Why 90% of Alzheimer's cases are preventable, with Drs. Ayesha and Dean Sherzai

Dementia is the fastest-growing epidemic in developed nations, poised to overwhelm healthcare systems and profoundly impact millions of lives.

But what if we told you that cognitive decline is not inevitable?

While many believe they’re destined for dementia due to genetics, groundbreaking research reveals that lifestyle choices hold the key to safeguarding brain health.

Drs. Ayesha and Dean Sherzai are neurologists and co-directors of the Alzheimer’s Prevention Program at Loma Linda University. With training from Columbia and Georgetown Universities, this powerhouse duo combines cutting-edge science with practical strategies to help you protect your brain.

They’ll reveal the lifestyle habits driving the dementia crisis and share how their NEURO plan, focused on Nutrition, Exercise, Unwinding, Restoring, and Optimising, can keep your brain healthy for years to come.

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Transcript

Jonathan Wolf: Ayesha and Dean, thank you very much for joining me today. 

Dr Ayesha Sherzai: It's such a pleasure to be here. Thank you so much for having us, Jonathan. 

Dr Dean Sherzai: It's wonderful. 

Jonathan Wolf: So we have a tradition here at ZOE where we always start with a quick-fire round of questions, and those questions come from our listeners, and we have these very strict rules; you can say yes or no, or if you absolutely have to, a one sentence answer, but it is frowned upon. Are you willing to give it a go? 

Dr Dean Sherzai: Of course. Of course. 

Dr Ayesha Sherzai:  Do it.

Jonathan Wolf: All right. I'll start with Ayesha. If both your parents have dementia, are you doomed to get it as well? 

Dr Ayesha Sherzai: No. 

Jonathan Wolf: Can dementia be reversed? 

Dr Ayesha Sherzai: No. 

Jonathan Wolf: Can you dramatically reduce your risk of getting dementia?

Dr Ayesha Sherzai: Absolutely yes.

Jonathan Wolf: Dean, are there foods that will reduce your risk of getting dementia? 

Dr Dean Sherzai: Yes. 

Jonathan Wolf: See, that wasn't so bad, was it? Finally, and you can have a whole sentence, what's the most surprising thing that you've learned about preventing dementia? 

Dr Dean Sherzai: The most surprising thing we learned was that 90% of Alzheimer's can potentially be avoided with five simple lifestyle changes.

Jonathan Wolf: So this is only the second time that we've had a husband and wife duo on the show and the first time was when I interviewed my wife. She's a dermatologist, so we were talking about skin health.

I can tell you, I'm feeling a lot more relaxed today. So I found interviewing my wife was the most stressful episode I've ever done on the show by far, absolutely. Now it went great, but I'll be honest. I was really anxious about it and what might happen afterwards if I messed it up. 

So I'm actually in awe of the two of you being able to work all together all day with your spouse. And I understand that you actually connected in the first place over dementia.

Dr Ayesha Sherzai: We did, yes. The first conversation we had was about our grandfathers. They were both incredible people who did wonderful things for their communities and for the society at large and they were highly educated.

We were both privileged to have lived with them throughout our lives. So they weren't the type of grandparents who were away, they were there with us. It's in our homes. 

To see someone so intelligent and so capable slowly and gradually lose parts of themselves and their memory, to the point where they can't remember the names of their grandchildren and they can't do their very basic activities of life was devastating. 

And it was incredibly empowering as well, to see someone change like that, there was no other way we could have dedicated ourselves to anything else. So we both went into the field with the promise that we were going to find a treatment for it and understand how this magnificent brain of ours functions. 

Dr Dean Sherzai: Remember, this is 20 years ago and we met while doing service. I had just finished my work at NIH, a National Institute of Health, and I had gone back to Afghanistan with the World Bank to help rebuild the country. I had gone back with Doctors Without Borders. 

It was an expat party in a post-conflict world, you know, difficult life that we had seen. And we sat next to each other and that's where it started 20 years ago, 21 years ago to be exact. 

Jonathan Wolf: That's a really beautiful story, and it's nice also to think that there could be nice things that come out of dementia.

Regular listeners of the show will have heard me talk about this in the past on other podcasts talking about dementia, but my grandmother got Alzheimer's, and she got it really quite young. I think the experience I had is, that not only was this a horrible thing to observe in someone that you love, but also it had a really profound impact on my father.

And I think that he's really spent the rest of his life in terror of the idea that this will happen to him. And he's in fact significantly older than his mother was when she got Alzheimer's. But it's really shaped in this fear of the impact on his brain and then how you come across to everybody.

It's a horrible disease and it does have this impact across the family, which is one of the things I think that's particularly striking. So I'm always really pleased when we talk about it. I think it's really important. 

I love that today, with these answers you've already talked about, they're profoundly different from what my father has always believed, which is that there's nothing he can do about it. It's entirely down to the genes, and he doesn't know whether or not he's got these genes that his mother has, and if he does, there's nothing he can do. 

I think you've already said, well, that isn't really true. Now, before we get into that, could you remind us, what is dementia and Alzheimer's, before we start to talk more about why it happens?

Dr Dean Sherzai: So dementia is the umbrella category. It's a group of symptoms where cognitive decline, whether it's memory or other cognitive elements, becomes so poor that a person can no longer do their daily activities. 

They're having difficulty driving if they were driving before. They were having difficulty cooking if they were cooking before. If they were having difficulty with their finances and things of that nature. 

It's a protracted period. Remember, if there's a short period of loss of consciousness, that's delirium, that can get better. This is protracted. That's a big category. Now, under that are many diseases that cause dementia.

Alzheimer's is the biggest category. Alzheimer's constitutes about 60 to 70% of all dementias. And it has a particular pathway, particular symptoms, and we can talk about that. We have Lewy body dementia. We have frontotemporal lobe dementia. We have vascular dementia. We have Parkinson's dementia. We have Huntington's dementia. We have metabolic disorders. And then there are reversible kinds of dementia related to depression and anxiety, where the depression and anxiety have gotten so bad, that the person's life is affected now. 

Those can be treated. Metabolic disorders can be treated. Things like Alzheimer's, where even though some people are making those claims, which is incredibly irresponsible because we've done the pathology, we've seen what the people go through by the time the disease manifests, those are not at this point reversible.

But the good news is that even prior to that dementia state, which is called MCI, mild cognitive impairment, so much can be done to prevent the progression. 

