The Diary of a CEOCognitive Decline Expert: The Disease That Starts in Your 30s but Kills You in Your 70s
EVERY SPOKEN WORD
105 min read · 20,651 words- 0:00 – 2:38
Creatine as a brain-protection supplement (sleep loss, stroke, concussion)
- SBSteven Bartlett
And we have this white powder in front of me. You've got a big smile on your face
- LNLouisa Nicola
I do, because I don't care who you are, you should definitely be having this. [bell dings] So let's talk about creatine. Phenomenal research shows you can creatine your way out of sleep deprivation. It can protect your brain against a concussion, stroke, from stress, and there was a study done on Alzheimer's disease patients, and they found that patients not only preserved their cognitive functions, but they had more energy and they were able to exercise more. And I know this because I'm a clinician, and over the last decade I've been surrounded by the greatest neurosurgeons in the world studying the brain. And so I'm here to tackle one disease, and that is Alzheimer's. Because it generally starts in our 30s, and 60 million people worldwide have Alzheimer's, 70% being women. And I get angry and I get passionate because women have been lied to, they've been underrepresented, they downplay their symptoms, or they're too scared to ask their doctor for advice. And what people don't really know is that it is a preventable disease, but it's like end-stage cancer. Once you get the diagnosis, there is no cure, and the fact that so many people are at the mercy of a disease that is preventable is not okay with me, and I don't think people understand these things. Like, people don't really know that we're becoming more sedentary, which is a disease. 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. And then we have several lifestyle factors that can lower your risk of getting Alzheimer's disease, as well as showing you what five minutes a day can do for your brain performance just using a tennis ball and an eye patch.
- SBSteven Bartlett
[inhales] Guys, I've got a quick favor to ask you. We're approaching a significant subscriber milestone on this show, and roughly 69% of you that listen and love the show haven't yet subscribed for whatever reason. If there was ever a time for you to do us a favor, if we've ever done anything for you, given you value in any way, it is simply hitting that Subscribe button. And it means so much to myself, but also to my team, 'cause when we hit these milestones, we go away as a team and celebrate. And it's the thing, the simple, free, easy thing you can do to help make this show a little bit better every single week. So that's a favor I would ask you, and, um, if you do hit the Subscribe button, I won't let you down, and we'll continue to find small ways to make this whole production better. Thank you so much for being part of this journey. It means the world and, uh, yeah, let's do this. [upbeat music] Louisa, what is it you do, in simple terms? And I guess most importantly, why is it that you do it, and why now?
- 2:38 – 5:25
Why Alzheimer’s is urgent—and largely preventable
- LNLouisa Nicola
Over the last decade I've been studying the brain. I'm both a clinician and an academic, so I get to see the brain and I also get to research it, and I'm really here to tackle one disease, and that is Alzheimer's disease.
- SBSteven Bartlett
Why is this so important now?
- LNLouisa Nicola
Right now because 60 million people worldwide have Alzheimer's disease. That number is going to triple by the year 2050. 110 million women will have Alzheimer's disease by the year 2050. This is a disease that robs you of who you are, your complete identity. So we're gonna get really into this straightaway 'cause I brought Henry with me, right? So-
- SBSteven Bartlett
And for anyone that can't see, Henry is a model brain that she's holding in her hands
- LNLouisa Nicola
... this is around two pounds, and if you actually feel it and, you know, if you actually feel a real human brain, it feels like tofu, but this is everything you are. And the fact that so many people are at the mercy of a disease that is preventable is not okay with me. It doesn't sit well with me. We used to think that women were disproportionately affected by Alzheimer's disease because we lived longer, because age played a role in it, but we now have substantial evidence to show that it's not the fact that women live longer, or people in general, because dementia and Alzheimer's disease are not part of the natural brain aging process. For women, and they differ from men, and we can separate the sexes and talk about it, for women it is purely because being a woman is a risk factor for getting this disease. Now, if we go through and we have a look at all of the people that currently have Alzheimer's disease, 95% of them could have been prevented because this is not a disease of genetics, it's a disease of lifestyle.
- SBSteven Bartlett
95% of it could have been prevented?
- LNLouisa Nicola
Correct. We're, we're born with our, with our genetic makeup, meaning that, for example, if you have a genetic mutation on chromosome 4, you will get Huntington's disease. There is nothing we can do about that. That's how you were born. But when it comes to Alzheimer's disease, there's around 20 to 30 genes involved in the disease. Only around 3% of the disease cases right now were driven through those genetic mutations. The genetic mutations that you are born with, you get them from mom and dad, are presenilin 1, presenilin 2, and the amyloid precursor protein. So you, if you have a genetic mutation in one of these genes, you will get some form of dementia.
- SBSteven Bartlett
What is the age range where people will start to experience Alzheimer's?
- 5:25 – 7:44
Alzheimer’s vs. dementia, and how it starts decades before symptoms
- LNLouisa Nicola
Let's just actually take a broad overview of what Alzheimer's disease is, okay?
- SBSteven Bartlett
Yeah.
- LNLouisa Nicola
So you've probably heard of dementia.
- SBSteven Bartlett
Yeah.
- LNLouisa Nicola
So dementia is the umbrella term. So Alzheimer's disease is, sits under the umbrella. It's a form of dementia. There's frontotemporal dementia, which is what Bruce Willis has. There's dementia with Lewy bodies. There's Parkinson's dementia. There's vascular dementia. This disease, dementia or Alzheimer's disease, is a disease of midlife, and so it generally starts in our 30s. It starts in our 30s, but the first symptoms show up in our late 60s, 70s, and beyond.
- SBSteven Bartlett
When you say it starts
- LNLouisa Nicola
Yes. Our brain fully develops at around 25 years old, 25 to 30. And after that, that's when we- if we don't take care of our brain, we start getting a decline in these functions. Now, let's go back to the brain. The brain is 87 billion neurons, around 5,000 to 10,000 connections per neuron. The, my favorite area of the brain is the cerebellum, and the Purkinje cells inside the cerebellum have upwards of 50,000 connections per cell. So, so tightly dense and there is so much happening, it takes 20% of the total calories that you consume every day to power this thing, and it's the most vascular-rich organ in the entire body. Over time, through things such as sleep deprivation, poor diet, lack of physical activity, environmental toxins, this slowly erodes at the functioning of the brain. And over time, this starts to compound because that's what biology is. Everything is compounding. One night of sleep deprivation raises your risk of amyloid beta, which is one of the hallmarks of Alzheimer's disease pathology, by 4%. That's just one night of sleep deprivation. Imagine a new mother or a shift worker or a physician in their residency getting countless nights of sleep deprivation day in and day out. Imagine all of that compounding. And what happens? Well, we end up with either neuronal loss, which is like the complete atrophy of certain parts of the brain, and that's what is mild cognitive impairment. Mild cognitive impairment is a pre-dementia state.
- 7:44 – 8:38
What brain atrophy looks like (healthy brain vs. Alzheimer’s)
- SBSteven Bartlett
So what is this that I have here, this photo, um-
- LNLouisa Nicola
So-
- SBSteven Bartlett
... of a brain
- LNLouisa Nicola
... you've got the sagittal view right now of the brain, and we're looking at a healthy brain on here. As you can see, I'm gonna show it up here. On the left-hand side, you can see that the brain is thick. We can see that the integrity of the gray matter which sits out here is thick. It's volumous. Okay? We can see that the ventricles are smaller. We go over here and we see thinning of the cortex. You can see these big spaces between the gyri. These are thick because the gray matter has atrophied. It's shrunk. You can see that the space between the cortex itself and the skull, there's a bigger space. You can see these ventricles here, these butterfly-shaped ventricles. This is thicker. This is thinner. We can see atrophy down here. So essentially, the brain is getting smaller and smaller.
- 8:38 – 11:52
Cognitive reserve: why some 60-year-olds stay razor-sharp
- SBSteven Bartlett
At the age of 30, if I do everything right, and we were to sort of plot this on a graph of where I land at 70, what is the variance of where I'll end up at 70? You know, my brain is quite important to me, and I do worry. I think, fuck, like ... I think I worry in part 'cause I, I, I sit and interview a lot of people at a lot of different ages, and one thing you notice as an interviewer is some people at 60 have, are razor sharp.
- LNLouisa Nicola
Mm-hmm.
- SBSteven Bartlett
And some people at 60 are not as sh- razor sharp.
- LNLouisa Nicola
Yeah.
- SBSteven Bartlett
Their, uh, ability to articulate their words, their memory recall, their ability to understand stats and stories, all of this. And I sit here and go, "I wonder what the difference is."
- LNLouisa Nicola
Yeah. And that's actually beautiful because it brings up this important concept in neuroscience called cognitive reserve, and that's your brain's ability to withhold capacity to overcome stresses, okay? So you've probably heard, for example, let's use the analogy of physical performance.
