Impenetrable Fortress: How To Fortify Your Brain Against Memory Loss (& Reverse Alzheimer’s)​

Dale Bredesen, M.D.

Thanks so much for having me, Heather, always great to talk to you and thanks for the fantastic work you’re doing with your patients.

Heather Sandison, N.D.

So one of the reasons I’m so excited to be recording this now at this time is because you and your group have just published a trial. Taking twenty-five page participants through basically your whole program. So I’m thrilled that we can finally share with the world what you guys are finding. There’s a study that we can point to, to not just the one patient here or there that is getting better in someone’s clinic, but that there’s robust science coming out. So would you please just describe the trial, how it was set up the protocol and then also what you found?

Dale Bredesen, M.D.

Yeah, great point. So, you know, way back in 2011, we proposed the very first trial that would address all the different pieces, the things that we have identified in the laboratory over the years that were critical things like specific pathogens, things like specific toxins and all the things that you deal with with your patients as well. And we were not allowed to do the trial back in 2011 because it was multi-variable and the IRBs wanted this to be single variable. So you just had drug or placebo. And so of course we objected and said, hey, wait a minute. This is not a one variable disease. So we wanted then to collect anecdotes. And as you know we published anecdotes 2014, 2016, 2018, we published a hundred with improvement that was documented. 

So then we went back in 2018 after that publication and said, okay, can we do the trial now? And they said, no. And so I know it’s still crazy. So finally, in 2019, we were allowed to do a proof of concept trial. It’s only 25 patients, but the idea was it would allow us then if we got good results with that to go to a randomized controlled trial, which was what we’re in the midst of doing so really very fortunate to link up with Diana Merriam and the Four Winds Foundation that supported this trial and were just fantastic. And then also also a three absolutely outstanding functional medicine physicians, Dr. Anne Hathaway, Dr. Kat Tubes and Dr. Deborah Gordon. So really honored to work with them. 

And as you know, we basically took this from the test tube straight to the people and to say, okay, what are the things for each person, instead of all previous trials, which as, you know, have predetermined, what’s going to be the treatment, which makes no sense. So they say ahead of time, everyone who comes in is going to be treated with drug X, no matter what’s causing the problem, which makes very little sense. So the idea for this trial was to flip the script and say, okay, for each of these people, we’re going to look at all the different determinants. 

And there are about 150 different determinants from their various genetic things. And we worked with Intelex DNA and Dr. Sharon Houseman Coleman, whom you know, to look at what the genetics, whether there were issues with the glutathione related, with methylation related, with thrombosis related or on and on. And then also looking at the various biochemical parameters, the various microbiological parameters, looking at gut status, of course, looking at all the different pieces. And for those, for them, for each person, we were able to construct a fairly, hopefully a fairly accurate map of what were the contributors. And as you know you virtually never see people with just one contributor. 

Typically there are multiple things starting of course, with the genetics, with a belief for very commonly in about half the people in the study turned out to be able to for positive, but we saw all sorts of different things, as you can imagine, across the spectrum, and then try to guide the in target to the treatment, to each of those things. And of course it included a core. So we had a mildly ketogenic plant, rich diet for people. We wanted to look at their sleep. 

We wanted to look at their nocturnal oximetry. We wanted to look at their stress levels. We wanted to look at their hormonal levels. So all the things that you know well from functional medicine world that are critical. I think what the science has taught us is what the priorities are. There are things that have a fairly small input into cognitive decline. And then there are things that have a huge input into cognitive decline. And so then we can look at each of these and target these. And as you can imagine, the people who were able to comply, and we have people working with health coaches. So it was really fantastic people working with nutritionists and people working with physical trainers and then working with neurofeedback and things like that did very, very well. And so we were very excited to see how much better the outcome was with these people than with a typical drug approach to Alzheimer’s disease.

Heather Sandison, N.D.

So how long did it take, how long were people in the trial? When were you getting the metrics?

Dale Bredesen, M.D.

Yeah, great point. So each person was on for nine months. And so the idea was we typically see people improving within three to six months. So we did there, we looked at several variables. So we looked at their MOCA scores. We looked at their CNS vital signs score, so we could get a more sensitive indicator and at also different domains. 

We looked at their AQ change score. So in other words, did their partner notice as you know, some of the drugs just barely reach statistical significance, but the partners couldn’t tell any difference at all. So we wanted to know, did the partner also notice that these people were better? Yes or no. And then we also looked at their MRI volume metrics. So we looked at what happened to their gray matter and what happened to their hippocampal volumes. And then we also looked at their brain HQ. So did they get better with their brain training or were they failing on their brain training? So that way it gave us a lot of different complimentary parameters that we could look at for these people.

