The Melanie Avalon Biohacking Podcast Episode #188 - Dr. Marc Milstein

TRANSCRIPT

Melanie Avalon: Hi, everybody, welcome back to the show. I am so incredibly excited about the conversation that I'm about to have. It is about topics that I am very obsessed with, so aging, but in particular the brain and brain health. When I became aware well, when the representatives that reached out to me about our guest book today, which is The Age-Proof Brain: New Strategies to Improve Memory, Protect Immunity, and Fight Off Dementia, I was immediately hooked just based on the title alone and the credentials of our guest. It's written by Marc Milstein. I sat down and read the book and "Oh, my goodness." I mean, no pun intended. It was mind-blowing. I learned so many things.

What I really liked about it is not only did it dive really deep into the workings of the brain and how we think and learn and create memory and the reasons behind cognitive decline, but it really provides a comprehensive picture of all of the factors involved in brain health. It doesn't just focus on the brain, it goes into all of the factors. Immunity and the heart and our body and even our gut microbiome. I am just really, really excited about this conversation. I have so many questions. I have no idea where we're going to go because there's so much we could cover. But Dr. Milstein, thank you so much for being here.

Marc Milstein: Thank you. Thank you for having me. I'm excited to be here.

Melanie Avalon: I will let listeners know little bit about you. You got your Ph.D. in Biological Chemistry, and your bachelor of science in molecular, cellular and developmental biology from UCLA, my rival school. We talked about this before, I went to USC. You've been published in multiple scientific journals and the press as well USA Today, Huffington Post, Weight Watchers Magazine, all the things. But yes, so your book, The Age-Proof Brain came out in October 2022. So yeah, thank you so much for being here. For listeners, to introduce yourself your back story, have you always been interested in the brain? What led to the trajectory to where you are today with all of the work that you're doing surrounding that?

Marc Milstein: Yeah, yeah, definitely. I actually started out at UCLA in breast cancer research, and I was part of a group of researchers that were looking at a protein that was not only involved in cancer progression, but it was also involved in memory. At the time that was really interesting that something and one part of the body also played a role in learning and memory. It was really just around the time that our understanding of the brain was really growing and there's all these breakthroughs. It really was just very exciting to see how understanding how the brain worked was really giving us insights into how to, for example, sleep better or improve our memory. It also really informed my interest in how, as you mentioned, different parts of the body, our gut, and our metabolism all impacts our brain health. It's not just about doing crossword puzzles or just something that you think is just happening in your brain. That was really where I shifted my focus and started focusing more on the brain because it was just this really revolution or understanding of it. The more we're learning, the more we can actually break this down into things that we can do that can be really helpful.

Melanie Avalon: So, that protein, what was its function?

Marc Milstein: It was called RIN1 and it was involved essentially in cancer progression. It was a signaling protein that basically told the cell whether or not to grow or not grow. In learning a memory, the same protein was involved in sending signals through neurons that were helping with consolidation of memory. It's just really interesting how the body uses these same proteins for very different functions in different parts of the body.

Melanie Avalon: That's really interesting. Are there a lot of other proteins like that throughout the body doing other things?

Marc Milstein: Yeah, yeah, there is. It's really fascinating how the body has used different proteins, different molecules in one way in one part of the body versus other parts of the body.

Melanie Avalon: That's insulin-degrading enzyme. Could you talk a little bit about that? Because I find that so fascinating, especially since I also host the Intermittent Fasting Podcast, we talk about insulin all the time, so I think people will find this really interesting. It's role in the brain.

Marc Milstein: Yeah, essentially what happens is that the way I always like to think about it is it's like your desk, if your desk gets messy or your desk fills up with papers, it's usually because you're distracted or you have so much work to do that you're not basically cleaning it. In the brain, what we see is that the part of the Insulin degrading protein can play a role not only in helping insulin function, but it also plays a role in clearing away waste, garbage, and trash in the brain. If there're issues with insulin that takes precedence, it's more important in the moment for the brain to deal with that so that we don't essentially collapse. So, that there is not as much cleanup happening in the brain. The insulin-degrading protein essentially doesn't function as properly. What we realize is that that can lead to this build-up of waste. That's how we now realize that there're many things that build up this waste in the brain that can have a negative impact on brain functioning, on memory productivity focus. But one of those factors in this complex puzzle is metabolism and is diabetes. If we don't take care of those things that can lead to or play a role in this accumulation of this waste or trash in the brain.

Melanie Avalon: Have they done studies specifically on people and their insulin levels and their brain health?

Marc Milstein: Yeah, definitely. We see that individuals who have diabetes, for example, if they're not treated effectively, it's one of the biggest risk factors for Alzheimer's and dementia. It raises the risk by about 65%. But we also see that if the diabetes is treated effectively that risk factor goes down significantly. It really shows us that we have ways to protect the brain through treatments we already have. We just want to take advantage of them. We want to be on top of these other aspects of our health. But it doesn't mean it's the only thing that we have to do, but it's accumulation of these factors. One of those factors is really being on top of insulin, insulin resistance and even early stages of it. We now know that can raise the risk for issues with mood, depression. People with insulin resistance have a higher risk of developing things like depression. We realize that these things are connected to brain health.

Melanie Avalon: This is what you talk about on the book and you just talked about it right now, how there are so many factors involved. I think that makes it really complicated because we want to find one cause and one solution which would fit really well with our medical conventional paradigm. Actually, question about that, I should know more about this, I really should. What was the controversy recently with that Alzheimer's medication that was not real or not what it was supposed to be doing?

Marc Milstein: There were two controversies. There are two new medications, basically the goal of them is to remove waste. The positive side is that they seem to be doing this, they seem to be helping remove the waste, which is, as you mentioned, it's not the only factor, but it is a factor. The concern about it is that, is it only working in early stages and also the concern about it is that there're some serious side effects with it. It's a step forward in terms of our understanding, but we need a lot more research. There was also some controversy and the fact that it was approved on a conditional basis, so it's not fully approved. It's something that people can try if their physician feels like it's warranted in that specific case, but it is not by any means a magic pill or something that's just going to cure Alzheimer's at this point.

There was another controversy that is important to talk about, where there was some research from a while ago where there was some overstating about the impact of this. This trash, I referred to it as trash. But what we're talking about here are these plaques, the amyloid plaques that build up in the brain. And they definitely play a role in the progression of memory loss and dementia and Alzheimer's. But they're not the only factor. That's why, just as you said, it's not just simple. It's not that, "Oh if we just get rid of this trash, then we cure this disease." But it's a piece of the puzzle. It's not the only thing that's happening. It's multiple factors. It's metabolism as we talked about, it's inflammation, it's our immune system.