Jonathan Wolf: I'd like to go back to this thing I just raised about my father worrying that this dementia is in his genes. Is that true? 

Dr Dean Sherzai: Everything we do, everything we are is genetically influenced.

Even, I just drove from Redondo Beach to LA. My driving is notorious, even my son, a teenager says that's the way, and it's because of attention and all these other things, even those have genetic components, these little micro behaviors. But genes manifest in different degrees for different conditions.

Huntington's disease is a hundred percent penetrant gene disorder. It means that if you have this gene, you're going to get the disease no matter what. There's nothing you can do about it. In Huntington's disease, there's a chromosome four abnormality. And even in their 20s, even in childhood, if we see that, we know they're going to get it in their 30s and 40s.

But for a great majority of diseases, genes are not deterministic to that extent. Genes affect risk, genes play around or interplay with environment, interplay with lifestyle, but they're not the determinant. And that's the case for Alzheimer's. 

In Alzheimer's, which is the big category of dementia, the percentage of Alzheimer's that's determined by 100% penetrant genes, meaning by genes that are absolute. That means if you have these genes, you're going to get Alzheimer's at an early age no matter what, is only 3%. 

The rest of it is genetically influenced, but it's the genes have to do with lifestyle. Genes are profoundly affected by lifestyle and environment and that's what we need to kind of highlight.

That's what we need to tell people, that it's that effect, that interplay of how you interact with your world that really determines the outcome, not as much as genes when it comes to Alzheimer's and many other diseases of aging when it comes to brain health. 

Jonathan Wolf: So are you saying 97% of people, if they could somehow have the perfect lifestyle, they would not end up getting Alzheimer's?

Dr Dean Sherzai: So we have to be careful. In our book, we said that 90% of Alzheimer's can be potentially prevented. You know, we live in an age where people are playing around with numbers and we have to be very careful as scientists. So, there's no direct evidence of that. 

Direct evidence says 60%, pretty much direct evidence. But we say that if you have optimal lifestyle elements, which we'll talk about, as much as 90% can be prevented. 

Jonathan Wolf: Got it. But you're saying even now there's clear data that 60% could be prevented. 

Dr Dean Sherzai: Absolutely. 

Jonathan Wolf: And your view is if you really took it to the extreme, you could actually get down to only 1 in 10 of the people who were going to get it would actually end up getting it.

Dr Dean Sherzai: Exactly. 

Jonathan Wolf: So that's a very positive story. 

You also said that dementia isn't reversible. So once you've got it, it's too late. I believe you talk sometimes about this concept of pre-dementia. Could you explain what that is? I mean, as soon as any of this happens, is it too late or…?

Dr Ayesha Sherzai: I think it's important for our lovely audience to understand that when people are diagnosed with the scary word dementia or Alzheimer's disease, it's not something that just popped out of nowhere right then and there.

Let's stick to Alzheimer's disease because there are other types of dementia as well. In Alzheimer's disease, there are multiple different things that are going on in the brain. There is deposition of these harmful, toxic protein byproducts. Specifically, the ones that have been studied are amyloid beta protein and tau.

And they essentially, deposit within a cell and outside of the cell, and they start damaging the infrastructure of the brain. The direct cause as to why that happens, we're not very clear right now. But there are some hypotheses, and one of the hypotheses is that the body has a difficult time getting rid of these toxic byproducts over many, many years.

In multiple studies, both imaging studies and biomarker studies, which means they look at people's blood levels of these toxic byproducts, or they look at cerebrospinal fluid, you know, the spinal tap fluid, and they look at the proteins there. It seems that the process of deposition of these harmful proteins, it takes decades for it to come to the point where people are diagnosed with dementia.

It takes nearly 20 to 30 years for this process to have been present, ever-present, and cause damage in the brain. 

Jonathan Wolf: Nearly 20 to 30 years of this slowly being laid down in my brain.

Dr Ayesha Sherzai: That is correct. And that is why now scientists and neurologists are addressing Alzheimer's disease as a disease of middle age, it's not something that manifests in our seventies, eighties, nineties, and beyond.

Yes, the prevalence increases because people, as they age, their risk goes higher, but the disease process actually starts in your forties. Maybe even 30s. 

Jonathan Wolf: It's amazing. This is taking a very long time, slowly. It's not like I'm driving my car every day. It seems fine. These days, your cars last forever, right? You're still driving a year 10 and they don't break down. It's not like when I was a kid. 

But eventually, it breaks down in year 12 because of this slow wear and tear over the previous 12 years. 

Dr Dean Sherzai: Absolutely. There are four processes that we know at this point. And, to the best of our knowledge today, is what we all should say.

And that's not a weakness of science, that's a strength of science, which is at this point what we know there are four elements that are contributing to the accumulation of this protein, these proteins, as well as damage to the brain itself. 

It's inflammation, oxidation, lipid dysregulation, which means this abnormality of fat levels, lipid levels, glucose dysregulation, sugar dysregulation, pre-diabetics and diabetics, and all these. 

As well as not getting rid of the toxins. So the things that accumulate and the things that are not taken away. And once we get to the part of sleep, you'll see that profound effective component for the brain. 

So if we understand those elements, and that's how we came up with our work, which is, that's how we work backwards and oh, what are the things that contribute to these damaging products, which not only affect your relation with Alzheimer's but most brain diseases and brain aging in general.

And why does it start 20 to 30 years earlier? Because it's a cumulative process. 

Dr Ayesha Sherzai: Coming back to your question, and I think it was very important for us to draw this picture, and the reason I just zoomed out to show everyone that it's essentially a spectrum of this condition slowly and gradually worsening to the point where it becomes Alzheimer's disease, that's the point when it becomes irreversible.

I think it's very important for us to say that because, you know, we have in the United States, we have over seven million people who are suffering from Alzheimer's disease and it's about 55 to 60 million around the world and we know that we can prevent it. 

Even before it is in the stages of early Alzheimer's disease, there is a lot of evidence that we can reverse it when it's in the mild cognitive impairment stage, which is the pre-Alzheimer's stage.

We know that we can slow down the progression of Alzheimer's disease once it's in the early and the middle stages as well. But to say that it can be reversed is irresponsible because we have no evidence for that. 

But I think that prevention is good enough and we have a tremendous amount of data that shows us that people can do incredibly well by living a healthy life. 

