Can Diet Stop Alzheimer’s?

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So I'm going to read you a little story.

Your task will be to try to repeat back as much of the story as you can remember.

Word-to-word repetition is ideal, but if not, just try your best.

And if you feel like it's going to help you out, you can choose to close your eyes to help visualize the details.

Are you ready?

Yes.

Okay.

Listeners, pay attention.

You can close your eyes too, although not if you're driving.

We're going to quiz you on this later.

Martha Jackson was riding through the forest near Lake Superior in Canada, picking blueberries for her grandmother when her horse was stung on the nose by a bumblebee.

The horse jumped over the bushes and left the trail.

She hit a tree branch and fell to the ground, and her arm was broken.

When she stood up, her horse had disappeared.

She called out powder puff, but the animal never returned.

So, what does Martha Jackson and her horse Powderpuff have to do with food, you may be wondering?

I mean, other than the blueberries she was gathering for her grandmother.

We promised to tell you, but first, you're listening to Gastropod, the podcast that looks at food through the lens of science and history.

I'm Cynthia Graeber.

And I'm Nicola Twilley, and this episode, we're in New York City with the scoop on some cutting-edge research into whether Alzheimer's can be prevented using food.

Alzheimer's is one of the most devastating diseases in the developed world, and there is no cure for it.

There's been decades of research, of course, and huge sums of money spent to try to find a cure, but still, all we've got is just a few drugs to help manage the symptoms, and we don't know how to prevent it.

Which is why this new research is so exciting.

Could preventing Alzheimer's really come down to what you eat?

Thanks this episode to the Alfred P.

Sloan Foundation for the public understanding of science, technology, and economics, as well as the Boroughs Wellcome Fund for our coverage of biomedical research.

So, before we get to whether food can prevent it, what is Alzheimer's?

So, Alzheimer's is a progressive brain disease where, as the disease progresses, individuals experiences changes in their memory, their thinking, their reasoning, and ultimately, Alzheimer's is fatal.

Heather Snyder is the Senior Director of Medical and Scientific Operations at the Alzheimer's Association.

She says there are a few other things that can cause dementia, but in general, if someone has dementia, it's probably Alzheimer's.

We often use the terms interchangeably of Alzheimer's and dementia because it is the most common cause.

Anywhere from 60 to 80% of individuals with dementia have Alzheimer's disease.

You can't tell for sure if someone has Alzheimer's until you look at their brain, hence the uncertainty.

And actually, we're going to come back to this issue of diagnosis.

But the point is, as we said at the start of the episode, this disease is a huge, huge deal.

Yeah, so in the United States, there are 5.7 million Americans that are living today with Alzheimer's and more than 15 million Americans that are providing care and support for someone with Alzheimer's or dementia.

Every 66 seconds someone in the United States develops Alzheimer's.

Every three seconds someone in the world develops it.

And we see this number continuing to grow if we don't have a way to stop or slow the progression.

By 2050 an estimated 15 million people in America will have Alzheimer's.

That's the population of New York, Chicago, and Los Angeles put together.

So it's a lot of people.

It's the sixth leading cause of death in the United States, not to mention the tremendous economic cost to our country.

For the second year in a row in 2018, costs exceeded a quarter of a trillion dollars.

These numbers might sound huge and terrifying, and they are, but the fear of Alzheimer's, it's deeply personal, too.

So my grandfather died sometime, I believe, in his late 70s of Alzheimer's.

And then my mother was diagnosed when she was 75.

And she actually just passed away this past summer.

She had a very slow but difficult to watch decline.

This is Aviva Schein.

She's a pediatrician based in New Jersey.

We asked Aviva, do you worry about developing Alzheimer's yourself?

So I think that everyone, well, maybe not everyone, but many people who have family members with Alzheimer's, every time they forget anything, they worry that it's the beginning.

So yes, every time I would forget something, I would think, think, is this, you know, a really subtle, early sign?

Then a few years ago, Aviva found out about the Alzheimer's Prevention Clinic at Cornell University in New York City, which is where we met up with her.

