Welcome to Zoe, Science and Nutrition, where world-leading scientists explain how their research can improve your health. Today, we're discussing a topic that's close to my own heart, and as many of us know, all too well, impacts millions of families around the world. And that topic is dementia. Nearly seven million people in the US and almost one million in the UK live with a form of dementia, like Alzheimer's disease. And these numbers are a concern for many of us. But today, we're not just discussing challenges. We'll learn what steps to take to help prevent dementia. We'll also hear how to recognize the early science, and we'll find out if promising new Alzheimer's drugs are worth the hype. I'm delighted to have dementia expert Professor Claire Steves back on the podcast. Claire is a medical doctor, a professor of aging and health, and head of the Department of Twin Research and Genetic Epidemiology at King's College London. She's also been a frequent advisor to Zoe for many years now. Claire, thank you for joining me again today.

Thank you very much for having me.

Now, you may remember that we always like to start with a quick fire round of questions, and Claire looked suddenly shocked because she's clearly forgotten about this, which we carefully designed to make professors deeply uncomfortable. Just to remind you, the rules are you can say yes or or if you absolutely have to, you can have a sentence to answer. Are you willing to give it a go?

Yeah, I'll give it a go.

All right. Is the brain the most complex structure in the known universe?

Yes, it is.

That's pretty cool. Is dementia inevitable as part of the aging process?

No.

Are women more likely to get dementia than men?

Yes.

If my parents have dementia, am I certain to get it as well? No. There are a bunch of new Alzheimer's drugs. Are Are they going to stop the disease for most people?

No.

If I change what I eat, can I lower my risk of dementia? Yes. Finally, what's the most common misconception you often hear about dementia?

That there's nothing you can do about it.

That isn't true?

That isn't true, no. That isn't true if you have it, and that isn't true about preventing it to happen.

Well, that's a wonderfully positive place, actually, I think, to start this conversation. This is a topic that's very close to my own heart. I think a lot of our listeners who've listened to the podcast very regularly will know that my grandmother got Alzheimer's. It's an awful experience for the whole family. It was awful for me, but particularly awful for my father. And not just during the period when my grandmother got this and got very sick and actually died quite fast. Basically, ever since that, my father has lived under this shadow, this fear that he was going to get Alzheimer's. And he's actually a lot older now than my grandmother was when she got this. But I think even now, he feels like he doesn't ever know. Is he just going to have another six months or twelve months of his brain working? And I think it's had this profound impact on him. So I think I've definitely seen this firsthand, and it's always struck me as one of the diseases that I'm most scared of having, partly for the effect on myself and partly for the way that it would affect my family and the way that my family ends up thinking about.

It's a topic that's close to my heart as a way of saying this. I'm really excited to talk about it, but also very excited that you started there by saying there's some things you can do, because I think I always assumed there was nothing you could do about this. This was something that just came externally somehow as a roll of the dice, a stroke of fate. I'd love to make sure we really get into today about how we can lower our risk. But I'd love to start right at the beginning, Claire. Could you just explain what exactly is dementia?

Dementia is actually an umbrella term. So lots of different things actually fit into that term of dementia. But if we want to classify it, it's a condition that involves cognitive function, so thinking and learning and memory, more than one domain of it, which is altered in somebody. That that's altered to such a degree that it then causes a problem in day to day living and that it's gradually progressive over time and needs to have been around for longer than a six months period at the very least. Actually, most people who get diagnosed with dementia have probably had some symptoms going back for maybe years, unlike your grandmother, maybe, who sounds like it was more rapid progression.

And how is that what you're describing different from normal aging? Because I think many people listen to this will say, I think, again, this is how I was brought up, and I know this is now more contentious. I was brought up with this idea that, well, when you just start to get old, then you fall apart, your body falls apart, your brain falls apart. So this is just literally the normal process of aging.

So there are changes that happen with age in most people, which we might call normal aging. And the typical things are, for example, the brain looks different when you look at it. There's some atrophy in older people.

Which doesn't sound good. Nobody likes the word atrophy. The older I get, the less excited I get about this idea of my body or my brain atrophy.

Yeah, so there is that. But of course, some of that might not be so detrimental. Then also there's some changes in processing speed in older adults, generally. The speed at which things happen.

When you say processing speed?

Yeah, so the ability for the brain to get through a problem or execute an action.

This is like do the crossword or what do you mean?

More simple than that, really. But basically any task, you're looking at the time it takes to do that task. One of the simplest is a reaction time task. Say, for example, you're given a stimulus and you have to say when you see it, or a choice reaction time when you have to press one button when one stimulus comes and another button when When the stimulus comes. Those are relatively simple tasks which measure the speed of processing.

I'm thinking a bit like whack-amal. Is this what you're saying? Something comes up and you're hitting it on the head. Is that what you're saying? Yeah. As we get older, we get worse at this. My son already feels that I've got slow reaction speeds, so I don't want to know what I'll be like when I'm 80.

Yeah. This is really important, and it's really important, that aging, because that's why some older people, when they fall or younger older people, they would fracture their wrist, whereas older, older people might fracture their hip because They've got time to put out their hand.

What you're saying is as you get older, things like just being able to protect yourself when you fall over by responding is slowing down, and that's your brain which is slowing down.

