloid itself, We know that it interacts with compliments, C1q for example. So it's part of the innate immune system, but it's also part of a thrombotic system. So you're also enhancing microthrombi. And so again, this is another thing that we're going to have to address. And I think that in some of these people who haven't done as well as others, one of the problems may in fact be that they have many, many microthrombi that haven't been addressed.
What Dr. Bredesen Has Learned Since He Published “The End of Alzheimer’s” Book
Dr. Heather Sandison: So this is one of the reasons why I have been following your work for so long is because complex systems comes up over and over and over again. And it's one of the concepts that I think a lot of people have trouble wrapping their minds around that it's not just one thing, that these are not mutually exclusive, that you can have herpes contributing, you can have a TBI contributing, a traumatic brain injury. You can have these transient ischemic events or these thrombocytic events contributing, you can have a toxin contributing and all of those can be playing a small role. It's not going to be one pill or one solution that's going to get you to the finish line of improved cognitive function.
So detailing all of those things is so important. Getting the data and understanding how you got to this point is key to unraveling how to get out of it. So one of the big questions that I want to ask you today is what have you learned since The End of Alzheimer's, the book was published in 2017? So what are all of the ... what's the new data showing you? What are the things that maybe you didn't realize were so important that you now realize people really need to look closely at?
Dr. Dale Bredesen: Yeah, that's a great point. So we're coming up on three years since the publication of the book and the next one will be coming out actually in August. And in fact, it came because people kept saying, "Hey, we want more detail about diet or more detail about stress relations or more detail about which pathogens and when to worry about those or which toxins to look for." We've had some remarkable stories of toxicity. All sorts of toxins that you would have never expected are going to turn out to contribute. So it's turning out that this is very important. So the things that have come up since I published this back in 2017, one thing that's turned out to be more important than I realized at the time has turned out to be desaturation. So oxygen desaturation at night and again, just like people are looking, I don't know if you have a little oximeter on your iPhone, but I've been using my little iPhone oximeter to check my own oxygenation.
Yep. Great to know. And I'm assuming you check this on all your new patients. It's a great idea to do. And who knew? In fact, there's a very interesting paper that looked at oxygenation for various people and then looked at brain volumes. And in fact, multiple regions of brain including hippocampal volume, which is so critical in Alzheimer's, turn out to be directly proportional to the mean SPO2 while you sleep. So it is strikingly important that while you're sleeping, you're not dropping. And that's an important thing to hack to know where you stand. And if you're dropping down to 92 or 85 or heaven forbid, 71 as we've seen some people do, just unbelievable. You are hurting your ... and you are putting yourself at increased risk for cognitive decline. In addition, you are putting yourself at increased risk for age related macular degeneration.
So this is a significant problem and much more so than I realized at the time of the book. The second thing that's come out is that the oral microbiome is turning out to be so critically important. And of course people have talked about P gingivalis. If you actually look in the brains of patients with Alzheimer's disease, then what do you find? Well, you find P gingivalis from your mouth. You find as you indicated, herpes simplex one, herpes simplex two, HHV-6a, HHV-7, T denticola, Cola, F nucleatum, Prevotella intermedia, candida. You see other fungi, you see spirochetes like Borrelia. So there are lots of different organisms. It's actually surprising how many of these organisms gain access to our brains. Of course, we were all taught in medical school that the brain is a sterile place. You shouldn't have anything growing in there.
But as we're all beginning to understand more and more about microbiomes, we realize there are the good guys and the bad guys. And so to some extent, we want the good guys just like in your mouth, just like in your gut. It's not just about sterility, it's about getting the good guys to keep the bad guys out. And of course this brings in issues of immunity. It brings in issues of barriers that are so critical. We talked to so many people who have cognitive decline where, oh wait a minute, you mean that chronic sinusitis for the last 15 years was related to this or the poor dentition or the poor gut health and the leaky gut. These are all related. And of course, research is coming out one after the other. The importance of gut microbiome in Parkinson's is a great example. Lots of interesting data on that.
To a lesser extent, interesting data with respect to Alzheimer's disease. And I think these are all going to be coming out over the ensuing months and years. So these different pathogens are all turning out to be important. And again, this again is no surprise then why your brain is saying, "Oh my gosh, this thing is attacking me. I'm going to make amyloid." Amyloid is a little bit like putting down napalm. You're saying my borders have been breached. I'm going to activate my innate immune system and amyloid is turning out the A-beta is part of the innate immune system. So you're going to cover this. And as you probably know, if you go into a beehive, what the bees do when you have something invading their hive is they cover it with propolis.
This is some stuff that is a gooey, very much like beta-amyloid. It is anti-microbial, very much like beta-amyloid. So you're covering this stuff and it isolates it essentially. Very interesting that you look at things, some of the very low evolutionary things like sea squirts, these things make amyloid to isolate themselves from each other when they encounter another one. But it's not the right genotype for sex. So you literally say no, it's like swiping left, right? So you just go, boom, I'm not interested in this one. And they literally put down this barrier. So this stuff is a really interesting anti-microbial, antitoxin barrier.
