RHR: How to Sharpen and Protect Your Mind for a Lifetime, with Dale Bredesen

In this episode, we discuss:

• Revolutionizing Alzheimer’s prevention and early detection
• Blood testing and the four stages of cognitive decline
• Objective assessment tools for cognitive health
• Breakthrough results in clinical trials
• Essential lifestyle interventions: diet, exercise, and sleep
• The role of supplements and brain stimulation in Alzheimer’s prevention

Show notes:

• The Ageless Brain: How to Sharpen and Protect Your Mind for a Lifetime by Dale Bredesen
• Order a BRAINSCAN by Neurocode
• Apollo Health Re-Code 2.0 Training
• Previous RHR episodes with Dr. Bredesen
  • RHR: Prevention and Treatment of Alzheimer’s from a Functional Perspective, with Dr. Dale Bredesen
  • RHR: Using Functional Medicine to Reverse and Prevent Alzheimer’s Disease, with Dr. Dale Bredesen
  • RHR: Preventing and Reversing Alzheimer’s Disease, with Dr. Dale Bredesen
• Follow Dr. Dale Bredesen on Facebook, X, and Instagram
• Learn more about the Adapt Naturals Core Plus bundle or take our quiz to see which individual products best suit your needs
• If you’d like to ask a question for Chris to answer in a future episode, submit it here
• Follow Chris on X, Instagram, or Facebook

Hey everybody, Chris Kresser here. Welcome to another episode of Revolution Health Radio. This week, I’m really excited to welcome Dr. Dale Bredesen back for his third appearance on the show. Many of you, I’m sure, have listened to the first two episodes or are familiar with Dr. Bredesen from other resources. He’s an internationally recognized expert in the mechanisms of neurodegenerative disease like Alzheimer’s and dementia. He graduated from Caltech, then earned his MD from Duke University. He served as the chief resident in neurology at UCSF before joining the Nobel Laureate Stanley Prutsner’s lab at UCSF as a postdoc. He’s held faculty positions at UCSF, UCLA, and UC San Diego, and he directed the program of aging at the Burnham Institute before coming to the Buck Institute in 1998. So a very storied background in the world of cognitive disease and neurology.

But what distinguishes Dr. Bredesen from others in the field is that about 15 years ago, he realized that the conventional approach to cognitive decline was failing and was also insufficient because it was just primarily looking at what drugs could be used to attempt to slow the decline of Alzheimer’s and dementia, rather than figuring out what the root causes were and addressing those. So without knowing anything about functional medicine, Dr. Bredesen basically developed a functional medicine approach to dementia and Alzheimer’s and then eventually did hook up with the functional medicine community. I met him about eight or nine years ago at a conference that I was speaking at that he came to at UCSF actually and we became friends and colleagues. And since then he’s published several books. He has trained over 2000 practitioners in his approach, functional approach to treating dementia and Alzheimer’s and preventing it. He has a new book called The Ageless Brain that we’re going to talk about in this show. But what really stands out to me about his work is that for the first time ever, we now have a way of preventing and protecting against dementia and Alzheimer’s from developing in the first place. And even now studies show that we can reverse it, especially at the earlier stages, once it has already begun. And that was simply not the case 15 years ago. And as you all know, getting a diagnosis of dementia or Alzheimer’s can be extremely traumatic and up until fairly recently, it’s kind of a death sentence and a horrible thing because there was really nothing that could be done to stop the progression or reverse it. And the landscape is very different now.

We’re going to talk about some new blood tests that can be used for early detection to give people a big head start on taking action and reversing the progress because the earlier you intervene, the easier it is to get results and the greater chances you have of reversing at a hundred percent. We talk about the four different stages of cognitive decline and how to recognize signs at the earlier stages. Talk about the objective cognitive assessment tools that you can use. We talk about some of the brain training programs and their results. Diet, exercise, sleep, and other lifestyle factors, environmental and lifestyle factors that contribute. So a fascinating conversation. I think it’ll be extremely useful for everybody who’s concerned about brain health as they age, which again should basically be everybody. And I hope you’re going to learn a lot and this is going to be of big practical value in your life. So let’s dive in.

Chris Kresser:  Dale, such a pleasure to have you back on the show for the third time.

Dale Bredesen:  Great to be here, Chris. Aida, my wife, and I are big fans of yours, so it’s always great to talk to you.

Chris Kresser:  We were just chatting a little bit before we hit the record button. We met, I think, eight years ago. And it feels, in some ways, like just the other day, but in other ways like whole generations have passed in terms of the amount of progress that’s been made in the world of dementia and Alzheimer’s and understanding it from a root cause functional medicine perspective, which you have really pioneered. Your first two books were huge contributions in that space and I know I’ve helped millions of people. I’m really excited to talk about your new book, The Ageless Brain, and maybe a good starting point would be where are we in this space now? What has really changed in the past few years since we’ve last talked? What are the things that you are the most excited about in the world of dementia and Alzheimer’s prevention? And even now, we can say treatment.

