Transcript of Most Replayed Moment: Alzheimer's Starts 20 Years Before Symptoms! How To Protect Your Brain Now New

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What's the most compelling study you've ever encountered that proves that exercise is central to Alzheimer's prevention and brain health?

When we look at all of the data, we can see that the biggest amount of return on investment is from resistance training.

Resistance training being strength training.

One of the most compelling studies was probably the, um, the SMART trial, where they took a group of people with mild cognitive impairment and gave them 2 3 times per week of resistance training, and they not only preserved their cognitive functions, they enhanced their processing speed, they enhanced their fluid intelligence, and they had slowing of the gray matter.

The gray matter?

Yeah. So your brain consists of both gray and white matter. So gray matter are the cell bodies that lives on the outer side, outer portions of your brain, and the white matter is deep within the brain, and that's where all of our myelinated neurons live. And over time, we see that we can have little lesions in the white matter of the brain. So a lot of the times people will ask me, Stephen, I'm scared. My mother had Alzheimer's disease. I'm scared I'm going to get it. And we were talking about genetics before, and there's another genetic risk factor that we didn't talk about. The APOE4 gene is one of the, the strongest risk factors of getting Alzheimer's disease, but it is not a foregone conclusion that you're going to get it. So Chris Hemsworth was tested and he has 2 copies of this gene. So you get 2 copies, one from mum, one from dad. It's the apolipoprotein E gene, and it comes in 3 main variants. So you've got APOE2, APOE3, and APOE4. So I'm a 3,3 carrier. I've been tested, and that's the general population. They're 3,3, so it doesn't raise my risk of getting the disease, but it also doesn't protect me.

If you've got a copy of the APOE2 gene, it protects you against the disease. But when you have a copy of the APOE4 gene, it raises your risk by 2 to 3 times. If you have 2 copies of the gene, it raises your risk by 10 times if you are a male. Here's the devastating thing: if you are a female with one copy of the gene, you are at double the risk than your male counterpart. So one copy of the gene, of APOE4 gene, for a female raises your risk by about sixfold, whereas two copies raises your risk by 15-fold.

And how would one go and get checked?

You can get the APOE4 gene checked out with your doctor. It's a simple blood test.

On this point of resistance training, I've heard you talk about how the legs are so important. Having strong legs.

Having strong legs is by far the most important tool in your toolbox for the prevention of Alzheimer's disease. And this was made certain to me when I read a study done on identical twins, exact same genetic profile, and they tracked them and they did cognitive tests and MRIs, and they tracked them over a 10-year period. And what they found was that the twin who possessed the greatest strength and the most leg power had a bigger brain, larger gray matter volume, they preserved their cognitive functions, they did better on different cognitive tests.

Why is resistance training increasing the size of my brain?

Resistance training does so much for your brain. The first thing is we have to think about the journey that we're going on, right? So when you look at all of the studies, I want to make it really clear, all of the studies show that in order to produce the neural effects of resistance training, you need to be lifting at around 80% of your one repetition So 80% of 1RM. So that's quite heavy. There is so much controversy on social media right now. Should I lift heavy? Should I lift light? And when it comes to hypertrophy alone, so increase in muscles, muscle mass, muscle cell size, you can get there. Men can get there, women can get there by lifting light, high reps, or you can get there by lifting heavy and low reps. It just depends on who you are and how much time you have. But when it comes to the brain specifically, you want to be lifting heavy for several reasons. The first one is when we lift heavy, when we literally like, when we contract our muscle like this, we are releasing a whole set of chemicals. They're called myokines. And when they're released from the muscle, they go up to the brain and they do beneficial things for our cognitive performance, our cognition, and they help with the growth and proliferation of new neurons in the hippocampus.

And it's the first thing to go during Alzheimer's disease. It actually shrinks. This holds our memory. This is where a lot of our memory consolidation and learning takes place, which is why short-term memory is the first thing to go during this disease, okay? And as we get older— and what we've found is that you can grow new neurons in the hippocampus from structured exercise and consistent exercise. The biggest growth is going to occur because of BDNF BDNF, brain-derived neurotrophic factor. So this is a growth factor for the brain and it gets released when we exercise. It gets released abundantly when we are doing aerobic training, when we're running, when we're cycling for long distances, but it also gets released when we do resistance training. Now here's the beautiful thing about it. When we do resistance training and we're releasing all of these myokines, these myokines are signaling molecules. They work together. So we've got one called irisin. Okay. And that's a messenger molecule. So what it does is it actually helps BDNF express itself. So when we release this myokine, it goes into the brain, crosses the blood-brain barrier, and it tells BDNF to express itself.

