Transcript
Claudia von Boeselager [00:00:00]:
Up. Welcome to the Longevity and lifestyle podcast, Dale. It is such a pleasure to have you back on the podcast today.

Dale Bredesen [00:00:07]:
Great to see you, Baroness. Thank you for having me back.

Claudia von Boeselager [00:00:10]:
Thank you, Dale. Dale, since our conversation, and I realize it's going back to 2021, time flies when you're having fun, as they say. What has been happening in the world of your research in changing the face of how we interpret Alzheimer's, as in dementia?

Dale Bredesen [00:00:26]:
Yeah, we're really entering a golden age. We have been kind of in the dark ages, where people didn't understand what actually drove these neurodegenerative diseases. And for the first time, we can now begin to look at the right various biochemical, genetic, epigenetic parameters. And we can see, for example, for the first time, there are blood tests for PTAU 217, PTAU 181, a beta 42 to 40 ratio, neurofilament life, GFAP. These are all things we can look at very simply now, and we can see whether we're headed for this, because people have thought of Alzheimer's as old timers. You get this when you're old, and it happens late in life. That's not the case. You can see changes in your will be diagnosed much later.

Dale Bredesen [00:01:17]:
So, in fact, we can all improve our cognition, no matter what it is. And we can also reduce our likelihood, reduce our risk for cognitive decline later in life virtually to zero if people get on early. And as you know, you go through these four phases, there's an asymptomatic phase, there's a subjective cognitive impairment, there's a mild cognitive impairment, and there's a dementia phase. If we could get everybody to come in on the first two, get in on active prevention or early reversal, we see virtually everybody get better and do very, very well. I just submitted a paper on people who have sustained their improvement for over a decade, which is unheard of in the past. So now we're seeing results like we've never seen before. New blood tests, new trials, and we are in the middle of a trial. We are definitely looking for more people.

Dale Bredesen [00:02:12]:
So there are six sites. Please look@dementiareversaltrial.org and just to point on.

Claudia von Boeselager [00:02:20]:
That, and I'd love for people listening if you know someone, to get involved with a trial, but what would be the stage someone is at? And maybe someone has not been fully assessed for early cognitive decline or dementia. So what would be some of the symptoms where you'd say that, yes, this would be an ideal person to participate in the clinical trial.

Dale Bredesen [00:02:39]:
Great point. So this is very much like any of the drug trials, except it is a precision medicine protocol and it is at the MCI, mild cognitive impairment or early dementia stage. So if you've had a mocha score, something between 18 and 28 is typical. If you've had a CNS, vital signs that's more sensitive, so you may be down at 80, 90, something like that. It's mainly about complaints, people who are saying, I can't remember where my keys are or I'm having trouble, my memory is not what it was five or ten years ago, those sorts of things. So it doesn't have to be too severe, but it can be. We are including people with early stage dementia as well.

Claudia von Boeselager [00:03:27]:
That's really helpful. I have a few ideas for you, Dale, that I will share with also to reach to a larger community, because I know, as we know, that my mother suffers from dementia. Unfortunately, it's very late stage now, and it's such a sad, sad disease. And I love that you are really made this your life's passion and life's work, and have found modalities that are helping to improve it. And perhaps for people who missed our first episode, can you share what this groundbreaking research that you've been doing and protocols and clinical trials and case studies that you've been able to. What has been happening, what have you been able to do and how have you been able to do this?

Dale Bredesen [00:04:04]:
Yeah, great point. And we spent 30 years in the lab looking at this, but I should mention, for anyone who is already in late stage, and we've had some mild improvements in late stage, but it's hard to bring people all the way back because there are so many things that contribute to this. So for anyone who's in late stage, please ask all of the children who are, as they turn 40, or if they are already over 40, please get on active fringe. Get a cognoscopy. It's fairly easy to do, I have to say. It's much more pleasant than a colonoscopy. Easy to do and get your tests evaluated and see where you stand. And please get on active prevention.

Dale Bredesen [00:04:43]:
So what we found in the lab is that what we call Alzheimer's, what has been called Alzheimer's for over 100 years, since Dr. Alzheimer first described this in 1906, people had thought it was about simple things. Oh, protein misfolding, reactive oxygen species, some simple thing like that. And it turned out it's not quite that simple. It is a network insufficiency. So in that sense, it's very much about supply and demand. There are two major things that drive this process. One of them is reduced energetics.

Dale Bredesen [00:05:21]:
So if you have reduced blood flow, reduced oxygenation, so many people with sleep apnea, for example, they're at increased risk. Reduced mitochondrial function, which is why it's so great to be getting out there and exercising. Reduced ketone levels, any of these things are reduced energetics supporting your brain. The other piece is driven by inflammation. So, as you know, there are so many things in our current world that can produce inflammation. It can be biotoxins that we're exposed to, for example, from molds and things like that. Change in your oral microbiome, leaky gut, chronic sinusitis, a tick borne infection, any of these things. Metabolic syndrome, one of the most common ones.

Dale Bredesen [00:06:07]:
There are over 80 million Americans who have metabolic syndrome. So any of these things that will cause this chronic, typically systemic, including the brain, inflammation is calling out your microglia, your cells in your brain, to come and try to protect your brain. And so, as part of that protection, you are literally changing. You're switching over your resources from making synapses, making memories, keeping memories. You're switching it over now to protecting yourself. It's very much like changing from building bridges to supplying an army. That's basically what's happening. And when the army is firing, there are going to be some people who get hit and killed.

