You Can Lower Your Alzheimer’s Risk, Even With the APOE4 Gene, with Dr. Peter McCullough

Show Notes

Both of Dr. Peter McCullough’s parents lived with Alzheimer’s. His father died with it. His mother has advanced disease right now. So when he says there is no medical topic closer to his heart, he means it.

This episode is a little different. Instead of hosting, Dr. Ravi Kumar was the guest, sitting down with Dr. McCullough on the McCullough Report to talk about Alzheimer’s and cognitive decline. It turned into one of Ravi’s favorite conversations on the subject, so he brought it home to share here.

They start with the scale of the problem, and the numbers are sobering. By age 80, roughly half of people have some cognitive decline. By 90 it is about 75%. By 100 it is 85%, and the vast majority of those brains would show amyloid plaque on a PET scan. That raises the question the whole field is wrestling with: is this normative aging or pathological aging? Dr. Kumar explains that everyone makes amyloid from the day they are born, that the problematic fragment is beta amyloid, and that decades of research aimed at clearing it has largely been a flop. We got good at removing the plaque. People did not get better.

From there the conversation turns to where the real evidence lives, which is prevention. Dr. Kumar walks through the modifiable risk factors that outperform every approved drug we have. Metabolic health comes first, because the brain is a three pound organ that consumes 20% of your body’s energy, and when insulin resistance sets in, neurons and glial cells cannot get the fuel they need. The housekeeping fails. Plaques and tangles stop getting cleared. Synapses stop getting maintained.

Then sleep, and this is one of the most striking parts of the episode. Midway through Dr. Kumar’s residency, researchers discovered the glymphatic system, a lymphatic drainage network in the brain nobody knew existed. At night, pulsing blood vessels drive cerebrospinal fluid through the perivascular spaces and flush out toxins, including beta amyloid. A single night of sleep deprivation raises beta amyloid in the brain by roughly 5%. Which is exactly why alcohol, a neurotoxin that fractures sleep architecture, does so much damage over a lifetime.

They also cover hearing loss, one of the largest and most fixable dementia risk factors, worth up to a 50 to 60% increase in risk when it goes uncorrected. Then APOE4: what the protein actually does, why the e4 variant holds onto the LDL receptor and starves cells of the lipid they need, and why Dr. McCullough’s own genotype made him rethink his routine. But the punchline is Nigeria, where APOE4 rates are very high and Alzheimer’s is almost absent among people eating a traditional diet. Genes load the gun. Lifestyle decides everything after that.

The back half is practical: the new blood tests that can diagnose Alzheimer’s before symptoms appear and have now surpassed PET scanning, what the approved drugs actually do (mostly symptomatic), the real bleeding risk with the anti amyloid antibodies, and the supplements worth knowing about. Dr. Kumar also carries an APOE4 variant himself, which is part of why this one matters to him.

Episode Resources

The McCullough Report
Dr. Ravi Kumar on LinkedIn
Dr. Ravi Kumar’s Website

In this episode, you will discover:

How common cognitive decline really becomes: 50% by age 80, about 75% by 90, and 85% by 100, and why so much of it never gets formally diagnosed
Why everyone makes amyloid: Amyloid precursor protein is made from birth, and only one cleavage product, beta amyloid, is the troublemaker
Why clearing the plaque has not worked: We learned to get amyloid out of the brain, and people did not get better, which says something important about what amyloid actually is
Cognitive super agers: The people who reach 90 or 100 fully intact, and why studying success may teach us more than studying failure
Why prevention is the honest goal: Alzheimer’s has never spontaneously reversed, and the strongest evidence we have is for stopping it before it starts
The single biggest lever, metabolic health: The brain burns 20% of your energy, and insulin resistance leaves it in an energy crisis that shuts down clearance and synapse maintenance
Walk every day, and walk outside: Sunlight, vitamin D, circadian rhythm, better indoor air, and the psychological effect of watching the world go past you
Resistance training as a glucose sink: Why muscle mass protects your brain by keeping you insulin sensitive
The glymphatic system: The brain’s drainage network, discovered only in the last 15 years, that flushes beta amyloid out while you sleep
One bad night matters: A single night of sleep deprivation raises brain beta amyloid by about 5%
Alcohol, plainly: A neurotoxin that fractures sleep architecture, drives atrial fibrillation and stroke risk, and compounds year over year
Hearing loss, the fixable one: Up to a 50 to 60% increase in dementia risk when left uncorrected, and the two theories for why
What APOE actually does: How the lipoprotein shuttles cholesterol from astrocytes to neurons, and why the e4 variant jams the LDL receptor
The genotype numbers: e3/e3 baseline risk, what e3/e4 adds, and why e4/e4 carries a lifetime risk around 65%
The Nigeria paradox: Very high APOE4 rates, almost no Alzheimer’s, and what that proves about genes versus lifestyle
The new blood tests: p-tau 217 and the amyloid beta 42/40 ratio, roughly 96% specificity, better than PET, and no spinal tap needed
What the drugs really do: Cholinesterase inhibitors and memantine treat symptoms, not the disease
The bleeding risk nobody mentions: Why clearing amyloid out of vessel walls causes ARIA, and why APOE4 carriers are at highest risk
Supplements worth knowing: Vitamin D above 30 ng/mL, magnesium L-threonate for the brain, and CoQ10, especially if you take a statin
The statin story is more nuanced than the headlines: 31 randomized trials, and the direction may surprise you

Key Takeaways

Alzheimer’s is not a fixed fate written by your genes. Even with a higher risk variant like APOE4, the lifestyle you build on top of that genetics does an enormous amount to decide where you end up
Most of what protects your brain costs nothing: walking daily, ideally outside in the sunlight, protecting your sleep, keeping your metabolic health in check, resistance training, skipping alcohol, and correcting hearing loss
Metabolic health is the biggest single modifiable lever. The brain uses 20% of your body’s energy, and insulin resistance starves it, which breaks the clearance of plaques and tangles and the maintenance of synapses
Deep sleep is when the glymphatic system flushes beta amyloid out of the brain. One night of poor sleep raises brain amyloid by about 5%, and alcohol fractures the sleep architecture that makes the flush possible
Uncorrected hearing loss is one of the largest modifiable dementia risk factors, worth up to a 50 to 60% increase, and it is fixable with today’s technology
Nigerians have very high rates of APOE4 and almost no Alzheimer’s among those eating a traditional diet, which is the clearest evidence that the variant alone does not decide the outcome
Blood tests measuring p-tau 217 now detect the disease process before symptoms appear, with roughly 96% specificity, and they have surpassed PET scanning. That turns prevention into something you can act on early
The approved drugs are largely symptomatic. The anti amyloid monoclonal antibodies do clear plaque, but they also destabilize amyloid laden vessel walls, causing swelling and hemorrhage in as many as one in four patients, with APOE4 carriers at the highest risk
Vascular health and brain health are the same conversation. Small vessel disease produces lacunar infarcts and cognitive decline, which is why cardiovascular risk factor control matters for the brain

About the guest host

Dr. Peter McCullough is an internist and cardiologist and the host of the McCullough Report. Both of his parents lived with Alzheimer’s disease, which makes cognitive decline one of the medical topics closest to his heart. This episode originally aired on his program and is shared here with permission.

Disclaimer: Dr. McCullough and Dr. Kumar are doctors, but they are not your doctor. This show is for informational purposes only and is not a substitute for medical advice. Take what you learn here, ask better questions, and work with your own doctor. This show is also separate from Dr. Kumar’s role as assistant professor at UNC.