Your brain is slowing down in normal aging. I think that's something that we definitely see. Then there are dementias which are really quite different from that, where there's progressive decline in other functions. Different dementias have different constellations of symptoms, but we don't always get it completely right. Sometimes, actually, what's going on in the brain is not not necessarily fully reflected in how people present.

And just before we get into that, I just want to make sure this difference between being health, like a normal age, if you like, or not. I think you're saying it is normal to slow down a bit in terms of the speed with which you respond. You can see changes. It sounds like you're saying, almost like if you're imaging the brain or something, you see this, but it's not normal for you to not be able to think and interact and all the rest. Where I'm getting this is, I think everyone listening to this can think of people that they know, relatives or friends who are very old who are incredibly sharp, exactly the same as they were many decades before. Is that what you would think of as typically normal or is the reverse, which is that they are the exception and your normal expectation should be that you lose your core personality and capability as you reach old age?

Really interesting questions. If somebody is changing in their function, and in particular, losing the ability to keep in mode of, for example, short term memory issues, then that's a warning sign. The other thing that's a warning sign is if they're not able to function in normal activities of daily life. So one of the first things that might be affected might be, say, ability to manage finances or medications. If someone else has to come in and take over because things are going a bit wrong. Those are the early warning signs for most types of dementia.

And that's because you wouldn't consider that just the inevitable normal part of age. Exactly. You're saying that actually... And the reason I'm asking this, again, is because I feel I feel that that's a bit of a shift from how I was brought up because you're saying, I guess, quite a positive thing, I think, Claire, right? That actually the normal expectation of aging is you can still manage your medication and your finances and your short term memory should still exist.

Exactly.

Tell us a bit about what happens with dementia. Why is it that this isn't the case for some people? Why is it that this is this thing that so many people are worried may happen to them?

The most common presentation and the most common cause of dementia is Alzheimer's Alzheimer's disease. Alzheimer's disease, characteristically, presents with a very gradual progression. And generally, the person is physically relatively well. And their gait, for example, their ability to... Their walking is not too slow, and it's not too altered. And yet they ask maybe repeated questions. They maybe don't catch hold of a full conversation. So they might ask the same question again. Or you might realize that actually you said something five minutes ago and they don't recall it. So that early laying down of that episode in a sense of tape recorder for short term items just isn't functioning very well.

So this is when you were mentioning short term memory of taking over. This is like remembering things just in the last few minutes, rather than something that maybe happened to you 50 years ago.

Of course, be careful because not everybody with short-term memory loss has dementia. Sometimes when the brain is really working on lots of other tasks, maybe in the subconscious, whatever, maybe there's a stressor or there's something else happened, then obviously short-term memory can be affected. It doesn't necessarily hold that short term memory loss is early Alzheimer's disease. But certainly, if it's there and consistently there, definitely that's the signal to say, We ought to get this checked out, see what's happening here.

What's going on? Why is this happening?

Most of the common dementias that are really brain-focused, as it were, are because of neurons dying, basically, in certain areas of the brain, in particular.

What are neurons?

Neurons are the nerve cells. They're dying probably from a combination of of factors in our genes and factors in our environment that contribute to that.

What we see- So they're dying a lot more in these people than they would be doing in an equivalent person the same age who is not having these dementia issues.

Exactly. And one of the things we see when we look at those cells under the microscope is we see inclusions of certain proteins. So certain proteins have aggregated together and either inside the cell or outside the cell. So there's something going wrong.

And that's not normal.

And that's not normal. This is one the big conundrums of dementia is why that happens, why some people are more resilient to those protein depositions in the brain and have relatively high degree of changes in the brain, but that's not necessarily translating into how they present.

Hi. I have a small favor to ask. We want this podcast to reach as many people as possible as we continue our mission to improve the health of millions. And watching this show grow is what motivates the whole team at Zoe to to keep up the really hard work of creating new episodes each week. So right now, if you could share a link to the show with one friend who would benefit from today's information, it would mean a great deal to me. Thank you. Just to make sure I've got this, you're saying that there are these proteins forming these clumps in these nerve cells in the brain, that that seems to be very related to whether or not you get Alzheimer's, dementia in general, or Alzheimer's specifically?

So Alzheimer's, specifically, has certain types of protein inclusions, and other more rare forms of dementia, rarer forms of dementia, have different sorts of protein inclusions. But ultimately, a lot of these neurodegenerative diseases that we call neurodegenerative types of dementia, they have protein depositions within the brain, in different parts of the brain, different patterns, different exact proteins as well.

But basically, there's a lot of stuff that isn't in your brain when you're 21 years old that is later, and there's a real link.

There's a relationship, but it's It's not a completely 100% link.

Complicated. I think one of the things I've learned on this podcast that most things are. It's interesting. When I hear that, I naturally think about these analogies that a lot of guests have talked about with cardiovascular disease and things being laid down in your arteries, mainly based on poor diet over decades, building up and eventually that leading to these pipes being blocked or something breaking free into the heart. Is that a terrible analogy or is Is there some similarity with what you're describing with things ending up being laid down in our brain that are not being cleared away?