Dale Bredesen [00:06:54]:
And that is the problem. You are literally doing a protective downsizing. And the problem, as you well know, it can sneak up on you so that you can have years where things aren't quite what you thought they should be. But, yeah, people say, oh, it's just normal aging. I think that's one of the most damaging things that doctors do. You go and you say, my memory isn't what it used to be. And they say, that's normal aging. We had someone recently who was all the way into the fourth phase, all the way into dementia, and he went to a neurologist who said, that's normal aging.

Dale Bredesen [00:07:28]:
Oh, my gosh. I mean, this is the worst thing you can do. So we want to get in early, then we want to look to see what actually drove it. As you know, it's different for each person. For someone, it might be sleep apnea. For someone, it may be a change in their oil microbiome. Often it's five, six, even ten or 15 different contributors. So changing diet, exercise, sleep, stress management, brain training, detox, some targeted supplements, these are all things that can enhance our cognition for normal people and can help people who have cognitive decline to reverse their decline.

Dale Bredesen [00:08:07]:
And when we first reported this, people just didn't believe it. They said you can't reverse cognitive decline, but if you understand the science of what's actually driving it, then indeed you can. And we've now published a trial. Dr. Heather Sanderson, whom you may know published a separate trial doing our same protocol, got very similar results to ours. All these are available freely online. So you can look at the data, you can look at the patients, and you can see how well they did.

Claudia von Boeselager [00:08:37]:
What were some of the biggest challenges of people who, I'm thinking of people listening right now and thinking, okay, I want to jump on this. I want to do this. Where do you see are some of the biggest challenges that people have in adopting the protocol? And what are some of the tools and strategies that you think would be most helpful so people can adhere to it to really see the results?

Dale Bredesen [00:09:01]:
Such a good point. And Ariana Huffington has been making a point, and she started thrive global several years ago and she's made a point that it's those micro steps. You just do a little bit better tomorrow than you did today and then you just keep doing that. And after a while, wow, you're doing really well. And so you're right. The biggest challenge is to realize that whatever it is that you've been doing for the last few decades is not working. Your brain is now downsizing to protect itself. So you need to start changing.

Dale Bredesen [00:09:33]:
And so, as you know, behavioral change is not easy. But when you get the positive feedback, when you say, wow, and I got one just, I get these all the time, these wonderful emails, which is one of the reasons they did this wonderful documentary and talked to people who went through this and got better. And so this is actually now streaming. You can get it on Amazon prime, you can get it on Google Play.

Claudia von Boeselager [00:09:57]:
Let's discuss that in a moment.

Dale Bredesen [00:09:58]:
Exactly.

Claudia von Boeselager [00:09:59]:
About memories for life.

Dale Bredesen [00:10:01]:
Yeah, but getting people to do this, so you have to start with the basics that I just mentioned. You have to change their diet. We have, as in the western world, we eat a relatively unhealthy diet with a lot of processed food. And as a scientist, I used to poo poo these ideas 2030 years ago. I thought, oh, come on now. It doesn't matter that much what you eat. And I was wrong. My wife, who's an integrative physician, said, whatever you guys find in all your test tube experiments, it's going to have something to do with the basics.

Dale Bredesen [00:10:33]:
Are you getting the right amount of sleep? Are you getting deep sleep? Are you getting REM sleep? All this. And I said to her at the time? No, we're going to find one fold of one protein, and we're going to get a drug that hits that one fold, and we're going to cure this disease. And I should have listened to her 25 years ago. She was absolutely right, because it's more complicated than one little protein. This is like running a country or running a big company. You have a lot of different moving parts, and you're literally changing a network function. And so when you change network function, you don't take a hammer and go, wham. You make little changes here and there.

Dale Bredesen [00:11:15]:
So you're changing your diet. You're now getting a plant rich, mildly ketogenic diet. We call it keto flex. Twelve three. And it's a way that actually helps your cognition. We've had lots of good results with that. You're now going to get both aerobic and some strength training. You're literally now going to change a few things, and you don't have to change them all at once.

Dale Bredesen [00:11:35]:
You have to remember, by the time you're having cognitive decline, you've typically had the underlying biochemical changes for about 20 years. That's well documented by serial PET scans and by serial spinal fluid analysis. Good news. Don't have to have spinal taps anymore. You can now get blood tests. That is another step forward in what I'm calling you, the beginning of a golden age. We are not only reversing aging that we're all hearing about every day, we're also reversing cognitive decline. And we've now started the first precision medicine program in the world to reverse all neurodegenerative diseases.

Dale Bredesen [00:12:13]:
So we will have larger data sets. We will now be able to look at ALS and frontotemporal dementia. We've already had some good results with Lewy body disease. We've already had some good results with dry macular degeneration. So I'm very enthusiastic. And this is going to be at Pacific Neuroscience Institute down in Los Angeles. So very excited about that.

Claudia von Boeselager [00:12:33]:
Can you share a little bit more about that? Because this is really phenomenal. And I've had people come that their parent has been diagnosed with ALS, et cetera. I've seen parents of friends who have passed because of ALS. I mean, these are really cruel diseases. Can you share more about the work that you're going to be doing there?

