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Reversing Alzheimer’s: An Interview with Neuroscientist Dr. Dale Bredesen (part II)

If you haven’t read it yet, make sure to check out part I of this interview with Dr. Bredesen to learn about his newest book, the success his team has had with Alzheimer’s, and why the approach has succeeded where drug treatments have failed.

Dr. Dale Bredesen has been developing a protocol to help people with Alzheimer’s for 30 years. This protocol, adapted from his research, is being embraced by more practitioners in the medical community. Dr Bredesen has become a New York Times bestseller. His first two books were The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline and The End of Alzheimer’s Program.

In the second part of our interview with Dr. Bredesen about his third book, The First Survivors of Alzheimer’s, we take a closer look at why lifestyle changes are more effective than medication, what the early stages of Alzheimer’s look like, and why many ignore them.

Editor’s Note: This conversation with Dr. Bredesen promotes his newest book and his specialized approach to slowing and potentially even reversing cognitive decline. We at The Paleo Diet® support the main tenets of his approach – optimizing nutrition, getting quality exercise, minimizing stress, and prioritizing sleep – as the best ways to keep your brain healthy.

“Miracle” Drug Treatments vs. A Healthy Diet and Lifestyle

The Paleo Diet: To quickly recap, you just published another book and a clinical trial. Can you tell us a little more about them?

Dr. Bredesen: Of course! The new book came out in August. The other thing is we’ve finished a clinical trial and it’s now public. It’s on medRxiv, so people can read the results. You can compare them directly to Aducanumab, which was approved on June 7, and really doesn’t improve people. So, just strikingly different results.

The Paleo Diet: I wasn’t able to read the study before this interview. I’m looking forward to it.

Dr. Bredesen: I can send it to you. Basically, 84 percent of the people actually improve their scores.

The Paleo Diet: I have to point out, that wasn’t all over the news.

Dr. Bredesen: Yeah.

The Paleo Diet: But right now there’s a new drug – Aducanumab – that is all over the news. They’re calling it the first hope for patients with Alzheimer’s. Tell us your thoughts on that drug and the results it’s seen?

Dr. Bredesen: With the drug, nobody improved, nobody stabilized. In one trial at one dose, which was their best trial, people only slowed their decline by 22 percent. That’s it, that was the thing and it’s a $500 billion drug, $56,000 per year, per person for that.

In ways some people have said, it’s the gaff that keeps on giving. Unfortunately, what happened was the FDA convened its panel of experts – there are 11 of them – and they looked at neurological therapeutics, and they all said, “This should not be approved” or ten of them said, “Do not approve this,” one said, “I don’t know.” So, nobody, none of the experts said this drug should be approved.

That’s because one trial showed no effect at all, if anything, it was worse than the placebo. Another trial only at one dose showed a slight slowing of decline. So, the people didn’t get better, they didn’t stabilize, but they slowed their decline by 22 percent in one trial at one dose.

Now, I understand the FDA was saying, “Well, we have nothing.” Well, of course, they didn’t read the literature. We published in 2014, as I said earlier, 2016, 2018, but people are not willing yet to go there. They say they don’t want to believe that there’s something new that’s really getting much better results. So, interestingly, the drug company – and this is public information – the drug company Biogen that stands to gain hundreds of billions of dollars from the approval of this drug, paid $1.4 million to the Alzheimer’s Association, and the Alzheimer’s Association went on television, to say, “Oh, this is a good drug.” Well, yeah, they were paid by the company.

So, interestingly, the same day that the Alzheimer’s Association went on The Today Show to say this, I was supposed to go on as well to talk about our work, but I received a note saying I was uninvited because, quote, “People don’t believe it yet.” Well, I mean, was it a coincidence? Maybe, but it seems like less than coincidence.

I see diet and medicine in a similar light. Why not feed our bodies what they need, instead of looking for a “miracle drug” that addresses the illness from a poor diet?