It's all these things that work together. Each individual with Alzheimer's doesn't necessarily have the same exact factors. It can be different factors in one person that are leading to the progression of disease and another person could be different factors too. That's what makes it complex. But in all this complexity, we do see that there's this hopeful insight that if we do certain things day to day, then we can lower our risk of memory loss by dealing with the things that age the brain.

Melanie Avalon: Diving deeper into this trash that you talk about, so with all of the-- and maybe we should also define the different types of dementia and cognitive decline. But is this trash, and I'm presuming this is beta-amyloid and tau, is it required to have cognitive decline? Can you have cognitive decline without it? And can you have it and not have cognitive decline? Like, what are the options?

Marc Milstein: Yeah, that's exactly what you're saying is an important point, is that there are people, and this is a big surprise in the research, that there are people who have lots of this. If you do a brain scan and you see that they have quite a bit of this waste or trash, which is either the beta-amyloid or the tau protein and those are the tangles that form inside the brain cells. The plaques are basically plaque formations that form in between the brain cells. You can see some individuals that have significant amounts of this trash inside and outside of their brain cells and you would say, "Oh, this person would have memory loss." And in some cases those people don't. What we believe is happening there is that it's not the only factor. It is a factor in some cases, it's not the only factor. I like to think of it like it's like a glass and each of these factors is like putting more water in the glass until it overflows.

But there're different ways to put water in the glass. That's why just removing the plaques and the waste is not going to be the only cure-all for Alzheimer's. It's a piece of the puzzle. But there are some cases where we believe other things are happening too, where the immune system is incorrectly attacking the brain. We believe there're cases where it's metabolism where the brain basically runs on its ability to utilize and use sugar and that response is not working correctly. And so, the brain is not able to signal properly or use energy. It's not one thing, but it's these multiple factors and it doesn't have to just be the waste or the trash. Some people have quite a bit of this, but there are other factors that are essentially working well and it's buffering and the brain is still functioning. That really gives us hope that because there're other things that we can do that it's not just reliant on the trash or the waste alone.

Melanie Avalon: Can you have a cognitive decline and no trash or is there always trash?

Marc Milstein: No, absolutely. There're many causes of dementia which we'll just say is dementia will define as memory loss to the point where it's interfering with the ability to get through the day. That can happen because of vascular issues, not enough blood supply to the brain, which would may or may not be related to this waste or this trash. Injuries can cause dementia or memory loss. There can be side effects to medications that can cause memory loss, deficiencies in nutrients, vitamins, all these things. That's why we don't want to just jump-- if somebody is showing any signs of memory loss, we don't want to just say, "Oh, it's definitely this specific thing." We always want to dig deeper and figure out what is the root cause, because actually about 18% to 20% of all cases of dementia are highly treatable. They're caused by things that are, as we mentioned, hormone imbalances, vitamin deficiency, side effects to medication. Really one of the important messages is that we don't want to just say, "Oh, there's nothing we can do," because in many cases there are things that can be done and that's why we want to get on top of these things early. It's hard to talk about these things sometimes, but that's why these conversations are important.

Melanie Avalon: Well, speaking of early, so to diagnose or see this trash, does that require open skull surgery?

Marc Milstein: No, no, there are brain scans available now. They can see this and also you can look at spinal fluid that can give an assessment of the amount of trash and there're all this really interesting ways on the horizon means to do this. So, for example, there's some excitement around blood tests that would be able to give a sense of build-up of some of this waste that's hopefully coming soon in clinical trials and there're some really positive results there. And there're even some studies where they look in the eyes. And they can see the build-up of some of this waste in parts of the eye that can correlate to the amount in the brain. That's really a key part of this, all of this is that we want to do everything we can do on one hand lower risk and that's really what the book is mostly about, is how do you lower risk? But also, as we move forward, how do we detect things early as possible? because when we can do that's when we believe we can make the most impact.

Melanie Avalon: One of the things you talk about is the three ways that you can take out this trash with learning, sleeping, or what's the third way?

Marc Milstein: Your immune system.

Melanie Avalon: Yeah. So how do those processes actually work?

Marc Milstein: Yeah, yeah, definitely. We want to think of it like the way I think about it is, your brain is like a factory, and it makes trash. Your brain is about 3 pounds and it makes 5 pounds of this trash a year. You have to get rid of it. You have to get rid of most of it. You don't want it. It's just like your house, your apartment, if it's filling up with too much of this stuff, it's hard to find things or focus. So, as you said, there're three key things that we can do to get this trash out. One of the most powerful things is all these really fascinating insights around sleep. When you go to bed at night, at certain parts of the night while you're sleeping, your brain-- think of it like a kind of sponge squeezing, it constricts, I know it sounds like a horror movie, but your brain is shrinking down while you're sleeping and it's squeezing out waste, trash, and toxins and because your brain is constricting during certain parts of the sleep cycle, it's squeezing this waste out into some empty space that's now available. And fluid then comes up from your spinal cord and washes this trash away. This is called the glymphatic system. It's a really new discovery and it's just amazing to think about.

We all know that sleep is important, but one of the top reasons why it's so important is it's when you wash your brain. It's when you wash out all this waste and these toxins. That's why we want to get enough of it. We want to prioritize it because it's something that we now know we can take a lot more control over. That's one thing is you want to wash your brain at night to wash out the trash and the waste, keep it clean.

The second thing is we see all these really interesting studies with super agers that these are people that live in their 80s, 90s, up to 100. They have the memory of someone, like decades younger and it's like, what's their secret? Well, they do several things that are important, but one thing is they keep learning new things. And again, not the only thing that's important. But we just want to leverage all the things that we know are important. This is on that list because when you learn something new, which is different than just rehashing information you already know, you're not only forcing your brain cells to make new connections, which is important because as we age, we lose some connections. But also, you actually are releasing something in your brain called norepinephrine. We believe that helps break up some of the trash formation in the brain. So, new, new, new, is important like, it doesn't matter what it is, but learn new things, new sports, new subjects, new languages. Just make it fun. You don't do all those things, but just pick something. I'm going to learn something new a couple of times a week. It's just really good for your brain.

The third thing is being aware that our immune system is really tied to our brain health. There's this basically, I like to think of it like, if you go to an aquarium, and you see that bottom feeder gobbling up the trapped waste at the bottom of the tank, you have something just like that in your brain. It's gobbling up waste and trash and garbage that forms naturally, and it keeps your brain clean. It's just like, imagine it gobbling up all the garbage. The problem is that the microglia can get confused, and instead of gobbling up the garbage, it starts attacking healthy brain cells. Not only does it not clean up the garbage, but when it attacks healthy brain cells, it basically destroys them and turns them into more waste and more garbage. That's why we want to really optimize and balance our immune system, because it's so tied to our brain health because we want to keep those microglia focused so they can gobble up the garbage for us and not make more garbage or miss garbage in the brain.