And I thought, wow, that sounds like a great thing to participate in.

You know, I'll get some advice.

I'll be able to stay on top of whatever is current.

And I maybe can make a contribution to finding either a treatment or, you know, what really, truly can be preventative.

The Cornell Alzheimer's Prevention Clinic was founded in 2013.

And it is the first Alzheimer's prevention clinic in the United States of America, and as far as I know, in the world.

Lisa Moscone is a specialist in neuroscience and nuclear medicine, which means in this case, she is an expert in brain imaging.

She's also associate director of the Prevention Clinic.

Lisa joined the clinic in 2016, but it was founded by Richard Isaacson.

So the Alzheimer's Prevention Clinic is very unique as we see people before they have cognitive symptoms or cognitive changes.

Like Lisa said, this was the first Alzheimer's prevention clinic in the US, and it's still one of very few in the world.

But of course, it's not like people have just been sitting back doing nothing up till now.

Researchers have been trying to find a treatment for nearly a century at this point.

As soon as you became like a separate diagnostic entity, which is still quite a long time ago, people have been looking for a cure.

And drug discovery in Alzheimer's disease has been really disappointing and frustrating and unsuccessful.

The disease was first described by a man named Dr.

Alzheimer a century ago.

He discovered that his patient had plaques and tangles in her brain.

These were made of different proteins, amyloid plaques and tau tangles, and these plaques and tangles have been the hallmark of the disease.

So scientists thought, okay, we'll develop new drugs to get rid of the plaques and the patient's dementia will go away.

And right now, I think a total of six very large-scale Phase III clinical trials have been done and they all failed.

All of them.

And it's not like they failed because the drug didn't remove the plaques.

That's the sad part.

So the plaques were actually removed from patients' brains, but cognition did not improve.

There were an enormous amount of side effects, and some patients actually got worse.

Some people died.

And that really, you know, it begs the question, what are we doing wrong?

So like Lisa says, this is obviously incredibly frustrating for researchers and for patients and for family members like Aviva.

There was no medicine for Alzheimer's when my grandfather was diagnosed with it 40 years ago and there has been no change in the treatment of Alzheimer's and I can't think of any other disease that's like that.

There are some drugs available that can help treat the symptoms.

And what they do is that they kind of improve the symptoms for a bit.

They're really not a cure so they can't stop disease progression.

So they work for a few years.

For some people they work longer.

For some people they don't work at all.

They seem to work better for men than for women.

But they can't stop Alzheimer's, so they're not a long-term solution.

Part of the problem here lay in the way that Alzheimer's has traditionally been diagnosed.

Historically, we've done a pretty complicated series of tests that measure memory, thinking, and reasoning, and where the changes in the individual's function happen.

So it's called neuropsychological testing, and it's a pretty extensive battery.

So this battery of tests is still generally how people are diagnosed based on their behavior and their cognitive abilities.

And usually they're diagnosed with the disease when they're pretty old, which is why until recently it's been thought of as a disease of old age.

We now know that Daredevil Simon's disease is not a disease of old age, but rather it starts in midlife.

In reality, the disease starts with negative changes in the brain.

And Richard says those negative changes happen a long time before you see symptoms.

So what we're realizing is that there is this long asymptomatic window, and it's this window that gives ample time to really make evidence-based and safe lifestyle and other changes so before symptoms occur we can try to protect the brain from developing dementia.

This is a big shift in how scientists are thinking about Alzheimer's and it's happened really just in the past few years.

We started the clinic you know just over five almost six years ago now and you really couldn't use the term Alzheimer's in prevention in a scientific community setting.

I would say those words and I would get tomatoes thrown at me in some of my lectures.

Most of Richard's colleagues in the field just didn't believe that prevention was a possibility.

But even at the time, there was some evidence that stress, sleep, diet, that lifestyle contributed to whether or not a person was diagnosed with Alzheimer's.

One study from 2011 said these factors could make up as much as 50% of a person's risk of developing the disease.