Dale Bredesen [00:12:49]:
Absolutely. Thank you for, you know, it's so interesting. We're all used to hearing about, oh, you know, when you first heard about Twitter, like, whoa, this is completely different. When you first heard about Facebook, when you first heard about these different things that you can know, you first heard about web browsers and all these things that have been so disruptive and really changed the way we live each day, we don't think about that for medicine, but we need such disruption in the whole area of aging and neurodegenerative disease. These degenerative diseases that we get then they are huge. Alzheimer's will kill 45 million of the currently living Americans so many times what the pandemic has killed. So it's a very, very common problem. So what we need is we need to change the idea of, you go in late, they often start these very late, as you know, and then they give a medicine that hits one little thing.

Dale Bredesen [00:13:48]:
As we always say, there are 36 holes in the roof. You got to patch all the holes to get things to do better. And so they go in late, they give a drug, and it just doesn't work. So we need to change that formula so that we are now going in early. We have early detection, we have early treatment, and we have appropriately directed, we're targeting the things that are actually causing the problem. This is so important, and so have a wonderful opportunity now. And actually, I just had a wonderful meeting with. Dr.

Dale Bredesen [00:14:19]:
Lee Hood is the inventor of the automated dna sequencer. Really is my hero. Incredible guy. He's now in his mid 80s, brilliant, brilliant scientist and physician as well. And he's looking at whole genomes and epigenomes and all this. So we are now in the new trial. We are looking at genetics, epigenetics, biochemistry, all these different pieces so that we can understand for each person what's happened. So, actually, I went into the Pacific Neuroscience Institute, talked to Dan Kelly, who's the director there, and also Dr.

Dale Bredesen [00:14:52]:
David Merrill, who is the director of the Pacific Brain Health center, which is part of the institute. And they were enthusiastic. And so we are now establishing this first new program that will take people from all over the world who have neurodegenerative disease, and we will study the disease, and we will also develop treatments for this. As I say, we've already had some good outcomes with lewy body with macular degeneration. So I'm very excited. We need to get rid of this idea that all of these things are hopeless. This will really offer hope to people. Again, as you said earlier, it is tough when you come in really late when you've had this for years and years and years.

Dale Bredesen [00:15:32]:
It is tough, no question. I hope someday we'll be able to do better with those as well. But we need to understand them better. And so we need to get the people who are early or who are interested in prevention and start with that to look to see what is actually driving this problem and how do we get best outcomes.

Claudia von Boeselager [00:15:50]:
Yeah, it's such an exciting time. And so when is early for you, Dale? Like, if someone's there, let's say they're maybe late 40s, early fifty s, and they don't know, is it just lack of sleep or stress that maybe they've become a bit forgetful or whatever it might be? So when should people already be sort of waking up? Or do you think it's just from the age of 40? Cognoscopy is, like, the way to go. What would you suggest for people listening?

Dale Bredesen [00:16:14]:
Yeah, such a good point. So there are two situations here. One is, yeah, when you hit 40, it's best to get a cognoscopy and get on active prevention. But if you didn't do that, that's okay. Then when you notice that things have changed, when you say, you know, I just can't do what I used to do. I can't remember phone numbers. I occasionally will have trouble when I'm driving, remembering, where am I going here? We had one woman who got on the plane and she got to the other end and she said, why did I come to this city? She ended up getting on the plane and going back. She didn't remember why she had come to that city.

Dale Bredesen [00:16:49]:
When you're having changes, that you know something's not quite right. Don't wait. Do not let your doctor tell you, oh, this is just normal aging. No, there are people who are 100 years old who have great memories. So please, when you've got changes, come in, and sometimes it'll be organization. We have people who say, you know, I got a new phone, new iPhone or whatever, and I can't work it the way. I just can't kind of figure out how to get this working. That's organizational skills calculation.

Dale Bredesen [00:17:19]:
One person said that she couldn't figure out a tip anymore. Things like that, you know that something is not right. You're getting in early. And to be fair, we, in our trial, took people down to mocha scores of 19, which is fairly significant. Dementia. The new trial, we're going down to 18. But you're right, if you're down in the single digits, it is definitely harder. We've seen people go from 18 to perfect 30s.

Dale Bredesen [00:17:47]:
We've seen people go from zero to nine, which they still, they start speaking again. They do better. But we've never seen anyone yet go from zero to 30. That's my goal. That's what I'm hoping. And then it may take stem cells, it may take intranasal trophic factors. This is what we need to understand.

Claudia von Boeselager [00:18:05]:
Yeah. Which is really exciting. And if people want to participate or if they want to be involved, where would you point them to, Dale?

Dale Bredesen [00:18:15]:
Yeah, great point. So if they want to be in the trial, go to dementiareversaltrial.org and check that out. If they want to come to Pacific Neuroscience Institute, please check. Look at Pacific Neuroscience Institute or Pacific Brain Health center, which is the part within the institute that is going to house this precision brain health program.

Claudia von Boeselager [00:18:38]:
And that's people around the world that you would take in.

Dale Bredesen [00:18:42]:
Absolutely. People could come from anywhere. And I should add, there's been a lot of interest in psychedelics recently. And the interesting thing is they do have a potential role here. As you know, one of the things that they do is enhance neuroplasticity. So what we're looking at now, and that's one of the projects we're going to be doing at PNI Civic Neuroscience Institute, is, look, let's start by removing all the inducers. If you're having no sleep, if you're having sleep apnea, if you've got a change in your oral microbiome, we can remove those problems. If you're living in a moldy house and that's triggering your brain fog and triggering ultimately your cognitive decline, let's remove those things first.