Melanie Avalon: Okay.

Marc Milstein: That was a lot. That was a lot. [laughs].

Melanie Avalon: So, it's great for listeners, learning new things, keeping our brain, so for the glymphatic system, I'm so fascinated because it was 2013, I think that they discovered it. That just seems so relatively recent to find something that was so huge. How do we miss it before?

Marc Milstein: Yeah, it's so amazing, if you think about how recent that is. We thought that we knew-- it's like a map. Like we thought we knew where everything was. If you think of a map of the United States, there's not some new city that's going to pop up. You're like, "Oh, we didn't know this was there." But it's in the brain. It's hard to visualize the brain. The technology and the ability to see these things has improved, and dramatically in the last 10 years, even five years. That's a key part of it, is just like, to see what's happening there on this very small level and really understand it. The other thing is that it was missed for several years. There were studies where people said, I think we see something like this happening, but we don't believe that there is a lymphatic system in the brain. From the neck down, we knew that the body is constantly, like, cleaning itself by using this lymph system, and we just thought it ended at the neck. That was the paradigm. That was the model.

And so, when people saw glimmers of this happening, they dismissed it. It wasn't until several studies started saying, "Wait, a second, there's something happening here." Plus, the technology of the ability to visualize it. Also, there were some subsequent studies that sort of all coalesced around the same time that gave us insight into not only where all the waste is going, there're these vacuoles like basically tunnels in the neck where we realized, "Well wait, a second, this is where the trash is exiting out of the brain." We see it clearly and it all makes sense and there's this new idea. Yeah, it's amazing that something that you would think is anatomical or physiological would be discovered so recently, but it's been such a breakthrough in our understanding.

Melanie Avalon: The actual trash that comes out, where does it go? Do we excrete it?

Marc Milstein: Yeah, it basically then works with the rest of your-- so you have all these lymph nodes and lymph system throughout your body, and so once it goes out of these vacuoles in the neck, it's processed there just like any other waste or toxins in your body and then it's excreted out.

Melanie Avalon: Is that system activated during naps or just during sleep, longer sleep?

Marc Milstein: Yeah. It depends on how long your nap is. You pretty much want to keep your naps short because if you go too long on your nap, you end up in deep sleep where you-- which is a phase of the sleep cycle where if you've ever woken up from a nap and you're like, I feel awful, I feel terrible, that's likely the nap went a little too long. The glymphatic system that washing is activated at the end of deep sleep. It's not really something we believe is happening during napping as we understand it. It's more something reserved for nighttime sleeping, but it doesn't mean a nap isn't great. There're other benefits for napping, but we don't believe the washing is happening in a short nap.

Melanie Avalon: Okay, got you. This is a super just random tangent question. My aunt had-- she was in a wreck like decades ago and she has a shunt in her brain and the doctors always say she shouldn't be alive based on the set up of her brain, but she doesn't have any fluid in her brain. Is that fluid related to this fluid? She says that there's literally no fluid. Her brain just rests physically in her head. It doesn't float. What is the role of that fluid around the brain?

Marc Milstein: No, I'm sorry to hear that. I'm sorry she went through that. The fluid in the brain in general is to-- and it's hard to know what exactly happened in that situation. In general, the cerebral spinal fluid is for washing, protecting, and it's a bit of a buffer system. It works with the blood-brain barrier. The brain is very protective about what gets in and out of the brain. It'd be hard for me to speculate on what's happening in her specific case, but that fluid helps, just a lot of protection, a lot of washing, and a lot of buffering.

Melanie Avalon: She has major problems sleeping because then her brain-- she needs to be constantly moving so that her brain will move around. Without the fluid, it just kind of sits. So, it's a really interesting situation. So back to cleaning the brain, you talked about how learning helps with that and the norepinephrine and everything. Does intelligence correlate to that at all?

Marc Milstein: That's an interesting question. There was a study that looked at, years of-- intelligence is so complicated and there're so many different types of intelligence. But one thing that was seen in some interesting studies was "Years of education can be helpful in terms of protecting the brain. But what they also found was that just keeping learning throughout your life, somebody doesn't have to have years of education that can be helpful, but they can kind of makeup for it if they just listen to podcasts, go to lectures, go to talks, learn new things. If they're engaged later in life that that can be really helpful too. It doesn't have to be just about, "Oh, in my early years I had this amount of schooling." It can be counterbalanced later in life and no matter how much schooling somebody had, thinking about continuing to learn new things throughout their life is important.

Melanie Avalon: You mentioned how with the glymphatic system and at night the brain is shrinking. You also talk in the book, "This was fascinating to me about how the size of our brain changes as we age, but not so much the number of brain cells, it's more the connections and everything in between." I'm really interested, can you talk more about that, the size of our brain and how it changes, and why?

Marc Milstein: Yeah, yeah, definitely. It's a bit shocking, but starting at the age of 40, the brain can start shrinking about 5% every 10 years. That shrinking can be devastating for memory, focus, and productivity because there can be damage done to the connections between the brain cells or just the brain cells themselves. But what we're seeing, and what is so hopeful is that by doing the things we've been talking about, optimizing sleep and taking care of your immune system and learning new things and some other things that we'll talk about, I'm sure as well that you can slow down this process. That's where it's really exciting to see that you take somebody and you have them to get a brain scan and not to say everyone needs to go out and get a brain scan, that's not necessary. The idea that we see in studies is that if people do these things, that part of how the brain ages as it shrinks and that process can be slowed down by lifestyle factors.

What's actually happening in the brain is that you have about 80 billion brain cells. As you mentioned, you're pretty much born with all of them, which people are surprised to find out, but what you're not born with is the connections between them. You have some connections for sure, but you don't have all of them. By the time you're an adult, you have 100 trillion connections in your brain. Those connections are how you think and how you feel and how you move and all your dreams and everything. As we get older, we can lose those connections. You make a connection pretty much by learning something. And that's where that synapse is formed. When you learn it, you make the connection. Interestingly just to kind of tie back to something, not to go on a tangent, but why sleep is so important?