But when you're putting it down in your brain, part of that is you're giving up a part just as you would pull back in a country. You're giving up and you're living in a slightly smaller system to protect yourself. So we want to get rid of that. Obviously we want to allow you to make your system, make your network larger once again. But again, simply taking away the barrier, taking away the anti-microbial, taking away the antifungal and the antitoxin is absurdly naive.
Dr. Heather Sandison: Right. Because they'll just run rampant and potentially cause even more disease and then more cognitive decline.
Dr. Dale Bredesen: And we have seen this where people will have anti-amyloid therapy and clearly get worse each time they have the therapy. And of course on other people you may get lucky and in fact, they may not have the exposure that they did previously or they may have had a good enough response to it. And then you're going to see someone who maybe gets better. So you see both. You see people who improve, you see people who get worse and of course you see people who don't change. But again, the overall, it doesn't make rational biological sense to be removing one player when there are so many other players that are critical. And when it's not the most upstream, it's not what's causing the problem.
Ketosis and Diet Type for People with Alzheimer’s
Dr. Heather Sandison: So what have you learned about the diet? In the back of your book, you have a green light, red light, yellow light to kind of be careful with these ones. And when we've talked more recently, you've asked the question when I consult you about my patients, are they in ketosis? Right? So has it become less about the types of foods that people are eating and more about the metabolic status? Or is it still really important that you're avoiding certain types of food? Or is there some middle ground? Like what is the concrete or practical advice about what people should be eating if they've started to experience some cognitive decline?
Dr. Dale Bredesen: That's a great point. And I have to say up front, I'm sure that many, many of your listeners know far more about diet than I do. I am learning this stuff because we've been interested in the signaling. How does the signal transduction work? What is your brain saying to itself when it's saying degenerate pullback, things are not good. So of course, as approaching a disease that has been completely unapproachable with nobody getting better, we were just trying to pull out all the stops. What are all the things we can do? As you and I have talked about before, the armamentarium for this disease, we've been told is zero. In fact, the armamentarium is massive and it has to do with lifestyle and it has to do with diet and it has to do with stress and it has to do with brain training and it has to do with drugs and it has to do with hormones and trophic factors and supplements and just on and on and on.
And you have to know how to use it optimally for each person, which starts of course, with understanding why they got to where they are. So you're right. With respect to the diet, people are studying all sorts of things. And again, as you indicated earlier, there are things that are not mutually exclusive. People will say, "Oh, it's all about Mediterranean diet." Well, yes, that can be helpful. What has been found though is that people who have cognitive decline associated with Alzheimer's or pre-Alzheimer's do have a decrease in glucose utilization in their temporal and parietal cortices. And specifically they often show in the precuneus and posterior singular. These are picked up on PET scans. So how do we bridge that gap? And of course one of the best ways to bridge that gap, and yes, originally it was thought, yeah, they just have degeneration so they're fewer mouths to feed.
It's turned out not to be that simple. In fact, you can improve that energy gap by supplying ketones. And now we all like alt for the long run. We like to see endogenous ketosis. But in fact, there's a nice publication showing you can simply take people like this, give them whether it's exogenous or endogenous and it will help them. So they really do have an energy emergency. So when you see people, yes, in the long run we want to get them to produce ketones endogenously because there are some advantages to that, such as things like anti-inflammatory effects. But in the short run, and I have this argument with my wife who's an integrative physician all the time because she really believes that the first thing you're going to do is you want to make them insulin sensitive. And I say, no, their brains are starving.
We have to get them rescued with ketones on day one, then we can work with them. Then we can help. And we know from the publications, and of course Mary Newport started all of this with her own husband years ago saying, "I can give him this." Now again, if you just give exogenous ketones, there are all sorts of negatives that you won't get ultimately within endogenous. So for example, you're not allowing them to generate their own ketones. You may, in the long run have a proinflammatory effect. You may allow them to be having a poor diet, all those sorts of things. But it gets people going because they have an energy emergency. And typically again, we went to this being agnostic and what we're seeing is the people that do the best typically do get into the 1.0 to 4.0 millimolar, beta-hydroxybutyrate range.
And some of them do it exogenously and some of them do it endogenously. But that does seem to be a critical feature. Now to do that, as you know, there are all sorts of ways to do it. And again, in the long run, we use what we call Ketoflex 12/3 and simply that means we want to generate ketosis. You can do this in a way that has metabolic flexibility so that you can now use, you can go back and forth between at appropriate times, using carbohydrates and at an appropriate time using fats. Hopefully good fats in the long run. That brings up another issue of course, which is when do you use saturated fats like MCT oil. If you're able to eat 4/4 okay, maybe you want to use ketone salts or ketone esters instead of using it. If you're able to eat 4 negative, you can do just fine with things like MCT oil or coconut oil or things like that.