Heather Sandison, N.D.

And what’d you find?

Dale Bredesen, M.D.

So, yeah, so we looked, it was interesting. We looked at three months, six months, nine months, and then nine months was the end, as I mentioned. And what was interesting to see was at three months, they had improved somewhat, but it was just reaching statistical significance. At six months, they had clearly reached statistical significance and at nine months they were still better. And at that time it was less than P, P less than 0.001. So really strikingly improved. And we had people who went from MOCAS of 19 to 30 perfect scores of 30. So we had some dramatic improvements and then we had some less dramatic improvements. And again we had just a few people. 

So 84% of the people improved their scores, improved their CNS vital science scores, 76% of the people improve their MOCA scores. And what was interesting is that their MRIs actually improved. So you can look at MRIs and there’s a great example of what actually happens with MRIs over time. If you have Alzheimer’s or MCI, you typically lose a significant amount of gray matter volume and hippocampal volume each year, you can see that going down. If you’re aging normally with no, no complaints, you actually still lose a little bit on average. So these people who actually had MCI or Alzheimer’s, and we had some with age actually did better in terms of their MRI volume metrics, the normal people who had no complaints. So their gray matter volume actually increased slightly. Their hippocampal volume was a slight decrease, but as I said, less decreased than just normal aging. 

So they, so for all these parameters, they did well. And by the way, their AQ change scores, their partners noticed that they did well as well. So by all these different criteria and actually a hundred percent of them improved their brain HQ scores. So just practicing getting on this, they actually, they all did better with that. So I think, again, it really supports the idea that targeting the things that are driving the decline really is the way to go. Now of course, we didn’t include people with MOCA scores of zero or five or 10. And that’s one of the reasons I’m very excited about your trial, where you’re looking at people with MOCA scores down to 12, ours was 19 through 30 and with CNS vital signs that were abnormal as well. And so I think it’s going to be very interesting and very important what you see in your trial.

Heather Sandison, N.D.

So one of the questions that I get asked most frequently in my office is if we do this, if we put the money and the effort and all of this energy, if I go to part-time work so I can help my mom or dad do this, how likely is it that we’re going to get benefit? And that really was what drove me to ask the question of, who’s going to get benefit and how often so that I can have a lot of confidence telling these families. I think one of the big things I want to come back to that you mentioned was the changes that the spouse is serving, the Alzheimer’s is so devastating, not only to that individual, but to the entire family network that’s affected and nothing, but sometimes it’s not even just the family. They’re out of the workforce and a caregiver can come out of the workforce often to take care of that person. 

Doesn’t just take down the patient. It affects many people around them and you measuring, we have failed to do that. In the next trials I think everyone should be doing that because how we define success is really important here. And that’s what I want to draw attention to for our listeners is that the changes that a caregiver notices can have that has more, you start to get exponential impact. And when we compare this to what some of the drug makers are looking for in terms of success, I want to be really clear about the differences there. What you’re talking about is improvement. What they’re talking about is a slowing of decline. So I know you have a slide that really represents this well.

Dale Bredesen, M.D.

Yeah. Let me just show this. That’s a great point. Let me just show the difference here. So I think you’re right. The semantics of success are very important. So this is just to illustrate that on average, if you have someone who has Alzheimer’s or MCI, and this is in published literature, then you lose on average about 3.4 points on a 30 point scale per year. So you lose whether you’re talking about MMSE or MOCA, you’re losing a little bit each year. The best and so Aducanumab which was just approved in June by the FDA. 

So-called Aduhelm this in its best trial. And I should say in one trial, it failed completely, but in another trial at one dose, only the best it did was to slow the decline by 22%. So it’s not making people have a better cognition. It’s just slowing the decline. And unfortunately, one of the years ago, one of the husbands to one of the patients said, I know the drug makers are trying to make drugs that slow the decline, but speaking as someone who’s the spouse of someone with relatively late stage Alzheimer’s, this is the last thing that I would want to see. So it’s really tough. And, we all want to get things earlier on, get people and I think that’s one of the big goals to get people to come in earlier. And I should say the Aducanumab trial, the range of cognitive scores that they took were very similar to what we did in our trial. 