But there was no actual evidence that changing those things early on, getting better sleep, reducing stress, changing what you eat, would actually stop you from developing the disease.

So, Richard decided to see whether he could get that evidence.

He started to recruit patients that were just like him, healthy, high-functioning, middle-aged people with no symptoms, but with a family history of the disease.

You know, I have four family members that have Alzheimer's, and you know, when my Uncle Bob was diagnosed with dementia at the age of 72, the disease in his brain literally started in his 40s and 50s.

So, the disease started decades before Uncle Bob began to maybe get lost or forget what day of the week it was or stop recognizing people.

And lifestyle factors like diet and exercise and sleep and stress were known to contribute to the development of Alzheimer's.

So Richard thought maybe he could intervene early focusing on just those lifestyle factors and maybe that could help.

You know, how do we help people?

We learn everything about them.

The little mnemonic that I use to try to explain this is called the ABCs of Alzheimer's Prevention Management.

A stands for anthropometrics, which basically means Richard measures everything about a patient's body that might be relevant.

Waist size and body fat and muscle mass mass and so on.

B stands for biomarkers, such as genetics.

Does the patient have a genetic mutation that might lead to a higher risk?

And then finally, the C of the ABCs is cognitive function.

Which they test like this.

So I'm going to give you a total of three letters, and you're going to have one minute per letter to name as many words as you can.

Okay?

Ready for the first letter?

Alright.

So your first letter is F.

Far,

fall,

farfigneugen,

fell,

funicular,

further,

finish,

uh,

fort,

fortune, fortuny,

feather,

fit, fib,

uh,

finish.

You can try this yourself.

It's surprisingly hard.

But here's the real test: it's been a few minutes, so it's time to ask: do you remember a story about a girl and a horse?

Can you repeat it back?

Ideally, word for word.

We'll give you a second to think about it.

Okay, try to tell the story about the girl and her horse.

Here's how Jessica did at the time.

She's one of Richard and Lisa's patients.

Martha Jackson was riding through the forest on her horse, and

she

this was also in Canada,

and

a bumblebee stung the horse on the nose.

And she,

the horse ran off, jumping over bushes, and she

grabbed a tree branch, and then fell and hurt her arm.

I guess she broke it.

And

then she called out to Powder Puff, her horse,

but he never returned.

Oh, and she was picking these blueberries for her grandmother.

That's why she was there.

These are the kind of things I can pull up right now.

Some details, names, the main events, maybe not in exactly the right language or order.

Is that good enough?

I mean, I can't imagine I would have done better, even when I was younger.

Jessica's test went on for another 20 minutes, but we'll spare you.

For patients, Richard's ABCs add up to a grueling day in the clinic.

And then every six months they come back and we're basically going to repeat all of these things.

Richard is tracking his patients over time, but obviously this is a prevention clinic, so he also makes very specific recommendations that are based on their own personal body measurements and genetics and so on.

He'll tell them to exercise and how much, to sleep, what to eat.

I would recommend, hey, eat a Mediterranean-style diet, eat less carbs, do this, do that.

You need to have more omega-3s, you need to eat more fish, and you need to do that.

And oh no, you need more vitamin D.

And Richard makes these recommendations based on studies that have shown the connection between certain diet and lifestyle choices and the likelihood of developing Alzheimer's.

And here's where we get back to food.

For instance, there have been studies that showed that people who generally followed a Mediterranean diet-whole grains, olive oil, lots of vegetables, fish, nuts, some dairy, not much meat-that they had improved cognitive function.

Scientists couldn't say definitively that it was the diet.

They just watched people over time, and their diets seemed to be linked to better cognition.

But so that's why Richard recommends it.

But so, then, how does Richard figure out if his recommended changes are actually working?

So, what we do is we implement these interventions and we track A,

do people change at a different rate over time compared to the controls and B, does compliance with the interventions matter?

Okay, but then how does he know which intervention matters?

Maybe diet doesn't matter and it's all about sleep.

