How Exercise, Sleep, and APOE4 Shape Brain Aging

Steven Bartlett: on this point of the brain then if if I I don't want to be an older person who can't remember things and stutters over my words and falls into cognitive decline. And I'm I'm 32 now. So I'm I feel like I'm in a moment in time where I can really make decisions now that have a really big impact on my 90-year-old brain and my ability to think straight and clearly and remember things. Are there things that I can be doing now that will have a profound impact on my cognitive performance at 90?

Dr. Rhonda Patrick: Yes.

Steven Bartlett: And what are those things?

Dr. Rhonda Patrick: Absolutely. Well, first of all, just to kind of wrap up the exercise story because I think this study is so profound and in fact it wasn't done in 32 year olds. It was done in older adults. So we're talking 60 year olds or a little bit older. And these individuals were put on a aerobic exercise training program for one year that was more of like a 70 to 75% max heart rate. So it wasn't so vigorous but it was pretty pretty vigorous for them right and um the the basis of this study was to look at brain aging as we age I mentioned our heart aging right it gets stiffer and shrinks with age our brain also shrinks with age it's called atrophy and as we age especially starting in midlife so around the age of 50 your your brain and certain areas of the brain like the hippocampus which is involved in learning and memory starts to shrink by about 1 to 2% % per year.

Steven Bartlett: I don't want that to happen.

Dr. Rhonda Patrick: Same. Same. The good news is um in this study after a year of this sort of aerobic exercise training program, they were doing three times a week about 30 minutes a day. Really not even that intense these individuals. And then there was a control group that was kind of the stretching. They like to use the stretching as the control group. So that let's talk about the the control group. the stretching group, they did lose about 1 to 2% in terms of the size of their hippocampus. It shrunk 1 to 2% after that year, which is what you would expect normally. However, the group that was training, not only did they not have their hippocampus shrink by 1 to 2%, it actually grew by 1 to 2%. Which comes down to that neurogenesis, that growth of new neurons, the brain-derived neurotrophic factor that's able to do that. you're actually able to grow new neurons even when you're in the age of 50, which is amazing. It's incredible. So, that study I love because a couple of reasons. One, it shows that it's possible to not only stave off, you know, some of the components of brain aging, but to reverse it and increase it, right, through exercise. And number two, I love it because it's never too late. like you can start this, you know, in your 60s and still have a benefit, right? You're you're talking about being in your 30s, but you know, some people watching the show, listening to the show, may already be in their 50s or 60s, right? So, it's never too late. Um, likewise, you know, we're talking about being cognitively sharp and not getting dementia. There's also studies showing that people like women that were brought into the lab, they had their cardiorespiratory fitness measured, those women with the highest cardiorespiratory fitness were 80% less likely to come down with dementia over the follow-up period of time. So it again, I think exercise is one of the big ones when it comes to brain aging. But you asked an important question. and you say, "What can I be doing now that's going to affect the way my brain ages, you know, for the subsequent decades of my life?" And there are other things that can also be done that don't even require as much effort as exercise. Exercise is the gold standard because I mean, being able to not only, you know, stave off atrophy of the of the brain, but to like regrow some of it is incredible, right? I mean, that's just mind-blowing.

Steven Bartlett: Have they ever taken people with dementia, Alzheimer's, and put them on an exercise program and monitored the decline of their cognitive abilities on an exercise program?

Dr. Rhonda Patrick: Yes. I mean, it's it's much harder when you already have someone who is in that pathological state because things just really snowball and accelerate. And there are some benefits. I mean, but it's not it's not prevention is always the best. Prevention is always the best. And so, you know, I I think that if there's any sort of take-home here, it's that like let's let's try to do what we can now so that we don't get to that point

Steven Bartlett: before we get into the the the easier ways of staving off cognitive decline. Do do we know what causes dementia and Alzheimer's yet? Do do we have any ideas? Because we can when they do the brain imaging, they can kind of see these plaques on the brain, they say. But