Jonathan Wolf: Well, that's exciting. 

I know that you're both co-directors of the Alzheimer's prevention program at your university and you already just mentioned, I think 55 to 60 million people around the world living with Alzheimer's. Are we seeing an increase or a decrease in the number of people with dementia?

Dr Dean Sherzai: In one way it's increase, in another way it's a decrease. And the way it's increasing is because we're getting older as a population. It's not necessarily related to anything else except that we're getting older and we're getting a little unhealthier. So that's one element.

The way that in certain places it's decreasing is because the population is decreasing in certain regions that were massively affected by Alzheimer's like Japan. Now there's a little bit of a decline there because the elderly population is decreasing. Population in general is decreasing. 

So, the more important point being that as we live longer. We're going to be more susceptible to Alzheimer's and other dementias because we're going to have more cumulative traumas, all these lifestyle factors that will increase our risk for dementia and Alzheimer's in particular.

Jonathan Wolf: And is that, I'm just thinking back a bit to my car analogy. I'm going to stretch this a little bit, but I think you're saying that in the past, your car might've just been written off at year seven because it got crashed off the road. And this is like all the ways that we might've been killed by a saber tooth tiger or just died before antibiotics of some infection.

Are you now saying in a sense, we tend to expect that we'll live to be 70 years old and at that point, your brain has been around for 70 years and so it's just much more exposed to the product of this damage over time. 

So it's almost like if you're lucky enough to live that long, this suddenly starts to become a big concern for you. But if you thought you were only going to live till 40, seriously, don't worry about it. 

Dr Dean Sherzai: Exactly. I mean, that's the whole point. We were not expected to live past 30. What was the point? You're going to run around, find some food, find a mate, reproduce, have children, and then you pass away. We're not making a sociological statement here. It's a reality. 

Now we're living way past that. Now, the good news is the brain has incredible capacity if we do the right things to not only not degrade, but actually grow. 

We're making the statement that the brain is the only organ that can grow continuously, but we have to give it the right environment and the right elements to grow. But as it is, it's the opposite. 

So people in their twenties and thirties, they're immortal. They think they're immortal. So we do things that profoundly damage the brain, but you don't see the effect because you have enough reserve. That you don't see the effect. But then what happens is, as you work through your reserve, your bank account of reserves, then you see the beginning signs.

But if you start early enough, or even in midlife, or even later, before you have dementia, you can build reserve. You can build incredible reserve and continually have a beautiful growing cognitive capacity. 

Jonathan Wolf: What does it mean to build cognitive reserves? 

Dr Dean Sherzai: So we have 87 billion neurons, one quadrillion potential connections. Each neuron can make a couple of connections or as many as 30,000 connections. And in your cerebellum, your Purkinje cells can make 50,000 connections. Imagine that connectivity. 

An average human being 50,000 years ago would need to hunt to get food and find a mate. A squirrel can do that. Let's go lower than a squirrel, a cockroach can do that. And that's a ganglion. That's a few thousand neurons. 

So what about all this extra neuronal power? We're talking about 1 times 10 to the 50th power of capacity per second. It's remarkable. Now, that's reserved. That's extra power that you don't use for finding the TV channel, Friends,  talking to somebody about the soccer game or football game or something else.

What is that? That's reserved. That's extra power that if these connections are severed because you had a bad night's sleep, or you had a head trauma, or you drank a little too much, that there's still more connectivity that preserves that function, that extra connectivity is reserved. 

Now that reserve is profoundly important. That's why every study that you've seen, that's legitimate, that looks at cognition, every study looks at people's education. Why? Because it's a rough estimate of cognitive challenge. It's a rough estimate. It really doesn't have to do with education. 

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I know people who didn't even finish high school, but they were mentally challenged. They have more neuronal connectivity than anybody with a PhD. So it's how you've challenged your brain throughout life. And if you push your brain, that makes more connectivity. That creates more reserve, that creates more protection down the stream. 

Jonathan Wolf: So I constantly tell my son that he never reads a book. He just  looks at his phone on social media. Can I now tell him that a bunch of scientists have explained that that is not building his mental reserve and he has not challenged himself properly and he isn't setting himself up for long-term health or am I stretching it a bit? 

Dr Dean Sherzai: No, you're not.

But I think we might be off on the wrong tangent. Maybe the medium of learning and pushing the brain might not be the book in the future. It might be cognitive games where it teaches you and pushes you. So it's going to be a different medium, but you have to push the brain.

It has to be challenged. It has to be pushed. Your whole dopamine pathway is based on this. It's not about getting the next piece of food, it's about the brain challenging and finding the unknown, the unexpected, and that creates new pathways. 

Jonathan Wolf: But you are saying that you've got to push yourself. So in some sense, my general message of this is sit back, passive consumption, that we all know we're incredibly addicted to, is not helping to develop that.  

Dr Dean Sherzai: It's worse. People who retired and were highly achieved and then for two years didn't do anything. They sat on the beach. I don't know if they sat on the beach, I'm just going to use the beach, and they didn't do anything. They had the greatest decline because this brain that was active is now expecting to be pushed. But it's not pushing. 

Jonathan Wolf: So I just want to check because I'm thinking about this analogy a bit of the brain being like a muscle and we have lots of podcasts talking about exercise, how important it is and you have to force yourself to use those muscles to preserve it.

I'm hearing this as the brain is a bit similar. You've got to stretch it, strain it in some way in order to set yourself. 

Dr Ayesha Sherzai: Absolutely. Yes. 

Jonathan Wolf: And that genuinely does, in a sense, make the brain stronger. And therefore, in later life, protects it better from dementia. 

Dr Dean Sherzai: I think we might be jumping ahead of ourselves, but the London taxi driver study…

Dr Ayesha Sherzai: I was just thinking about that. The concept that most people think that you have to do this during your youth and very early in life to create that bank account that Dean was describing. 

But your brain can create more connections at any age. One of the examples is the London taxi driver study, a phenomenal study where they compared London taxi drivers to bus drivers. Apparently, to become a taxi driver, this is the pre-GPS time, the candidates had to go through this arduous testing technique or mechanism called the knowledge. 

They had to learn the names of the streets and the locations. I don't know if you've lived in London or you are from London, but it's pretty intense and it's very chaotic. And so to memorize the different elements takes a long time and it takes some effort. 

