Unlock Your Mind: Combat Cognitive Decline From Lyme

Richard Horowitz, MD

My wife and I were traveling through Massachusetts. We decided to stop for a cup of coffee in a little cafe along the road. All of a sudden, how these downloads sometimes come. You get inspiration. The whole song Yes was downloaded within 2 hours of a couple of espressos in a Massachusetts cafe, where I was just laughing my brains out as the words were coming with the rhymes and everything. Then Daryl, and I met Daryl Hall at one point. We’ve been friends for a long time, and I took out my guitar and played it for him. He was laughing so hard. He said, Rick, why don’t you come into the studio and record it? I thought he just meant I would record, not that he would be singing backup for me and playing Hammond organ with T-Bone Wolk playing backup mandolin and guitar, and Daryl was doing double backup vocals. I mean, it was a tremendous amount of fun.

Dale Bredesen, MD

Yes. For anyone who hasn’t heard it, they’re in for a real treat. I think it’s fabulous. I enjoyed it. I’m glad. I’m glad you mentioned it. Great stuff. Give some information to people, and it’s something that people don’t know enough about, despite everything you’ve done—all the books you’ve written, all the papers you’ve published—it’s still not widely enough known. Of course, our interest is in cognition and cognitive decline. It’s interesting that if just a few years ago you had had a summit where you said this is a Reverse Alzheimer’s Summit, people would just have said, What are you out of your mind? Nobody reverses Alzheimer’s, but we see people getting better all the time now. Of course, especially people early on. I always talk to the physicians and say, have you ever seen anyone who truly went on prevention, asymptomatic, doing well, scoring well, and then still developed Alzheimer’s, still develop dementia while they were on prevention? No one has seen it. Yes, it may happen, but it’s not common. It’s certainly something that this disease, as we’ve all been told, is inevitable. Things are changing rapidly, in large part because of your efforts. I wanted to talk a little bit about the idea of the tick-borne illness. If you go back to the iceman when they thought when he was thawed, as I recall, he was found to have Borrelia, was he not?

Richard Horowitz, MD

That is correct. The Ötzi man who was frozen about 5,000 years ago, did find Borelli burgdorferi. That’s correct.

Dale Bredesen, MD

I thought so. My question is, to what extent should we be considering these various tick-borne illnesses, which are essentially part of the microbiome? It’s more like how you respond. To what extent are we saying, No, these are not part of the normal microbiome; these are infections?

Richard Horowitz, MD

Yes, I think in the case of Lyme disease, these are infections, not part of a normal microbiome. You’re correct, of course, that the organism has been around for ages. Babesia, the tick-borne parasite, has been around for over a million years. They found that also when they went back and looked at records from a long time ago in fossilized specimens. These are not new diseases, but the problem with Lyme disease spirochete is that it’s very similar to syphilis, and it gets into the brain. One of the major problems with Lyme disease is that now that it’s grown to 14.5% of the global population, has been exposed to this illness. It means roughly one out of seven people on the planet has been exposed to Lyme. 

Some of these people go on to develop chronic Lyme, and because it’s a spirochete-like syphilis, it causes cognitive issues. There have been approximately, at least in the last decade or so, seven or eight articles in the medical literature by Judith McCloskey from Switzerland, Eva Sapi, and Alan McDonald found that beta-amyloid is co-localizing in the brain with Borelli burgdorferi, and based on Koch’s and Hill’s postulates. There’s a relationship between borrelia and Alzheimer’s. We know that these infections—viruses, bacteria, parasites, fungi—there are a lot of infections that are causing it and driving inflammation. But my concern is with the worldwide epidemic of Lyme, to which one out of seven people has been exposed. This may be a cause of dementia and cognitive decline that people are not looking for because the tests are just not that reliable. If you don’t know how to look for it,

Dale Bredesen, MD

Exactly. That was my concern. We see, okay, thousands of people coming in saying, I’m not, I’m having cognitive problems, etc. Of course, unfortunately, the standard is that people say, this is Alzheimer’s disease. They get a tiny data set. They don’t even think about Lyme. Some published papers are saying that if you look at people with and without Lyme, there’s no difference in the likelihood of cognitive decline. Therefore, it’s not a cause. Well, wait a minute, what about when it is a cause? This is a huge issue. As you indicated, there are probably a lot of people out there who could be helped by addressing tick-borne illnesses instead of just saying you’ve got a misfolded protein and we better put you on an anti-amyloid antibody that’s going to make your brain bleed. It’s a disaster. Here’s the big question then. Someone comes to you; they’ve got cognitive decline. What can you do to say? I can tell this person that it’s not due to a tick-borne illness. In other words, what makes you comfortable saying this is not a tick-borne illness?

Richard Horowitz, MD

We published an article in the medical literature about seven years ago with researchers from the University of New Paltz researchers from the State University, of 1600 patients, we validated a Lyme questionnaire, which I call, the HMQ, The Horowitz sense questionnaire was validated in 1600 people from three medical practices. You can get this questionnaire from my website and www.cangetbetter.com. Just look under symptoms and you’ll find the questionnaire. You can download it. If someone comes in with cognitive issues, but they also have the story that I have good and bad days, my symptoms come and go. I have migratory joint pain, migratory muscle pain, and migratory nerve pain, which is tingling, numbness, stabbing, and burning sensations. 