Transcript

[00:00 –> 00:43] Dr. Ravi Kumar: Welcome back to the Dr Kumar Discovery. I’m Dr. Ravi Kumar, and today’s episode is a little different. This one isn’t me in the host chair. I was a guest this time sitting down with Dr. McCullough on the McCullough Report to talk about Alzheimer’s. We discussed a whole range of things, like how common cognitive decline really becomes as we age, the new blood tests that catch it before symptoms ever show up, and the diet and lifestyle factors that actually move the needle on prevention. Peter brought his own family story into it, and it turned into one of my favorite conversations on this subject. So I decided to bring it home and share it here. So before we get into it, I wanted to ask you for one thing. About 100,000 people tune into the Dr Kumar Discovery.

[00:43 –> 01:44] Dr. Ravi Kumar: Every month, but only a fraction of you are subscribed. If you’re finding value in this conversation, hitting subscribe on YouTube or following on Apple Podcasts or Spotify takes about three seconds, and it’s the single biggest thing that helps this show grow and reach more people. And a review on Apple Podcasts is a real gift, so if you have access to Apple Podcasts and you’re feeling generous, please leave me a review. Also, quick disclaimer, Dr. McCullough and I are doctors, but we’re not your doctors. This show is for informational purposes only. Take what you learn here, ask better questions, and work with your own doctor. And just to be clear, this show is also separate from my role as assistant professor at UNC. All right, let’s get into it. My name is Dr. Ravi Kumar. I’m a neurosurgeon in search of causes of human illness and the solutions that help us heal and thrive. I want you to join me on a journey of discovery as I turn over every stone in search of the roots of disease and the mysteries of our resilience.

[01:45 –> 01:59] Dr. Ravi Kumar: The human body is a mysterious and miraculous machine with an amazing ability to self heal. Let us question everything and discover our true potentials. Welcome to the Dr Kumar Discovery.

[02:02 –> 02:42] Dr. Peter McCullough: Let’s get real. Let’s get loud on America Loud Talk News. This is McCullough Report and focal point substack. And for triple exposure, we are going to rebroadcast on Dr. Kumar’s Discovery Channel because we have in the studio for the first time Dr. Kumar, and he’s going to introduce himself. We’re going to go over a complicated topic, but a topic that is of interest to many of you out there. You know, both of my parents have Alzheimer’s disease. My dad died with it. My mom has advanced Alzheimer’s disease right now. So there’s probably no medical topic that’s closer to my heart. Dr. Kumar, welcome to the program.

[02:42 –> 02:44] Dr. Ravi Kumar: Yeah. Thanks for having me, Peter.

[02:45 –> 03:03] Dr. Peter McCullough: Well, I tell you, you came highly recommended from another guest, Todd Born, a naturopathic expert in attention deficit hyperactivity disorder. Tell us about your background, which I think is a little different And, you know, where you’re practicing now.

[03:03 –> 03:20] Dr. Ravi Kumar: I’m practicing in North Carolina. I’m an assistant professor at UNC in neurosurgery. I did my training at Mayo Clinic. And I’m I’m a board certified neurosurgeon, but I have a podcast. And that’s I interviewed Todd Born as well on my podcast, and he connected the two of us. Yeah.

[03:20 –> 03:24] Dr. Peter McCullough: Wow. So did you, also go to Mayo medical school at Mayo?

[03:24 –> 03:29] Dr. Ravi Kumar: Or I went to medical school at Texas A and M, which I heard you are Yeah. You’ve been connected with as well.

[03:30 –> 03:40] Dr. Peter McCullough: Yeah. Oh, so so medical school at A and M and then off to Mayo Clinic. Mayo Clinic for neurosurgery. And then you did you do fellowships beyond that?

[03:40 –> 03:55] Dr. Ravi Kumar: No. And, you know, it was a seven year residency, and I was I was I was ready to move on. So no. I I’ve been in clinical practice since then with a couple interesting adventures in the in the meantime. But, yeah, I’m I’m full time basically full time practice now.

[03:55 –> 03:59] Dr. Peter McCullough: And do you do any skull based surgery? Is it or was it all spinal?

[03:59 –> 04:28] Dr. Ravi Kumar: No. I do I do both brain surgery and spine surgery. I Mhmm. Skull based surgery is very specific, and I’ve done a lot of it. I don’t do it anymore because of the the clinical environment I operate in. With skull base surgery, you have to it’s very high risk. You’re going at the base of the skull around all these very important structures. And Mhmm. You need a ton of clinical resources to do that surgery safely. And I I’m just not in a place where where that’s appropriate. So I don’t do it anymore.

[04:28 –> 05:07] Dr. Peter McCullough: Yeah. Well, you know, I think a lot of people don’t know this, but when doctors go through training, one of the difficult things we do is we figure out what we don’t do in our clinical practice. So I was trained in trained in angiography and actually coronary intervention, although at the time I didn’t do extra training in that pacemaker insertion, what have you. And I ultimately narrowed it down to basically, I do both internal medicine and cardiovascular disease. But, you know, you had a seven year residency, I’m sure four years of college, four years of medical school. So that’s eight plus seven. So that puts you at fifteen years right there. Fifteen years. Yep.

[05:08 –> 05:31] Dr. Ravi Kumar: It’s a long time. And, you know, you have to definitely be all in for that period of time. You know, I love neurosurgery, but I do love education as well. So I’ve been basically kind of putting my foot in both worlds for now doing clinical neurosurgery and also educating on the side, which is, you know, what I do with my podcast.

[05:31 –> 05:51] Dr. Peter McCullough: Well, as a neurosurgeon, you have to be able to do a very good neurologic exam, and you have to be to be able to assess cognitive function. So you, like me, I’m sure must be sizing up kind of the enormity of of cognitive dysfunction as people age.

[05:52 –> 06:19] Dr. Ravi Kumar: Yeah. So, you know, there’s no I would say this. There’s no surgery for neurodegenerative disease, dementia, Alzheimer’s. It is but it is something that affects a lot of people going into older age. And, you know, it’s hard to put a number on how many people actually become develop Alzheimer’s or mild cognitive impairment because it’s it’s very underdiagnosed, honestly. But it is it is

[06:21 –> 07:14] Dr. Peter McCullough: Ravi, this is a great, great application of AI. So I’ve I finished with a patient, and I had some time just before we came on. So these are the numbers that AI assemble. By age 80, 50% of people have cognitive decline. Half of those have a formal diagnosis of Alzheimer’s. By 90, a lot of us want to make it to 90. My wife’s mother lives with us. She’s 93. At age 90, it’s 75% have cognitive decline. Know, somewhere around 40% of Alzheimer’s disease. And at age 100, 85% have cognitive decline. The vast majority, if they underwent a PET scan, would actually have amyloid plaque in the brain. Yeah. So the question is, is this normative aging, or is this pathological aging?

[07:15 –> 08:20] Dr. Ravi Kumar: Yeah. Well, that that’s an open question, honestly, because we haven’t ever been in this point in human history where people routinely live this old. Yeah. But I would say this, amyloid is made by everybody. Even even, you know, from the day you’re born until the day you die, you’re making a protein called amyloid precursor protein or APP. And that is a, basically, a cell surface protein in the neurons in your brain that gets cleaved, and it makes a number of different types of amyloid proteins. The one that’s problematic is beta amyloid, And that’s the amyloid protein that accumulates and actually aggregates into these plaques that is associated with Alzheimer’s. And it’s been the focus of all the research. How do if Alzheimer’s patients have all this beta amyloid plaque, if we get rid of it, maybe we’ll cure Alzheimer’s. And we can talk about it, but it’s generally been a flop doing that. We figured out how ways to get it out of the brain, but people don’t get better.

