Claudia von Boeselager (00:00)
Welcome back to the Longevity and Lifestyle Podcast. My returning guest today is Dr. Dale Bredesen. Dr. Dale Bredesen received his undergraduate degree from Caltech and a medical degree from Duke. He was a postdoctoral fellow in the Laboratory of Nobel Laureate, Professor Stanley Prusiner and then held faculty positions at UCSF, UCLA, and UCSD.

He was the founding president and CEO of the Buck Institute for Research and Aging and his laboratory studied mechanisms for neurodegeneration and published over 230 scientific papers leading to the first publication on the reversal of cognitive decline in Alzheimer's disease and two successful clinical trials. He's the author of three New York Times bestselling the senior director.

Of the first precision medicine program for neurodegenerative disease at the Pacific Neuroscience and Chief at Apollo Dale is a repeat guest and a true trailblazer in leading brain health research and a cause, as many of you will know, close to my heart. enjoy.

Claudia von Boeselager (03:11)
Dale, welcome back to the Longevity and Lifestyle Podcast. Round three. I'm so honored and excited to have you back on.

Dr. Dale Bredesen (03:17)
Great to be here. Always wonderful to talk to you. Thank you.

Claudia von Boeselager (03:20)
Thank you so much. So, Dale, I'm so curious to hear more about what you've been working on. The space is exploding. The awareness about brain health is finally catching up to a certain extent, I believe. Can you share about some of the highlights and what you're most excited about, what you've been working on? what's been happening?

Dr. Dale Bredesen (03:37)
you know, when we started in the lab, you know, 35 years ago, we were interested in how does it work? We got to a place 15 years ago where we could say, okay, this is a complex network insufficiency. So what we have to do is identify the network parameters.

Then we have to increase the supplies, decrease the demands, and that has been what's worked better than anything else. So that's where we were 15 years ago when the first people started getting better. And by the way, we have people who started 15 years ago who are still doing great. So, more recently, then the idea was okay, we need to keep taking steps toward randomized controlled trial. We've just finished a randomized controlled trial at six sites around the US. Very excited about the results. They are better results.

Than have ever been published by any group. So we're very excited about that. And we've improving dramatically. And 90% of the people in the trial improved. Now it wasn't 100%. So we need to understand what about the other 10%? What were we missing? what didn't go right? And also within the 90% who improved, some improved dramatically, some improved modestly. We need to understand that.

So there's a lot of new stuff to understand. Then the other piece that we're working on is how do we adapt this general idea? The idea being you have various insults, you are responding to them with these proteins, with these PTAW, with amyloid, with TDP43, with alpha synuclein and these various responses are part of your innate immune system. So how can we adapt this

approach to all of the neurodegenerative diseases. What about ALS? What about Lewy body? What about vascular dementia? all these different problems, Lewy body disease, frontotemporal dementia. And so we now have beginning results with just the first couple people. We have some people with Lewy body who've done well, some people with progressive supronuclear palsy, some people with posterior cortical atrophy. Dr. Craig Tanio just published a wonderful study of a patient that had

corticobasal syndrome, a relatively rare disease. It's essentially like having a combination of Alzheimer's and Parkinson's. So we're trying to use the biochemical parameters to address these appropriately, the right ones in the right people at the right time, in the right way, to get the best outcomes. And of course, to sustain the outcomes. So we published the first paper about a year and a half ago showing sustained.

positive outcomes, sustained improvements for in some cases over a decade. So very exciting time because we've really gone from there's nothing you can do about neurodegenerative diseases to there's a lot you can do and there's more to be

Claudia von Boeselager (06:19)
Yeah, just for somebody maybe hearing this for the first time and perhaps hasn't been party to our previous conversations and they're like, hang on a second, what? Like how is this even possible? Can you explain and also through your research what is actually possible what you know now about reversing cognitive decline?

Dr. Dale Bredesen (06:35)
Yes, great point. So I started my laboratory as a professor down at UCLA in 1989. So it's been a long time. And for 30 years, I ran a lab first at UCLA and then later at the Burnham Institute and finally at the Buck Institute for Research on Aging. And the whole idea was: since these diseases are untreatable,

Can we find the basic mechanisms? Can we understand these at a more fundamental level? You know, you go back to all the previous ones, for example, tuberculosis. People didn't know for years that this was caused by a tubercle bacillus. And so finally, when Koch figured that out, and they said, wait a minute. Okay, so now as people realize this is a communicable disease, and ultimately, of course, developed antibiotics for it.

then TB went from a big problem to a small problem. Most of us don't wake up in the morning worrying about TB. Similarly, most of us don't wake up worrying about leprosy or syphilis or things like that. But at in their eras, they were like Alzheimer's. These were major, major problems. So we're trying to do the same thing with Alzheimer's. Let's relegate it to the dustbin of history by understanding it better.

And so we published over 230 papers looking at the molecular mechanisms. What actually drives, why is this happening? How does it relate features that occure during aging And it turned out to be an absolutely fascinating story. You can literally trace the molecular pathways.

That are driving this loss of connections in the brain. You know, normally you have about 500 trillion connections in your brain. It's absolutely fascinating. And what we realize is so cool because it tells you a little bit about evolution and how we live and genetics and all this. So, what we found was that as we've evolved, we have always selected for performance over durability. And of course,

The organisms that selected durability without such good performance were killed by the ones that selected performance over durability, sadly. But that's what's happened. So, what happened is you have an amazing nervous system. You've got a subsystem for neuroplasticity. You can store more than 2,000 home computers in your one brain. It's incredible. Similarly, you have a different sub-network.