Another reason besides that washing process is anything you learn during the day, you make the connection the moment you learn it between your brain cells or connections. But when you sleep at night, while you're dreaming, during the dreaming process, your brain finds every new connection you made that day, and it makes the connection stronger. That's why if you don't get a good night's sleep, you don't remember the things you learned as nearly as well the next day. That's why sleep is so important for memory. As we get older for many factors, we can be losing connections which can be negatively impacting our memory. Part of this is that not only just taking care of the health of our brain, but just by actually learning new things causes us to make new connections and learning new things can be everything from "I'm going to learn a language, I'm going to learn a musical instrument, I'm going to learn a sport." Or it can just be "I'm going to be more social; I'm going to hang out with my friends and meet new people" because that also is a key part of how our brain learns. A take home in all of this is that fun is actually really good for your brain too. That's good news because people always think, "Oh, you're taking all this stuff away," but really want to say that there's a lot of stuff that's additive and that you can embrace that's part of your daily life that's really good for your brain.

Melanie Avalon: That's fascinating. So, a nuance about learning. When we say learning, okay because you said at night it revisits everything that we learned, what is required to make something learning, is literally just taking information learning or is it something else?

Marc Milstein: Yeah, just taking information and making a new connection.

Melanie Avalon: Like a new thought?

Marc Milstein: Yeah, a new thought. So, like active learning. So, there's definitely passive learning and there's unconscious learning and all those things. The brain is so complicated, works on many levels, but when we're talking about this, we're saying, I'm going to pretty much focus on learning a new language. I'm going to learn some brain science or art history or whatever it is, whatever the subject is, it doesn't seem to really matter as long as it's new and interesting to you, or I'm going to read a book or play a musical instrument, all that stuff where you're like, I'm going to focus on it. I'm going to actually make a new connection in my brain. That's what we're talking about. At night, your brain finds those new connections and makes them stronger.

Melanie Avalon: Does that also include things that might not feel like learning, but it's a new environment? Like if you just go to a new store and you see a new store.

Marc Milstein: Yeah, yeah, so that's all newness is good. So, it doesn't have to be, I always say it's like, you don't have to go halfway around the world, that's good, but if you just want to pick a new street in your neighborhood to walk on, you might notice, like, when you do new things or even little new things, you tend to feel good. During the last couple of years our ability to do newness was subdued for obvious reasons. A piece of a very complex puzzle is that we actually saw people struggling. People would say, like, I can't remember what day is it. Everything feels like a blur. I feel like-- How much time has passed. It's because we were lacking some newness in our day, like, simple things just to counterbalance that is, like, try to cook a new meal, watch a new show, go for a place in your neighborhood that has a new walk or a different part of your town or city. All these things are really good newness. But that's why people who go, like, on a vacation or something, they're like, "I had all these new ideas," because it's very stimulating to the brain to have a new environment.

Melanie Avalon: But I'm really interested in the pruning process, so I was wondering if you could talk about that. And also, how does the brain decide what to prune? Like, who's making that call?

Marc Milstein: Right, right that's a good question. What you're talking about that's in the book is this idea that when you're born, as we said, you have pretty much all your brain cells, the 80 billion, but you don't have a lot of the connections. That's why babies can't do that much. They have trouble even, like, coordinating or moving or thinking, these are obvious statements. Then as the child grows up and they see new things and they hear new things and they experience new things, they keep making new connections. What's amazing is that there's a certain period of life up to around the age of, like, 7, 8, 9, 10, where we call it synaptic exuberance. And they're actually, like, over connect their brain. Their brain has more than 100 trillion connections, way, way more. What's happening there is that the brain is just learning so much to just think about. The world is so new, everything you see and smell and taste and experience.

During this process of pruning your brain decides, "Which of these connections now are we going to keep and which are we going to get rid of?" Part of that form aspects of your personality, what you're going to be like, things you're going to remember, and things you're going to forget. And it's kind of like a garden. If you let your garden grow and then you pull the weeds or pull things that you feel like, "Oh, I don't think that matches here." That's basically what's happening in your brain during this process. This pruning process, not to go off on another tangent, happens the rest of your life. Part of it happens while you're dreaming. Your brain goes, "Oh, you learned something new here, let's scan the brain and see if there's something we should get rid of that we don't need and that's we believe, is part of why our dreams are oftentimes not always, but a mix of things that, you just learned or just experienced and things you haven't thought about in a really long time. Dreams are very mysterious and we don't completely understand them, but that's part of what we believe is happening.

But going back to the pruning process is that your big question is we don't 100% know why we get rid of certain things. The brain prioritizes things that it believes are important. We know that when we make memories that are based upon our survival. Things that are funny, things that are emotional, the brain tends to tag them in a way where we go, this is important, like, keep this one and get rid of other things because things that are emotional are often tied. If you think of our ancestors, things that were scary, those are things that we had to remember for our survival. So, we know that's tied in there somehow. But beyond that, that's a big question, that we don't really understand is why does the brain say this stuff is important and this stuff isn't? But it seems to do a pretty good job of removing quite a bit of things and keeping things that are important. But things that are tied to motor skills and things that are essential, obviously, for the most part stay and things that we take in so much information, so much stimulation, that the brain has to filter a lot of it out and get rid of a lot of connections.

Melanie Avalon: I really want to know, is there "A nature versus nurture debate about pruning?" Like, do some people think it's more genetic what your personality becomes and some people think it's more environmental.

Marc Milstein: Yeah, I think that you're getting to the essence of some humongous questions, which are if you take twins and you raise them in different environments, so that their brains prune differently. It seems like there's aspects of that are genetic that you see in twin studies. There are certain things that even if they're raised apart, they're similar and they're things that seem to have a high environmental influence. Same for just certain diseases, certain underlying conditions seems to be the same. It's so complicated at this point and you're asking one of the most fascinating questions. But we don't really understand exactly how much of this is genetic or how much of it isn't. We see, like, talent definitely is something that seems to be preserved in the brain in generations in general, but in a very complex way. If somebody practices something that's related to their talent in a sport or a musical instrument or anything like that, it seems the brain prioritizes that and builds upon it and those connections are made more readily and more easily. And that's a mix of genetics being in the right environment. But beyond that, there's a lot we have to learn there.

Melanie Avalon: Like, if a parent is raising their child because you spoke about how emotion really affects it and then I imagine repetition also affects it, does that mean when you're raising your kid that-- if you're making experiences really emotional, it's going to affect more how that child turns out in the end? Or on the flipside, like repetition, the things that you do more? I'm just really interested by the power that the parent has over affecting the child's future personality.

Marc Milstein: Yeah, that's huge and something we need to talk about. And it's child development. The brain is-- What you're getting at is that and what you're speaking about is that there's this time in our life where the brain is going through a lot of developmental-- Basically it's like your home or your apartment under construction and how well it's constructed in those times can make a difference in terms of raising the risk for anxiety, depression, other issues. Because essentially the brain is developing itself in a way where it is responding to the environment. An environment where somebody is supported, they feel like they can flourish, they're being listened to. All these things impact how the brain develops.