So they looked at the brains of those who went through this testing versus the brains of bus drivers who had a specific route and they didn't really have to memorize anything. And at the end of that particular study, they found that taxi drivers had actually grown their brains.

Jonathan Wolf: They'd grown their brain. 

Dr Ayesha Sherzai: Particularly the part of the brain that is responsible for encoding memory called the hippocampus, while those of the bus drivers didn't. 

And these were individuals who were over the age of 50. And that in itself is an example of how dynamic the brain is. Obviously, they did neuropsychological testing or memory testing them as well, and they scored higher as far as their memories are concerned. 

Jonathan Wolf: That's extraordinary. So really your brain, you can build this in this, this matters. 

I'd love to go back to this topic that you just picked up Dean earlier about saying that these four contributing factors, I think you said inflammation, oxidation, some problems with fat, and problems with sugar.

Could you help me to understand a little bit more about that? A little bit more about how that is driving this. 

Dr Dean Sherzai: Yeah. So a lot of times people say Alzheimer's is type three diabetes. But when we look at the data downstream, there seems to be lots of other pathways that can lead to this trauma that then accumulates into amyloid later and then accumulates at the disease.

You can come to it from diabetes or pre-diabetes. We did a study in Haines, which was a nationwide study, we looked at it and it was published a few years ago, looked at pre-diabetics. And not pre-diabetics in their 70s, pre-diabetics in their 50s. And even they had lower cognitive states. And other studies have shown that as well.

Jonathan Wolf: People who have pre-diabetes, which means their blood sugar levels are higher than normal, actually their brain is influenced by that in a bad way.

Dr Dean Sherzai: I mean, we have to be careful not to overstate that because different conditions, different people, how well you can control that and how well you control your pre-diabetes and diabetes matters.

Just because you have diabetes, that doesn't mean you're going to develop dementia. In fact, if it's treated well if it's controlled well, not at all. 

So uncontrolled pre-diabetes and diabetes does influence cognition over time. Same thing with lipids. There's a lot of data on LDL and cholesterol, specifically LDL, and many, many studies.

Ayesha will tell you all these studies that show that people with high LDL, even in midlife and even earlier, have a much greater risk of dementia later on. So that's a different pathway, right? LDL. 

Sometimes it's both of them. Sometimes people have both and then people who have chronic inflammation have the same thing.

So those are the four pathways that can either be separately or together, which often with metabolic diseases, they often happen together, can contribute to enough damage, enough abnormal systems, and protein production that can later manifest into either vascular dementia or Alzheimer's dementia. 

Jonathan Wolf: Ayesha, can you help us to understand what's the lifestyle?

What are people doing that are contributing to these different factors that you're describing causing this risk? 

Dr. Ayesha Sherzai: So in studies, especially the types of studies that look at large groups of people over a long period of time, have shown us that there are a number of factors that matter and especially their existence throughout the span of our lives can either increase or reduce the risk of developing Alzheimer's disease. 

The Lancet magazine, so it's well-known medical journal, and they come up with a consensus report every three to four years. And recently, just a few months ago, they created this beautiful picture of the risk factors during childhood, midlife, and late life.

And they have listed a number of different factors. And Dean and I have kind of made it easy for our patients to remember these factors. So we've created this acronym called NEURO, N-E-U-R-O, self-serving because we're neurologists.

N stands for nutrition, E, exercise, U, unwind or stress management, R is restorative sleep, and O is optimizing cognitive activities or building cognitive resilience.

And under each of them, so for example in nutrition we have lipid metabolism, LDL, cholesterol that contributed to or are affected by the kind of foods that we eat. Smoking comes under that as well. Alcohol comes under that as well. So all of these factors play a very, very important role in either reducing or increasing our risk factor for Alzheimer's disease.

Jonathan Wolf: And we talk a lot across this show, I think, about how modern Western lifestyles have had a lot of unintended negative consequences. So we talk a lot, obviously, about nutrition here, impact on microbiome, impact on the rest of our health. 

I think everybody here listening to this show knows if you eat the wrong sort of diet, then it increases your risk of a heart attack or indeed getting diabetes. I think a lot of people will be more surprised that it's linked to something like Alzheimer's. 

If we just take this back to simple aspects of lifestyle, what are the aspects of lifestyle, if you were going to try and explain to my son or my daughter,  that actually matter for Alzheimer's, what do they need to worry about?

Dr Dean Sherzai: So the organ that's most affected is brain. This little three-pound organ, which is 2% of your body's weight, consumes 25% of your body's energy. At any moment. 

It also is the most vascular organ in the body. It has more arteries and veins than any other organ in the body. If you connect all the arteries and arterioles and capillaries end to end, it's 400 miles. 

There's a picture, people can actually search for this, they've denuded, they've gotten rid of all the other tissue and all they've left behind is a vasculature and you look at it and you say, how come there's room for anything else?

There's room for about 87 billion neurons, one quadrillion connections. So it's a really well-compacted system. So anything that affects vasculature, well, guess what? The most vascular organ is the brain. Metabolic, 25% of your energy. oxygenation, 50% of oxygen at times.

So it's the organ that's going to be most affected by all the metabolic things that affect everything else. 

Dr Ayesha Sherzai: Absolutely. 

Jonathan Wolf: So when you're thinking about your exercise or your nutrition or any of the rest of these things in your health, anything you're thinking about that might affect your heart, it's also directly affecting your brain, maybe even more so.

Dr Ayesha Sherzai: Yeah. People always think that the brain, you know, just the organ that's above your neck is somehow disconnected from the rest of your body, and it's not. 

If we think of everything that affects our gut, our heart, our kidneys, our skin, affects our brain as well, I think it will make more sense.

Dean and I, you say that your brain gets affected most by anything you do. So the kind of foods that you eat, the kind of people that you surround yourself with, the kind of activities, movements that you choose to partake in, all of these impact your brain health significantly. 

Dr Dean Sherzai: The reason we say that 90%, and we haven't seen that because we don't really optimally do all those things. Which is optimally eat, optimally exercise, optimally stress manage, and we'll talk about stress and it's effect, it's profound effect, optimally sleep. The only cleanse is sleep and water.

We will describe the process of what happens during sleep. It's literally the most efficient city-cleaning mechanism you could ever imagine. And then mental activity, challenging your brain to keep these billions and trillions of connections connected and making more connections in your 60s, 70s, and beyond.

