The Best Diets for Alzheimer’s Prevention, According to a USC Neurologist

By | May 23rd, 2024

How does your diet affect — or protect — your brain? USC neurology and nutrition expert Dr. Hussein Yassine explains the research on the link between eating patterns and brain health, particularly for those with genetic risk of Alzheimer’s disease.

While Alzheimer’s disease isn’t curable, research shows it may be preventable or postponable by controlling lifestyle factors like diet. Yet, with so many diets emerging, it’s hard to know what’s a fad and what lifestyle changes can actually support brain health. At the University of Southern California, neurologist Dr. Hussein Yassine studies how different diets and dietary patterns affect brain health, particularly regarding Alzheimer’s risk. For him, it’s not just about looking at individual diets but at the whole dietary pattern and focusing on diversity.  

“The more diverse your diet is, the more likely you’re going to get a lot of beneficial effects,” Yassine said. “Diversity requires different ingredients that not only include fats, but other things.”

Yassine teaches neurology in the department of physiology and neuroscience at USC’s Keck School of Medicine. At his lab there, Yassine Lab, his research team studies the effects of lipids — particularly omega-3 fatty acids — on the formation and progression of Alzheimer’s disease. He’s also the director of the USC Center for Personalized Brain Health, which launched in 2023 to advance personalized health and cut Alzheimer’s risk by building research on the APOE gene and the role of fatty acids in the brain. 

In conversation with Being Patient founder Deborah Kan, Yassine answers key questions on how diets can support brain health, particularly for people at risk of Alzheimer’s disease. Read or watch the conversation below. 

Being Patient: Your research focuses on what we eat and how that directly relates to our brain health. Tell us how much we know so far.

Hussein Yassine: We know a little bit. We know, in certain areas, that certain dietary patterns are associated with better brain health, and we know that other dietary patterns are associated with worse brain health. There have been really elegant studies in the last 20 or 30 years that have informed us on possibly what works and [what does] not.

Being Patient: The Mediterranean diet and the MIND diet are frequently cited as the gold standard for brain health. What do we know about them?

Yassine: We know that the MIND diet, which is a combination of the Mediterranean diet and the DASH diet, is particularly good for the brain. We also know that we probably have to move from the concept of a dietary pattern.

“We know that the MIND diet, which is a
combination of the Mediterranean diet and the
DASH diet, is particularly good for the brain.”

Being Patient: What do you mean by that?

Yassine: That means we have to take the whole as opposed to the individual components. For example, if you’ve got somebody who loves fast food, and you give them an element of the MIND diet, that’s not going to be similar to somebody who doesn’t eat fast food and they’re eating the MIND diet. Basically, you have to take the whole dietary pattern and not just isolate individual components.

Being Patient: When someone has a diet rich in olive oil, fish, and vegetables, how does that translate directly to the brain?

Yassine: Very good question. I would have to start by saying that the quality epidemiology data discusses the concept of lifelong dietary patterns and their association with brain health. We’re talking about something that’s chronologically happening on the order of many, many years, possibly starting through middle life. 

That means that individuals who are taking a healthy MIND or Mediterranean-like dietary pattern are probably consuming a lot of fiber, a lot of good fats, and a lot of polyphenols. Those remodel and allow the body to create a niche or an environment that’s protective— whether it’s going to be at the level of the gut microbiome, or at the level of the blood, or maybe at the level of the brain itself. These all interact to help the brain function and to stave off any risks for diseases like Alzheimer’s. 

Being Patient: If someone who ate junk food when they were younger switched to a strict Mediterranean, DASH, and MIND diet, would they be able to repair the damage, or is it a cumulative effect over the course of their lifetime?

Yassine: It’s both. Let me explain. [It] definitely is better switching off no matter what time but the degree of benefit is probably a function of how long you are on the good diet. People who have been on a good diet for many years have less risk and less disease than people who have been on the diet for a short amount of time. 