[08:22 –> 08:52] Dr. Peter McCullough: Well, it and also to the observation when you get to a 100, almost everybody has the amyloid plaques. The older you get, the less they correlate with cognitive dysfunction. So there can be people with a lot of amyloid plaque and the cognitive function is normal. There is a term I’m interested in, and that’s cognitive super agers. To find people who have made it to 90 or a 100 and who are perfectly cognitively intact. Now they’re the minority.

[08:53 –> 08:53] Dr. Ravi Kumar: Right.

[08:53 –> 09:18] Dr. Peter McCullough: But they must have very interesting and unique and special protective factors or have unique things about their lifestyles or their genetics or epigenetics or proteomics. And so I’ve always thought that medicine would be better off in something in a problem like this to actually study success as opposed to study disease and failure.

[09:18 –> 09:27] Dr. Ravi Kumar: Yeah. Absolutely. I mean, if if nature has already figured out a way to get by this problem through

[09:27 –> 09:27] Dr. Peter McCullough: Mhmm.

[09:27 –> 09:44] Dr. Ravi Kumar: You know, evolution, environment, epigenetics, whatever it is, why don’t we figure out what that is and see if we can apply it to the rest of the human population? It’s a fantastic idea, and that’s usually not how medical research goes about it, unfortunately. But, yeah, we do know.

[09:44 –> 10:55] Dr. Peter McCullough: Well, you know, I was gonna say that my co author on one of my books, John Leake, at one side of his family was afflicted by Alzheimer’s. So, you know, they take their loved one with Alzheimer’s to the medical school, but where I went to medical school at Southwestern, and they said, listen, we wanna give you a lot of money to do Alzheimer’s research. Well, you know, really, they ask is take my my poor relative who has severe Alzheimer’s and bring it back to normal. Restore them. That’s really what people want. They want they want cures. And, of course, this giant amount of money goes to Southwestern. Not a single bit of progress on a cure, was made, and, you know, there’s hopes to maybe slow down decline. But, if we have something like Alzheimer’s disease, and there’s never been spontaneous reversal in the natural history, even the treated natural history. Is it is it reasonable to make that a research goal? Or should we shift and make the research goal prevention? Say, listen, we can’t reverse it, so therefore, we must prevent it.

[10:56 –> 11:26] Dr. Ravi Kumar: Yeah. It has to be prevention. Least our initial focus should be prevention right now. Because we know we know for a fact that there are risk factors that can be modified that change your risk of developing Alzheimer’s in the future. Oh, That’s our strongest body of evidence. They blow any drug out of the water that we have right now, and it’s it’s these diet and lifestyle and environmental factors. You modify those, the risk of Alzheimer’s goes down dramatically.

[11:26 –> 11:30] Dr. Peter McCullough: Wow. Okay. So walk us through these risk factors.

[11:30 –> 11:52] Dr. Ravi Kumar: Okay. Well, I think the number one is metabolic health. And this is one of the three hypothesis of or theories of Alzheimer’s is that the brain, which consumes 20% of all the energy in your body, this little three pound organ right here consumes 20% of all your energy.

[11:52 –> 11:53] Dr. Peter McCullough: Mhmm.

[11:53 –> 12:46] Dr. Ravi Kumar: It’s not getting the energy it needs because of insulin resistance. So basically, the brain runs on glucose. And when you become insulin resistant, the neurons and the astrocytes and all the glial cells, they can’t get glucose into the cells because they’re resistant to insulin. So they’re in an energy crisis, and they start the housekeeping functions start falling apart. You don’t clear that beta amyloid plaques. You don’t clear the neurofibrillary tangles, the tau tangles. You don’t maintain the synapses, which make the connections that help us function cognitively. So that’s probably the biggest risk factor that we can modify and that we’ve seen has a direct correlation with Alzheimer’s development and neurodegenerative diseases is improving our metabolic health, not being insulin resistant.

[12:46 –> 12:50] Dr. Peter McCullough: Wow. So does that mean for many losing weight?

[12:51 –> 13:59] Dr. Ravi Kumar: Yeah. I mean, potentially. Right? So losing weight, I I feel like it’s a little too simplistic when talking about metabolic health because if you lose a bunch of muscle and you lose fat, you’re likely not going to improve your metabolic health. Mhmm. Metabolic health is all about eating a diet that doesn’t give you big glucose spikes, which means you don’t put on fat around the peritoneum and in the liver and these places that are put on metabolically active fat that make you insulin And it means exercising the way humans were evolved to do throughout their whole life. It might not have been intentional exercise like we do now, but they had to walk up the mountain to herd the sheep or they had to, you know, go catch the seafood or the hunt the animal. And that was a part of daily life, walking, moving, maintaining strong bodies, which in turn optimizes your metabolic health. And we don’t do that as much now. And that’s why they show also that exercise increases BDNF, that’s brain derived neurotrophic factor, drastically modifies your Alzheimer’s risk.

[13:59 –> 14:07] Dr. Peter McCullough: Right. So what type of exercise are we talking about and and how frequently and Yeah. And, you know, over the duration of your whole life? Or

[14:07 –> 15:09] Dr. Ravi Kumar: Over the duration of your whole life. Yeah. I mean, we’re all pretty much active as kids, at least we used to be. Maybe it’s not like that. It’s not like that anymore. Most kids are active, though. But what I tell people when people ask me, what kind of exercise should I do? I say, well, walk. Walk every single day. Human body was meant to walk. Human beings since the dawn of civilization, since the dawn of our species have been walking, walking a lot. And there’s something about walking that’s very curative to the body. In fact, when I operate on someone’s brain or their spine, the first thing I want them to do is walk. Because it doesn’t matter if I operate on their neck or their head or their lower back. If they walk for some reason, that just heals better. The patients do better. They get less blood clots. They get they don’t get atelectasis in their lungs, which is collapse of the little alveoli, the air sacs in the lungs. They don’t get infections in the wound. The wounds which have stress on them from walking, think, oh, you don’t want to put stress on the wound.

[15:09 –> 15:50] Dr. Ravi Kumar: Actually, they heal better. And so walking, I think, is the number one thing. Second thing I tell people is do resistance training. Because we used to, you know, lift logs and throw spears and, you know, cook with heavy pots or whatever it was. But now, you know, you might not have to do that. So go do some resistance training. It could be with bands, it could be with weights, It could be body weight exercises. But you you should your muscles should be fit and strong because they’re huge glucose sinks. You eat Mhmm. You decide to eat the wrong thing one day, you’re if you have good muscle mass, they it sucks that glucose out of your blood, and it keeps you insulin sensitive.

[15:50 –> 15:53] Dr. Peter McCullough: Have you ever done a burpee?

[15:53 –> 15:56] Dr. Ravi Kumar: Oh, yeah. I do them all the time, actually. I love it.

[15:56 –> 16:07] Dr. Peter McCullough: That’s the simplest thing. Get on the ground, get up, do a jumping jack, go back down. I mean, it seems like if I do three of them, I get short of breath. Yeah. Yeah. And I’ve always said

[16:07 –> 16:14] Dr. Ravi Kumar: Try do 50 in a row without stopping, Peter. You’ll you’ll be you’ll be dead for the rest of the day. That’s just 50. You know? It takes it takes five minutes.