Well, so yes, I think that's really interesting. Yes, the clearing away bit is absolutely the case. But the difference in a way between the cardiovascular disease, as you mentioned, is that the focus is really on the arteries and the blood vessel lining. Whereas in dementias, the focus is on the actual neuron cells and the cells beside the neurons that help keep them healthy. So the microglia or the other cells that are around supporting those neurons to function.

Is everyone having these proteins laid down in their brain, but normally we're unable to clear them away? Do we understand, I guess, what's going on here? And therefore, does that help us to understand? We're just going to start to talk more about what we might do, why the things that help, in fact, do help.

Our cells, very complex organisms, complex structures that are constantly rebuilding the structures within the cells, but also things, the ways in which they communicate outside that cell. What's happening when you get these proteins deposited is that there's a problem with the clearance, either the manufacture or the clearance of those proteins.

We had a really interesting podcast with a This is called Matt Walker talking about sleep quite a long time ago. I remember one of the things that he talked about was decided that when you sleep... Again, I was brought up to think that nothing happened when you slept. You just had to sleep for some reason. He was saying, No, actually, we now know your brain's very active and that one of the things that's going on is somehow or a clear up of your brain. Is that in any way related to this?

Or have I just put one and one together and made seven? No, there is evidence that the clearance of protein also, just simply the way that the fluid system around the brain, the CSF, the cerebral spinal fluid, the way that flows around the brain is affected by sleep. Then probably there's something that's happening much more deep within the brain tissue, which affects the clearance of these proteins. I think there is a relationship between sleep.

I I would love to shift maybe to one step away from the detail of what's going into the brain and more about people listening this, trying to understand, Okay, what are my risks? Are some people more at risk of dementia than others?

That's true. We know that genetic factors are important in the development of dementia, and they're most important in the early onset dementias. People who have developed dementia in their 50s or 60s, there's some stronger genetic influences on those. It doesn't mean that they're definitely going to be-I was going to say, does that mean that if I have bad genes, I'm doomed to get dementia? No, it doesn't. And of course, there's an interaction between those genes and the environment, which might be very important. So one of the most talked about, because it's actually really important gene, is APOE, of which all of us have two. There's an APOE4 is associated with increased risk of dementia. And so if you have two of those, you're actually much greater risk of having dementia. It doesn't mean it's definite.

And how bad, just to help us understand, if you have these two, what do you call them, E4 genes?

It's about eight times greater risk.

Okay, so that sounds pretty bad. How many people will have two of these E4?

Not very many. I think it's about 25% of the population have one There'll be a couple of % of people, like 2 or 3 % people listening to this who could have both, and their risk really would be much more, because eight times higher on something that's relatively common sounds like that's a very high risk. Yeah, and that's one of the reasons.

But you're saying they're not doomed to get this if they have these two genes?

No, no, actually not. Well, we don't actually know completely why APOE4 confers the risk, but it's something to do with the way that our brain cells use fats in the body. It's Probably influenced by things in our diet and maybe medications that we take. So that's why you can still increase your resilience, even if you have two of those APOE4, Alex.

So could you talk a bit more maybe about the thing? Because I think The thing about jeans is always it's so depressing, right? You have your jeans and you're stuck with them. I think one of the joys for me about this journey with Zoe is realizing that almost everything that I've been taught, that basically we were just this victim of our jeans that was going to define our health. It turns out not to be very true, and that actually the way that we live our life is much more important in terms of certainly most aspects of our health. Though, as I keep telling my son, it seems like our jeans are still quite important for your height. And since I'm rather short, he's rather disappointed that he's not going to be 6'5. But it seems that in general, actually, the height is a bit of the exception. In generally, our health, we have much more control. What are the other things that mean that people are at high risk of dementia?

Well, if we start early on in life, really important, because ultimately, all of our cells in our body are aging right from the beginning after we've conceived. Even things in utero can be really important for later life development.

This is while I'm a fetus.

If any pregnant mums out there, actually, what you're doing is preparing child for the whole of their life. It's really important to be thinking about that and making sure that you're giving them the optimum amount.

I always think it's also terrible as we both have children. There's enough pressure, I always feel, on pregnant mothers. It's pretty tough, I think. Then now you're just about to layer on some more. But go on. I know this is a science. Tell us the science.

But also society needs to do that as well. That's really a key message for society. We need to really look after pregnant mums.

That seems unobvious. What happens to me is a fetus effect. What are the things that will change my risk of dementia?

It's about cognitive reserve. That's the maximum cognitive ability that we might have, not just in terms of intellectual ability, but also psychological state as well. The reason why that's really important for dementia is that dementia is something whereby our functions are interfering with daily life. Obviously, if we start off with really high functioning, then we get to that point much later in any disease process. You can put off significantly the time at which you fall below that threshold of being able to function in daily life much, much later.

Could you explain a bit more what you're describing? What is it that some people are getting and other people are not?

We can think about it from multiple different ways. We can think about it in terms of the stimulation that a child is being given through education, through parental influence. We can think about it psychologically around that development that's happening in early childhood. But we can also think about it about nutrition, as we talked about before. I'm sure we'll talk about again, nutrition starts in utero. There are factors which affect how the brain actually develops right from the beginning. Then we can then go even further than that and talk about things like smoking and alcohol, which have significant effects on the brain development of children.