If you have a single copy of four, you probably have your choice. You can go either way, but be careful. Follow your LDL particle number, make sure that you're not going to have any vascular disease. If there's a question, of course, get a calcium score, get an agatston score. All these sorts of things you can do. So there's, again, so many ways you can hack the system, but the system has to work together. So much of the research has been, okay, we're studying this incredible orchestra. We're going to check each instrument to see which one is the orchestra. Is that the French horns? Is that the orchestra? No, it's not. Is it the violins, is it the bass? I mean, it's just, it's silly. It doesn't make sense. It's an orchestra. It has to work together.
Insulin Resistance Doubles your Likelihood of Developing Azheimer’s
Dr. Dale Bredesen: And that includes all the signaling related to your pathogens and related to your inflammation and your toxins, be they organic Metallo toxins or biotoxins. And part of this of course, is people who have insulin resistance. Insulin resistance as you know, it's very common. Over a hundred million Americans have insulin resistance. It is a critical contributor. It more than doubles your likelihood of developing Alzheimer's, especially if you have metabolic syndrome, then you have a high risk for Alzheimer's disease. So when we look at these profiles for these different patients, and when I see someone who's got a HOMA-IR of four and who's got an HSCRP of three and a half, I say, "Wow, this person is going to be better for sure." They're easy to fix as we say because you know what you're going to ...
Now that doesn't mean that's all that's contributing, but you've got some very addressable, low hanging fruit and you can get them to do the right things. So to your point about the diet, sorry, this is a long winded way to get back to the diet. But yes, the diet is incredibly important for many things. For as you know, all the different polyphenols and all the different critical things that we're getting from the beautifully colored vegetables and all these things. And you come down essentially to a plant rich, doesn't have to be all plants, but a plant rich, mildly ketogenic diet with some fasting periods. And again, you have to adjust it. If your BMI is 17 and a half, you're not going to start with a big fast. But if your BMI is 23 or 26 or 29, then fine, do some fasting.
So we say typically minimum of 12 hours at night and minimum of three hours before going to bed. If you're ApoE4 positive, you want to adjust that to 14 to 16 or even longer because it takes some time to induce the autophagy. It takes some time to get you more insulin sensitive. It takes some time to give you that period where it's affecting everything from your blood pressure to your insulin sensitivity, to your inflammatory markers. So again, we're coming at this from the biochemical side. How can we generate sAPP-alpha and alpha-CTF? How can we generate BDNF? And great way to generate BDNF is with ketones. So beautiful work out of Cornell showing that in fact your ketones, BHB specifically, interacts with specific markers that are involved with preventing, essentially inhibiting transcription of DNA. So these are specific histones that are inhibiting BDNF production.
It essentially relieves that inhibition and allows you to increase your own BDNF. And of course, this happens with exercise. There are also supplements like whole coffee fruit extract that can be helpful. So again, we're trying to use everything that we can get our hands on to optimize the biochemistry that is driving you away from the synaptoclastic state and back into the synaptoblastic state. And that does have to do with your diet and your exercise and your sleep and your stress and all these other things. So plant rich ketogenic and couldn't overemphasize fiber. I know there's a whole group of people right now that say, "The only thing you should do is we should all be pure carnivores. And we want to eat nose to tail." I get it. And certainly when you've got auto-immunity as a significant problem, for some people that's a good approach.
Plants, they don't do well with plants. That supports the auto-immunity and so great. Again, whatever works. But in general, for people who are interested in optimizing cognition and preventing decline, we want to include a diet that has all these different things. There was just a paper published. People with low polyphenols increase risk for dementia, no surprise. And so we want to have high fiber in this diet. And I know all of us have had different things that we've done during COVID-19 and I've been doing more on home blood pressure cuffs and iHeart and all these things. And one of the things that I started to do was track myself on chronometer every day. And Julie, actually Julie G had recommended this in the book and I thought what a great idea. So I started going through and no surprise, what I found is I'm a little too high on the carbs.
I'm a little too low on the good fats sometimes. So okay, I need to adjust accordingly, but it's a great way to track yourself and you want to get these ... you can see on there all the different nutrients that you're lacking. You can see what you need to make up for. By the way, you asked about what we didn't know three years ago. One of the things we didn't know is how incredibly common choline deficiency is. And of course acetylcholine is the most important neurotransmitter, arguably. Now to make new memories, yes glutamate also important. Yes, dopamine reward also important, but the critical one as you know, drugs that are anti-cholinergic, what do they do? They mess up your memory. They increase your risk for cognitive decline. So acetylcholine is critical and most of us in the US are deficient.