[16:15 –> 16:55] Dr. Peter McCullough: Yeah. There’s there’s no way. Doesn’t take any special equipment. I’ve always thought if I’m in a hotel room, gosh, if I could just do 10 of these, I you know, I’d be in great shape. Now I had a chance to interview the founding president of the American College of Lifestyle Medicine, a very interesting guy. And he told me he also said exactly what you said about walking, but he said walking outside. He said the human body was actually meant to be outside, that there’s something about it that, you know, has some special effect. He thinks it’s very different than walking on a treadmill in in in a home gym. What do you think?

[16:55 –> 18:06] Dr. Ravi Kumar: I totally agree. Well, one, there’s this there’s this psychological phenomena. They’ve actually studied this greatly of seeing the world pass by you. It sends an input into the brain that makes you feel good. You feel like you’re going somewhere. Also, sunshine exposure. Yes. The sunshine exposure is so important because you it helps you create vitamin D. It it regulates your circadian rhythm. And it’s much different than being inside under fluorescent or LED lighting Mhmm. Where you’re not getting any of those hormetic inputs that the sunlight gives you. Also, indoor air quality is usually not good even in a healthy house. Even in the rooms you and I are sitting in right now, we probably have CO2 levels that are much higher than the ambient CO2 levels outside. Wow. And so being outdoors, I mean, there’s a reason you feel good outdoors. Right? You go swim, you go walk, you go hike, you go play tennis or pickleball. Afterwards, you just feel so good. You’re like, oh, that was exercise. Well, guess what?

[18:06 –> 18:23] Dr. Ravi Kumar: It probably was some exercise, but it was probably being outside. You know, the Japanese call it forest bathing when they go outside and treat depression that way because there is something very healing about being outside, and I totally agree with your colleague on that.

[18:23 –> 19:12] Dr. Peter McCullough: Right. So so this idea of a couple of things came to mind. One, I I think of two populations that just love to see the world going past them outside. One is little kids in baby joggers. Have you ever seen I mean, as soon as a child gets in a stroller or a baby jogger, they just seem to love it. You know, again, this world passing by and the other population is pets, especially dogs. Have you ever seen dogs in cars? They love to stick their heads out the window, you know, feel the wind. They just love to be outside. And and I also think that another big benefit of being outside and having this daily exercise is sleep, getting good sleep. And it it is is are sleep habits somehow related to chronically to cognitive function?

[19:12 –> 19:59] Dr. Ravi Kumar: Absolutely. So when I when I started residency, it was 2010. And at that time, we did not think that there were some lymphatics in the brain. So for your audience that doesn’t know what lymphatics are, it is this drainage of extra or interstitial fluid, which is outside our cells, through a separate vascular system, not like our blood vessels, but the lymphatic vessels, and it drains into our blood, and then we we we excrete the waste. We didn’t think that our brains had that. But midway through my residency, they discovered that there is a lymphatic system in the brain called the glymphatic system. Really? Yeah. And it is so if you when I operate on the brain’s spine, I open up this sac around the brain or the the Mhmm. The spine, and it’s called the dura.

[19:59 –> 20:40] Dr. Ravi Kumar: It’s this this very thick sac, and that’s why it’s called dura. And inside there, there’s a clear fluid called cerebrospinal fluid. And the brain and the spinal cord, they float in it because the brain and spinal cord are mostly fat. And so they float in this aqueous medium. And at night, when you sleep, your blood vessels pulse, like, almost like peristalsis of your intestines, and they drive cerebrospinal fluid through the brain, through and in between all the perivascular spaces all around the brain, and they flush out toxins, including beta amyloid, which is what creates those beta amyloid plaques in Alzheimer’s.

[20:40 –> 20:41] Dr. Peter McCullough: Oh, okay.

[20:41 –> 20:54] Dr. Ravi Kumar: And so if you don’t get sleep in fact, they’ve done studies on this. If you are sleep deprived for one night, your beta amyloid in the brain goes up by 5%.

[20:54 –> 20:55] Dr. Peter McCullough: Oh my lord.

[20:55 –> 21:09] Dr. Ravi Kumar: Yeah. So sleep is essential. Deep sleep, particularly, is essential at flushing the toxins out of your brain, including the the Alzheimer’s plex that we call beta amyloid plaques.

[21:10 –> 22:08] Dr. Peter McCullough: Wow. This is so fascinating. So, you know, big inputs to sleep are good sleep habits. And for most people, that means not napping during the day except for some kind of special cultural groups. And then, having lots of physical activity, certainly a very healthy diet. And it’s been my observation that what’s key to good sleep is actually the avoidance of alcohol. This has been studied. And alcohol, even as little as a drink, disrupts this delicate sleep architecture, this REM and non REM architecture. Once the architecture is is, you know, disturbed or fractured, that there’s a bad night’s sleep. And then when there’s a bad night’s sleep, there’s higher stress hormones the next day, epinephrine, norepinephrine, dopamine, cortisol, they’re all elevated. And so then the next night is a bad night’s sleep, and it becomes a vicious cycle. Mhmm.

[22:08 –> 22:42] Dr. Ravi Kumar: Yeah. No. Absolutely. I I don’t drink alcohol except on very rare occasions. And it’s just you can only state it one way. Alcohol is a neurotoxin. It was designed by fungus to hurt animals with nervous systems. That’s that’s what it’s that’s evolutionary design. Okay. So that’s why when you when you drink, you do get effects on the central nervous system. It is poisoning your it’s activating your GABA receptors, which slows your whole system. And if you drink enough of of it, it obviously can be fatal.

[22:42 –> 23:44] Dr. Peter McCullough: Wow. Well, you’re you’re listening. You’re hearing it from an expert, everybody. Yeah. Now my audience knows, you know, I don’t drink either. I I know what it tastes like, and and I I you know, when I was younger, almost certainly had a propensity to drink too much. And I’m I’m so happy I haven’t had a drop in a very, very long time. But, you know, I can tell you, I can look at my dad as a case example. So his mother, my grandmother, my family’s Irish, she lived to 99. 99. Now towards the very end, she had some cognitive decline, but it wasn’t bad. She she actually died of renal failure, end stage renal disease, and she didn’t go on dialysis at age 99. But my dad was a very heavy drinker, smoker, you know, just a cussing man. And, you know, he died basically with Alzheimer’s, severe Alzheimer’s at age 83. So sixteen years of life cut off, and I I think alcohol played a role. He had another alcohol related problem. A lot of people don’t know this, and that’s macular degeneration of the eyes.

[23:45 –> 24:06] Dr. Ravi Kumar: Yeah. Which, you know, the eye is part of the central nervous system. The retina of the eye. Yeah. It’s it it it’s it is the during neurodevelopment, the brain sends these little shoots out that become your eyeballs. And so yeah. And but yeah. That was certainly contributed to his Alzheimer’s if that’s what his diagnosis was at the end of his life. Yeah. They have

[24:07 –> 24:31] Dr. Peter McCullough: His diagnosis was Alzheimer’s. I have to say one more thing about alcohol since it kind of relates to another complicating factor. It just happened in my mom. My mom has Alzheimer’s, and that is alcohol is probably the single greatest risk factor for atrial fibrillation, which is a common heart rhythm. About 15% of adults get it. Atrial fibrillation is one of the major risk factors for embolic stroke.

[24:31 –> 24:32] Dr. Ravi Kumar: Yep.