If somebody's in a threatening environment or a traumatic environment, the brain develops in a way where it's often more likely to have like a fight or flight response in moments where it could cause the brain to essentially panic. That's understandable because that individual was raised in an environment where they needed to survive, they needed to flee, they needed to protect themselves. That can carry over later in life. The take homes from all of this are that we want to make sure that the environments for children are healthy, stable as best we can. We want to prioritize this at home and school and everywhere that we can. This is an important piece of brain development and impact the rest of one's life.

The flipside to it is that the brain, although a lot of the development takes place early on, the brain is malleable. It can change, it can adjust, it can heal. Of course, we never want these things to happen, but things do happen in life that are traumatic and that are difficult, and that's just some of those things are very much out of our control. But we see that the brain can heal. For example, if we go back to this idea of making connections, if somebody experiences something traumatic, that connection because it's emotional, sometimes the brain will make that connection stick. We see that, for example, in a very simple version of PTSD, is that connection just keeps being revisited and revisited and revisited. Things we're talking about are highly complicated and we're distilling them down to things that we just don't want to make major assumptions, but we're just saying that this is a part of how the brain works in these processes, and that if those connections are made, what's very hopeful about how the brain works is that later in life those connections can be readjusted. That's why therapy really works, is that you're working with somebody who can take those connections, break them apart, and reconnect them in a way that is more positive, that is more able to have perspective, or more able to move on.

So. the brain isn't really good in accuracy of memory, but it is much better at adapting. And that's what's amazing about our brain is that we don't really remember things that accurately, because our brain is constantly changing and evolving every time we remember something. And that's why, in a very simple way, you might talk to somebody, remember that party we went to 10 years ago when were kids, and you have two totally different versions, because every time you revisit a memory, you actually break those connections apart and put them back together, which actually gives us hope-- in therapy we can take connections and rebuild them in a more positive way. It's a big, big topic, but it's important. I think the take home to say is that we just want to take care of our brain in early stages and then throughout our life.

Melanie Avalon: I love it. This actually haunts me. Every time I have an experience that's a story worth telling, I get a little stressed about it because I know that the first time I retell it to somebody, I'm crystallizing the way I remember it at least that time. Every time I retell it, I'm further crystallizing my version of it. It's like I'm getting farther and farther away from probably what actually happened.

Marc Milstein: That's normal though, that's very very normal, that's how our brain works. Every experience that we've had in between the times that we tell the story, it can inform how we retell it. We really believe that the latest version is what happened and that's why eyewitness testimony and all these things are actually not that accurate because every time somebody retells a story, it very likely has drifted.

Melanie Avalon: The APOE4 gene, why is that connected to cognitive decline? Like, what is it actually doing?

Marc Milstein: Yeah, that's a really good question. So, part of this we understand and part of it we're still understanding. But what's happening with this gene is that, there're a couple of things that are happening is that there is a relationship with this gene into how much trash is formed in the brain. Basically, when certain parts of the brain, certain fragments are recycled, they're recycled in a manner where they're chopped up and they are reused. What can happen with this gene is it causes more chopping, more breaking up, and less recycling. So, there's this accumulation of this waste. But that's not the only thing that we believe this gene is involved in. Just like we talked about actually bringing it back to RIN1 what we talked about in the very beginning that this gene can be involved in breast cancer and involved in learning and memory. We believe the same is involved in APOE and the different versions of it.

We believe it's involved with recycling of aspects of fragments in the brain that are broken down and then reused. It's not as efficient in certain cases. We also believe this gene plays a role in metabolism in the brain. If that's not functioning properly, then that can have a negative impact on how brain cells communicate. It's like they're not using the fuel properly. Other aspects of this is that we still are learning about how APOE works. We also believe it plays a role possibly with cholesterol as well and how cholesterol is utilized in the brain, which cholesterol is actually important, it's a signaling molecule in the brain, but it might go awry with certain variations of this gene. Not just one thing is the take home, but it has multiple factors. We seem to be learning more and more about how it can have different relationships to multiple parts of our health.

Melanie Avalon: Do we know why it developed? Because I would assume that it had a purpose. Was it based on the diet of the people at the time, or the environment, or what was its purpose?

Marc Milstein: Yeah, that's such a good point. There is this interesting research that in different environments that these genes might have had different functions. That now that we are in a world where we have certain lifestyle factors that might compound a negative impact of a gene that might not have been as impactful in other environments. That's a big area of future research in trying to understand this, but we don't clearly understand, you know sometimes mutations are protective in ways that we eventually understand, and sometimes they're just mutations that are there and they're inherited in a way that we want to try to diminish their negative impact.

Melanie Avalon: How does it affect the risk for cognitive decline if people have it?

Marc Milstein: Yeah, so it's not determinant. It raises the risk. It's a significant increase. The key point is that this is something people can test for. It's something you'd want to talk about with a physician or a genetic counselor because some people take this information or people take this information in different ways. Some people say, I want to know, and if I know I have this gene that it raises my risk, then I'm going to really double down on all these lifestyle factors. I'm going to be on top of everything I can to be on the latest research and early detection. I'm going to work with a neurologist. Some people say, well, this information is not determinant. I'm going to just try to live a healthy life and knowing this information if I have it or don't have it is actually going to stress me out and worry me. And that's not good for your brain health if you're constantly, chronically stressed out and worried. It really is at this point an individualized decision about whether or not knowing that information is appropriate for the person. But being aware that it's not determinate, it does raise the risk, it doesn't mean its destiny, but it can be very helpful for some people to know, and for other people, they might just want to focus on all the healthy things they can do. That's a complicated conversation for somebody really trying to sit down and think about what information is of benefit to them as an individual.

Melanie Avalon: Well, and either way, that's why I just think it's so valuable, the work you're doing, because reading your book provides so much power for people to do the things to support their brain health. So, thank you for that. So, memory, I loved the memory section of your book. Okay, first of all, it blew my mind. You said, okay, our memory capacity is 2.5 petabytes, which is the equivalent of 300 million hours of TV daily?

Marc Milstein: No, that would be the amount, that's the storage capacity, which is like--

Melanie Avalon: Oh, storage capacity? Okay. I mean, that's crazy. Okay, so memory formation, how does it actually happen? I love the whole concept of the waiting room and the 7 seconds and what's important. Could you tell listeners about how we actually form memory? This is just fascinating to me.

