Cognitive Decline Is Now Optional: Here’s Why

Dale Bredesen, MD 

Yeah. Thank you, Terry. So I have been interested in cognitive decline. I’m a neurologist and neuroscientist by training and ran a laboratory for 30 years in which we studied the basic research on the mechanisms that drive the neurodegenerative process. So we have been interested in that for many, many years. I’m a professor at UCLA. Currently, I was the founding president of the Buck Institute and was there for many years. And so we have then translated our work, and we were the first back in 2014 to report reversal of cognitive decline in patients with Alzheimer’s and Pre-Alzheimer’s.

Terry Wahls, MD

I love your work and I know you had this international reputation for all of your work with Alzheimer’s. And the reason I asked you to come today is that I think Alzheimer’s and the cognitive decline with MS are parallel diseases that they share so many of the same problems. And we know that for MS, cognitive decline is very common. The longer you have your MS, the greater the risk you are to develop cognitive decline and brain fog. And it is the leading reason people leave the workforce. So let us talk about the major contributors to Alzheimer’s and the cognitive decline that is so common with MS.

Dale Bredesen, MD

Yeah, that is a great point. You know, I think of these as what we call deflamatory diseases because they are both degenerative and inflammatory. And what happens in Alzheimer’s we think of as a degenerative disease. But it certainly has inflammatory components. And as we think, as an autoimmune disease with a lot of inflammation and recurrent inflammation. But of course, as you just indicated, it has a degenerative component. So in a way, you know, they are related. Certainly, again, with MS, we think of it more on the adaptive side where you have autoantibodies, you have your adaptive system that is hyper-activated. In Alzheimer’s, we tend to think of it more like a COVID-19 where you have a mismatch between the adaptive system and the innate system, where the innate system is on. So, of course, we think of COVID-19 as killing people due to a cytokine storm, whereas Alzheimer’s is more cytokine drizzle. And I suspect just what you are saying is true, that with MS, you have the same sort of thing. So, you know, the big message that we have today is Alzheimer’s is now optional. And hopefully, the cognitive decline of MS is now also optional because we can, for the first time, we can really look at what is driving these things and get at the upstream drivers of the problem. And in Alzheimer’s, it is for major groups of things. It is anything that causes ongoing inflammation and that is leaky gut or chronic sinusitis or Lyme disease or viral infections, all these things, you know, poor oral microbiome, inflammation, any of those things. 

Number two, it is anything that causes ongoing toxicity and that can be organic, inorganic, or it can be biotoxins like micro. Thirdly, anything that reduces energetic cerebral blood flow, oxygenation, so like things people who have sleep apnea are at increased risk, mitochondrial function, and then things like ketones that actually give you the substrates to burn. And then the fourth and final thing is trophic activity and that is growth factors like NGF and BNDF. It is hormones, estradiol, progesterone, testosterone, thyroid, all critical. And then it is nutrients, things like vitamin D. So those are the four big groups and I suspect that they, similar things are happening in patients with MS.

Terry Wahls, MD

Absolutely. Dale, you have such seminal work in Alzheimer’s, but everyone who is listening, Dale and I agree that these same concepts are very applicable in mice, and these are the same concepts I use when I’m seeing my patients that I walk through to sort out how we can best support them on their healing journey. Now you have published a bunch of really interesting papers. When I went to medical school, I was taught that if you have Alzheimer’s, if you have cognitive decline, and if you had cognitive decline from MS or Alzheimer’s, that there was no coming back.

Dale Bredesen, MD

Right.

Terry Wahls, MD

But you have published a number of papers that called into question. Your thoughts about that?

Dale Bredesen, MD

That is a great point. We began publishing after the first example, in 2014, and have continued now. And this year, actually, we published a clinical trial in which 84% of the people actually improved their cognition, not just slowed the decline, but actually improved their cognition. We have people now ten and a half years on the protocol who still have improved cognition from ten and a half years ago. So unprecedented improvements and sustainable improvements. So that is you know, that is the idea here. And as you said, now we are really being able to take these principles that we discovered in the lab over the years and now apply them to MS and apply them to other things. And by the way, along those lines, we are beginning with other diseases and we have fantastic initial data on wet and dry macular degeneration. So as you know, there isn’t anything for dry macular degeneration right now other than a red two, which has almost no effect. And we have got dark adaptation studies that show dramatic improvements in people with dry macular degeneration. So we should be able to take these principles and adapt them for Parkinson’s, Lewy body, MS, frontotemporal dementia, cortical basal degeneration. Just go right down the list.