[24:32 –> 25:20] Dr. Peter McCullough: And so there you go. There’s there’s part of the the framework here that there’s cognitive decline or these risk factors for it. And then there’s these superimposed issues. We’re not gonna cover stroke today, but, you know, stroke of three different varieties, embolic from the heart, embolic or atheroembolic from the great vessels in the aorta and the neck, and then kind of in situ stroke from hypertension and atherosclerosis in the arteries in the brain. But stroke on top of that, there is something called multi infarct dementia, which we’re not going to cover as well. But I could tell you my mom has Alzheimer’s superimposed stroke, it clearly had a precipitous decline in her functional status. But back to Alzheimer’s, what are some other risk factors that you’ve identified?

[25:20 –> 26:12] Dr. Ravi Kumar: Yeah. So hearing loss. And and this this is a big one, Peter, because a lot of people are walking around with hearing loss, which is sensorineural hearing loss. It happens in older age, especially if you were worked in loud environments when you were a young person. And that hearing loss can lead to up to a 50 to 60% increase in in dementia, namely Alzheimer’s Wow. If you don’t correct it with hearing aids, which so this is a what I’m saying here is this is a huge modifiable, very easily modifiable risk factor with today’s technology. If you know if you have hearing loss or you know someone who does and they are not treating it, they are missing one of the biggest things they can do to prevent Alzheimer’s.

[26:12 –> 26:21] Dr. Peter McCullough: Okay. But I wanna hear your explanation of why. Why does hearing loss act as a risk factor? Because I have my theory, but I wanna hear yours.

[26:21 –> 27:04] Dr. Ravi Kumar: Okay. Yeah. So I there I mean, there’s a couple theories out there. Right? One is that you the brain’s basically, processing power is being overloaded by trying to interpret interpret sound where that’s not properly being received. So they’re not getting all the audio signal that they need. So their brain is working overtime to try to interpret this sound that that’s coming in from the world. And it’s basically dedicating more synaptogenesis and all this stuff to just processing sound, and it’s leaving out the cognitive aspects. And that’s that’s one theory. The second theory is that when you can’t hear properly, you become socially isolated.

[27:05 –> 27:05] Dr. Peter McCullough: Mhmm.

[27:05 –> 27:19] Dr. Ravi Kumar: And social isolation in itself is a risk factor for dementia. Mhmm. Yeah. Among other things. Mean, social isolation is almost as bad as smoking for your cardiovascular system. But

[27:19 –> 28:02] Dr. Peter McCullough: Right. I’ll say that hearing loss goes along with something else. And I’m observing this, by the way, in my mother-in-law who lives with us, is that it’s associated with reduced talking and speech. So if you can’t hear much, you don’t say much. And so that’s part of the social isolation. So as we’re processing auditory stimuli, we’re speaking, our brain is synaptically firing all over the place. And I do think there is a diminution of all of that. Even some of the drugs we’re gonna go over, you know, one of their major mechanisms of action is just to keep the the synapses firing. And there’s fewer synapses if I what else is in the list of risk factors? It’s been pretty helpful.

[28:02 –> 28:54] Dr. Ravi Kumar: Yeah. So smoking is a big one. Hypertension, a big one. Anything that basically affects increases your oxidative stress and affects your vascular system. Because like you said, there’s a there’s a vascular dementia. Mhmm. And oftentimes, it’s superimposed with Alzheimer’s. I mean, they’re almost like part of the same spectrum. And because you’re not getting enough blood and nutrient delivery to the brain, so there’s this energy crisis, and you get the same basically sequelae or or end result. Mhmm. A big one, risk factor wise, is genetics as well, Peter. And there’s something that people have likely heard of. It’s called APOE. Yeah. It’s a it’s a lipoprotein that in the brain specifically, it transports lipids from astrocytes to neurons.

[28:55 –> 28:55] Dr. Peter McCullough: Mhmm.

[28:55 –> 29:48] Dr. Ravi Kumar: And remember how I said the brain is mostly made of fat? It’s mostly cholesterol and fat. That’s the largest component besides water. And when a neuron is sending out synapses, which are these, you know, axons send out these little fingers called dendrites that make these connections called synapses with the other neurons, and that connectivity is how we create this supercomputer in our head. When it’s doing that, it needs a lot of fat, a lot of cholesterol, a lot of phospholipids, a lot of nutrients. And these things are packaged in these lipoproteins that are the main structural component of it is APOE. Mhmm. Now there’s a variant of that called APOE4. Mhmm. And APOE4 is basically a variant that has some certain, like, very particular characteristics.

[29:48 –> 30:44] Dr. Ravi Kumar: And one of them is that it holds on so it attaches to this LDL receptor. It’s like this receptor on the cell surface. And it it fits into it like a little little little ball, and it gets in that endocytosis, so the whole thing gets pulled into the neuron. So when the neuron’s receiving a package, wrapped wrapped and delivered by APOE4, it pulls the whole thing into the cell. And then APOE doesn’t let go of the LDL receptor like the other APOE variants. So APOE4, sorry, doesn’t let go of it. And so the whole thing gets destroyed in the or broken down and recycled like it’s supposed to. But normally, in the other variants, that LDL receptor gets pulled off and then goes back up to the surface to receive another package. APOE4 doesn’t let go of it. And so you get reduced cholesterol transport to the cells and lipid transport to the cells because there’s less LDL receptors available.

[30:45 –> 31:12] Dr. Ravi Kumar: And so you get accumulation of more cholesterol outside the cells. APOE4, this variant APOE4 in particular, also doesn’t basically pull amyloid plaque out of the extracellular space like the other APO Es do. Mhmm. And so it’s and it can promote aggregation of beta amyloid plaques and all and these it has a bunch of characteristics that lead to more beta amyloid plaque.

[31:12 –> 31:20] Dr. Ravi Kumar: This used to be an advantage to us evolutionarily. Now it’s leading to higher rates of Alzheimer’s. And so that’s another risk factor I think people should know about.

[31:21 –> 32:06] Dr. Peter McCullough: Yeah. Let me lay this out. Actually, that’s probably the best explanation I’ve ever heard about APOE4 in in cognitive function. But let me kinda lay this out for people. So the normal alleles are APOE e3, e3. So that would be normal. So someone who is normal, the lifetime risk of Alzheimer’s disease as quoted from the studies is about 15%. That’s normal. If you get a normal one from mom or dad, e three, and you get an e4 from mom and dad, and so you’re e three, e4, that jacks up the lifetime risk to I’m sorry. The baseline risk of e three, e three in in a published study is about 5% for the clinical diagnosis of Alzheimer’s.

[32:07 –> 33:12] Dr. Peter McCullough: If you get e3/e4, now the lifetime risk is is up to about 15%. When I mean lifetime in the studies, they’ve only, you know, carried out to age 65 or 75. But if you get e4/e4, and there’s a New England Journal of Medicine paper to support this, now the lifetime risk is about 65%. So it’s it’s really high, and it’s actually super high, and the data are even stronger in African Americans compared to Caucasians and particularly those who drink alcohol. So the worst would be an e4/e4 patient who’s African American and drinks alcohol. Well, that person is over 65% chance they’re gonna develop Alzheimer’s and actually at an early age. So, you know, I checked myself. Of course, you’d imagine I would. And, I’m actually an e two, e three. So e two is interesting because e two is actually protective against Alzheimer’s. So one of my parents was carrying an e two, and I got an e three from the other one. But the way they’re behaving right now, they’re like they’re e4 heterozygotes.