Dale Bredesen [00:19:23]:
Then the second step is let's get you to be resilient. So let's get you on the right nutrition. Let's get you, if you need specific medications, whatever it is, let's get your resilience up there. One of the things we need to do is optimize your immune system, because just like in long Covid, where you have too much inflammation and too little adaptive clearance of the virus, in Alzheimer's, it's the same thing. You have this ongoing inflammation. You have much less here, you've got much less of your adaptive system. So same idea. So we need to optimize now.

Dale Bredesen [00:19:57]:
After we do all of those things, now we want to rebuild because you've lost some synapses. Let's rebuild that plasticity. And there's a lot of promise, especially in starting with these micro doses and just getting people to enhance their plasticity now, essentially, to regrow and get synapses where they were lost before. You don't want to do it while you still have the inducers, because they're just going to be damaged as soon as you make them. But once you've controlled all that, that's the time to look at these. So I'm very enthusiastic about that. There's so much in the armamentarium, Claudia, stuff that we just didn't have five or ten years ago. The armamentarium is huge.

Claudia von Boeselager [00:20:40]:
So exciting. And I was having conversations. I was speaking at the conference in Miami, people doing ketamine assisted therapy for healing chronic pain, trauma. I mean, it's so beautiful. I know Dr. Pamela Crisco up in Canada with the roots to thrive program, what they're able to do to help patients to recover within months, what 20 years of talk therapy was not able to do with ketamine assisted therapy as well. So there's a really exciting time and space for this as well. I'd love to talk, Dale, about memories for life.

Claudia von Boeselager [00:21:10]:
Can you talk about this beautiful documentary that you have put together and obviously with a team, what was the goal of this? And can you share for my audience a little bit more about the documentary?

Dale Bredesen [00:21:21]:
Yeah. Thank you so much. So NHK is the CNN of Japan. There is a big concern in Japan because of the fact that there are so many older citizens in Japan. And so the government has said that dementia is the number one concern in Japan. So back in 2017, I was approached by a director, Yuki Tokagawa, fantastic director, who's an award winning director in Japan. And he said he would like to do a documentary about the work we've been doing and talk to the various patients who've gotten better. And let's get it from the horse's mouth.

Dale Bredesen [00:21:55]:
Let's hear, what did you go through? What did you have before? And so he started to collect stories and indeed has completed the documentary. And in fact, interestingly, one of the patients, who's from a very famous family on the east coast, said, I would like to support this documentary, and I'd like you to make specific edits, et cetera, and really try to enhance it because I think the first version was a little too scientific and maybe not as watchable. He's done a very nice job. I give great credit to Yuki and his team. He has interviewed, as I mentioned, various patients. He talks a little bit about the work we did in the lab, and how did we come to the conclusion that this wasn't about just giving a single drug, that you have to actually look at these different parameters. And then, of course, the skepticism, people say you just can't reverse cognitive decline. Well, we've seen it again and again and again.

Dale Bredesen [00:22:48]:
So he talks to some of the patients and shows how much better. One of the people that he interviews was an attorney who was also working in Broadway and off Broadway productions and things like that. She lost her ability as an amazing person. She spoke some Chinese, some Russian, and played the piano. She lost all of those. She got them all back. So she's now playing piano again. She's now able to speak Chinese again, and she's now able to speak Russian again.

Dale Bredesen [00:23:17]:
And she's not perfect with her Chinese and Russian, but she went where she had zero. And she said, as she was driving along one day when she was on the protocol, the Chinese just started spilling back. I mean, it's such an amazing vision to imagine yourself kind of driving along, and all of a sudden, all these chinese words are just, like, reappearing things that you knew before you lost, and now they're just streaming back in. One of the things that people had always wondered if you actually do get better, have you lost the memories that you lost forever, or do they come back? Well, she showed they often come back. You can actually get things back that you had truly forgotten. She had a point where she would sit down at a piano, couldn't read the music anymore, and then suddenly, she sat down at the piano, this was, like, a year later, and said, oh, my gosh, I can read music again, and just started to play. So if you see these stories and it doesn't choke you up a little, then you probably haven't lived with someone with Alzheimer's. It's something that touches so many of us, as I mentioned.

Dale Bredesen [00:24:22]:
And to see people getting better, it certainly makes my day. Anytime I hear about someone getting better, it's so exciting. And as you know, not everyone does. So we're still trying to understand how can we make it so that every single person gets better. In our trial, 84% of the people got better. But to be fair, we didn't take people in the trial who had single digit mocha scores. As I mentioned, we went down to 19. There's so much more work to be done.

Dale Bredesen [00:24:55]:
And as you mentioned, what about people with ALS? What about people with other diseases? Als has been one of the toughest. I used to see it as a practicing neurologist years and years ago, and it was my least favorite thing to see walking into the clinic, because it was 100% death sentence, and typically within three years or so. So now we have some hope that we may be able to do something. And there's a wonderful neurologist from Duke who's published some work showing occasional cases. And why did they get better? They had a number of things that happened to them. Is there something we can learn from these people? So it's a new day, and I think even five years from now, we're going to see a lot of improvements.

