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

In 2020, neuroscience researcher Dr. Dale Bredesen published his book The End of Alzheimer’s Program, detailing his ReCODE (reversal of cognitive decline) formula designed to help people with Alzheimer’s disease.

The formula, with its many moving parts, was the culmination of 30 years of research, including 230 peer-reviewed papers and direct experience helping countless people with the condition.

The Paleo Diet® team interviewed Dr Bredesen when that book was released, diving deep into the ReCODE formula and Dr. Bredesen’s nutritional advice.

In August 2021, Dr. Bredesen published his next book, The First Survivors of Alzheimer’s: How Patients Recovered Life and Hope in Their Own Words, which picks up where the last one left off.

While The End of Alzheimer’s Program explained the “how” of his approach to preventing and reversing Alzheimer’s, this next book tells the stories of seven of his patients, giving hope to the countless people suffering from the early onset of the condition and believing—like Dr. Bredesen’s patients originally did—that there is nothing they can do.

In part I of our interview with Dr. Bredesen, we revisit his ReCODE formula and talk about why it was originally hard to get the medical community on board. Fortunately, Dr. Bredesen persisted and around the same time that he published his most recent book, he and his team also published two peer-reviewed studies showing a reversal of the condition in a large sample of participants. [1,2]

Ironically, while Dr. Bredesen’s team was publishing this research showing improvements in the Montreal Cognitive Assessment (MoCA)—a gold standard test for Alzheimer’s—and getting little press, a new drug called Aducanumab was hitting the front pages of the media. The drub was bringing in $500 billion in funding because it merely slowed—it didn’t reverse—Alzheimer’s progression by 22 percent.

As Dr. Bredesen points out in this interview, Alzheimer’s is a complex condition. Simply looking to drug therapy may not be sufficient. Like many of the current chronic diseases of civilization, this is a condition where diet and lifestyle are critical.

“The Man Who Offers Hope”

The Paleo Diet: Dr. Bredesen, it’s great to talk with you. I’m shocked to see that it was exactly a year ago that we talked to you. It feels like it was only a few months ago.

Dr. Bredesen: Yeah, for me as well. Thanks so much for having me back, appreciate it.

The Paleo Diet: It’s a real pleasure. I was trying to think of how to introduce you and I want to start with a line out of your new book. This is on page 112. One of your patients introduced you at a conference, and here’s what she said: “I ended by saying it’s my honor to introduce the man who offers hope, Dr. Dale Bredesen. That is what he did for me and for countless others in an environment that otherwise offered nothing but despair.” I couldn’t think of a better way to be introduced than that.

Dr. Bredesen: Absolutely. Thank you very much, I appreciate that. As you know, we spent 30 years in a laboratory, looking for hope, looking for whether we could understand the fundamental nature of the neurodegenerative process, the actual molecules involved, why is this happening? Why is it so common? What are the pathways? What are the alternative pathways? All the above, so that we could ultimately translate that into the first effective therapeutics.

We’ve had thousands of people now, who’ve gone on the protocol, and as you know, that book has seven people who were all told that things were not looking good for their futures, that they should give up, essentially. One of them was told to get ready for a nursing home. And all seven are doing very well, some as many as nine-and-half years since they started the protocol.

People were crying, to hear that there was nothing that could be done. And then to actually see people get better for the first time was so compelling.

Dr. Bredesen

Why Another Book Just One Year After His ReCODE Book?

The Paleo Diet: We had you on the show a year ago, because you published a fairly lengthy book describing your whole ReCODE formula, and here we are a year later, and you’ve published another book. So, I wanted to start right there with why the new book?

Dr. Bredesen: Yeah, great point. Since we put out the first book back in 2017, the thing that gets me the most is to hear from people who’ve actually gotten better, emails, discussions, phone calls, meetings, just to hear people talk about their stories, I’ve always thought it was so compelling. When we had the very first book, a whole group of people gathered in an auditorium at the Buck Institute and started telling their own personal stories, I mean, people were crying, to hear that there was nothing that could be done. And then to actually see people get better for the first time was so compelling. I thought, “Wow, we really need to get some of these stories into a book so people can read them.” First of all, to give them hope and incentivize themselves, but second of all, to read the specifics. What are the workarounds? What are the issues that people dealt with to get themselves better? How did the rest of the family help them? Did they get the right doctor? How did they find the right person? Was a health coach helpful?