You need to get between 450 and 550 milligrams of choline per day. And so I was looking at my own and thinking there are days when I'm not quite high enough on choline. Okay. This is one of the reasons we like people to take citicholine or GPC-choline, because most of us are in fact not getting enough. Same story. Of course, most of us not getting enough iodine, not getting enough magnesium, not getting enough potassium, not getting enough Zinc, especially if you're on proton pump inhibitors. So all these things are turning out to be critical for the signaling that's required for best cognition. And one of the cool things is people who have "normal cognition" are doing much better when they simply look at these sorts of items.
Creating Apollo: Integrating Tech and Medicine
Dr. Heather Sandison: So this can get really overwhelming for people pretty quickly, particularly if you're struggling with cognitive decline or if you're even a family member who's been caring for someone with cognitive decline. And now you're reaching out to someone like you or I who might be able to help, but you're sleep deprived and your bandwidth is almost gone. So one of the things that I certainly see in my practice, and I know you've heard a lot of these stories, is people just feeling totally overwhelmed and they want to help, but they just don't even know where to start. So you've created, you talked about being a bench for a long time and you're a medical doctor. You're not in clinical practice, you're working at Apollo. And at least from the outside, to me it looks like what you're trying to do is make it easier for people. Really trying to distill the most essential information, individualize it, and then allow people to incorporate this into their lives as seamlessly as possible. So can you talk a little bit more about your journey to creating Apollo and working on more of a tech side?
Dr. Dale Bredesen: Yeah, so here's the thing. I mean, I went to school with a bunch of engineers. If you go to an engineer and you say, "Okay, I've got a problem for you. I'm dealing with this machine, this human organism, it's unbelievably complex. I mean, the DNA, 3.3 billion base pairs of DNA, that's the simplest thing. That's just uni-dimensional. But then you have the microbiome and you have the full dome and the expose dome and the interact dome and all these things that are critical in this machine. Now the machine is not working well. Something's wrong. It's not doing something. In this case it's part of its central nervous system is degenerating." And so the engineer says, "Okay, this is an incredibly complex system. I'm going to need lots of statistics." And I'm going to say, "Well, no, I just have serum sodium, serum potassium, thyroid, B12, a couple of other things."
That's a joke. The engineer will look at you and say, "You're trying to solve a problem in a very complex system. You don't have anything close to even the order of magnitude of data that you need." So it's very clear that going forward we need more data. And as people have said, "This is the era in which the physical sciences will really help and the mathematical sciences will really help the biological sciences." So we need to go from old fashioned medicine, 19th and 20th century medicine. You have the doctor and the doctor says, "Okay, I'm going to check your blood and I'm going to check your sodium and potassium and a few things and then I'm going to kind of guess what's going on." Those days are ending for the future of medicine. And of course we see this very clearly with Alzheimer's.
And by the way you see it also in cancer where at least in cancer, you can sequence and you can look at the proteome and you can look at the genome of the tumor cells and say, "Okay, what changed?" And we can attack that. And that is the basis for precision oncology. Well, if we're going to do the same thing in neurodegenerative diseases, the problem is slightly different because we have an ongoing problem. In other words, in a cancer, once you've had those somatic mutations, you've got the cancer. Now it's going to continue to evolve, so you have to address that. But you can look after the fact. Well, in some ways, we have an advantage. With a degenerative process, you have ongoing exposure, you have ongoing pathophysiology, so you can address that in real time. So you need to start by looking at much larger data sets.
We need to know not only the usual things, the historical things and genome and microbiome, but we need to look at what's driving this. And as you know, a few years ago, published a paper on the different subtypes of Alzheimer's. So you can see when someone has more of an inflammatory driver as the main driver to this degenerative process. You can see when it's more of a glycol toxic driver, when it's more of a toxic driver or an atrophic driver or a vascular driver or a traumatic driver. These are the various pieces of this. So the bottom line is we need to have help, support. There should be a seamless interaction. Essentially, the doctors should have very simple help just like he or she would have help from an intern. You need to have someone who's in this case, a digital who can say, "Okay Dr. Sandison, here are the data that you need. Based on this person's genome, based on their exposures, based on what we're seeing in the urinary talks for example, these are all the things that are likely to be driving this synaptoclastic state."
It makes your job so much easier and so much quicker. And then you can focus on the top things. As we've said before, there are dozens and dozens of things that may contribute. But as you know, for most people, there's a top several. And if you can get those things and get them optimally treated, you're going to do much better. And on the other hand, if you're always treating the same one thing, yeah, sometimes you'll get success. Many times you won't. So the idea for Apollo was we need to bring together tech and medicine in a way that is mutually reinforcing where the medicine helps the tech to get better and the tech helps the medicine to practice better. And so to have the appropriate code, to have the appropriate ultimately AI to evaluate all the different data that are coming in, this will help us to make the approach better and better and better.