I think I'm understanding better now. I think you're saying right back, even when you're as a fetus, depending upon the nutrition that your mother is having, that's going to affect the way your brain is developed then after you're born, continuing the food that you eat as a child, but also you're saying the stimulation you get, I'd love for you to talk a little bit more about that. You're saying that somehow the way that the world is interacting with you is going to give me, I guess, a healthier or more robust brain that is actually going to have an effect on whether I get dementia 70 or 80 years later. Is that?

You might still get dementia, but the chances are that the more that we can do to increase brain reserve, the later-Brain reserve is the capacity of your brain to do that? Yes, exactly. Humans are incredibly varied in terms of their cognitive functioning. If you have a high cognitive functioning, obviously, you've got further to fall.

It's a bit like saying my tank is... I'm thinking about now a bit like a car. The fuel in the car is your reserve, When it goes below a certain point, the car stops working. Is that your analogy a bit here with the brain? You're saying you might have dementia, so your reserve is being reduced. But because it's very capable, you can go a lot longer before it stops working.

Is that... Actually, the processes might still be happening within that brain, but actually, then it doesn't play out in life. This is really important because obviously, that investment that we give or we can give, if we have the capability to give it, that investment will last out and make a difference later on.

Got it. Because it might be that, okay, yes, you are starting to have dementia, and if you became 100, it would be really affecting you. But actually, if you die at 85 of a heart attack or something, then actually your brain was fine. Is that what you're describing? Could you talk a little bit more, therefore, about this? I think everyone listening to this is probably thinking, Okay, how do I make sure that maybe starting with perhaps thinking about their children or their grandchildren, how do they make sure their reserves are good? And then also perhaps what's happening later. But right now, I think you're talking about earlier life. What is it that gives you these higher reserves before you're 18, I guess. Yeah.

I think we've already talked about diet, we've talked about intellectual stimulation, also that stability, psychological balance, which is really important, mental health.

That's So mental health is linked to- Mental health is really interesting because good mental health sets you up for a cascade of good things then happening to you late in life, which then give you more opportunity, more capability to take on these opportunities to then improve your brain reserve and stimulate your brain.

Whereas problematic mental health then can lead to difficulties in the capability or the opportunities and motivations to take on these things that are going to then help your future brain reserve. So talking about some of those, the key things are around social stimulation, things like physical fitness. I think I talked about that a lot in the last podcast, that we know that physical fitness is really beneficial for brain health. And of course, we can then put in some physical reserve as well and habits of daily life that then increase our physical activity and continue it going through midlife, which is going to be good for vascular health, but it's also really good for brain health.

So if I am doing more physical activity, what does that mean for my brain?

The habit is good. It's the daily regular physical activity, which doesn't need to entail exercise. It's the reduction, even in sedentary time, that we see has an effect not just on dementias, but actually on brain aging as well.

That just means my brain is effectively younger. It increases that reserve. That description you gave at the beginning, which is a bit depressing about not being able to respond to anything or really know what's going on. If I'm regularly active when I'm 70 or 80 or 90 or 100, my mental clarity is just going to be a lot better, is that what you're saying? Because I've been consistently active.

Active, yeah, that's right. So active, but not just in terms of physical activity, active in terms of social activity, and all those things, those all contribute to brain reserve. But then there's also things that alter brain reserve and make it more tricky for us to maintain those cognitive functions. I'm not talking about the proteinopathies now. I'm talking about the reserve capacity. Of course, that's where interaction with other body systems is really important. We know that there's a real strong interaction between cardiobitabolic health and brain health. We know that there's a really strong interaction between, say, for example, our hearing ability, our sensory ability, and brain health. Then likewise, infections can tip the balance of brain health, but chronic inflammation can also affect how our brain is resilient to those changes which might happen in that balance between proteins being set down or not.

Before we start to talk about prevention, which I know everyone listening is like, That's really interesting. It all sounds quite scary. Let's talk about everything we can do. I'd love to talk a little bit about symptoms and what the status of treatment is at the moment first. Could you tell me if someone's thinking about the symptoms that they might notice in themselves or a loved one that would probably trigger this thing that I think We should maybe go and talk to a doctor. What should they be looking for?

Really, it's about a change in cognitive function. Different dementias have different patterns. But as I've talked about, we've got things like Alzheimer's dementia, which starts with short-term memory loss. There's other forms of dementia that can start with personality change. Again, further forms of dementia, actually, the first presentation is around falling over and maybe difficulty with the blood pressure regulation, sleep even. Sometimes can be the very earliest presentations of some forms of dementia.

When those start to become common enough that you might be on the alert for it, because again, I think many people are listening to feeling like, Oh, as people get old, I'm expecting this to happen, and I'm on become very vigilant about it?

Good question. Most people that are referred to my memory clinic are probably in their 70s. It's quite rare to see people in their 40s being referred to me. If people do have these problems happening in their 40s, then they're more likely to go and see a neurologist for an examination. But yes, so those are the more common ages.

The 70s is when you're tending, in fact, to see them in your clinic. What are the treatment options? I think I've definitely seen there's been a lot of press about new drugs starting to come on board. What's the situation today as a doctor thinking about a treat for somebody who comes in and who you do diagnose?