These migratory patterns are the hallmark of Lyme, and in fact, migratory neuropathy is the only disease you’ll see where Lyme is. When people come in with these multisystemic good and bad day symptoms coming and going migratory, it’s a chronic, fatiguing musculoskeletal neuropsychiatric illness. They get sleep disorders; they can’t fall asleep. They keep waking up. As you and I both know, sleep disorders are associated with dementia. They come in, and they also say My mood changes; I’m depressed; I’m anxious. Loneliness, even now, has been associated with cognitive decline. But these people come in with this multisystemic illness. If you score high on the questionnaire, over 63, you’re two standard deviations above the mean. There’s a very high likelihood you have Lyme, and then yes, you do the testing. 

The most important thing with the test to know for people out there is that there’s a lab I use; it’s the number one lab. It’s IGeneX in California. We know that at least 16 or 17 pathogenic species of Borrelia exist. Borrelia sensu stricto—the one they discovered years ago—there’s all these cousins of Lyme disease now. If you just do a standard, ELISA, and you’re looking for all these other Borrelia species, Borrelia afzelii, and Borrelia garinii in Europe. Borrelia Valaisiana, all the ones in the South United States are in California, you’re not going to pick them up. The advantage of the IGeneX immunoblot is that it picks up at least eight of the major strains of Borrelia in the U.S. and Europe. I call it Lyme Bingo. You just have to look at the immunoblot and see if any of the five bands show up positive. If you have 23 out of a surface protein C, 31 out of a surface protein A, 34 out of a surface protein, the B. 39, or 83/93, Any one of the numbers that I just mentioned, and these are, by the way, in all my published papers and both of my books, Why Can I Get Better? How Can I Get Better? It is all in there. 

Any one of those bands in the clinical setting from an immunoblot—not a regular Western blot where you can get false positives with autoimmunity, but immunoblot recombinant DNA—means you’ve been exposed to a Borrelia species. Then, if you’ve got cognitive difficulties, you’ve got to ask yourself, Okay, is Lyme one of the factors? The other thing we’re seeing that causes a lot of cognitive problems is Bartonella. There are also over 17 species of Bartonella now that are showing tremendous cognitive decline. The problem is that most doctors don’t even know about Bartonella. They don’t even check for it. These are, I think, hidden factors that we’re going to have to look at as time goes on.

Dale Bredesen, MD

Yes, so interesting. and we certainly have seen one of the patients, for example, who had a tick bite 10 years ago, got a rash, got the ECM, and got treated, but nothing else. Then, 10 years later, he noticed things weren’t quite right with his cognition and turned out to have Babesia. As you pointed out these co-infections, well over 50% of the people who get Lyme seem to have co-infections. Do you feel that the same is true for the IGeneX approach to these other co-infections as well?

Richard Horowitz, MD

I do because the thing about IGeneX is that they have a Babesia immunoblot where they don’t just let go of the Babesia microti or Duncani; they have a Babesia FISH fluorescent in situ hybridization. It’s an RNA probe, and I find it positive with many of the patients with Babesia, but also for someone listening who says, Well, how do I know I have Babesia? It’s a malaria-like illness. If in the Lyme setting you have day sweats, night sweats, chills, sometimes shaking chills flushing air, and air hunger, I can’t catch my breath. Unexplained cough. Those are classic symptoms of Babesia, and most of these people who are co-infected with Lyme, Bartonella, etc. don’t have the classic presentations in the textbooks. Interestingly enough, the Chinese government called me up about 10 or 12 years ago and asked me to fly to Beijing because they thought they were having a Babesia outbreak but that it wasn’t like having hemolytic anemia. They didn’t have renal failure. The liver function wasn’t in any of the textbook presentations. 

They flew my wife and me over first class. We met with all of the people from their national academies. I was there for about a week or 10 days, and I brought IGeneX along. and they brought their FISH test and proved to them, yes, in fact, it was a Babesia species, not a Microti Duncani, but a different Babesia species showing up. This parasite is showing up in a lot of the Lyme patients, and they also have Bartonella immunoblot and Bartonella FISH. Again, we’re finding a lot of these Bartonella species. Can be picked up by Quest’s Lab Corps and BioReference Standard Labs, because these 17 different pathogenic species, but the FISH in this RNA test will again fluoresce green when you find it, so we used T-Labs and other labs, of course, not just IGeneX, and I use Quest and LabCorp for Standard tickborne. But it’s a great lab when you’re looking for these tickborne infections. For those of you who might be concerned that you have it.

Dale Bredesen, MD

Yes, fantastic. Do you think the amyloid plaques are essentially the gamma of Borrelia?