Marc Milstein: Oh, sure, sure yeah, definitely. This idea that we have essentially almost unlimited memory capacity. There're always these things like, "Oh, you're only using 10% of your brain." Really, we want to think about it this way. You can remember a lot, a lot, a lot of information, but your brain doesn't want you to. That's the thing is your brain wants to forget. It doesn't want to fill up with useless information. It doesn't want anything that's not important. Your brain is constantly filtering things out. Part of this is that there's just so much happening in the world. There's just like even right now in the moment that we're talking, there's what's happening outside through the window, there's how the floor feels and all these things. Your brain is trying to shut all that stuff out so that you can just focus on what's important. Sometimes that's working and sometimes it's like you're just so distracted.

But the idea is that anything new that you're learning or seeing or experiencing has to go through certain stages in the brain. It's not like your brain is a video camera and it's just recording everything you're seeing. You're like, "Oh, I want to pull up that video file and play it back." Instead, what's happening is that the information goes first essentially to a part of your brain called the hippocampus and this part of the brain is the waiting room, and the information waits there, so anything you see or you experience goes there and it waits. The rest of your brain decides is this information worth it? Or is this a complete waste of my time? Because again, your brain doesn't want to fill up with useless stuff. If it's important, it leaves this waiting room and it's transferred on to other parts of the brain we're actually going to remember it.

If it's not worth it, your brain basically disposes of it. It just doesn't prioritize it. We live in a world where you might be saying, "Where did I put my keys? Or where did I park my car? What was I just doing?" A lot of this relates to the fact that we're so either multitasking or we're just onto the next, onto the next, on the next, you don't spend 2 seconds remembering where you put your keys or parked your car, you're onto the next, because we realized that part of what helps our brain determine if something is worth remembering is if you're focusing on it for about 7 to 10 seconds. In that time, while the information is in the hippocampus and it's waiting there, if you're focusing on it and you don't have distractions, your brain goes, "Oh, this information is worth it. It's important and it transfers it onto other parts of the brain instead of just throwing it away. In all this complexity, something that's remarkably simple and effective is the next time you want to learn something, just say to yourself, "I'm just going to focus on this and nothing but this for about 7 to 10 seconds. People are surprised how much more they remember because we're so often just onto the next that we're just wondering why we're forgetting so much. Or we're on two, three screens at the same time texting while we're talking, and we're like why are we not remembering this stuff? Well, your brain figures this is all probably not that important because I'm not focusing on it.

Melanie Avalon: My aunt with a brain issue, she has a lot of trouble creating. Okay, well, actually before I say that, so when the information comes in and then it decides that it's important and you keep it, is that moving it to short-term memory?

Marc Milstein: Yeah. We actually call short-term memory day to day life. People say, "Oh, what did I have for lunch? Or who's that person I met a few hours ago?" In brain science, we pretty much think of short-term memory as like these 7 to 10 seconds and then once it's passed on, should we say that's long-term memory? Yeah. It's different than how we usually think about it, but once it's past this threshold or this filtering step, we're pretty much saying this is long-term memory now.

Melanie Avalon: And what is working memory?

Marc Milstein: Working memory is like you can think of it like scratchpad memory, where let's say you're doing math. That's a really good example of it. You have to remember in your head what the last step was so you can solve the next step. It's the ability to just kind of hold multiple pieces of information in your brain while you're working through a problem. It's also like in music, you have to be able to quickly reach back and remember something because you're in the process of problem solving or navigating somewhere and you're like working with the memory.

Melanie Avalon: Got you. Okay, so she must have issues forming long-term memory. So, what she has to do and now this all makes sense, talking to you and learning this. She told me when she learns something, she has to write it down and she has to focus on it for a certain amount of time.

Marc Milstein: Yeah. That's helpful for a lot of people, is that writing it down not only forces you to spend some time with it, it's also a motor skill. A motor skill actually bypasses the hippocampus and that's why riding a bike is something that people pretty much don't forget, is because anything motor is like it's like a shortcut to memory for the brain. It doesn't need to be filtered as much. So, if you are writing something down and you're tapping into some aspects of motor memory, which can help you remember better. It also is taking a little bit extra time, which also helps in this dual benefit of helping with getting past the hippocampus.

Melanie Avalon: Is it true, they say that you never actually-- well, it doesn't make sense. They say that you never lose any of your memories, is that true? once they're in long-term memory?

Marc Milstein: Yeah, that's a really good question. We don't really know. We think that they're always there, but they are unless there's some damage done to the brain in an accident or a traumatic injury. This idea that if you think of the brain cells and you think of when you remember something, there's basically that connection there. What happens is that that connection essentially moves apart a bit and that's how you forget or you get rusty at something and then when you practice, you move the connection closer together. It's interesting, there is this idea that possibly the connection is always there, but it just moves apart until you reprioritize it again. But in terms of significant memory loss or damage to the brain due to an underlying condition or disease, that connection might or those brain cells might be damaged. In other situations of just remembering things, it is possible and there is a theory that you just never really forget it, you just kind of move the connection farther apart.

Melanie Avalon: Yeah, I guess like an analogy would be if memories is like stuffing stuff in your closet, it's the stuff always in there somewhere.

Marc Milstein: What's interesting is like music, for example. You say, "Oh, I've never-- Or smell that's an example where you will smell something and it's like all of a sudden it ignites or connects up in your brain these things you haven't thought about in a really long time or a like song, and all of a sudden all these memories flood back. It's this idea like those connections are-- I like the way you could say that it's in the closet, but it wasn't quite connected and then once you kind of tap into that, it's like, "Oh, this is all this stuff is still here.

Melanie Avalon: Yeah. They also often say that scent is the strongest sense connected to memory. A is that true? and B if so, is that just because of the proximity of the olfactory nerve too? Is it a physical thing?

Marc Milstein: It's several things. It depends upon the person. So, some people are really-- their memory is really strong, like auditory. Some people are really strong visually. Some people are really strong with smell or touch, it really depends. But scent, is really, really strong, visual is really strong too. It's a mix of what you're saying is that the proximity of-- we don't tend to think about it, but you brought it up is that your brain is really at the top of your nose. And so that's part of what's happening and also that smell is so important for survival that it's just highly prioritized. If you think about how our ancestors would get hurt, yeah, obviously you have to hear things, you have to see things, but smelling your food or smelling a predator, all these things are critically important to know if things are spoiled or poisoned or things like that.

Melanie Avalon: I'm so interested by it, because I feel like people don't really or maybe I'm just not the type that smell and scent is the main thing for me. I personally don't think about smells that much, but if I smell something then it's like bam. You get hit with a memory. I just find that really interesting. I don't easily remember a scent. Like if you tell me to remember a scent, it's hard for me to conjure that in my brain. If I smell something I immediately get hit. So, I just find that really interesting.

Marc Milstein: Yeah, yeah, that is interesting. Yeah.

Melanie Avalon: And I was excited you mentioned something. I was wondering if you're going to mention it. The thing that happens where you have a task to do and then you walk into another room and then you forget, and you walk back into the room and you remember what's going on there.