Yeah. It's really exciting that we now have some new drugs because we've been waiting actually about 20 years for some new changes in drugs. What these drugs are doing, actually, it's a really amazing proof of concept that these medications, they're basically antibody-based medications that are sticking to the proteins and getting rid of them, clearing those proteins that we talked about at the beginning. We've known for some time, actually, that we can do this and take them out, for example, from animal studies. It's only really been in the last year that we've had evidence that taking out those proteins in the case of Alzheimer's disease actually has an effect on human progression of the disease. But the issue is that actually when we do that, the level of gain is actually quite modest.

It doesn't- You mean when someone takes these drugs?

Yeah, so we can take the proteins out of the brain. But it doesn't necessarily mean that we've significantly affected their cognition and their function.

We hear about all sorts of wonder drugs, right? That suddenly solve everything. Then you hear about other drugs where people say, Oh, well, it ultimately didn't really make much of a difference.

How excited are you about these drugs? Well, I'm excited in principle. I'm excited in principle because we've shown a proof of principle that this works in humans, and therefore it could be developed on. But the issues are this, that first of all, the gain over a year is only a few points on a cognitive measure. It doesn't mean that the person then doesn't have dementia. It's just that their dementia is- They're not cured. They're not cured. The process is slowed, though. That's the game changer. The process is slowed. Whereas before, we've been able to give drugs that manage symptoms, but ultimately the process isn't slowed. So that's the really exciting game change.

How much slowing down are they delivering?

So at the moment, not very much slowing down. But we haven't talked about the main problem with it. The main problem is that actually there's increased risks. So as you're taking away the proteins from the brain, you're also increasing the risk of edema happening in the brain. So that's swelling in the brain, which can It's really quite catastrophic. If the brain swells a little bit inside a fixed space, there's an increased risk of hemorrhage, little microhemorrhages within the brain. People that are having these drugs-That's bleeding, isn't it? That's bleeding, yeah. The people that are having these medications have to have a scan Every month.

What does that mean in reality there? Because those sound like quite scary side effects.

Are they very rare or are they quite common? It means that actually the balance of risks and benefits is not totally clear, ultimately.

As a doctor, does that mean you're not necessarily just saying to everybody who comes in, you should take this?

Well, they're not approved in the UK for that reason.

And they have been approved in the States?

They've been approved in the States, yeah.

But the number of people that will- But the number of people that will- That tells you it's a bit on the edge. Is that what you're saying about the balance of benefits?

I think the benefit and risk is definitely on the edge If you had all the resources available. And then you've got to think, well, actually, how are we logistically going to get everybody to be able to have scans every month? And what knock-on effect is that going to be on being able to get scans for cancer or scans for other things? So there's a resource issue as well. So if the gain was massive, then you might say, well, that was worth that risk personally and also as a health care system.

And how many extra years of well-functioning brain am I going to get?

We don't really know yet as well, because we've only had A couple of years of lead time.

Got it. But if you're going to guess, are you talking about a year or are you talking about an extra decade?

Yeah, it's not an extra decade.

This is not the transformational drug that means we feel like we've conquered dementia.

No, but it is It's a transformational drug because it's showing us the proof of the idea that it is possible to take away the proteins from the brain. So all we need to do is do that more safely. Got it. And we need to try doing it in different proteins because it may not be the proteins that we've gone after.

That's the key. You're saying it's like, proves that this approach can work. Exactly. Then maybe this generation of drugs are not ideal, but you're sounding quite optimistic that maybe this means there's a path to a next generation.

There's a path to a next generation. Within the next five years, we need to really get our services in order so that we can be thinking about delivering these things because it's coming.

That's very exciting. If you're living with maybe a family member who's having this today, then it may not be as positive as you'd like. But if you're thinking about what might be happening in a decade to a family member or yourself, then actually it sounds like this is quite positive, which is exciting. The science is really moving forward. I know you're quite careful, Claire. The fact you're quite positive here makes me feel that you're feeling actually really quite enthusiastic about the potential in the longer term.

Yes, that's right.

Well, look, I think I would love to switch to the stuff that doesn't involve taking a drug that might make your brain explode because I can understand why that might not be ideal. Let's start with me. I'm someone in my late 40s. I really want to make sure that I don't have dementia. Give me the advice. If I was walking into your clinic, tell me what you would be saying that I should be doing in order to try and make sure I never had to come back to your clinic in 20 years.

Actually, what I realistically say to patients is it's about getting as many different colors of fruit and vegetables into your diet as possible and making sure that you're getting good plant-based fats into the diet. Because the brain is hugely metabolically active. It needs a lot of nutrients. We know that a wide variety of plant-based nutrients is really important for brain health. I talk about colors because actually there's evidence that flavonoids are really key phytonutrients for brain development. It may be because you're changing the microbiome, because there's such a thing as a gut-brain axis. We think that there's a very strong relationship between what's going on in our gut.

Lots of plants with lots of fiber, lots of different colors. Then you said lots of healthy fats, which means a lot of plant-based fats. I think you were mentioning nuts. We often talk about things like avocados, right? At Zoe, these are the things that you're talking about.

Yeah, and I think- Olive oil, I guess. That's right. There's quite a number of studies now showing Mediterranean diet. It helps to improve cognitive health.

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Yeah. So you just You just mentioned the other thing, which is meats and white bread. We know that there's a relationship between vascular health and brain health.

Vascular health means?