It’s also public information that money went from Biogen. So, when you have these sorts of large sums of money involved, you don’t really have an unbiased approach. This is why the unbiased; the 11 people on the FDA panel; none of them suggested approval, but unfortunately, it was approved anyway.

Unfortunately, there are all sorts of side effects, as you know. [The drug] causes micro-hemorrhages in the brain. It causes swelling in the brain. It costs a tremendous amount, about $100,000 a year, the drug itself is $56,000 per year, but you’ve got to add MRIs and infusion costs before and after MRI. I mean, just on and on.

This is a huge expense for something that actually does not work. Unfortunately, in contrast, as I mentioned, we actually saw not just slowing but actual improvements in cognitive scores with our approach.

The Paleo Diet: I hate to say it, and again, I don’t want to give wrong impressions here, but we are a society that is very, very drug-centric right now. We think the solution to things is medication. The analogy I give people is a car. Imagine if instead of putting motor oil in it, you put olive oil in it. The car is probably going to work, but it’s not going to work well. The engine’s going to start breaking down pretty quickly, and you’re going to constantly go to the shop to get it fixed. Now imagine the mechanic says, “Add this ‘pill’ to your olive oil. It’s going to make it last much longer and you’re gonna have fewer issues.” You’d think, “Well, that’s miraculous. That’s great.” My response to that is why not just use motor oil in the first place?

I see diet and medicine in a similar light. Why not feed our bodies what they need, instead of looking for a “miracle drug” that addresses the illness from a poor diet?

Dr. Bredesen: Absolutely. We’re all interested in best outcomes for people with cognitive decline prevention and reversal. Ultimately, I think the best outcome is going to combine targeted drugs with specific protocols.

Again, going after what’s actually causing the problem should be a no brainer, but because there are literally hundreds of billions, hard to believe but literally hundreds of billions of dollars at stake, there are going to be biased approaches. And yes, we are by our history, a culture in which we’d like a drug. Even though this particular drug is hard, you got to go in for injections once a month, you got to have PET scans and MRIs and all these sorts of things.

So, I think that ultimately people are beginning to realize, hey, we can do much, much better by actually attacking the problem instead of trying to go after it with something that doesn’t target what’s actually causing the underlying decline.

What Do the Early Stages of Alzheimer’s Look Like?

The Paleo Diet: Let’s shift gears a little bit. For anybody who hasn’t seen the book, the first part of the book is seven chapters, and each chapter is a story written by somebody who has seen a lot of success on this protocol, describing their whole experience. To me, it was very fascinating reading these stories: what it was like for them; the emotions of the diagnosis; realizing at first that they were on this unavoidable path; and then what it was like for them when they actually started seeing some hope.

I wanted to start with asking you about those early stages. There seemed to be a lot of commonalities in the symptoms that they saw, but also in all of them saying, “Well, I was aware of it, but I just wrote it off as stress. I wrote it off as aging.” I wanted to ask you about that, and what are those common symptoms that you see very early on?

Dr. Bredesen: That’s such an important point because this is why people get late-stage Alzheimer’s. They wait, and wait, and wait, and wait, and they’re often told, as you said, by their doctors, “You’re aging, it’s not a big deal.”

No, if we just wake up and realize it’s not just about aging here. People are sharp at 100. Some of the people, as you know, were in their 40s when they noticed things. Others were noticing it in their 50s, or 60s, or even 70s. You shouldn’t reject these signs. You shouldn’t just say, “Hey, this is something that is just normal.”

If you can’t remember phone numbers or organize things the way you used to [early intervention is] a great idea.

Our belief is it starts with an unhealthy lifestyle, and then your genetics determine whether that unhealthy lifestyle pushes you towards neurodegeneration or cancer, or heart disease, or autoimmune disease.

Dr. Bredesen: Absolutely. And again, this is all internally consistent. This has been one of the biggest problems in science. Things must be internally consistent. If a proton acts this way on your left side, it should be acting this way on Pluto as well, right? Protons are protons. People throw out these ideas, “well, how about if it’s just this one little thing or just that thing.” Well, that doesn’t fit the epidemiology, it doesn’t fit the genetics, it doesn’t fit the biochemistry.

