Webinar: New Clinical Trial Achieves Reversal of Cognitive Decline

On Friday, July 14th, Dr. Bredesen and Dr. Rao joined Dr. Heather Sandison on a webinar to discuss her recently published peer-reviewed paper that demonstrated cognitive improvement through the clinical application of the Bredesen Protocol®.

The study was designed to determine if cognitive function would change in response to a multimodal, individualized care plan that addressed personalized contributors to cognitive decline (e.g., nutritional status, infection, etc.). You can review the study co-authored by Dr. Rao here. For your convenience, we have included the full transcript and recording below.

Transcript:

Dr. Dale Bredesen: And I see we’re live now. I just want to kick off and say welcome, Heather. Always great to talk with you. Always great to see you. Welcome, Ram. Always great to talk with you. Such exciting times here. As a neurologist who spent decades being told that there’s absolutely nothing that can be done for neurodegenerative disease, whether you’re talking about ALS, whether you’re talking about Alzheimer’s, whether you’re talking about frontotemporal dementia, what have you, there just wasn’t anything.

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Dr. Dale Bredesen: So, of course, our long-term lab goal, as Ram well knows because we worked together in the lab for many years, was to see if we could understand the fundamental nature of the neurodegenerative process. Why do the cells die? What are the signals? And that sort of thing. So, of course, every time I hear about people getting better, I’m very, very excited about that. So, Heather, you’ve just published this fantastic paper. Ram, you’re a coauthor on this paper. This is fantastic. Heather, can you go back? Let’s go back to the beginning. What prompted you to do this study that you’ve now published, this clinical trial?

Dr. Heather Sandison: Well, Dr. Bredesen, I owe it all to you, really, because I had the privilege of studying under you in 2017. And very quickly after that, I was on your list of trained providers, and I had people coming to my office asking me to help them implement this, implement the Bredesen Protocol, implement what you described in your book, The End of Alzheimer’s.

And I was a little skeptical, I’ll be honest. It was complex. People had cognitive decline, it took extra effort, and there was a lot to do. We were essentially giving them access to all of functional medicine all at once, and I saw it work. And I didn’t just see it work once, and I didn’t just see it work a little bit. I saw it work dramatically. And so then, I ran into the questions that a lot of providers, I think, in my position run into, which is, “Well if I spend the time and money, how likely is it that this is going to work? How do I know that this is going to work? And what exactly do I do? And can I do part of it? How fully do I jump in?”

And those questions led me to basically say, “How do we get more research?” There’s a lack of research, and I heard that from other people as well. My brother-in-law doesn’t believe this will work, or my dad. I want to support my mom, who has dementia, but my dad doesn’t believe it, and so he’s not willing to do it. And I realized really quickly that we needed more research. So, I was in a very fortunate position of having a philanthropist visit me as a patient and have a good experience, and he offered to help by funding a trial. And this was back in 2018, and this takes a village to conduct a trial, as you well know.

It is a huge team effort. So, it needed funding. It needed research, and I felt really fortunate. My friend, Ryan Bradley, who is a fellow naturopathic colleague, he’s up at what was NUNM and at the Helfgott Research Center in Oregon, he and another colleague, Nini Callan, helped me put together the research, the IRB proposal. They helped with everything from start to finish.
And then I was super fortunate to be introduced to Ram, just one of my favorite people who’s joining us here, who helped us push it across the finish line to get the publishing finally done. And we ran into COVID. There were all kinds of things that came up along the way. But in the end, what we saw was what I was seeing clinically. It’s that the people who are able to get access to this medicine, able to put the protocol into place, by and large, get to benefit from it, and everyone should have access to that.

Dr. Dale Bredesen: Yeah, that’s a great point. And so, tell us a little bit, a few of the details here. So how many patients in your study? And how many of them actually showed improvement?

Dr. Heather Sandison: So, we had 23 participants in the trial who made it through the six months of intervention.

Dr. Dale Bredesen: Okay.

Dr. Heather Sandison: So, we recruited, I think there were 34 who enrolled, and people dropped out for COVID and other reasons, an inability to do the protocol at home. It does take effort. And so, there has to be a willingness and an engagement in that process. And so, some people just weren’t up for it.

We had about the same amount of withdrawal as a typical Alzheimer’s study, about 30%, a little bit more, and 23 participants stuck with it for six months. And 17 of those 23 had improvements in their MoCA scores as well as their Cambridge Brain Sciences scores, which is another way that we were measuring, with a little bit more nuance, their cognitive ability.

Dr. Dale Bredesen: Absolutely. Very, very interesting. And did they notice improvements subjectively? And did their partners notice improvements objectively?

Dr. Heather Sandison: Yeah. You guys did a great job in your trial that Dr. Kat Toups published in July of 2022 in the Journal of Alzheimer’s Disease. You guys asked the significant others, and I think that that’s something we’ll want to add in the future. We did do quality of life scores; we did sleep scores, and, of course, we have lots of biometric data. So, the results so far that we see there are encouraging, and Dr. Rao is also going to help us get those published as well. We’ll be able to elucidate a little bit more of that. But certainly, the experience of our participants was gratitude from everyone. Yeah. Really profound changes.