So ours were 19 and above for the MOCA scores. And so you can see here in the trial, in our trial on average, there was a 3.89 point improvement. So they actually had improved cognition. Now, as I said, we had people going from 19 to 30, but on average it was 3.9. And a lot of them, there was a bit of a ceiling effect because people would start at 26 where you can’t go up too much from 26, you could only go to 30, but this is what we saw on average. So I think that you’re absolutely right. It’s important to talk about the semantics of success. So many people have asked me, well, I shouldn’t, should I put my spouse on this drug because do you think it will help? Do you think it will make them better? Well, that’s not what the drug is for. 

It’s simply too, in the best case scenario, slow the decline. And of course that’s with a 17% of them developing micro bleeds in the brain about 40% developing some form of edema swelling in the brain, headaches, all sorts of issues. And with the April before positives, there was about 50% who had complications. So I think as many neurologists have said, this is not the drug we were looking for. This is a drug, but it’s not the goal.

Heather Sandison, N.D.

So that’s another point that I really want to drive home here is the difference in side effect profiles. So this we’re talking about a drug that can cause micro hemorrhages, so bleeding in the brain, swelling in the brain, high cost burden to Medicare, whoever’s paying for it to make sure that these side effects are managed. On the flip side, what are some of the side effects of your intervention?

Dale Bredesen, M.D.

That’s a great point. So the intervention that we use and the side effects have been a better weight control, improved lipid profile, improved glycaemic profile, improved insulin sensitivity, improved microbiomes, improved depression, more joy, happiness now to be fair. Yes. It’s a complex approach. You’re hitting various things. And so you do, it definitely helps to have a health coach, but what people found is that they have more energy, they do better. They feel better, they sleep better. Their whole lives are improved. And again, I think this comes back to this fundamental schism in medicine when I was trained in medicine.

 And I’m sure when you were as well, there was a lot about writing a prescription and a lot about kind of non physiologically relevant. Although I know you were trained in a more physiologically relevant environment, which has fantastic. Human beings are complex organisms. And I think we’re now understanding that there is so much more that we can do to address the physiological parameters that are driving the decline to begin with. We are unfortunately still laboring under this whole, the Flexner Report of over a hundred years ago that changed American medicine and said, medicine should be more scientifically based. 

Great. The science has moved on by more than a century and the medicine really hasn’t. So it’s now time to increase our data set size, to have more complex algorithms, to have deeper dives into what’s actually causing these problems. So I think that that is the future. And I think that the part of that future is going to be a future where we really pretty much end these complex chronic illnesses from Alzheimer’s to Parkinson’s to Lewy body disease, you know, on and on.

Heather Sandison, N.D.

Yeah. This is such a really great point is that the science and the paradigm that we’re using, they don’t match anymore. And we have the ability we have the intellect we have the people, we have the technology to really start to match the complexity of the human body with our intervention. And there’s nothing stopping us other than sort of these social constructs.

Dale Bredesen, M.D.

Right. It’s interesting to me that, Google knows where you shop. They know how you’re living your life. They know a lot of things about you, and they have some very, some very complex algorithms to use. Now, why are we not using that same sort of technology to identify people in their earliest changes? And there’s been discussion about using changes in keystrokes, for example, or using changes in pickup when Alexa is listening to you, Alexa can tell you, hey, your voice is beginning to change in a way that suggests that you may beginning maybe at the earliest stages of cognitive change. So I think for the future, having the earliest ability to get people, to make sure that you now are going to reverse your cognitive decline is absolutely feasible and will be the way of the future. If we simply get people to come in earlier, either for prevention or earliest reversal, we really can make neurodegenerative diseases rare beginning with Alzheimer’s then including these others. And let me just make one other quick point here. 

One of the biggest things that has held all of us back and I think has actually hurt millions of patients is the term mild cognitive impairment. So if you look at what happens to all of us, to people who are developing Alzheimer’s, there are these four stages. So you have a presymptomatic stage where you can already pick up changes on PET scan and spinal fluid and things like that. And so we call this presymptomatic, then we have SCI, Subjective Cognitive Impairment, which typically lasts about 10 years. It’s easy during that time to reverse the decline, but very rarely do people do anything about it. 