The model has to fit everything we know about this disease, and so when we look at this as an insufficiency, we’re looking at all the pieces that have to go together, and that is an internally consistent model. So, optimizing those things does make you healthier, this is something that is a disease of ill health, no surprise.

The Paleo Diet: The rise in chronic diseases, particularly in the last 40 years, has been quite extraordinary. Our belief is it starts with an unhealthy lifestyle, and then your genetics determine whether that unhealthy lifestyle pushes you towards neurodegeneration or cancer, or heart disease, or autoimmune disease. But they all generally start with not living a healthy lifestyle or diet.

Dr. Bredesen: Absolutely, I couldn’t agree more. One of the most fascinating things to me, as we dive deeper and deeper into looking at the genetics and the biochemistry of these people with these diseases is that you can see why each of these people got the problem. We will have a person, for example, who gets type three in a toxic form, and we’ll find out, they have no alleles in some of their glutathione related genes. They simply can’t detox the way other people can. Nobody ever knew it, nobody ever looked for it.

So, you can see why each person has the problem that they have, and as you said, so many of us are getting this condition because of the horrible mix of modern lifestyle, modern toxins, modern diets that just don’t go together. As Professor Kristine Yaffe from UCSF has found, Alzheimer’s is now the third leading cause of death in the United States. It’s actually the number two leading cause of death in the UK, and among women in the UK, it’s the number one cause of death. So, yes, it’s been on the rise, and it’s because we’re not recognizing the things that are putting us at risk.

The Role of Inflammation and Leaky Gut

The Paleo Diet: In our research we have seen that chronic and inappropriate inflammation seems to precede almost all of these chronic conditions – whether it’s cancer, heart disease or autoimmune disease. I haven’t looked at Alzheimer’s yet, but I’d be willing to bet some pretty good money that there’s research showing the same thing?

Dr. Bredesen: Absolutely. There’s no question that neuroinflammation and chronic inflammation are present. What’s interesting is you can do the same sort of thing looking at the M1 and M2 ratio with the peripheral blood mononuclear cells. These are blood macrophages, and the M1’s are more pro-inflammatory, and the M2’s are more anti-inflammatory.

Interestingly, the people with Alzheimer’s break down into two groups. You see the people with high M1/M2 ratios – you should be about 2.5 to 1 – you see them with 6, 8, 10 that are clearly pro-inflammatory, and this is our type-one inflammatory Alzheimer’s. Interestingly, you also see people where it’s flipped. It’s too low. These are people who are atrophic, they’re simply not supporting the ability to have an appropriate amount of inflammation, so you’re not dealing with pathogens and things like that.

Interestingly, as you treat these people, and they get better, they converge on an optimal ratio of 2.5. There is some beautiful work out of UCLA from Professor Fiala, who showed that when people go on our protocol, you actually do see this increased back to normal or decreased down to normal so that they converge with appropriate treatment. And when they go off, and when they get worse, no surprise there, M1 to M2 ratios get worse as well.

The Paleo Diet: The other thing that you point out multiple times in both books is leaky gut.

Dr. Bredesen: Absolutely. It’s one of the most common problems of a chronic inflammatory state. So many people have it, but they don’t know. The doctors don’t look for it, the doctors aren’t treating it, but treating it is an important part of optimization overall.

I should add, another key piece of this is not to just write a prescription and do the same thing forever. You want to tweak this down the road, you want to continue to optimize over time so that you get best outcomes. We do see people who will improve and then plateau, and then we have to keep looking. Then we find something additional, now we treat that and now they get even better, their plateau is higher.

Other Factors – Sleep, Stress, and Meditation

The Paleo Diet: Before we finish up, I wanted to ask you about some of your other solutions. You talked a lot about sleep, you talked about toxins, you talked about oral health, I was wondering if you could expand on those.

Dr. Bredesen: Absolutely. Again, as you and I talked about before, I’m [a dietary] agnostic; whatever works. If it turns out that the thing that helps Alzheimer’s the best is eating meat 24/7, then hallelujah. Whatever it is. It’s just that the publications so far haven’t shown that.