- SBSteven Bartlett
Mm-hmm.
- LNLouisa Nicola
Your VO2 max, which is a measure of your peak respiratory fitness, you know, how well you can utilize oxygen-
- SBSteven Bartlett
Mm-hmm
- LNLouisa Nicola
... when you are at a, at a high-intensity state. How well does your body utilize oxygen? The h- the fitter you are, the more reserve you have to overcome stress. Stress such as a- an infection, everyday stresses, sleep deprivation, surgery. The more reserve you have in your bank to overcome that. The same is with your brain. The more cognitive reserve that you have, the more cognitive capacity that you have been training year on and year out will save you at 60 from har- harmful insults, such as you can get a woman at the age of 80 with a head full of amyloid beta.
- SBSteven Bartlett
Amyloid beta being?
- LNLouisa Nicola
The, one of the hallmarks of Alzheimer's disease. You can get somebody with a head full of amyloid.
- SBSteven Bartlett
Which is like a plaque on the brain.
- LNLouisa Nicola
Yeah. It, it's a protein that's actually ... It's a, it's a protein that lives inside the neuron itself, and we can explain what that is, which I will in a second. But let me just tell you, you can have a head full of amyloid in this person, and they have retained their cognitive functions. Then you can have somebody else with hardly any amyloid, but they've lost their cognitive functions, and this all comes down to cognitive reserve.
- SBSteven Bartlett
And cognitive reserve lives where in the head?
- LNLouisa Nicola
You've got around 5,000 to 10,000 connections per cell. Over time, those connections fail. Now, those connections are responsible for your thinking, your processing speed. Every time you have a thought, you build a new connection. The more connections that you have, the more things that you see, the more novelty that you give your brain, the richer it gets, the more stable it gets. So the ends of these, of the neurons, we have dendrites. And coming off the dendrites are these little trees. Imagine a, a branch. That's the dendrite. And all of the leaves that come off it, all these little dendritic trees, if you will, and they connect to nearby cells, 10 to 10,000 cells. Over time, those are the connections that fall. Those are the connections that fail. They fail because you don't utilize them.
- 11:52 – 13:44
Building reserve: exercise, reading/handwriting—and why scrolling harms focus
- SBSteven Bartlett
So the way that one would build reserve at the age of 30 is to ...
- LNLouisa Nicola
Is by exercising. We can build reserve in a number of different ways. In fact, there was a really wonderful study that just came out that I just read about, and they found that those who preserved cognitive capacity at 75 years old were handwriting and readingSo handwriting and reading preserves cognitive functions. Exercise is one of the most potent stimulus for brain health and Alzheimer's disease prevention and cognitive reserve. The more you exercise, the bigger your brain.
- SBSteven Bartlett
What about scrolling on social media? D- does it improve my reserve if I'm watching videos?
- LNLouisa Nicola
It's in the opposite.
- SBSteven Bartlett
Why would that be? 'Cause I'm still learning stuff-
- LNLouisa Nicola
Yeah
- SBSteven Bartlett
... when I'm on the internet.
- LNLouisa Nicola
Because what you're doing then is you are relying on short dopamine hits. Every time you scroll, you're sending signals to your brain that you're getting a dopamine hit, and your brain gets used to it. Remember, your brain is only there for two things, survival and reproduction. So every time that you stress your brain in the smallest amount of times and you're giving it dopamine hits, it doesn't allow us to do other things for a sustained period of time, like focus, read, have a conversation.
- SBSteven Bartlett
So writing and reading are good for building up my neurological reserves.
- LNLouisa Nicola
Yeah, neurological reserves. It doesn't compare to what exercise can do for the brain. And it's so sad because around 80% of the US population don't exercise for at least 30, 30 minutes a week, which is actually quite scary. The physical activity guidelines are 150 minutes to 300 minutes of moderate to rigorous physical activity per week.
- 13:44 – 17:20
Strength training for the brain: trials, genetics, and ‘strong legs’
- SBSteven Bartlett
What's the most compelling study you've ever encountered that proves that exercise is central to Alzheimer's prevention and brain health?
- LNLouisa Nicola
When we look at all of the data, we can see that the biggest amount of return on investment is from resistance training.
- SBSteven Bartlett
Resistance training being?
- LNLouisa Nicola
Strength training. One of the most compelling studies was probably the, um, the SMART trial where they, uh, took a group of people with mild cognitive impairment and gave them two to three 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.
- SBSteven Bartlett
The gray matter?
- LNLouisa Nicola
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 ask me, "Steven, 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, uh, 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 two copies of this gene. So you get two copies, one from Mum, one from Dad. It's the apolipoprotein E gene, and it comes in three 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 two to three times. If you have two 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.
- SBSteven Bartlett
And how would one go and get checked?
- LNLouisa Nicola
You can get the APOE4 gene checked out with your doctor. It's a simple blood test.
- SBSteven Bartlett
On this point of resistance training, I've heard you talk about how the legs-
- LNLouisa Nicola
Mm-hmm
- SBSteven Bartlett
... are so important.
- LNLouisa Nicola
Yeah
- SBSteven Bartlett
Having strong legs.
- LNLouisa Nicola
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.
- SBSteven Bartlett
Mm-hmm.
- LNLouisa Nicola
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, uh, did better on different cognitive tests.
- 17:20 – 23:26
Mechanisms: myokines, BDNF, inflammation, and ‘lift heavy’ neural drive
- SBSteven Bartlett
Why is resistance training increasing the size of my brain?
- LNLouisa Nicola
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 l- lifting at around 80% of your one repetition max. 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, 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 relis- 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.
- SBSteven Bartlett
What is that, sorry?
- LNLouisa Nicola
The interleukin family is a, 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-
- SBSteven Bartlett
Mm-hmm
- LNLouisa Nicola
... 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, uh, one of... this was one of the, uh, 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.
- SBSteven Bartlett
How much exercise does one need to do to avoid the, uh, cancer-related, um, side effects, but also the Alzheimer's problem?
- LNLouisa Nicola
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 three 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 heavy weight as opposed to a light weight, it takes more neural real estate to lift that heavy weight. So the heavier you lift, the greater the neural drive. The greater the neural drive, the better it is for your brain.
- SBSteven Bartlett
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?
- LNLouisa Nicola
Deadlift.
- SBSteven Bartlett
Why?
- LNLouisa Nicola
If done correctly, the deadlift can use almost every muscle in your body. Erector 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.
- 23:26 – 25:39
Sedentary living as a disease—and the ‘10 air squats per hour’ fix
- SBSteven Bartlett
According to the World Health Organization, we're getting increasingly more sedentary.
- LNLouisa Nicola
Mm.
- SBSteven Bartlett
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 was, that's annoying to read because I feel like that's me
- LNLouisa Nicola
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, uh, 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, et cetera. Yep, you can do it
- SBSteven Bartlett
Like, like this?
- LNLouisa Nicola
There you go. 10 of those. If you do 10 of those, you can outweigh the benefits of a 30-minute power walk.
- SBSteven Bartlett
Every hour?
- LNLouisa Nicola
Yeah
- SBSteven Bartlett
For how many hours?
- LNLouisa Nicola
Eight
- SBSteven Bartlett
Okay. So I could set an alarm on my phone
- LNLouisa Nicola
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?
- SBSteven Bartlett
Mm-hmm
- LNLouisa Nicola
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, a fast run, do an air squat, bring that, uh, bring that glucose level back to baseline
- 25:39 – 35:20
Aerobic training, Zone 2 vs Zone 5, and remodeling the heart for brain health
- SBSteven Bartlett
And do you think much about aerobic training as a preventative measure for Alzheimer's?
- LNLouisa Nicola
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?
- SBSteven Bartlett
What is zone 2 exercise?
- LNLouisa Nicola
So we can think of, uh, physiology in zones. Zone 1 is what you and I are in right now.
- SBSteven Bartlett
Mm-hmm
- LNLouisa Nicola
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, uh, w- 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 two to three sessions of resistance training a week. And if you have time left over, that's right there, I've just described around four 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, uh, 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.
- SBSteven Bartlett
Is it better for me to do five kilometers on a treadmill or outside?
- LNLouisa Nicola
I would say it's better for you, for the brain, to do a smaller amount of exercise and a higher threshold
- SBSteven Bartlett
'Cause I, I was, I think I read somewhere one time that running outside is better for the brain because-
- LNLouisa Nicola
Well-
- SBSteven Bartlett
... it stimulates the brain
- LNLouisa Nicola
... of co- 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 see 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 down regulates inflammation. So you get so many other things from doing that. Yes. But five 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 gonna grab this. We've got a little model here. And we can see that we have, uh, a left chamber. We have a right chamber. We have actually four 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 muscleRight? 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 get s- we get something called 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 they were first starting the protocol, what does their heart look like? He then subjected them to around four 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 two years. At the end of those two 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.