Revolutionizing Alzheimer’s Prevention and Early Detection

Dale Bredesen:  Yeah, it’s a great point. We have literally gone, since you and I have known each other, from the dark ages of saying could we, you and I were talking about desperation before. It looks we can reverse the first cases of cognitive decline, which our first case was 2012. And so we were very excited about that and we were talking about things like the rhinocidal microbiome and is that important and all these things. We’ve now moved to an era where we can say that age-related cognitive decline, including Alzheimer’s, is really optional. If everybody would get on active prevention, if everybody would get the new blood tests, so there are some fantastic new blood tests that literally look inside your brain and tell you are you on the way? Very much when we first had fasting insulin and hemoglobin A1c, we could tell people long before they had diabetes. Now we can see people coming toward decline in the years ahead. We know that the biochemistry starts 20 or more years before a diagnosis. So the world has really changed. And we’ve got, you mentioned the new book, Ageless Brain. The whole point of that was, let’s take this beyond Alzheimer’s and let’s help every single person have a brain span that is equal to their lifespan.

So I often ask people, who wants to live to 120 or 140, whatever, a bunch of hands go up and say spend half of that time in a nursing home, and of course, people’s hands go back down. So we want to make sure that whatever your desire is, whatever you plan to do in terms of your longevity, let’s make sure to take the brain span along with you. And with the blood tests, we’re in the middle of a randomized controlled trial, and the results are outstanding. We have statistically significant results, even though we’re only halfway through, we have statistically significant improvements in people who are on the protocol whereas the people who are on standard of care are continuing to decline. So you can see the huge difference between the people who are being treated appropriately and not. We’ve got people, over 2,000 people who’ve now trained and are taking care of people around the world. And we find that some do it better than others, no big surprise. We’re seeing that this is much more like surgery. It’s a procedure where you really have to know what you’re doing, when to use what, etc. And all the things that you are talking about and have talked about over the years are important contributors to our brain health and our risk for cognitive decline and Alzheimer’s disease.

Chris Kresser:  Amazing. Yeah, I just want to linger on this for a second because prior to the past, let’s say 10 years, it really wasn’t, maybe not that valuable to have early detection because then you would just have more years of knowing that you were doomed to a horrible fate, right? Because there weren’t that many, there was poorly understood at that point what the interventions were that you could do that would change that trajectory. And most of the drugs, as you’ve discussed in the past, were ineffective. Really didn’t halt the progression, certainly didn’t reverse it. So it seemed like in many ways, knowing early was worse than knowing late, because at least you could enjoy your ignorance for a period of time until the symptoms came on. But now that equation has dramatically changed as you mentioned. Knowing early is a huge advantage because as Ben Franklin said, an ounce of prevention is worth a pound of cure. I know that that’s especially true here. The earlier you intervene, the better the chances are of halting and reversing the progression, never ending up with full-fledged dementia and Alzheimer’s.

Blood Testing and The Four Stages of Cognitive Decline

Dale Bredesen:  That’s exactly right. And when you develop Alzheimer’s and we think of it as well, Alzheimer’s is a disease, but the reality is we all undergo some degree of brain aging. And as you develop this, you go through these four phases. You have an asymptomatic phase. Then you have what’s called SCI, subjective cognitive impairment, where you know something’s wrong, but you’re still able to score normally on testing. Third of the four is MCI, mild cognitive impairment. It’s too bad that term was chosen because it’s really a relatively late stage. It’s saying mildly metastatic cancer. It’s a relatively late stage. And then the fourth one is dementia, where by definition you’ve begun to lose your activities of daily living. When we see patients, so everybody in the first two groups does great. And in fact, in SCI, virtually 100 percent of these people can turn it around completely and do great. MCI in our trial, 84 percent of those people got better. With dementia, now when you get all the way to dementia, you see improvements. And we’ve had people even with MOCA scores of zero, that’s Montreal Cognitive Assessments of zero, the end stage, who do better, but they don’t any longer come all the way back to perfect. In fact, that’s one of our interests in research. How do we take someone with a MOCA of zero and give them a perfect MOCA of 30? Nobody’s done that yet, and we’re interested.

So therefore, just as you said, you want to get in early. And we recommend anyone who’s 35 or over, please get your blood tested. There’s something called, a new thing called Brain Scan, where you can actually check for your GFAP, your neurofilament light, and your p-Tau 217. So these are tests that tell you just what you were saying. Are you on your way in the future so that you can prevent and reverse any mild decline? Because as you know, it sneaks up on you. People say, well I’m just getting a little bit older. We hear this all the time. My doctor said, I’m in my 40s now I should expect this sort of thing. No, you shouldn’t expect it. You should find out, is it because you’ve got metabolic syndrome? Is it because you’ve got a tick-borne illness? What is it? There’s a reason that these things happen and we can absolutely do something about it.

Chris Kresser:  So yeah, let’s talk a little bit more about the blood tests and the panel that you just mentioned. So what is the name of the panel again and how do people access it? Is this something they can order themselves online and then go to a local lab? Do they need to go into their primary care doctor and get them to order it? Which can, as you know, be a challenge sometimes because of lack of awareness.

Dale Bredesen:  No, that’s exactly right. So the group that has done the most sensitive p-Taus and the most well validated by far, they’ve validated in thousands is a group called Neurocode. And so they offer a test and it’s under brain scan. So if you just look up brain scan, in fact, you can do it at GetABrainScan.com is the way to get this and you can get it at your home with mobile phlebotomy, which I did. So I think everybody, if you know your blood pressure, if you know your lipid panel, it’s a really good idea to know your P-Tau 217, GFAP and NfL. I had mine done just a couple of weeks ago. I was very happy to see that they’re all looking good. Since I am now in my 70s, I mean, I’m going to do them again in two years. But if you’re less than 60, just do it every five years. You don’t need to check it often because you can see this coming for a long time ahead of time. And what these measure is really important and was not available until very recently.