Then the third stage out of four, we call mild cognitive impairment. At that point, you’re relatively late in the pathophysiological process. So this is very much like saying, oh, don’t worry. You just have mildly metastatic cancer. It’s really a late stage. And so to me, MCI should be called advanced stage Alzheimer’s it’s the third of four stages. And by the time you’re actually told you have Alzheimer’s, that is final stage Alzheimer’s, you’re actually now losing activities of daily living. Typically, you’ve now had the underlying process for two decades. So we’re hurting the patients, we’re hurting our practices and we hurt we’re hurting the global burden of neuro degeneration by saying, oh, don’t worry. It’s just MCI. We really want to get people in far before that hopefully for prevention or at the latest for SCI. SCI, which really should be called early Alzheimer’s disease. That’s when the changes are actually there and they’re already symptomatic.

Heather Sandison, N.D.

The reason this is so important is because this drives human behavior. There are so many people who are still told the old, outdated factually inaccurate narrative that there is nothing you can do by their neurologist. Who’s very well-meaning, but who doesn’t realize that there are interventions that can work. And so people are driven to either hide it or go further into denial. And they delay getting the care that could help. So changing the storyline so that people hear go soon, it go immediately. When you start to notice change, that’s when we can have the biggest impact. That’s when we can really prevent this disease from essentially torturing you and your family.

Dale Bredesen, M.D.

Exactly. Right. So the number of people that were in the book, that’s coming up, “The First Survivors of Alzheimer’s”, they’re worried about their families. So now the idea is you’re going to end it with this generation and none of the future generations should have this problem.

Heather Sandison, N.D.

Alzheimer’s is optional. There are things that we can do, especially if they’re done early on, that can prevent the progression of the neuro degeneration. So there’s a lot, we know a lot certainly than even it, a handful of years ago. What are some of the intriguing things to you that we don’t know? What are some of the important questions that are left unanswered?

Dale Bredesen, M.D.

Great point. And I think there are a couple of directions that things are happening. So we looked at initially in the laboratory at what is the fundamental nature of this problem? And what came out of this was surprising and interesting to me in that it really is. If you look at the fundamental nature of this problem, it is a network insufficiency. So just as you would have a deficiency of vitamin C giving you scurvy, this simply is a more complex insufficiency. It’s an insufficiency of a network. So that now the network demand exceeds the network supply for years. And then ultimately you start, bringing the network down very much, by the way, what a very much analogous to what happened with COVID-19. 

We had an insult SARS, COVID-2. Everyone was told to shelter in place, pull back, go into a protective mode, a downsizing protective mode. And of course, we end up with a recession. Your brain is doing the same thing. It’s exposed to pathogens, things like P- Gingivalis and things like, various fungi, herpes simplex, Lyme disease, toxins, all of these sorts of things. And your brain is saying, okay, I’m going to go into a protective downsizing mode. So we then simply have to address these things. 

So we look at that and then there kind of two critical directions. One is, can we now adapt this and look at the specific neurochemistry for other diseases? So we’re now starting what we call the ARK project ARK because the ark was two by two, by two, this is small numbers of patients. And we’re dealing with the first ones who have macular degeneration. So we’re very excited it’s a different chemistry, but there are some of the same sorts of things. And then the next one is going to be Parkinson’s, Lewy body and on and on. So we’re very interested to go in that direction and see if we can adapt this approach to all other neurodegenerative diseases. At the same time, as you kind of applied, we’re also looking at how do we now make this better? What about people who come in with single digit MOCA scores who truly have very late stage Alzheimer’s? And so we’re, I’m very interested in setting up another trial that we would call the SARA trial, Severe Alzheimer’s Reversal Attempt. 

So this is an attempt, what do we need to add? So for example, what if you take these people now and who we, there are no question. Anecdotally, there are a few people who will improve their MOCA scores. We’ve seen people go from zero to six, seven, nine. We’ve never seen anyone go from zero to 30. What are we missing? What you know, is there, do you need a brain transplant? Do you need stem cells? Do you need intra-nasal trophic factors? Do you need, what it that you need, to make people do even better? Of course we hope that ultimately, that won’t be an issue because nobody will wait that long, but we, so we’d like to understand. So all sorts of interesting new areas, as you know, Plasmalogen is all really interesting work by the biochemist Dr. Dayan Goodnowe on Plasmalogen, which are typically low in people. How do we improve those? And is that going to turn out to be critical? I think the jury’s still out. We don’t yet know, but they certainly look very promising. 