“People who start these healthy diets
before they have a diagnosis of disease
tend to have more [benefits] than after
the diagnosis of disease.”

This question is particularly important in the setting of disease. For example, people who start these healthy diets before they have a diagnosis of disease tend to have more [benefits] than after the diagnosis of disease. This is particularly important in the brain because we know that brain cells, once they die or degenerate, [are] really hard to regenerate, and dietary interventions may not be effective in doing so.

Being Patient: So, there must be benefits as well to your brain, if you really change your diet.

Yassine: There is benefit to the brain, but the earlier you start, the better. 

Being Patient: I’ve heard that it really matters what type of oil you cook with, like that some of the seed oils can damage the brain. Can you tell us if that’s true or not? What do we know about cooking and eating different types of oils?

Yassine: Let me just answer this in two ways. One, I want to reiterate and emphasize the importance of the diet as a whole pattern as opposed to an individual component, because you can possibly have a little bit of bad oil and bad foods— but your body can compensate if the overall pattern is healthy. The other way is true. If you have a really poor diet and then add healthy olive oil or something good to your diet, that may not be very effective. 

I just want to reiterate [the] concept that one ingredient does not seem to do a lot. Let’s go back to your question of fried oils. Part can actually mean oxidation of oils, they can be damaged oils that can increase disease. When we try to create foods with minimal processing and less frying, I think we can get more benefits from the individual components that we were discussing. 

“There isn’t really very good research saying that
vegetable oil is superior to corn oil, or you
can fry this kind of oil or that oil.”

Is there any particular oil that can be fried or not? There isn’t really very good research saying that vegetable oil is superior to corn oil, or you can fry this kind of oil or that oil. I could tell you that frying polyunsaturated fat is not a good idea because the benefit comes from these unsaturated bonds, which have antioxidant properties. So, if you take, for example, olive oil or an omega-3 oil and deep fry it, you completely destroy that, and it’s no longer behaving as it’s supposed to.

Being Patient: Regarding these oils, what do people need to know about getting the benefits of, say, olive oil, and what to stay away from? As nonscientists, what do we need to know?

Yassine: Well, don’t burn the oil. Let’s distinguish heating up oil from burning oil. So, you can take any vegetable corn oil, heat it up and maybe fry with it, and it’s good. The problem happens when these oils are past the boiling points, and they’re burned. Then the color changes, the smell changes, and you’re seeing a black color. This is particularly worrisome in fast food chains that reuse the oil again and again. 

Basically, the concept isn’t that sophisticated. Any oil that’s not polyunsaturated, when you actually heat it up, if it’s not burned, it’s probably okay to consume. I’m not advocating for using fried food. I’m just pointing out that there is a point when even the best oils, when you start burning them, and they change color, change odor, and they change texture, and you’re dealing with something completely different. That’s not good. 

Being Patient: What do lipids have to do with our brain? What must we know about metabolism, lipids, and how they relate to brain health?

Yassine: There’s a simple answer, and there’s a complicated answer. The simple answer is that the brain is really made of good lipids, like polyunsaturated fats, and that we need those components because the brain cannot make them from scratch. 

The complicated answer is that it’s probably a multi-system approach where these good fats are interacting with your gut microbiome, with other tissues that are making it optimal for brain health. Whether it’s going to be blood flow, blood vessels, liver adipose tissue, insulin resistance, diabetes— good fats have pleiotropic effects that can make the brain happy. 

It’s not as simple as supplying the brain with just a source of fat that it likes. I realize that I’m touching on a complicated topic, but basically, chronic consumption of good polyunsaturated fat, particularly plant-based polyunsaturated fats, has beneficial effects on the body as a whole and on the brain in general, specifically.

“Whether it’s going to be blood flow,
blood vessels, liver adipose tissue, insulin
resistance, diabetes— good fats have pleiotropic
effects that can make the brain happy.”