The first thing is something called p-Tau 217. So Tau is like a bolt, and it helps bolt down your microtubules. As you are putting out neurites, making connections, maintaining connections, just like if you were to build a structure onto your house, to put an addition onto it, this is the bolts that help the rafters be strong. When things are good, these bolts are held in place. When things are bad, you have too much inflammation, not enough blood flow, you’ve got sleep apnea, on and on, all the things we talked about with the 36 holes in the roof years ago, what happens is your body literally switches from a mode of connection to a mode of protection. And that’s something actually we just discovered a couple of years ago and since you and I have talked. There is a whole panoply of things that will change. And one of the things that changes is your Tau. You phosphorylate your Taus, so you put phosphorus and oxygen onto your Tau at multiple sites. And the one that correlates best with cognitive decline is amino acid 217. So you put this on, and what it does is it changes the charge on the Tau, and it changes the shape on the Tau. So instantaneously, this thing pops off your microtubules, allowing them to collapse. And interestingly, it becomes an antimicrobial protein. So phospho-Tau actually goes around killing these various insults that you have, killing the viruses and the microbes in the various bacteria, etc. It’s really striking. And when this happens, it also interestingly becomes a prion. So it begets more of itself. And we believe this is because you’re now fighting things that are dividing. So you are using an amplification mechanism itself.

Chris, one of the things that’s happened over the years in all of the studies of neurodegeneration, the focus has been on neuropathology instead of neurophysiology, looking at what is the organism actually doing? And this cognitive change as we age has turned out to be much more about a normal function of our brains. We are trying to deal with these organisms and these various insults that we have as we get older. So that’s the p-Tau part of it. GFAP is really interesting. It’s a complementary test. And what it does is tell you if you have ongoing inflammation and repair in your brain. And it’s a very early marker, which is nice, which is why it’s included. And then the third one is called NfL, or neurofilament light. And what that does is it looks specifically at neuronal damage from any cause. So for example, we can then get a profile. If you have a normal p-Tau, but you have a high NfL and a slightly high GFAP, you may well have frontotemporal dementia, but you don’t have Alzheimer’s. On the other hand, if you’ve got just the p-Tau high, you’ve got Alzheimer’s, but it’s not very active. But we see other people who have all three of them high. Now you’ve got very active Alzheimer’s disease. So this really helps tell us, and as you said, very good point, there’s no reason in the past to find out these things because there was nothing you could do about them. And of course now with all these wonderful functional and precision medicine approaches, there is a tremendous amount we can do. We can identify for each person what the drivers are and we can address those.

Chris Kresser:  Great. All of these tests are included in a single panel?

Dale Bredesen:  Yes.

Chris Kresser:  So you can get that by GetABrainScan.com.

Dale Bredesen:  Right. These tests are all included in that panel. So basically there are then two panels and the one that you and I talked about years ago, which is the recode, which is just looking at all the different homocysteine, HSCR-

Chris Kresser:  Functional markers.

Dale Bredesen:  -Functional markers, exactly. The other one, which is the new one, which tells you that’s the brain scan, which tells you what is going on in your brain. In the past, you had to spend thousands of dollars and go get a PET scan and there’s a Tau PET scan and there’s an FDG PET scan and there’s an amyloid PET scan. It was really pretty onerous and invasive if you’re going to go and get a spinal tap, which is what a lot of people did as well. Now you don’t need to do the spinal tap or the PET scan. You can get a simple blood test and look to see what’s actually going on inside your brain.

Chris Kresser:  Great. I want to ask you about another blood test that literally I just saw an article on Science Daily this morning. So I thought, oh, I’m going to ask Dale about this. It was a study in Nature Medicine you may have seen published on March 31st. And it was looking at MTBR Tau 243 as a marker of toxic accumulation of Tau. Is that something, is that a newer test that’s promising but just not available yet? Or is that something you look at as well?

Dale Bredesen:  Great point. So there are multiple new Tau tests. And the reason is when you look at an amyloid PET, and you look at the amyloid accumulation in the brain, the thought years ago was that’s going to associate with the disease. It hasn’t really associated very well. There are a lot of people who have amyloid positive scans and have no symptoms. And we understand now that that’s because this amyloid is like igloos. It’s surrounding the pathogens, sequestering them and killing them and trying not to put too much stress on your brain. Basically, you can have it for years because you are protecting your brain. So no surprise, the drugs that go after amyloid are not working well. However, when you look at a Tau PET scan, that correlates much better, both regionally, so it tells you, this area of the brain is not functioning very well. So it is a better association with cognitive decline. So from that, people started looking at p-Tau181, p-Tau 217, etc. And as I mentioned, p-Tau 217 worked best. Now people then said, okay, what’s the next generation? How can we look even better?