- SBSteven Bartlett
Four hours a week for two years.
- LNLouisa Nicola
Four hours a week for two years.
- SBSteven Bartlett
And what kind of exercise was it?
- LNLouisa Nicola
So he got them to do, l- 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 wanna get the heart-related changes that he did, what you wanna do is you wanna do 20 minutes of VO2 max per week just to keep your VO2 max, because it does decline-
- SBSteven Bartlett
Mm-hmm
- LNLouisa Nicola
... 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 wanna be doing a, what we call the Norwegian 4x4. It's the gold standard of increasing your VO2 max. So you wanna get your heart rate elevated to 90 to 95% for four minutes on, four minutes off, repeat four 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 [laughs] the gym, and I put my stepper onto, I think I'm at, like, level 14, and I'm working my way up and I'm staying on there for four minutes, and then I'm having a complete stop and a complete rest for four minutes. And I'm repeating that four times.
- SBSteven Bartlett
Mm-hmm.
- LNLouisa Nicola
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.
- SBSteven Bartlett
So that's once, once a week in Levine's study-
- LNLouisa Nicola
Yeah
- SBSteven Bartlett
... that reversed these guys' hearts by 20 years.
- LNLouisa Nicola
Yep.
- SBSteven Bartlett
Um, that you do that once a week.
- LNLouisa Nicola
You only have to do that once a week, but he also did, um, he did around 70% of maximum heart rate for around two hours a week, and he also threw in one resistance training session. So consistency is key.
- SBSteven Bartlett
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.
- LNLouisa Nicola
Yep.
- SBSteven Bartlett
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 to that 20-year reversal.
- LNLouisa Nicola
Yep.
- 35:20 – 40:16
Blood pressure, capillaries, and protecting the blood–brain barrier
- LNLouisa Nicola
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 exist in the vertebral arteries.
- SBSteven Bartlett
Mm-hmm.
- LNLouisa Nicola
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, uh, 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, um, a breakdown of the blood-brain barrier itself, which is scary, and we see that in patients who have got mild 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.
- SBSteven Bartlett
What's that?
- LNLouisa Nicola
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 st- 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 to 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.
- SBSteven Bartlett
And then if it's high, what do I do about it?
- LNLouisa Nicola
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.
- SBSteven Bartlett
I was just looking at the, um, the study that reversed, uh, the heart by 20 years and trying to figure out what exercises they did. And as you said, the first one was a high-intensity workout-
- LNLouisa Nicola
Mm-hmm
- SBSteven Bartlett
... the four-by-four.
- LNLouisa Nicola
Yep.
- SBSteven Bartlett
Um, 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-
- LNLouisa Nicola
Mm
- SBSteven Bartlett
... of exercises that caused such a profound impact on the heart. And I think cardiovascular diseases are the single biggest killer.
- 40:16 – 44:10
Why Alzheimer’s kills—and what Louisa would do if diagnosed
- LNLouisa Nicola
Yeah. Cardiovascular disease. Dementia is the number one killer of women in the UK. The number one.
- SBSteven Bartlett
Really?
- LNLouisa Nicola
It's the number one cause of death in Australia for both men and women.
- SBSteven Bartlett
How does it kill you? 'Cause we all think about memory loss and stuff like that, but-
- LNLouisa Nicola
Yeah. 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 you, 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, uh, moment, but it's not like you die of Alzheimer's disease specifically.
- SBSteven Bartlett
If you were diagnosed with Alzheimer's disease... It's an interesting reaction.
- LNLouisa Nicola
Because I would have no hope. I think a, a better question is-
- SBSteven Bartlett
You'd have no hope?
- LNLouisa Nicola
If I was diagnosed with Alzheimer's disease, there is nothing I could do.
- SBSteven Bartlett
How would that change your life and the decisions you make, or would it at all?
- LNLouisa Nicola
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
- SBSteven Bartlett
During Alzheimer's
- LNLouisa Nicola
During Alzheimer's, but also during this window in, uh, uh, 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, uh, 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, uh, 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.
- SBSteven Bartlett
So on that point of the ketogenic diet, the reason is because ketones are an alternative fuel source to glucose-
- LNLouisa Nicola
Yep
- SBSteven Bartlett
... and the brain likes ketones.
- 44:10 – 52:54
Women, menopause, and brain energy: estrogen, ketones, and HRT nuance
- LNLouisa Nicola
The brain loves ketones, and it actually utilizes them more effectively than glucose, but glucose is the primary fuel source for the brain. And here's what's really interesting, uh, and devastating, if you will, for females. During the onset of perimenopause, right, when we see a decline in estrogen, right? We see a decline in estrogen. What happens is a 30% reduction in brain glucose metabolism. So when these receptors start to die because we don't have, uh, we don't have a lot of estrogen circulating in the bloodstream anymore, what happens? Well, we can't utilize glucose as effectively. So during that state, that's when we start to get the breakdown of the myelin sheath to use that as, uh, as ketone bodies, as an alternative brain f- fuel source.
- SBSteven Bartlett
So do you think women going through m- menopause should be considering a ketogenic diet?
- LNLouisa Nicola
Yes, I do think that. I think that women who are going through perimenopause and who are at the mercy of this brain energetic crisis should be adopting, if they can, a ketogenic diet. It's one of the best diets for the brain.
- SBSteven Bartlett
I didn't really understand this idea that during menopause there was a glucose deficiency or metabolism problem in the brain.
- LNLouisa Nicola
30% reduction in brain glucose metabolism.
- SBSteven Bartlett
Is this why women report having brain fog and all these kinds of things?
- LNLouisa Nicola
Yeah, absolutely, because when the brain can't utilize its fuel source effectively, what happens? Well, metabolites start to shift. We don't sleep properly. A- around 60 to 65% of women in menopause report having a hot flash or night sweats. It wakes them up at night. That's also causing cognitive decline and brain fog.
- SBSteven Bartlett
So I mean, this graph's pretty shocking.
- LNLouisa Nicola
Mm.
- SBSteven Bartlett
Um, can you explain what it shows?
- LNLouisa Nicola
Oh, this is showing the, um, estrogen levels at birth, going through all of the life cycles that a woman will go through, puberty, perimenopause, and then eventually menopause. There is one thing that is certain. After age, I mentioned earlier, being a woman is the next strongest risk factor for getting this disease. And-
- SBSteven Bartlett
For getting Alzheimer's
- LNLouisa Nicola
For getting Alzheimer's, and that l- largely lies in our per- in our menopausal shift that occurs, the downsizing of estrogen. However, we do have forms of estrogen that we can, you know, supplement with.
- SBSteven Bartlett
So I just need to keep the estrogen up-
- LNLouisa Nicola
Yep
- SBSteven Bartlett
... because then the brain health is gonna be up and normal.
- LNLouisa Nicola
This is where the controversy lies. Yes and no. So I want everyone to understand, I am sitting right now. So my entire doctoral thesis is focused on women and Alzheimer's disease, and I'm Switzerland right now when it comes to hormone replacement therapy. That is replacing your hormones.
- SBSteven Bartlett
You're Switzerland.
- LNLouisa Nicola
I'm Switzerland, meaning that there is no evidence to suggest, right now we don't have large-scale randomized control trials to show that hormone replacement therapy prevents dementia. So what I will tell you is this. It is a signal. It is a supporter. It will help you do the things that can lower your risk of dementia. We've seen multiple times that having hormone replacement therapy can reduce your risk of getting Alzheimer's disease by up to 30%. We know that. But it's not because estrogen alone is minimizing your risk. It's because when you have estrogen, it helps get rid of the hot flashes. It helps with the night sweats because during menopause, when we actually have a dysregulation of the, of estrogen in our brain, what happens in the hypothalamus, which is an area in the brain that controls our temperature regulation, when we lose the ability to monitor our temperature, for a woman, what will happen is when she feels the slightest bit hot, her temperature, you know, is rising a little bit. The hypothalamus doesn't know what to do, so it signals, "I'm super hot." So it'll raise your temperature right up, and that's a hot flash, and then it'll bring it right down. And as a result, this is keeping women up at night.And we know that sleep deprivation is a risk factor for Alzheimer's disease. Of course it is. Compounding sleep deprivation will accumulate amyloid beta in your brain. So if we can replace, if we can use hormone replacement therapy as a signal and as a support to help us sleep at night, then that's a good thing. Another thing, estrogen is anabolic to muscle.
- SBSteven Bartlett
What does that mean?
- LNLouisa Nicola
It means that it helps with muscle protein synthesis.