Admittedly, the original recode protocol, it's just a beginning. It's very much what you'd say an early, early approach to this. But even that gave us some really exciting improvements. It also showed us things that weren't improving. So as we continue to make that better, the computer will really help us in evaluating this. And so that's the idea with Apollo interacting with a wonderful group, Lance Kelly and his group from Silicon Valley, and that now will generate for you a report and tell you here are the various things that are driving this process. And help you, now, as you indicated earlier, it can be overwhelming. No question about it. However, we have to remember that even doing one thing is better than nothing.
Importance of Health Coaches in Helping People Get Better
Dr. Dale Bredesen: So start at the beginning. I really believe that the health coaches are playing a central role in helping people to get better. They're the ones that are interacting more commonly. They're helping them to stay on the right track. The doctors are really helping to look at the overall thing and decide with their wisdom and their experience, here are the things that are the best. They've got to use psychology to get the best approach to help people to get better. But they've also got to use their many years of experience to figure out what are the most critical things. And then their knowledge of the armamentarium to say, here are the things that are going to work best for this person. However, they are busy. They don't have as much time to interact day in, day out with these people as the health coaches do.
And the health coaches therefore have to establish a good relationship both on the doctor's side and with the various patients. And that's the way I think that a successful team, and of course that includes nutrition. It includes nurses, it includes various people, even psychologists and these sorts of things that are critical to the best team going forward. But the exciting thing is this area is changing from an area of total hopelessness to an area of incredible success and an area of really growing success and growing learning so that we're now learning with each person what can we do better? We've got some amazing, amazing n of one stories as you know, and as you've seen yourself. So each one of these is teaching us something. We're having a really interesting story right now with someone who is in the very, very rare category of APP mutations and we'll see how it goes.
But so far, this has gone from completely hopeless to, okay, things are looking pretty good. And so this would change the way all future generations for the family, if we can continue to have good outcomes here. So I think that this is an area that there's so much excitement for the future and there's no question that Silicon Valley is going to play a prominent role in improving medicine and medicine is going to play a prominent role in altering the things that Silicon Valley does for human outcomes.
Assisted Living Facilities for People with Dementia
Dr. Heather Sandison: I was at Marrama this afternoon having lunch with the residents who are there and as you know Marrama is brand new. It's the residential care facility where we're creating an immersive experience in this protocol. And one of the residents was just sharing with me. She has all of these ideas about how she wants to participate in the world with her grandkids and the things that she feels like she still has contribute, yet she feels like her body and her brain hold her back. And already she's been there for two months now and already her incontinence has improved. So we haven't worked. We're waiting for 12 weeks and we're going to retest her mocha. But her incontinence has improved. Her vision has changed a bit for the better, and she's actually reading and comprehending more and she can already tell that and we can see her interacting with staff and with other residents in a new way. So it's been really fun to be able to watch it even day to day with these amazing souls who do have so much to give but are really restricted by this disease.
Dr. Dale Bredesen: Yeah. You know, the most exciting thing to me over the last decade has been going from what was a theory on a yellow pad of paper 30 years ago, to starting to see people there as you know, the wonderful stories about people who have improved and what they start to do again. And in the past, there has never been. I mean, Marrama is the first, and I've told many people about it. It's such a great idea. There's never been a time when a person went to an assisted living facility with the idea of, here's what I'm going to do when I get out. It just, it wasn't part of what you thought about. It wasn't in the lexicon, the return from the assisted living facility. And at the same time as you indicated, you have to keep tweaking. You have to keep looking.
You can keep getting better and better and better. And we see this all the time. One of the most common things I hear from the spouses is they're simply more engaged. They interact with me more, they respond better, they're quicker. I mean, it's the light went on and then they start to get things back. Like the reading that you mentioned, we hear that a lot. They like to read again. They like to do active things again. So you're absolutely right. It's as if there's something weighing down their brains. They're just not hitting on all cylinders. And as that begins to lift because you've identified the very things that are holding it back, you now start to see improvement. And now you also start to see, ah, how could we make it still better?
How can you keep going, keep going? And it's just been so great to hear these wonderful stories for people who get back in the flow of things. And people who say, "I have my wife back or I have my husband back. I have my grandmother back." These things are just so wonderful. And of course, most importantly of all, these people sustain their improvement. Now the first people that were on this protocol are now beyond eight years and still doing very, very well. So very excited. I mean, that was unheard of before someone sustaining improvement for eight years. So I'm very excited to see that.
How to Prevent Dementias and Slow Aging
Dr. Heather Sandison: So what are you inspired to do personally to prevent dementias or slow aging process? What do you do every day?