Dr. Dale Bredesen: Fantastic. One of the things that I was struck by is how similar your results were to what we saw as well. It’s just validating because I think, as we all are aware, if you’re going to do something that’s quite different from the standard of care, then it’s great to see it once. It’s great to then start seeing it case after case after case. And, of course, we published cases over the years, but people always want to do a clinical trial, so you get a denominator. What percentage actually improved? So, you can actually now see that which is really important.

And I think it’s really critical to put this in perspective. We’ve just heard about a drug, Leqembi, that has just been approved by the FDA. Billions are going to be paid by all of us through Medicare to the drug companies to use this. Now, this does not make people better. This does not keep people the same. What it does is, instead of going downhill as usual, you go downhill 27% slower. So, this is a minimal, minimal effect.

In your study, you actually saw people improve. And I know we’ve had people now, over a decade on this approach, who have sustained their improvement. So, my question for you is, do you have any follow-up? Have you heard from these people? Have you continued to see… Where do they stand? And have they continued on the protocol, or have they gone back to doing other things?

Dr. Heather Sandison: Yeah. Many of them still are my patients. I was the very lucky clinician. I got to see all of these patients throughout this trial, and many have continued to see me. And so, I came to you with exactly that question. I was surprised because at Marama, the residential care facility where we offered an immersive experience and your protocol, we have had people there now for three years.

And so, I remember coming to you and saying, “I was expecting they would plateau after a year, maybe 18 months.” And what we see is that three years later, people are still getting better. They’re still getting improvement. And, I mean, it was just great how you said it, like, “Of course they are. Of course, they’re getting better,” because there’s this ability for the brain. Once it’s healed, there’s this neuroplastic effect. There’s this ability to build new neurons and new connections, and that doesn’t go away.

Yes. To answer your question, there are some study participants. The ones who have stuck with it have done really well. What we see is that those who get off of it, they tend to go downhill, and that’s challenging to watch.

Dr. Dale Bredesen: It’s such a good point. Patient zero, back from 2012, was the first one who called me up and said she’d gone off. And within ten days, she was already noticing that things were not so good. So, I think it’s not magic. You see, it’s just biochemistry, and you see it again and again and again. I think this is very exciting. Let’s talk a little bit about something that I think is left out of so many of these conversations.

When you hear about Leqembi, you hear about these drugs, what you hear about is, “Okay. These people had Alzheimer’s disease, or they had mild cognitive impairment due to Alzheimer’s disease pathophysiology.” But our argument has been you don’t want to have a period after the term Alzheimer’s. It’s Alzheimer’s due to what?

In this approach, in functional medicine or a precision medicine sort of approach, you want to know what drove the problem, not just say, “It came from outer space. It’s magic. You just got this problem. One of your proteins misfolded,” something silly like that. You want to be able to understand what drove this. So, let’s talk a little bit about the patients that came to you. How many of these people, for example … And Dwayne here is asking an important question, “Did any of the patients have a tick-borne infection at baseline?”

Dr. Heather Sandison: Yeah. So, I believe three. I’m going to pull it up real quick right now because, in the paper, we published a table of all of the types of Alzheimer’s that someone might have and what might be contributing to it, and I essentially just put a number out of 23 of how many of our participants had that when we tested, so things like glycotoxicity. Did they have diabetes? Five of our participants had diabetes, and one of them was a type 2 diabetes. And then many of them have blood pressure issues.

So that’s in a table that explains exactly what everyone had, and they’re not mutually exclusive. What you’ll see is that I think 22 of our 23 participants had gut issues. They had some sort of gut complaint. This is very, very common. The vast majority of our patients … And, of course, they’re older. Right? We’re asking them about cognitive decline, and this is much more prevalent in an older population. We only recruited patients over 45, and they’ve had a lifetime to collect toxins to be exposed to toxins.

And so, you’ll see in that table many of them were also exposed to toxins. And so, you can see that just as … What we want to get is a synergistic stacking effect in a positive direction. Many people, when they arrive in a clinic that uses your protocol, we’ve seen a synergistic stacking effect of the negative things, toxins plus infections, plus stressors, plus traumatic brain injuries, plus nutrient deficiencies, plus gut issues, and these things work together. Basically, it synergizes in a negative way, this downward spiral of cognitive function.

Dr. Dale Bredesen: Absolutely. And I think that whole point of negative synergy is such an important one because, as you indicated, these people have all these things that are colluding to give them this cognitive decline. And our research showed that, basically, this is a mismatch. You have certain signals coming in, and we did a lot of work in the lab, Ram and I, and others in the lab, on APP signaling, and it interacts with a molecule called Netrin-1, but it also interacts with other molecules as well.

And ultimately, it can either be cleaved in one fashion to say, “Okay. Things are good. We’re going to grow. You have sAPP-α (alpha) and alpha-CTF,” or it can be cleaved in an alternative way to say, “Things are not good. We’re going to have to be downsizing and protective.” And so, then you’re getting sAPP-β (beta), A-beta, that’s what gives you the A-beta, C31, and Jcasp. So, there is this difference, and unfortunately, adding all these things can be a real problem.

And so, now, when you did this, the approach you’ve got then is really a personalized approach. You’re not going to treat a tick-borne illness in one person who doesn’t have it the way you’re going to treat it in a person who does have it. So, with your different people, how many different protocols are you actually using for these people?