Richard Horowitz, MD

Well, of course, this is the big question, because we know that it has an antibacterial effect. Amyloid is being produced. The problem, and this is a hypothesis, is that I think it has to be proven, but they’re finding Lyme under biofilms. The success we’ve had with that is some combination therapy. We just published our eighth article in eight years in Microorganisms in September 2023, and we proved that these high-dose Dapsone pulses, two-week antibiotic pulses, and six days of zap zone have tremendous effects on people with cognition, fatigue, and pain. There are no more long-term antibiotics in our practice. But the problem, of course, is that Bartonella is a biofilm infection. They’re also finding it in some of these patients with dementia. When you look at the combination of viruses, of the herpes viruses and the parasites and the fungus and bacteria like Lyme spirochete, but also, well, Porphyromonas gingivalis from the teeth, chlamydia pneumonia, and even H. pylori has been showing up in some patients. 

I think it’s a mixed infectious bag. I don’t think they’re ever going to prove it’s one organism causing this. Then, JAMA years ago published that pesticides and DDT were a problem. Creating amyloid production. The best take I have on this is that it’s multifactorial. The 16-point M-since model that I’ve been developing and seeing in these 13,000 chronically ill patients, I describe as six rivers of inflammation going into an ocean of inflammation, and we know that Alzheimer’s and dementia are an inflammatory process, microglial activation, a lot of inflammation in the brain and that all of the MSDs maps are showing up in Alzheimer’s. I did; I think I sent it to you maybe a few months ago. I did research for about three months to see if every MSD factor was published in the medical literature on Alzheimer’s. Yes, it was infections. It was toxins like heavy metals, mold, and pesticides. It was a microbiome problem with Clostridium. Not enough Akkermansia species. It was mast cells and a leaky gut. It was nutritional deficiencies and sleep disorders. Those are the six rivers. Then those lead to mitochondrial dysfunction and hormone dysregulation. 

You’re dealing ultimately with all of these sources of inflammation with downstream effects,  POTS Dysautonomia, which we’re getting in the Long COVID. My concern, by the way, with these viruses like COVID, and I’m sure you must have the same, is that these people lose their sense of smell and taste, which is a hallmark of neurodegenerative diseases in the past. It’s like, is this going to be a precursor for people later on having a problem with them? I mean, this could be a massive problem. I think the model, and I know you use a similar model to the one I’ve been looking at, is going to be applicable. I don’t think in this day and age, for any of these chronic diseases, we’re looking at one cause, one disease model. We learned in medical school about Pasteur’s postulate. Koch’s postulates don’t apply to chronic diseases anymore. It’s usually multifactorial. If you agree, I mean, I think that’s where the answers, if anything, will be found, which is, like you said earlier, just don’t throw drugs at disease prevention. But also figuring out how we unravel all of these different elements causing inflammation and what downstream effects. I think that may be where some of the solutions are going to be found.

Dale Bredesen, MD

Well, yes, I think you mentioned it several years ago. The whole idea of precision medicine is understanding what the things are driving. I mean, people keep saying, Well, why do you do this multifactorial approach? What we do is simple. We ask, What’s causing the problem? Figure that out, and then we go after those things that are causing the problem. The tough part, as you mentioned earlier, is to figure out what’s causing the problem, because it’s often multiple things. When you’ve got 17 species of something that you can only test for a few of them, you’re in a tough situation. It’s interesting to me that we came to the same conclusion. We came from the test tube and looked at APP signaling in molecular biology and said, Wait a minute, all these things trigger this pathway. It came this way: You look at all these things; there are all these changes. This is an infectious, multiple-infectious problem. 

I think we came to the same conclusion. This is a thing that you are driven by; we always say that it is driven by energetic reductions and inflammatory increases, which are the two major. Of course, toxins can be in there as well because they drive those things. But the bottom line is the same. It’s not Koch’s postulates. This is not a 1-TB organism. It looks like there are multiple things. As you said, COVID is going to be a real concern both for Parkinson’s, for which there are already a few cases, and for Alzheimer’s. Unfortunately, it’s already been shown that if you’ve got COVID, your Alzheimer’s risk will increase. something we have to think about. Therefore, treatment is going to be so important, and you’ve got this interesting depth on approach that I want to get to in a second, but I want to ask you first about why mycotoxins and tick-borne illness are so commonly running together.

Richard Horowitz, MD

I think part of that has to do with climate change because a lot of people are flooding their homes. Years ago, I used to joke with Neil Nathan, a colleague of mine who’s a mold expert, and I used to say, Neil, we’re finding the mold, but it doesn’t seem like it’s playing the primary role in keeping our people ill. But I will tell you, as time has gone on, in this last article we just published in Microorganisms, 84% of our patients had up to five mycotoxins. They had aflatoxins, ochratoxin, Zearalenone, and Trichothecenes. I mean, they were loaded with these toxins, and there is a subset. It overlaps cognitive issues, fatigue, and pain because I would give them the Dapsone protocol. They’d say, Hey, I felt better, but I’m relapsing. They weren’t getting the improvements I was seeing from other people. Then I looked for mold, found it, and started using things like phosphatidylcholine, glutathione, binders like charcoal clay, and sometimes glucomannan. If they have Trichothecenes, I would be pulling out the toxins. Interestingly enough, the patients would say who was resistant to those and didn’t get the effects I wanted. Hey Doc, once I pulled the toxins out. My cognition was so much better. 