How would he know?

Richard and his team look at all the data and then they compare their patients with groups of people that are being studied at other institutions that aren't taking a preventative approach, those are the controls, and they tease out which interventions are working using statistics.

And Richard told us that his data show that, yes, these prevention strategies work and that diet has a big effect.

He's still analyzing the data to see exactly how big that effect is, but the early results are promising.

What Richard's using to figure this out is those cognitive tests that he gives the patients every six months.

He checks to see whether there's been any type of decline in cognition, in memory, and comprehension, so on, and those are specific declines that would be related to Alzheimer's.

Because his patient's test performance related to these Alzheimer's-specific markers improves, Richard is able to conclude that his interventions are preventing or delaying Alzheimer's.

But these cognitive tests, like we said, they're just kind of a proxy for Alzheimer's.

The only way to truly prove this, the only way, is to assess and track a biomarker of disease.

A biomarker means, you know, that amyloid, for example.

So to do that, you need an unbelievable amount of money and funds and planning and resources and expertise and knowledge and power and the only way to do that is to create a robust state-of-the-art brain imaging research program.

And that is where Lisa comes in.

This is the brain imaging facility.

It's a very brand new state-of-the-art center.

We have three PET scanners, a number of MRI scanners, so it's really good.

They're actually beautiful machines.

So we're here because the patient is in the MRI.

She's getting her brain scanned.

She's coming out in 30 minutes.

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Lisa Moscone grew up in Italy and she's been studying Alzheimer's disease since college, which frankly is kind of young to be interested in the topic, but she has a personal connection.

My grandmother had Alzheimer's disease and then a few years later her younger sister developed exactly the same thing and a few years later the youngest of three sisters also

was diagnosed with dementia.

But that was horrible, of course.

And you know, it's really heartbreaking.

I would say it's a heartbreaking disease, and

you don't really, you're kind of powerless in so many ways, and then you worry about your own risk.

So, Lisa cared about Alzheimer's, and then she also cared about food.

Yeah, so I'm Italian, so I believe in food and good food.

And

I never, actually, I never thought the food would impact the brain.

In her neuroscience classes in Florence, Lisa heard that the brain was pretty much isolated from food, but she also learned that the brain needed specific nutrients to do its work.

And I would take all these neurochemistry classes and read about sodium, potassium, omega-3 fatty acids, and saturated fat.

And I just thought, well, these are things that just happen to be inside the brain.

And then at some point, I realized, oh, actually, these are nutrients from food.

And so finally, I connected the dots.

I was like, oh, let's look into that.

And yeah, so that's how we started.

I was at the NYU School of Medicine back then, and I started my very first lab.

It was called the Nutrition and Brain Fitness Lab, which is not a good name, but my chairman picked it.

This was back in 2012, right about when Richard Isaacson was starting to think about prevention too.

Like we said, before then, what people had been doing was these long-term observational studies connecting lifestyle and diet.

It's made for some intriguing findings but there was no way to be proactive and see if any changes a patient made in their diet helped.

Also there was no way to see in the brain what types of dietary changes affected the brain and how.

Now it's a new year, it's a new decade and we're doing amazing things in neurology and neuroscience 2019 folks and brain scanning is real and heather says it's completely changing the game i think studying alzheimer's has been really challenging because our brains are a really well protected organ It has been only in recent years that we've been able to look at what or even have a hint of what's happening in a living person.

So things like the ability to take a picture, use imaging, and using that as a window into what might be happening in the brain.

That's really only been in the last few years, less than the last decade, that we've had those types of tools.

And I think that's opened up a window for us to start accelerating our understanding about what might be happening.

And that's exactly what Lisa is doing.

Like we said, Richard monitors his patients by giving them all sorts of cognitive tests to see if the interventions he's prescribed for them are working.

Lisa does those tests too, but she also looks at their brain very, very carefully each time they come into the clinic.

This is the scanner.

and what you do is they just lie down on the bed and then the bed goes inside the machine and then

that comes up on the screen.