- SBSteven Bartlett
Oh, it helps me make muscle.
- LNLouisa Nicola
Yeah. We've got estrogen receptors on our bone. We've got estrogen receptors on our muscle. So if estrogen is anabolic to muscle, if estrogen helps with muscle protein synthesis, if ef- estrogen helps with bone mineral density, then replacing estrogen during that menopause state is going to help us with all of the risk factors o- of Alzheimer's disease.
- SBSteven Bartlett
So when does estrogen ... I mean, it really, in this image, drops off a cliff.
- LNLouisa Nicola
And it, and yeah, and it varies. So it tends to generally happen at around 45 years old as an average, and that, that perimenopause stage lasts around 10 years.
- SBSteven Bartlett
But it starts going down on this graph at a- about 30.
- LNLouisa Nicola
It starts to go down, and everyone's different, okay? You can have a woman in her late 30s go into perimenopause, or the general age is around 42 to 45. Most OBGYNs that I've spoken to say that you need to start checking in with your doctor at around 40 years old to check for this.
- SBSteven Bartlett
So do you think, thinking about my fiancée now, do you think that someone like her should go on hormone replacement therapy at, like, 40?
- LNLouisa Nicola
Well, so that's the, that's the big question. That's the elephant in the room. Should you go on hormone replacement therapy or should you not? And that's definitely a conversation between you and your physician. However, we've got large-scale studies right now to show that we don't have to be afraid of hormone replacement therapy. And without going too deep into the weeds, there was a massive study that was done, the Win- Women's Health Initiative, that scared women out of taking hormone replacement therapy in fear-
- SBSteven Bartlett
Breast cancer
- 52:54 – 1:01:22
Core biology: amyloid, tau, and the role of deep sleep (glymphatic cleaning)
- LNLouisa Nicola
I mentioned earlier plaques, right? So a lot of people ask, "Well, what distinguishes Alzheimer's disease from the rest of the dementias?" And it comes down to two proteins, amyloid beta and tau protein. And here's where it gets really interesting, and actually dates back to 1901, the first ever Alzheimer's disease patient, Auguste Deter. She was 52 years old, and she went to the hospital, her and her husband went, complaining of difficulties of word-finding, word fluency, and she couldn't remember where she put her keys. And her husband said, "She is delirious." And Auguste told the doctor on board, he was a psychiatrist, his name was Alois Alzheimer. She said to him, and I quote, "I don't know who I am anymore." As I mentioned, this disease robs you of who you are. In 1906, Auguste Deter died, and that was the first ever patient to be recorded of having Alzheimer's disease. And so postmortem, they cut her brain open and they found that she had these plaques in her brain, and they didn't really know, they didn't really understand what it was, but that was the first ever induction of this disease in society. And ever since then, ever since then, we are still trying to tackle this disease. In the 2000s, we had this notion that Alzheimer's disease was the amyloid cascade hypothesis, meaning that, great, Al- Alzheimer's disease means when you get a head full of amyloid, this toxic protein that builds up. So we were demonizing this protein. We were demonizing this peptide protein that builds up in the head. And so then came theMedications, okay, in the form of IV drugs. So you go to the hospital, you get an IV in the promise that it will clear out amyloid. Great, we've got a cure. But what they found was that when they were taking out the amyloid in these brains, they were taking with them brain tissue and causing microhemorrhages, and in some patients it was resulting in death. So we now know that the problem here isn't amyloid. In fact, amyloid is a antimicrobial peptide. So amyloid is actually a good thing. Amyloid beta is a good thing because it protects the brain cells. Now, here's what happens. We have this beautiful process during sleep that occurs. When we get into deep sleep, we activate the glymphatic system. Okay? So the glymphatic system comes from the word glials, glial cells. We have glial cells in the brain. They sit outside of the neurons, and this is what, uh, is responsible for immunity. They're our chief, um, immune response cell. During deep sleep, they shrink, and when they shrink, all of this amyloid beta that's floating around in the cerebral spinal fluid gets washed out. So it's like a washing machine that occurs in your brain, right? But what tends to happen in Alzheimer's patients is they don't get a chance to wash out the amyloid. What happens in perimenopause and menopause due to the hot flashes, you don't get to get into deep sleep because you're having a fragmented sleep because you're waking up due to hot flashes and night sweats. So that is what's do- that is what's causing the buildup of amyloid. Now stick with me. We've got another protein that is a hallmark of Alzheimer's disease. It's tau protein, and tau lives in the axon of the cell, the one that I said is covered in the myelin sheath. And what happens under times of stress, what happens is this tau protein phosphorylates. So it breaks off, and basically tau protein stabilizes the microtubules. Okay, imagine these railw-road tracks in the axon, okay, just going up and down the axon. They're-
- SBSteven Bartlett
The axons in the, in the cell or in the brain?
- LNLouisa Nicola
And so the, the, the brain cell itself, the neuron is the neuron cell body, and the axon is like the trunk of the tree.
- SBSteven Bartlett
Okay.
- LNLouisa Nicola
Right?
- SBSteven Bartlett
Yep.
- LNLouisa Nicola
So holding up the tree are microtubules, and those microtubules are bound by tau proteins. The, the tau proteins keep the microtubules intact, so the trunk of the tree is stabilized and it sits there. Why does it need to be stabilized? Because that's how speed of thought travels. Information processing speed travels up there. When the tau protein phosphorylates, it starts to form tangles. They're called neurofibrillary tangles. So that happens in the axon, and when all these tangles clump together, we get the collapse of this axon, the collapse of these microtubules. So we're not just having a cascade of environmental disaster inside the cerebral spinal fluid of the brain and inside the brain, outside the cells. We've also got this cascade happening inside the cell body itself. So the brain is under attack inside the cell and outside the cell.
- SBSteven Bartlett
Why?
- LNLouisa Nicola
Why, exactly why? Why does this happen? Because of how we treat our brains.
- SBSteven Bartlett
Because of how we treat our brains?
- LNLouisa Nicola
Yes. The reason why your brain is hyperphosphorylated and the reason why these tau proteins are hyperphosphorylated is because of many things. One is we have seen time and time again that we have estrogen receptors that are on, in the brain cell themselves in the axon. So when we don't have adequate estrogen, estrogen actually is so smart, what it is doing, it's blocking an enzyme that is responsible for phosphorylating the tau. So if we don't have the estrogen there, then the tau, the enzyme is there to phosphorylate the tau and break it down and cause these neurofibrillary tangles. But let's just say you're a man and you don't have, you don't need the, uh, testos- you don't need the estrogen there, although testosterone is neuroprotective. Testosterone actually aromatizes into estrogen, which is why you actually have an extra added protection in your life. Um, what else causes this? Well-
- SBSteven Bartlett
Sleep
- LNLouisa Nicola
... stress.
- SBSteven Bartlett
You were talking about sleep then.
- LNLouisa Nicola
Yeah. So sleep is, I think by far, the most underrated Alzheimer's disease prevention tool that we have.
- SBSteven Bartlett
Mm-hmm.
- LNLouisa Nicola
It's underrated because we have been doing it all our lives, and we think that we can just go to sleep and the magic happens. But I think now in 2026, we actually need to train for sleep. So, uh, during deep sleep, we activate the glymphatic system, and sadly, a large proportion of us aren't getting into deep sleep. So sleep is, uh, one of the reasons.
- SBSteven Bartlett
How do you sleep?
- LNLouisa Nicola
Yeah, I sleep- I make sure I sleep seven and a half hours a night.
- SBSteven Bartlett
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- 1:01:22 – 1:09:16
Sleep as the most underrated prevention tool—and practical protocols
- SBSteven Bartlett
A lot of people struggle with sleep, and, um, they've just kind of gotten used to itI, I hear this from friends of mine that will say, "You know, I'm a bad sleeper. I'll sleep for five hours." And they kind of have just gotten used to it. Do you think that's okay?
- LNLouisa Nicola
No. And they will pay for this in their 60s and 70s.
- SBSteven Bartlett
How do you know?
- LNLouisa Nicola
Because I know that just one night of sleep deprivation is raising your risk of amyloid beta by at least 4% to 5%.
- SBSteven Bartlett
Just one night?
- LNLouisa Nicola
And what's serious, just one night. So you can imagine the accumulation of this. Not only that, we know that you're interrupting with the hormones that are responsible for hunger and society. We know s- [laughs] for hunger and satiety. We know that you're increasing your risk of type 2 diabetes with, um, sleep deprivation. But not just that, we also see that this compound effect can't be reversed, meaning that a lot of people think, "I'll just sleep for six hours a night and then just bank on it on the weekend." But sadly, that's not how our brain works. It's not like debt that we can repay to the bank.