Dr. Heather Sandison: Right. And you described these differences in the pathophysiology. Right? I think of it as the pathway we took to get to Alzheimer’s. We can all arrive at a similar destination, but we’ve taken different pathways there. Well, absolutely. Right? I wouldn’t treat everyone for a tick-borne illness if they don’t have it. That doesn’t make any sense. But also, one of the other individualizing characteristics I’m looking for is bandwidth. What is somebody able to do? Some people can’t swallow a bunch of pills. Some people haven’t even been walking to the mailbox, let alone getting regular, vigorous exercise. Some people struggle with insomnia.

And these really basic foundational pieces are so critical to success in the program. So individualizing it, really, going back to that doctor we thought of maybe in the movies from the ’50s, this kind of idealized person who really gets to know you, who really has a quality conversation about what your life looks like and what’s going to be feasible, what kind of support you have from a caregiver or other providers, and how to put a protocol and a plan together that’s going to really serve you.

Dr. Dale Bredesen: Yeah. Great point. Let me bring in a question here from Mustafa. Mustafa is saying, “Thoughts on having saturated fat mainly from coconut oil and butter on the protocol. Is it really bad for you?” This is a great question because there are pros and cons, so you really have to weigh these. So, number one, saturated fat has an interesting phenomenon that if you look at your innate immune system memory, and the memory of the innate immune system lives in three places, and this was actually pointed out by Dr. Alexei Kurakin, who is an interactomics expert.

So, it lives in your endothelial cells, so unfortunately, increased risk for thrombotic events, just as we saw with COVID-19. It lives in your bone marrow, and it lives in your microglia or your tissue macrophages. So, unfortunately, it sets you high so that any sort of insult you have, boom, you’re already on that. And in fact, it was Ram’s work that showed that APOE4 does the same sort of thing. It gives you a pro-inflammatory, rapid response to inflammation, which is great if you live in a Third World (Country), but unfortunately, can increase your risk for Alzheimer’s in the First World.

The issue here is saturated fat, and by the way, also mental trauma. Both of those things set this level high. So now, unfortunately, you’re going to respond at a moment’s notice. Now, the other thing you should look at is your LDL particle number or your sdLDL, whatever you like to look at.

As long as your lipids are great and as long as you are not pro-inflammatory, then with those caveats, it’s fine to have some of this. But in general, we like to go more toward the monounsaturates and polyunsaturates. So let me ask you then. Heather, in your study, did you have people taking coconut oil? Or what sorts of things did you do for ketosis in your study?

Dr. Heather Sandison: Yeah. So, we weren’t shy about animal protein, including cheeses and butter, and also MCT and coconut oil. And we certainly had a representation of people with APOE3/4 and 4/4, and we watched closely what their lipids did. And we saw that, by and large, their lipids improved. So even with the addition or the increase of saturated fats, now, it was really important that we also limited those carbohydrates. They needed to actually get into ketosis.

And I think one of the struggles that people face is that when they’re trying to get into ketosis, they increase their fats, but they don’t reduce or limit their carbs enough. And the magic really happens when you flip that metabolic switch, and you start burning the fat for fuel. If you still have those carbohydrates present, then you’re doing damage, generally in terms of inflammation, the cardiovascular risk goes up, and we’re not getting any benefit for the brain.

What I’ve started, basically, what I recommend to my patients and people in my community, is to go into ketosis but don’t expect to be there forever. Get solidly into ketosis, do it for three or six months, get the brain-healing benefits, and then maybe switch to more of a vegan diet or a plant-based diet, or a Whole30-type diet, and keep an eye on your lipids. Everybody’s metabolism is a little bit different.

And so, if we have that data to come back to … Or a CGM. The continuous glucose monitors are just magic for getting that information about how you’re metabolizing things in real-time. So if we have the data and we have some flexibility, and we’re changing our metabolism, getting that metabolic flexibility, I think we win, and we don’t have to be dogmatic about what we cut out all the time.

Dr. Dale Bredesen: It’s a good point because when you look at the energy, the brain has to have either ketones or glucose. And so, most people that we’re seeing, they’ve lost both. I mean, the signature of Alzheimer’s on a PET scan is reduced glucose utilization in the temporal and parietal lobes. So, there it is right in front of you that you’re not handling the glucose appropriately, but also, because you have these high insulins as you are becoming insulin-resistant, that prevents you from making ketones. Your brain is literally sputtering, hitting on just a cylinder or two.

And so, it’s interesting. You’ve got to restore the insulin sensitivity. You’ve got to restore the ability to make and burn ketones. But you’ve got to be careful because people can be frail, so you can’t fast them for too long because then they’re now, unfortunately, losing it. You’ve really got to make sure that they can get both of those substrates. And, of course, the energetics are huge. Now, coming back to what it takes for energetics, did you look at your people, for example, with their SpO2, their nocturnal oxygen saturation? And how were they there? Because, again, an important way to drop your energetics.

Dr. Heather Sandison: Well, so now, in retrospect, we started this whole process five years ago, and WatchPAT didn’t exist. But now, really great, easy logistically is something called WatchPAT, which is a bracelet you wear overnight with a ring, and it somehow magically beams the information up to a sleep doctor somewhere in the world, and they can use that data to at least rule in sleep apnea. And just for feasibility’s sake, we did the Garmin watches during the trial.