Being Patient: From what I understand, it depends on what you’re ingesting and how your body is metabolizing those lipids. Is that correct?

Yassine: We do have to move away from single fats and look at diversity in the diet. I think the concept that I’m trying to illustrate is that the more diverse your diet is, the more likely you’re going to get a lot of beneficial effects. Diversity requires different ingredients that not only include fats but other things. 

“We do have to move away from single
fats and look at diversity in the diet.”

I really want to emphasize, for example, the importance of fiber. Having a high-fiber diet can significantly remodel the small gut microbiota or microbes that are actually eating as we eat, and they produce compounds from our own diet that can go into your brain. 

Being Patient: I’ve been told not to drink orange juice in the morning but to eat an orange. If you eat the whole fruit, it has fiber. That serves a purpose, right?

Yassine: There are many reasons why fiber is quite important in our diet. It regulates the absorption of sugar in the case of orange and orange juice, but it also regulates trillions of microbes living in us. They outnumber the actual number of cells that we have; they eat with us, and we are in a symbiotic relationship. Keeping those microbiota diverse by taking in a very diverse diet is a good thing.

Being Patient: What types of fiber should we be eating? Is there a best type for supporting brain health?

Yassine: I don’t think there’s a best type. I think there are multiple types of fibers, and the more that you can diversify your diet and take fiber from whole grains and wheat [the better]. Take fiber from fruits, take fiber from vegetables, take fibers from nuts and seeds. There are many sources of fiber. The point is, the more diverse your diet is, the more likely you’re going to get benefits. The more restricted your diet is, you’re kind of forcing certain ingredients to be really high and others not to. I think the science is telling us diversity is a good thing.

“The more diverse your diet is, the
more likely you’re going to get benefits”

Being Patient: I remember interviewing another scientist who likened the microbiome to a rainforest. A rainforest can only survive with a lot of diversity within it, right? Would you say that’s a good analogy to make?

Yassine: That’s an excellent analogy. Let’s also put omega-3 fats in context because they require this diversity, the rainforest you’re discussing, to work. If you just take one element, let’s say DHA, which is one of the essential omega-3s, and take it in isolation, it’s not very effective. But if you actually put it in the context of a very diverse nutrient background that contains choline, B12, folic acid, and short-chain fatty acids produced from those microbiomes, the same ingredient, DHA, can lead to much more effect. So, we do have to consider the whole and not the individual.

Being Patient: How much of these nutrients can we supplement? Would taking a supplement for omega-3 do the same thing as actually eating the food?

Yassine: I don’t think so. I don’t think taking supplements can be as good as taking diverse foods. Now, having said that the bigger, more complex question that we don’t have an answer to is: can people have a healthy, let’s say vegan or vegetarian, diet that excludes fish? Can this diet stand alone without taking supplements? I don’t think we know. I think some people would advocate taking omega-3 supplements because those diets are deficient in fish. 

Some people would say that there are vegetarian and vegan populations. We can talk about countries like India and other places where they have little access to fish and don’t have an epidemic of Alzheimer’s dementia. The point is, if you have a healthy diet that contains diverse entities, you may not need particular supplementation. 

“If you have a healthy diet that contains
diverse entities, you may not need
particular supplementation.”

Now, that’s general population advice. My lab is interested in a specific gene variant known as ApoE4 in white individuals. Ethnicity is quite important here and is associated with an increase in the risk of dementia. E4 carriers who have very low levels of omega-3s have more dementia than E4 carriers who have good levels of omega-3s. So, we’re testing the hypothesis that raising the amount of omega-3s in E4 carriers might make a difference. This might be very specific and personalized but may not apply to the general population.

Being Patient: I’ve been told that ApoE4 is an important cholesterol transport gene. Is that true?

Yassine: Not exactly. It’s a lipid carrier. Cholesterol is one of the components in lipids. It transports cholesterol, but it’s not just a cholesterol transporter.