We used to do the same with heavy metals years ago. We checked everybody for mercury, lead, arsenic, and cadmium in the blood. as we’re finding quite a bit in the bloodstream or sometimes on a six-hour urine DMZ. For some of these people, we chelate the metals if it’s high in the blood, and their cognition gets better. It’s multifactorial but I think it’s the climate. I think it’s the amount of flooding that people are getting. Truthfully, the houses are not well constructed. We had a mold problem in our house because they didn’t finish the chimney properly. Five years later, we found out the floorboards underneath the house had a problem. We had to rip everything out. House construction, flooding with the climate, and of course the ticks are increasing also because the climate’s warming up these insects, reproductive abilities as the planet heats up. That’s why these tick-borne infections are about roughly half a million in the U.S. But a year or two ago. But I suspect it’s probably a lot more than that. All these chronic fatigue fibro cases are showing up. The same symptoms as chronic Lyme. Unless you know how to diagnose it, you’re missing the whole picture.

Dale Bredesen, MD

Yes. Interesting. Do you. If you’ve got someone with both of those, do you go after the usual Dapsone first and then, or do you do these concurrently?

Richard Horowitz, MD

It’s a great question. the reason I usually will do Dapsone first unless somebody comes in, let’s say, and they’re loaded with toxins and they say to me, Doc, I’m a multiple chemically sensitive patient, I walk into an apartment or house and I get sick as a dog, and then you try giving them an antibiotic and they get sick. It’s like, I need to work on your microbiome. I need to work on your detox pathways first and unload you with infrared saunas and the rest to get it out. But the reason I usually do the Dapsone first is because the Dapsone protocol is nine weeks, and then you stop. Then afterward, if you have BART, it’s two weeks’ pulses. If you only have Lyme, you can indeed go into full long-term remission. 

My wife has been in remission for four and a half years since she did this Dapsone protocol a couple of years ago, and she only did a month of the Double Dapsone. I mean, she had chronic Lyme for 20 or 25 years, but the reason she is now, well, she had every message factor that I had to address. She had POTS Dysautonomia. Her adrenals were low, she wasn’t sleeping properly, and she had histamine mast cell disorder with migraines because she was eating the wrong thing. It’s important to think, well, let me do the Dapsone first and knock the low down because then if I do clear the Lyme or at least knock down the load, what’s going to happen is I can go for months clearing out the mold, and then if they need another pulse of Dapsone, it’s a two-week antibiotic pulse. It’s like I put my foot on the gas with the Dapsone, take it off, and do the mold for a couple of months, then look and see. What do I think is the Lyme part? Put the foot on the gas to let the pulse go back to the mold. I’m going back and forth, detoxing the patients, and treating the infections. It seems to work quite well for our population.

Dale Bredesen, MD

Yes, very interesting. Dapsone is an interesting choice. I wanted to spend a fair amount of time talking to you about your protocol because it’s been so interesting. Essentially like an anti-nutrient. Yet, yes, these organisms are highly sensitive to it, and you do get away with it pretty well with humans. Here’s the question, then. When you’re doing this, as you pointed out, you are causing some degree of anemia. One of our big concerns, of course, is a reduction in energetic support for the brain. The question is, I mean, it sounds like what you’re saying is that it’s worth it, that some degree of anemia is not going to compromise them nearly as much as you’re going to be helping them by giving them the Dapsone. If you could talk a little bit about your current protocol, how much depth would you give? How long? What do you look for if someone crashes in terms of their hemoglobin? Or do you see that? What things do you give with it? Do you ever give leucovorin rescue with it? Or what sorts of things do you do?

Richard Horowitz, MD

The side effects of Dapsone. When I talk to people about it, I describe it as Do No H.A.R.M. H- is Herxheimer reaction because, when you’re killing off the bacteria, you’re going to get a big cytokine release. A – is for anemia. It’s folic acid-induced anemia. Just as you mentioned, we use massive doses of folic acid and leucovorin. We use 100 milligrams of leucovorin twice a day, which is what we use. Like if you had methotrexate toxicity in rheumatoid arthritis. With that, I use 100. Well, yes, it’s a 25; it’s 15,000 mc each. It’s about 60,000 micrograms twice a day of l-methyl folate. I’m using methylated folate. I’m using over 300 milligrams of different folic acids to stop the Dapsone anemia. We use methyl B12 in case we’ve occasionally seen a few people with it with a lot of acids; they’re B12 deficient; they didn’t know it; and even iron in the women who are still menstruating. 