Terry Wahls, MD

You know, when I think of macular degeneration, that is millions and millions of people. I believe that is the leading cause of blindness right now. And, you know, this is something that I think about a lot, Dale. I have aunts that became blind at an early age and then began having hallucinations and had, you know, cognitive issues as well. And so as I watched their lives unfold, I’m thinking about your work and my work and that this was the root cause in those four big buckets that were driving their blindness and their brain fog and hallucinations.

Dale Bredesen, MD

Absolutely. These same sorts of things, again, you know, all of these are turning out to have one thing in common. You have a supply for a specific neural subsystem. And of course, in MS, you are talking about the white matter, you are talking about your immune status and any sort of pathogens that you are chasing, of course. EBV has been the big one. There is been so much press on in the last few months, but likely there may be others as well. So you have got this situation where you have got this balance between the supply and the demand. 

And, you know, when you get these diseases, you have a chronic mismatch where the demand exceeds the supply and they are nowhere. Is this more obvious than in macular degeneration, where blood flow is critical, as you know, if you have atherosclerosis, you are at increased risk. You increase your demand by going to lots of blue light, living near the equator, or decrease your supply by living at altitude, by having sleep apnea. These all increase your risk for macular degeneration. And you are absolutely right with what you said. There are 11 million Americans with macular degeneration almost twice as many as have Alzheimer’s disease. So this is a very common problem, as you indicated.

Terry Wahls, MD

Yeah. You know, they revised the number of folks with MS, to a million. I think that is still probably an underestimate. And then if I think about the neuroimmune, systemic autoimmune diseases that have neurologic symptoms or psychiatric symptoms, you know, again, that is probably 10 to 15 million that have a systemic autoimmune disease, that has brain fog, anxiety, depression, irritability. And then I can think about the folks who had COVID, who are left with brain fog, anxiety, irritability, or having difficulty working because they just can not problem solve as well. Or they are having difficulty getting along with folks that it is the same type of problem and a cure for them, that they are at much greater risk of developing a new immune problem.

Dale Bredesen, MD

Absolutely. And I think brain fog is becoming a huge issue in this country and elsewhere. And, of course, COVID has brought this to the fore, but in fact, it is such a common problem. So it is actually, to some extent, a favor that was done for us to brain says, hey, wait a minute, there are a lot of people out there. And as you mentioned, anyone who has neuroimmune problems. So many people just with their diet that they are doing, their sleep schedule that they are doing, the stress that they are under. So many of these people, and I’m sure you saw this just this week, this new report that people with adult ADHD are at increased risk for cognitive decline, which, by the way, fits with our research perfectly. I was always wondering over the years, why were people denying that. But it is turned out it is actually true. If you have adult ADHD, you are at increased risk. So brain fog is becoming a huge issue for so many of us and there is a tremendous amount you can do about it.

Terry Wahls, MD

You know, look at the number of people who are relying on energy drinks to try to get through the day because they are so fatigued or they are relying on a lot of caffeinated beverages to try and maintain their focus and their attention. And again, to me, that is just another indication that brain is not function as well, that there is excess inflammation. And so those are the kind of people that I wish would reach out to you or reach out to me because we could help them in a whole lot. Easier to help early in the disease process. Then after you have been diagnosed with Alzheimer’s or diagnosed with your MS.

Dale Bredesen, MD

Absolutely.

Terry Wahls, MD

Now, there are no millions, probably billions being spent on research for be myelination drugs. What do you think? Are these drugs going to be any more successful than the drug development for Alzheimer’s?

Dale Bredesen, MD

Well, I’m so glad you brought up the drug development for Alzheimer’s. What a mess. So recently we heard that looking a MAB, which does not make people better, it does not prevent decline. What it did in its trial was it slowed the decline by 27%. Now, Terry, imagine that Elon Musk said everybody perishes in space, x rockets, they explode, everybody dies. But we have a breakthrough. They die 27% later, you would say. Really? Really. Elon, is that really a breakthrough? So this is what we have been hearing, that there is this historic breakthrough that slows the decline. So the bottom line is absolutely what you said is correct. The drugs have not worked well, partly because they are not getting at what is actually causing the problem. And I do think in the long run, we need to have these precision medicine protocols that look at what is actually driving the problem and then add targeted drugs. That is going to be critical. But doing this as a monotherapy, as a drug, it just makes no sense. So what I’m doing right now is compiling a list of all the things that have had better outcomes than lecanemab. Here is a partial list for you. Number one, extra virgin olive oil by itself better outcome than lecanemab. Number two, refined olive oil. Number three, Polyphenol alone. Better outcome. Number four.