[33:13 –> 34:19] Dr. Ravi Kumar: And that’s very interesting because Yeah. You can take APOE so you’re right. APOE e2 is protective because it actually grabs onto beta amyloid and exports it out to the Yeah. The recycling centers, which are either in cells or out into the bloodstream through the arachnoid granulations. But there are populations with very high APOE4 variant ratios in their their in their group. So like the Nigeria and Nigeria is a good place, a good example. Nigerians have a very high rate of APOE4, very high. And they have almost no Alzheimer’s in people who eat a traditional diet and practice traditional cultural practices. So even though APOE4 should basically guide them down this path of Alzheimer’s, they’re not getting it. So it’s not just these variants that cause it. You have to take these variants and you have to load them with a certain lifestyle diet and lifestyle characteristic to

[34:19 –> 34:54] Dr. Peter McCullough: Right. So so for any complicated diseases, this is true for most neurologic diseases. It’s true for atherosclerosis. There’s no single cause. And and so what we in epidemiology, we use the word determinant or risk factor, which I think is really a good word. So it’s a risk factor, but let’s go through some of these other tests quickly. The blood tests that have come out on this include p-tau 217, p-tau 181, amyloid beta 42/40, GFAP and NfL. What have you learned about the utility of these new blood tests?

[34:54 –> 35:49] Dr. Ravi Kumar: Yeah. Well, it’s it’s been an evolution, Peter, for sure. You know, they they started off with just clinical diagnosis, and then they started realizing that they could see these this change in the ratio of beta amyloid 42/40. And Mhmm. I’ll explain that real quick. You cleave beta amyloid off the cell surface, this enzyme called gamma secretase can cut in different spots. And if it cuts it at the fortieth amino acid, then it actually doesn’t make any plaque. It’s very it’s it’s very not offensive. If you cut it at the forty second amino acid, then it tends to aggregate and form these plaques. If you looked at someone’s bloodstream or their cerebrospinal fluid, you could see this ratio of a beta 42 to a beta 40.

[35:50 –> 36:49] Dr. Ravi Kumar: And if the a beta 42 was higher or that that ratio 42 to 40 was higher, then you’re actually getting rid of a lot of your this amyloid forming version. And so they said, oh, that’s a good sign. But if you’re not if that ratio was lower, then they’re saying, oh, you’re you might be retaining, you know, amyloid beta 42 and developing plaques. And so that’s how they started off. It wasn’t super accurate, honestly. So now they’ve moved more to this blood test where you could look at phosphorylated tau. Mhmm. Which is this protein in neurons, 217, that’s the variant of it, and its and its ratio to amyloid beta 42. And they have got like a 96% specificity with that. So now you can actually go get a blood test even if you’re not symptomatic, by the way, and know whether you’re developing Alzheimer’s or not.

[36:49 –> 36:58] Dr. Peter McCullough: That’s what I’m asking you. So is it detecting disease, or is it prognostic for the development of future disease or both?

[36:58 –> 37:12] Dr. Ravi Kumar: So it is detecting disease, actually. In fact, you can get a you can get a diagnosis of Alzheimer’s without the clinical symptoms, or at least it’s there that’s that’s the way the the world is moving right now.

[37:12 –> 37:25] Dr. Ravi Kumar: It’s saying, hey. If you’ve got this elevated phosphorylated tau 217, you know that you’re forming these neurofibrillary tangles, which destroy and kill neurons.

[37:26 –> 37:26] Dr. Peter McCullough: Mhmm.

[37:26 –> 37:52] Dr. Ravi Kumar: So you’re headed in that direction. And that’s great because you now know that you can actually start working on your risk factors to try to improve that. It’s almost like a sign before there’s any symptoms. And so that’s that’s where the the the world of medicine is moving is towards making it clearly a biochemical diagnosis rather than just a clinical diagnosis.

[37:52 –> 38:25] Dr. Peter McCullough: Okay. And just on the clinical side, I’ll say quickly there, certainly our scores, the one we file for therapeutic research is called the ADAS Cogs score. Zero would be the best you can do. 70 is a is a terrible, terrible score, but moderate dementia is at 40. And, you know, sadly, the interventions only move that score by a point or so. I mean, it’s Yeah. Very, very disappointing. But are the diagnostic tests good enough, the blood tests, where we don’t need to do spinal tabs, or do does everybody need a spinal tab?

[38:25 –> 38:28] Dr. Ravi Kumar: Can do blood tests now. Yeah. It’s good enough now. It’s good enough.

[38:28 –> 38:30] Dr. Peter McCullough: And then what about the PET scanning?

[38:30 –> 39:00] Dr. Ravi Kumar: So the PET scan and these blood tests are better than PET scans now. So Oh, okay. Before, basically, what they were doing is they were doing PET scans where they looked at a beta amyloid in the brain. And they could you know, because you can basically have a marker that attaches the beta amyloid. You can see how much of it is in your brain. Beta amyloid is and we can talk about this more, is a very poor marker for Alzheimer’s.

[39:01 –> 39:01] Dr. Peter McCullough: Mhmm.

[39:01 –> 39:06] Dr. Ravi Kumar: Phosphorylated tau 217 is a great marker for Alzheimer’s.

[39:06 –> 39:07] Dr. Peter McCullough: Okay.

[39:07 –> 39:10] Dr. Ravi Kumar: Because it’s what’s happening in the neurons that’s pathologic.

[39:10 –> 39:52] Dr. Peter McCullough: Okay. So so that’s the nugget. We’re moving to blood tests, don’t need a spinal tap. The PET scans are used in research. I’ve had a few of my patients go through them. Know in Dallas at Southwestern, they have the PET scans available. There’s kind of three different tracers that are attached to fluorodeoxyglucose to kind of kind of nail down these plaques in the brain. But, let let’s move on to what a lot of people want to know about, and that’s treatment. So as I count up, I think there’s seven or eight FDA approved drugs for Alzheimer’s. The cholinesterase inhibitors, donepezil, rivastigmine, galantamine. What’s your opinion of the cholinesterase inhibitors?

[39:52 –> 40:46] Dr. Ravi Kumar: So, acetylcholine is a neurotransmitter in our brain that is involved in cognitive function. Mhmm. And acetylcholinesterase inhibitors block the breakdown of acetylcholine, so you potentially have more acetylcholine in your synapses. And so you can have more hopefully more cognitive function. These don’t change the course of the disease at all, and they may improve some of your cognitive capacity early in the disease. But they’re just they’re just drugs that try to block some of the symptoms or slow down the progression of some of the symptoms. They don’t even touch the disease. So they’re just symptomatic. It’s almost like taking a pain med for for, you know, a cut on your arm. It doesn’t fix the cut, but it it blocks the pain.

[40:46 –> 40:58] Dr. Peter McCullough: That that’s been my review. Now the NMDA antagonist memantine, that’s used also in in combination with donepezil, that works on n methyl,

[41:00 –> 41:02] Dr. Ravi Kumar: D aspartate. Receptors. Yeah.

[41:02 –> 41:06] Dr. Peter McCullough: Yeah. Is that is that the same idea? It’s affecting neurotransmission, essentially.

[41:06 –> 41:55] Dr. Ravi Kumar: Yeah. So basically, what that is is when you have later in the disease, Alzheimer’s disease, people can get very agitated, angry, wild, you know, they’re biting, they’re hitting, they’re they’re not nice to you anymore. Your sweet mother who was always the the best person in the world you knew, now she’s not that. That’s agitation. And the basically, the NMDA receptors are these excitatory receptor receptors that glutamate attaches to, and they they cause agitation. So memantine basically blocks the NMDA receptor, so you don’t get that agitation associated with cognitive decline. Again, it’s just trying to block some of the bad symptoms of this disease. It doesn’t do anything to stop it or or turn it around.