So, we put that together, and it was actually going to be part of the second book, but there were too many words to get all into one book, so they were separated into the two books, the one that you mentioned, which was about the fundamentals of the program itself, and then this new third book, which is all about the stories. And then, of course, we updated the protocol and talked a lot about what it takes for normal cognition to enhance. I think most of us recognize, we’re probably not operating at full capacity, at perfect capacity for our own selves, and so the idea that really what we call normal cognition isn’t always the best for each given person. So, I was very excited to get that out, and it’s just been very compelling to hear these people and to see what they wrote about their own stories and their own struggles.

Is What We Consider “Normal” Actually Normal?

The Paleo Diet: I really liked that one of your final chapters in the book was about addressing—and you put it in quotes—”normal,” because that’s certainly a conversation I have with people all the time when it comes to diet. When I try to explain The Paleo Diet to people, they go, “Well, I eat junk food, I eat all these grains, and I’m just fine.” I always look at them and ask, “how do you know what fine is?”

Dr. Bredesen: Exactly. So many of us know, if we stay up all night, we’re not going to be as sharp the next day. It’s the analogy, eating junk food is like staying up all night, doing the wrong things, having some chronic inflammation is like staying up all night, being under chronic stress, having insufficient various vitamins and minerals, all of these things, having a leaky gut that you may not know about. People say, “Oh, I’m just getting a little older. It’s normal. I’ve got some joint pains.” No, that’s not normal, that’s not what should happen. So, you’re absolutely right, people who think they have normal cognition could actually do better.

The Paleo Diet: I really like that analogy, because if all you ever get is three hours of sleep a night, then you never have the experience of being rested.

Dr. Bredesen: Exactly. It’s amazing. When I finished my residency, where we were staying up all night, all the time, and this was a five-year internship, and then four more years after that. When I finally finished that, it took a few weeks, but I started to notice, “Wait a minute, I’ve got a real brain fog that is lifting here.”

It just becomes part of your new normal, and after a while, you forget that really, you’re capable of much better. So many people will say, “Wow, not only am I sharper, but I’ve got more energy, I feel better, I don’t have the aches and pains I did, I jump up in the morning, I feel better.” So, all of these things start to improve. It’s basically better health, more resilience. Of course, then you do better when you are exposed to COVID-19 and things like that, so there’s so many of these things that we tend to live with not realizing that it’s really sub-optimal for each one of us.

Getting Your Body Out of Protection Mode

The Paleo Diet: That’s a great point. I want to dive into all this, but I’m going to start by saying that in your previous book, you talked about your ReCODE formula. Could you give us the quick 10-minute summary?

Dr. Bredesen: Absolutely. We had a clinical trial that we just posted on medRxiv, the same place where a lot of the COVID-19 research is published, just back in May. So, what we found was that there are four major groups of contributors to cognitive decline and risk for decline, and if you look at those—and you’ve got to look fairly deeply into each one—you can identify what your risks are, or what the contributors are that are actually driving this, and then you can address those. So, the protocol is all about identifying and then addressing those things.

If you think about it, the current approach makes no sense because the current approach to cognitive decline doesn’t really look to see what’s causing it, it just gives you a medication, which doesn’t work, and says, “We’re gonna treat everybody the same.”

The idea of treating the contributors, treating the cause is obvious, it makes sense, but it has not been done with neurodegenerative diseases, because people just say, “Well, we don’t know what causes it.” Well, that was what the research shows that there are, in fact, a lot of things that contribute to it, you’re really looking at the change in a network function, a network in your brain that is critical for neuroplasticity. So, when you’re on the wrong side of that you’re literally dismantling things in an attempt to protect yourself.

There’s a direct analogy here to the pandemic. So, what were we all told a little over a year ago? We were all told that there’s an insult, SARS-CoV-2, and therefore, we have to shelter in place, we have to social distance, we have to pull back, and we have to go into protection mode. What happened? The whole country went into a recession. That’s exactly what your brain is doing with cognitive decline. When you have insults, leaky gut, insulin resistance, toxin exposure, and things like that, your brain literally signals itself to go into a pullback protection mode.