That's about motor modulation. It fine-tunes so it allows you to play the violin or the piano or do gymnastics. It's amazing what people can do. That mitochondrial complex one to do that because you really got to have this snappy little modulations perfect. That's the one that goes awry in Parkinson's. Similarly, you have a third one, which is for power amplification.

And you amplify more. You can go from a thought to the maximum strength contraction of your muscles in a few milliseconds. Very quick that you can do this. And it's actually more power change, power amplification than you get when you stomp on the accelerator in your car. It's incredible how much. So all of these systems are so finely tuned. But as I mentioned,

You have now sacrificed some durability. So as we live, we can have problems with neuroplasticity and develop Alzheimer's. We can have problems with motor modulation and develop Parkinson's. We can have problems with power amplification and develop ALS. And you can begin to see why we get these. In each of these systems, you have a bunch of things that represent the supply. It's your growth factors, it's your nutrients, it's your hormones, it's your oxygenation, your mitochondrial function.

All the things that you study and talk about. Lifestyle-related things, longevity-related things. If not sending blood enough to your brain, you have got a downsize. On the demand side, you have the requirement for dealing with infections, dealing with toxic exposure. These things all put a greater demand on these systems. So now you begin to have too little of a supply and too much of a demand.

And so you're now literally downsizing, trying to fight these various organisms that we now know invade your brain, things from chronic sinusitis, oral microbiome, gut leakiness, tick-borne illnesses through the blood, all these things your brain has got to deal with. And so now, as you're starting to fail on that system, you can now identify the things that are driving this, address them.

And of course, optimize your blood flow and mitochondrial function, make sure you don't have sleep apnea. So now we finally have a formula for understanding what goes wrong in these different neurodegenerative conditions. We can identify the contributors, we can address the contributors. There's not a single contributor where there isn't anything you can do about it. And of course, then you can start building back up again with things like when needed, stem cells and

Obviously, there's a lot going on with stem cells these days. The problem is that people are trying to use them with nothing else. And it's a little bit like trying to rebuild a house as it's still burning down. So we want to put out the fire first, find out what's causing it, now bringing back these things. So as we combine these things, I think we're going to see better and better results. And by the way, in some of the an example, one of the six sites, Dr. Kat Toups every single person she treated got better.

So that's the future, getting people and understanding. but it's not simple. We've got some practitioners are out there that are getting very few people better. And we have others who are very well trained and experienced, and they're getting virtually everybody better. So it really does make a difference to understand, seek, find, and address those things that are happening. And so, yes, for the people that weren't here for the first two, let me say the old antiquated idea.

That there is nothing you can do about cognitive decline is gone. Even though people will still claim it, we are publishing it. Take a look at the papers, they're freely available online. You can see where we've published this. You can take a look at the books, The End of Alzheimer's, The End of Alzheimer's program. So I published one called Ageless Brain about a year ago. and the idea there was we should all be preventing cognitive decline and optimizing our cognition.

And we can now do that. We understand these processes like never before. So this is a very exciting era where we are really taking Alzheimer's from impossible to the same direction that leprosy went and things like that. it's quite exciting to see. And of course, it's just great to see people who were told that things are hopeless and they're now doing better and staying better. And there's an Alzheimer's Survivors Foundation that was started by Judy.

Patient zero, the first person I treated. and you can see her if you go to Judywalks.org. She recently walked from the Pacific Ocean to the Atlantic Ocean, 2,700 miles. And this summer she is going to walk from Land's End to London. So she's doing great. I treated her when she was 67. She's now 82 and doing absolutely great. So this is a new era.

And it's wonderful to see these things happening.

Claudia von Boeselager (13:56)
So exciting and just congratulations and thank you, Dale, for the work that you're doing. I want to unpack is first of all the diagnostics in terms of understanding what people need to understand and that also to understand that not every medical practitioner that they will seek or neurologist that they will go to will know about this. So I think this is really, really, really important. I've had multiple conversations with my mother's neurologist who was like, no, we have FDA-approved drugs, nothing else. And then to look at some of the interventions and therapeutics

Dr. Dale Bredesen (14:05)
Yeah.

Claudia von Boeselager (14:23)
so maybe we could start there so people can understand s what they should be looking for and potentially why behind some of them.

Dr. Dale Bredesen (14:30)
Yeah. You know, you brought up a really important point because we are in this era as there is change, just like anything else, as there is change, there is upheaval. And so what happens, you know, I used to say that change never occurs without some friction. you know, progress requires some friction and there's going to be some pushback as people are embracing these new approaches. And so we're in this strange era.

Where on the one hand you have pseudoscience. People are telling you, you know, if you just buy my crystal and put it on your forehead, then you're gonna be cured. You know, I see this all the time. I saw a thing the other day where a guy was on the internet saying, if you buy my potion, he said, This is why there's not a single case of Alzheimer's in Israel, which is of course a complete lie. It's ridiculous. But he's trying to sell you his potion, you know.

So there's a lot of pseudoscience out there. We have to be so careful. On the other hand, as you said, you've got these experts that I would call pseudo-experts because they're not keeping up with the new literature. They're not keeping up with what's actually working. And so each of us kind of has to decide. you can go with the crystal on the forehead, you know, maybe it's gonna work for you, but usually it doesn't. Or you can go with experts who are telling you there's nothing.