We’re supporting the pathway of how you make red cells. R – which is rashes, but even people who have rashes from things like Bactrim, sulfamethoxazole, and trimethoprim can usually take Dapsone. The other side effect you have to watch for is hemoglobin anemia. This is where you don’t carry oxygen well in the blood. Interestingly enough, methylene blue, which we now get compounded, they’re used for mitochondrial regeneration. It’s being used in Alzheimer’s. In these trials. The interesting part is that methylene blue reverses the problem with the methemoglobin but also helps the mitochondria. We also reverse methemoglobin and use mitochondrial protocols like NADH, so we’re using NT Factor, Inara, CoQ10, MitoCORE, and MitoNR, and are with Nicotinamide riboside. We’re using all of these different things to support mitochondrial function during and after the protocol because we know that any free radical oxidative stress can damage mitochondria. The thing about anemia is that you have to watch it. What we’re doing, the Dapsone, is usually not bad until you get past 100 milligrams. 

The way I designed the protocol is that the double dose of Dapsone is an eight-week protocol. If you only have chronic Lyme, it’s four days of high-dose Dapsone in 400. if you have BART, it’s six days of high dose. We watch the anemia weekly and in the second month, and when we’re giving all this amount of folic acid, we keep upping the methylene blue gradually so you don’t get serotonin syndrome and problems with it. We keep people on low-histamine diets because you can also have problems with raising blood pressure with methylene blue. You have to be off all your psych meds in narcotics when you do this drug. But it’s protecting people and helping people. Because we’re using glutathione on an alpha lipoic acid, which is both water-soluble and fat-soluble, getting up into the brain, we are protecting against free radical stress by blocking in Kappa B, one of the major ways you get inflammation with alpha lipoic acid, and NAC glute stimulating the inner F2 pathway using sulforaphane glucosinolates Broccoli, seed extract, resveratrol, green tea, and Tumeric Cucurmin, which has been shown to help in cognitive dysfunction. 

Low-dose melatonin, a milligram to block, and NLRP3 inflammasomes are associated again with Alzheimer’s and Dapsone. interestingly enough, blocks, NLRP-3 inflammasomes, and methylene blue also degrade Tau proteins in the brain. When I started looking at Alzheimer’s, looked at Dapsone, and did the research, I realized tetracyclines and rifampin were affecting amyloid, methylene blue was affecting Tau proteins, and Dapsone was affecting amyloid deposition, and it was like they’d published this stuff in the literature, having nothing to do with the Lyme protocol, which is why maybe one day you and I, I would love to do this together with you, get a group of Alzheimer’s patients, give them the Dapsone protocol, and do the MSD’s map and then take a look and see what we got. 

But I’ve always wondered whether low-dose naltrexone with Dapsone and a little melatonin might be a prophylactic to block the NLRP-3 inflammasomes and get some antioxidants because they had a double-blind placebo-controlled trial in Korea in 201 patients who might have a cognitive impairment, and downstream versus cognitive impairment they did was over 8600 leprosy patients could just get someone for 15 years and the Alzheimer’s rates were minimal. It was like five or six times higher when they didn’t take that. The question is, was that Dapsone hitting the lime in Alzheimer’s, or was that just stopping inflammation as a neuro-inflammasome inhibitor? Stopping inflammation in the brain or both.  We just don’t know at this point.

Dale Bredesen, MD

Did you see the article? It just came out yesterday claiming that when you fast, you increase transiently arachidonic acid. that leads to an inhibition of the NLRP3 inflammasome, the opposite of what you would expect. Presumably, it is sending it to a different pathway, but it is very interesting. Of course, arachidonic acid has been shown to have some neuroprotective effects in the past, but it is also something that we typically think of as pro-inflammatory. Yes, it has this interesting anti-inflammatory and LRP-3 inflammasome effect.

Richard Horowitz, MD

I mean, you think it’s mostly like, I mean, we know that sugar and insulin resistance are big factors driving some of that; do you think it’s maybe related to that?

Dale Bredesen, MD

It could be yes, I mean, I guess they need to do a little more work on where and what signaling is happening. Because my guess is you’re changing the typical signaling of the arachidonic acid. But we know we’ll see more work that would be helpful. Everyone agrees that fasting can be helpful for inflammation.

Richard Horowitz, MD

By the way, for anyone interested in the Dapsone protocol, it would take me a long time to explain all the details. The entire protocol is written in it, and you can just do a PubMed search. Look up, Horowitz, microorganisms with the Journal September 2023. Just look up Dapsone. The entire protocol for how to do it. All the nutritional supplements, all the drugs, when to add them, and when do you do an EKG to rule out possible prolongation? Everything is in that article, so any doctor can pick this up and do this for their patients. I will tell you, I’m amazed. Day by day, people are telling me how much help they’re getting from this protocol. 

I just think what’s going to be interesting in the future is the applicability of Alzheimer’s, because we don’t know how many spirochetes it’s published. But there’s a difference between association and causation. They’ve shown some causation, but we just don’t know. I think the Alzheimer’s rates they said are about doubling between 2020 and 2040. There are 46.5 million Americans with preclinical dementia. It’s like, Why don’t people know that number and go? We better be doing something. Looking at your protocol for reversing Alzheimer’s,? Looking at these maps, the MSD map that I’m looking at, it’s like that is a dangerous signal that I don’t think we’re paying enough attention to.