That's the patient's brain.

Lisa was looking at Aviva's brain on the screen.

Aviva lay on her back surrounded by the machine and the loud buzzing and in the next room Lisa was looking at a screen at Aviva's brain from the top down and from the front and from the sides in shades of white and gray against a black background.

It's a good brain.

It's a very good looking brain.

And then you want your brain to be as big as possible and to really fill up your skull.

It is a very healthy looking brain.

What Lisa is looking for though are the very first signs of Alzheimer's because the first signs of damage to the brain show up years, decades even before a viva would start failing her cognitive tests.

We're looking for atrophy, which is brain shrinkage due to aging or pathology or other factors.

We're looking at the concentration of specific metabolites in the brain.

In this case, you're looking for mitochondrial activity.

Measuring mitochondrial activity helps her figure out how much energy there is available for your brain, so that's a big deal.

And Lisa is also looking for signs of inflammation and glucose activity and so on.

If there's a lot of inflammation or not enough glucose metabolism or mitochondrial activity, those are some of the earliest signals of Alzheimer's.

Signals that would be invisible without brain imaging.

And then, like Richard, Lisa gives the patients very specific dietary instructions to help shore up their brains.

And Lisa doesn't just recommend these changes, she checks up on her patients too.

We do a thorough assessment of the way you eat and all the nutrients.

We measure them in plasma as well because people just lie openly when you say, how often do you cook?

It's like

once a month.

It's never true.

And so we measure nutrients in plasma and serum.

And then we would do brain scans.

And we would keep doing these examinations over time and really try and correlate diet and dietary changes with the changes that we could see inside the brain.

And over the past few years, Lisa has been able to find very specific connections between what her patients are eating and their brain activity, their brain health.

Last year, Lisa published a big paper in the British Medical Journal.

She followed a group of patients over three years and she didn't just show the connection between diet and Alzheimer's changes in the brain, she showed how much of a difference diet makes.

And what we see is that in terms of brain activity, those on the Mediterranean diet pretty much remain stable over time, whereas the Western dieters decline.

I think the rate is like over 3% a year, and it's pretty steady.

And at the same time, they start accumulating Alzheimer's plaques.

So the Mediterranean dieters don't show any Alzheimer's plaques to start with, and they remain pretty much stable over time.

But the Western dieters show more plaques the first time they come to the study, and then the accumulation also progresses.

It's like a 2% increase a year.

And they're literally in their 40s and 50s.

So it's a very early finding and I think it's pretty convincing.

This is actually a really big deal.

That's a huge difference and Lisa has managed to show that it's all down to diet.

I think also because we really

account for everything else.

So it's not just we're comparing these two groups, but we have no information on their exercise activity or intellectual activity or vascular risk factors.

They're all in there.

They're all in the model.

And in Lisa's study, once she factored diet into the model, that was the only lifestyle difference that affected the brain structure markers she's looking at, those early signals of Alzheimer's.

Not sleep or exercise, diet.

If everybody exercised the same way, if everybody stimulated their brains, you know, their brain the same way, if everybody had the same vascular risk factors, diet would still come out on top as the factor that really impacts brain health, at least during middle age.

There's a lot more studies to be done, Lisa says, but it's a pretty exciting result.

So you might be thinking, okay, we have already heard that this pattern of eating is good for us.

Everyone everywhere is always talking about the Mediterranean diet and oily fish and leafy greens and how they'll help you live to a healthy old age.

So what is different about Lisa's research showing that it's good for our brains?

Didn't we know that already?

So what we have that is new now is the technology and the understanding.

And this is important.

Knowing that diet is correlated with healthy brains is one thing.

Actually documenting those brain changes and their direct connection to diet is something else entirely.

So when I first started, I couldn't get a grant.

I was writing these grants, trying to get funding to look at diet and lifestyle, couldn't get any.

And then we started publishing preliminary data, and the reaction was

very polite, I would say, but not like, oh, wow, that's really interesting.