You gotta go on a drug. And unfortunately, the drugs just have not worked. I look forward to the day when they will, but right now they're not making people better. And that's been published repeatedly. Check out the literature. we've posted our preprint, by the way. it's still in the peer review period, so we don't have it published yet, but it's freely available, citable, searchable, and public. So if you go to preprints.org.

You can you can look under my name and Kat Toups who is the PI in this, and you can see this. And you'll see there at the end, we've compared it to all other published treatments, and it comes out ahead of all other published treatments. So we're very enthusiastic about that. So, you know, we want to make it so that ultimately this is the mainstream. But for now, the best thing to do is see someone who has been well trained. And you know, the easiest thing, you can get a free cognitive test.

Go on to my CQtest.com and you can get a free CQ is cognitive quotient. And you can see, you know, where do I stand? Because as you know, it often will sneak up on people. So they don't realize that wait a minute, you know, things aren't quite what they were. And so the best is to get started early and to get on if possible prevention or earliest treatment. You know, as you go through cognitive decline, you go through four phases.

A pre-symptomatic phase where you can already see changes in blood biomarkers and imaging and things like that. The second phase is SCI, subjective cognitive impairment. By definition, that means you know something's not quite right, but you're still able to score normally on testing. The third phase is called MCI, mild cognitive impairment. And I should say that second phase lasts on average 10 years. So we have a great window of opportunity to make sure that everybody gets better.

That third phase of MCI, by definition, that's mild cognitive impairment, which means you're now not doing well on the cognitive test, but you're still able to take care of yourself. You can balance your checkbook, drive, things like that. The fourth phase is dementia. And unfortunately, people in MCI, about 10% of them per year, will convert to that fourth phase, which means that you're now having trouble with activities of daily living. You may have trouble driving. People often get lost.

They're not recognizing people, they're having trouble balancing their checkbooks, they're having trouble ultimately taking care of themselves. And as you go through, just like with cancer, the later you wait, the harder it is to get a complete kit people to return back to normal. So, therefore, we recommend everyone please start early. As I say, you can get the my CQ test for free. you can also see where you stand with, and I think this is an important thing going forward. There is a

simple blood test and it's called ptau 217. We've put together the best ones as part of a collaboration with Neurocode has the most sensitive tests as something called brain scan so you can go to getabrainscan dot com if you like or ask your doctor about this and you can get an idea ptau 217 is just like getting

hemoglobin A1C to see if you're on your way to diabetes and so that you never have to wait for having problems with diabetes like blindness and kidney damage and strokes and heart attacks and things like that. Same thing with Alzheimer's now. You can see it coming. If your P tau is going up, it says that your brain is now responding to that mismatch between supply and demand. The P tau, interestingly, is an antimicrobial protein.

So it's your brain responding to these insults and saying, uh-oh, I need to get out there and address these things. So, okay, now you know, right, I'm okay now, but I'm on my way. So I can go in and get treated. Let's find out what's triggering that. And by the way, there's a great recent publication from Dr. Richard Horowitz, who's the Lyme expert. And actually, he and going to be doing a podcast together today.

our webinar on this very topic. So he has a patient who had long term Lyme and she was having some cognitive issues as so many people do with chronic Lyme. And she had a high PTAW. So she was on her way to Alzheimer's. When he treated her for the chronic Lyme, just as you would expect from the fact that this is a response, not only did her Lyme get better, but guess what? Her PTau 217 came back to normal.

So this fits exactly with what we saw in the lab, exactly with what I've been saying for 15 years. This is a response to various insults. And of course, one of them happens to be the borrelia of Lyme disease. And this person also had other tick borne infections. So these are all important in driving your brain. and here's a really fascinating scientific piece.

We know about how your immune system responds. So you've got the innate system, which is the early defense and less specific. And then you've got the adaptive system, which is the later part, and that's the more specific piece. Well, we now believe that before early innate part, there is a pre-inflammatory component where all you're doing, you're saying, as soon as I start having inflammation, I'm going to be compromising my brain. So first I'm going to just coat these things. It's a little bit like

if you've got a robber, you know, ⁓ moving around your neighborhood, but it's just one, you don't want to shut down your whole neighborhood and have everything shut down so that you can find this one little guy. you can coat him in molasses and let it harden and you just can't move, and you're okay. And that's what your brain is doing. It's saying, there's some herpes here, or there's some P. gingivalis here, or there's some barrelia here. because there's not a lot.

And I want to keep functioning well, I'll just coat it with amyloid and it will sequester it and inactivate it. And this is why people can have amyloid in their brain for 20 years and still do just fine. But it's a great time then to say, okay, let's start getting in better shape. Let's start making sure we don't have too much exposure and let's optimize our cognition. As you know, there's so many things that can be done. And so again

If we understand this pathophysiology, virtually nobody needs to get dementia. And that's the really exciting breakthrough.

So the diagnostics have two pieces. Do I have it? If so, why? In other words, am I on the way? And if so, why? for the do I have it piece, that's the biomarkers. P tau 217, GFAP, NfL which is neurofilament light, and (Aβ) 42 to 40 ratio. So you can get those biomarkers now. and then you want to know why. What are the things that are driving this? And so you want to look at chronic infections.