One of those next generation ones, and I don’t believe it is available yet, but it will be out at some point, is this MTBR that you mentioned. And these are fragments actually. So it’s EMTBR, fragments of Tau that bind the microtubule. And you mentioned this particular one, phosphorylated 243. That seems to be a very good association. However, there are others. The second one is called a seeding assay, and this is offered by a company called Verovis. They argue, look, you’re only looking at a biochemistry. We want to look at a functionality. And so we’re doing an assay that says, if I have Tau that alters its structure to become that antimicrobial protein, that will become a prion. We can use that in a seeding assay and tell you how much functional active Tau that is literally going to damage your brain is going to be there. So that’s the second one. The one that I think is actually the most interesting will be out in the next couple of months, and it’s called Super p-Tau217. It’s a much more sensitive marker of p-Tau 217. So it will pick up changes before you have any cognitive symptoms. That is really exciting. So it’s basically doing an oral glucose tolerance test with insulin. You can pick things up long before you ever have diabetes. So I think that’s part of the future. But I recognize there are these multiple tests. People have focused on Tau because it does look so promising in being associated with future cognitive decline. And by the way, you can also use it to follow. So as you improve, you see your Tau going back down toward normal.

Chris Kresser:  Okay, let’s talk a little bit about, you mentioned the phases, asymptomatic, SCI, MCI. What are some of the signs and symptoms in SCI that people should be looking out for? And if you could rank them maybe if this is possible in order of most concerning to least concerning. The reason I ask is I often have patients, for example, who the only symptom they have is difficulty with word recall.

Dale Bredesen:  Yes.

Chris Kresser:  Every other way they’re firing on all cylinders, doing great, no other cognitive issues. It’s just that one issue. And they often ask me, should I be concerned just with this one symptom? I’m doing great in every other domain. So what are the areas of concern for SCI?

Dale Bredesen:  Yeah, this is such a good point. And yes, we’ve seen so much of this. And these are people who are perfect examples of people who should know what their p-Tau, GFAP and NfL are. Am I going in the wrong direction or am I okay? And unfortunately, we do have most doctors are not as sophisticated as you and your team are. So they look at these things and they say, you’re just getting a little older. And I’ve seen people even into the stages of dementia where the doctor will say, yeah, you’re just getting a little older. This is normal aging. No, this is not normal aging. So to go back to the SCI that you mentioned, there are two general groups that we see, amnestic changes and non-amnestic changes. And actually the non-amnestic changes are more concerning because that actually was, the amnestic ones are more common. The non-amnestic ones are more concerning because they are often associated with a worse course. And by the way, the people who have the non-amnestic are the ones that lose their jobs very quickly, whereas the ones that have the amnestic changes do quite well and may retain their jobs for years.

Chris Kresser:  Dale, can you just define those terms for folks who are less familiar? What’s the difference between amnestic and non-amnestic in this context?

Dale Bredesen:  Great point. So amnestic means memory problems. So you’re having trouble with remembering things. And the common thing is someone will say, well, I was at dinner with my spouse last night and he or she said, ask me the same question three times during the dinner. It’s clear he or she is forgetting their keys. He or she is forgetting when they go out to a parking lot where the car is, things that. Kind of typical memory loss problems that we think about in association with future Alzheimer’s. So people always will say, gee, am I on my way to having Alzheimer’s disease? And it’s a legitimate concern. And the good news is we can now tell you if you’re on your way, and we can make sure you never have dementia associated with Alzheimer’s. So that’s the big change. So common ones, as you said, with SCI, asking the same question multiple times, probably the most sensitive is some trouble remembering names. We see it all the time. And it’s the most mild, it’s the least concerning of these because so many of these names, there’s no functional association. If it’s John Brown, what is that? You can’t tell why he would be John Brown, right? Whereas things that you’re doing, you can say, well, I do this because of this. So that’s a common one and I would say the least concerning. The more concerning are when you are forgetting why you came. So we had one person for example who got on a plane and while she was on a plane she got to her destination and said I have no idea why I flew here. She got in the plane and flew home. That’s concerning. So those are the sorts of things you really are concerned about.

But other common ones are facial recognition. So they’ll say gee I don’t really recognize faces anymore. So I look at a face and I say is that someone I know? That is a non-dominant parietal lobe symptom. When you are developing cognitive decline, you have the temporal lobe and the parietal lobe are the two regions of the brain that are most affected typically, that are on your way to future Alzheimer’s disease. The amnestic problems, the memory problems are associated with temporal lobe more than parietal lobe, whereas these non-amnestic ones, and that’s trouble calculating, trouble recognizing faces. There’s something called PCA, which represents five to 10 percent of people who develop Alzheimer’s, and that’s posterior cortical atrophy. And they have trouble with all visual processing. So they’ll look at multiple things in a visual field, but only be able to see one of them. They’ll have trouble with driving and crashing because they didn’t see that other car, things like that. And we’ve just seen the first case, to my knowledge, of reversal. Very excited. And this is working with a wonderful, wonderful health coach, Carrie Rutland in New York. And a wonderful example of someone who got back the ability to read, got back the ability to use her computer. This person, by the way, Chris, turned out to have Bartonella, mycotoxins and here are things that should be looked for, but weren’t being evaluated by standard of care medicine. And addressing those with some consultation from Dr. Neil Nathan, who’s done such a great job in this area, and you’ll love his book, The Sensitive Patient’s Healing Guide, been really, I think these are really helpful, and this has really helped this particular patient to improve. So these are the sorts of things to look for.

One of the other common things, people will pull up to a stop sign and say, wait a minute I’m kind of familiar with this area, but I really, for a moment, have kind of lost my bearings. Should I be turning left? Should I be turning right? That’s a relatively common problem and a concerning one. Losing your job is a concerning one. People will find that they’ll get a new iPhone, for example, and they’ll have trouble this time figuring out the new things on an iPhone. So any of these sorts of things which are executive function related, the planning and structuring and things that, that’s concerning. And those are the people that tend to lose their jobs early on.