If everybody does that optimally, you're not going to avoid for a great majority. We want to be responsible, there are those that are genetically driven. We talked about 3%. We even pushed the edge all the way to 10%. So for about 90%. But that means optimal.

But here's the good news and Ayesha did a study in California, a teacher study, the population 133,000 people, she won the youngest researcher award for this. What the study showed that it's not all or none, every positive move you make, incrementally helps the brain. 

Whether it's small changes in nutrition, small changes in movement, small changes in stress management, small changes in sleep, where you get those four to five cycles of deep restorative sleep, you will make profound changes.

So this is an empowering message. And it doesn't rely on some tricks. 

Jonathan Wolf: Ayesha, earlier you mentioned the NEURO plan, but can you remind us what is it and who should follow it? 

Dr Ayesha Sherzai: NEURO is an acronym that Dean and I created, self-serving, because we're neurologists, but it stands for Nutrition, Exercise, Unwind or stress management, restorative sleep, and optimizing cognitive activity.

And these are based on evidence-based lifestyle interventions and lifestyle factors that improve brain health and prevent cognitive decline on Alzheimer's disease. 

Jonathan Wolf: Amazing. And who should be following them? 

Dr Ayesha Sherzai: Everyone, whether you're nine or 99. So N, nutrition, very important. And I think you know this more than anybody else, and you do such a fantastic job in this podcast, empowering people about nutrition.

So in the realm of neurology and neuroscience, we have a tremendous body of evidence showing that the types of food that people choose directly impacts their brain health and it can prevent devastating diseases like stroke, Parkinson's disease, Alzheimer's disease and other types of dementia, particularly vascular dementia.

When you look at the different dietary patterns, it's essentially a variation of the same theme. Diets that are high in plant-based foods, fruits, vegetables, whole grains, legumes, nuts and seeds, and sources of polyunsaturated fatty acids. They tend to do very well. 

So that could be a MIND diet, a Mediterranean diet, a dash diet. It could be any cultural diet that highlights the importance of foods that are high in polyphenols that are high in fiber, good fats, which is polyunsaturated fatty acids. And they're low in processed foods, in refined carbohydrates, in sources of saturated fats, which are the type of fats that can increase your LDL cholesterol and can potentially harm the brain.

The numbers are incredible. For example, there was a study that was conducted at Rush University in Chicago here in the United States. Dr. Martha Morris, she was the lead researcher, the late Dr. Martha Morris, and she looked at adherence to the MIND diets. 

The MIND diet is a hybrid diet. It stands for Mediterranean Dash Intervention for Neurodegenerative Delay. Thank goodness for the acronym MIND. The Mediterranean Dash Combination. And when you look at the diet, it's not a cultural diet per se, it's essentially a scoring system. 

When people adhere to the MIND diet, they get a high score for consuming green leafy vegetables, cruciferous vegetables, other vegetables, fruits, specifically strawberries and blueberries that are high in polyphenols and flavanols. When they consume whole grains, when they have less refined carbohydrates such as white bread or added sugar to foods. When they consume nuts, seeds, which are great sources of polyunsaturated fatty acids and omega fats, when they consume extra virgin olive oil, which could potentially have high polyphenols and mono and polyunsaturated fatty acids.

They get a high score and sources of omega three fatty acids, which are found in fatty fish or flax seeds, chia seeds, hemp seeds. And they get a low score when they consume a lot of red meat, a lot of high-fat dairy products, which may be higher in saturated fats, and if they consume too much alcohol. So, that is essentially the concept that you find in all of these dietary patterns.

In this population, when they adhere to the MIND diet, they reduce their risk of developing Alzheimer's disease by 53%. And even moderate adherence reduced the risk by 37%. And in my study, in the California teacher study, the same thing. We looked at the Mediterranean diet and we looked at the scoring system.

And the beautiful thing was, it was not an all-or-none phenomenon. So, every small incremental change towards that positive outcome, say, for example, adding a cup of green leafy vegetables or switching a donut for some fruits, it actually made a huge difference. 

I think that's pretty empowering for people to know that you don't have to jump into it wholeheartedly. You can start by simply changing a few things moving forward. 

Jonathan Wolf: I'd love to ask you a question that I think quite a lot of our listeners will have right now. So a lot of listeners to this podcast are also ZOE members. And so that means that they're using our app. They've used a test kit to then get this personalized advice.

That advice was built really to optimize overall health. And so it's very much focused on gut health. It's very similar to a lot of the advice you're talking about with a Mediterranean diet. It doesn't have a particular focus on trying to be a brain-specific diet. It's reducing inflammation, all of these sorts of things.

I think what they're going to be interested in listening to this is, is there anything different and specific that you would be recommending for somebody who's worrying about dementia or given what you were saying about how the brain is just even more affected by what's happening everywhere else?

Is the best brain diet the same as the best overall health diet? 

Dr Dean Sherzai: Yeah. I mean, just for transparency, we're a whole food plant-based ourselves. We don't push that aggressively on others because we think that you can achieve brain health in many other ways. In most cases, it's the same.

It's the same diet, whether it's for heart, for everything else. A couple of things to be aware of. At this point, I mean, as I said earlier, I love the concept of, to the best of our knowledge today, the three elements that are important for brain, B12, make sure that your B12 levels are normal or on the higher side, vitamin D and Omega-3.

We just did two reviews, two comprehensive reviews, one on Omega-3 and the developing brain and Omega-3 on the aging brain. And in both of them, there seems to be trends towards needing Omega-3, being extra aware of Omega-3 because Omega-3 has that much effect. It's the only fat that the body doesn’t make, well, Omega-6 as well.

In the Western diet, you don't have to worry about Omega-6. In fact, we have excess of Omega-6. So Omega-3 is very, very important.  DHA for the brain in particular makes up more than 50% of brain's volume. So it's critically important and we don't make it. So we have to kind of be aware of it.

So that's basically whether you get it from fish or in our cases and other people's cases, they can get it for chia, flaxseed or supplements. And that's basically it. The acronym is SMASH; salmon, mackerel, anchovies, sardines, and herring. The fatty fish.

But it's not the fish, the fish gets it from the algae. So it's the Omega-3 in particular, there's no uniqueness beyond that. So that's important to kind of know where are you going to get your Omega-3 and be aware of it and get it. 