The blood vessels within your body and your heart. That's because one of the other types of dementia we haven't really talked about is a vascular dementia. Often, there's a combination, actually, of vascular factors that then bring on those other processes like Alzheimer's.

If you're eating a diet that's good for your heart, basically, then that's also going to be good for your brain.

Yeah, it's going to be good for your brain, and it's going to put backwards the balance of things that are going on in your brain that might relate to Alzheimer's.

There is real scientific evidence that this shift in diet really can reduce your risk of dementia?

For example, in the Mediterranean diet, there have been really large randomized control trials that conducted over a year period in five different countries in Europe. When they compared the group that were randomized to the Mediterranean diet against the control group, they didn't find very significant differences.

If you manage to change your diet in a sustainable way, it really can reduce your risk of dementia, but you have to stick at it. You have to stick at it. You can't just do it for a few months.

And the trouble All is, that's difficult.

What else would you tell?

So the second thing is about physical activity. I do tell all my patients to make sure they're physically active at least three times a week, and they're going out every day. These are really important things to do. And That can help preserve your physical function as well and your cardiovascular function. It's probably the biggest thing that you can do to help your overall fitness.

When you say physical activity, when you think about dementia, what's really required? Because we talk to a very wide range of people who vary between if you even get up from your chair for two minutes, you've done everything amazing, to if you're not doing a massive workout four times a week, then you're dooming yourself. But What should people be thinking like, This is what I really need to make sure that I'm building in my life.

To improve your cognitive health, you need to do more exercise than you're doing now. Okay. Up to a point, unless you're an Olympic athlete. I'm not an Olympic athlete. That's the This is, again, about the difference between scientific proof and practical advice. The reason why there's this debate between scientists about what is the dose required of exercise is because to show a change over a short period, you have to have a big enough dose to be able to detect that effect. Whereas if we look at really big population studies, we can see effects even with minimal levels of exercise, and it's fairly linear. So even Even being more up and about, less sedentary time makes a difference. But then you can still make more difference by putting every egg on. So whatever you're doing, if you go up by a third, you'll be improving yourself.

And is there any particular sorts of exercises you're thinking about this Probably the most evidence is around resistance training exercise for overall frailty and so on.

Then for cardiovascular fitness, there's aerobic exercise.

I'm one of your patients. I'm not very physically active. What would you be telling me that I should do that can really make a difference?

Walking.

Walking.

I think you need to get out and do walking 45 minutes, at least three times a week.

That would really make a difference. If I'm not doing that, that will really make a difference from everything. So that, I think, again, it's amazing. There I think you were like, Well, it seems obvious. But again, I think many people listening to this grew up with the assumption there is nothing you can do about it. It's just literally a consequence of getting older. And you're saying, actually, if you went for a walk three times a week, compared just not doing that, you're going to make a really significant reduction of risk. It's rather extraordinary and does suggest that our current way we live our life is not very well optimized for avoiding this. If that is almost like your starting advice to people, One thing I haven't really talked about ever before with you is teeth, the importance of teeth.

In the UK population, about 35% of older adults have periodontal disease, inflammation of their gums. We know there's quite a strong tight relationship between periodontal disease and cognitive- You believe this is true?

Because we had somebody on, just if anyone's interested, a few weeks ago, we'll put a link who was a dental researcher saying this. But I was curious because obviously, if you're a dentist, you're going to be convinced that the teeth are important.

Oh, no, I really think it's really true.

You're not a dentist, so therefore you're unbiased on this. This is really true, isn't it?

It's really true. There is a vicious cycle, though, obviously, because as you start to get dementia, it's more difficult to look after your teeth. Also, we know that looking after teeth, actually, diet is really important in looking after teeth. So teeth are much more healthy if you have a good, varied diet that we've been describing and less sugar and so on, so forth. But actually, this is a very common inflammatory load, which is tickling the systemic Which is amazing.

I just heard this literally a few weeks ago. I was shocked to hear this.

Yeah. Actually, when I see my patients in clinic, the thing that... Just eyeballing. The thing that's related to that cognitive reserve we were talking about, i. E, the difference between what's in their brain and how they're actually living, how they actually present, the people that have the bad teeth will be doing badly. The people that have the good teeth will be doing well.

You would be saying if someone is having problems with their teeth, absolutely go and get it fixed right away because that really could be a big risk factor. What else could people do? I feel like you mentioned a little bit about intellectual stimulation and social stimulation. Is there anything you can do with your... Is this all fake? Or that Doing things with your brain can help prevent dementia, or is there something real about this?

Well, no. I think the thing is it's about that cognitive reserve as well, again. We mustn't be getting the idea that if you have got a managerial high paid job, whatever, you're doing lots of intellectual activity that you're immune to dementia. Everybody can get dementia. It's just that you will present later.

I'm in my late 40s. I'm thinking about this right now. Is there anything that I could be doing with my brain over the next 20 years that will change my risk factor? Is there anything I can do there that is actually going to shift it?

Probably one of the most complicated things that we do in our brain is to really interact socially. And so that's a brain workout.

So that is better than a crossword puzzle.

It's better than a crossword puzzle.

I think much more fun as well. So it's good news. I know not everybody feels that way. Some people who are more introverted feel this is hard work, but that is really good for your brain.