Marc Milstein: Yeah, it's similar to this idea that the distraction of the new environment causes that information that was very likely in the hippocampus to just sort of be ignored for that moment and thrown away. That's why people say, "Oh, retrace your steps, that can be helpful. But something that is like a dramatic shift in what you're seeing changes your focus and your brain just doesn't hold on to that information that you were thinking about what you needed to do. A very common one is the refrigerator. You go to the refrigerator, you open the door like why am I standing here? Why did I walk in this room? Just kind of saying, well, what happened in the last 10 seconds? Did I get a phone call, a text? Did I check Instagram? Was there any sort of distraction? Because that distraction is what is often keeping us from remembering what we just had to do. It's really helpful for people because people start to worry and they say, "Oh no, I'm starting to noticing that I'm starting to forget things. Of course, we don't want to ignore that. That's a key point of everything we're talking about is we don't want to just say, "Oh, it's nothing." But one of the first things to be aware of just says like wait, am I being distracted? Am I multitasking? Nothing wrong with multitasking. But in the moments we want to remember things and learn things, it's important to say, wait, let me just focus on this one thing. People are often surprised how that can be very helpful.

Melanie Avalon: It sounds like, so say you're in a room and you want to do something in another room and so you're thinking about it for 7 seconds and then you go into the new room or I guess maybe you didn't think about it for 7 seconds, you didn't think about it long enough to remember it. You go into the new room and you forget. And so, then you go back and then you remember but it sounds like, you're not really remembering if you didn't keep it. Are you just re-exposing yourself to the stimuli that made you think of doing the action in the first place?

Marc Milstein: Yeah, that is actually what you're saying is what we believe is happening is that you're putting yourself back in the position where you're going to reignite that thought or you're jogging your memory. Our memories are all connected. In those hundred trillion connections, there're a lot of intertanglement and that's why one thought leads to the next. In this idea of like if you notice this is happening and you're going from one room to the next, just be like, "Okay, I know I'm walking to the next room. I'm going to just really focus on this thing I have to do and not be on my phone or distracted and just focus on this. People are often surprised that they stay remembering what they need to remember.

Melanie Avalon: Another thing, so talking about like scent and you also mentioned our other senses. You talk about the connection between people losing their eyesight or their hearing and how that affects their dementia risk. What's happening there? Does that relate to-- Why does that increase dementia risk?

Marc Milstein: Yeah, that's so important and that's something that is not being talked about enough is that these aspects of our senses like hearing and sight and hearing is the one we actually know quite a bit about is that even mild hearing loss can double the risk of memory loss or dementia risk. If it's like moderate, it triples the risk. If it's severe hearing loss, it's like five times the risk of losing memory or developing dementia. We believe what's happening. Before I go any further, I should say that it's important to note that in most of these cases if you just treat the hearing loss with something like a hearing aid, these risk factors go down significantly. So, it's highly treatable in many cases. But what we believe is happening is that if we're not hearing, we're not learning, we're not engaged. That goes back to the idea of one of the most important things for our brain is to learn new things. If you think about when people are being social, oftentimes when they can't hear they feel isolated. They might not be listening to conversations or absorbing the information. That's why we want to get the word out that if you're noticing-- get your hearing checked and if you're noticing any subtle signs, get on top of it right away. We want to keep those nerves stimulated and we stimulate them by using them and it's all these things are use it or lose it. Another example you brought up, which is important too, which is sight. people who get cataract surgery when they need it, they lower their risk of dementia 10 years later for the next 10 years. We just want to be doing everything we can to leverage all the miracles of modern medicine, the things that we know work that can be helpful in keeping our brain active and engaged.

Melanie Avalon: For people who are born blind or deaf, I would guess there's not that connection.

Marc Milstein: Yeah, yeah. We don't see that in those cases. We believe that's because there're other senses that are being utilized and that's an important distinction.

Melanie Avalon: That's so interesting. It's like if you get hearing loss later in life or losing your sight, if you could have always been that way, you would be okay, but because you knew what you were before in a way, or not knew what you were before. It's just interesting that you have to have something to lose it for it to have the negative effect.

Marc Milstein: Yes, it's the loss of the engagement. If an individual who is born deaf or blind, if they lose engagement through the other sense that they're using, that would be then something to be rectifying or concerning.

Melanie Avalon: Speaking of learning. So, you talk about-- and for listeners, you're just going to have to get the book because there's so much information and we're only barely touching on it. You talk about ways to learn and also ways to innovate which is really, really interesting. Is it the pomodoro method?

Marc Milstein: Yeah, yeah, so that's an older method, but it's still very helpful. It's really just the idea that we tend to multitask. Again, that can be okay sometimes during the day, but in those moments that you really want information to stick, just setting aside like a few minutes, even setting a timer. This method is usually setting a timer, eliminating all distraction, and just saying, I'm going to just do this task that I need to do for 20 to 25 minutes and then I'm going to take a quick break. There's no hard and fast rule that you have to like it has to be this exact amount of time with this break, but somewhere in the range of 20 to 30 minutes and then a few-minute break. People can work up to that. They can find what's comfortable for them. But the key take home in all of this is that there can be this feeling like we're answering emails and texts and bouncing between sports scores and travel sites and the weather and our work and then you get to a point in the day and you're like, did I get done as much as I wanted to get done? Or I just felt like I was on that hamster wheel all day long.

There're these really fascinating studies that were done where they looked at people who were basically like real innovators in their field and they looked at like directors and musicians and scientists and business people. didn't matter what they did and they're like, let's follow them around for a couple of weeks and just see what they do. The scientists who did this was actually several studies, but they were like, it's going to be different for everybody. They found that pretty consistently, people who were high achieving in their field didn't matter what field they were in. They followed this pattern where they spent some time during the day doing what we just talked about they're like, I'm going to eliminate all distractions. I'm going to just focus on what I have to get done my work, and then I'm going to take a break. It's like, "That sounds kind of obvious," but if we assess sometimes our day, it's like, "Wow, how much of the day am I actually taking for total focus and total relaxation?"

They found that some of their best ideas happened in the relaxation moments where they weren't like, "I'm going to answer a work email while I take my walk." It's like, "No, they went for a swim or they took a walk." Their brain played with all the information that they were focused on earlier. It's not like the breakthrough thought or the innovative idea happened while they were, like, really working hard. It's like, it planted the seed and allowed it to bloom in the moments that they were just doing something more fun or mindless. That just thinking about, "Oh, in my day, I just want to have those moments of pure focus, pure break, and a couple of cycles of that. It doesn't have to be all day every day, but that's just something interesting that's been found in this kind of this pattern that seems to be really helpful.