Dale Bredesen, MD

Yes. One of the interesting things to me there is that we have, here’s an approach we have. We started back in 2011, 2012, and okay, this helps so many people. But then there’s this group that doesn’t help. That’s what led us to Mycotoxins. What I’m thinking is that it may be that, look, we need that some of the ones that are currently not doing well are going to do much better in the Dapsone. Thank you for the reference. I love to make all of these discussions very actionable. I think it would behoove us all to look further at your Dapsone protocol and look at, okay, what percentage of people coming in with cognitive decline would benefit from your protocol?

Richard Horowitz, MD

I think the easiest way, again, is you just go back to the nine IGeneX ImmunoBlots, which, by the way, are covered by Medicare completely. But even if that was the only test you ever did, and let’s say you had mild, moderate, or severe cognitive impairment, I’m not sure if it’s Lyme. I have some aches and pains, but as I’m getting older, you don’t know. Just do the IgG Immunoblot and play Lyme bingo, as we explained earlier. Any one of those bands there would say, the Dapsone protocol may indeed be something that I should be discussing with my doctor because it is a key marker that there had to be a Borrelia species that got into your body that’s causing the problem.

Dale Bredesen, MD

It sounds like, There are FISH for all of these. Which ones are there? There’s FISH for Bartonella, and I assume for Borrelia as well.

Richard Horowitz, MD

No, it’s mostly Borelli; it’s mostly PCR. They’ve got no good FISH yet, although T-Labs does have a FISH test for it, not IGeneX. They do. We do use T-Labs also, but it’s mostly Bartonella and Babesia. They’ve got the FISH testing, and I find the FISH testing and the RNA much easier to find than trying to do PCR analysis. But there are also great labs like Galaxy Labs, which does direct droplet PCR. I’ll check all these Bartonella species. Vibrant Laboratories will check six different Bartonella species. A lot of the functional medicine doctors use Vibrant and T-Labs, and MDL laboratories in New Jersey will do some of it. In the IGeneX,  T-lab, and even ArminLabs in Germany will do T-cell assays. You can use T-cell assays to look at exposure. There are a lot of ways to look at it. But there’s both direct testing of antibodies, and I’m sorry, direct testing like PCR FISH, and then indirect testing like antibody testing.

Dale Bredesen, MD

What happened several years ago, there was a urinary test with urinary PCR, supposedly for tick-borne species. They would tell you a lot of times, it’s got a deletion in it. Either way, the product isn’t what we expect it to be, but it’s still positive. It never went anywhere. What happened with that?

Richard Horowitz, MD

Yes, there were questions about it. I mean, they still have one with the urine multiplex that I IGeneX, but the nano trap is the one that I think is being used more often. This is, yes, a good test also. I can’t get it in New York, but if you want to see if you have Lyme, the nano trap test is N-A-N-O Trap. They look for 31 ASP, an antigen in the urine. This is a direct detection test instead of the DNA, PCR, and RNA FISH that we’ve been discussing. This is, yes, a good urine test if you want to see it. It has pretty good sensitivity and specificity. 

Yes, there’s politics. I don’t need to probably tell you anyone out there who follows Lyme. I think politics had something to do with this because IGeneX has been one of the greatest tabs on, first in the field, for a long time. But I used it years ago during their It was called Looe to Lyme Regis antigen test. We did see it showed up more positively in women around their cycle because when the estrogen goes down they produce more spirochetes. You would find it more often also you can use biofilm agents to open up the biofilms and then do PCR FISH because these organisms are under biofilms. There are lots of ways to try to increase the sensitivity of the testing. But generally, if we use a range of these labs, you’ll find them if you look hard enough.

Dale Bredesen, MD

Yes. With the Nanotrap, how many of the different species does that pick up?

Richard Horowitz, MD

That’s a good question. I’m not sure, but I know that it picks up the OspA. The OspA is common in all the Borrelia species that I know of. If you were talking about Afzelii in Europe, which causes a skin rash called Acrodermatitis Chronica Atrophicans, is the equivalent of our EM rash here. They have an OspA. It’s the same thing as STARI in the Midwest. In the southern tick-associated rash-like illness, there is OspA. I’m pretty sure the OspA, the 31 is common to all the Borrelia. and that’s why the ImmnunoBlot works because if you do a Western blot, the 31 can be falsely positive for Epstein-Barr or from an autoimmune illness like lupus or something else. Whereas if you do an ImmunoBlot, it’s recombinant DNA. There are no false positives. The 31, the OspA you’re talking about, you’d only want to do it on an ImmunoBlot or a Nanotrap if you were going to try and prove that it is related to Borrelia.

Dale Bredesen, MD

Exactly. What then? Let’s assume that Dapsone is going to be an important part of the armamentarium going forward for people with cognitive decline, as it certainly sounds like it’s got tremendous promise. Of course, we’re always interested in how we get better results and how we get more people to get better. Where would you say, Please be careful; don’t use it with these people? Like, if you’re 95, if you’re frail, or if you’re anemic, one of the people you would say, but don’t use it here.