Dr. Dale Bredesen: Yeah. You know, I'm a little embarrassed you asked that question because I haven't done enough and I've been, especially since COVID-19 trying to focus more on that. So looking more at my basic parameters. And so what we've done, my wife and I over the last several years is to get on a more ketogenic same sort of diet. Plant rich, lots of salads, oil. And I know some people, any single thing people argue about, there's all sorts of argument about oil. I happen to like it. I think it's, olive oil is a good fat. We've done with apoe4.info and Julie G. You know that she was the one who originally suggested if you're ApoE4 positive, for a short period of time, you use the saturated fats like MCT oil, but slowly you move yourself over as you become insulin sensitive to more the monounsaturates and polyunsaturates. And I think that's great.
So good olive oil and salads and things like that. I've actually been looking at my own blood pressure more every day and looking at when I'm in a situation A or B or C, is it better, worse, doing more sauna, more basic detox, more filtered water, more castile soap, more exercise. One of the hardest things for me to change has been sleep because of course as an intern, I stayed up all night all the time, as we all did. It was, when I think of all the lost sleep and what it probably did to damage my brain, it really drives me crazy. So I tend to be someone who works at night. It's easier for me after everybody else goes to bed is when I can do my writing. So I usually write from 10:00 to 2:00 or 3:00 or 4:00, and that's not good.
So I'm realizing I need to dial that back and do much more early morning work and much less late night work. It's just not good for your circadian. So of course, I am doing some melatonin as so many people do. And then standard things including magnesium, including vitamin D. Of course in the COVID period, vitamin D, zinc. I take some age CC because of the support of the cellular immune system. And actually, you probably know Jeffrey Bland has just got some new stuff out, which I've just been looking at and taking. I think it's a fantastic idea. As usual, Jeff's a great biochemist and he's right on target.
And so immune system stuff is critical. And so those are the sorts of things that we're trying to address. We do, my wife and I do a lot of hikes here where we are in California. And all these things are great. Interestingly, we're learning from our two daughters. So our two daughters, from their generation, a lot of this stuff which to my generation was new, to them as like, well, duh, of course everybody does that. Of course everybody eats a ketogenic plant rich diet. What's wrong with you guys? And so I said to them, "When I grew up, smoking was the big issue for people in the generation ahead of me. Everybody was smoking of course, post world war two, and into the mad men era. It was all about smoking and drinking and partying."
And we watched what happened to people with that and it was trying to get off smoking. The smoking for my generation is sugar. Everybody's having all sorts of processed foods and all sorts of carbohydrates. And so from my generation, you want someone to come to your meeting, you serve pizza or you serve cookies. And how many medical meetings and scientific presentations I went to that had cookies, that had pizzas, that sort of thing. That's what you did. And you get to the point where that's the thing that gives you a kind of a quick high. I never have drunk a cup of coffee in my life because I never was interested in coffee, but what would I do if it's 3:00 AM and I'm dying? I would drink Coca Cola. I mean, when I was an intern because it would allow me to finish my work. Otherwise, I'm going to fall asleep.
So I realized this is horrible for my health. It affected my blood pressure. It affected my cholesterol numbers and things like that. So trying to dial back to get into a more resilient and healthy state. Of course, I recognized I'm in a poor age group for getting COVID-19, so I need to be very careful and very resilient if I'm going to survive this pandemic.
Dr. Heather Sandison: Yeah, you've got lots more work to do after this pandemic. We've got to keep you around.
The ARK Project
Dr. Dale Bredesen: We're just getting started. There is so much for all of us to do in neurodegeneration and in chronic illness. And one of the things we're actually doing is called the ark project, ARK for like the animals two by two by two. So we're beginning to look, and you and I have talked about this a little bit in the past, just a very small number of other degenerative diseases. One at a time, looking at their biochemistry, their genetics and what are their triggers. Because if you think about it, for each of these, we have a wealth of information but we don't have internally consistent models that predict outcomes and that can predict effective treatments. It's turned out to work quite well with cognitive decline. What about these other things? So we're just beginning those studies and we'll see what happens over the next few years. So we're absolutely at the very beginning of all this and all of us have a lot of work to do.
Acute Effects and Neurological Complications for People with COVID-19
Dr. Heather Sandison: Yeah. With COVID-19 and the connection with neurodegenerative diseases, I worry a bit about all of the ... I worry a lot in fact about all of these people who have been on ventilators for weeks and weeks and weeks and sedated. So both of those medications and then plus the low oxygen, how detrimental that will be. Plus the PTSD of being away from family is not hearing any loved ones voices for weeks. The damage that that will do and how much support that cohort of people will need over the coming years. Do you have any insights? And then also the strokes you mentioned. There's just so many things here where this model may be able to help people suffering directly from COVID-19.
Dr. Dale Bredesen: Absolutely. And this is such an important issue. And as I mentioned earlier, we're seeing all the sorts of things that are risk factors for chronic decline scrunched down here into two weeks or so with COVID-19. And as you indicated, there are all these acute effects. So people with COVID-19 have very frequent neurological complications and this has been published. Typically 60, 65% of them will have something neurological. As you know, anosmia is a common one, Gaucher's is a common one. There are cases of guillain-barré. There are cases of encephalitis, just on and on. Myalgias, pain, I mean just all sorts of syndromes. And interestingly-
Dr. Heather Sandison: Psychosis.