But it doesn't necessarily mean that some of these brain games aren't helpful. I think the thing is what brain gains tend to do is they tend to make you better at that brain game. They don't necessarily- You need to have lots of different brain gains. You'd have to have lots of different brain gains.

Okay, so it's not that bad, but actually, you're saying social interaction is so complicated for our brain. That's really exciting, which also, I guess, ties into why another reason why loneliness is not good for us. Yeah.

Then certain physical activities are really taxing for the brain, aren't they, in terms of activity? If you're cycling in London, that's for sure quite taxing.

Yes. I always think that it might be lowering your life expectancy for other reasons.

Yes. But there are other forms of that physical activity, like dancing, whatever, which is quite a good cognitive task.

It's interesting because your brain is having to think quite a lot as well. So basically what you're saying is using your brain, making it have to do something that is actually going to build what you're calling this reserve, which is basically meaning you're less likely to-Your tank.

What's in your tank?

We had a lot of questions from our listeners about the link between blood sugar levels and the risk of dementia. And in fact, some of them said that they've been hearing people refer to Alzheimer's disease as type 3 diabetes. In other words, that because we've seen this huge rise in number of people with type 2 diabetes because of our diets and all of this high blood sugar, that actually this was potentially a risk that was increasing the risk of Alzheimer's. Is this true or another one of these pseudoscience?

No, we know that having diabetes increases the risk of dementia. Is that right? Probably of all types, actually. Significantly? Significantly, yeah, significantly. Then you do have to be a bit careful if you have dementia and you have diabetes because it's not quite as simple as having really tight control of your diabetes in that case, because we know the brain in the context of dementia does need blood sugar, and actually low blood sugar is really dangerous.

This is once you have the dementia, but if this is what you're saying, or once you have the diabetes.

If you're early in life, and we're talking about the preventative stage, everything you can do to help your blood sugars be normal is better. So over control probably isn't very good for the brain, but ultimately the bigger thing is around.

For eating too little is not a good thing. Is this what you're saying?

Well, no, it's not about eating too little because, of course, the liver produces the glucose and so on. So having a really low blood sugar is not good for the brain, for sure. But the main problem is around prediabetes or diabetes.

This is real. This rise in prediabetes and diabetes is a real contributory factor to dementia. It's a real contributory factor. Then, presumably, that means if you can reverse the prediabetes or suddenly control the type 2, so it doesn't continue to get worse, that would lower your risk of getting dementia?

That would lower your risk of getting dementia.

Brilliant. We had one other question from the community that I definitely want to ask because it came up quite a bit. Should women be taking HRT in order to reduce their risk of dementia as they go through menopause?

That's a very interesting and controversial question. There's quite a few studies that you may be aware of that have happened in the last year which have produced conflicting evidence on this.

I'm not aware of them, but I can tell that some of our listeners are, and they, of course, therefore, probably sitting here trying to decode that. What do those things say? What's your reading of what that means as best we can understand with the latest science as it is today?

Hrt is not going to be a cure all. That it probably will contribute to reserves, but also It really helps in active day to day cognitive function of people going through the menopause. That's probably where it's really important to use it, because people who are going through the menopause often have problems with brain function, which can be really debilitating.

I've heard some extraordinary and awful stories. I've talked about this before that I've been shocked because it's not something when I was growing up that my mother never talked about, nobody I knew talked about. As I started to hear some of these stories more recently, it's really extraordinary to me how some people have such a tough time for years.

The reason to take HRT is to help that, which is really important.

It can really help brain function through this.

Yeah, that's right. Then dementia But later on, I don't think that's a reason to take HRT.

Got it. You're saying at this point, there isn't data that says this has this profound impact later on that makes you shift?

No. In fact, there's studies that go both ways on this. Okay. So I don't think we should be taking HRT because of future risk of dementia at the moment, unless... Let's see what happens, because actually the longitudinal studies, bear in mind that people have only been using HRT for the last 30 years or so. Who took it and who didn't take it is confoundered by other things. It's a space that is uncertain. But what's not uncertain is that many women who have problems with cognition during the menopause benefit from HRT.

One of the things I've been really struck through this Zoe journey over the last seven years is how much in science we don't know the answer to and how much is this constantly ongoing investigation. I think one of the ways I always judge whether you're talking to a really good scientist is their caution in lots of areas where they say, I think as you just have done, Claire, the evidence isn't really there yet, and there's lots more studies. I think one of the joys of science is that, however, we are making progress. We definitely do know more than we did 10 years ago. I think this is a lovely example of that where I think you're saying it's not yet clear. It sounds like it could be. You might be sitting here in five years time saying, actually, I'm looking all the data, and I do believe that this can really be beneficial long term against dementia, but that actually at this point the data isn't clear. I feel that happens a lot in science to do with the human body because it's so complicated. I have so many more questions, but I think that we have run out of time.