Getting people into these mildly ketogenic diets; absolutely huge. Getting rid of things like grains, dairy, and stuff like that; huge. Optimizing their B12, optimizing their Vitamin D, these are all huge.

As you indicated, other pieces as well. Again, we go back to the orchestra. You want to get the whole body to play together. In terms of exercise, you want to combine strength training, which is particularly good for your insulin sensitivity, with aerobic training, which is particularly good for your oxygenation and blood flow, and also, interestingly, for things like getting your ketones increased.

If you like HIIT, fantastic. One of the things that I really like is EWOT, the exercise with oxygen therapy because you’re hitting multiple things that are contributing to cognitive decline. You’re getting improved blood flow, you’re getting improved oxygenation, but you’re also getting improved strength as well.

Then another one is KAATSU bands. When I first heard about KAATSU bands, I thought, “Oh, come on, is this really anything that’s important?” Well, again, I’m surprised the data are showing that KAATSU bands do seem to help people. Is that because they improve blood flow? Because your muscles are now saying, “Hey, please enhance the flow here,” and that’s also helping your brain? I don’t know yet, but just what we’re seeing with people who use them is that they are getting good results and that they’re relatively benign.

Then there’s stress. I’ve been surprised at how important stress is. As long as your amygdala is perceiving a threat, there’s stress. Stress is a huge contributing factor to cognitive decline. Dr. Clawson has really been a proponent of this in pointing out that the brain’s perceiving stress or threat is a huge negative and can keep you in that cognitive decline. So, huge issue.

Then sleep, I think sleep is one of the most important aspects to improving cognitive decline and optimizing your cognition. So, checking to make sure that you’ve got appropriate oximetry nocturnally. And, again, the wearables are very helpful. You can do this with an Apple Watch, you can do it with a Dreem 2, you can do it with all sorts of ways to look at your oxygenation. Even just a little finger oximeter, lots of ways to do this.

The wearables are going to be very helpful. Continuous glucose monitoring (CGM), as you know, is really revolutionizing the way we get at appropriate diets. So many of us with a standard American diet are doing the worst. We’re spiking up our glucose and then we’re troughing it. We’re going down at night. Both of these things bad for our brains.

Then getting people to improve their heart rate variability, appropriate breathing, appropriate meditation, which again, as a scientist, I used to laugh at meditation. It turns out it’s very important, very helpful, I can’t ignore the data.

So, just go right down the road here, looking at the critical pieces for optimizing the variables that are critical for cognition. This is an exciting time. We’re seeing the first turnarounds, we’re seeing the first improvements, we’re seeing the first survivors – which is why I put together this book – we’re seeing how we can improve things.

New things like plasmalogens, are they going to turn out to be critical? Of course, there’s some outstanding work from the biochemist, Dr. Dayan Goodenowe, looking at plasmalogens. The jury’s still out, but he’s getting interesting results, so we’ll see.

We’re understanding the underlying problems better and better. Things like Methylene Blue, is this going to turn out to be something that’s really helpful? Very interesting work on that as well. Toxins like cyanobacteria that Dr. Paul Alan Cox has worked on. These also may be very important. So, we’re getting a better and better look at why so many people are getting cognitive decline.

Let’s Talk About the Role of Diet and Supplements

Critical vitamins for brain health include omega-3s, vitamin D, magnesium, and B12. And it’s preferable to get these nutrients from your diet, instead of using supplements.

The Paleo Diet: I did want to touch on diet. I wanted to bring it up because, in Julie’s story, she talked about The Paleo Diet.

Dr. Bredesen: Right.

The Paleo Diet: Actually, there was a bit of a misinterpretation here because she talked about it being mostly meat-based. I know that’s becoming the popularized view, but we have written about this a lot. By volume, it is much more plant food than animal food. She says in the book that you had her modify the diet, and she said, “I replaced foods like bacon, butter, and coconut oil, high in saturated fat that had a negative effect on my lipid profile, with fatty fish, extra virgin olive oil, avocados, nuts, and seeds.” I found that interesting, because if she came to me and said, “I want to go Paleo,” I would do the exact same thing. Bacon and butter aren’t Paleo.