Terry Wahls, MD

Well, hang on. Polyphenols. Let us play. What? What is the polyphenol audience?

Dale Bredesen, MD

So just polyphenols. Things like, you know, there are and there are dozens and dozens of plant polyphenols that, you know, these are basically multi ring structures that are wonderful and support it, you know, support cognition and support anti inflammation. And they include things like Quercetin, for example, 5 to 10 things like that. And there are many of these and they are typically plant derived. So these work better than Lecanemab which by the way, Lecanemab has a side effect of brain hemorrhage, brain swelling, and in a couple of people so far, death. So I think we can do better. And of course, the Recode protocol that we use and the protocol that you developed work better than these drugs as well. 

So I think that, you know, the future is to bring these together, but start by going upstream. And you mentioned the re myelination idea. Great idea. After you determine what is causing the problem. So start with identifying that. And to me, that is the fundamental of new medicine. New medicine is asking what caused the problem and then addressing those things. Of course, this is, you know, root cause medicine, functional medicine, however you want to think about it, this is going after what is actually driving the problem. Once you have got that in hand, then sure. STEM cells and myelination and all these things are great after the fact. But start by asking what is causing the problem and get rid of that.

Terry Wahls, MD

You know, when I talk with people about re myelination, I have to remind them that you can not remind the brain if the microglia are still reactive, still driving the innate and adaptive immune system to attack the threats, whatever the perceived threats are. And so we in order to do that, that is all about diet and lifestyle, sleep, exercise, stress, relationships. I’m sure you have similar conversations in your Recode protocol that you are talking about the person’s diet and lifestyle.

Dale Bredesen, MD

And you know, you brought up a great point, which is microglia. So microglia are the macrophages of the phagocytes of your nervous system. They are sitting in there and they are trying to take up these various things, like these various pathogens and things like that, but also swallowing things like damaged neurons and fragments of myelin and things like that. So interestingly, two groups reported two completely different ideas. One said all we have to do is ramp up your microglia because then it will sit there and eat away the amyloid and you’ll be fine. The other group said All we have to do is turn off the microglia because they are spewing out these cytokines and if we just turn them off, everything will be fine. So you can see the conundrum here. The problem is microglia are physiological activators. So as long as they are being activated and inflamed and told, you have got ongoing pathogens, of course, they are going to be active and of course, they are not going to be taking away the amyloid because the amyloid is there to fight the infections. It is an appetite, microbial peptide. So this simplistic notion that you either activate them or deactivate them does not make sense. You have to get at what is causing them to be activated.

Terry Wahls, MD

And I do not think there will be a drug solution that will address that. That is going to be really coming down to what in the environment is causing that increased reactivity.

Dale Bredesen, MD

You know, it is so interesting to me that we are all used to now large data sets with, you know, Google knows where you shop and where I shop and where everybody shops and what you are doing and all that. And yet we are not using these sorts of sophisticated algorithms nearly enough for looking at what is actually driving these various complex chronic problems that we are all suffering from. And so we need to kind of get into a new world of medicine where we understand what is driving these problems, and we need more Silicon Valley, which is why I work with a software company to develop better algorithms so that we can understand more about what is driving these problems.

Terry Wahls, MD

So I think what I hear you talking about is having a deeper understanding of my family history, my genetics, all of the environmental factors that I was exposed to growing up as a child, young adult, my current environment. So a much more robust history than probably a much more robust assessment of biomarkers. You know, I think of the biomarkers that we can now investigate metabolites that can look at nearly two so literally many thousands of chemical metabolites that can be correlated with outcomes. And will that be the future we are looking at by the microbes that live in my mouth and my stool, the metabolites in my urine, my stool perhaps in my blood? And then we have a much more comprehensive guide on what diet will be best, what supplements may be best, and what probiotics may be best. How far is that kind of approach in the future?

Dale Bredesen, MD

I do not think it is too far in the future where in fact we are including it in our upcoming clinical trial. So as I mentioned earlier, we published a clinical trial this year that showed 84% of people actually got better. We are now expanding this and doing a larger randomized controlled trial. I know you have done a number of clinical trials as well. And so as you know, these take some time. But the good news is, with this new one, there are all of these new ways that we can now look to get a better handle on what is actually driving the problem. We have to quit thinking of people as a prescription pads. What do I write on my prescription pad? One little molecule for these complex diseases makes no fundamental sense. We have to start thinking of people as complex systems. Something went wrong. Somehow this system got out of whack and it created a mess or somehow it got out of whack and it created Alzheimer’s disease or other things. And we can now understand what actually went wrong with this complex machine, and we can now begin to fix that network. And interestingly, when you fix a network, you are not using a hammer, you are doing much more like what you do. You are changing the diet. You are telling people what to eat. You are changing their inflammatory parameters. You are changing their hormonal parameters, you are changing their lifestyle parameters. And then you tweak here and there, as you know, we can, but we can now look at fast motile in the blood, look to see whether there is damage ongoing. We can now look at beta in the blood to see if there is what is ongoing. 