Being Patient: When we’re talking about a deficiency in omega-3 leading to a higher risk of Alzheimer’s in the E4 population, what specifically is interesting about that in terms of the gene versus what they are or aren’t getting or processing?

Yassine: The analogy I give is that different engines of different cars may have different requirements. For example, if you buy a Lamborghini or a really expensive car, and you take it to a repair shop or the dealer, they will tell you that this kind of engine will require certain oils, hybrid oils, for that engine to have a given life. If you use poorer engine oils, the car can still run, but it’s likely that you’re decreasing the lifespan of that engine. 

In my mind, this is too simplistic, but perhaps it can serve a point that the E4 brain requires higher-quality oils to keep firing at a certain rate. If it’s not supplied by that high-quality oil at some point, compared to a different engine, you would see the actual engine light, and that’s one of the signs of dementia.

Being Patient: What are the best sources of omega-3s? Is it mainly fish?

Yassine: I would probably say land-based omega-3s are as good as seafood-based omega-3s. You can get omega-3s from nuts. You can get omega-3s from algae, which is how fatty fish get their own seafood. Among the actual fatty fish groups, salmon, red herring, and sardines have the highest concentrations. 

Basically, there’s many sources. That doesn’t mean people have to be binging on fatty fish. The requirement isn’t that huge, but what we’re trying to say is that in a very unique specific population at risk of dementia, more research, and we are part of those groups that are interested in finding out whether increasing omega-3s in this sub population can make a difference and we don’t know if it does. 

Being Patient: Can a ketogenic diet provide benefits for brain health? What are your thoughts on the diet?

Yassine: We have a paper that’s going to get published in the next couple of months in Nutrition Reviews that looks at all diets for ApoE4 carriers. We go into all individual diets, including the ketogenic diet, and My opinion, based on my understanding of the literature, is that a ketogenic diet is a little bit restrictive, and can be hard to maintain, but has good elements. 

So, you have to be creative, and go beyond simply a ketogenic diet. Meaning, if you can get away with a ketogenic diet based on good fats from plants, that’s probably the diet, but if you go onto a ketogenic diet, living on steak, that’s probably not a great diet. Ketogenic by itself doesn’t give us enough information to tell you if it’s a good or a bad diet. 

A ketogenic diet is, by definition, simply a low-carb diet. However, there are carbs that are good, and there are fats that are relatively not as good. I would just walk away from just being on a ketogenic diet and think about the components of the diet itself.

“Ketogenic by itself doesn’t give us enough
information to tell you if it’s
a good or a bad diet.”

Being Patient: Glucose is the natural fuel for our brains, and as we age, I’ve been told we metabolize glucose less efficiently. Ketones are an alternative source of fuel for our brains because they actually cross the brain blood barrier. Do you have an opinion on following a ketogenic diet or fasting for specific periods of time to burn ketones? What do we know about that in terms of how to sustain energy in our brains?

Yassine: Let me just try to explain a little bit. It is true that glucose metabolism in the brain is decreased as we age and this decrease is accentuated in diseases like Alzheimer’s, but that’s not simply crossing into the brain. That’s the whole metabolism of glucose. So, we don’t really know how much of that decrease is a function of transport into the brain versus actual lower metabolism by the brain cells themselves. 

I would argue that we don’t know much about ketone brain uptake in disease states because there are some studies suggesting that in patients who carry the ApoE4 allele, the brain may not be efficiently capable of breaking down ketones to generate ATP as a replacement for glucose. To make the assumption that if the brain cannot use glucose, it can use ketones instead I don’t think that’s fully supportive. 

“Having a diverse form of energy, in general,
is a good idea. Whether that means
switching on and off or having intermittent
fasting or intermittent or time-restricted
diets, I think there’s some
good science to support that.”