- SBSteven Bartlett
I heard from Matthew Walker the other day, though, that we can save it up. He said, um, he said, "You can't make up for lost sleep."
- LNLouisa Nicola
Exactly.
- SBSteven Bartlett
But if on Monday I've got something where I know I'm gonna be deprived-
- LNLouisa Nicola
Mm
- SBSteven Bartlett
... he says on the weekends, like Saturday and Sunday, if I got a huge amount of sleep, it's kind of like I can use that-
- LNLouisa Nicola
Yeah
- SBSteven Bartlett
... like forwards-
- LNLouisa Nicola
It's kind of like-
- SBSteven Bartlett
Yeah
- LNLouisa Nicola
... it's kind of like-
- SBSteven Bartlett
For like back
- LNLouisa Nicola
... the reserve. Yeah.
- SBSteven Bartlett
Yeah.
- LNLouisa Nicola
Actually, I do this. I do long-haul flights. I'll be at, like six hours between LA and New York, but also to Australia. And so if I know I'm going on a long-haul flight, I'll bank on my sleep for about a week leading up to that, 'cause I know I'm gonna be sleep-deprived on the plane.
- SBSteven Bartlett
So if you were one of those people that struggles with sleep that's listening right now, and they're slightly concerned that, you know, you talked about this, um, glymphatic system, which-
- LNLouisa Nicola
Mm
- SBSteven Bartlett
... sort of comes out at night and cleans up the brain, and they're hearing, "Sh- you know, shit, my glymphatic system isn't gonna be optimal if I'm not sleeping."
- LNLouisa Nicola
Mm.
- SBSteven Bartlett
If that was you, and for whatever reason you start sleeping poorly-
- LNLouisa Nicola
Mm-hmm
- SBSteven Bartlett
... what would you do about it?
- LNLouisa Nicola
I would get really serious about examining my lifestyle the day before. So this generally involves two things. You have to ask yourself, are you having trouble falling asleep, or are you having trouble staying asleep? A lot of women report trouble falling asleep, meaning they've got a racing mind. Men, too. They've got this racing mind. They can't, you know, just stop that default mode network and the, the racing thoughts that happen. That's one thing. And then there's the, "I can't stay asleep," meaning that, uh, I'm waking up due to heat. I'm waking up because, uh, I'm stressed and I'm having bad dreams. There's all different reasons as to why you wake up. So for the person who is having trouble falling asleep at night, I would strongly recommend introducing a supplement called GABA, which is gamma-aminobutyric acid. It's our chief inhibitory neurotransmitter. And when you have this, it really helps stabilize all those thoughts. It helps with a racing mind, and it can help calm you down at night. The next thing I'll do is I will think about what I'm eating. Actually, it turns out that, um, eating starchy vegetables, something that's gonna make you... Like, you know, sweet potatoes, for example. It's gonna have a better benefit, uh, backloading, uh, your carbs at night for helping you sleep. If you start training for sleep as if sleep is your marathon, and start preparing for that at 8:00 PM at night, getting off, you know, don't email, don't have any hard conversations, don't watch anything crazy at night, you'll settle your mind down. You'll settle your nervous system down. But where I think, uh, most of the optimization occurs is when you're actually in sleep. I would also work on, um, sleep regulation. So what we know is that in order to fall asleep and stay asleep, our core body temperature needs to drop at least two degrees. And I'm doing this with a temperature-controlled mattress 'cause it's working on thermal regulation. A lot of people who don't have that can do, uh, several things, like sleeping with their feet outside of the sheets or tur- turning the, the air conditioning on, the thermostat on to cooling the room, to cooling down your body temperature, core body temperature. One thing that, um, you can supplement with is glycine, which I think is amazing because it helps with sleep by way of temperature regulation. It can bring down your core body temperature. And in fact, and I don't know too much about the mechanism behind this, glycine itself has one of the greatest longevity benefits for improving lifespan. So taking glycine can also help with that. Now, in terms of the person who is having trouble staying asleep-
- SBSteven Bartlett
What about this one? You don't talk about the, um, the old ashwagandhanda.
- LNLouisa Nicola
Oh, yeah. Ashwagandha's great, okay? Ashwagandha is going to help you with stress, and you've got here ashwagandha rhodiola. So what they both are, they are adaptogens. And basically an adaptogen is great because it, it goes in and it adapts to what is happening in your body. So let's just say you have elevated cortisol, and this tends to happen, you know, during different cycles during the day, mainly during the n- uh, daytime when we wake up, where cortisol levels are at its peak. But it can also happen at night. Having this can actually stabilize that cortisol because it can go in and combine to cortisol and bring it down. Likely, if something is not elevated and it's low, it can bring it up. So it's really good. It's an adaptogen, and studies show that you can actually take this three times a day and you won't feel fatigued. It doesn't disrupt anything, and it pairs really well with caffeine, for example. So does theanine. So this is actually a really great, um, adjunct to your supplement stack
- 1:09:16 – 1:26:51
Supplements for brain aging: omega-3, vitamin D—and a deep dive on creatine dosing & safety
- SBSteven Bartlett
Sticking on supplements for a second, omega-3.
- LNLouisa Nicola
Yes.
- SBSteven Bartlett
Um, I've got some omega-3 here. I've only, I've got two of them here.
- LNLouisa Nicola
Mm-hmm.
- SBSteven Bartlett
But when I brought both of them out, you said that I've gotta be quite careful about what brand I buy, but also s- uh, something about temperature.
- LNLouisa Nicola
So by far, out of all of the supplements, omega-3 is probably the only one that you have to make sure that you look at the supplement label for. Um, there, there was this study that was done that showed that around 95% of the most popular omega-3 supplements in the US, and there was about 85 of them that were tested, exceeded the normal oxidation level. Meaning that these pills, because they're omega-3 fatty acids, they come from fish oil, they are oil, they can become rancid and oxidized, and they usually do this when they're in a heated environment. There are the, here are the rules of thumbs. O- one, you wanna look for a manufacturer that is highly credible and that is certified.
- SBSteven Bartlett
Certified?
- LNLouisa Nicola
Yeah. So NSF certified. So it's an external governing, uh, board that certifies them on, you know, everything. Heavy metals. They make sure that the, um, oxidation levels are met, and they make sure that, you know, what's in the capsule is actually in the capsule. That's another thing that is scary. The supplement industry is highly unregulated. And I treat my omega-3s the same way I treat my olive oil. You want to get oil that is sourced in the area that you are. We're in California right now, so you might want to find an omega-3 that is sourced in California.
- SBSteven Bartlett
Do I wanna put it in the fridge?
- LNLouisa Nicola
You wanna put it in the fridge the moment that you get it.
- SBSteven Bartlett
Really?
- LNLouisa Nicola
Yeah.
- SBSteven Bartlett
Why does nobody talk about that? Uh-
- LNLouisa Nicola
I'm not sure. But, um, it's just the same as olive oil. You don't want the olive oil to become rancid, so you don't leave it near the, near the stove. You wanna put it in a cupboard away from the stove.
- SBSteven Bartlett
And these are good for the brain?
- LNLouisa Nicola
Omega-3s by far are one of the most potent stimulus that you could have for the brain. They help with cell membrane fluidity. So where your cells meet neuron to neuron, they create something called a synapse. And in order for that to occur, we have a massive influx of all of these neurotransmitters, dopamine, serotonin. We've also got calcium and potassium, and these help our brain cells communicate, okay? We wanna make sure that our membranes, the cell membranes, are fluid and they glide in order to help with that synaptic transmission. Another thing that they do is they are comparable to an NSAID, an anti-inflammatory medication. These have massive anti-inflammatory effects. In fact, I think that these have the safety profile of an FDA-approved drug, and there's only benefits from it. There's no side effects from it. Uh, not just that, 60% of our brain is made of fat. 70% of that is made of DHA, and DHA comes from omega-3 fatty acids. So why do I not want to replace my brain or the fat in my brain with what it's made of? And that's what you do when you have omega-3 fatty acids. In fact, there's been several trials, um, to show that omega-3 fatty acids are most beneficial and most effective for mild cognitive impairment patients, people who have the APOE4 gene, and people who have got Alzheimer's disease. Because when I told you that our, we get the breakdown of the blood-brain barrier, those parasites on the blood-brain barrier require DHA. In fact, there's a transporter on the outside of our brain that allows the, um, that allows the DHA to come in and get into the brain.
- SBSteven Bartlett
And I know you're a big fan of, uh, vitamin D as well, because there's been some very encouraging studies done there.