Objective Assessment Tools for Cognitive Health

Chris Kresser:  Okay, so let’s move on to discussing the more objective assessment tools. When we talked last, MoCA, and you mentioned it a couple times in this conversation, is that still the gold standard for cognitive assessment? If someone wants to take, let’s say someone’s experiencing some subjective issues, they’re concerned, and they want to take the next step, what would you recommend for that?

Dale Bredesen:  Yeah, that’s a really important point because in our trial we use MoCA and we found out that there was quite a surprising learning effect on MoCA. So in other words, even the people who weren’t getting better symptomatically and by other measures were able to do better on the MoCA when they retook it. They essentially learned how to ace the MoCA. So it’s a good screening tool, but it’s not a good following tool. That’s the difference. Great for screening because it’s quick. So there are other ones that are more sensitive that are online tests, things like CNS vital signs. Cambridge has one. I think BrainCheck has one as well, those sorts of things. And also now on the brain training ones like BrainHQ, that will also look to see whether you are improving. I find that helpful to see, is someone improving on BrainHQ or are they actually declining on BrainHQ? So those are all objective tests. And then you can add to that and complement that with what’s happened to your p-Tau, what’s happened to your MRI. We saw on the trial that people actually increased their gray matter volumes as they did the right thing and improved. Whereas usually over time, as you know, they begin to shrink. There’s also electrophysiology things like EVOKE and Brain Catch and things like that. So you can look at these things over time and see if there’s improvement.

Chris Kresser:  Okay. So just to summarize, MoCA is still good for the initial assessment. And I know, I think on the MoCA cognition website, there’s a way to do it digitally. There’s also, think the duo app that allows you to do the assessment. And then we have things like Brain HQ, which is, I want to come back to that because I want to ask you more about those from a therapeutic perspective of the brain training tools. And then I think you mentioned Brain Check. So those are all pretty comparable ways of getting that initial assessment, but then the better way to track progress over time, in addition to the blood tests is measuring your progress on Brain HQ and some of those.

Dale Bredesen:  And CNS VitalScience is a particularly sensitive one. That’s the one that we ended up using in this trial. And it’s been very helpful because you can see the ones who are on standard of care. You can see them declining on their ability. They can’t learn to take the test better. And the ones who are on treatment are clearly going up and doing better.

Breakthrough Results in Clinical Trials

Chris Kresser:  All right, great, that’s super helpful. All right, I want to talk now about some of the clinical trial results. I know you’ve got some exciting stuff happening here at six different sites. So let’s talk about the interim results.

Dale Bredesen:  Yeah, very excited and working with some absolutely outstanding physicians and grateful there for their tremendous work. Dr. Kat Toops, Dr. Anne Hathaway, Dr. Christine Burke, Dr. David Haas, Dr. Craig Taneo and Dr. Nate Bergman. So really fantastic physicians and getting really outstanding results. This will finish at the end of October this year and it is, the way this is structured, it’s a randomized controlled trial. So you have the control group that gets the standard of care. They don’t get placebo, they get standard of care for people with Alzheimer’s disease. These are people who are in the MCI and early dementia phase. So it’s not late stage dementia, but it’s also not SCI. They have to have demonstrable changes. So that’s literally the third and early fourth stages of this. And again, earlier on, it’s even easier. So they’re having a standard sort of functional medicine evaluation. They are getting their p-Taus evaluated. They are getting volumetric MRIs, all of these things and looking. And then they are treated by addressing the things that are critical. And we think of this in terms of the seven basics and the two specifics. The seven basics are plant-rich mildly ketogenic diet, exercise, sleep, stress, brain stimulation, which includes brain HQ and photobiomodulation and things like that, and then detox and some targeted supplements. And then the two specifics are, do you have specific infections that we need to treat? Do you have specific toxins that we need to treat? And with that, it’s striking.

So they have improvements in their overall cognition, which are statistically significant. They have improvements in their memory, which are striking. The memories are declining in the control group. They are improving in this group. And we just published a paper recently showing over 10 years of sustained improvement in people who were on the protocol and doing the right things, as you know. And then we look at executive function, and that is improving as well. So all of these things are improving. Their cognitive symptom trackers are better. Their AQ change. So AQ is you’re asking now the partner to say, do you see a difference in this person? And the partners are noticing that the ones on the control arm are not getting better and the ones in the treatment arm are getting better and better and better over time. So very enthusiastic about these results. They should be published next year. We’ll probably have a pre-printout the end of this year and then a peer-reviewed publication out next year. We did have a previous trial that was a proof of concept trial that also showed improvement, but with that one, they didn’t allow us to do a control group. So this now, we have a nice control group to show the striking differences between the two.

Chris Kresser:  Amazing. I’m looking forward to that. And just, I think we’ve talked about this the first two times you came on the show, but I want to mention it again for people who haven’t listened to those yet. And if you haven’t, definitely go back and do that. Compare the results that you just mentioned to the results of the drugs that are currently used for Alzheimer’s.