So then BDNF goes in and it helps grow new neurons in the hippocampus. But then we've got another myokine. Let's just take IL-6, interleukin 6. It comes from the interleukin family.

What is that? Sorry.

The interleukin family is a class of pro-inflammatory cytokines. So these get released when we are under stress or you've got an infection or a virus, for example. But when we exercise, it depends on where the site is. Interleukin-6, instead of acting as a pro-inflammatory cytokine, instead of creating inflammation, it acts as an anti-inflammatory cytokine. So it goes into the brain and it lowers inflammation. In fact, this is one of— this was one of the first ever myokines to be studied, and they showed that interleukin-6 is also responsible for the downregulation of tumor cell growth. So exercise is a potent anti-cancer intervention as well, by way of myokines.

How much exercise does one need to do to avoid the, uh, cancer-related, um, side effects, but also the Alzheimer's problem?

Well, just 30 minutes a day of aerobic physical activity can downregulate 13 types of cancers, and the most prominent ones being breast cancer, colon cancer, and prostate cancer. So these 3 have been studied most, and you get your anti-cancer effects from the myokine release. So quite specifically, when we exercise, we're getting a robust release of something called natural killer cells. And when we get these natural killer cells into the plasma and into the bloodstream, they go into the tumor site and they do what they were born to do— they kill. So they go into the tumor site and they start to kill the tumor. And this is where you get your anti-cancer effects of it. But you can also get it from the anti-inflammatory effects of resistance training, anti-inflammatory effects of aerobic training. So these myokines are really powerful. In fact, pharmaceuticals are spending billions of dollars trying to replicate these myokines in a bottle, and they can't do it. I want both men and women lifting heavy because you've got areas in your brain— right across here lives your motor cortex. Think of your brain as real estate. There's real estate in your brain reserved for lifting heavy.

So every time you lift, a heavyweight as opposed to a lightweight. It takes more neural real estate to lift that heavyweight. So the heavier you lift, the greater the neural drive. The greater the neural drive, the better it is for your brain.

If you had to do just one exercise for the rest of your life to protect your brain, and you could only pick one, what would it be?

Deadlift.

Why?

If done correctly, The deadlift can use almost every muscle in your body. Erectus spinae, you've got the glutes, you've got the quads, you've even got serratus anterior, you've got the— you've got your calf muscles. There is so much compounding in that one lift. Would probably be comparable to a barbell squat as well.

According to the World Health Organization, we're getting increasingly more sedentary. I— we're moving less and less, in part because of technology, but also there was this really interesting study done by the Cleveland Clinic where they talk about people who are active sedentary. And this, this felt a little bit personal, if I'm honest. It says a major finding in 2025 found a danger of being active sedentary, which is people who exercise for like 30 to 60 minutes but sit for the remaining 10 hours a day. If you sit for more than 10 hours a day, your risk of cardiovascular disease increases even if you meet weekly exercise goals, because prolonged sitting shuts down lipoprotein lipase 'an enzyme essential for burning fat and cleaning glucose from the blood.' That wasn't— that's annoying to read because I feel like that's me.

Yeah. And being sedentary is a disease. You can change the trajectory of your life by doing 10 air squats every hour on the hour. And there was a study that was done on this that showed that if you do 10 air squats every hour, this can compensate for your sedentary lifestyle. Because unfortunately, this is the life we're living in. We are becoming more sedentary in our day-to-day lives. We're sitting more, we're not going out as much. There's younger kids on video games, they're scrolling. There's so much happening that is involving our sedentary lifestyle, which is obviously, like you said, increasing our risk of type 2 diabetes, cardiovascular disease, etc. Yep, you can do it.

Like this. There you go.

10 of those. If you do 10 of those, you can outweigh the benefits of a 30-minute power walk.

Every hour?

Yeah.

For how many hours?

8. Okay, so I could set an alarm on my phone every hour, just get up, or every 45 minutes get up and do an air squat. And this is primarily because— have you heard that when you eat, you get a massive spike of glucose? And the best way to bring that glucose spike back down is by doing any form of exercise. You can, albeit, go out and go for a fast run, do an air squat, bring that, uh, bring that glucose level back to baseline.

And do you think much about aerobic training as a preventative measure for Alzheimer's?

I love aerobic training. Women are facing a dilemma on social media because they're being given so much information. There is this huge uproar of, should I do zone 2 exercise or should I not do zone 2 exercise?