It was like, yeah, you know, whatever, it's food.

I think really being able to show people their brains made a big difference to convince convince not just the public but also other investigators.

It's not just numbers.

You know, you can actually pull up a brain scan and you can see it.

And there's a huge difference.

So it works.

Okay.

But how?

How is what we eat making such a huge difference to our brains?

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There is a lot to talk about when we talk about Donald Trump and Jimmy Kimmel.

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What even is your brand anymore?

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It's very hard to change your brain from the outside, and that's the way we were engineered to be.

Because if starving for three months could affect your brain so substantially, the human race would never have been at this point.

So it really takes a lot of time to make a meaningful infect, a meaningful change inside your brain.

This goes back to what Lisa was saying about what she learned during her very first classes as a neurochemist.

The brain is kind of separated from the rest of the body.

So how can what we eat affect it so dramatically?

Oh,

there are many different mechanisms of action.

So for instance, the number one food to parent Alzheimer's is probably fish.

And that's because fish contains omega-3 fatty acids of a very specific kind.

It's called DHA.

Okay, neurochemistry.

Here we go.

And yes, the neurochemistry, Lisa explained, is a little complicated, but generally, not all kinds of fat that we eat can get through the barriers around our brain.

You know, we just inject fat, literally, in the brain, it's labeled with a radioactive isotope, and then we can see if it gets inside the brain or not.

Cholesterol, for instance, never gets absorbed by the brain.

Saturated fat is pretty much the same deal.

Super minimal uptake, at least after adolescence.

But polyunsaturated fat instead can get inside the brain very easily and does so all the time.

And especially, cell membranes inside the brain are made of a specific kind of pollen-saturated omega-3 fatty acid called DHA.

And the only natural source of DHA is fish, seafood.

I mean, also like crustaceans.

Yeah, what's it called?

Shellfish.

So that's a really good food to eat.

like constantly.

There are other ways food affects the brain.

You've probably heard of antioxidants.

These are chemicals in foods like, yes, leafy greens and colorful veggies and berries.

Here's how they work.

Your brain uses a lot of energy, and all that energy has to get made inside cells by mitochondria.

And every time your mitochondria produce energy, they also produce oxidative stress.

It's a byproduct.

It's just natural.

And the brain has very limited antioxidant defenses on its own.

So we have to keep importing these antioxidants from the diet.

So oxidative stress is basically like a rusting mechanism that makes your brain age faster and it can trigger apoptosis, which is neuronal death.

So we bring in the antioxidants from the diet, so

we bring down the oxidation.

So that's another way that diet can affect your brain.

And now onto sugar.

Your brain is fine if you eat sugar.

The problem is that the rest of your body is not.

So if you eat too much sugar or too much refined sugar, that really affects your pancreas, right, and your insulin levels, and it can cause insulin resistance and pre-diabetes and diabetes.

And then all the inflammation that you have in the rest of your body ends up affecting your brain.

And not in a good way.

Inflammation is very aging for the brain.

All the ways that food can either hurt or protect your brain-oily fish and colorful fruits and veggies helping it, sugar hurting it-these are physical and chemical changes that Lisa can track pretty much in real time with all her super cool high-power machines.

They are slow, small changes because, like Lisa said, the brain changes slowly, but she can see them and they add up over time.

And they increase or decrease your risk for developing Alzheimer's.

So as you can now see, Lisa is obsessed with food, but she's also obsessed with another aspect of Alzheimer's.

This is also something that usually doesn't come up in conversations around Alzheimer's, is that Alzheimer's affects more women than men.

So every three Alzheimer's patients, two are women all over the world.

And usually when I say that, people will tell me, well, you know, women live longer than men, right?

So the fact that Alzheimer's really affects an enormous amount of women is kind of just explained away because we tend to live a little longer.

And I have done a lot of research on that.

And it's just not the case.

After all, if it's just that women live longer than men, then women should also be more likely to get Parkinson's and other kinds of non-Azheimer's dementia.

And we aren't.