Dale Bredesen:  Yeah, that is the important point. So I’m glad you raised it. The best we can do with drugs right now is to slow the decline. So they don’t make you better, especially these new anti-amyloid drugs. And I should mention the earlier drugs like Aricept and Namenda, what was really scary about those is that when they looked out years after starting those, the people who had been on those did worse than the people who were never treated. That is really concerning. So that has not worked well. Then the newer, quote, breakthrough drugs where you’re literally ripping the amyloid out of the brain with antibodies, they have not made people better. They have slowed, in the best case scenario, they slowed the decline by about 25 to 30 percent. So you’re decelerating a little bit on this curve going down. Whereas in the trials, we’re actually making people better. We’re improving their cognition. And we know now, from the paper I mentioned, we can actually sustain their improved cognition. In fact, the very first person I ever treated, the first reversal of cognitive decline was April of 2012. She has now, she’s just turned 80. She came to see me when she was 67 and she’s done great. She continues to do very well at 80. She is starting a coast-to-coast walk on April 5th out of San Diego walking to Florida. Now we’ll see if she makes it to Florida, but she’s got a great team. She’s got sponsors. It’s really going to be interesting to see. She’s done marathons. She’s done a hundred mile bike rides. So she’s a pretty amazing person and she’s done very well with her cognition. She actually now works as a brain health coach. So, we do see improvements that are sustained. And I think this is, this is the way things are going for everyone to avoid that full on dementia.

Chris Kresser:  Incredible. So you have a new book, The Ageless Brain. Maybe before we dive into the specifics of that, you could put it and place it in context with your other books. Just a 30,000 foot view, especially for people who are new to your work, how this fits in with your previous work.

Dale Bredesen:  Yeah, great point. So it’s very straightforward. The very first book was about, oh my gosh, can we actually reverse cognitive decline? It’s the science and it’s the first people, etc. The second one, people said we want more details. We want more. What websites, what tests do we get and all that. And that was The End of Alzheimer’s program. The third one was really more my own interest, which was the first survivor. So I had this seven people who had done really well and I wanted them to let the world know, hey, we did well, please don’t give up. We can help you. And so they wrote their own stories and that was The First Survivors of Alzheimer’s. So then people said, well, look, you’ve written about Alzheimer’s, but what about brain aging and what about brain function? So the goal of this one is basically save brain cells. How can we give everybody more brain cells? And so the idea is for everyone, what happens when you get a little older? What happens? And the scary thing is, there are differences seen now and recorded in research for people who have the common Alzheimer’s gene, which is APOE4. If you can believe this, in the 18 to 25-year-old range, they can already see the beginnings of changes. Okay, so all of us want to get on optimal performance and protection. We’re going to do better, as I started out the book by saying, whether you’re in your 20s, or your 90s or anywhere in between, your most important asset is a highly performing brain. It helps you at your job. It helps you in your interaction with other people. It helps you at every step of your life. It helps you with playing sports. You need that brain to function well. So anything you’re doing, you want to do that. We now know how to tune it up better than ever before and how to protect it better than ever before. And so I give some illustrative examples there of people who discovered early that they were headed for problems and then never allowed themselves to get there, worked on optimizing where they stand. And so we can protect and improve the performance of the brain like never before. And that’s what this book is about.

Essential Lifestyle Interventions: Diet, Exercise, and Sleep

Chris Kresser:  Fantastic. So let’s talk about some specifics. My non-expert perspective, just for seeing, I have an RSS feed set up for studies related to brain health, dementia, cognitive decline, etc. And I would say from a lifestyle perspective, the intervention that seems to make the biggest, the two that seem to make the biggest difference, but maybe the number one, I’m curious what your take is on this as the expert, is exercise. So yeah, how does that rank with your understanding in terms of exercise and diet maybe being two of the top factors?

Dale Bredesen:  Yeah, I mean, so this always comes up and I think it’s a little bit like saying, I think you and I talked about this years ago, what’s the one instrument that makes the orchestra? Well, you could say, well, you’ve got to have the violins, but without anything else, it’s not an orchestra. So I would say if you had to pick a couple, it would be diet, exercise and sleep. Those are probably the biggest three. But you have to remember where this is coming from. So the major drivers of our brain aging are three. It is reduction in energetics, and that’s blood flow and oxygenation and ketone levels and things like that. It’s inflammation, that’s oral microbiome changes and the rhinocidal microbiome changes that you and I talked about years ago. And leaky gut and all these things that we think about. Chronic pathogens and biotoxin exposure. And then the third one is toxins. And that’s the inorganics, the organics and the biotoxins. And boy, with the California fires, that’s been a real concern. And I have to say microplastics are moving up the charts unfortunately. They’ve just shown recently that these are concentrated in our brains more than our livers, more than our kidneys. And at least association-wise, they are associated with cognitive decline. Whether that is causal or not, we don’t know. There are now studies suggesting that you can reduce these with plasma exchange. But are we all going to have plasma exchange? I mean that’s a very expensive thing for everyone to think about.

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Dale Bredesen:  So this is an area where we really do have to think hard going in the future. How do we do this? How do we reduce this exposure? But I would agree with you that exercise is right up there. And especially, I love EWAT, it’s been very helpful for people. Katsu bands, very helpful for people. And HIIT, I mean HIIT alone has shown dramatic increases in your BDNF, your brain-derived neurotrophic factor, which has a demonstrably anti-Alzheimer’s effect and really supports brain function. So I would certainly include that. Exercise is important. And again, plant rich, mildly ketogenic diet, detoxing diet, supporting your gut microbiome, striking and so many people will say to me, well, there’s this new thing, I put a crystal on my forehead and it’s supposed to make things better. And I keep telling them, look, the diet is what you’re missing here.

Chris Kresser:  Get the basics down first.