[41:56 –> 42:27] Dr. Peter McCullough: Okay. I see. So it’s kind of used maybe at that extreme edge of the agitated. And now the anti amyloid monoclonal antibodies, lecanemab, donanemab, you you know, they’re they’re targeting the beta beta amyloid, the amyloid plaques, but, gosh, this hemorrhage, this brain swelling and hemorrhage sounds terrible with it. It’s called ARIA-E and ARIA-H. Mhmm. What’s the deal there?

[42:28 –> 43:35] Dr. Ravi Kumar: So okay. So these monoclonal antibodies, they’re going up into the brain. They’re infusions, by the way. Mhmm. And they’re very, very expensive. Right. And they go up into the brain, and they attach to amyloid. And they basically tell the immune system, hey. I caught this thing. Take it out of here. And they’re very effective at removing beta amyloid. But beta amyloid doesn’t just accumulate outside the neurons. It accumulates in the vessel walls in the brain as well. It’s called amyloid angiopathy. And Alzheimer’s patients don’t always have amyloid angiopathy. But if they have a lot of amyloid burden in their brain, they certainly have amyloid in their vessel walls. So you you start clearing these amyloid plaques out of the vessel walls with these monoclonal antibodies, and all of a sudden, these vessels become leaky. So you get you get a swelling and edema and inflammation around the vessel walls, and you get these punctate microhemorrhages, and sometimes you get large intraparenchymal hem hemorrhages in the brain. And so and and it’s as high as, like, one in four with these monoclonal antibodies.

[43:35 –> 43:41] Dr. Peter McCullough: And you have to if you’re gonna get these infusions, you have to get serial MRIs. Right?

[43:41 –> 43:55] Dr. Ravi Kumar: Yeah. You do. You you have to because it’s part of the the monitoring the safety of these drugs. And the people at highest risk for ARIA are APOE4 carriers, which are the highest risk for Alzheimer’s in the first place.

[43:55 –> 44:24] Dr. Peter McCullough: Right. Yeah. So the APOE4 is in some studies, a third of them get this. They get hemorrhage. But, you know, I have a patient who has this amyloid angiopathy. He’s a great guy in Texas. He’s he’s about my age. He’s not much older. And, he’s also followed at UT Southwestern at their Alzheimer’s Center. And, you know, his problem is he hasn’t taken these antibodies. His problem is hemorrhage. He has little bitty hemorrhages

[44:25 –> 44:25] Dr. Ravi Kumar: Yep.

[44:25 –> 44:29] Dr. Peter McCullough: That are kind of knocking down his cognitive function over time.

[44:29 –> 44:54] Dr. Ravi Kumar: Yeah. It’s it’s it’s really a progressive disease. I I just saw a patient in the hospital yesterday with it having these little microhemorrhages that were causing seizures and and other things that were were problematic, and it’s it is we don’t have a good treatment for it right now. But these monoclonal antibodies do clear that same amyloid protein out.

[44:55 –> 45:10] Dr. Peter McCullough: Right. Right. And may there may be I haven’t used them, but maybe there’s a select case of premature advanced disease or something unique that would prompt that. Now, what about nutraceuticals and supplements? Is there anything out there that looks promising?

[45:11 –> 46:20] Dr. Ravi Kumar: Yeah, I mean, there’s a lot of potentials out there, right? One, if you’re vitamin D deficient and if if anyone has ever seen or been vitamin D deficient, you know that basically no matter what age you are, you look like you have dementia. I mean, personality’s flat, You’re depressed. You’re thinking slow because vitamin D is a master regulator. It goes into the nucleus of every cell in our body and dictates transcription of of certain genes. So if you’re vitamin D deficient and you’re older, which a lot of older patients are vitamin D deficient, that should be replaced. You should be optimal on your vitamin D, which is above 30 nanograms per milliliter on the 25 hydroxyvitamin D test. So that’s number one for supplements. Okay. Number two is magnesium. Magnesium is very important for a number of functions in the brain. Mhmm. There’s those NMDA receptors that we talked about. Well, there’s a they act like a voltage gated gated block. So you can’t overstimulate your NMDA receptors if you have adequate magnesium in your brain.

[46:20 –> 47:11] Dr. Ravi Kumar: They also stimulate GABA receptors, which calms you down. Your magnesium is important for making serotonin, which is very important for cognitive and emotional function. And, you know, it serves as a cofactor in hundreds, like over 300, maybe even more different reactions and transcription processes in the brain in the brain and the body. So magnesium is very important. There’s one form of magnesium that enters the brain more easily than all the rest, and it’s called magnesium L-threonate. And so you can get this on Amazon or, you know, anywhere, but make sure it’s a good quality supplement if you’re gonna supplement. But you can take magnesium L-threonate, and there’s a clinical trial showing that it improves cognitive function. It it it was a small trial and it and it was Okay. The results were modest, but it it did show a positive result, which is something.

[47:12 –> 47:13] Dr. Peter McCullough: And take it at night?

[47:13 –> 47:33] Dr. Ravi Kumar: Yeah. I do. I take magnesium glycinate, which is a different form every evening before I go to bed. Helps with sleep. You sleep great when you take magnesium. And that’s one of my I have a protocol for sleep, and that’s one of the things that’s on there. And yeah. And it it it actually keeps your bowel function a little bit normal too, which is very important for your microbiome maintenance. So

[47:33 –> 48:15] Dr. Peter McCullough: You know, I have a few points on magnesium as well. It’s been studied. You know, the the magnesium content in the water supply around The United States is low. It’s particularly low in some areas. And believe it or not, it’s it’s related to sudden death rates, geographic differences ecologically. And, it’s filtered out of a lot of water treatment processes. A lot of people are drinking bottled water, filtered water, even lower magnesium. It’s a leading cause of palpitations, premature atrial and ventricular contractions, sometimes even atrial fibrillation for the heart. We always teach that the ideal magnesium is for the myocardium, magnesium malate, but you’re convincing me that maybe a blend, and there are some of these blends out there available, make a difference.

[48:16 –> 48:22] Dr. Peter McCullough: Now let’s stay on Alzheimer’s cognitive decline. What else in the supplement space?

[48:22 –> 48:29] Dr. Ravi Kumar: So there’s there’s some other supplements that that can be looked at, like coenzyme Q10 is a big one.

[48:30 –> 48:30] Dr. Peter McCullough: So you’re

[48:30 –> 48:37] Dr. Ravi Kumar: if you’re on a statin, that inhibits enzyme called HMG-CoA reductase.

[48:37 –> 48:37] Dr. Peter McCullough: Mhmm.

[48:37 –> 49:10] Dr. Ravi Kumar: And an interesting thing is most of your cholesterol is made in the liver, and it’s distributed to the rest of your body. And that’s where statins block the formation of or the production of cholesterol that’s in your liver. But some statins cross the blood brain barrier, these lovastatin, simvastatin, atorvastatin. They cross the blood brain barrier, and they go into your brain. And your brain cannot receive cholesterol from the rest from your liver. It it’s blocked by the blood brain barrier. So your brain has to make all its own cholesterol in the astrocytes, which are these supportive cells that support the neurons.

[49:10 –> 49:11] Dr. Peter McCullough: Mhmm.

[49:11 –> 50:13] Dr. Ravi Kumar: So if you’ve got and remember I said the brain has a ton of cholesterol in it. It’s it’s an I can’t remember the exact amount, but it’s an extraordinary amount of your body’s cholesterol is in the brain. Mhmm. Mhmm. So now imagine you send a statin up there because you might need it for some other biological cardiovascular process, and it’s blocking the production of cholesterol in your brain. Well, that’s that’s one thing. Downstream from the cholesterol is another ends production, and it’s coenzyme Q10. That’s also produced in that same bile biochemical pathway. And coenzyme Q10 is very important for the electron transport chain, which produces energy in your mitochondria and your neurons, which are super energy hungry. So I always tell people that the evidence is not strongly supportive of it because there haven’t the studies haven’t been done for it. But coenzyme Q10 should be a part of your regimen because it’s very important for energy production in the brain. And if you’re on a statin, you might be blocking production.