Now, having said that the concept that I’m trying [to get] your listeners and readers to understand is that diversity is really good. Diversity could mean that you’re alternating your sources of energy, sometimes coming from glucose, sometimes coming from fat or ketones. Having a diverse form of energy, in general, is a good idea. Whether that means switching on and off or having intermittent fasting or intermittent or time-restricted diets, I think there’s some good science to support that.

Being Patient: We have a comment from a listener asking if you could be more specific about what type of plant-based diet you recommend. She says her doctor recommended she avoid meat substitutes like the impossible burgers. Do you have any advice on that?

Yassine:  I would refer to a paper we published, either this year or last year in a journal called the Current Opinion in Nutrition, where we talk about plant based fats and their sources. In a nutshell, the less process, the better. If you are ingesting extremely processed forms of fat, whether it’s meat, or it’s plant based, there are ingredients which we don’t fully understand. They may be packaged in preservatives that allow them to last six months or more on the shelf. 

We don’t really know what that means, but [you can] go back to plant-based diets that we’ve had for many, many, many years. When we talk about fats, we’re talking about seeds and nuts. We’re talking about many sources of fat: avocados, as an example, have a lot of good fat. Avocados are monounsaturated fat, and nuts like almonds and walnuts have polyunsaturated fats. Coconut has saturated fats; these are all healthy fats coming from plants. So, a plant source of fat is generally healthy fat.

“A plant source of fat is generally healthy fat.”

Being Patient: How big can lifestyle adjustments like exercise and diet play in staving off Alzheimer’s?

Yassine: Excellent question. The answer is: it is good. The reason why we say that is because not all ApoE4 carriers get dementia; that’s particularly true with heterozygotes, which have one copy. If we assume you’re following E4 carriers, we see that a small portion of them— less than 25% of those carriers will get dementia, maybe 75% or more will not get dementia— so why are they protected? 

“I think as we study more why some people
get dementia and others [don’t], we’re
learning that certain habits and
patterns can be protective.”

You might argue, or maybe they have other genetic factors that protect them, and that’s true. But often, genetics doesn’t explain a lot of why these individuals are not getting dementia. Often, it is lifestyle. It’s exercise, its diet, it’s stress, [and] it is social integration connections. It’s being less stressed, less anxious, [and] less depressed. It’s being mentally and cognitively stimulated. I think as we study more why some people get dementia and others [don’t], we’re learning that certain habits and patterns can be protective. Unfortunately, clinical trials often have limitations in terms of their design or duration that may not allow us to mimic epidemiology. 

Being Patient: Do you practice what you preach? Do you eat a really diverse and healthy diet?

Yassine: I try to, but I have to admit that we all have our vices, and sometimes we have our weak points, especially when we are stressed out. I’m discovering myself— I’ve tried different diets. I’ve been on all kinds of different foods just to see what my body likes and whatnot. What I’ve discovered from my personal journey is that sometimes you have to understand what you can do and what you can’t do, which diet you can take, and the idea is sustainability. 

I want to be on a diet I like. I enjoy eating. I don’t want to force myself to eat something I don’t like. I can tell you, based on my own personal experiences, that if you look deep enough, you’ll find a lot of combinations of foods that are very appetizing, and they don’t have to be quite restrictive. It’s just a luxury. Can we have the time? Can we have the resources? Can we create an environment that allows us to enjoy what we eat?

depression diet, brain-healthy diet
“I think as we study more why some people get dementia and others [don’t], we’re learning that certain habits and patterns can be protective.”

Being Patient: Absolutely. To a certain extent, we’re all built differently, so it’s very complex. How I metabolize something may be completely different from how you do it. How closely is the way we metabolize linked to the benefits of food?

Yassine: It definitely [has] a role, and metabolism changes across race, ethnicity, and disease states— but I will tell you that it is not a major determinant. The major determinant is possibly access to food, socioeconomic status, and stress. 