Dale Bredesen:  It’s like, wow, get the basics. Because people think it’s not, it doesn’t have a big effect. It does have a big effect. And sleep is the other big one. So you want to know, did you have at least seven hours of sleep each night? Did you have at least an hour and a half of REM? Did you have at least one hour of deep sleep, especially for the detoxers? That is a really important thing to get that deep sleep. And then while you were sleeping, did you keep your oxygenation at 94 percent saturation or above? These are all critical parameters that I talk about in the book there that are important for getting your best results from sleep. Patient zero that I saw all those years ago in 2012 was getting about four and a half to five hours of sleep a night. Tremendous stress. She was flying around the world for her job, eating the wrong things, doing the wrong things, not getting enough exercise. She became a yoga teacher. She really got into this and she’s done so well. She’s driving her HRV up just doing an absolutely great job. So these things do matter. As I started to mention, I saw a guy the other day, very smart guy, ApoE4 positive, who was unfortunately had MCI. And he was doing a little better, but he said, I’m not all the way back to normal. So he started going through why not? And he said, well, wait a minute, I mean, pasta, bread, these are all fine, right? No, you missed the diet part of this. These are really important pieces.

The Role of Supplements and Brain Stimulation

Chris Kresser:  Yeah, I just want to emphasize this again and agree with you 100 percent. I’ve treated a lot of patients in my lifetime as I know you have and I think we also have maybe or somewhat atypical patient population, or I did at least where I would, a pretty high prevalence of biohacker types, people who are following all the latest trends. And what I often found was that many of those folks were not, they were focused on the wrong things. They were not doing, there’s no point in biohacking if you’re not getting seven hours of sleep, eating a good diet and getting the right, a good amount of physical activity. That’s where all of your attention and energy should be going initially. And you can’t biohack yourself out of a bad diet, not getting enough sleep, not getting exercise. So the challenge I think is that those are, those changes are often difficult to make and it’s relatively easy to buy a fancy device and use it because it doesn’t require significant lifestyle change. But you’re going to see far better benefits from getting those basics right. Everything you talked about diet, exercise, sleep, reducing toxic exposure. And then if you have all that stuff dialed in, great, then you can layer in sauna and cold plunging and that sort of stuff.

Dale Bredesen:  Yeah, and those are all great, but you can build the coolest house with no foundation and it still may collapse. So you really do want to have, you do want to have those basics. And then, as you said, you want to layer on these other things because the armamentarium for cognitive support is huge and growing. I was taught as a neurologist, the armamentarium is zero. There’s nothing you can do to prevent, reverse or delay. And now it turns out that that’s absolutely wrong and that there’s so much. And yeah, cold plunges are great for your mitochondria. There are mitochondrial transfusions on the way. These are going to be really exciting and I think are going to be very helpful for people with things like Parkinson’s and Alzheimer’s and even just brain aging because our mitochondria don’t function as well as we age. There is so much that’s great, but you’ve got to start with the foundation to get the best outcomes.

Chris Kresser:  Along those lines with supplementation, I just want to emphasize should be added to all of the basic stuff we’re talking about now. But let’s assume that someone is doing the right things. Do you have a sort of, and then you and I both would say we want to look at this from a functional medicine perspective, the ideal supplement regime will depend on individual factors, lab test results, all of that. So let’s assume that’s true. Still, there may be three to five supplements that you find yourself using more frequently than others or in a higher prevalence of cases. What would those be?

Dale Bredesen:  Great point. And Dr. Kat Toops in the trial has had a couple people finish the trial and then just go off their supplements and they crashed after that. So although the mainstream will tell you supplements don’t help brain health and they’re oversold, well, the reality is they can be very important, just as you indicated. And so, yes, we want to look at things. We want to go back to the fact that the big three that are hurting us are energetic reduction, inflammation, and toxicity. So I target the basic supplements for that. So I like resolvins as an example. They’re quite good for anti, as resolving your inflammation. I like to increase your energetics. And so things like actually this new EpiCatechin, very helpful. Also things like just increasing your NAD. And I don’t know, Chris, do you NMN or nicotinamide riboside? Or do you niacinamide? There are lots of ways to increase your NAD, and it’s another important one. And again, just getting enough, getting your homocysteine down. just a methylated B12 and methylated folate and P5P. I happen to like those. Magnesium threonate, that’s been published in a study. So you can actually look and see. And actually I have to give credit to a supplement group that actually did two nice controlled studies where they showed improvement in cognition. So this particular group, Life Seasons, and full disclosure, we’ve worked with them, but I was impressed with them. They did, completely separate from me, they did their own trials on this and showed cognitive improvement. Now these were people, to be fair, who were early on. These weren’t late stage dementia patients, but they showed improvements. And I think it’s important, anytime someone pushes X, Y, or Z, if you’ve got a trial behind you, that really gives you more confidence that you’re on the right track.