When we treat you, what we want to do is identify those insults, and then address those and get you back into growth and maintenance mode, and out of protection mode.

We’ve had over nine years where people improved their cognition, when most would have been in nursing homes by now.

Dr. Bredesen

So, how do we do it?

The four things that I mentioned. Number one is anything that causes chronic inflammation. So, we look for leaky gut, chronic sinusitis, oral microbiome changes, chronic pathogens, such as Beryllium or Bartonella, any of these things. Herpes Simplex, by the way, on your lip repeatedly, that’s been shown to increase risk for cognitive decline. So, anything that causes inflammation, and if you’ve got those things, number one, we want to take those away, we want to get rid of those. Number two, we want to resolve the inflammation and that’s using resolvins—things like SPM Active, and things like high dose Omega-3 and things like that. Step three, we want to prevent further inflammation, it’s critical to remove that to get yourself back on the right side.

The second piece then is anything that is a toxic exposure—we want to identify and remove those and then detoxify. The toxins are in three different groups. Number one, inorganics like metals, mercury, and also things like air pollution. So, anyone, for example, in the California fires is now at increased risk for cognitive decline. People who were in the World Trade Center, unfortunately, back in 2001—14 percent of them by 2016 had already developed cognitive decline, really horrifying. The second group is organic toxins. So things like benzene, toluene, glyphosate, all those sorts of things increase risk for cognitive decline, and so we want to detoxify after we identify those. The third group is biotoxins. A surprisingly common cause of cognitive decline is toxins typically made by mold, mycotoxins, trichothecenes, gliotoxin, ochratoxin A, things like that. So, we want to identify those and detoxify, and that may take months and even some years to get rid of those.

The third piece out of the four then is reduced energetics, and one of the most common and often overlooked problems is that people who have cognitive decline have an energy deficiency, and the energy deficiency is based on four things. Number one is cerebral blood flow. You’ve got to have the blood flow, so if you’ve got vascular disease, no surprise, you’re at increased risk for Alzheimer’s disease and for cognitive decline in general. Number two is mitochondrial function. So, your mitochondria have to be able to generate energy. Number three is oxygenation. Many people don’t realize that they’re dropping their oxygenation at night. So it’s critical and yes, many of them have sleep apnea, but not all. There are other things like upper airway resistance syndrome. Anything that drops your oxygen at night. It’s easy to check, I have a whole chapter on the book on wearables; they are changing the way we think about this. They’re changing our ability to pick up these changes early on, which is when it’s easiest to treat this.

You have to remember, you don’t get a diagnosis of Alzheimer’s for about 20 years after the pathophysiology begins, so we really have a tremendous opportunity, a tremendous window to treat that.

The fourth thing is ketones. So, the ability to get into some degree of ketosis because you have this energy gap. You can see it on a PET scan: the hallmark of Alzheimer’s disease. The PET scan changes may actually come in the 20s or 30s, believe it or not, so what we have always thought of as an old person’s disease actually can start much, much earlier. If you’re APOE4 positive—which is the common risk factor gene—about 75 million Americans have a single copy, about 7 million Americans have two copies. Most don’t know it, so it’s really helpful to know about this. If you have that you can see changes on the PET scan in your late 20s and early 30s, and what is it you see in the temporal region and the parietal region? A reduced utilization of glucose.

So, you have an energy emergency. You can bridge that gap as Dr. Steven Kinane has taught all of us with ketones, so we want to get people up between 1.0 and 4.0 millimolar of ketosis. So, here’s the interesting paradox, we’re saying this disease is fundamentally an insufficiency, just as we’ve known about insufficiencies like Scurvy with Vitamin C deficiency, or Rickets with Vitamin D deficiency, this is also an insufficiency. It is a chronic insufficiency in a complex network, so it’s not good enough to just give Vitamin C or just give Vitamin D. You need to look at the dozens of things that support that network.