But there's something more.

that we need to talk about.

And Lisa says that thing we need to talk about are hormones.

We call estrogen, testosterone, progesterone sex hormones, but that's just just because the people who discovered them were interested in sex and not in brain, right?

But these hormones are also neuroprotective hormones.

The connection between hormone levels and brain health is still being figured out.

And obviously, a lot of things can affect hormones, like puberty or menopause.

And Lisa says that actually the hormonal changes that women go through during menopause might somehow harm our brains.

She's trying to figure this out.

She recently got a brand new grant to study exactly what's going on.

But meanwhile, it turns out there's a place for food in tackling these hormonal brain health issues too.

In reality, many foods have a strong hormonal effect in the body and the brain.

After all, there are actually hormones in our food naturally.

So the first thing to know is that estrogen is a very ancient hormone.

It's actually the most ancient of all hormones, which means that we share it with plants, we share it with animals, and is not unique to humans.

So plants make estrogens.

Plant estrogens are a weaker form of estrogen than our own body makes.

But still, when we eat foods that contain plant estrogen, it will affect our brains.

Lisa says these plant estrogens might protect against the harm of losing our own estrogen as we go through menopause.

Soy is an obvious one.

You've probably heard that soy has these plant estrogens, but there are lots of other sources.

Like flaxseeds, chickpeas, sesame seeds, strawberries, watermelon, apricots, dried apricots.

These are all very high in photoestrogens.

This is a new area of research for Lisa.

It's like with Alzheimer's and diet connections, the connections are there, but not the tangible proof yet.

So

there are notions around women's health and what kind of foods or nutrients are particularly good for women's brains.

I think what's missing in the research is evidence from actual brains.

And that's what Lisa's new study is going to add.

So stay tuned for her findings in a few years.

Today, Lisa and Richard aren't the only ones working on how lifestyle changes can affect and protect our brains as we get older.

But there are more and more investigators looking at diet with brain scans.

And they think that's wonderful because, you know, usually we're able to replicate each other's findings.

And that's really nice.

This idea of using brain scans to try to figure out the effects of diet is catching on and scientists now accept that lifestyle affects Alzheimer's.

So what's next?

Are these food and Alzheimer's findings still preliminary or are they ready for prime time, ready to be tested in big clinical trials?

Lisa's studies are clinical trials but they're a little different from normal clinical trials.

She treats everyone in the group so there's no control group that's not getting treated.

But there has been a more classic clinical trial with a control group.

It was done in Finland and the results were published in 2015.

It's called the finger

trial, unfortunately.

The finger trial.

In the finger trial, one group of patients just lived their normal lives and another had to follow all the best prevention recommendations.

So they really they've revamped everything from their diet to their exercise, cognitive stimulation, they use computer testing as well, vascular risk reduction the same way and they followed patients for two years and at the end of the study the treated group showed 150% improved cognition in some specific domains.

So I think that's really encouraging evidence.

And for diet.

The Alzheimer's Association is helping sponsor another major study in the U.S.

right now.

Heather told us it's basically looking at the same thing.

A very specific recipe that combines that best scientific information and testing it to say is this beneficial to cognition over a specific period of time in individuals at an increased risk.

That study is called the U.S.

Pointer Trial, and we're very proud to both be funding it but also helping to lead it.

Both finger and pointer use the same markers of improvement that Richard's using.

They're testing the participants' cognitive skills.

They're not doing Lisa's high-tech brain scans.

But the value of Finger and Pointer is that they use a really big group of participants, thousands to Lisa's dozens.

That's important to make sure these results are really significant.

What's also important about Pointer is that it's going to be studying a much more diverse population than the Finnish group in the finger study, which unsurprisingly was mostly white people and mostly in roughly the same income bracket.

When Richard started his prevention clinic, he practically had tomatoes thrown at him.

When Lisa started her diet and Alzheimer's research, she couldn't get funding.

That has all changed in the past few years.

When I think there really is an excitement and an enthusiasm around lifestyle and behavioral-related studies.