We just had a conversation with a world-renowned lipidologist and Omega-3 expert who said that even people who are just taking it from chia and flaxseed, if they're extra aware of it, they should be fine.

Dr Ayesha Sherzai: Yes. If they have healthy livers and if they're eating a healthier diet, that we should be able to convert ALA into EPA and DHA, which is important for brain health. 

Dr Dean Sherzai: And also being aware of Omega-6 because there seems to be a competition with enzymes. So lowering your Omega-6, which is processed foods, right? And making sure that alcohol does not affect the liver to the extent that it's going to affect the transition. So that's basically it. 

Jonathan Wolf: Am I allowed a glass of red wine a few times a week? What does the brain doctor say about that? , 

Dr Dean Sherzai: That's interesting, that's a funny thing. So I think we've got a pretty big following on social media and I've never been lambasted more than when I said, the amount of alcohol that's good for your brain is… Zero. 

But does that mean that I never drink alcohol? I do, once a month, once a couple of times a month, if there's a glass of wine, I sip it. But I say that I will never create science for my hypocrisy. So once in a while, it's not going to damage at all, but it's the chronic use of alcohol that's going to affect the brain.

Dr Ayesha Sherzai: Some of the intermediary factors that are important that are affected by diet and that in turn affect brain health and Alzheimer's risk is LDL cholesterol.

I'm very aware of that fact and it's almost become a jingle wherever I go and there's a one minute, if you could just tell me one thing that I need to do for my brain health. What would it be? And my answer is usually, keep an eye on your LDL cholesterol. 

It was recently added by the Lancet Committee for Dementia Prevention as one of the major risk factors for dementia in midlife. And so because we know that there is almost a direct relationship between saturated fat consumption and LDL, it's important to keep that under the radar and address it as much as possible.

Jonathan Wolf: So my conclusion is I can go to my dad and tell him what I tell him all the time, but he doesn't listen to me anyway, which is that changing your nutrition, moving towards, the sort of diet that we probably talk about on this podcast all the time can have a profound impact on your risk of dementia.

Dr Ayesha Sherzai: That is very evidence-based and yes, absolutely true. 

Jonathan Wolf: He still won't listen to me, but at least I can, at least I can say that. 

Could we move on? So I think we are on N and so I guess the next one must be E. 

Dr Dean Sherzai: Yeah, yeah, exercise. Exercise is tremendously important. Both Ayesha and I have degrees in nutrition, she's also a culinary chef and she knew the importance of nutrition when she was doing her fellowship at Columbia University in New York. 

In the morning she would be in a fellowship in the ICU and at night she would take cooking classes, realizing that that's how important it is to teach people how to eat healthy, but also tasty, right? So the taste is important. 

Dr Ayesha Sherzai: Oh, very important. 

Dr Dean Sherzai: But recently we realized that exercise is as important, if not more, let's say as important so that we don't create a competition between the nutritionist and the exercise people now. Exercise is tremendously, probably more important for the brain.

Again, I think we're being selfish because we're a neurologist, but it's extremely important. It actually grows the brain. So we say that nutrition, stress management, and sleep create the environment for the brain to thrive. But the two elements of neuro that grow the brain are exercise and mental activity.

Jonathan Wolf: So I think most listeners will think that nutrition makes sense, I understand why that's affecting my brain, it's really obvious. But the exercise seems a lot, I can't think of any exercise my trainer has made me do where I'm stretching my brain. My biceps and my legs yes. So could you help us to understand?

Dr Dean Sherzai: Have you ever done leg exercises?

Jonathan Wolf: Yes. 

Dr Dean Sherzai: Yes. So leg exercises, in one study they compared MCI patients, pre-dementia. It was a really, really well done robust study. One arm was told to do leg exercises. The cases. And the other arm was stretching. Not that stretching is bad, but in this case, let's compare the two.

Dr Ayesha Sherzai: They didn't really do any resistance training. 

Dr Dean Sherzai: No resistance training. Exercise reduced the chance of progression from MCI to dementia by more than 35%. So how could it do that? Multiple ways. 

One is we know that people who exercise increase this hormone called BDNF, brain-derived neurotrophic factor, which is basically if a fertilizer is powerful for plants, BDNF is a thousand times more powerful for the brain, that's how important it is. 

But it's not just BDNF, it's GDNF and VGF as well. VGF is vascular. Remember that the brain is the most vascular organ and there are hormones that keep the brain vasculature healthy and growing. So VGNF grows with exercise and GDNF is glial cells, which is the protective cells.

So it directly affects the infrastructure and the hormones and the chemicals and the building blocks of the brain every time you exercise. 

Jonathan Wolf: It's not like a muscle. I'm not directly stretching my brain during the exercise, but when I'm doing this exercise, it's then creating these hormones and other chemicals that are going into my brain and they're having these really beneficial impact.

It reminds me of many of the conversations we have, talking about the microbiome and this understanding now that the food we eat is affecting these microbes that are then creating these chemicals that go to the brain. But am I stretching this or there's an analogy here?

Dr Dean Sherzai: A hundred percent. Yeah, that's the microbiome. But this is directly every time you exercise, especially leg strength. It has a direct effect on the brain. 

Jonathan Wolf: Can I ask, because you just mentioned leg strength? So is there a particular types of exercise that are better for the brain? 

Dr Ayesha Sherzai: So, yes, it seems that for a long period of time, we thought that walking and running, which is phenomenal and walking is amazing, running is great if people want to do it, but building muscle specifically makes a huge difference. 

Because we have the largest groups of muscles in our legs below our belt, those activating those muscles can create more of these growth hormones that Dean was talking about, specifically brain-derived neurotrophic factor.

So doing things like squats and lunges, and sometimes we joke and say bigger, bigger legs, bigger brain. That could be a title for a really nice book. But really focusing on our glutes and our hamstrings and our quads is incredibly healthy for the brain. And it also prevents falls.

As we grow older, our balance and our mobility get affected. And the number one reason why a lot of our elderly community members end up in the emergency room is because of imbalance and falls. By strengthening our legs, we actually reduce the risk of falls as well. So it has so many different benefits from multiple angles.

Jonathan Wolf: That's amazing. I never heard that before and I'm going to be discussing that with my son as well as a teenager. So he's really gone into the gym. 