Claudia von Boeselager (22:00)
well

Dr. Dale Bredesen (22:22)
Metabolism, you want to know if you have sleep apnea. there's a set of things that we do. And the good news is we can identify for just about everybody what are the drivers. It may be poor methylation, it may be poor detox, it may be a leaky gut, it may be chronic sinusitis, as I mentioned earlier, maybe change in the oral microbiome. Interestingly, when you look at the normal brain microbiome, what do you find?

You find mostly oral organisms. So there is this communication going on, not only from the oral cavity, but also from your sinuses, back into your brain. These are going back and forth. And so that your brain is now seeing: ⁓ do I have pathogens like P. gingivalis in my brain? Do I need to coat these things with amyloid and then kill them with some tau? The amyloid and the tau both kill organisms.

So that's the piece of what we want to know. So when we get a report, we have people get of blood tests so that they can look at these things. And you can see these on drbredesen.com for example. Then as you said, you now want to treat. Now the good news is we can now translate all this beautiful molecular biology into what do we actually do to impact that?

So we want to address the three big players: the reduction in energy, the inflammation, and the toxicity. So that's what the therapeutics are directed toward. And when you translate this into, okay, what do I need to do for best outcomes? It comes down to seven basics and two specifics. Seven basics are ones you know about. So it's a plant-rich, mildly, ketogenic diet. You gotta get there's so many things that that does for you. It helps you with detox, it improves your microbiome.

It improves your energetics, it reduces your glycemic load, it improves your lipid status, all these things really helpful. Your brain needs either glucose or ketones for it to function. And as we age, you lose both of those. In fact, that is the signature of an Alzheimer PET scan. You see a reduction in glucose utilization in the temporal and parietal lobes. And you can't make ketones because you're now insulin resistant.

So your insulin goes up. So you've lost the ability. So literally your brain is sputtering. And so we need to improve both of those. We need to be make it so you're insulin sensitive and so you're capable of making ketones. And at the beginning, we just give some exogenous ketones. So it's diet, exercise, sleep, stress, brain training, detox, some targeted supplements. Those are the big seven. And then for the specifics, it's infections and it's toxins. So there's a lot to unpack there.

But you can take it at your own pace. The good news is this disease is not like pneumococcal pneumonia. It doesn't kill you overnight. In fact, many people will have it underlying for 20 years before they know they have it. So now with these improved blood testing, and treatment again, nobody needs to get this. You can find out, you can treat early, and you can get people again and again and again.

To improve. And people will say, you know, I started when I thought I was doing normally. I just thought I was doing prevention, but I realized, wow, I'm so much sharper. Now, all of us can be sharper doing the right things, as you well know. and so this is again very exciting time when you're able to look at this. Now, I would mention one thing about sleep. I check mine every morning. I just turned 74. So I'm trying to keep my cognition years to come.

Claudia von Boeselager (25:50)
Happy Growing younger there. younger.

Dr. Dale Bredesen (25:53)
But you know, we all age. And so every morning I check to see, okay, there are four targets. Number one, did you get at least seven hours of sleep? Did you get at least 90 minutes of REM sleep? Did you get at least 60 minutes of deep sleep? And that's particularly important for detox. Deep sleep is where you have the lymphatic cleaning of your brain and all this. Really important. And then finally,

Was your SPO2, in other words, your saturation of oxygen in your blood at least 94%? If you've got sleep apnea, you are hurting yourself. You're dropping this, you're boosting up your blood pressure, which is another mechanism to hurt your brain. So sleep apnea is a really damaging problem and very common. And people have said to me, I would rather die than go on a CPAP. Okay, if CPAP is not for you, well, okay, then.

Get a dental device or work with an expert. There are ways to open up your airway, dental ways, for example. Vivos has a whole set of things you can do to open up your airway. So there are multiple ways to do this. But whatever you do, don't allow yourself to live with significant sleep apnea. We had an example of a woman recently who was doing well for years and then she started to decline. And it turned out in evaluating her, we found out she had.

very significant sleep apnea. and just getting that back to normal really helped her. And her husband said, Yeah, great. She's not snoring anymore. So yeah, these you know, they affect so many of us.

Claudia von Boeselager (27:23)
So just a point on that, I had a Hollywood voice coach on the other day for an interview, Roger Love, and he was saying also that people have stopped snoring so when they came to training their voice and also singing which also brings up joy and happiness and feeling of connection. So maybe that can be part of the Dr. Dale Bredison protocols of encouraging people to sing more to avoid the sleep apnea

Dr. Dale Bredesen (27:33)
Yes.

Well,

and as you know, not just singing, humming, what does humming do? It increases your nitric oxide. So humming turns out to be a very good thing. And also, of course, just reducing your inflammation will often take people from mild sleep apnea to no sleep apnea. So again, that's another piece of this. All of these things, you know, we're seeing this beautiful human physiology emerging from all these studies.

Claudia von Boeselager (27:45)
I'm gonna think of

Dr. Dale Bredesen (28:07)
And what's exciting to me is that we're seeing what we studied in a petri dish for all those years is really translating so beautifully to what happens in a human brain as we start to have these degenerative processes and we can make sure that we don't have them. So absolutely all these things work together so

Claudia von Boeselager (28:27)
it's incredible because it's such a complex

organ that we're still learning and understanding from the pioneering research that you're also doing. I want to ask a question, also particularly for inflammation, but also insulin sensitivity in the brain. What is your view on GLP ones, also for people who are on the trajectory for Alzheimer's and GLP twos, and obviously there's retitruitide, which they're researching now What is your take on that? Have you been looking at that?