And then, there are other things I think that can be helpful. I happen to like Pectasol because it is something that is, it helps to reduce inflammation via Gal 3 that turns out to have an impact on the oligomerization of the amyloid. So the amyloid you’re trying basically to sequester and kill microorganisms. And it’s been fascinating that there is a normal brain microbiome. I was always taught that the brain was a sterile organ. That’s turned out to be wrong. And interestingly, many of the organisms in your brain are oral organisms. So there does seem to be a very important connection there. So Pectasol is another one of the ones I like. As with many other people, I like curcumin. It is, interestingly, it has this nice anti-inflammatory effect. It also, by the way, is a very tight binder of amyloid and Tau. So you don’t want to remove those before you do the right things, but once you are supporting your brain, you want to begin to remove that amyloid and that Tau that has been fighting these microbes and things over the years. So I think curcumin is another good addition to the armamentarium. And you can go on healing your gut. Detoxing, actually high fiber diets are incredibly helpful. Glutathione, so NAC and s-acetyl glutathione and liposomal glutathione, very helpful. We see, Chris, I’m sure you’ve seen the same thing. So many of the people who have cognitive changes associated with toxicity have very low glutathione. And they do well with things anything from IV glutathione to intranasal to inhaled to just oral glutathione can be very helpful to them.

Chris Kresser:  Do you have a take on creatine? It’s getting a lot of attention lately in terms of, not in terms of the muscle performance, strength and performance, which is the tip, which it definitely does, but more in terms of brain health and particularly recovering brain function after a poor night’s sleep. I just saw a study published about that. I’m curious if you have an opinion on creatine.

Dale Bredesen:  I’m a big believer. It addresses that number one issue which is energetics. And now do you like five grams a day or what do you typically use for creatine?

Chris Kresser:  Five or 10 would be standard, but I saw this study that I just saw was a higher dose of 20 grams post a poor night’s sleep. Cause one thing about sleep is there’s, in some cases it’s people not, just not making enough time for it. But as you and I know, in other cases it’s because they don’t sleep well. And there are just inevitably times where we don’t sleep well. And this particular study showed that 20 grams, is a very high dose of creatine, restored normal function of the brain after a poor night’s sleep. So this isn’t a get out of jail free card. It doesn’t mean you can not sleep well and just take 20 grams of creatine. But it was, I think, because of what you said, restoring normal mitochondrial function in the brain helped to bring back function online.

Dale Bredesen:  And this is what the book is about. You want performance and protection. So you can take Adderall the next day too. That’ll work fine. But it does not protect you. That’s the whole issue. There is a CMA, I don’t know if you’ve seen this combined metabolic activators. So it was the same sort of thing, combining things that supported energetics in the brain. And they did see improved scores in people with MCI over several months. The problem is these were extremely high doses. So you look five years down the road, you may not see such protection. So this is why we want that space in the middle where you’re getting the right amount to give you performance, but you’re also protecting the brain over the long run.

Chris Kresser:  Makes sense. Let’s just chat really briefly, I know we’re coming up on the end of time here, on brain training programs. And I’ve heard a lot of opinions about these, everything from they’re the best thing ever to they’re completely useless. So I’m curious what the research shows and how you use them in your protocols.

Dale Bredesen:  So there’s some exciting, yeah, we use them, absolutely. And we used them in the first trial and actually everybody in the first trial improved their brain HQ scores. We are using it again because it works and there’s a lot published now. So, a lot of these arguments you brought up, this is a controversial area. And several years ago, a couple of groups got together and said, this doesn’t really improve you. You’re just learning to that particular test, but it doesn’t help you in general. Also, there’s a very interesting paper coming out where they showed improvements in their cholinergic status in the brain. So this is having an impact. But all of these things that have been used as monotherapies, and this has happened with supplement after supplement, drug after drug, this sort of thing, when you don’t observe functional medicine, when you don’t look at this as a symphony, of course, very few things work very well by themselves. So you want to have as part of an overall program to get much better results. Yeah, you can improve energetics for someone, but if they’ve got a dramatic amount of toxicity, it’s not going to help much. So addressing all of these things together. When you do that, that’s where you see the really great outcomes. And there’s no question that brain stimulation, and that is not only the Brain HQ approach, but also things like photobiomodulation. Some people to use magnetic stimulation. I know Dr. Toops really liked, is a fan of origin. We’ve also used things like V-Lite or Neuronic. They all make excellent and different approaches to photobiomodulation.

Chris Kresser:  Great. Dale, thank you so much again. Always a pleasure to speak with you. Let people know where they can find out more about your book, The Ageless Brain, and more about your work. And if somebody wants to explore working with your team, how they do that.

Dale Bredesen:  Yeah, thanks so much, Chris. I appreciate the great work you’re doing. So many people that you are helping and you’re getting the word out there, which is so important. You can see more, you can get these on Amazon. The Ageless Brain, you can get it, Barnes and Noble, any place where books are sold. You can get more information. I mentioned the GetABrainScan was an easy way to get that particular test, which is so critical. You can get more information on Facebook, Dr. Dale Bredesen, Instagram, X, Blue Sky, all of the above. So there’s lots of ways to get more information. And there’s also training, Recode 2.0 training. We’ve trained over 2,000 physicians from all over the world. So there are lots of ways to get information. And I think all of us should be able to help people to have long-term protection of the brain, long-term performance. There’s so much we can all do.

Chris Kresser:  Dale, thank you so much for the work that you’ve done and the hope and inspiration you’re providing to people with cognitive decline or people who have family members. I’ve referred so many in the past to your work and will continue to do that because it’s really a life-changing realization to know that there’s something that you can do to protect and prevent this from happening in the first place and even reverse it if it already is happening. That is just, there’s not much more that I can think of that would be of greater importance to people as they age. So again, thank you for your fantastic work and I look forward to having you back on for the next book and the fourth conversation sometime in the future.

Dale Bredesen:  Thanks so much, Chris. I’m truly grateful.