But of course, diet isn't everything.

You've probably heard that there are genetic mutations that can give you a higher risk of getting Alzheimer's.

And this is why some of Richard and Lisa's patients are more likely to develop the disease.

Your genes are important, of course, they are.

But Lisa says having those mutations is not a guarantee that you will get Alzheimer's, it just increases your risk.

Just like eating a Western diet also increases your risk.

I think they interact.

What we find is that an unhealthy diet seems to really activate your genetic predisposition and not in a good way.

Everything is connected.

Diet and stress and sleep and genetics and also medicine.

Once there are drugs developed that actually work, all the prevention researchers say we'll need a holistic approach to protect our brains.

It's very unlikely that any one thing will cure something that is as complex as Alzheimer's disease.

In the last three years, I think we've seen an incredible growth in the conversation around combination therapy and that idea of, you know, think of other complex diseases like heart disease or cancer.

We don't treat it with just one drug or one intervention.

It's really a combination of factors.

So thinking of that same kind of thing with Alzheimer's.

Pretty much everyone now agrees it's going to take a combination of approaches to prevent and treat Alzheimer's.

But we now know for sure that what you eat is an important part of that combination.

And ultimately, it looks as though diet may be combined with other lifestyle changes, like staying mentally and physically active and getting enough sleep, that together those changes can prevent Alzheimer's in a lot of people.

35% of global dementia could be preventable by modifications in these behaviors.

That's a lot.

That's more than a third.

And when you think that there are nearly 6 million people living with Alzheimer's today in the U.S., just imagine if nearly 2 million of them had never come down with a disease.

For us, everything that can be prevented is worth it, right?

Which is not saying that genes are not important or amyloid is not important, it's just that you need to start somewhere.

We have a very practical approach, so we will modify everything we can modify.

And

when amyloid drugs become available, wonderful, we will send patients to clinical trials.

But in the meantime, there aren't drugs.

And even if you're one of the unlucky folks and diet doesn't prevent you getting Alzheimer's, well, it can still buy you time.

And that's what Aviva Shine is hoping for.

That's why she's taking part in Lisa's study.

If you could just delay the onset for five or ten, maybe that's optimistic.

But any delay, because most people are so old when they get it, that even delaying the onset or slowing the course would actually be really significant.

So, you know, that's why all you need to do is kind of push it off a little bit to be significant.

Diet isn't a drug.

It's not going to prevent Alzheimer's for absolutely everyone.

But let's say that that Aviva is, in fact, likely to get Alzheimer's because of her family history.

Maybe changing her diet will help stave it off so long that maybe she'll never even actually get it.

I don't necessarily think of diet as a treatment for Alzheimer's.

I think about it as something that can help you fend it off if you're predisposed and can help you minimize your risk and can help you really retain your mental capacities for the long term.

Thanks so much this episode to the the Alfred P.

Sloan Foundation for the public understanding of science, technology, and economics, as well as the Borough's Welcome Fund for our coverage of biomedical research.

Thanks, of course, to Lisa Moscone, who let us shadow her for the day, to our patients, Aviva Schein and Jessica Sheet, as well as to Richard Isaacson and Heather Snyder.

We have links, as always, on our website, gastropod.com.

If you're a special supporter of Gastropod at $9 per month on our website or $5 an episode on Patreon, we'll be sending you some of the fascinating stories that we couldn't include, such as how and why women are frequently mis or underdiagnosed when it comes to Alzheimer's, and what the gut microbiome might have to do with the disease.

Microbes, drink, and sign up.

We'll be back in two weeks with the twisted tale of one of our favorite circular foods, the bagel.

We have a lot of fun flavors, spinach bagels coming up for St.

Patrick's Day.

Started doing pretzel chocolate chip bagels on Mondays, which are fun.

Yeah, and then our usuals.

We have plain pretzel sea salt, sesame, everything,

onion, cinnamon, raisin, seeded wheat, black olive, poppy seed, and deli rye.