And then we had a threshold where if somebody came back with a low pulse ox at night, then we sent them for a sleep study. And usually, for an overnight sleep study very rigorous in a clinical setting, not from home. And so, we certainly were looking at that, and I asked every single patient, “Do you wake up feeling rested? Do you snore?”

And anyone at this stage with cognitive decline, because that WatchPAT is so easy these days and it’s covered by Medicare, I just refer them directly to that because I’ve just seen it too many times where someone is adamant, “I don’t snore. I’m thin. I’ve never had an issue with sleep.” And lo and behold, they actually have sleep apnea. And getting a CPAP or an oral device, that makes a big difference. And we see the MoCA score come up. We hear it from their families. We see in them that there’s an improvement. So, it’s too big of a thing to leave on the table and not assess.

Dr. Dale Bredesen: Absolutely. And again, a critical part of your energetics, and this ultimately boils down to energetics and inflammation. And so, you’ve got to increase the energetics and reduce the inflammation. All right. This is really, really interesting. Let me go to the next question here. There’s a question here. “Did any of the participants have a neuropathy, peripheral neuropathy, feet or hands affected?” Sometimes patients do, and they can be from toxins. It can be from nutritional deficiencies. Did any of your patients have peripheral neuropathies?

Dr. Heather Sandison: That’s a great question. It doesn’t stand out to me. It’s a relatively common symptom, but I don’t recall that that was something that was consistent amongst them or a big consideration as we went through it. We certainly would’ve asked and attempted to treat it with either B vitamins or lowering the glucose levels, whatever might have been causing it. But I don’t remember that standing out.

Dr. Dale Bredesen: Yeah. I have to say it’s not common in Alzheimer’s patients. Even though there are some things that would overlap, you don’t see it a lot. And then the next one here is from Mustafa again, who’s asking about benfotiamine, B1. And I assume that all your patients got B1, certainly thiamine, with respect to history. That is the classic for Wernicke-Korsakoff syndrome and does, no question, having low B1 will impact memory dramatically. And in fact, you see people who have it so severely that no matter how much you give them, they’ll never recover their memory. They damage their neural subnetwork and especially the mammillary bodies of the brain. It’s a classic one. And so, do you include B1 with your patients on the protocol?

Dr. Heather Sandison: Yeah. So, what we do with nutrients, and the vast majority of them that you can test, we test, and we look to see if there are deficiencies in them. And then also, many of our supplements that are our go-to are either B complexes or nootropic compounds or combinations that include that, as well as detox supplements that often include B vitamins.

We want to make sure people aren’t getting too much but also catch any deficiency, whether it’s B1 or any of the other B vitamins that can be so essential. I think of them as playing well together. I don’t usually use one B vitamin in isolation. I tend to want to make sure that they’re all there because so many biochemical… That cascade of biochemical events in our system really requires multiple steps and cofactors and B vitamins. It’s so many steps along the way, not typically one in isolation.

Dr. Dale Bredesen: Yeah. And there’s a question here from Robin and a shout-out to Robin, who’s out in North Carolina. Thanks for the question, and thanks for all the great work you’re doing. She says here, “Were any of your participants taking Aricept or Namenda?”

Dr. Heather Sandison: Yeah. We had two participants on Aricept and one on Namenda. And we asked them to hold that steady, basically to not make any changes while they were in the trial to increase the dose or decrease the dose just to keep it very stable in the six months of the intensive intervention.

Dr. Dale Bredesen: Absolutely. Yeah, that’s a really good point. And, of course, the thing we always worry about is the sudden cessation of taking Aricept because it’s been well-documented. People can have a problem when they suddenly cease. The next one here. Let’s see. “From what you’ve gathered, in what ways is the hope similar or different between the many forms of dementia and cognitive decline? For example, what about observing more or less success with moderate-to-advanced Parkinson’s, moderate-to-advanced Alzheimer’s versus Lewy body?”

So, this is an excellent question. It’s really been the big issue. Can we now adapt this sort of approach to all of the neurodegenerative diseases? And I have to say; it’s not going to be exactly the same for each one, as we know. And so the theory is that each of these involves a neural subnetwork. So, of course, Alzheimer’s, as Heather said, it’s all about neuroplasticity. Parkinson’s is all about motor modulation. You’ve got this fine modulation. Different parts of the brain, different requirements, different signaling, different protocol.

Now, on the positive side, we have seen good results with Lewy body patients. We have seen good results with vascular dementia patients. And let me ask you, Heather, have you been treating patients with Lewy body and with vascular dementia, and have you seen good results?

Dr. Heather Sandison: Yeah. One of the participants in the trial, I believe, had Lewy body. He was experiencing hallucinations and pretty significant changes in his personality. And although he hadn’t been diagnosed with Lewy body by a neurologist at that point, he had been diagnosed with Alzheimer’s, and he stabilized. He didn’t even get into ketosis, but he stabilized and had no decline through the process and a slight improvement. He had no decline in his MoCA. It was the same at the beginning and the end, and then he had a slight improvement in his Cambridge Brain Sciences.