Claudia von Boeselager [00:25:39]:
Which is so exciting that these things are not death sentences, as you said yourself, anymore, and that there are modalities to do. And obviously, the prevention is better than cure. Getting on top of it and being proactive is so fundamental.

Dale Bredesen [00:25:52]:
And I should mention to follow up on memories for life reversing Alzheimer's. Sorry about that. I kind of got off track there. So it's called memories for life reversing Alzheimer's. And it is now streaming, actually starting yesterday, streaming on Amazon prime, on Apple TV and on Google Play. Soon it will also be on voodoo.

Claudia von Boeselager [00:26:12]:
And, and I mean, I've seen it for anyone interested, I was even watching it with my seven year old daughter, who found it very interesting as well. I think it's for the whole family to just realize that there are so many beautiful cases and it is reversible if you know somebody who's suffering to take action sooner than later. Yeah, Dale, I'd love to touch on the naysayers. Right. So I've been to, with also my mother, to many neurologists as well, that are just like, no, there's nothing you can do, or, oh, well, the FDA has approved this drug, we should try this drug, but nothing else is going to work. What is to help people understand that may have gone to the neurologist and said either, oh, you're fine, or, oh, this is just age related cognitive decline. Why is this happening in the first place? So can you just shed a bit of light to that? And then also, why has there been some people who don't believe fully in the protocols that you're doing, et cetera? Let's discuss the skepticism a bit there.

Dale Bredesen [00:27:10]:
Yeah, such a good point. So what's happened is because for over 100 years, this has been a disease where there's nothing to do and therefore everything is upside down. What they say is don't bother to check your genetics because there's nothing you can do about them. Well, actually, now there is, and there's a wonderful website, as you know, started by Julie G. Called apoe four info. If you find out that you're apoe four, and that's a quarter of the population, so 75 million Americans, about 7 million, have two copies of apoe four. So one from the mother and one from the father. If you have zero copies, your lifetime risk is 9%.

Dale Bredesen [00:27:49]:
Not too high. It's not zero, but it's not too high. Single copy, you're at 30%. Two copies, you're about 70%. So, yeah, so you want to get on some prevention and listen, you should never have to worry. As I told our daughters, who are now both in their thirty s, you are in the first generation that does not fear Alzheimer's. You don't have to fear it. Either get on prevention or get in early treatment.

Dale Bredesen [00:28:17]:
You will never have to worry about this problem. And I know, again, that sounds crazy, and people will push back. The idea is that because people had nothing, they tell you it's just normal aging. There's nothing you can do. Oh, you can try a drug, but it's not really going to help you. All these things. Don't check your genetics. My gosh, this has all changed now.

Dale Bredesen [00:28:40]:
The modern view is there's a lot you can do and start early. Get in there. Don't keep saying, that's another thing. Doctors kept saying, pretty good chance it's not Alzheimer's, just come back next year. And they'd keep saying that until they say, oh, yeah, it is Alzheimer's. Sorry, you're going to die. I mean, what a barbaric way to practice medicine. Now, as you can imagine, we came out with the first paper in 2014 and said, we have now been the first to reverse cognitive decline in patients with Alzheimer's disease.

Dale Bredesen [00:29:10]:
And to be fair, they weren't late stage Alzheimer's, they were early stage Alzheimer's. We got very good results with them. And so people said, well, we're not going to believe it until you have 1000 people and have double blind, placebo controlled trial. Well, there's something in medicine that these people obviously weren't thinking about, which is called compassionate use. If you have something for, let's say you've got an untreatable cancer, let's say late stage esophageal or pancreatic, these are kind of typical ones that are very hard to treat. If you have something that is promising, then there is something called compassionate use where you say, okay, let's try this. Even though it hasn't had many, many years and FDA approval, let's try this. So this is what we've been doing, compassionate use, to help as many people as we can.

Dale Bredesen [00:30:00]:
We've now had over 7000 people go on the protocol. But meanwhile, in the background, of course, we're building the plane as we're flying it. Right? So we've now had over 100 people. So we documented, we published that. These are all peer reviewed publications. Then we did a proof of concept trial. Then Dr. Heather Sanderson did her proof of concept trial.

Dale Bredesen [00:30:21]:
Now we're doing a randomized controlled trial. So we're getting all these things going. But if you tell the people who've gotten better between 2014 and now, and by the way, I just had lunch yesterday with patient zero, who started this in 2012, she is now 79 years old. As she pointed out, she would be dead and gone by now. She is now a brain health coach and is doing absolutely great. She just did 100 miles bike ride.

Claudia von Boeselager [00:30:52]:
Wow.

Dale Bredesen [00:30:54]:
That's amazing.

Claudia von Boeselager [00:30:55]:
Yeah.

Dale Bredesen [00:30:56]:
If we had told all these people, no, you can't do any of this, because we're going to wait until it may take us 15 years to do all these trials, then we'll offer it to you, they would all have passed away. You really think that's the right way to go? So, interestingly, the one who was patient zero was sent by her friend. Her friend had two friends at that time who were both at about the same relatively early stages, but clearly both struggling. One of them came west and came and started this. And she's the one who's 79 and doing well. The other one decided not to. She passed away about a year and a half ago and did develop more significant cognitive decline. We know what the natural history of this problem is, so let's not pretend that that's not what it is.