- LNLouisa Nicola
Oh, vitamin D is phenomenal. We have vitamin D receptors all over our brain, brain stem, and, and they're abundantlyFound in the hippocampus and the memory centers of our brain. And there was this ac- there was actually a study done on centenarians in China, which-
- SBSteven Bartlett
Centenarians
- LNLouisa Nicola
... yeah, those who live to 100, but it was done in women. And they showed that the women who preserved their cognitive functions and who didn't get Alzheimer's disease had high levels of vitamin D, so they weren't vitamin D deficient. In fact, being vitamin D deficient can increase your risk of all-cause dementia by 40%. Likely, being, having a high level of vitamin D, which is around 60 nanograms per deciliter, can lower your risk of getting Alzheimer's disease by around 80%.
- SBSteven Bartlett
And then we have this white powder in front of me. You've got a big smile on your face.
- LNLouisa Nicola
[laughs] I do because there is just so much benefit to this, depending on which brand you've bought, of course, but I can't say enough about creatine. I have my parents on creatine. They're 71 years old. I've got my dad on high-dose creatine. I've got my mother on low-dose creatine. It's the most widely studied supplement on the market. And-
- SBSteven Bartlett
I've never seen you this excited
- LNLouisa Nicola
... I'm so excited because I think that this is a really cheap and effective way to get everything you want from both your physiology, an upgrade on your physiology, and your neurophysiology. So let's actually talk about creatine because I know it gets a lot of airtime, but women and men are still scared of it, and they're scared of it for two reasons. One, they're scared it's going to cause kidney damage, and two, it's they're scared their hair is going to fall out. And I'm going to address both of those fears, but first let's talk about what it is. So creatine is a naturally occurring molecule. We, it's, we get s- we, we produce around two to three grams of creatine per day. Gets secreted from, a bit from the brain, but a lot from the liver. And two to three grams a day is great, but it's not enough, so we have to supplement with it. And all through the '90s and all through the 2000s, people were supplementing with five grams a day. That is this scoop here. Five grams of creatine per day. Now that we're getting more, uh, rigorous with our brain health studies, we have found that creatine has enormous benefits for the brain. But here's the problem. When you have five grams of creatine, you're saturating the muscles. Okay? Remember, the muscles are so hungry, so they get first dibs, and they take up all of that creatine, so then there's none left for the brain. We also lose a bit of the bioavailability when the creatine goes into the brain. It crosses the blood-brain barrier, but when it goes into the brain, we lose some of it. So we have to supplement with more than five grams. And one of the studies that changed my thinking came out last year. It was the first-ever pilot study done on Alzheimer's disease patients. You're talking about patients whose brains are under attack. They're in an energetic crisis. They cannot produce energy effectively. ATP is all skewed. Brain glucose metabolism is skewed. They don't remember left from right. Cognitive functions are declined. They put them on, uh, 20 grams of creatine per day.
- SBSteven Bartlett
Which is how much? I mean-
- LNLouisa Nicola
That, well, actually, that is four of this. So you wanna go one, and I don't know if they did this all at once, that's two, or if they did it, like me, over four separate intervals throughout the day. There we go.
- SBSteven Bartlett
That's a lot of creatine.
- LNLouisa Nicola
That's a lot, which is why you probably wanna have this skewed throughout the day, which is what I did. I had 20 grams today. I had five grams in the morning, five mid-morning, and then I think I had 10 all at once before I got here. So that is a lot for all at once. And what they found was that these patients not only preserved their cognitive functions, but they had more energy and they were able to exercise more. And it blew my mind that it does not matter how old you are. It doesn't discriminate based on gender. Creatine doesn't discriminate based on age. It doesn't discriminate based on weight. It doesn't discriminate based on pathology, or disease states, or ethnicity. It is just there. It is there to support you. It's the most widely studied supplement on the market.
- SBSteven Bartlett
What is it doing?
- LNLouisa Nicola
And it's all risk.
- 1:26:51 – 1:29:47
Testing and early detection: lipoprotein(a), Alzheimer’s blood biomarkers, and processing-speed demo
- SBSteven Bartlett
What do you test for with your own health, and how frequently do you test?
- LNLouisa Nicola
I test every three to four months.
- SBSteven Bartlett
What do you test?
- LNLouisa Nicola
Oh, I do everything.
- SBSteven Bartlett
Really?
- LNLouisa Nicola
Um, oh, I've... I, I just did, um, lab work, uh, December 15th, th- the day before my birthday. I do it, you know, around that age. But every year, funnily enough, I test my biological age.
- SBSteven Bartlett
What is your biological age?
- LNLouisa Nicola
It came back as 22.
- SBSteven Bartlett
Fucking hell. What's the most important test they don't typically do that you think everybody should be doing?
- LNLouisa Nicola
Lipoprotein little A raises your risk of having a heart-related event or raises your risk of getting cardiovascular disease, but it's hereditary.
- SBSteven Bartlett
And then for, for dementia?
- LNLouisa Nicola
This is a really exciting part, at least in the US. We now have a predictable way of picking up on mild cognitive impairment and picking up on these Alzheimer's hallmarks. Tau protein, p-tau 217 it's called on blood work, and amyloid beta. So we can now pick up on this with 90% accuracy of a PET scan.
- SBSteven Bartlett
What are these cards over there?
- LNLouisa Nicola
[laughs] These are here to test your processing speed.
- SBSteven Bartlett
Pink.
- LNLouisa Nicola
So-
- SBSteven Bartlett
It says pink on it.
- LNLouisa Nicola
Yeah. So this is actually a great measure of brain function. Your brain processes visual information 15 times faster than written words. And so this is gonna test your, uh, brain function.
- SBSteven Bartlett
Okay.
- LNLouisa Nicola
Okay? So what I want you to do is you're gonna see the color.
- SBSteven Bartlett
Yeah.
- LNLouisa Nicola
I want you to actually say the color of the card, not the word.
- SBSteven Bartlett
Okay. Let me just program my brain. Say the color, not the word.
- LNLouisa Nicola
Yeah.
- SBSteven Bartlett
Okay.
- LNLouisa Nicola
Are you ready?
- SBSteven Bartlett
Green, orange, yellow, green, orange, green, orange, yellow, pink, orange, green.
- LNLouisa Nicola
Now let's do the reverse. I want you to say the words.
- SBSteven Bartlett
Ugh. Wait, let me just... [laughs] Okay. Yellow, blue, green, black, purple, brown.
- LNLouisa Nicola
Okay, so you're good.
- 1:29:47 – 1:35:52
5-minute neuro drills: tennis ball + eye patch to train reaction time and reserve
- LNLouisa Nicola
This actually involves us standing up-
- SBSteven Bartlett
Okay
- LNLouisa Nicola
... and using a tennis ball. So we're gonna train your visual cortex, which sits at the back here in the occipital lobe. We're gonna train your, um, processing speed, your reaction time, your hand-eye coordination. One of the best exercises that you can do, physical exercises, is actually hand-eye coordination drills, tennis, racket sports. But I'm gonna show you what five minutes a day can do for your cognitive reserve and your brain performance, just using a tennis ball and an eye patch.
- SBSteven Bartlett
Okay.
- LNLouisa Nicola
So first things first, I'm gonna give you this tennis ball.
- SBSteven Bartlett
Yeah.
- LNLouisa Nicola
And for the whole time, I want you to throw the ball with an overhand grip.
- SBSteven Bartlett
Oh, like this?
- LNLouisa Nicola
Yep.
- SBSteven Bartlett
Okay.
- LNLouisa Nicola
So I want you to just throw it with the right arm and catch with the right arm.
- SBSteven Bartlett
Over... I mean, what's this one saying?
- LNLouisa Nicola
That's underarm.
- SBSteven Bartlett
I'm just checking the wall. Okay. Okay. So, like this?
- LNLouisa Nicola
So you might wanna move back where the chair is. Okay. No, you're good.
- SBSteven Bartlett
Cut that. Cut that out.
- LNLouisa Nicola
Good. So now throw with the right and catch with the left and alternate. Yep.
- SBSteven Bartlett
Oh, okay.
- LNLouisa Nicola
You've got it. So what we're doing, we're engaging almost all the executive functions now. You've got hand-
- SBSteven Bartlett
Cut that out
- LNLouisa Nicola
... You should be able to do this for a minute. Okay?
- SBSteven Bartlett
Okay.
- LNLouisa Nicola
Now we're gonna make it even harder. It's like placing weights on you.
- SBSteven Bartlett
Go on, you do some.
- LNLouisa Nicola
Well, I, I'm not gonna do the one with the eye patch. I'll do the next one. Okay. So basically what you wanna do... And if you do it with a black ball, it's actually, oh, even better. So now we're gonna make it a bit hard and a bit neurally demanding. We're gonna put an eye patch on you, which is really gonna block out, like, 50% of the vision.
- SBSteven Bartlett
Okay. Which eye?
- LNLouisa Nicola
Any eye.
- SBSteven Bartlett
Let's do the left one.