So, on the one hand, we’re telling people, “Yes, your energy is insufficient,” and on the other hand, we’re telling them, “Oh, don’t forget fasting.” So, we have to be very careful. There’s a bit of a paradox there. Some people will just jump into fasting and not get enough calories. You actually have to have good nutrition. It’s just to get people into insulin sensitivity, which is an absolutely critical part to making people with cognitive decline better. So you want to eat, but then you want to have the time for autophagy, you want to have the fasting time, so that’s the third group in the energetics.

The fourth is reduced trophic support and that’s three different things. That’s growth factors, nerve growth factor, BDNF, things like that. Number two, hormones, estradiol, testosterone, progesterone, pregnenolone, DHDA, all of those, thyroid as well. The third group is the nutrients, Vitamin D, as I mentioned earlier, Vitamin B12, things like that, that are absolutely critical.

So, that’s the set of things that we look at, and we address it by combining and by giving a personalized protocol. We have a computer-based algorithm that will generate an optimal protocol for each person, and it does, of course, include diet, exercise, sleep, stress, brain training, supplementation with, again, targeted supplements. It’s not just about random supplements. You’re targeting the things that are actually needed, that are actually changing in the network, and then detox is the seventh piece of this.

So, for each person, it’s going to be different, depending on what’s actually causing their problem, which is why we set up the protocol, but we’ve had some very exciting results. In our trial, we had 84 percent of the people actually show improvements in their cognition—not just slowing their decline—but actually showing improvements in their cognition. As I mentioned, we’ve now had over nine years of where people have improved their cognition, and sustained their improved cognition, when, of course, after nine years, most of would have been in nursing homes by now.

Why We Need to Address the Cause in All Chronic Illnesses

Cancer, heart disease, and other major killers are complex, chronic illnesses, The old-fashioned prescription pad medicine does not work very well for these things.

Dr. Bredesen

We’re taught that someday there will be a treatment, so let’s just keep trying one thing at a time. It is an old-fashioned approach that is fundamentally flawed.

Dr. Bredesen

Dr. Bredesen: Exactly. Unfortunately, that’s what we’re taught. We’re taught that someday there will be a treatment, so let’s just keep trying one thing at a time. It is an old-fashioned approach that is fundamentally flawed. So, we’re looking at well, okay, this drug failed, and that drug failed. Of course, in Alzheimer’s, over 400 drugs have failed in significant clinical trials. So, maybe that’s not the best way to go about it.

That’s why the research that we did over the years was to ask whether we could understand the fundamental nature, as I mentioned earlier, of the degenerative process. When you look at that, what you see is that this is about a complex system. It’s a little bit like saying, we’ve got an open pit, we want to have beautiful orchestral music, what do we put into that open pit? Do we put a violin? Do we put timpani? Do we put a clarinet? Well, you try one after the other and it just doesn’t sound like an orchestra. But wait a minute, maybe you have to start filling that pit with all these different things that work together to make it function. It shouldn’t be a surprise. Human beings are complex organisms and we’re gathering right now in standard of care medicine, datasets that are far, far too small to understand what’s actually going wrong.

So, we need to expand our view of human physiology and human pathophysiology. And that is what we’ve been trying to do and then translate this into what is most important for each person.

The Paleo Diet: Right. So, I found it very interesting in your book, you talked about how in 2011 you tried to submit a study for review of your protocol, and basically, they refused you saying there were too many variables.

Dr. Bredesen: Absolutely. This is such a good point because there’s an assumption. So, for all of us, we get trained in a certain way where if you’re going to do a clinical trial, you have a placebo control, you have randomization, and then you have one thing that you do. It could be drug A, it could be instrument B, procedure C, whatever it’s going to be, it’s one thing. Well, of course, as you can hear, that presupposes something that may be wrong. When you have a disease that’s responding well, like pneumococcal pneumonia, fine, see if you can get better and better antibiotics, but if you have a disease that has not responded to treatment—and Alzheimer’s is a great example—then maybe you have to take a step back and say maybe the classic way to do it, the way that you’re expecting to do this, the next drug or the next instrumentation, maybe that’s not the best way to do this.

So, in 2011, we put in the first request for a trial in which we would use a whole protocol. The idea was we’re going to do a placebo, we’re going to do a drug, we had a specific drug that we would use, which we recognized only does a few things, it’s not going to be perfect, but it’s a start, and then we had a protocol with a placebo and a protocol with drugs. So, we were really hoping that the drug and the protocol together would give us a big boost.