Dale Bredesen [00:31:44]:
Let's get people in as early as possible. And as you know, youngsters like you are the first that you really don't have to worry about this problem. Get on active prevention or earliest treatment, and you really don't have to worry about this.

Claudia von Boeselager [00:32:00]:
So exciting. And so, Dale, I'd love to, if you can shed light with my audience, to why the Alzheimer's drugs that are there, that look for one specific cause, why that doesn't work, and why there's, I believe it's up to 38 different underlying drivers that you've identified that lead to it. Maybe you can expand a little bit on this and what they are just to help people to understand why we need to look at this from a different.

Dale Bredesen [00:32:23]:
So, you know, a lot of people have talked about Twitter now has become x thanks to Elon Musk, and know they want to make it better. In fact, when Elon Musk bought it, he said, I want to make it better. So if you say, how are you going to make it better? And he, you know what one janitor are we going to hire that's going to make X suddenly the whole world be using it? It's not that simple. You're going to have to look at the content and who's allowed, who's not allowed. How do you control that? There's all sorts of. This is a complex system. Whether you're talking about a company like X or whether you're talking about a country, you've got to look at how the whole thing works. So when you look at Alzheimer's, unfortunately, it hasn't turned out to be a simple switch.

Dale Bredesen [00:33:11]:
You just go from, oh, just, let's remove the amyloid. So the thought was in the past that amyloid was the cause of Alzheimer's, and many people still believe that, but it's not that simple. So what is amyloid? It's turned out that amyloid is part of your innate immune system. So when you get exposed to various insults, and they can be the things we talked about before, it can be biotoxins, it can be some oral microbiome. They show repeatedly that oral bacteria show up in your brain. So they do get in there. And what does your brain do when it gets assaulted like this? It now coats these bacteria with amyloid. It is a sequesterant and it is an antimicrobial peptide.

Dale Bredesen [00:34:00]:
So it's like putting little igloos around that actually have an atmosphere of cyanide. So you're killing these bacteria and you're coating them so that they can't get. And they can't cause more inflammation. So amyloid is really just part of inflammation. And, of course, your microglia get activated. It's much more than just amyloid. Your astrocytes get activated, all these changes that occur. Your brain is not trying to give you Alzheimer's, it's trying to protect you from these various problems.

Dale Bredesen [00:34:35]:
So what happens when you take this anti amyloid drug? You're removing one of the protectants. So we see, fairly frequently, people actually get worse. And, in fact, Sally, who's one of the ones who's in the film, went on an anti amyloid trial and actually clearly got worse with each injection, which was once every couple of weeks, she would get worse. And so after eight injections, she said, something's wrong here. I'm getting worse with each of these. And so she went off. She then went on her protocol. She went from 24 on her mocha to perfect 30.

Dale Bredesen [00:35:09]:
She's done great. She's now seven years in, still doing very well. And interestingly, she did have one backslide after six years. And so we looked for what's causing that, and she had three new insults that we identified. Those were treated by her physician. She got better again. So this is a response. Now, let's be fair to the pharmaceutical companies.

Dale Bredesen [00:35:32]:
There is a time when you want to get rid of the response. And here's an example. If you are dying of cytokine storm from COVID an acute Covid, people will give you dexamethasone or prednisone. They'll give you steroids because you've got such a strong response, you are dying of cytokine storm. So essentially, you're giving up something to get something. You're saying, I'm going to lower your immunological response. That's not a good thing for the long run, but it's going to save you from dying of this hyper response. In Alzheimer's, you are dying of a chronic mild.

Dale Bredesen [00:36:08]:
It's not cytokine storm, it's cytokine drizzle. And so to remove some of this, you are going to remove a little of what's essentially a long acting cytokine. However, in the long run, what you need is to reduce the actual insults themselves. Then you want to start cleaning up the amyloid down the line, and not with such high doses. They're using these massive doses to just rip out the amyloid. Well, the amyloid is in the blood vessels. So what happens when you rip that out? You bleed. And so people have developed hemorrhage, they've developed brain swelling.

Dale Bredesen [00:36:45]:
I mean, it's just barbaric. Once again, so I look forward to the day when people do the right things, identify things, and then, fine, use the drugs later at lower doses to begin to remove that slowly so that you're not just ripping this stuff out of the brains. And so if you actually look at the data, they're quite clear they do not. You take those drugs, such as Lakembi Dananumab is one that they're looking for approval on. Adecanumab was the earlier one that failed a trial, barely succeeded in another trial. They do not make you better. That's something that people don't understand. They don't make your cognition better.

Dale Bredesen [00:37:25]:
They don't keep it the same. What they do is instead of going down this fast, you go down slightly more slowly. And in women, by the way, it didn't work as well. And, of course, women are the majority. It's about two thirds of people with Alzheimer's. So you have only an 11% slowing. Also, people who are apoe four positive. And again, that's most of the people with Alzheimer's.

Dale Bredesen [00:37:49]:
The drugs didn't really work in those people. So it's the early people who are apoe four negative who are men. Those are the ones where there seemed to be a little effect to slow the decline, about 27% to 30%. In that range, 27% was for the overall group of men and women. And since women didn't do very well, the men did a little better than that.

Claudia von Boeselager [00:38:12]:
Why are women so affected? This is a really important point. As we know, they've been omitted from clinical research for so many years of childbearing age. But what is going on? And how much does oestrogen and its neuroprotective factors play a role when menopause strikes, et cetera? What is going on there for women?