What about stem cells? And are there specific ones that are going to be better than others? And are you going to have to administer them in a better, you know, in a different way, do you want to open the blood-brain barrier, which is a common thing that’s done when stem cells are administered? Is that going to be more helpful? I think there’s a lot of promise for some of the intra-nasal trophic factors. So things like Davunetide, which failed unfortunately in the past, but of course it was used as a monotherapy. So all of these things where they try to use it as a monotherapy, I do think the future is going to be, to combine targeted drugs, along with the protocols where we can target the things so that you’re now going after what’s causing the problem. But you also have very powerful drugs against specific molecular targets. I do think it’ll be interesting to see when you take things that are antiamyloid, which I think are not a great idea at the beginning, the amyloid’s there for a reason, but now after you’ve addressed those things, isn’t going to be okay secondarily, to begin to remove the amyloid. And I think, that is going to be an important question. The concern is are we going to cause cerebral hemorrhage? So we’re still arguing about whether we should be trying to include this as a control in this next trial.

 My concern is it might be a bit dangerous. I mean we don’t want to cause cerebral hemorrhage in people we don’t want to cause edema and things like that. However, maybe very low doses over time to help slowly remove that amyloid, which you now no longer theoretically need, because as you don’t have the same insults, of course, there’s a lot now on micro dosing of various things like LSD and various things, the ayahuasca and silicide, but in all these sorts of things. So there is some promise there, with small doses of these as well. You have to be a little bit careful. There’s some interesting work on cannabinoid receptors and fairly direct roles in the process of amyloid and cognitive decline. So I’d think that the what’s really interesting to me is we’ve been taught that the arsenal is zero. 

There’s nothing you can do to prevent or reverse or delay the decline of Alzheimer’s. And therefore don’t check your APOE status, you know, don’t look. And I think the truth is just the opposite of that. The arsenal is huge and the critical piece is knowing when to use it, how to use it, what to target and knowing what the critical species are. Now, one thing we are finding, and I’m sure you’re seeing the same thing, people will improve and then plateau and there’s something being missed. And sometimes we’ll say, okay, this turns out. And one example, for example, is a person who did it very well. Then starting to have a little problem actually it turned out to have undiagnosed Babesia. And when that was addressed, she then did very well once again. I mean, other people, it turns out to be things like leaky gut, or it turns out to be things like unnew, undiagnosed or unrecognized toxins that were present. 

One recent one turned out to be just a person who was now under additional stress and just removing that stress that I was, as a scientist, I used to think that stress wasn’t particularly important. And I have to say, I have to say it’s turning out to be very important. And of course, I can’t argue with the data. So things like meditation, which we never considered in a laboratory turn out for some people to be absolutely crucial to getting best outcomes. So I think we’re all once we kind of have the background, we have the template, we’re now all seeing how we can make this better, better, better, better. 

And so I’m really interested to see what you see now, I should say we just looked at the data. So we published the data on the pre-print server med archive. We’ve now looked at what happens when you just don’t do the trial, but you just take large sums of data for many, many practitioners. So we’ve had, as you know over 2000 practitioners who’ve now been trained. They’re not, no one’s following them so that therefore, if you don’t have the same level of compliance with the program and no surprise the data, show that on average, people did a little better, but it clearly wasn’t as good as the trial. So getting people to do the right thing and optimizing things really turns out to be important. And this is much more like surgery than it is like medicine. There are doctors who are getting almost everybody to get better, and there are doctors who are getting almost nobody to get better. So it really does depend on because you know you become good at this over time and working with people in getting your best outcomes.

Heather Sandison, N.D.

So one of the things that people can do right now that they could take away today is a cognoscopy is what you call it. So if someone is listening to this and they’re saying, this makes a ton of sense, what can I go do tomorrow? Can you describe what they would ask their doctor to do essentially?

Dale Bredesen, M.D.

Yeah, that’s a good point. And so, the idea was simply that we all know that when we turned 50, we should get a colonoscopy so that we know we stand and we can make sure that we lower there our risk of dying from colorectal cancer. So our idea was, okay don’t forget the cognoscopy. You want to, if you’re 45 or older, and certainly if there’s an Alzheimer’s in your family, you probably want to do this at 40. So at some point you, you want to find out where do I stand? And it’s really the four big groups of things that you want to know. You want to know, are there ongoing pathogens? 