Dr. Dale Bredesen: Psychosis and poor response to hypoxemia. That's another one that's an issue. So on and on and on with all of these things. But separate from that and then as you indicated, all the stress related things. Separate from that, the big worry right now, and we don't yet know what's going to happen is will there be major sequelae to this in the neurological system? And of course the example, you go back to H1N1, 1918, over a hundred years ago, we had this huge wave of neuropsychiatric problems following that and the most well known of course was postencephalitic Parkinson's. Interestingly, it turns out that postencephalitic Parkinson's was probably not directly due to H1N1 itself, but rather due to another virus that was trailing it at the same time, which was probably an enterovirus based on subsequent research, probably a relative of the polio virus. And it caused a specific type, a specific syndrome which was often called sleeping sickness, but it was a viral form of sleeping sickness. These people would then come back but then subsequently, they had had damage and subsequent years they would develop postencephalitic Parkinson's or other things.
Of course, we saw that a lot of this in Oliver Sacks' writing, Awakenings, and then of course in that wonderful movie with Robert De Niro and Robin Williams, Awakenings. And so the big question is whether we're going to see the same sort of post viral chronic syndrome. And as you indicated, there are all sorts of potential contributors like hypoxemia, like severe stress on and on and like viraemia, like cytokine storm, immune system activation. Are we going to see a lot more multiple sclerosis-like immune responses? We just don't know yet. And that's going to be important. Are we going to see a bump in Alzheimer's? We already know we are seeing bumps in it from all these other things. We're seeing bumps from all the toxicity, we're seeing ... So for example, if you're living with heavy air pollution, you are at increased risk.
If you've got a lot of mycotoxins around, you are at increased risk. When I was training back in the early eighties, we never saw people in their fifties with Alzheimer's unless they had the rare cases of familial Alzheimer's which represents less than 5% of all Alzheimer's. Now we're seeing it in the sporadic Alzheimer's cases all the time. It's one of the most common things we see is people in their fifties with sporadic Alzheimer's disease.
Dr. Heather Sandison: Yeah. So there's this model of complex systems and of looking at multiple parameters influencing how susceptible someone might be to these longterm sequelae has a lot of potential value. And I hope that the world will take your lead and start applying it.
Dr. Dale Bredesen: I hope so as well. And I think as we have, again, as we have more and more with more sequence genomes and more look at larger biochemical data sets and in interactions, we'll be able to get a better idea of who is at highest risk, who's at intermediate risk, et cetera.
Next Steps for Making Alzheimer’s a Rare Disease
Dr. Heather Sandison: You talk about a world where Alzheimer's is a rare disease. What are the steps you think we need to take next to get there?
Dr. Dale Bredesen: Yeah, that is such a great question. Yeah, our goal as you know is to reduce the global burden of dementia and ultimately of neurodegenerative diseases, multiple neurodegenerative diseases. And so if you look at what it would take to make this a rare disease and the interesting thing, we have what it would take to make Alzheimer's a rare disease today. So it's not about the knowledge, it's about the implementation. So you would have to set up, just as we've set up in the past global systems for doing polio vaccines as an example. We now need to have a "vaccine" for Alzheimer's. But as you know, it's a very different vaccine. It's not a simple injection.
You're now looking at a protocol that would be used widely. And it will take setting up a global program to get people to look at these parameters and to get people to do the right things. The great news is the earlier you start, the better. And as I indicated earlier, people who have no symptoms and even follow a very simple protocol are just having really outstanding results. And so this is the way to go for the future and we need to look at global programs that will get people to do the right things, to recognize when they are exposed to various things. And by the way, there's interest in the same sort of thing for Parkinson's. There's a nice book that just came out recently called Prescription To End Parkinson's and it calls for people to be more aware of the toxins around them because these are such important contributors to Parkinson's disease.
So the good news is there's a finite number of things that contribute to our cognitive decline. And in a way, we simply are set up in an old fashioned way where we go along until we have symptoms of a chronic illness. That actually makes no sense. That's fine for acute illness. If you want to go along until you start sneezing and now you're going to get a ... If you're on your way to getting pneumonia and you're getting a fever and a rigor, okay, now you can treat it and you can do just fine and essentially return to normal. But the problem as you know with chronic illness is that we go along oblivious to the fact that it's been happening for years. And with Alzheimer's, you may go 20 years before you recognize that there's something wrong.
So we want to get people early. The good news is that you have a large window for treatment and prevention and so simply changing our views and simply changing the way we deal with this could change everything. So yes, I firmly believe that Alzheimer's should be a rare disease, can be a rare disease and will be a rare disease.