Dr Ayesha Sherzai: Don't skip leg day. 

Jonathan Wolf: But he feels that for the full aesthetic, maybe the legs doesn't have quite the same impact and so now I'm going to tell him, well, you got to still care about the legs.

I think that at his age, worrying about dementia is very, very low on the list of concerns. 

Dr Dean Sherzai: One other element to add is frailty and a new study shows that the one variable that determines length of life is frailty. The main determinant of frailty is leg strength. 

So in many ways, I think people focusing on leg strength in a responsible way, you're not going to be a bodybuilder, so don't do squats with weights on your shoulder, things of that nature.

People have knee issues and back issues, taking all of that into consideration, creating a program that builds your legs, is probably the most effective thing you can do for your longevity and your brain health. 

Jonathan Wolf: Ayesha, I'd love to move on to the next one, which I think is going to be you. 

Dr Ayesha Sherzai: Yes. So you, unwind, or stress management is critical. We're learning more and more about it. 

We know that when people are under a lot of stress or if they are chronic worriers, which I think is such a ubiquitous condition. We're worrying about things and we're constantly inundated with information. And we never really were trained to deal with it. We're never trained in school to deal with stress.

It's not something that is a part and parcel of our life and we're just assumed to live in it and just brush it aside and not even complain about it. 

But we now know that when people have adversities early in life or when they go through periods in life that are difficult to manage, whether it's loss of a loved one, the loss of a job, divorce, or family issues, all of that can impact our brain.

There is a cycle, it's called a pituitary hypothalamic adrenal axis, which essentially translates as how you feel affects you physically. So when we experience stress and adversity, our body starts secreting specific neurochemicals and hormones that can be damaging, specifically adrenaline and cortisol.

Jonathan Wolf: You're saying that this stress really is a real physical effect on my brain. 

Dr Ayesha Sherzai: Absolutely. I mean, they've done studies in individuals who've been through stressful life situations or people who have immigrated from one country to another or who have tremendous anxiety as just a habit of being in that stressful situation.

And they have realized that the chronic secretion of cortisol and adrenaline affects the different parts of the brain and it shrinks the brain. People who have been stressed for a long period of time have smaller brains. 

Jonathan Wolf: It shrinks your brain. 

Dr Ayesha Sherzai: It shrinks the brain. And specifically the part of the brain, the hippocampus, which is responsible basically for memory, but it has a lot of other responsibilities as well. It is very sensitive to the level of cortisol and adrenaline in our body and it shrinks. 

Therefore people have difficulty memorizing things or paying attention or even solve their problems, make a good decision about things. So globally it affects our cognition and specifically it really, really impacts our memory.

And if this is continued over time, it can result in Alzheimer's disease. And so that seems like a very dark subject, but the good side, the positive side of it is it can be managed. Stress management in itself is a whole conversation that we could probably spend a lot of time on, but it starts with perception.

Identifying bad stressors in our life, and especially in this fast-paced life that we live in, we're not able to actually identify our stressors very well. And so identifying bad stresses and differentiating them from our good stresses, the kind of stresses or activities that we bring on ourselves to help us grow, to be better versions of ourselves, whether it's going to school or doing a podcast with you or having cameras and the microphone in front of you, feel responsible. You want to make sure that you bring out the best to the audience so that it's helpful. 

These kinds of activities are ones that grow the brain that really puts a purpose with an activity rather than something that's dark. 

Jonathan Wolf: So not all stress is a bad thing.

Dr Dean Sherzai: It's actually the opposite. There's good stress and bad stress. And we want people to actually increase their good stress. Remember, that's the part that challenges the brain continuously.

The way you differentiate those is, bad stress is the kind of activities that are not driven by your purpose, that don't have clear timelines or clear direction. And that sense of uncertainty and lack of purpose actually creates this indolent feeling, then that translates through the limbic hypothalamic pituitary pathway, chronic adrenaline cortisol overload, which then also affects inflammation, by the way. So this is absolute plenty of data that shows this repeatedly. 

Now the other side is good stress that's purpose-driven, has somewhat of a clear direction, somewhat of clear timelines when you achieve it. All these books about dopamine, that's what that is. Dopamine is not the joy hormone. 

Dopamine is not the success, it's the anticipation hormone. Because the moment you have the climax, it's not at the climax, at the climax, dopamine actually drops. Dopamine is the anticipation of building of that tension. In this case, knowledge, challenge, taking on things that have somewhat of a clear direction, you know you're going to achieve it, there's a direct timeline.

The anticipation builds dopamine which has a direction with happiness also grows the brain. This is the beauty of separating good stress from bad stress. So the secret comes to the language you have in you. 

Jonathan Wolf: What does the R stand for? 

Dr Ayesha Sherzai: So R is restorative sleep, and it is so important. I think we've said all of these elements are really important, but sleep is one of the newest members of the family.

For a long time, we took pride in not sleeping enough and just existing on fumes. We were talking about it, I was like, how on earth did we actually function when we were residents in the hospital on such little sleep? But sleep is probably the most dynamic and active stage of our brain.

Even though we're knocked out and we're unconscious, the brain is awake and it reorganizes itself and it cleanses itself. 

To summarize what happens in the brain during sleep, two very important things happen. The first thing that happens is we have a very elegant cleansing system, a janitorial system you should say, that gets activated when we go through the deeper stages of sleep.

So when you look at the sleep architecture, you have wakefulness and then you have REM, and then stage one, two, and three. During the stages, the third stages is when we have the microglia, which are the cells that are responsible for cleaning the brain gets activated. And then we have a glymphatic system, which is a system of lymph fluid that flows through the brain.

Imagine your brain being a building or a city, and you have these janitorial teams that go into the building, and they start collecting all the trash and the garbage, and they clean the floors and the walls. That's exactly what happens during the deeper stages of sleep. 

But it only gets affected when we actually go there. And when people don't necessarily go there, how does that happen? Say, for example, if they don't get enough sleep, or if they have had too much caffeine, or if they have had too much alcohol, or if they have some sleep disorder, like sleep apnea, restless leg syndrome, that doesn't let them to go through the deeper stages of sleep, that cleansing doesn't happen.

Jonathan Wolf: Or they've flown in eight hours of time zones for this conversation the night before. 

Dr Ayesha Sherzai: Yes, but hopefully the conversation is going to build a lot of resilience and going to negate the impact of sleep. You know, it's a comprehensive system. 