If you are likely to be developing Alzheimer’s, we can do epigenetic studies to see whether someone has issues with methylation, whether they have what their biological age is, and whether their brain is aging more rapidly or more slowly. And we can follow these in real-time. We can now look at electrophysiology, we can look at your p300, which is how quickly your brain is recognizing something new. We can look at your quantitative EEG so we can get an idea of where did this system go awry? And we can now tweak at the various places. And as you know, you indicated earlier, a lot of the things that you are going to tweak are going to be things that you might not have thought of, like improving your sleep that is not necessarily a drug that does not work and gives you all sorts of side effects. 

But Terry, you know, you and I, well, we trained as physicians, we were taught to give drugs for these various problems. And great at certain times, you know, penicillin has saved a lot of lives. Let us be fair. Yes. But when you any time you throw in a drug, what you are saying is, I believe I know better than nature. And a lot of times that is got all sorts of side effects. And you are now looking at all these drugs. And again, with the ones for Alzheimer’s disease, you are talking about brain hemorrhage and brain swelling and just horrible, horrible side effects. So you really have to use these judiciously and know what the side effects are and know when you are tweaking the system. What is actually wrong with it? What are you trying to do? What is the outcome you are looking for? Instead of just saying, Ah, this is EMS, I write a prescription for Copolymer know what have you. Do you really have what is driving these things?

Terry Wahls, MD

You know, I want to take a moment to remind everyone just the magnitude of the work that you have been doing. Dale Alzheimer’s, I learned, was a one-way street that once you are diagnosed, you have progress of decline and to you no longer know who your loved ones are, you no longer know yourself. You eventually become unable to feed yourself and have a terrible, terrible prognosis. But that is no longer inevitable. People with Alzheimer’s confirmed Alzheimer’s have worked with the team. They have not all. And for many, just stopping the decline would have been like an astounding home run. But what Dale’s describing is that people are improving, they are thinking that they are cognitively performing, and it is their memory, their ability to recognize family, and friends, and interact that has been transformed. That is staggering. A similar cognitive decline happens with our math that I’m very optimistic that these same kinds of approaches, very similar with addressing the toxins, addressing nutrition, and addressing hormones can stop the decline in improved thinking and cognitive performance.

Dale Bredesen, MD

And the earlier, the better.

Terry Wahls, MD

It is so much easier, so much easier. The sooner you come in. Now what is going to happen in the future for your deal. What is, what is immediately coming?

Dale Bredesen, MD

Yeah so what is happening right now we are just getting the IRB approval for a randomized controlled trial, really excited to work with six absolutely outstanding physicians on that. So we have six sites, Miami and Cleveland and Nashville and Sacramento and Oakland and San Francisco. That’ll be starting early in the year. We are very excited about that and we’ll be able to do the test that I mentioned earlier, which we were not available before, as well as using the overall protocol to show improvement in these patients. As I mentioned earlier, also, we are doing something called the ARC Project, which is to now take the biochemistry and the genetics of Alzheimer’s and now change it, adapt it for the unique biochemistry of each of these. 

And you mentioned MS, I think is a great example and doing, you know, what you are doing, doing it in getting people to to be on an optimal cognitive protocol from the beginning, I think is is likely to give you best outcomes is when we see people who either get on prevention or earliest reversal, people who have subjected cognitive impairment, they all do great. We have not had a single example yet. Out of thousands where people got on prevention but ended up developing dementia, dementia is a late stage of this problem. So get on early and do well. Now with the ARC project, we are starting with macular degeneration. 

As I mentioned, we had the initial data look great. Then we are going to be looking at Lewy body disease and Parkinson’s and cortical basal degeneration and progressive supranuclear paralysis and frontotemporal and als and all of these things. And the other thing I’m doing is putting together just single cases of each of these things that have shown clear improvement to show that the approach that we are all now taking is actually the way to go. So we have these wonderful single cases that really kind of get you started. Alzheimer, AMR’s, familial Alzheimer’s. That is rare, less than 5% unheard of to keep those people doing well. We have a great example there. Craig Tanen down in Miami had a wonderful example recently of cortical basal degeneration, a rare degenerative condition. And that has done very well on the protocol. And then people with Lewy body who’ve done well and then I mentioned the PCA before, so we have a case of PCA recently.