Dr. Heather Sandison: And if your datas are any indication, things that for the next generation will go in that direction.
Dr. Dale Bredesen: I hope so. They're checking their own parameters and I hope that they're going to live till a hundred very successfully.
Dr. Bredesen's New Book: The End of Alzheimer's Program
Dr. Heather Sandison: Yeah. So the name of your book that's coming out in August.
Dr. Dale Bredesen: Yeah, so the one that's coming out in August was named ... So here's what happened with that. I originally wrote a book that was about the first survivors of Alzheimer's and I called it The First Survivors of Alzheimer's. And we had some wonderful stories about first person stories. And then it was followed by a handbook. And I worked on the handbook actually with Julie G and my wife because I thought it would be great to have the three of us. One person's a clinician, one person's a scientist, one person is a user who's actually doing absolutely great herself. And so I thought this would really give a unique perspective to people. So you've got very practical things. Well when we submitted the book, Random House said, "Okay, but this is too big for one book. It doesn't fit in one book, so we're going to make it two books."
So the first book they decided they want to do the handbook first and The First Survivors will come out a year from now. So that's that one. So then the current one, they named The End of Alzheimer's Program. I have to say, I wasn't thrilled with that name because it sounds like it's the end of the program. But they argued, look, the end of Alzheimer's, people get that and so now we want to give them a program to follow it. A lot of people had said, "We want more detail. We want more practical things, we want more URLs, all that sort of stuff. And we also want to know what's happened in the last three years." Just as you mentioned earlier. So that's what's in the book that's coming out in August.
Learn More About Apollo
Dr. Heather Sandison: All right, so I'll be on the lookout to get that in August. And in the meantime, can listeners learn more apollo.com. Where's the best place to learn more?
Dr. Dale Bredesen: Yes, you can learn more at drbredesen.com. You can learn more at apollohealthco.com. You can learn more also at my cognoscopy. We recommend that everybody over 45, just as when we all turn 50, we should get a colonoscopy, when we all turn 45 or more, we should go ahead and get a cognoscopy and you should know where you stand. Again, if we're going to make this a rare disease, you need to know where you stand so that you can prevent yourself from showing up in late stages and suddenly, oh my gosh, this is very late stages. Just like we think about with cancer. You want to look as early as possible.
Dr. Heather Sandison: Get all that data. And then another question I get all the time is where can providers, health coaches, get your training, be trained in this Bredesen approach?
Dr. Dale Bredesen: Yes. Thank you so much for mentioning that because that does remind me that. So the next training, so ReCODE 2.0, all the new things, this is coming out in June, so next month. And so we've been hard at work on that for the last several months. We have some just wonderful training with Dr. Neil Nathan who's a real expert as you know in biotoxins and Dr. Chris Shade who's an expert in chemo toxins, Dr. Cyrus Raji who's an expert in neuro imaging. And I'm talking about the science on there. Dr. Anne Hathaway is talking about BHRT and Dr. Sharon Houseman Cohen who is talking about her work with genetics and cognitive decline and on and on. We have some, just some wonderful things.
And of course we're hoping to have a piece from you on there, which so what we're trying to do is we're starting with the initial piece and then adding on from practitioners who are doing this. And so we're hoping that you will be talking to us about what is it like to start an assisted living facility that is looking to return people to better health? Something that by the way, no one has ever done before. So you're the first.
Dr. Heather Sandison: Well, thanks. It's so much fun. Yeah. The day and just getting to meet people. I know that you've had a bit of this experience, but just hearing the stories is the absolute best part of my job. Dr. Bredesen-
Dr. Dale Bredesen: Sorry. I should have mentioned the training. So training is coming out. You can go to apollohealthco.com and we have over 500 people who are on the waiting list for the training. We're excited to have more people because there's just been, they've helped ... So the people out there who are doing this have helped so many people and it's just great to see. And of course they bring their own expertise to this. And everyone is different. Every patient is different, every practitioner is different and everyone brings their own expertise to do new and exciting things as you are doing.
Dr. Heather Sandison: It's so fun. Thank you for leading the way, leading the charge, letting people know that this potential exists to reverse cognitive decline. We are getting back this potential from people who had lost it, who weren't able to contribute, who weren't able to show up at the height of their wisdom and experience and to have that back is more valuable than anything I can think of. So thank you for everything that you do. It's been an absolute pleasure and thank you of course to all of our listeners for hanging in there with us and getting all of this insight and wisdom from Dr. Bredesen today.
Dr. Dale Bredesen: Thank you so much Heather. And please also, I know you already do this, but I think we have the ability to tell the families when you have a loved one who is suffering, make sure that all the children, I think of this as children of Alzheimer's. If you have someone in the family who is suffering, please make sure that we end it with this generation.
Dr. Heather Sandison: What a good call to action.