- LNLouisa Nicola
Now let's see how many you can do. You... I think you... we counted around eight before.
- SBSteven Bartlett
A pirate. Can I just get you to look here? What? Oh, wait, this is not flattering. Okay, cool.
- 1:35:52 – 1:44:38
The ‘willpower’ brain: AMCC growth through doing hard things—and modern ‘brain rot’ risks
- LNLouisa Nicola
So doing hard things is what is going to improve brain function over the lifespan. Doing hard things tells your brain that you can do hard things, meaning have you ever heard of this, um, brain area, a little area in the brain called the anterior midcingulate cortex?
- SBSteven Bartlett
Midcingulate cortex. Yes, I have.
- LNLouisa Nicola
What do you know about it?
- SBSteven Bartlett
I'll let you say it.
- LNLouisa Nicola
Well, it's shown that it's larger in what we call super ages and people who age really well and who can, uh, withhold a lot of, uh, cognitive capacity. And it's really profound in people who can diet well. It gets bigger when we do hard things. So when we do really hard things, this area in the brain gets bigger. And basically, what that is, it's reserve for when life gets hard. It means it basically tells your brain that no matter what happens, no matter what event comes my way, I have the ability to go in, welcome it, and push through it, no matter how hard it's going to be. When you give up or when you don't do hard things, this little area doesn't grow. It doesn't get bigger. So doing these neural activating, uh, drills that we just did, going to the gym and pushing well above your threshold and pushing really hard is going to help, uh, grow this little area of the brain.
- SBSteven Bartlett
And they call this the willpower muscle.
- LNLouisa Nicola
The willpower. This is why I think that, um, when people go out to set their goals during the year and they say, "I'm gonna lose 20 pounds. I'm going to do this. I'm just gonna increase my willpower," I think it's not willpower, it's neurobiology.
- SBSteven Bartlett
I think it's really important to just spend a little bit of moment talking about this part of the brain, 'cause when I discovered it, I found it absolutely fascinating. And I think it was Andrew Huberman who said-
- LNLouisa Nicola
Yeah
- SBSteven Bartlett
... either to me or he said publicly that he thinks it's one of the most fascinating or important discoveries of the last century.
- LNLouisa Nicola
Of course. Well, you think about, um, how we're living our lives. We're, we're punishing ourselves-For not being able to read a book, for not being able to pay attention. How many, you know, people are now diagnosing, self-diagnosing themselves with ADHD, low attention spans, and they're blaming it on environment. They're blaming it on circumstances when they should be blaming it on neurobiology, and they should be blaming it on their brain state. This area of the brain, if you can push ... And this is why these SuperAgers seem to have-
- SBSteven Bartlett
What's a SuperAger?
- LNLouisa Nicola
A SuperAger is somebody who is aging well. So they're going through life, uh, low, uh, cardiovascular disease state. They've maintained their cognitive functions. They're at the age of 80, 90 with a, a VO2 max profile of maybe a 50 or 60-year-old. So they're aging quite well biologically. So these, you know, SuperAgers have many, many different facets to them, and one of them is a, a larger midcingulate cortex.
- SBSteven Bartlett
Conversely, the AMCC, anterior midcingulate cortex, shrinks in people who live sedentary lives or avoid challenges. It literally atrophies if you play it safe in life too often. Growth only occurs during resistance. If you love taking ice baths and you take one, your AMCC doesn't change. If you hate the cold but force yourself to do it anyway-
- LNLouisa Nicola
Yep
- SBSteven Bartlett
... the AMCC grows. Scientists now view the AMCC as the seat of the will to live. Its size and activity level are strong predictors of how long an individual will survive after a major setback in their life, whether it's a health setback or a surgery.
- LNLouisa Nicola
There's something really philosophical about that as well. You know, if you ... I don't know if you read, um, stoicism or anything, but it, it, it really dates back to how the stoics lived their life, especially Marcus Aurelius, with being able to push through hard times. Little did they know that it was this little area in the brain.
- SBSteven Bartlett
Yeah, I think I s- was telling the story the other day of Roosevelt and what happened in his life as a young man when he came home one day on Valentine's Day and found that his mother and his wife of ... who had just had his newborn baby, had both died, one upstairs, one downstairs. And he went off to the Badlands for two ... I think it was two to four years. The Badlands in America were just this, like, horrific, um, natural place where he'd get up at 4:00 AM, ride these, like, horses in the freezing cold where, like, the horses would literally die standing still because it was so horrific. He did that to two years to, like, deal with the grief. But when he came back to New York City after this two years in the Badlands, all of his friends said he was just a completely different man. That he had, like ... And what they now know from a neuroscience perspective is that he didn't just build his muscles. He literally, like, rewired his n- his brain. He went on to become the youngest US president of all time. He got shot, um, during a speech and carried on doing the speech. He led the charge in various wars. He's just this unbelievable pe- I think he won the Nobel Prize, and they point at those two years in the Badlands and say actually that, that forged not just the man, but his, his brain, his AMCC. The studies also show that athletes consider- consistently show much larger AMCC volume, and studies show that individuals struggling with obesity often have smaller AMCCs. But again, but, but it begins to grow the moment they start a successful challenging dietary or exercise intervention.
- LNLouisa Nicola
That it's that word challenging because when you place stimulus upon a system, it adapts and grows, and that is neurobiology at its most infinite source, and this is why we get the breakdown of these synapses. This is why we get into a place of going from 5,000 to 10,000 connections to 2,000 or no connections. These dendritic spines end up breaking down because we don't do the hard thing. And also think being deep-rooted in neurobiology, you can see that everything is cause and effect, and it's a cycle. Uh, if you don't do the hard thing, you don't grow the AMCC. You don't grow the AMCC, you don't do the hard thing again, and it's just this loop, and it's this cycle, which is why so many resolutions, New Year's resolutions, end by February 1st. It's why we have the obesity epidemic. It's largely why I think we've got a, a crisis of people not being able to, uh, meet their goals.
- SBSteven Bartlett
I'm just fascinated from an evolutionary perspective as to why we needed one and, like, why it wasn't just always big.
- LNLouisa Nicola
In the pursuit, uh, you know, evolutionarily, uh, in the pursuit of hunting and going out and, and hunting for food sources and being motivated to do that in a near starvation state when times were tough, weathering storms.
- SBSteven Bartlett
And so when times got easier, we didn't need it as much, so we could conserve, I guess, our energy, so we could, like, scale down our willpower when times were good?
- LNLouisa Nicola
Well, it's interesting that you say that because this brings up the whole brain rot and AI era. Just like with, you know, in, uh, 2024, Oxford Dictionary, I think, named brain rot the word of the year. And it's interesting because it plays into evolution and what's happening with this AMCC, meaning, like, we're just there scrolling at mindless information every day, training our brain to get these small dopamine hits, these small rewards from doing absolutely nothing.
- SBSteven Bartlett
What do you think of these, uh, chatbots that everybody's using at the moment to write for them and think for them, et cetera?
- LNLouisa Nicola
Oh my God, I think it's, uh, on the spectrum of being so incredible but being so detrimentally harmful. I know this with myself. So I was a mathematician. I did my master's of mathematics, and I was able, Steven, to ... The trigonometry and pure calculus that I could do back then with just my head and a pen was fascinating. Now, I'm going to ... I'm going out and I'm calculating on ChatGPT the bill, the tw- the, the 20% tip on top of this bill. How much does it cost? And I think how dumb am I actually getting? So I think-It's both good and bad. I think the rate of decline we're seeing in people reading books and exercising their brain is declining, um, and our ability to think and, and use our, our cognition is declining
- 1:44:38 – 1:54:36
Why Louisa is obsessed: women’s underrepresentation, caregiving burden, and her grandmother’s story
- SBSteven Bartlett
Louisa, I've, I've, um, waited, uh, a long time to ask you one particular question, which is, I think is very important, which is you're clearly very passionate about this stuff. One might say you're pretty obsessed with it. You come across as pretty obsessed
- LNLouisa Nicola
[laughs] Do I?
- SBSteven Bartlett
You do, yeah. Why?