Richard Horowitz, MD

Yes, there are certain contraindications to Dapsone. First of all, you’re not supposed to have glucose-6 phosphate dehydrogenase deficiency. If you aren’t G6PD deficient, you can get an increase in hemolytic anemia. The anemia will be worse. Now, I will tell you, there was one patient in my practice who was extremely ill. He was G6PD deficient, but his hemoglobin started at about 15 and a half. 16: We gave him 25 Dapsone and looked at 50 of them. He got through the whole protocol. Believe it or not, it had no problems and is now in remission. But that is one patient in 13,000 I’ve treated; everyone else has G6PD, but this one guy was so sick and his hemoglobin was so high. I said, Listen, we’re going to follow you carefully, but I would not suggest to anyone out there listening not give this drug to anyone who is G6PD deficient. That’s number one. 

For women, it gets trickier because men’s hemoglobin is higher. You’d like a woman’s hemoglobin to be at least over 13; if they’re iron deficient, wait to get their iron levels up or their B12 levels up before you start Dapsone. Certainly, you’ve got to be careful with people who have underlying medical conditions, like the elderly, congestive heart failure, or stroke. I mean, with any serious medical illness, you’ve got to be careful. But have I used this protocol with women and men who are 80 years old? I have. Now the beauty of the way we keep tweaking the protocol, I just had a woman, and she’s agreeing to do what you want to be done in Zoom interviews very shortly. She’s a well-known writer. She could not; she had kids. She’s working at Yale University. She could not do the full Dapsone. I said, Listen, do a two-week Dapsone pulse like I use after people do the initial double dose; just use six days of high-dose Dapsone because she was Bartonella FISH-positive. 

I spoke to her yesterday. She said, I got to tell you, Dr. H., I can’t believe the improvement. My cognition is better, and my energy is better. Usually, every time I get COVID, it is the third time she crashes. She said I was barely ill, and that’s because we knocked the load of the organisms down. Now we didn’t knock it out completely. But one of the studies I plan on doing is a double-blind, randomized, controlled, multicenter style, hopefully, later this year on Dapsone, because I’ve got to prove to the world that I think I’ve discovered that if it’s not the cure, it’s at least lowering the load of these organisms by 99 point something percent. But interestingly enough, Tulane research was published several months ago in the animal model of mice. That Rifampin and Dapsone combined eliminated Borrelia in the animal model. We may be eliminating it with a real cure. I suspect in some cases it may happen. Others were probably lowering the load so far that the immune system could handle it, as long as they didn’t have immunosuppressive molecular toxins like Leo toxins. 

A lot of my lying patients, by the way, are immunosuppressed. In the immune system, they have low IgGs and low subclasses. You have to be careful. Natural killer cells can be low. You’ve got to check on these people for it. But if I could do a four-arm study, one of the arms of the study would be 50 people. The way I do the Dapsone, another arm with a placebo, everything’s the same. Just no Dapsone on placebo, another arm plaque, or minnow control group, but another group. Just two-week Dapsone pulses. It’s only six days in Dapsone every two months, and you follow this group for a year. If I can get $6 or $7 million from the Lyme Foundation, that would be the study I would like to do. Then I’ll come back to you. Dale and say, Hey, these are the results. Maybe we could look at how we could do this for some of the dementia patients and see what we’ve got, especially if any of the bands on the ImmunoBlot are positive and they have migratory pain scoring high on the HMQ.

Dale Bredesen, MD

Yes, it’s a great point, and we always hear, well, but just this one band, we don’t think it’s positive, etc. We hear this all the time, and I do wonder how many. It looks like we’re very interested in the various contributors. As you said earlier, it’s amazing how many contributors there can be. It is mycotoxins, it is heavy metal exposure, and it is various HSV and HHV-6A, just go down the list. I guess that you’re going to be an incredibly common and very important contributor. These various tick-borne illnesses, begin with Borrelia but do not end with Borrelia. That is fascinating. Well, this is just fascinating. I appreciate your mentioning the article so that everyone can understand your protocol. This is helpful. Now, you were saying when we talked before, this was several months ago, that you are doing some training and recruiting, having many people who are trained and following your protocol. What’s the current status of that?

Richard Horowitz, MD

Every year for the last, I don’t know, maybe seven or eight years, I’ve been doing doctor training once a year on the slide set from the prior year, and it takes about a month. You probably do this too. I have folders on my desktop at any time. When a new article comes out of the last training, I stick it in the folder, whether it’s Long-Covid, Bartonella, or whatever. Every August, I’ve usually been doing this training. In the last training we did in August 2023, I think we trained about 70–75 doctors. We’ve trained several hundred doctors at this point on the Dapsone protocol. I’m trying to get the word out only because I’ve been doing this now for close to 40 years in clinical medicine. This is the most effective. It’s all generic medications that are oral. There are no I.V. medications here. It’s a very highly effective protocol. 