We were not allowed to do that trial. Multiple IRBs turned it down and said, “No, this is not the way you do trials.” We said, “Yeah, but you guys don’t understand Alzheimer’s. This is a multivariable disease.” So, we thought okay, first, we need to publish some anecdotes to show that yes, this really does work, and we did that in 2014, 2016, and in 2018, we published 100 documented cases of improvement, which just hadn’t been seen before.

So, then we went back in 2018 after all of that to the IRB. We got turned down again, believe it or not. Finally, in 2019, we got the approval just to do a small proof of concept trial, which we did, and we just completed that at the end of 2020, the pandemic notwithstanding. Now we’ve just posted it, as I mentioned earlier. I’m very excited to work with three absolutely outstanding clinicians, Dr. Ann Hathaway, Dr. Cat Tubes, and Dr. Deborah Gordon.

As I mentioned earlier, 84 percent of the people showed actual improvement, not simply a slowing of decline, but actual improvement. We had people showing MoCA scores of 19, which is fairly significant, to 30, which is a perfect score. So, we had some really striking improvements. And of course, we had some less striking improvements as well. The people who didn’t improve were also very informative, because you could see why they didn’t improve. So, for example, we had one person who had very high levels of mycotoxins in her home, and she said, “Well, I’m not fixing that, and I’m not going to move.” Okay, so no surprise, she stayed in the home during the pandemic, and things didn’t get better.

We’ve learned a lot from this, and we’re now strategizing for the next trial, which will start in January of 2022, assuming that the IRB will now allow us to do the next one. This is a larger trial, which is a randomized controlled trial. So, we’re very excited about that.

I think for the first time we can begin to say that, hey, the Alzheimer’s disease is now optional, if you get on appropriate prevention, and we recommend that everybody who’s 45 years of age or older, get on prevention, or early reversal, then virtually no one needs to get this disease. It sounds crazy, but this is what we’re seeing.

There is something called mild cognitive impairment, which is the pre-Alzheimer’s condition. So, the doctor tells you, “Don’t worry, you’re not that bad yet, you’ve got mild cognitive impairment.” That’s like saying, you’ve got mild metastatic cancer. It is a late-stage of the pathophysiology.

Now, for the people who are waiting till really late, yes, much harder, and we have some people with MoCA scores of zero who got better, but they didn’t get all the way better. They started dressing themselves again. They started speaking again, and things like that, but they didn’t get all the way better. So, as long as you start either with prevention or the earliest reversal, you should do very, very well.

Again, this leads to another big problem, which is that people wait and wait, because they are told that nothing can be done. One of the biggest problems is a semantic one, there is something called mild cognitive impairment, which is the pre-Alzheimer’s condition. So, the doctor tells you, “Yeah, don’t worry, you’re not that bad yet, you’ve got mild cognitive impairment.” Well, actually, that’s like saying, you’ve got mild metastatic cancer. It is a late-stage of the pathophysiology.

If you look at the four stages of Alzheimer’s, there’s a stage where it’s pre-symptomatic, you can pick it up on a PET scan, but you don’t feel anything yet. Then there’s a stage called SCI, subjective cognitive impairment, and that’s where you know that there’s something wrong, but the tests aren’t really showing it yet. So, the third of four, is what’s called mild cognitive impairment, MCI. It should be called advanced-stage Alzheimer’s, because it’s the third out of four stages – it’s a relatively late-stage. Many of the people in our trial had what was called MCI. They’re significantly impaired, and their pathophysiology has been going on for years. So, by calling it MCI, we’re actually hurting people, and we’re hurting physicians, because they hear the term mild. The fourth one, the final one, is what we call Alzheimer’s disease, where you’re actually losing activities of daily living, have trouble dressing yourself, toileting, things like this, I mean, this is a very late-stage of a process that we can do wonders with, especially early on. So, we need to change the way we think about this, change the way we prevent it, and change the time when we treat it.

It tends to sneak up on people, as you know, people will often say, “Oh, well my spouse isn’t that great either,” but that just means your spouse needs to be checked out as well. If you’re in late-stages, please have all of your children evaluated and get them on prevention.