Dale Bredesen [00:38:30]:
Yeah, that's such an important point. And as Maria Shriver has said, this is a woman centric disease. 65% of patients and 60% of caregivers in Alzheimer's are women, unfortunately. And so there are multiple mechanisms, and many of them are hormonal, and I'm sure there are others that we don't know about yet, but here are a few. Number one, estradiol, as you know, is a very good trophic support for brain. And, Claudia, you can literally trace the molecular pathway. Estradiol binds to the estrogen receptor. That complex then enters the nucleus of the cell and actually triggers hundreds of genes.

Dale Bredesen [00:39:13]:
And guess what? One of the genes it triggers comes back out. It's called the alpha secretase. It cuts the app, the parent of amyloid, to make non amyloid, to make the side that goes toward productivity, making synapses, keeping synapses. So estradiol, just as you said, is actually support for your brain, for making memories. Now, what happens is you drop off fairly quickly at perimenopause and menopause, as you know. And the worst thing you can do is that rapid drop, which is why I really believe in BHRT and, of course, Dr. Anne Hathaway and Dr. Kat toops and Mary K.

Dale Bredesen [00:39:53]:
Ross and on and on and on. So many wonderful people. Prudence hall is a world expert, and there's so many people who've done such a great job with BHRT. So I think that's so important. And then the second thing is that you also have progesterone. Progesterone turns out to be very important for detox. So when you start losing your progesterone, you're actually not doing as well. We all have toxins we're exposed to.

Dale Bredesen [00:40:21]:
We're not living in a detoxified world. We're exposed to things all the time, and that's air pollution. And it's the mercury in some fillings in the amalgams. It's the food that you're eating. It's the mycotoxins, it's the mold in your house. It's the cosmetics. It's, oh, my gosh, there are just so many things. So we are constantly fighting that, which is why things like sauna can be so helpful.

Dale Bredesen [00:40:45]:
And so what happens as you lose the progesterone? Your detox capability is going down. So now you're accumulating. And if you're already kind of close to what you can handle, you're now over the top. If you're low, great. You're still going to do well for a while. And then there's a third mechanism. As you know, during the time you have what's called an osteoclastic burst. So you're now changing normally.

Dale Bredesen [00:41:10]:
You're making bone, you're laying it down with your osteoblasts, and you're picking it up with your osteoclasts, and you're doing that constantly, remodeling to make your bones strong. As you enter the perimenopause and menopause, you now have more osteoclastic and less osteoblastic. So you are now picking up the bone, and you've sequestered these toxins, some of them in your bones. So now you're re releasing these, and we see so many people, 52 year old woman going through menopause who's developed Alzheimer's. It's something I never saw when I was training back in the 1980s, it was rare. Now we see it all the time. It's one of the most common presentations. We see late 40s, early 50s, getting a toxin related Alzheimer's due to this osteoclastic burst and this entering menopause.

Dale Bredesen [00:42:08]:
So I recommend to everyone, keep an eye out for that. Make sure your detox is good, make sure that you are optimizing things and preventing yourself from cognitive decline. And talk to an expert in BHRT, because it may really help you and certainly may help your cognition tremendously.

Claudia von Boeselager [00:42:28]:
Yeah. And for those maybe unfamiliar, BHRT is bioidentical hormone replacement therapy in parts of the world called body identical hormone replacement therapy. Just to be clear, so there's any ambiguity there with that. You were mentioning the hope of people who are in the single digits. MocA score. So the Montreal cognitive assessment score, perfect cognition is 30. Right. And it declines in over time for people listening.

Claudia von Boeselager [00:42:56]:
What do you believe? Or what are your hunches? I'm just curious, Dale, what do you think could be the drivers that would help people that are already down to a single digit get back up to, ideally, twenty s or even higher up to 30.

Dale Bredesen [00:43:11]:
So, one of the projects we've started, one called the Arc project, which looks at different diseases, but the other one that I'm very excited about is called the Sarah trial, severe Alzheimer's reversal attempt. And at this point, it's only an attempt because we just don't. No one's done it. As I say, we've seen people go from zero to nine. We've never seen them go from zero to 30. So what we'd like to do is literally just take a couple of people, look at their entire genomes, epigenomes, look at everything possible, and see what actually drove this. And then this is now going to have much more on the rebuilding phase because you've lost a lot of synapses. So what I would include in that would be, number one, stem cells.

Dale Bredesen [00:43:52]:
You're going to need to rebuild these synapses. And the stem cells can be helpful. Both. They have multiple wonderful effects. They have effects on your immune system, as you know. They have effects on your trophic factors, for example, all of those things. Second thing is intranasal trophic support. Intranasal trophic factors, things like C LANC and Cmax and ADNP.

Dale Bredesen [00:44:16]:
There's an interesting molecule called devunitide that was tried years ago intranasally, but it was tried as a monotherapy. That's not the way to test these drugs. And so as a monotherapy, it failed. No surprise. I think it has great potential as part of an overall protocol because it has tremendous. It's highly potent as a neurotrophic factor. And I would put as number three, after the stem cells, the trophic support things like intranasal. And I like intranasal because it gets into the brain much better when you do intranasally.