Dr. Dale Bredesen (28:49)
Yeah, this is such an interesting area because I always think it's so important to take the theory as long as the theory is accurate and gives you a good model, and it has really helped us a lot to see, okay, this is what's actually driving this. This is why you get the amyloid, this is why you lose the synapses, this is why you get the atrophy and how to address that. Now, when you look at GLP ones, they make a lot of sense in one area. And yet, as you know, the initial trial failed.

on GLP ones, where it shouldn't have. So there's more than one thing going on here. So what we recommend currently is if you can do it without GLP ones, if you can get metabolically flexible, which means insulin sensitive and able to get into ketosis when you need to, so that you go back and forth. And this is tough for people who are very frail. So you really have to take a different approach for someone who is frail

Versus someone who is a little overweight, for example. It's actually easier to treat someone who's got some fat to burn. So you've got to be very careful about people who are frail. Now you still work with them, you give them some exogenous ketones. Now, for people who say, Yeah, but I just can't do this stuff and I really want to go on a GLP one, okay. Try it for six months. But what you want to avoid is staying on it for life because we just don't know. There's no study.

Claudia von Boeselager (29:49)
No.

Dr. Dale Bredesen (30:09)
That shows what happens when you stay on this for life. So my argument is here's a great way to get started. So if you want to do this as part of the overall protocol, have at it. Great. But as you now start to become metabolically flexible, ease off it after six months, nine months in that range. Get the good part without having the long-term bad part. For example, you know, people are reporting, hey, you know, my muscles wasted away, you know, my face changed.

you know, I had problems with gastroparasites. I mean, there are clearly defined and clearly published side effects. So if you're going to do it, no problem. include it as part of the overall because ultimately we want to optimize your physiology. You know, your body is not trying to give you Alzheimer's, it's trying to help you to respond to insults that are coming your way. So let's get rid of the insults.

Let's optimize your resilience, and then you won't need these other things. We've had numerous people. They no longer need their statins. They no longer need their anti-diabetes know, on and on. And so again, optimizing your physiology in the long run, you won't need the GLP ones. But if you want to try them for some period, especially if you've got some type 2 diabetes that you're having dealing with.

Or if you want to use them for weight loss, fine. But again, I would try to stay away from staying on them forever.

Claudia von Boeselager (31:35)
That's great advice And then what about other peptides, right? So we're hearing more about C-Lank or CMAX. And I had a Russian scientist on this week who back in the 1980s was working on different peptide protocols, seeing incredible results what is your view, obviously, with the US regulation, et cetera, things are changing in different countries, there's different regulatory environments, but have you been looking at different brain-specific peptides and their impact?

Dr. Dale Bredesen (32:00)
Yeah, so this is such a good point. So again, I would urge everybody give do the basics first. so often people will say, Well, I didn't do any of the basics, but you know, there's this new cure. There's no miracle cure that's one thing. So this is a network, and you've got to find, the issues, address it. You know, if your Wi-Fi is not working, you don't take a hammer and whack it and and break it. You look at you know what's actually going wrong here. So do

Claudia von Boeselager (32:20)
Sure.

Dr. Dale Bredesen (32:24)
Do the basic, get yourself so you're metabolically flexible, get yourself so you're now doing appropriate exercise, get your sleep optimized, get your stress level down, do your detox, do the optimal supplements. If you've got some inflammation, you want to use some SPMs. There's so many good things. If your mitochondria needs some boosting, you might want to use some Urolithin A The armamentarium is huge. Once you've done that, now these other things like peptides, like stem cells, will work better.

Claudia von Boeselager (32:52)
Mm-hmm.

Dr. Dale Bredesen (32:52)
And

so now, absolutely, I'm a big believer in peptides, on top of doing the basics. So, I have to say, some of them there just aren't enough data. As an example, people have touted cerebral lysin as something that's been really helpful. It just hasn't done it. It just hasn't met the criteria. There is no publication showing, look how great cerebral lysin did. It's just not there. I remember being at some of this talks now. This is

25 and years plus ago on early studies of cerebral lysin. It was very promising. So you have to look at what's real. Again, go back to what's pseudoscience and what's real. And I won't say cerebral lysin, pseudoscience. There's real science there. It's just that it hasn't moved the needle the way we'd all hoped. So again, we're all interested in the same thing: best outcomes. Beware of the people that are putting the incomes ahead of the outcomes.

We want to put the outcomes ahead of the incomes, right? We want to get the people to get better. And so this is why, you know, if something's working, I'm all for it. CLank and CMAX, Epitalon is another one that's worked with well. thymus and alpha one, thymus and beta four. Again, in the right settings, these things can be helpful. And of course, there are hundreds more. I find it very disappointing.

Claudia von Boeselager (33:49)
Like that.

Dr. Dale Bredesen (34:10)
That the FDA has been pushing so hard against these. Now, as you know, the HHS secretary said when he came in, we're going to be supportive of peptide use. Great. I haven't seen it yet. Have you?

I mean, I'm waiting for them to say, look, let's support these studies and let's get grants for people to do more on this. We need more information. so I do agree with you. There's tremendous opportunity here, and I do think there is tremendous promise. But so far we're in that gray zone where the actual proof hasn't been. Now, to be fair, some people, no matter how much proof you give them, they just keep saying, I don't believe it, I don't believe it, I don't believe it.

Claudia von Boeselager (34:48)
Yeah.