- LNLouisa Nicola
We are living in a society that doesn't allow women to ask for what they want. We're living in a society that doesn't allow women to ask for what they need, and when this happens, it results in 70% of all Alzheimer's disease cases being women. It results in 80% of all autoimmune diseases being female, and these are largely preventable diseases. And when I ask why, and I hear that women are wildly misrepresented in academic literature, when I, when I see women who downplay their symptoms or they're too scared to ask their doctor for advice or they're too scared to ask somebody else for advice because of what they're going through or they're ashamed of some of their symptoms, I get angry and I get passionate, and it reminds me of my grandmother who, uh, she was my best friend. Her name was Louisa, and-
- SBSteven Bartlett
You're named after her
- LNLouisa Nicola
... I was named after her, yes, and we spent every day together and, and I'm getting emotional now 'cause I remember her, and she sadly died of pancreatic cancer. It was ovarian cancer that went to pancreatic cancer, and she never asked for what she wanted, and she never asked for what she needed, which was help. She didn't understand her symptoms. She didn't go to the doctor when she needed to because she was just more inclined to look after the family and look after the household, and when the time came that she was given her diagnosis, I was sitting there with her. It was, um, it was at home, and the doctor came. She did a house call, and my grandmother looked at her. She hardly spoke that much English, and she said, "Please, is there something I can do? I don't want to die." And the doctor said, "There's... I'm sorry. There's nothing you can do." And I spent every day with her in the hospital, and I think about that. It's been almost 20 years now, but I think about that moment, and I kick myself, thinking, "Why didn't we, why didn't we get her a scan?" She told us several times that her stomach was hurting. She told us several times that she felt pain. She never-- She hid her symptoms. She hardly ever ate at one point, and we never stopped to think about why, and she never stopped to think about why, so I think about her every day. And then I think about my mother, too, and these women, you know, first generation, they came, uh, we migrated to Australia from a country called Cyprus, and they've just been so... They put themselves second, and they, they just look after the family, and I can't stand that. And when I see women coming in as patients or caregivers, I think to myself, "Do you not know that there is something for you to do?" And most women don't, and I, I can't believe the amount of money that we are spending that is going towards putting us on rockets to go to Mars, but we haven't yet found a cure for this disease that is largely preventable. It's just not okay with me, and I would hate to see women go through this
- SBSteven Bartlett
The emotion is still very present in your face even though-
- LNLouisa Nicola
It's very present
- SBSteven Bartlett
... it was so long ago.
- LNLouisa Nicola
It was so long ago. I mean, I, I was very close to her. I'm very close with my mother. I, I check in with her twice, three times a day, and I just don't think it's fair. I think women deserve the truth. They've been lied to. They've been underrepresented, and we need to change that
- SBSteven Bartlett
With Louisa, your grandmother, what, what are those range of emotions that have turned into this in- incredible fire you have?
- LNLouisa Nicola
Anger-
- SBSteven Bartlett
Anger at-
- LNLouisa Nicola
Anger is one of the emotions. Anger at society that places women to be everything, to be a, a mother, a caregiver, to go to work, to represent the family. Women represent 51% of the total population. And then it becomes, I feel, political, if that's an emotion, because you think about healthcare, you think healthcare should be accessible to everybody, but it seems as though, especially in this country, that healthcare is only really accessible by those with a high socioeconomic status, and that I'm not okay with. So it does become political even though healthcare ... I guess healthcare is political because policies have been set, but a woman in need is apolitical, and my grandmother was apolitical, and her needs just were not met
- SBSteven Bartlett
Anger
- LNLouisa Nicola
Frustration-
- SBSteven Bartlett
Frustration
- LNLouisa Nicola
... at the system, frustration at the fact that we still have only 4% of women taking hormone replacement therapy in fear that they're going to get this disease, uh, that they're going to get breast cancerUtterly frustrated at the cycles of administration who vouch to help you. You look to your, you know, your government and your administration to look up to, to guide you. When you have Secretary Kennedy in 2014 go on national television and say, "Vaccines are totally safe. I had all my kids vaccinated. They've eradicated some of the most deadliest diseases that have plagued this world. Vaccines are so safe," to fast-forward to 2025 saying, "Vaccines are so unsafe. Do not trust your medical doctor. You need to take your health into your own hands," you start to lose trust. And it's not that we're uninformed, it's the fact that we are confused because we hear, "Vaccines are bad. Oh, vaccines are good. Vaccines are, are, are really good. Take them. Don't get your kid vaccine." You've got women here who don't even know they're-- they, they don't even know how to get on the internet or order a blood testing. You're expecting them to take their health into their own hands? So it upsets me that you see women who are so vulnerable being sold a, a, a vaccine lie which could potentially save them from a disease, which could potentially save them or their child from getting the flu, hepatitis B, meningitis, which was just eradicated from the vaccine schedule. Um, I'm not-- this is not meant to be political. I am, I'm a scientist. I am not-- this is not propaganda. This is not ideology. This is just women who deserve to be treated better.
- SBSteven Bartlett
You're 36. Louisa passed away when you were how old?
- LNLouisa Nicola
Oh, I was, uh, probably 18 at the time.
- SBSteven Bartlett
You were 18 when she-
- LNLouisa Nicola
Around that. 18, 19.
- SBSteven Bartlett
When she got the diagnosis?
- LNLouisa Nicola
Yeah. It was very fast. It was within a two-month timeframe. Not even.
- SBSteven Bartlett
And had she not got that diagnosis, and had you not sat there and watched her ask that doctor if there's something that she could do, do you think your career would've taken this course?
- LNLouisa Nicola
I became utterly obsessed with disease management. But when I first saw a human brain, I was 21. I was in a lab, and we had to go into a cadaver lab, and I saw a brain being harvested from a, a body that was donated, and I stayed back that day, I remember, and I helped in the pathology lab. And when I saw that brain, I knew that I wanted to dedicate my life to it. So ever since then, I've been in ORs, and it's where I feel most alive.
- SBSteven Bartlett
Why? Why did you wanna-
- LNLouisa Nicola
Because-
- SBSteven Bartlett
... dedicate your life to it?
- LNLouisa Nicola
Because when you know what the brain is, that it is responsible for the life that we have, and you can use it for your advantage to overcome any obstacle that comes your way, you become obsessed with understanding it. Metacognition is thinking about your thoughts. And every day, if you can think about why you think about the things you think about, you can challenge yourself to o- overcome any adversity.
- 1:54:36 – 2:04:41
Success, brain-state control, and closing reflections on meaning, faith, and hope
- SBSteven Bartlett
So what is success to you, then? At the deepest possible level, what is success? You, we meet again in 10 years' time, you say, "My life has been a success," or, "I feel successful. I'm a su-" Louisa says, "I am a successful woman." What does that mean? What happened?
- LNLouisa Nicola
Being able to control my brain states.
- SBSteven Bartlett
Being able to control your brain states.
- LNLouisa Nicola
I think that the ultimate form of success and high performance or being able to perform at your peak is being able to go from brain state to brain state and then be able to recover.
- SBSteven Bartlett
What do you mean by brain state?
- LNLouisa Nicola
Meaning, like-
- SBSteven Bartlett
Tides
- LNLouisa Nicola
... being able to get switched on when you need to be switched on and invite the neurotransmitters involved in that, norepinephrine, adrenaline, dopamine, but not having that in constant overdrive and being able to know when to switch off, and I think that that is what high performance is. The book that changed my mind on that was Flow by Mihaly Csikszentmihalyi, which actually speaks about the flow state. So being able to know how to, uh, separate yourself in these states.
- SBSteven Bartlett
Any goals outside of your professional-
- LNLouisa Nicola
[laughs]
- SBSteven Bartlett
[laughs] Goals.
- LNLouisa Nicola
Kids, family, life.
- SBSteven Bartlett
You have kids, family?
- LNLouisa Nicola
Yeah. Definitely.
- SBSteven Bartlett
It's tough, innit? It's tough. I was saying earlier to my friend that, you know, kind of just thought the minute I wanted to have kids, they would just appear. [laughs] But it's not so straightforward.
- LNLouisa Nicola
That's what I thought, too, until I realized, oh, but I'm the woman. [laughs]
- SBSteven Bartlett
Hmm.
- LNLouisa Nicola
I actually have to bear the, the children as well.
- SBSteven Bartlett
Which is a big sacrifice. And an honor and a privilege.
- LNLouisa Nicola
A sacri- It's an honor and a privilege-
- SBSteven Bartlett
Yeah, and a sacrifice
- LNLouisa Nicola
... and a sacrifice that I think everybody, yeah, I, I mean, I think I, I definitely want.
- SBSteven Bartlett
Are you hopeful for all of your professional endeavors?
- LNLouisa Nicola
Yes.
- SBSteven Bartlett
You are hopeful?
- LNLouisa Nicola
I'm in control
- SBSteven Bartlett
You think we're gonna move in a good direction as a society as it relates to-
- LNLouisa Nicola
Hmm
- SBSteven Bartlett
... Alzheimer's and-
- LNLouisa Nicola
Yes. I, I'm hopeful for that. I'm hopeful for the message that I'm getting across. I think, uh, social media is providing the platform for free education and for people to understand that they have agency over their brains. Uh, I'm not hopeful for, um, anybody saving us or coming in and giving us a easy way forward.
Episode duration: 2:04:42
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Transcript of episode 0t_DD5568RA