What is zone 2 exercise?

So we can think of physiology in zones. Zone 1 is what you and I are in right now, right? Zone 2 is that next level up. And that's generally when we're looking at exercising at around 60% of our maximum heart rate. It's where you can— where you're jogging, but you can have a conversation, but where you're huffing and puffing. When we're exercising, we need to produce energy, and that energy firstly starts in the mitochondria. So we need— all of our energy gets created, we create ATP, and that's how we are able to perform the given task. As soon as we get out of that zone and we go into zone 3, zone 4, and zone 5, we're producing energy outside of the mitochondria. In the cytoplasm. And when we're doing that, in order to do that, we're breaking down glucose so fast via a pathway called glycolysis. The byproduct of that is lactate, and then we produce lactate, and that's actually a fuel source for the brain. It's also a myokine, right? So that's when we're in zone 3, zone 4, zone 5. So a lot of women have been doing Zone 2. They've been going to the gym, they've been doing Zone 2, and I'm trying to push women to get out of Zone 2 for several reasons.

Not because it's not good for you. I think all forms of exercise are good for you. The more you move, the better, right? But let's be really honest, a lot of people in midlife are busy. They're time poor. Men actually get a greater return on investment by doing Zone 2. Women don't get the same return on investment from doing Zone 2. So I'm trying to push women to first work on Zone 5, Zone 3, Zone 4, Zone 5. If they can just do Zone 5, then do 2 to 3 sessions of resistance training a week. And if you have time left over, that's right there. I've just described around 4 hours of exercise. If you have time left over, then you can work in Zone 2. Now, Zone 2 is great if you're going to go out and go for a long run. You're doing many things. You are secreting a lot of BDNF, which we need. It's a growth factor for the brain. You're getting a massive amount of blood that's going into the brain, which is great as well. It's sustained blood, delivers oxygen and nutrients to the brain. You're doing a lot of things, right?

But what you're not doing is having a complete effect on the chambers of your heart.

Is it better for me to do 5 kilometers on a treadmill or outside?

I would say it's better for you, for the brain, to do a smaller amount of exercise and a higher threshold, because I, I was—

I think I've read somewhere one time that running outside is better for the brain because it stimulates the brain.

Well, you're outside, so you've got so many things around you. Imagine your brain. I told you it's got prime real estate. Every part of the brain is responsible for a different function from what you to what you hear. You go outside and you can see so many things. You've got forward ambulation, so that's going to help you with drive, motivation, dopamine. But then you're also taking in the sounds, the senses. It downregulates inflammation. So you get so many other things from doing that. Yes, but 5 kilometers outside compared to 20 minutes of high aerobic physical activity What is better for the brain? I would say that the Zone 5 is better for the brain. The Zone 5 training does a lot for the chambers of your heart as well. Now I'm going to grab this. We've got a little model here, and we can see that we have a left chamber, we have a right chamber. We have actually 4 chambers of the heart, but we have something in the heart called a ventricle. We've got a left ventricle and we've got a right ventricle. Now the left ventricle delivers oxygenated blood to the entire body.

It's really interesting because the chamber of the left ventricle is like a— is like a muscle, right? It's responsible for pumping blood to your entire body. It first gives blood to the brain, which means it's the most important part of your body. After it's done giving blood to the brain, it goes through to the rest of the body. As we get older, we get stiffening of these arteries, okay? Stiffening of all of the arteries in the heart, and we we get something called a left ventricular hypertrophy. So that's when the ventricle, the left ventricle, it starts to get thicker. And when it gets thicker, that means that we can't— it's not as strong, it can't pump a lot of blood as much as it could when it was younger to the rest of the body. Ben Levine, Dr. Ben Levine, he's a sports cardiologist, and he did this landmark study which changed how I thought about Zone 5 training. He took a group of sedentary males average age, I think it was around 47 to 55, so around 50 years old. And he scanned their hearts. He did, you know, he looked at— he did echocardiograms, he took photos of the heart, he did everything he could to see when I was first starting the protocol, what does their heart look like.

He then subjected them to around 4 hours of exercise per week, and that was stratified against— he did one resistance training session a week, one was high-intensity physical activity at around 90% of the maximum heart rate, the VO2 max heart rate. And then in between, he did some long sessions as well. Right. But it was all moderate to rigorous exercise, and that was done over 2 years. At the end of those 2 years, what he found was that he remodeled the heart by 20 years. So he reversed the age-related effects and defects of the heart by 20 years, essentially turning the 50-year-old hearts into 30-year-old hearts. Just from physical activity alone.