Dr. Dale Bredesen (34:48)
But if

you again focus on the best outcomes, there's a lot you can see they're addressing some of these pathways that we want to be addressed. They're addressing inflammatory pathways, they're addressing trophic pathways. One of the ones that I've been most excited about is called Davunetide Now, it failed also years ago in a trial for Alzheimer's. Well, but it was used as a monotherapy. We now understand.

This is not a monotherapy disease. So I would love to see Davunetide make a comeback because it's a fragment of ADNP, which is a very potent pro-trophic neuropeptide. I think there's a real opportunity and role for that. But because it failed, people have been reluctant to bring it back. So I do think we need to relook at things that were only tested as monotherapies. Let's test them on the backbone.

of doing all the right basics. You know, again, now that we understand what's driving this problem, we can see when to use CMAX, when to use CLank, when to use Thymus and Alpha One, all these different things and all these ones that have such tremendous potential.

Claudia von Boeselager (35:59)
So powerful. And let's look at stem cells, right? Or ECVs. what is your view? And maybe you can explain to people unfamiliar, they've maybe heard the term, they're not really sure what it is, and obviously there's different types which part of that do you find most promising around brain health?

Dr. Dale Bredesen (36:13)
Again, you know, I'm looking for even small studies to show that, hey, okay, this really worked well. and as you know, there are multiple different ways to do stem cells. you know, the vesicles, another piece of that that's also very helpful. They carry all sorts of important targets. and in fact, we were interested in those years ago because they're very good for diagnostics. You can get a very good look at what's going on in the brain.

By looking at these exosomes. And so they're very, very promising on the diagnostic side as well. So again, the armamentarium is huge and it's growing. We need more support. We need a more supportive government, less about taking the grants away and more about giving the grants for innovative new things like exosomes and like stem cells. I do think for people interested in stem cells.

Since there are autographs that you can use from yourself, which I think is a good way to start, because now you're not worrying about things that could be brought to you, pathogens potentially from others. So I like that idea. F things, for example, like ADRCs, these are adipose derived mesenchymal stem cells. They're very promising. then you know.

Try that, they definitely help with inflammation, they definitely help with support, but again, as a monotherapy, they're not a cure. And then you can go to things where you're looking at lines from other grafts that are gonna be different, but have their own place. And each of these things kind of has its own place. Again, don't try to rebuild the house as it's burning down.

get evaluated, address these. And I do mention one thing, which, because it's really important, in our trial, there were six sites around the country. And I really appreciate working with these fantastic physicians like Dr. Kat Toups and Dr. Craig Tanio and Dr. Ann Hathaway all these various people who really did a great job. And four of the sites got tremendous results, two of them did not.

in one case, it turned out to be very clear. The person who was running the trial there just relegated the patients to an untrained physician, and which was horrible. we were not made aware of this at the beginning. And we could see, wait a minute, you know, this group is is not getting anybody to be better. So it really does matter. It's just like when you choose a surgeon, choose someone who's done the operation successfully many times before. You may want to ask the doctor.

Claudia von Boeselager (38:14)
What a

Yes.

Dr. Dale Bredesen (38:30)
Have you reversed people's cognitive decline before? Let me talk to a few of them. you know, or have you published anything on it? so you've got a lot of claims. As they say, when all is said and done, a lot more is said than done. So you gotta you gotta work with the right people, make sure it's someone who's well trained and who's had good experience with good outcomes.

Claudia von Boeselager (38:49)
Yeah, and not to be shy to ask those questions, right? I think some people are intimidated and they just assume and they see all the accolades after the title, et cetera. But those are really good questions. And I think your average neurologist is gonna say, Well, you can't reverse it, right? So already there you know, go find someone else. Let's dig a little bit deeper into the trial. can you walk us through that, Dale? And it's such a amazing feat. So now you know that one of the centers what went

wrong, unfortunately, that it was delegated to an untrained person, unfortunately. But okay, leaving that aside, what were you seeing in some of the other ones? And also one question I think is very important. How advanced were the people? We know prevention is better than cure, and that there is a certain tipping point, if I'm not mistaken. So is there hope for everyone or is it only people who are not as far progressed? Maybe you can walk us through that part

Dr. Dale Bredesen (39:32)
This is such a good point. And there is hope for everyone, but the outcomes are different. If you've gone from a MoCA score of 30, which is perfect, down to zero, which is end stage, we've seen people get better, but they don't go from zero to 30. They go from zero to five or zero to nine. Now that makes a big difference in their lives. They're dressing themselves again, they're talking again, and things like that, but they're not all the way. This is why we say please come in early. So we mentioned the four phases before. For the people who are in prevention,

We've never had a person who went on prevention, did the right things, and still went on to get dementia. So it'll happen someday, but whatever it is, it's very, very effective. When you have someone with SCI, virtually all of those people get better. So those groups weren't even in the trial. Our trial was for people who were further along simply because that's where all the different treatments are being tested now.