Dale Bredesen [00:44:51]:
And so I think there's tremendous. Now, the problem has been that the FDA has just come out against compounding peptides. I think that's a huge. And I'm very, very sorry to see this. I think they really kind of throwing the baby out with the bathwater. They're not realizing there is such great potential here. So I hope that they will, at some point, wise up and come into the 21st century and actually allow people to use these because I think they can be very helpful. And until then, I think people will use them in trials.

Dale Bredesen [00:45:24]:
And then there are other things that can be helpful as well. I like Ewat exercise with oxygen therapy. I recommend that for everyone, though, that's something relatively easy. It can get better oxygenation into the far reaches of your brain, these sorts of things. And then this is where I would add the psychedelics, because they are supporting neuroplasticity. Remember, you're trying to rebuild something, and so of course, the earlier you start, the more there is there to work with. When you're starting with mocha scores of zero or one or two, you have lost so many synapses. And Cyrus Raji is a professor at Washu that we work with fantastic neuroradiologist, and he was showing just recently on some of the patients, this was a person with a score of 17 on the mocha.

Dale Bredesen [00:46:14]:
So dementia, but not too late stage of dementia yet. But looking at the support for that region of the brain, you could see how much was lost already. It was just a striking view of what this does to your brain. So what we need to do now is everything possible to return and enhance neuroplasticity. And the good news is that the psychedelics do support plasticity. So done in the right way, at the right doses, in the right time, I think they have a real potential to be part of the armamentarium to improve people. So for the Sarah trial, we would want to include all of those things.

Claudia von Boeselager [00:46:56]:
Very exciting. And I'd be curious, first of all, for the psychedelics, is it psilocybin, is it LSD? What psychedelics would you be looking at for these trials?

Dale Bredesen [00:47:06]:
You know, it's interesting. They all interact with the same serotonin receptor. So I think that it's going to be more getting the right dose, not hurting people, but just getting to the point where you're actually tweaking this receptor. So yeah, it would probably be psilocybin, but it could be others. And certainly people are using ketamine a lot. LSD is another possibility. Actually. You want to be careful not to scare people.

Dale Bredesen [00:47:42]:
Obviously, people have so called bad trips. Boy, that's from the 1960s and Timothy Leary and all that stuff. But I think bringing this back under the umbrella of neuroscience could definitely help people if done in the right way, at the right doses, with the right other things. I think, again, you've got to have the right armamentarium. And, you know, Claudia, we're seeing there are physicians. This is a lot like surgery. There are physicians who are doing this really well and getting people to respond and do very, very well. When I say this, I mean the protocol, the approach, and getting a lot of people to do better.

Dale Bredesen [00:48:18]:
There are others who are cutting corners and just not doing it the right way and they're just not seeing people get better. So it is a real skill to be able to use the right things in the right way at the right doses, at the right time for the right people and to get the best outcomes.

Claudia von Boeselager [00:48:34]:
Yeah. And I think for people perhaps unfamiliar with the psychedelic research that is out there, I mean, John Hopkins and Imperial College in London have some phenomenal results. But many other institutions now around the world that are working on psychedelic assisted therapy for many different. It's really, really promising and very exciting. So I think if people are interested to just educate themselves a little bit more on this. Dale, at what stage are these Sarah trials? What is happening there? And are you directly involved with it? What's your role?

Dale Bredesen [00:49:06]:
I propose this, but we're probably six to nine months away from having this star. We're starting with the arc, the other pieces, we're putting these all together at PNI. So yeah, I will have to convince others at PNI that a serotrial is a good thing. I've also, as I mentioned earlier, Dr. Hood, my hero and role model, such an incredible and brilliant scientist and physician. He's doing these very large data sets, omics work, and he's published with his team. He started a new company which is called Phenome Health, which is actually a nonprofit looking at things like Alzheimer's disease and diabetes and getting these much larger data sets. So this would be the sort of thing that I would love to collaborate with his group to see whether if you look at these much larger data sets, can we really get a firm understanding for each person exactly why this happened and what are the things that we need to address now? You're going to still have to rebuild things when that's over, but starting with looking at what caused the decline is critical.

Claudia von Boeselager [00:50:16]:
Dale, as we finish up today, what are some things that you would want everyone listening to really realize from our conversation to take action for? What do people really need to know and really understand?

Dale Bredesen [00:50:30]:
Yeah, the most important thing is that Alzheimer's is now optional. And I know this sounds crazy, and you mentioned the pushback earlier. Yes, there have been pushback for people who want more and more trials. Fine, but let's not withhold this from people who need it today. Because we've helped a lot of people by having compassionate use. So I would recommend everyone please get a cognoscopy if you are 40 or over, please get evaluated. Get on active prevention. It's becoming easier and easier.

Dale Bredesen [00:51:01]:
There's now a meal service. We work with nutrition for longevity that will deliver plant rich, mildly ketogenic diet to your home. So it's very easy. You don't have to go and search for all the different things. Let's all change from hopeless to hope because that's what has been proven again and again by the studies that we've done.

Claudia von Boeselager [00:51:27]:
So beautiful. Dale, thank you so much for your time for coming on today. It's always been such a pleasure and I want to share afterwards actually a few things with some ideas for you as well. But thank you so much for coming on.

Dale Bredesen [00:51:40]:
Great to talk to you, Claudia. Always happy holidays to you and your family.

Claudia von Boeselager [00:51:43]:
Thank you so much.