I'm going to try and do a playback. This is a new topic for us and quite complicated one. So please correct me if I get any of this wrong. Is that all right? I think what you describe, to start with about What is dementia is really contrasting it with normal healthy brain behavior. And so, for example, you said the warning signs are things like starting to lose your short term memory, to not remember something maybe from five minutes before or not be able to function with something that seems like normal life, it maybe is a bit complicated, like managing your finances or making sure you're doing your medication properly. We have to bear in mind, however, that our brains do age as well, even though that's hidden to us. I think you're saying, if I looked inside my brain, you said this horrible word, the atrophies, which is a really depressing idea. But also, for example, you can see that your reaction speed just naturally gets slower. The point is, it's outside of that. But generally, this is a slow progression. So unlike A lot of diseases, it's like bit by bit rather than suddenly presenting with this very clear different function than you had last week.

But it's caused by nerve cells in our brain dying. This is what's causing the problem. But that we can see the cause over time with these proteins being stuck in these nerve cells. And that indeed you're quite excited because there are some new drugs coming that are clearing these proteins away. And although this current generation, you feel like the The balance between benefit and harm is not that great. You're quite excited about where it might go in the future. Then we talked a bit about why you might get dementia. You talked there are some specific genes. I think you said something like an E4 gene, is that right? If you had two If you have those, then you have not won the lottery. But even then, it's not guaranteed that you're going to get this. So that in all cases, actually, there's a lot through your lifestyle that you can do. I think the way that you helped me to understand it is to think about your brain has this The brain reserve. It's not a word I'd ever heard before, which is like this tank that you're filling up with all this capacity. That starts actually even when you're a fetus.

We can build the brain reserves of unborn children by the food that their mother is eating, but then as they're born, how much stimulation they have, their own food, all the rest of it. But you can keep building this reserve as we're older. Even if we might start to be getting this dementia, if your reserve is big, actually, you can live much longer in a healthy way. And then I think in terms of the things that we can do, I think the number one thing you talked about was diet. And I thought it was interesting. You were very strong about how switching diet to something that looks like a diet that is very plant-based with lots of different sorts of plants. You were describing eat the rainbow, things with a lot of fiber in them, lots of healthy plant fats. I think you mentioned nuts, for example, specifically. That's the number one thing. I think the number two thing you said is physical activity. I think you made this great quote, To improve your health, you need to do more than you are doing today. So almost whatever you're doing, if you want to reduce further your risk of dementia.

But interesting, you were saying that actually for most people, just like going out every day, going for a walk, if you're not already doing that, we'll have a profound reduction. And Claire is nodding her head hard at this point. If listening on audio. Profound reduction in your risk of dementia. Look after your teeth and then intellectual stimulation, particularly just meaning with other people. So social interaction actually being almost the best brain training you can do. And you said there are all these different brain training tools, and that's fine, but actually they need to be changed all the time. But actually just interacting with other people a lot probably is pushing your brain more than anywhere else. And then I think, finally, we said diabetes is a risk. So you want to avoid diabetes or you want to have it under control if you have type 2 diabetes. Hrt, the evidence isn't there as a cure for dementia in the long term, but there is great evidence about how it improves your cognitive function during perimenopause and menopause, and that's a big deal. So you should embracing it if you have those issues. How did I do?

Yeah, really good. Can I add a couple of little things? Of course. So one is around dementia. When we were talking about it, we were mainly talking about the biggest form of the most common cause of dementia, which is Alzheimer's But remember, it's an umbrella term. There are lots of, about 25 different other types of dementia, and they do present differently. Ultimately, that key is, is there something changing and changing consistently over time in the functioning of the mental capacity of that person? That's when to seek help. Don't not seek help just because short-term memory isn't the issue. Got it. Then the other thing that we didn't talk about today, but is really important is sensory inputs. Yeah. So ultimately, in the same way that social interaction is really important, our interaction with the rest of the world, sensorially. So we know now that actually hearing aids, if you've got hearing impairment, delay the presentation of dementia.

That's amazing. I think I remember you talking about this in our conversation a long time ago. You're saying if you get a hearing aid, that actually reduces the point at which you get dementia.

Exactly. So don't delay on doing those things. I think some people think, Oh, I don't really want to hear. Actually, it does make a difference. So do get those hearing aids, even if it's a pain to start wearing them at the beginning.

Because you're like, and that's as good as going for a walk. I'm not saying it's instead of, but we're talking about it has the same impact as you're describing with going for a walk.

Actually, I don't know whether I can quantify It's not going to identify the difference. Yeah, I think it's probably- But it's significant. Yeah, exactly.

This is like a big deal.

Yeah, it's a big deal.

Amazing. Well, I think the hearing aid providers around the world are going to have a busy week, I think, after that. Claire, thank you so much for unpacking that. I think it was really clear this is a complex topic I think having done that first overview, I am sure we'd love to come back and dive into some of that again in the future.

Thank you very much.

Brilliant. Thank you. Thank you for joining me on Zoe's Science and Nutrition Today. It was incredible to learn from Claire just how much we can reduce the risk of dementia, including the critical role of eating the right food for your body. Now, if you'd like more actionable tips from the podcast, you can download our free guide with 10 of the most impactful things you can do to improve your health. Simply go to zoe. Com/podcast. Podcast or click the link in the show notes. Now on the same link, you can also learn more about how becoming a Zoe member can give you specific advice about what to eat for your body that can help you feel better now and reduce the risk of dementia in the years to come. You can also get 10% off your membership. As always, I'm your host, Jonathan Wolf. Zoe Science and Nutrition is produced by Yellow humans Martin, Richard Willen, and Tilly Fulford. See you next time..