So that feels like a win. I have to say, what we’re asking for here is a miracle. Right? We are asking for the reversal of Alzheimer’s. And when we get a stabilization in six months, we celebrate that all day long, whether it’s with Lewy body or Parkinson’s or even MS or frontotemporal. And we see these, they’re much less common than Alzheimer’s and dementia, kind of general dementia that I feel like I see a lot of. However, I serve patients that have those diagnoses pretty regularly.

Dr. Dale Bredesen: Yeah. And let me come to Ram for a minute. So, Ram, could you talk a little as a … And for people who don’t know Ram, he is not only an outstanding scientist, and he’s actually the one who discovered, which I think is a critical discovery, that APOE4 has this phenomenal effect of entering the nucleus, interacting with DNA, and actually reducing the production of about 1,700 different proteins. And the critical ones, such as SIRT1, which he showed in Alzheimer’s brains, is actually dramatically reduced, and this has been published in multiple different publications.

But he’s also an Ayurvedic physician, so he really has very complementary views of this. So, Ram, for this sort of approach, could you maybe talk a little bit? You’ve published all about critical herbs and critical Ayurvedic approaches. Are there favorite ones that you have for optimizing things for trials going forward?

Dr. Ram Rao: You know what, Dale? If you talk in terms of Ayurveda and what we are doing in terms of the program and what Heather has done with her clinical trials, it goes very well with the Ayurvedic concept, wherein in the Ayurvedic concept also, they talk about not using … I mean, there’s nothing like a pill. There’s nothing like a single herb, especially for neurodegenerative conditions like Alzheimer’s or Parkinson’s or Lewy body and all that. Even though there are known herbs, they never tell you to take those herbs in isolation.

Dr. Dale Bredesen: Yeah.

Dr. Ram Rao: First of all, they always talk about nutrition and diet as being the most important and the most basic necessity in order for the gut to become optimal enough because the main theory is that herbs will not help if your digestion is not proper, if your digestion is not optimal, because the herbs will not get digested and it won’t give you those benefits.

So that’s the reason why any Ayurvedic practitioner, typical, classical Ayurvedic practitioner, will always make sure that your digestion is optimal. And once the digestion is optimal … And when you talk about nutrition and diet for optimizing digestion, it’s very similar to our ketosis or KetoFLEX containing diet, similar to those approaches, timely meals, making sure that you’re eating at the right time, making sure that you’re not snacking all the time, making sure that you’re leaving enough gap between your last supper or meal and your sleep. So that three to four hours of gap is extremely important.

Ayurveda also recommends that you have a 12-hour fast between your last meal of the day and the next day’s morning. And so, all those classical things that we follow in our approaches here at Apollo Health and what Dr. Heather Sandison does with her clinic, same principles in Ayurveda too. And then they say, once you have all those optimized, then you can start adding on herbs, adding onto yoga, adding onto meditations, and all that.

And some of the herbs that are classically used for such conditions are things like ashwagandha, shankapushpi, Triphala, and Brahmi or Bacopa, gotu kola, and then turmeric to bring down inflammation. And the idea behind all these herbs was the same thing. How can you address the numerous factors at play so that they all work in tandem?

And so, your point, Dale, about Alzheimer’s disease due to what is extremely important because this is what Ayurveda also says. Alzheimer’s disease, but where does that come from? What have you been doing? Is your liver not proper? Is your detoxification to be controlled? And so, when you add all these herbs, it’s like taking into account each of these factors and then giving it.

Dr. Dale Bredesen: Yeah. And it’s interesting to me. We live in a world where data collection … It’s Silicon Valley. This is a huge, huge issue. And Google knows where we all shop, what we all do, these sorts of things. And yet, this hasn’t really worked its way into the medical practice enough. We need to be more aware of physiology, of human physiology, and all of its complexities. And the idea that you’re going to just write a prescription for one thing and it’s going to magically reverse Alzheimer’s really doesn’t fit with human physiology, unfortunately.

I do think that the drugs are going to be very helpful when used as part of an overall protocol where you know why you’re targeting what you’re targeting. So, let’s come to another question here. This is, “As a previous college football player, I’m concerned with the possibility of CTE. Would your protocols help with CTE?” So, great point. I’m glad you raised that. Absolutely. We recommend that anyone who has played football, anyone who has had a history of head trauma, who’s had an automobile accident, who’s done a lot of heading of soccer balls, who’s played volleyball and got hit in the head, who’s played baseball, and any of these sorts of things, please get on active prevention.

And, of course, beyond that, we’d recommend that anyone, no matter what your history, who’s 40 years of age or older, please get a cognoscopy. Just as we all know, when you turn 50, you get a colonoscopy. So, if you’re 40 or over, please get a cognoscopy, and get on active prevention so that we can really make this a rare problem, as it should be. Very few people should be getting all the way to dementia. We should be getting people in the early SCI stages where they’re easily reversible.

Yes. College football is fantastic. We all love it, but please get on some active prevention as soon as your college football career has ended. Next one here, “Is a vegan diet compatible with the program?” And Heather, you’re an expert in this area. Maybe you could talk a little bit about vegan diets versus the KetoFLEX 12/3 sort of diet.

Dr. Heather Sandison: Yeah. So, what I’ve seen, what I care about most is “practicalities.” We need to flip that metabolic switch. We need to burn fat for fuel, not sugar.