4 hours a week for 2 years?

4 hours a week for 2 years.

And what kind of exercise was it?

So he got them to do, like, let's say for example, one of the, um, one of the protocols was exercising at 90% of your maximum heart rate. So when we do this, we're generally looking at increasing our VO2 max. So you've probably heard that VO2 max along with strength, but VO2 max is the strongest predictor of all-cause mortality, right? So if you want to improve your VO2 max and if you want to get the heart-related changes that he did, what you want to do is you want to do 20 minutes of VO2 max per week just to keep your VO2 max, because it does decline year on and year out. Starting at the age of around 35, we start to see a decline in VO2 max. So If we want to work on our VO2 max, we want to be doing a— what we call the Norwegian 4x4. It's the gold standard of increasing your VO2 max. So you want to get your heart rate elevated to 90 to 95% for 4 minutes on, 4 minutes off, repeat 4 times. So how do I do this? Well, I actually do this twice a week. Because the more you do, the better.

I do this on a stepper. I do this at the gym, and I put my stepper on to— I think I'm at like level 14, and I'm working my way up, and I'm staying on there for 4 minutes, and then I'm having a complete stop and a complete rest for 4 minutes, and I'm repeating that 4 times. So what I'm doing in that moment, I'm not just getting a massive shunting of blood to the brain, okay, which is good. I'm not just getting a massive release of myokines and exokines to the brain, I'm also remodeling the heart. I'm downregulating tumor cell growth. I'm improving my cognitive performance. I'm doing so much more than just exercising alone.

So that's once, once a week in Levine's study that reversed these guys' hearts by 20 years. Um, that you do that once a week.

You only have to do that once a week, but he also did, um, he did around 70% of maximum heart rate for around 2 hours a week, and he also threw in one resistance training session. So consistency is key.

I'm just looking at some of the findings of that study, and one of the surprising things is it showed that there is a biological exploration date, per se, for the reversal of the heart.

Yeah.

And then the heart retains its plasticity, the ability to remodel itself, until the age of 65. If this intervention had started after the age of 65, the heart was too stiff to be physically remodeled to get that 20-year reversal. Yeah, you have to start in late middle age.

Exactly. So midlife is the window of opportunity for brain health and for longevity.

I didn't realize you sort of remodel the heart yourself. That's interesting.

Yeah, you can remodel the heart, and the heart is amazing, okay? Because what you see with the aorta, right? So the aorta goes up, and we've got— we've got two— we've got, uh, the main blood supply for the brain exists in the vertebral arteries, okay? So there's branching off of the aorta, comes from the heart, vertebral arteries, which supply the posterior part of the brain and the cerebellum with blood. And then you've got the carotid arteries, so one on each side branching off the aorta, which supply the frontal and middle part of your brain with blood. The brain is the most vascular-rich organ in the entire body. In times of stress such as hypertension, okay, that is elevated blood pressure, we see that we can actually kill off the tiniest parts of the blood vessels, which are called the capillaries. You can see the capillaries up here. They supply even the blood-brain barrier, so they supply mainly the outer cortex. Of the brain with blood. When we have elevated blood pressure, we are starting to kill off those tiny little capillaries of the brain. Those capillaries are feeding different neurons in the brain and also feeding the blood-brain barrier.

So when we get breaking off of these, we lose the blood supply, we lose the oxygenation, we get a breakdown of the blood-brain barrier itself, which is scary. And we see that in patients who have got mild cognitive cognitive impairment. You can call it— you've heard of leaky gut, we can call it leaky brain. If you have a leaky brain, what happens eventually is— so your blood-brain barrier sits like this, okay? And there are cells, and we call them parasites, for example, and they're bound together by tight junctions. That's what the blood-brain barrier is. It's like a— you think of the blood-brain barrier as the bouncer of a nightclub. They are all standing there like this, responsible for who can come in and who can't. And they don't allow some molecules to get in. But over time, when this starts to degrade and become leaky, they start to spread apart. And when they do, you can have the passive diffusion of all these molecules coming in. And that's really bad for your brain. So we want to maintain the integrity of the blood-brain barrier by maintaining the capillary health. We don't want the capillaries to die.