Are there ongoing toxins? Are there, what’s the status on trophic support, cell hormones and nutrients and things like that. And then what’s the status on energetics, which means, it’s going to mean cerebral blood flow, oxygenation, and especially people who have sleep apnea. That’s a huge issue, mitochondrial function. And then your ketones are you getting combustible substrates there? And that’s where you can even see on a PET scan that people who have Alzheimer’s and pre Alzheimer’s are not doing well with utilization of glucose in their temporal lobes and parietal lobes. So for a cognoscopy, we look at that set of things. We’re looking at the various nutrients and the various hormones and the various inflammatory metabolic and inflammatory parameters and looking at gut microbiome and those sorts of things, which are critical to know. And again, it’s so interesting to me that a hundred years ago, we were all dying of acute illnesses like TB and all and Pneumococcal pneumonia, and diphtheria and things like this. 

And now we’re all dying of these complex chronic illnesses. And the bad news is you don’t get the symptoms until relatively late in the disease, just as we see with Alzheimer’s, the good news is if you know what to look for, of course you can see them coming 10, 20 years ahead of time. So if you simply know what to look for, then you can look at these. And just as we all know our cholesterol, we all know our blood pressures. We should all know these other parameters. And what’s been really interesting. I think wearables are going to be so helpful as everyone’s now being able to follow themselves. So you can see where your glucose stands, you can eat and do it day to day. You can even do CGM, continuous glucose monitoring, which is so surprising to so many people. 

They find out that they have these huge peaks and valleys, both of which are bad for your brain, so that they’re developing their insulin resistance. But then they’re also crashing at night and waking up in the middle of the night, not realizing, oh, my glucose is 45. That’s why I’m waking up your heart rate variability. I can, I’m following my own. And I can see, when I’m under a lot of stress, it’s going to get way low. And then when you’re just relaxing and you’re doing some deep breathing and things like that, boom, you’re so much better. So that’s a critical variable, just simple things. Following your blood pressure, looking at your nocturnal oximetry, making sure that you’re getting enough oxygen, you’re sleeping at night, looking at your sleep stages, looking at your ketone levels. 

These things are looking even at your vascular elasticity. These are all things that we can all do fairly easily and monitor ourselves. And at the same time we can see, are we getting too far? You can use things like a breathalyzer. So a couple of weeks ago I decided, okay, I’m going to try to my wife, my daughter. And I all said, we’re going to try fasting, mimicking diet. And it was very interesting. I mean, my ketones went off the charts high, but actually it was too much, too soon. I actually had to back down a little bit because I started feeling horrible. It was like too much. So I had to kind of ease into it a little bit more. And so for all of us, we can now see these things, which really gives us a leg up to see, okay, I am in a situation where I am at high risk for Alzheimer’s. And of course, knowing you’re APOE four status or APOE status and to other genetics as well can be very, very helpful for this as well. So we really have so much control over our own future. As you just said earlier, Alzheimer’s is now optional.

Heather Sandison, N.D.

So this can feel, I know for a lot of patients or people listening, if you’re new to this, this can feel a bit overwhelming. And if you would like a guide or a coach, whether it’s a doctor or a health coach or someone to help you through this, the Apollo website is a phenomenal ones that Dr. Bredesen and his team has developed the Apollo website. And you can now access practitioners. So you can find practitioners who have been trained by Dr. Bredesen and the team there to do this work. 

So don’t let this be discouraging. This is a very very hopeful time where there is a lot of access. Like you said, there’s over 2000 doctors or providers who have been trained. And so the help is out there. The word is getting out out. Also your books are very, very informative. So you can get started on your own. I’ve seen lots of patients who they get better. They follow the book, they get a lot better just by doing the diet and lifestyle things they can do on their own. And then six or eight months later, they come to me and say, I think we’re plateauing as a husband and wife team, I want to get more out of this. And then we do all the lab work. So there’s a lot of ways to kind of interface with this and use this information at home. Do you have anything else to add to that, about how people can get those, those really vital resources?

Dale Bredesen, M.D.

No I think that you hit on all the critical things. So you can go to dr.bredesen.com. I mean, go on the Apollo Health Co website and this will give you information. We also put it in the second book of “The End of Alzheimer’s” program, a lot of specifics on where to go to get additional information. And as you said, people will often get improvements just on their own doing some of the basics. And then we’ll say, okay, now how do I have to keep tweaking to get better and better outcomes? And that’s one thing I think that’s been very interesting to see. It’s not like classical medicine where you write a prescription and say, come back in two months, you’re continually improving, improving, improving, because you are dealing with a very complex system. 