[50:13 –> 50:16] Dr. Peter McCullough: And and how much coenzyme Q10 do you recommend?

[50:16 –> 50:30] Dr. Ravi Kumar: So, you know, you can take the standard. You can buy it at Costco, and I don’t know the dose, but it but it is offhand. But it’s it’s whatever’s on that bottle is the generalized standard dose based on what the this clinical studies that we have.

[50:30 –> 51:39] Dr. Peter McCullough: You know, we did a review at this, the McCullough Foundation. We published it on focal points. And, you know, the human body can’t make can’t make its own. I mean, you can’t you can’t make it. You’re you’re reliant on external ubiquinol, which is the active CoQ10. And we found that in the published meta analyses for survival, and most of this is cardiovascular survival, the number you need to hit is about 600 milligrams a day. It’s way higher than what a lot of people think. Yeah. So I personally recommend a vegan 800 just to cover it. You can’t overdo it. And just because we’re close on time, I’m going to take on this statin issue. Because atherosclerosis or the cardiovascular risk factors are dominant for Alzheimer’s, you wouldn’t be surprised by learning. There’s been 31 randomized trials of statins and cognitive function and dementia, and statins actually prevent dementia and prevent cognitive decline. It’s just the opposite of what people think of in the lay literature. There’s been studies of people with, who have congenital hypoapo B, and they make very little VLDL.

[51:39 –> 52:26] Dr. Peter McCullough: So therefore, there’s very little circulating LDL and total cholesterol. Very little. Like, you know, LDLs below 10 their whole lives, and they have normal cognitive function. And then with the PCSK9 inhibitors that we use, we’ve tested LDLs way below 10, total cholesterols way below 50, no difference in cognitive function. So the brain seems to, with most of our drug assault, the neurons the still seem to be able to kinda chug away and produce the cholesterol that you need. But I like your point about statins. You know, I do not prescribe the legacy statins. I prescribe I think the best in class is rosuvastatin. I don’t prescribe atorvastatin or the other ones. But I wanted to get that out there since there’s great confusion on this.

[52:26 –> 53:06] Dr. Ravi Kumar: So I think another really important thing to mention there is that a lot of neurodegenerative disease is vascular related. Oh, yeah. So, you know, if you’re developing small we call it small vessel disease where you get atherosclerosis of these small perforating vessels throughout the brain, you see it. You see these we call them lacunar infarcts. They’re these little areas of lucency in the brain, and it’s from cardiovascular disease. So if you are high risk for cardiovascular disease, then even though statins might be lipophilic and might be inhibiting cholesterol production in your brain, you’re gonna benefit more by preventing Right. Progression of cardiovascular disease.

[53:06 –> 54:11] Dr. Peter McCullough: Especially long term use. We have hardly any time left, but, you know, I did wanna mention some research done. And, Ravi, I really suggest you have him on this podcast. You really like him. Dr. John Lewis from University of Miami. And he studied some of these nutraceuticals and particularly derivatives of aloe vera that are consumable, actually polymannose conjugates and derivatives in a capsule. And he studied them prospectively in patients with, you know, ADAS cog scores of 30 or 40. They were pretty significantly into dementia. He studied them in the nursing home, and he actually showed improvements over six months to a year. And the point improvements was about 4.5 points. It was actually bigger than the prescription drugs. And I’ve asked him, I said, how does this work? And he thinks it does have some anti beta amyloid effect. And some of it may just be a GI detoxification microbiome strategy. But it’s called Dr. Lewis Brain Care.

[54:11 –> 54:27] Dr. Peter McCullough: I personally use it based on his prospective studies. There’s been four of them. So not only did the scores go in the right direction, but all the cytokines and all the kind of intermediate variables did as well. I think it’s ready for a large randomized trial.

[54:28 –> 54:49] Dr. Ravi Kumar: Very interesting. Yeah. Because you know what? I feel like this targeting beta amyloid based on the data that we’ve seen so far is not the strategy. But if this thing is modulating the the microbiome, there’s a direct connection between the microbiome and the brain through the the vagus nerve. I mean, it’s like literally a direct line to your brain stem.

[54:49 –> 55:57] Dr. Peter McCullough: Right. And I asked them, yeah, I asked them about this, these, what’s called DAMPS and PAMPs, these molecular patterns, maybe detoxification of heavy metals. We didn’t get a chance to talk about trace aluminum and and lead and other things, mercury, that can affect the brain. But, take a look at Dr. Lewis Brain Care. It’s basically it’s aloe, polymannose, and some other, ingredients. You take it at pretty high dose. I’m about ready to take mine actually before I go home. You know, the other reason why I take it right around this time, Ravi, is I find that it’s a great appetite suppressant for a few hours. So usually about this time, I’m hungry. And if I can go home not so hungry, I’m gonna go work out, get outside like I should, then eat later on. So it’s been part of my routine. Check it out. Yeah. So with two out of two parents with Alzheimer’s, I figured, listen, I have to do something to change the natural history of this. We’ve been talking to Dr. Ravi Kumar. Dr. Kumar’s incredible adventures, question everything. I think he’s the smartest doctor I’ve had on so far.

[55:57 –> 56:11] Dr. Peter McCullough: So if people give us their feedback, I’m going to recommend, if everybody agrees, I think Dr. Kumar ought to go on Joe Rogan and Theo Von and just kind of, you know, help us with his wisdom. You’ve been great to have on the program.

[56:12 –> 56:14] Dr. Ravi Kumar: No. Thanks a lot, Dr. McCullough. It’s been great.

[56:14 –> 56:31] Dr. Peter McCullough: So let’s get real. Let’s get loud on America Loud Talk News. This is McCullough report and focal point substack and Dr. Kumar’s discovery. And his mantra is question everything, and that’s what we did today. I think it’s a very comprehensive program on Alzheimer’s and cognitive decline. Thanks for listening.

[56:32 –> 57:34] Dr. Ravi Kumar: Okay. I hope you enjoyed that conversation with Dr. McCullough. It was a fantastic discussion, but I know we covered a lot of ground. So here’s what I want you to walk away with. Alzheimer’s is not a fixed fate determined by your genetics. Even with a high risk variant like APOE4, which I have, the lifestyle you build on top of that genetics does an enormous amount to decide where you end up in the end. And the beautiful part is, most of what protects your brain costs you absolutely nothing. Here are the most impactful things you can do. Walk every single day, outside if you can and in the sunlight. Protect your sleep, because deep sleep is when your brain flushes out the very proteins that build up in Alzheimer’s disease. Keep your metabolic health in check so your neurons can actually use the fuel they need when they need it. Do a little resistance training so your muscles stay strong. Skip the alcohol. And if you or someone you love has hearing loss, get it corrected, because that alone is one of the biggest modifiable risk factors we have.

[57:35 –> 57:56] Dr. Ravi Kumar: So if this episode felt valuable to you, do me a favor and share it with someone you love. Maybe it’s a parent or a spouse who’s scared about their memory. Maybe it’s a friend who has a family history and doesn’t know where to start. Information like this can be super empowering for them and make a real difference. Alright, folks. Cheers, and I’ll see you next week.