Dr. Bredesen: Well, that’s fantastic to hear. It’s great to hear you say that because, again, we’re agnostic, whatever works best for people with cognitive decline or risk or decline, it sounds like absolutely, The Paleo Diet is part of that.

The Paleo Diet: It seemed in your book that there is a perception that The Paleo Diet is a heavy meat-based diet. That is something we want to dispel, I think that’s become the fad version, it’s not the true diet.

Dr. Bredesen: Well, thank you so much for that. I appreciate it because what’s happened is we get a lot of people who say, okay, you’re telling me to get into some mild ketosis, so I’m going to have a bunch of bacon, and we say, no. This is, as you’re describing it, more of a Paleo Diet. We’re getting rid of the grains and the very modern processed foods.

The Paleo Diet: Yes, I’ve been reading your suggestions on diet, and there’s a couple of minor differences, but for the most part, your suggestions look very Paleo to me. So I was very happy to see all of that. But, I did want to ask you about supplements because I did notice that in some of these stories, there’s a lot of supplements.

Dr. Bredesen: Yes, you know, this has been a very good point. I’m hoping that in the long run, we will have fewer and fewer of these, but you have to remember when we started our research 30 years ago, and when the very first patient went on this approach in April of 2012, we realized if we fail, the person dies. When someone comes to us with cognitive decline, there are only two outcomes, either we’re going to help them or they’re going to die. So, of course, we were pulling out all the stops and saying, “Is it possible? Maybe we need this, maybe we need that.”

As we come to understand this better and better, and I mentioned the big four areas, the trophic responses, the energetics, and the inflammation and the toxins, we’re understanding better and better what’s needed and what’s not needed.

So, yes, there are some critical things like resolvins at the appropriate time, omega-3’s, I happen to like whole coffee fruit extract because of its increase in BDNF, some critical things like making sure that you have appropriate Vitamin D, appropriate magnesium, appropriate B-12, appropriate homocysteine levels.

You’re right, a lot of these things you can do without needing supplements. So, we started with, “let’s do anything possible to make these people turn around,” but now that we’re understanding this better, we’re finding that we can begin to reduce the supplement number for many people. It is often said, it’s preferable to get it from diet, instead of getting it from supplementation.

The Paleo Diet: I’m really glad to hear that. My uncle is very early-stages, I sent him a copy of your book, and mentioned the supplements to him. I even told him that “you really shouldn’t need supplements, but you are dealing with something scary, I would try a bunch of these things and see what works for you.”

But that was the question you’ve already answered. Is the future of this protocol about figuring out which are necessary and which you could probably survive without? It sounds like that’s the direction you’d love to go in.

Dr. Bredesen: Absolutely. Again, you know, we’re looking at the biochemistry. What does it take to turn you from synaptic plastic? Your brain has literally gone into a protective downsizing mode. That’s what Alzheimer’s is. We want to switch that into an upscaling mode where you’re now in a good situation, you don’t have the stress, you don’t have the inflammation, you do have the energy, you do have the trophic support, and you’re now going to go into a synaptic plastic mode.

That’s what we want to do, and so it’s whatever will move that biochemistry, and when you can move it without supplements, great. So, you want to continue to look at anything that you do. Did it help? Did it improve things? Or did it worsen things?

It’s About Nutrients, Not Calorie Counting

The Paleo Diet: This is a minor point, but I really liked that you brought up a tool that I love multiple times in the book, which is this app called Cronometer.

Dr. Bredesen: Yes.

The Paleo Diet: Which tracks diet. I love it because it shows your nutrient balance, it shows if you’re getting enough nutrients, it shows things like your Omega-3 to Omega-6 ratio, your calcium to magnesium ratios. It shows the more important things about health, and forgive me, I might be stealing your thunder here, but what I heard in your book when you talked about not fueling our brains, it’s not calories, you can get a whole lot of calories from McDonald’s, you’re still starving your brain. It’s about getting the nutrients that you need and getting them in the right ratios. Is that how you see it as well?