Your brain synaptic connections, and there are multiple things that will impact this. And so in fact, you can continue to get better. And the most important thing of all, interestingly, something that you don’t get just from the trials is the sustaining. So if you look at, for example, a drug like Aricept, you get a little bump, but then you go right back to decline again. In fact, over the time course, over several years, what’s actually been published, is that people who are on Aricept, it’s slightly worse than people who weren’t on them, unfortunately because yes, they got the initial bump, but they went right back to declining. 

Whereas when you do the right things that you’re actually addressing the things that are causing the decline, when you get the improvement, you sustain the improvement. And if you continue to optimize, you can actually even enhance the improvement. And we now have people who are on for over nine years, who have continued their improvement for this nine years.

Heather Sandison, N.D. 

Wow. So kind of taking this back to a bigger, more kind of global scale, the population is aging, right? We have more and more of us are older and we are going to need some solutions. Otherwise, literally in this country, Medicare may go bankrupt. And there are many people who, not to be too negative here, but I see it. I have patients who show up in my office and they didn’t have kids. They don’t have close family are the youngest of their siblings. And they’re terrified of getting older and not having either the financial resources or the network, the social network that’s necessary to age gracefully and age in a way that they would look forward to. And so we really need to start re imagining as a society, what aging looks like and how we address these neurodegenerative disorders that are so common in the senior population. So I’m curious, if we were to take that step back and look at what, what are the global solutions look like? What are, what’s your vision?

Dale Bredesen, M.D.

This is such a good point. And I was just talking to a professor yesterday who was talking about the amount of money he was spending over $200,000 per year for his poor wife who’s in late stage. Also just, it was so sad to hear, and this has been a burden. It’s been a burden in so many ways. Finances are one way, but there’s so many other things and torn families apart. It’s of course ruined the finances of the families, the interactions with the children and the spouses. And of course it’s just the psychological, psychological impacts are huge. And so this is a problem as you indicated, in fact, as Professor Christine Yathi published a few years ago, this is now the third leading cause of death in the United States. 

It’s actually number two in the United Kingdom. So this is a huge and growing problem. And so you’re absolutely right. We really need now to fashion, what would it be like a global program? It would be like a global vaccine program, but in this case, it’s a global program to prevent neurodegenerative disease. And in cases where it hasn’t been prevented to make the earliest reversals possible. And if you think about this, you want to have a way that’s efficient. That’s the key. You want to have a way that, where you really get everybody without bankrupting Medicare. And so the idea would be to have a layered program. So it’s a little bit like a pyramid. You’re starting out with a simple set of things. Just as you talked about earlier with people do some basic diet and lifestyle things. 

Everyone can do some simple things and even get evaluated for a couple of simple points, like their genetics, and very inexpensive and do that. So the vast majority of these people should never suffer cognitive decline. And then what you could do for essentially free is once a year, you simply check to see where they’re going. Again, you can do it by CNS vital signs. You can do it even by the people are now looking at keystrokes and things like this. So there are other ways to go. So you’ll look to see where people say now what’ll happen is most of these will not go on to starting to have problems, a small subset will. Those people now you have to take the next step. 

So they’ll have a little more evaluation. They’ll have a little more, there’ll be a more extensive program. The majority of those will turn around and do very well. A small number of those will go on. So we have, as you now have a graduate hierarchical approach where smaller and smaller numbers of people. So you’ll only ultimately have a very few people that will actually break through these different layers and actually have cognitive decline despite an evaluation. And those people, ultimately, they will have some time in the hospital and you have to look very deeply at all the different parameters. Why did they break through these relatively straightforward programs? I think you’ve done an absolutely fantastic job by setting up Marrama where you’re taking. Now that the course, the disadvantage is you’re seeing people relatively later in the process. Ultimately, what we like to see is that the vast majority of people would never get that far along, but for those who do you have a fantastic program. 

And that really the first of its kind, I think is a real role model for so many other places around the world that we’ll be looking, instead of simply watching people decline, we’ll be actively involved in improving them and sustaining some level of cognition so that they now aren’t lost to the family. So I really congratulate you for such an outstanding job for setting up Marrama.

Heather Sandison, N.D.

Thank you. One of my big goals is to, I would feel successful if we could shift that entire senior living industry a little bit in our direction. Kind of like what you’re saying. Like if we just got the food, right. What would be the change? Even just if we looked at the numbers, right? The healthcare dollars that are spent in the people living in kind of a conventional setting where there’s, cake cookies, ice cream, pasta, cereal, versus what we know is a very brain-healthy diet. So what would all of, what would the financial impact just be at the healthcare level? Right not to mention all of the other pieces.