They're being tested in MCI and early dementia, typically not late-stage dementia, because early drug trials failed with that. So they said, okay, maybe we we try to check the drugs earlier on. So MCI, which is the third phase, and early dementia. And that's exactly where ours was, and it's exactly where the drug trials are. And so these people had, you know, clear problems. So they had.

a what's called AQ21, which means their partners, their spouses typically, was saying yes, they have different they clearly noticed some problems. You had to have a high score on that to say yes, you've got MCI or early dementia. They were not scoring well on the MOCA test, which is the Montreal cognitive assessment, and a more sensitive test, which is CNS Vital Signs, they were not scoring well on that. So we knew that yes, they have problems.

and it was progressive. So we knew that they have a tip. Now, not every single one had Alzheimer's. some of them were likely to have either Lewy body, vascular dementia, but the majority of them had abnormalities to suggest they had Alzheimer's. So, for example, on the A beta marker, 63 out of 66 who did that marker had an abnormal A beta 42 to 40 ratio. But a marker which is a little further along, P tau.

Half of them had a normal PTAW. So they were relatively early in the process. so that's where they were. Now they then went, it was nine months. So they were first they were randomized. So two-thirds of them went on to a precision medicine protocol, which is our protocol. One third of them went to standard of care. So they were just referred back to their physicians and said, okay, treat them as you would anybody who has cognitive decline.

And if they had dementia, if they had early dementia, they would be put on Aricept as an example, or tip the typically put on a drug like that. Otherwise, they would just tell them, go home, there's not much you can do, maybe do a little exercise, you know, eat better. They really don't have a good approach for this. It was kind of standard of care. So on average, the standard of care over nine months went downhill, just as you'd expect.

Now, the disease is not quick, as I said, it's not overnight. So they didn't go downhill a lot, but they definitely went downhill. On the other hand, the ones, the group that was treated, clearly improved and just dramatic, and you can see on the preprint, just dramatic differences between the people who were treated who increased their cognitive scores, and the people who were treated with standard of care who decreased their cognitive scores. And so then we looked, and so the

The very important piece is what's the statistics on this? You know, if this is not statistically significantly different, then it doesn't tell you a lot. But as it turned out, it was highly statistically significantly different. p value was less than one in a thousand. They look for less than five in a hundred, so one out of twenty. Ours was less than one in a thousand. What that means is there was less than a one in one thousand chance.

That what we did had no effect. In other words, that it was just random chance that showed such a huge difference. So it's pretty clear that this is different. Now, people have said, well, that this trial, the total number of people in the trial was 73. The key is it was a huge difference statistically. When you have something that has barely any impact, of course you have to have a thousand or two thousand people because the impact is so small. When you have a big impact, as we did.

You don't have to do so many patients. Now, I would love to do a trial with a thousand patients that will cost eighty million dollars. So we don't have the eighty million dollars today to do that trial. The trial that we did cost six point six million dollars. We were really grateful to Diana Merriam and her Four Wins Foundation, which supported this trial, and she's been absolutely fantastic as a supporter. she's looking for.

Claudia von Boeselager (44:04)
Yeah, two years.

Dr. Dale Bredesen (44:18)
How do we reduce the global burden of dementia, make fewer people get Alzheimer's disease and get dementia? And you know, really happy. And we've worked with her for almost a decade now. So very, very happy about that. And she and her foundation supported the first, the proof of concept trial that we did, which also the majority of people improve their scores as well. But of course, everybody's gonna say, well, do you know 1,000, 5,000, 10,000? Okay.

ready to do that tomorrow, but we'll need eighty million dollars to do that trial.

Claudia von Boeselager (44:50)
So if anyone is looking to donate, Dale, where should they contact you if they're interested in donating to the front?

Dr. Dale Bredesen (44:55)
So we have set up a nonprofit, which is called APRP. It's Alzheimer's Prevention and Reversal Project. so not to be confused with ARRP. this is APRP, Alzheimer's Prevention and Reversal Project. And so, yes, thank you. We're looking for and and the money that comes in to there, we use to support improved treatments.

for people who can't afford the testing or can't afford the treatment, and of course for trials. And APRP, with the tremendous support from Diana is what funded this trial. again, this is a time of of great ⁓ progress. We, you know, when people ask me what what do I do? I just found out I have a high PTAW. 15 years ago I would have said there's nothing to do.

We just have to unfortunately sit there. Now there is a tremendous amount that can be done. And so my hope is we will end this as a major threat with the current generation. I told our two daughters who are in their 30s now, you know, you are from the first generation, just like you. You are from the first generation that does not have to worry about dying of dementia. Isn't that a wonderful change? From my generation, it was the biggest concern.

Claudia von Boeselager (45:59)
Hopefully.

Dr. Dale Bredesen (46:07)
that you were going to get dementia and die from it. So now, okay, get evaluated early, get on early prevention or earliest treatment, and you'll do very, very well.

Claudia von Boeselager (46:18)
Incredible, Dale. And before we finish up today, I want to touch on a interesting topic that's getting more and more airtime, let's say, is psychedelics. And there's been some really interesting research around this topic, comparing it to for depression, PTSD, reversing brain aging in terms of neuroplasticity. Dr. Nolan Williams when fourteen passed away last year.

Dr. Dale Bredesen (46:25)
Yeah. Yes.

Claudia von Boeselager (46:38)
out of Stamford showing that ibogaine, for example, can reverse or improve neuroplasticity as such that it reverses brain aging by a year and a half. what is your view on the psychedelic landscape? Have you been looking at this a lot? Maybe you can share a little bit about what you're seeing and hearing.

Dr. Dale Bredesen (46:42)
Yeah.