Dr. Dale Bredesen: Yup.

Dr. Heather Sandison: And when we are restricting carbohydrates, and we’re restricting animal protein or animal sources of food, we end up with very, very few things that we can eat. And for the vast majority of people, that’s just not practical. I have met vegans who are able to get into ketosis. Now, they’re going to be having a lot of coconuts. They’re going to have a lot of avocados, a lot of hemp hearts, and a lot of chia seeds. And there are certainly sources where you can get that from. But things like rice and beans, where a lot of people think about getting their protein, that’s going to kick you out of ketosis. And so, for anyone who is committed to a vegan diet who wants to get into ketosis, I say no more than two or three weeks because it just is too restrictive of a diet, and I start to worry that there’s going to be deficiencies in certain nutrients when we have so little variety.

And so, most of the time, I am trying to ask vegans, “Are you willing to maybe temporarily get into ketosis and add some animal protein? Maybe some eggs. Maybe still stay vegetarian but get into ketosis with some animal-based protein and fat. It just makes it so much easier. And then, as soon as you have gotten the benefit of ketosis for maybe four, five, six weeks, let’s switch you back into a plant-based vegan diet.” It doesn’t have to be forever, but I don’t want vegans to never get the benefit of ketosis, and I worry that there are health risks of being vegan and keto at the same time for too long.

Dr. Dale Bredesen: Yes. A very good point. And Julie G has written a lot about this in the past as well, that, “Okay. If you’re going to be vegan, it’s fine.” And in fact, it can be very good for people who have a vascular component especially. But then please make sure that you’re getting adequate vitamin B12, vitamin D, things that we … And as you mentioned, getting into ketosis, all these things.

So, again, it’s not that you have to do one specific diet; it’s the goal of getting the energetics and getting the inflammation down, the energetics up; however, you’re going to do that. So absolutely, certainly fine to be vegan. All right. And then, Heather, maybe you could tell us about one of your patients. I think it’s always so helpful to hear, “Here’s one person. Here’s their story,” because it’s hard to believe it when you’re just looking at numbers. But when you actually hear people come in and say, “Oh my gosh, I can do this, that, or the other,” it is such a striking lesson.

Dr. Heather Sandison: Yeah. One of our patients, I’ll call her Mary, she came in. And if you had asked the health coaches, if you had asked anyone in my clinic if she was ready to take on this protocol, they would’ve said there’s no way. She was living alone. She was highly anxious. The reason she joined the clinical trial was because she wanted to move into the assisted living facility in L.A. where her cousins were living. She had no other living relatives. Her older siblings had passed away. She had no kids, and she was unpartnered.

And so, she was terrified, absolutely terrified of growing old and having dementia and living alone. And she was overwhelmed. She hadn’t paid her taxes. She had clutter piling up all over the place, mail unopened. Her yard was out of control, and she just looked like a deer in headlights, just terrified and worried, anxious. And we just thought, “We don’t know if she’s going to be one of the people that’s going to be able to implement this protocol.”

She blew us away. By the end of six months, she was like, “I’m not going to assisted living. I’m out on the dating apps. I’m going thrifting with my friends.” She had gotten her taxes paid. Her house was uncluttered. And you know what she did that I thought was so … I have chills right now just telling that story. What she did was she made it about other people. She had a neighbor who had cancer, and she said, “I’m going to get on this organic ketogenic diet. I’m going to make it super plant-forward, and I’m going to make the same food for me and make double so I can deliver it to my neighbor who needs it too.” And that really gave her a lot of meaning and purpose. And her labs shifted. Her life shifted. She lost weight. She looked healthier. Somebody asked about parasites, and sure enough, lo and behold, she had some parasites in her stool tests. She also had a lot of issues with yeast. And because she was so anxious and depressed, she would binge on ice cream. And we got her off of that. The yeast issues went away. A lot of her mental health issues were resolved. And, I mean, her entire life transformed.

Dr. Dale Bredesen: Very, very exciting. Very interesting. Well, congratulations. It’s a great story.

Dr. Heather Sandison: There are so many fun ones.

Dr. Dale Bredesen: Yeah. So maybe it would be important to take a minute because, as you pointed out, the gut is so important. And also, as Ram pointed out, in Ayurveda, it was clear that the gut, even thousands and thousands of years ago, it was clear that the gut was critical for health. So, what sorts of parameters? Presumably, you were looking at dysbiosis and leaky gut and things like that, but maybe you could spend a minute talking about what sorts of key parameters were you looking for and what did you find in these patients? Were many of them abnormal? Were most of them normal, and that wasn’t an issue here? Maybe you could talk a little bit about the gut status and how you evaluated it in these patients in your trial.

Dr. Heather Sandison: Yeah. My evaluation first starts with these questions, “Are you having a daily bowel movement? Is it well-formed, easy to pass, and complete? Are you seeing undigested food in your stool? Do you experience indigestion, heartburn, gas, bloating? What is your experience of eating, and what is your experience of digestion?” That is crucial to me, and kind of like sleep. The most important question around digestion is, “What does it feel like?” The most important question around sleep is, “Are you waking up feeling rested? Is that organ doing the job that it needs to do?”