You could take populations, identical populations— the classic example is E4 carriers in Nigeria. There have been studies where they followed these individuals who have one or two copies of ApoE4 and they migrated from Nigeria to a suburb in Indiana, and they looked at what percentage of these people got dementia. They found out that a lot more [of these people] got dementia on the Westernized diet in the US compared to the traditional diet in Africa. 

That also holds true for Japanese populations, Asian populations, and even Indian populations that stayed in India versus migrated to England. Long story short, genetics haven’t really changed in Nigerians who went to Indiana, Indians who traveled to England, and Japanese who traveled to the US. The metabolism possibly is similar, but what has changed is the exposure to fast food, a less active lifestyle, more processed foods, faster life, more stress, and those add up and take a toll on the brain. 

Being Patient: What do we need to know about sugar?

Yassine: I would say simple sugar is pretty bad; complex sugars not as bad.

Being Patient: Is white sugar simple sugar?

Yassine: [Yes], simple sugar. [Though] white sugar is not as bad as [simple] syrup. The more concentrated it is and the more consumed at higher concentration, and has rapid access to your liver, the more likely it’s going to induce different bad things. 

The more diluted it is, the more spread out within the fiber of your orange or complex with potato starch, the less damaging it is. So, this is not just labeling sugar; it’s the dynamics of sugar, sugar metabolism, absorption, and so forth.

Being Patient: Do certain food combinations offset the risk of other certain foods? For example, is it not as bad if you eat sugar with fiber?

Yassine: No. Let me give you an example. They follow tribes in Brazil and Bolivia. Colleagues of ours have looked at the diets. They’re not obese, they don’t have diabetes, they don’t have heart disease, they don’t have dementia. You think, “Oh, well, we’re eating a lot of good fat. They’re eating a lot of omega-3s.” That wasn’t the case. 90 percent of the diet or so was Yukon potatoes. This is starch. This is sugar. 

We have to be humble and recognize that if you can adapt to an environment where you walk an average of 17,000 steps per day, you can adapt and take complex sugars and burn them and convert them into something else. You don’t react the same way. If you took the same Shimane population, moved them to the US, stopped them from walking 17,000 steps a day and gave them Coke and simple sugars— you’ll see something completely different.

Being Patient: It’s so interesting because when I was wearing my glucose monitor, I ate a lot of pasta, but I ran every day, so pasta didn’t impact my metabolism. I never spiked when I ate pasta. Someone explained to me that it’s because I run all the time. When you run you’re burning off those carbohydrates. It’s worth the exercise to wear a glucose monitor because then you better understand how you metabolize food.

Yassine: Right. Exercising means that you are shuttling glucose to certain areas to break them down, as opposed to creating fat or triglycerides. So, it’s a completely different network or fate. When people are exercising versus people sitting and watching TV, the same diet can lead to different effects.

“When people are exercising versus
sitting and watching TV, the
same diet can lead to different effects.”

Being Patient: Where’s the research on diet and brain health? What do we need to find out next?

Yassine: In the world of nutrition and the brain, [there are] two kinds of research going. There’s personalized research, where you take a population like E4 carriers and give them customized recommendations based on their own dietary needs and brain consumption. There’s also large-scale population research, [which is] going toward resources and affordability and making tomatoes cheaper than, for example, burgers. 

We have to think [about] two things when we talk about nutrition and the brain. We have to look at the population level. What are the barriers [to] accessing real food? How can we make real food cheap? How can we make processed food expensive? This is regulatory to some extent. On the personalized level, if you knew that you have certain genes or risks, is there something you can do today to prevent dementia a decade later?

Being Patient: There’s so much mixed information about alcohol and the brain. What’s your take on it?

Yassine: I would say it depends on what kind of alcohol. Moderate consumption in the context of a good dietary pattern is okay, but excessive alcohol consumption in the context of a poor diet is bad. Again, I step away from individualized components of the diet and let’s look at the big picture. 

Katy Koop is a writer and theater artist based in Raleigh, NC.

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