We think in terms of, “Oh, let’s have fewer calories.” It’s not about fewer calories, it’s about the right types of calories. We have to get down on the carbs and get up on the nutrients, on the high nutritional value foods, on the protein, and on the good fats. That is what is an anti-Alzheimer’s diet.

Dr. Bredesen: Yeah, that is a great point. In fact, we have a Facebook Live on that this week. The key is that we think in terms of, “Oh, let’s have fewer calories.” It’s not about fewer calories, it’s about the right types of calories. That is the paradox of Alzheimer’s. Alzheimer’s is typically hitting people who have too many carbs, so they have a highly caloric diet, but it’s not a highly nutritional diet. They’re not getting the appropriate things. They’re getting a disease of insufficiency, which is due to excess. That’s the paradox.

The Paleo Diet: Yes.

Dr. Bredesen: So, we have to get down on the carbs and get up on the nutrients, on the high nutritional value foods, on the protein, and on the good fats. That is what is an anti-Alzheimer’s diet.

The Paleo Diet: Unfortunately, we’re running out of time. So, before we finish things up, just one last question for you. Could you tell us a little more about your trial and about how you determined if they were getting better?

Dr. Bredesen: That’s a great point. I think that’s the key point for trials – what makes you think these people actually got better? So, here’s what we did, we looked at MoCA scores: Montreal cognitive assessment, a very standard test. We looked at CNS vital signs, which is actually a more sensitive indicator. We did that so that we could look to see whether people who had early MCI – where they’re still doing fairly well on MoCA – what happened to their abilities? It also gives you different areas: verbal memory; spatial memory; executive function; and processing speed.

Then the third thing we looked at was the AQC, which is a change score. There are some trials where people will say, “Oh, well, I got a slight improvement.” But you know, the family didn’t notice it. So this actually says, “Okay, did the spouse or partner notice?” It’s filled out by the spouse or partner.

The fourth thing we looked at was brain training, so brain HQ. It looks at how these people did with their training. Were they getting worse? Were they getting better? The fifth thing we looked at was the MRI volumetrics. We looked at their gray matter volumes, we looked at their hippocampal volumes.

So, interestingly, they improved in all five of those criteria. Seventy-six percent of them improved their MoCA, 84 percent of them improved their CNS vital signs, 84 percent of them improved on their AQC change. Interestingly, 100 percent of them improved on their brain training scores and then even with their MRI volumetrics, they did better.

So, when you have Alzheimer’s or pre-Alzheimer’s, over time, your scores, the size of your volumes of your gray matter, and your hippocampus decline. If you just have normal aging and no complaints, they still decline just more slowly. The people in the trial, despite the fact that they had AD or pre-AD, actually did better, historically, than people who have normal brains who are just aging. So, they actually did better than normal aging on both their gray matter volumes and their hippocampal volume.

We are very excited to see that by all of these different parameters, they improved.

The Paleo Diet: That’s extraordinary. You said you’re doing a full study as a follow-up now, I’m very excited to see your results.

Dr. Bredesen: We are as well. Thanks very much.

The Paleo Diet: Well, Dr. Bredesen, great as always to talk with you. The book is The First Survivors of Alzheimer’s. It was a great read, especially for anybody who’s facing this sort of situation. It can feel lonely, it can feel hopeless, and here’s a book where you can read about people going through that experience and turning it around into a success. That gives hope, which is probably the most important thing that we can all have. So, thank you for coming on the show and sharing your research.

Dr. Bredesen: Thanks so much, Trevor. Always great to talk to you, please stay healthy.

Trevor Connor, M.S.

Dr. Loren Cordain’s final graduate student, Trevor Connor, M.S., brings more than a decade of nutrition and physiology expertise to spearhead the new Paleo Diet team.

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