I feel, I mean, I think you, and I we can predict what that would look like, but just showing people how those relatively simple interventions with using information that we already have, can really shift the trajectory of someone’s health and the quality of life is another thing, I’m sure you guys measured that we’re measuring quality of life scores in our study and, you expect improvement because people feel generally healthier. Yeah. It’s such an exciting time.

Dale Bredesen, M.D.

Absolutely. So as you, yeah, absolutely. And I would just add, in addition to all the things that we’ve been talking about, there was a nice paper recently, as you know, by Dr. Kara Fitzgerald, who was looking at aging parameters, looking at essentially methylated regions of the DNA that are shown to be associated very closely with biological aging and showing that doing some of these same sorts of things, not only is it making your cognition better, but it’s actually giving you a reversal of your biological agent so that she saw about 3.26 younger years on people who were on a protocol. 

That again, some of the same sorts of things compared to the ones who weren’t on that. So as we’re going to be doing, looking at biological aging with her on this next study. So it’ll be very interesting to see, can we see cognitive improvement, but can we also see improvement in biological aging?

Heather Sandison, N.D.

So Ryan Bradley, I mentioned to you earlier, he’s my co PI. And he, my co-primary investigator on our trial and he reported her as her co PI on her trial. So I’m very familiar because I know that they’re my naturopathic colleagues, very familiar, and I know the metric they used the gentlemen at UCLA, the professor there who–

Dale Bredesen, M.D.

Professor Horvath.

Heather Sandison, N.D.

Yeah Horvath has created that kind of in that way to test it. So for people interested, you can actually get a test. Is it true diagnostics? I think is the name of their company.

Dale Bredesen, M.D.

I think it is yeah.

Heather Sandison, N.D.

Yeah. And so we–

Dale Bredesen, M.D.

The company was published so you can take a look at what they use.

Heather Sandison, N.D.

And they have a lifestyle intervention. There was another one, I think that used DHEA and something else. They didn’t get quite as good data as Dr. Fitzgerald did, but there’s a few people looking at this at how do we reverse the aging clock? So not just neurodegenerative things, but even taking that a step further and say, how can everybody get benefit? We don’t just have to focus on the brain, but how do we get, yeah. How can we live better? Not just longer lives, but better lives. 

One of the fun conversations I had recently was with the another woman who is imagining kind of place a place like Marramma on the east coast. And we were talking about how fun it would be if by the time we retire, there’s sort of this expectation that maybe you, you and your spouse, or you and a friend go to sort of a retreat center for six to 12 months and you basically learn, okay, it’s that shift in your life, right? Where you kind of graduate into retirement and how you want to live it. Maybe you could go somewhere in the mountains or at the beach, whatever sounds nice and learn to live the healthiest lifestyle for aging, and then take those patterns back to, your home and your family, and start to incorporate that. So like a Marrama but earlier on so that we can do that prevention and how fun I would sign up for that.

Dale Bredesen, M.D.

Yeah. No, and I think you’re right. I mean, taking this to more like, well, what would people would think of as a senior center where you don’t wait for it for cognitive changes or other changes. And yeah, I think we’ve all been taught that it’s all about a drug, just get a drug for each problem. And instead of the fact that in fact, as we understand more and more getting a healthy set up and understanding what’s driving a lack of health is so much more powerful than we were taught in medical school. And so you’re right. Going to a place where you’d actually learn essentially learning to live healthily, which we kind of take for granted. Oh yeah. I’m just going to eat, change this or that. No, there are a lot of things, again, there’s so much more biochemical manipulation that can be done in a very healthy way. Than we were taught. And so the fundamental way we think about retirement and we think about medicine really needs to change.

Heather Sandison, N.D.

Amazing. Dr. Bredesen, thank you so much for taking the time. I know you and I both are in hotel rooms at conferences, meeting with other people, rarely doing the work of changing this narrative. And I couldn’t be more grateful to you for your support of Marrama. And you giving me the tools so that we could have this impact, on the lives of those who are suffering essentially unnecessarily at this point?

Dale Bredesen, M.D.

Yeah. Yeah, you’re absolutely right. And I think many places are, ignoring the wonderful data that are coming out from numerous places like yours. And therefore they’re putting people unfortunately at risk. And so I look forward to a day when we really make these problems rare and congratulations, once again, on all the great work, I really look forward to reading about your exciting results in your trial.

Heather Sandison, N.D. 

Thank you again.