And then we used a comprehensive stool analysis that looked at all of the bugs that might live, all the microorganisms that might live in the gut, the good ones and the bad ones, and were there too many bad ones and not enough good ones. We used probiotics in every single patient. We know that gut bugs have a lot to do with cognition, directly with inflammation, with, of course, neurotransmitter status, not only in the gut but also, you would think, in the central nervous system. And we also looked for inflammation in the gut, leaky gut via zonulin, calprotectin, beta-glucuronidase, and lots of things that we tested in the … Is it okay if I share the name of the test? Dr. Dale Bredesen: Sure.

Dr. Heather Sandison: The GI-MAP test is the one that I use. I like it because it’s just a single collection of the … It’s not very glamorous to be testing your stool, to be collecting that. And so, nobody likes to do it, but we get so much information from it that we can use to look at … Secretory IgA, for example, is a measure of gut immune function. Are you able to mount an immune response should you be exposed to a pathogen via food? And we look at elastase levels. Are you able to digest so that you can then absorb those nutrients? And these things can give us a really clear picture of how to best support you. Do you need digestive enzymes, or do you need immune support? Do we need to eradicate some of the bad bugs, including parasites? Do we need to give you more probiotics? That kind of thing.

Dr. Dale Bredesen: Yeah. Such a good point. Okay. Next one here is “How to clear brain fog.” So, it’s interesting because brain fog … People have said for years everything has been backward in the Alzheimer’s field. They say, “Don’t get your APOE status checked because there’s nothing you can do about it.” Well, there’s actually a lot you can do about it. When you have brain problems, they say, “Oh, it’s probably not Alzheimer’s, so don’t think about it.”

And actually, we’re hearing now with these blood tests that have just come out, like pTau181, where people will find out, “Yeah, they’re already into SCI.” And they thought, “Oh my gosh, it was just minor, aging-related things.” So, we’re going to be seeing this more and more and more, where people have always said, “Oh, it’s brain fog. It’s not Alzheimer’s. Don’t worry.” I think that’s changing. It’s telling you these may be the earliest, earliest stages.
You don’t have any Alzheimer-related dementia today, but you may be, just as you would be with insulin resistance, heading to type 2 diabetes down the way. You’re in the earliest changes. Your energetics maybe aren’t perfect, and your inflammation is maybe also not perfect, and you’re headed down that pathway, even though it may take 20 years. And by the way, the studies show that you can find changes in the brain 20 years before a diagnosis of Alzheimer’s.

We know this is a long process. We’re hearing a lot about brain fog because of COVID-19, and it’s a very common symptom of long COVID. And so, there are lots of things to do. Again, the critical point here is not that there’s one simple protocol. If you have brain fog, please get a cognoscopy. Find out what is driving this problem. It may be leading to Alzheimer’s later, or it may not. But at this point, it doesn’t matter because anything that it’s doing, brain fog, is a relatively early phenomenon. So, you’ve got stuff you can attack.

It may be that you’ve got some long COVID. It may be that you need something like low-dose naltrexone to improve your immune status. It may be that you need to do some EWOT to get better blood flow and oxygenation. It may be that you got some sleep apnea that you’re not aware of or that you’ve got hypothyroidism. There are hundreds of things that can contribute. Please get it checked out. It’s absolutely something you can do something about. And Heather, I would ask you, in your practice, are you seeing a lot of people with brain fog?

Dr. Heather Sandison: Well, brain fog and fatigue are, by far and away, the most common complaints of people who show up in my office. I want to just add, Dr. Bredesen, that this work is so fulfilling, and so many patients are here, but I know a lot of practitioners are here as well, and I would just like to invite them into the community. We need more people who are doing this work, who are treating patients with brain fog and subjective cognitive impairment, and measurable cognitive impairment prevention because they have a family history, and there are so many people who are hungry for this.
We have over 500 people here on this Zoom webinar who are joining us to get answers about this. I owe my entire career to you that you have made it possible for other providers to offer this to people and get this really meaningful experience from their clinical practice. I have friends who are medical doctors, who never get that satisfaction that I have, the privilege of seeing people with an irreversible disease getting better, watching the dynamics and the relationships and their families change.

And it’s not impossible. It can feel a little bit intimidating at first, but there is so much support in the Apollo community and through the ReCODE training. And I just want everyone to know that this is an option for you. And if you’re thinking about this, whether you have a personal connection to this or a professional connection to it or an interest, please, please, please join us in this. We need you.

Dr. Dale Bredesen: Yeah. This is a really good point. And to put this into perspective again, over a million people have died now of COVID-19, but about 45 million of the currently living Americans will die of Alzheimer’s. It’s about 15% of the population will die of Alzheimer’s. It’s going to take an army out there for all of us to get these people to come in earlier. Don’t wait until late. Please come in. Get on active prevention or earliest reversals. And literally, we can dramatically, together, drop the global burden of dementia, and I think that’s the future.

I look back to times when there were global … Smallpox vaccine, polio vaccine. We need to do the same thing now. Of course, it’s not just a jab; it’s going to be a different approach. But the idea here is, let’s really work to reduce the global burden of dementia. And there are so many people in need out there. And unfortunately, they’re going in and being told the wrong thing. We had an example of a guy just the other day where he went in. This guy, unfortunately, was already into the dementia phase, and he saw a neurologist who told him, “This is just normal aging.”