Jonathan Wolf: But I need to have that deep sleep. There's not just any sleep that does this cleansing. You need to get into this deep sleep.

Dr Ayesha Sherzai: 7 to 8 hours of it. Of deep sleep. 

Jonathan Wolf: And so that is then when the brain, which is obviously on all the time when I'm thinking presumably. It's switched. This is somehow switched off and therefore it can be cleaned out.

Dr Ayesha Sherzai: Absolutely. And the second thing that happens, your memories get organized. Initially, it seems like a chaotic group of just messy words altogether. But when we go through the deeper stages of sleep, it gets organized in the right file folder cabinet. So it's easier for the individual to retrieve it later on.

Jonathan Wolf: Wonderful. I think we have one more, which I think is the O if I've got that right. 

Dr Dean Sherzai: Yes. The optimize we touched on a bit earlier, is about mental activity. Challenge your brain. Any activity is great, even simple games like Sudoku, even though I usually attack Sudoku, but the Sudoku or crossword puzzles are great.

And we did a meta-analysis in 2019 and looked at all the data and looked at what works. All activities work, but complex behaviors are better. 

Complex behaviors are real-life activities that engage multiple domains of the brain. For example, learning a musical instrument, learning how to dance, learning a new language, using that language in public or with others, running a group, running a podcast. 

Activities that push you. that challenge you, that are ever-changing, you have to adapt to it but also involve multiple domains. When you're learning a musical instrument, guitar in my case.

Ayesha is an amazing singer, I'm a terrible guitar player. But when I'm playing guitar, I'm learning, I'm reading the notes, that's your left parietal lobe. The language centers, word and keys, and progress. 

You're processing, it's your frontal lobe. You're visually processing, it's your occipital lobe. You're being dexterous, it's your cerebellum and your motor cortex. You're being creative, it's your parietal lobe. You're emotionally involved, and for my listeners, it's bad emotions for me it's good emotions. 

So it's all of the brain being challenged and pushed around novelty around the next level. Learning new things. That's what makes the connections and optimize is critically important. 

No matter how old you are, no matter what you've been doing, please get engaged. Not in one thing. If all you're doing is crocheting, it's great, it's good. But add two or three other activities that are a little more diverse, taking a class online, learning how to dance. 

These diversity of actions involves multiple domains of the brain, which grow the brain powerfully. 

Jonathan Wolf: Thank you both so much and I love that you've offered so many tips that our listeners could actually start implementing tomorrow, right? Many of these are things that you could change immediately.

I'd like to try and do a quick summary and please correct me if I've got any of this wrong.

So I think I’ll start with this is amazing thing you said that  90% of Alzheimer's cases you believe could potentially be prevented with the right change in lifestyle. So it just transforms this from being this death sentence in front of you, which is, as I said, very much how I was brought up, to this idea that actually, for the vast majority of people, you could change your behavior and mean this didn't happen.

You also explained that today, once you have Alzheimer's, it can't be reversed. That's not currently possible with the medicine we have. But it takes decades and decades. So actually, although we think about this as being an old person's disease, actually, you're saying it's really in middle age it's all already starting to happen.

Because your brain is struggling to clear these deposits. But therefore, if you make the changes now, little by little, you can push this off. 

I'm thinking about this idea that you build up this capability. Therefore, whatever age our listener is right now, they can be doing things right now that are building up their capabilities.

And you talked about this reserve of potential with this brilliant acronym NEURO. So I'm going to try and see if I can remember what was in there. 

So N was about nutrition. So we're very pleased to hear that you started with nutrition. That makes you a great guest on this show. And interestingly, you talked about this MIND study, that I think you said a 53% reduction of Alzheimer's with a diet that looked very similar to the Mediterranean diet, a gut health-friendly diet that we tend to talk about a lot on this show.

You know, if you're going to pick out one specific area of food that you really, really focus on maybe about the brain. I took away Omega-3 as this thing you were saying in particular, and we've talked about it on the show a number of times. My colleague, Dr. Sarah Berry is focused on fats and you can get that from fatty fish, which is often called oily fish in the U.K. So that's a good one to learn. 

Supplement if necessary, but actually, you're saying even just with a really healthy diet, you should probably be getting this.

Then talked about exercise and amazingly exercise is really important for your brain, even though it's not a muscle and you said that basically, these hormones that are created by the exercise you're doing is actually having this amazing impact on your growth. 

Not all exercises are equal. So if you focus on your legs, because that's your biggest muscles and you're doing squats or lunges, that's where you'd really particularly suggest to somebody focus on that. And amazingly, you're not just going to be making yourself healthier because of exercise, you're directly going to be supporting your brain.

We talked about stress. There is such a thing as good stress, but there's also definitely bad stress sort of chronic stress This is real, I wish I could tell my grandparents this it's too late, but it is real; it actually shrinks your brain. So you can actually measure that. But there are things you can do about that and we didn't have a chance to get into that on this podcast.

Then you talked about restorative sleep. Amazingly, if you can get into this deep sleep, basically, all the cleaners come out and they clear away everything. So it's really important to be having that deep sleep and enough sleep. So my flying backwards and forwards to the States is probably not ideal for that reason, on top of everything else. 

And then finally talked about optimize. And this was, I guess the challenge in your brain that if you are doing hard things. You talked about this amazing London taxi driver study that they learn all the roads in London in their fifties and their brain actually gets bigger. 

It's not just whether or not you studied when you were a kid. You're saying there are behaviors now that can really make a difference. And you want to be doing things that are complex. You're saying Sudoku or crossword is okay, but actually, the more that it's challenging you and different, the more that you're going to learn.

And if you do all of these things together, does that get me to the 90%? 

Dr Dean Sherzai: Presumably it does, yes. We can't say individually, at the individual level. At the population level, absolutely. 

I think that the cumulative effect of this is so powerful for the brain that it will definitely avoid dementia, but more importantly, you'll be able to live resilient, powerful, empowered mentally, cognitively empowered lives.

Jonathan Wolf: Wonderful. Thank you so much. I enjoyed it very much. I can see that we didn't manage to pick up on some of these areas, so I hope we can get you back in the future. 

Dr Ayesha Sherzai: Oh, we would love to. Thank you so much for having us. It was fun. 

Jonathan Wolf: Thank you.