Terry Wahls, MD

What is PCI of not real cortical atrophy?

Dale Bredesen, MD

And this actually came from Kerry Mills Rutland in New York, who is a wonderful brain health coach and dealing with a patient who has PCA, which is one of the non-domestic presentations of Alzheimer’s. So it is someone who is developing Alzheimer’s but who did not start with memory loss. In this case, it is visual perception loss. And this person is doing very well. And the cool thing is the MRI. The initial MRI showed parietal lobe at 0.6 percentile because that is where PCA happens. It is parietal and occipital. That is why posterior cortical atrophy described by Professor Frank Benson years ago. And the interesting thing is the follow up scan showed 22nd percentile, so oh 6 to 20 second, just dramatic and other improvements on the scan. But because parietal is really where this disease lives, we were so excited from a very atrophic parietal lobe to a relatively normal parietal lobe in terms of volume metrics. So she’s continuing to work with that patient and the patient is able to is doing somewhat better. But we need to keep improving the visual perception issues for that patient as well. So I think this is telling us this is giving us a this is pointing us in the right direction for the future.

Terry Wahls, MD

So and again, anyone who is listening, if you have been told that brain volume loss is irreversible, the cognitive decline is irreversible, I think what you are telling us still is that is old thinking. That isn’t matching your clinical experience in the research experience that you have.

Dale Bredesen, MD

Exactly right. And I should say, Teri, when you were first diagnosed with MS, of course, I’m sure people did not tell you you were going to be doing great and you are going to be doing all these wonderful things and getting better. You broke the mold. And I think that is what we are all doing as we are getting at what is actually causing the problem.

Terry Wahls, MD

Dale, you may not know this. I’m now jogging.

Dale Bredesen, MD

Oh, my God.

Terry Wahls, MD

So that is pretty exciting. I’m very excited about that.

Dale Bredesen, MD

Yeah, I congratulate that. Well, you know, this is we are all seeing that if you if we kind of ignore this claim that you can not do it, that there is just nothing that helps and actually look at Will. But why are we there? What has happened then? We are you know, we are seeing, we are all seeing unprecedented results.

Terry Wahls, MD

And were you criticized at first for talking about this stuff?

Dale Bredesen, MD

Oh, not just the first one. Still, I’m still getting nasty emails, nasty comments, nasty publications. And it is interesting, none of these complaints says, oh, we evaluated one of your patients and did not agree. Or, you know, we looked at your paper and we did not agree with the data. They all say things like, you know, you did not you did not do enough people in your trial. Well, it was statistically significant results. So apparently we did you know, you did not include the control group. We were not but one of the things is you published it in the wrong journal. Really. You know, let us talk about the data. Do you really care?

Terry Wahls, MD

You know what? I tell my post-doc that if you have a really new idea, it is very difficult to get it published the first time because it is so new. You have to, you know, struggle through or find a journal, get it published. Then the next paper is a little tiny bit easier to publish than the next one. A little bit easier. And if you want to do really new innovative stuff, that is the process. It just has to persist, persist, persist. So, Dale, I am so glad that you have persisted, persisted, persisted. I think you are doing amazing, amazing work. Now, Dale, where do people find you if they want to come to check out your work if they have a family with dementia or multigenerational. I’m sure that they get tuned in to your work. How do they find you?

Dale Bredesen, MD

So we recommend anyone who is 45 or over. Please have a cognoscopy just like you have a colonoscopy when you are 50. So you can go mycognoscopy.com. That has some information. You can look at the books. We published three books, “The End of Alzheimer’s, “The End of Alzheimer’s Program”, and “The First Survivors of Alzheimer’s.” Please take a look at those. We go through some of the things that can be done. You can look at dr.bredesen.com or you can follow us on Facebook or Instagram. Dr. Dale Bredeson. So any of the above, you can see the work that we are doing.

Terry Wahls, MD

And everyone who is listening. Please download Dale’s gift that will have tremendous resources for you. Dale, I love you. I love the work that you are doing. Keep up the good work. I can not wait till the next time I see you at one of our conferences.

Dale Bredesen, MD

Thank you so much, Terry. Thank you again for the invitation. Love what you are doing for all these years and congratulations. Enjoy the jog. And great to hear.