And oh my gosh, I mean, nothing could be further from the truth, and this guy should have gotten evaluated previously and should have gotten on treatment. But that does bring up an interesting point. And Heather, you spoke to this in your trial. We generally think as you’re going later and later and later, it is tougher and tougher and tougher. Although we have seen people, even with MoCA scores of zero, improve, it’s not as common, whereas the ones who are in the MCI phase and the SCI phase do much better.

Now, in our trial, we took people only down to MoCA scores of 19, and we did see some people go from 19 to 30, which was exciting. In the new trial, we’re only taking it to 18. Now, I believe you came all the way down to 12. Wasn’t that what it was?

Dr. Heather Sandison: Mm-hmm. Yeah.

Dr. Dale Bredesen: That is courageous. But tell me what you saw. Was there a difference between the response in the 12, 13, 14 versus the, say, 23, 24?

Dr. Heather Sandison: Yeah. So, there is a difference. And I want to start, though, by saying I will never tell someone there isn’t hope again, ever, because I have watched the impossible happen too many times.

Dr. Dale Bredesen: Yeah.

Dr. Heather Sandison: Last week, I had a patient whose MoCA score went from 8 to 13. The neurologist at their office, they did both of those MoCAs. So, they didn’t believe it. They thought that they’d done something wrong and asked, “What are you doing?” And so, of course, they shared your book. But yes, get started early because my confidence goes down. It’s right around that 16 or 18 in the MoCA. And the reason I designed the trial to be this really measurable cognitive impairment. It’s real dementia. This is not, “My brain isn’t working as well as it used to. I’m losing my keys, and I can’t remember my distant neighbor’s name.” This is measurable. This is having an impact on their lives.

And I wanted to answer that question because those are the people who show up in my office looking for help. I wanted to know how likely it was that we could help them. And so, in the interquartile range, so 75% of the participants in our study had MoCA scores between 17 and 22. So they were a little bit higher, but we had people with lower scores. A couple of them did better. However, the majority of the people in that lower range did not. It is hard.
And one thing to ask is, does it maybe take longer than six months? Right? Again, we’re asking for a miracle. We were asking for significant change in just six months, and I wonder what would happen if we had done it for 12. And as we have mentioned previously, people tend to get better and better. And then also, there are just extenuating circumstances.

We had a participant who ended up being diagnosed with cancer right after the end of the trial. So, she had cancer while she was in the trial. We just didn’t know it yet. And then, another participant had prostate hypertrophy and horrible urinary symptoms that were interfering with his ability to fully engage with the protocol. So, life happens, especially with elderly folks. The earlier we can intervene, the earlier we can get on that positive, upward spiral of basically better longevity and health span, brain span, certainly the higher my confidence and the better the outcomes.

Dr. Dale Bredesen: Yeah. Yeah. And I think we have to remember that part of this is removing the causes and then resilience. But the other thing is, you have to remember you’re starting with a synaptic loss already. So, it’s actually a different strategy now to build back the synapsis that has been lost, and that may take other things, like intranasal trophic factors, peptides, stem cells, and other sorts of things that are quite different from what you can do.

So, when you’ve got someone who’s got a fairly good MoCA score but still has MCI, it’s easier, whereas the people who are down at 12, now they’ve lost a lot of synapses, and now you’ve got to have a second strategy to rebuild that. The brain, by itself, may not be able to do that. You can stop the process. That’s beautiful, but then you’ve got the problem that’s underlying.

The other thing you have to remember is, at some point, there is a threshold where this prionic effect, where you just get … It’s almost like going viral. This thing then continues. And so, you’ve got to fight that as well. Okay. Last quick question. I know we’re running out of time here. And so we’ll take the rest of these, but there’s a question about glucose monitors. And “Did you use a continuous glucose monitor in this trial?”

Dr. Heather Sandison: We did it in the trial, but I highly recommend them.

Dr. Dale Bredesen: Yeah. And we are using them in our current trial. And I should mention the Evanthea Trial just starting up. It’s at six sites, Hollywood, Florida; Nashville, Tennessee; Cleveland, Ohio; Sacramento, California; Oakland, California; or just right near Oakland, California; and then San Rafael here right near San Francisco in Marin County. So very, very enthusiastic to be working with six absolutely outstanding functional medicine physicians.

This is a new era. As someone who looked at neurodegenerative disease in the laboratory for years, I am just thrilled to have the younger generation, you, Dr. Sandison, and your colleagues, who are going to carry this forward and hopefully make it so that all of these neurodegenerative diseases are preventable and reversible and that we really don’t have this huge global burden of neurodegeneration. Congratulations, Heather. This is, again, taking the next step toward making this part of mainstream medicine and really to the next step toward making it so that millions of people will not have to go to a nursing home. We’re grateful for that. Ram, thank you for your many years of outstanding research for showing us all what APOE4 is actually all about and for bringing Ayurvedic medicine and all the herbal approaches to this field of neurodegeneration, which is so, so important. Thanks to both of you and we’ll take the rest of the questions online. And everyone else, have a great weekend.

Dr. Heather Sandison: Thank you so much you.

Dr. Ram Rao: Thank you. Thank you very much.

Dr. Dale Bredesen: Thank you, guys.

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