Dr. Rhonda Patrick: I mean there's a lot of different it's multifactorial which means there's a lot of different causes of dementia and Alzheimer's disease. So I would say you mentioned plaques amyloid-beta plaques. What happens is you know that's the aggregation of a protein in our brain called amyloid that typically is cleared from our brain and um what happens is this abnormal you know thing happens where you're not clearing the amyloid and so it starts to kind of form these clumps and aggregates with the amyloid proteins that are not being cleared. And that essentially is happening outside of your neurons, but it's happening where the synapses are formed between neurons. And so what happens is it kind of disrupts the synaptic connection between neurons, which is essentially forming a memory. And so when you start to disrupt that connection, you lose not only the the memories start to go away, but the whole purpose of the neuron is to kind of I mean, one of the purposes is to to form a memory. And so you start to like neurons start to die, right? when they start to lose their purpose. Amyloid aggregation is linked to a lot of things. So for example, I mentioned it being cleared when we sleep, particularly when we're in our deep sleep stage, slow-wave sleep, that is um something happens that's kind of incredible. It's called activation of the glymphatic system. So you've heard of the lymphatic system. Well, the glymphatic system is essentially this series of like networks and like almost like these like highways and essentially roads and stuff all like throughout the brain where you're squirting this cerebrospinal fluid throughout the brain and it's clearing away all the garbage things like proteins that didn't get cleared and it's sort of squirting them out and clearing them out through this lymphatic system. that lymphatic system is activated during sleep. And it's one of the reasons why people that don't get good sleep over the course of decades have a higher risk of Alzheimer's disease is because they're getting these amyloid plaques built up in their brains. But there's other causes as well. So for example, glucose metabolism is disrupted in the brains of Alzheimer's disease. You need glucose, your neurons need glucose. And so the you know the essentially um your your brain isn't able to make energy correctly without the glucose getting into your brain. And so that's another sort of metabolic underlying cause of Alzheimer's disease where you're essentially I mean it's thought to be where you're eating a lot of refined carbohydrates, refined sugars and you're not exercising and essentially you're you're disrupting the glucose metabolism in the brain as well as the whole body. Right? So the brain and body are connected but um there's also genetic causes as well and you know some people have genes that can increase the risk of Alzheimer's disease because they're not able to clear amyloid as well because they're not able to repair damage as well. So the the blood-brain barrier which is really important for filtering out toxic things from getting into the brain it starts to break down and that's one of the I would say early early signs of Alzheimer's disease is that breakdown of the blood-brain barrier and that happens in people that have a genetic risk factor called APOE4. You may have heard of this but this is probably one of the biggest genetic risk factors for Alzheimer's disease. About 25% of the population has one copy of this gene. That increases the risk of Alzheimer's disease by twofold. If you have two copies of it, it increases the risk of Alzheimer's disease by tenfold.

Steven Bartlett: So twofold being 200%.

Dr. Rhonda Patrick: Twofold being twice twice as much. Yeah. 200%. And tenfold being a thousand%. Right. You're you're you're basically I mean it's it's pretty bad. And it's not like um it's not your destiny to get the Alzheimer's disease if you have those genes. You can do things in your lifestyle that can sort of turn the table. So you're not you're not essentially going to be getting that that Alzheimer's disease and a lot of different lifestyle factors like getting good sleep like exercising, avoiding alcohol, avoiding smoking, not being overweight and obese. Like those affect your Alzheimer's disease risk. More importantly, if you have one of those genes, then you really have to be cognizant of those things because if you have one of those, you know, APOE4 genes, then then essentially your lifestyle matters even more than people that don't.

Steven Bartlett: And you can do a test to figure out if you have those genes.

Dr. Rhonda Patrick: Yes. Yes. There's a a variety of genetic testing services that can be done. Pretty much all the ones that are out there on on the market, you know, Ancestry DNA. I mean, depending on where you live and what there's so many out there right now that will that will test for that.

Steven Bartlett: I'd be mortified if I found out I had two of those genes.

Dr. Rhonda Patrick: Two of them is less common. When I mentioned the 25% of the population having it, it's usually one allele. Alcohol essentially can really increase the risk of Alzheimer's disease if you have one of those genes. And I think that there's really no safe amount of alcohol that can be consumed for people that have APOE4 if you're concerned about dementia and Alzheimer's disease. The other thing is contact sports and traumatic brain injury. People that have any of the, you know, any one or two of the APOE4 genes, if they have that, then if they get a TBI, like if they're playing American football or they're playing soccer or MMA or boxing, whatever, then you talk about like going up to a tenfold risk of Alzheimer's disease when you get like an injury because people with those genes don't repair damage as well. And so it affects their their brain's ability to repair damage. And so that's also really important to consider.

Steven Bartlett: So moving back then to this the simple things that we can do to improve our cognitive performance as we age, the things that are simpler than doing the vigorous HIIT.

Dr. Rhonda Patrick: There's actually quite a few. And first and foremost, the one I love the most is a simple multivitamin. And the reason I love this is because I don't know it was about 10 years ago there was a a huge study that was published and it was published in the Annals of Internal Medicine and it was called Enough is Enough. Multivitamins are not only useless, they're harmful and it was essentially looking at a variety of studies and arguing that multivitamins are expensive urine. You're just not really doing anything. And in fact, if you take a multivitamin, you might even be increasing the risk of disease. That study was terrible. And I 10 years ago went and just broke it down and, you know, pulled it apart piece by piece. But here we are 10 years later. Three large clinical trials have been done. These are randomized controlled trials where older adults were given either a multivitamin and this was just your standard run-of-the-mill multivitamin Centrum Silver or they were given a placebo and they were given this for a couple of years. And what three different studies showed was that a multivitamin improved cognition, improved processing speed, it improved what's called episodic memory. So the kind of memory where you're remembering experiences and you can recall events, things like that. And not only did it improve it, it improved it so much that it was equivalent to reducing the aging of the episodic memory by 5 years. So a simple multivitamin and why is that important? Because you know multivitamins have a variety of these vitamins and minerals that we're not getting from our diet that are important for everything. for metabolism, for the way our neurotransmitters are firing, for reducing damage that's causing, you know, oxidative stress, right? So, a simple multivitamin, how much easier can it be than taking a simple multivitamin? And the fact of the matter is that we're talking about a randomized control trial. This is showing cause, right? This isn't just an association. This is showing that you took a multivitamin for a couple of years and improved your cognition more than a placebo. So, I think that's pretty incredible and it's one of the examples that I like.