Yeah, I'm very excited. me before I say that, let me just mention for anyone who finds out they have this is a common thing now. People find out they have a high PTAL and they say, like, hey, I'm doing pretty well. I have a high PTAL. What do I do? I would again go on to mycqtest.com. You'll see where you stand. It's free. You'll see where you stand with your cognition. And then let's find out what's driving it. We should be able to address it in the vast majority of cases. Now, psychedelics and their place. And again, what's so fascinating to me.

as someone who ran a neuroscience lab for all those years, what's so exciting for me is to see how these things all fit together. So here's an example. We know that depression is related to cognitive decline. These two go together frequently. they're they're almost cousins. And now we understand, yes, inflammation drives both of them, as an example. And what's happening with depression is that your body is saying,

⁓ again, I'm not quite hitting on all cylinder here. Whatever I'm doing in my life is not giving me the positive feedback. So it literally is activating a program to say, okay, I'm gonna force you to sit on the couch for a few months. You're not gonna be feeling like like moving. You're gonna have to change your direction in life, and then you're gonna hopefully be more successful. And it's because you've got inflammation coming in, you've got toxins coming in. Well, now we understand this. We can look for these things and address it.

And of course, Dr. Christopher Palmer from Harvard is doing a lot of interesting work on psychiatric-related functional medicine, essentially, and looking at these things for things like bipolar syndrome, et cetera, you know, affective disorders, things like that. It's a very exciting. Now, where do the psychedelics fit in? So there again, there's this fascinating program. Again, your brain's not trying to to mess up your life, it's trying to help you.

And it looks like where this is coming from. And it's really, as you know, it's the 5 HT2 receptors. So it's a subgroup of the serotonin receptors, which Ibogaine and LSD and ayahuasca, all these things are acting on that part of the nervous system. Why did your nervous system produce this? And again, it looks like it's what it does is it gives you this enhanced plasticity. And again, it's saying, okay.

In certain situations in life, it may benefit you to have this, and you may have to be looking, you know, looking at new vistas, looking at new things. There may be times when things aren't going the right way. Okay. So you've got this amazing ability to kind of reformulate life. And these psychedelics are taking advantage of that. the research is interesting so far is that it's showing clear increase in neuroplasticity.

And that's what we want in Alzheimer's. But again, if you try to increase the plasticity and you don't have the fuel to make it work, you're not going to get a good benefit. So again, what I say is do the basics first. Make it so your brain has plenty of fuel, plenty of trophic support, appropriate hormones, all the things it needs to hit on all cylinders. Then do things like bringing in the psychedelics.

So that now you're saying, now I have the ability to take advantage of that enhanced neuroplasticity instead of trying to do it. People have been trying to do all this stuff in an overly simplistic way. You've got to understand the whole, the workings of the brain. All these things work together. Again, it's like saying, No problem, just get in your car and go 100 miles an hour. Well, if you haven't put any gas in there, it's just not gonna work. If you haven't, you know, if you've got a flat tire.

And someone says, okay, just go 100 miles an hour. You can't do it. So you've got to get everything in a row here, get these things working, and then stem cells, peptides, psychedelics. Isn't it an exciting time here? The armamentarium is huge. We just don't have enough data yet on all these things. And it's partly because people are trying these things without doing the right stuff first.

And yes, I understand scientifically you want to look at one variable at a time, but you also need to have a separate group of practitioners that is always asking the same question. How do we get the best outcomes with everything we know today? And that's what we're so interested in doing because there should be a place for people to go. They shouldn't be told by their doctors, well, we just don't have enough data. So just go home, go home and and decline while we get our next grant.

we really need to have, okay, how do we get the best outcomes with everything we know today? What is the best approach?

Claudia von Boeselager (51:22)
Dale unfortunately, we're at time. I have about 40 other questions as always that I would love to cover. such a fascinating space. You're doing so many amazing things in this First of all, where can people find you, see what you're doing, your research, your work? Where would you like to send them to? And we'll obviously link everything in the show notes.

Dr. Dale Bredesen (51:27)
Ha ha ha

Yeah, thank you. So for anyone interested in in what we're doing, there are four books: The End of Alzheimer's, The End of Alzheimer's program, The First Survivors of Alzheimer's, and The Ageless Brain, which is the most recent one. And actually now starting on a new one, which is about all the new things coming out in in Alzheimer's disease related treatment. then you can go to you can see on Instagram, Dr. Dale Bredison on X.

on Facebook, all those you can get information there. And also you can just get into it by looking at my CQ test and or drbredesen.com Any of those things you can see what we're doing. Always great to talk to you and happy to come back anytime and update and talk about what's new and interesting because this is a very active field and really making huge impacts on people's lives every day.

Claudia von Boeselager (52:25)
So so exciting. Dale, do you have any parting thoughts or message or ask from our audience today?

Dr. Dale Bredesen (52:31)
Yes, so my message is let's all work together to reduce the global burden of dementia. we have the ability to do that now. Please don't wait. just had an email from someone yesterday saying, yes, I've got some decline and I know it needs to be addressed, but I'm going on a trip for months and you know, I'll think about it when I get back. if you found out you had cancer, you would not go on a long trip until you knew whether you had metastases.

Cancer spreads and so does Alzheimer's, unfortunately. It spreads within the brain. So please, for anyone, if you've got issues, please take some time. it'll pay you with huge benefits in the future to just address it early.

Claudia von Boeselager (53:07)
Beautiful. so so much, Dale, for taking the time. Know how busy you are. Thank you for the amazing work you're doing in this world. It's such an honor and pleasure. Thank you.

Dr. Dale Bredesen (53:14)
Thank you, Baroness.