They're one cell thick. Any type of damage can damage them and kill them. Hypertension. There was a really great study. It was called— it was actually the SPRINT trial, and it was— it's now the gold standard for the recommendation of 120 over 80. So when you have your blood pressure taken, we get the systolic over diastolic. And you've probably— I don't know if you take your blood pressure, but doing your blood pressure every day is a really great, inexpensive, and effective tool for maintaining good brain health. So you measure your blood pressure, and if you are hypertensive— this is anywhere over 135, okay, systolic over 135— that's when things start to break down. That's when we start to get the breakdown of those small, one-cell-thick capillaries. So in this trial, in the SPRINT trial, what they found was that when they aggressively manage these patients and they bring their blood pressure down— they did it pharmacologically through something called an ACE inhibitor, it's a medication to drive down blood pressure— when they bring it down pharmacologically, these patients preserved their brain gray matter and their cognitive functions. So we now have a gold standard, and this is what I would recommend anybody.

On Amazon, it costs about $25 for a blood— an automatic blood pressure Monitor, do it every single morning, and watch your blood pressure.

And then if it's high, what do I do about it?

Well, outside of pharmacology, if we don't want to take a medication, we want to get stronger, and we want to do this via exercise. Stress is one of the biggest things driving high blood pressure. Manage stress, manage cortisol, manage chronic inflammation by way of exercise, sleep, all of the things that Mother Nature gave us.

I was just looking at the study that reversed the heart by 20 years and trying to figure out what exercises they did. And as you said, the first one was the high-intensity workout, the 4x4.

Yep.

Then they did a long aerobic exercise. Again, this is all once a week. So 60 minutes once a week doing a longer exercise, like it could be hiking or tennis or cycling. A moderate-intensity workout, 30 minutes, where they did the talk test. You should be able to break a sweat but still be able to speak. So that was once a week. And then lastly, strength training once a week. So it's really a variety. Of exercises that caused such a profound impact on the heart. And I think cardiovascular diseases are the single biggest killer.

Yeah, cardiovascular disease. Dementia is the number one killer of women in the UK. The number one, really. It's the number one cause of death in Australia for both men and women.

How does it kill you?

Because we all think about memory loss and stuff like that, but And so this is the actual devastating part. We don't die of Alzheimer's disease specifically. Over time, what happens is in these patients, you have to remember Alzheimer's disease is like end-stage cancer. Once you get the diagnosis, there is no cure, there is no going back, there is no reversal. You have the disease and that's the scariest part. Mild cognitive impairment, you can slow the progression of that. Like I said to you, it goes for 20 years, mild cognitive impairment. You can slow the progression of mild cognitive impairment, but as soon as you get diagnosed on that awful day that your mother or your friend gets diagnosed with Alzheimer's disease, it's a sad day. And what ends up happening with these patients is you can die of asphyxiation, you can die of— your brain loses the signal to swallow. It loses the signal to— maybe you fall because you've lost balance. It's really, it's a really scary moment, but it's not like you die of Alzheimer's disease specifically.

If you were diagnosed with Alzheimer's disease, it's an interesting reaction because I would have no hope.

I think a better question is—

You'd have no hope.

If I was diagnosed with Alzheimer's disease, there is nothing I could do.

How would that change your life and the decisions you make, or would it at all?

I would aggressively, aggressively exercise. I would monitor my diet. I would aggressively monitor my diet, and I would potentially have a ketogenic diet. Because what we've found is that during this metabolic crisis that happens in your brain, okay, where you lose the ability to use glucose as your primary fuel source. So the brain doesn't know how to use glucose as its primary fuel source. So it's under attack during Alzheimer's, during Alzheimer's, but also during this window in— for women as well in the perimenopause state. So the brain cell, when it's under attack and it can't utilize glucose effectively and it doesn't have any energy, it starts to think about survival. It starts to think, what can I do? I'm under attack. So it starts to break down the myelin sheath. And in that moment, it's actually the astrocytes— they're the supporters of the brain, so of the brain cells. So they start to think, okay, let's break down the myelin sheath. From that, the astrocytes produce ketone bodies, and then the ketone bodies get shuttled into the brain. And that's how we use energy in the brain. So in that state of metabolic crisis, I would make sure that I am having a ketone-rich diet, or I may be getting exogenous ketones.

I would aggressively exercise. I would aggressively manage my, my lipids. I'd have a high intake of omega-3 fatty acids, and I would preserve, if I could, any form of cognitive function by way of talking to people, by going outside, socializing, having hard conversations if I was intact and I could do so. I would throw tennis balls to the wall.

What you just listened to was a most replayed moment from a previous episode. If you want to listen to that full episode, I've linked it down below. Check the description. Thank you.

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