The Paleo Diet: I was going to ask you about that, because that was something that was very clear in all the stories in the book. You point out the fact that at these early-stages, you see the symptoms 20 years ahead of when you actually get the diagnosis. But the interesting thing is you go and see the doctor and the doctor says, “Well, you don’t have Alzheimer’s yet, come back in a year.” They keep having you come back in year, and then finally they say, “Well, you have Alzheimer’s, now there’s nothing we can do about it.” The question is why aren’t they addressing it much earlier or when they first see the signs?

Dr. Bredesen: Exactly. That is a huge part of the problem. Can you imagine if your cardiologist said to you, “Don’t worry, your blood pressure’s high, your vessels are closing down, but you haven’t had a heart attack. Come back in a year.” You’d fire your cardiologist and move on to a good cardiologist. Why are we not doing the same thing for cognition? We should be optimizing it from the get-go, and not waiting for these things to happen, because again, that’s too late.

If you look at Deborah’s story, one of the seven, just a wonderful story. Brilliant woman. She talks about when she watched her grandmother die of Alzheimer’s. She watched her father die of Alzheimer’s, unfortunately. And of course, as she began to get her symptoms and found out that she was APOE4 positive, she looked at her children and said, “Oh, my gosh, this is going to go through generation after generation.”

So, one of the exciting things is we can now end it with the current generation for pretty much everyone. Again, if you start early. She went into a university and they said, “Yeah, your tests are not doing so great, but come back in a year.” Then after she got on the protocol, she went back about nine months later, and at the university, they said to her, “Wow, what have you been doing? Your test scores are excellent now.” Then when she told them what she’d been doing, they said, “Well, would you consider just stopping a few things? Because we’d like to know what it is that’s actually doing good.” She said, “No, you guys stop some stuff. I’m going to continue because this is what actually works for me.” So, yes, absolutely, we want to end this with the current generation.

The Paleo Diet: Again, I don’t want to be too negative to the medical community, but it seemed like in all these stories, there was a certain lack of empathy often from the doctors. I’m looking at page 106 here. This is Julie’s story. She talked to a doctor when she realized she was early-stages and I’ll just read right out of the book, “I asked them what I could do to prevent them from worsening or better to reverse them, his response, ‘Good luck with that.’”

Dr. Bredesen: Yeah, isn’t that amazing? To be fair, I mentioned in the first book, we neurologists aren’t known for our bedside manner. We tend to be very exacting types of doctors. People who go into brain disease tend to be very exacting, and of course, unfortunately, neurology has selected for people who aren’t particularly interested in therapeutics often.

Now, of course, we all want the same thing. Ultimately, we want people to get better. But training in neurology over the years has meant that you typically are a very good diagnostician. Lots of training and diagnostics. A fact that you may know, Sherlock Holmes the character was based on a real neurologist, who was quite good at figuring out what had happened to people and what had given them their disease.

Unfortunately, we haven’t had much to offer in neurology, so we see people with strokes, and we see people with MS, and we see people, and to be fair, there are now some drugs for MS that work very well, but again, they’re not getting at what’s actually causing the problem, unfortunately, and therefore, they can sometimes have very bad side effects. We’ve had things like neurodegenerative disease, Alzheimer’s, Frontotemporal dementia, Lewy Body disease. This is the area of greatest biomedical therapeutic failure. We just haven’t had anything to offer. So, these people die, these are terminal illnesses, and to change that we need to change the way we think about them. We prevent them, we evaluate them, and we treat them, especially early treatment with multi-pronged therapies.

References

[1] Toups K, Hathaway A, Gordon D, Chung H, Raji C, Boyd A, et al. Precision Medicine Approach to Alzheimer’s Disease: Successful Proof-of-Concept Trial. Medrxiv 2021:2021.05.10.21256982. https://doi.org/10.1101/2021.0…;

​[2] Rao RV, Kumar S, Gregory J, Coward C, Okada S, Lipa W, et al. ReCODE: A Personalized, Targeted, Multi-Factorial Therapeutic Program for Reversal of Cognitive Decline. Biomed 2021;9:1348. https://doi.org/10.3390/biomed…