Believe me, I have tried everything under the sun. It’s not like other persistent drugs, like disulfiram. Antabuse doesn’t have any effects. We’ve used it. It does help some people. But you can’t give chronic antibiotics to these people because, first of all, you don’t want to ruin the microbiome of the gut. You don’t want people to get c-death. We’re loading them with probiotics. But now they’re showing that these biofilms—these most chronic infections in the body—whether it’s otitis, media, sinusitis, prostatitis, whatever—are biofilm infections. They’ve now shown that if you post the antibiotics and open up the biofilms, it’s indeed much more effective in lowering the load of these bugs. The energy is going to shift as the years go forward in the medical literature, no more. We didn’t have any answers before, and a lot of my Lyme doctor friends do use long-term. I don’t use any long-term antibiotics anymore. This is all pulse therapy. The longest antibiotics are nine weeks for Dapsone. 

But since this woman just came back yesterday and said, I didn’t even do the initial Dapsone. 

What her result was? It turns out that the higher the dose of the Dapsone pulsed, the more effective the Dapsone is. Maybe I don’t even need nine weeks of Dapsone. Maybe it’s two pulses six or eight times, and you clear the organism. We’ve got research to do, but it’s very exciting and gives a lot of hope to the Lyme community. But, for Alzheimer’s dementia patients, knowing that 14.5% of the global population has been exposed to Lyme disease and knowing mold is showing up in people, you’ve got to ask yourself: This has got to be a contributing factor in a certain percentage of these dementia cases that were missing. I mean, somebody high up NIH or whatever, somebody has got to take your model. My model. Put them together and go. Listen, we’ve got to change the model of chronic disease medicine that we’re using here because 87% of the health care costs and 70% of the deaths in the United States are caused by chronic disease. We don’t have an effective model. But you and I have been working with these multifactorial models, saying, Hey, this is the only thing that seems to make sense.

Dale Bredesen, MD

Yes. They’re going to rename Dapsone, Horowitz’s mice I think. That’s a great way to go. The last thing would be, and so is there any advantage to intranasal introduction to this, or is it because this is a systemic illness that you don’t want to just be getting the brain? Certainly intranasal peptides and intranasal trophic factors. These have such great promise. What about intranasal Dapsone?

Richard Horowitz, MD

The only reason I mean is that it’s possible it would work great, but the only reason you don’t need to do it is one of the great characteristics of Dapsone. By the way, I think I probably pissed off some of the university researchers because I didn’t go through 7,000 FDA drugs to see how I could repurpose a drug. What I did was when John Hopkins, seven or eight years ago, said, Hey, Lyme is a persistent bacteria, meaning not that it doesn’t persist, but that I knew it persisted. But persistent bacteria like TB leprosy. I said, Hold on. When I was at Mount Sinai in New York doing HIV, I was seeing MIA mycobacterium and, interestingly, TB. I said I use the I and H rifampin isoniazid pyrazinamide all the time. I said, Hold on, let me look at the TB drugs. 

I looked at Dapsone, and one of the first characteristics was fabulous penetration into the central nervous system, anti-inflammatory, anti-excitotoxic. If you’ve got too much glutamate running around in your neurological system and your synapses, the Dapsones block it. It has all these effects. They use it for traumatic brain injuries. It increases the amount of flow in your brain. I mean, they’ve shown that Dapsone has fabulous CNS penetration, it’s antiparasitic, antimalarial. It helps autoimmune diseases, which you see in Long-Covid, which you see in Lyme disease It checks off all the boxes that persist in your drug: autoimmunity, anti-parasite, and good CNS penetration. I don’t find, truthfully; I have not had to use any IV drugs ever since Dapsone has been in my armamentarium. 

The only time I used it was when a patient in the last several years came in with Bell’s palsy after being on doxycycline, and I said, Okay, no choice. I got to use IV dox7, and eventually, this patient cleared. This was, by the way, Borelli mayonii. It was a different Borrelia species from the Midwest that caused a macular popula rash, not the usual standard. By the way, half of the rashes are not bull’s-eyes. They’re like solid, spreading rashes. But this was Borelli mayonii, I had to give them Rosetine. That’s the last time, by the way. I’ve had to use it because Dapsone penetration into the CNS is great. That’s why I believe in Alzheimer’s prevention in the future. 

What I would love to see in a Framingham-type study. If 50 of MiniONE and 25 Dapsone, a little low-dose naltrexone, and a milligram of melatonin for a bunch of people. You could do it like they did the nurses’ study. then take a look at the MSD factors, look at your model the way you did it, and then just see by stopping inflammation in the brain and blocking in NLRP3 inflammasomes and blocking enough Kappa B and stimulating and NRF2 to work all these inflammatory pathways because it’s ultimately an inflammatory illness. I think you may be able to prevent some of what we’re seeing, but we need a Framingham study to follow people for decades to do this. I don’t know if anyone is doing this now because I’m not aware that anybody is.

Dale Bredesen, MD

Not aware of either. I think people have Dapsone, you always think of it as leprosy, and so they’re like, Wait, what are you talking about? I know I think getting your word out could help all of us get better outcomes for people with cognitive decline. 

This has been fantastic. It was just an honor and a pleasure. It’s always great to talk to you, Richard. Thank you so much. Thanks for the great work you’re doing and for training others to do the work. I look forward. I’m going to stop the recording here, and I look forward to talking to you again. as you and I talked about before.