Melanie Avalon: Is that a reason that historically and then probably especially now, because we're so distracted by our phones, and this is one of the only time you cannot be on your phone when you're in the shower? Like having a shower insight?

Marc Milstein: Yeah, yeah that's part of it. The example I use in the book is also Billy Joel was talking to Don Henley. They're like, "When you come up with your best song ideas?" And they're like, "When we're washing dishes." They both said the same thing. It's probably you can't look at your phone, you shouldn't be looking at your phone when you're washing dishes. It's like this mindless activity, shower's the same thing, it's like you're just relaxing and you're not distracted. You're letting your brain play with information. And that's what we want to do. We just want to let the brain-- The brain can really figure things out. You might wake up in the morning and you're like, "Ah, I have this new idea." My brain played with the information while I was asleep or we go back to the idea of getting out of your environment a little bit and you go for like a vacation or even just a new area of your town, a new street and you're like, "I'm having all kind of these new ideas because we just break out of, it's kind of a repetition that we tend to fall into, that's easy to fall into.

Melanie Avalon: One last topic I'd love to just briefly touch on and I will refer listeners to your book to learn more. Historically on this show, I've had people in two camps for Alzheimer's specifically and diet. I had the Sherzais at Loma Linda who run the Alzheimer's-- I'm not sure the department there at Loma Linda, they propose a very heavily plant-based diet for brain health. And then I've had Max Lugavere, who is very much on the other side of things as far as the importance of animal products. Where do you fall on the spectrum when it comes to diet and brain health? I know that's a huge question and we're running out of time, just briefly.

Marc Milstein: Yeah, now, that's a good question. I think there's room for both. What I would say is that the diet that we see a lot of evidence for is something in the world of Mediterranean like diet. There's the MIND Diet that is kind of like a Mediterranean diet mixed with a heart-healthy DASH diet. It focuses on a lot of fruits, a lot of vegetables, I should say more vegetables than fruits but includes fruits because blueberries is a fruit, some other fruits too, but it includes nuts, beans, there's lean meat, there's fish that sort of diet we just have a lot of evidence that it's beneficial. Purely vegetarian diets and plant-based diets can be really good too. I think there is a concern that if somebody is on a vegetarian diet, just to make sure that they're getting adequate B12 and choline, which are important for the brain and specifically choline is often found in more meat products.

I think if we look at all the data, its diet is individualized and there's room for some versions of these diets that people find. This one diet is not the cure, it's not the perfect diet for everybody, but we tend to see that in all this complexity for diet, there's some pretty simple takeaway rules that apply and one is minimizing the processed food. I was just actually reading a study this morning that was really interesting that they found that if people had 20% of their diet had processed food in it, they had about a 30% increased risk of developing dementia or memory loss. The average American is having 56% of their diet processed food. And so, really just something that's really simple, whatever diet you find works for you make a part of it to minimize the processed foods. It doesn't have to be completely eliminated because they actually found in the same study that there is room for an indulgence here or there.

People who had most of their diet-- most of their diet was minimally processed, fruits, vegetables, lean meats. If that works for the person, fiber, then the impact of a small amount of these ultra-processed ingredients didn't seem to have much of an impact. But when it's in the 20% region or more of the diet, then we're getting concerned. I think that things that are too restrictive are hard to follow for people. That's why Mediterranean-like diets are more easy, they're more lifestyle based. There's a lot of good, tasty, healthy food there. But again, within these parameters of-- look at your plate, try to have a handful of colorful fruits and vegetables. Not to just throw up study after study, but another study that came out a few weeks ago is that just think about like, broccoli, spinach, kale, beans, tomatoes, tea, you might not love all of them, but some aspect of those things in your diet.

The study found that people who have those things in their diet lower the risk of memory loss or dementia by about 30%. So, there's these flavonols, we believe they're very protective to the brain so, minimizing processed foods, adding these brain-healthy foods on the plate most meals is a really good first step and then beyond there, I think there's room for people to say, the Max diet, the Max Lugavere diet is something that really works for me or the Loma Linda diet is something that really works for me. I think there's room for these different avenues.

Melanie Avalon: How about the recommendation in the MIND diet to have one glass of red wine per day?

Marc Milstein: Yeah. I always like. I do a lot of speaking and the only time I've ever gotten a standing ovation was when I said that. Alcohol is one of the most controversial aspects of brain health. You look study after study just conflicts. I think that if the MIND diet it's included in a moderate amount, there's evidence that wine has some anti-inflammatory benefits, antioxidants, it can have some relaxing benefits. But the only caveat is that I'll take one step back. This is what we know, past moderate alcohol intake, there's a lot of evidence that's not good for the brain. We're not at the point where we would say people need to start drinking for their brain health. That's not what we're saying. But we would say that moderate alcohol, there's evidence in the MIND diet that it can be a benefit.

But there are people who have underlying conditions or genetics that make alcohol not a good choice for them and they should, once or twice a year, just bring it up to your doctor and just say, based on everything you know about me, is there any reason why I just want to be more careful, I want to be aware of anything that's going on with me individually. But I think that there's this evidence it can be a benefit in moderation and then taking that one step to make it individualized.

Melanie Avalon: I think you said that the APOE4 gene made it. There were not the benefits associated?

Marc Milstein: Yeah. So that's what we see. If you have certain underlying genetics or let's say you have a condition where alcohol might exacerbate that condition, and then that condition also impacts your brain health, then you want to say, "Okay, let me just think about what is the right amount for that individual and taking it to the point and also saying, we always want to look at the-- it's not one factor, it's all these factors together and thinking about how do we leverage sleep and diet and exercise and eating and all these things together to say, "What is the right formula for a person?"

It's not that everybody has to be on this strict, strict plan, but saying like, "Okay, which of these things are things that I can do easily and simply in a way that I can optimize my life and feel my best?" That's a really big measure of this is how are you feeling day to day and keeping it simple and saying, "What are these things that I can do that can have a big impact?"

Melanie Avalon: I mean, that's a perfect way to end because that really sums up what you're doing with this book, which is showing all the things people can do to best support their brain health. And I just find it so, so valuable. And one of the things you talk about is the importance of mindset and positivity and happiness and how that affects things and gratitude and loving, compassion, and meditation. So, the last question I ask every single guest on this show actually relates to that and it is what is something that you're grateful for?

Marc Milstein: So, I'm grateful for so much. I'm grateful that you took the time to talk to me. I'm very grateful for that. I'm grateful for my family, health is something I've had some issues in the past, and that's what inspired me to really get into this field. Every day I am so grateful for my health. I would say that those are the top things. It's just my health, my family, and being able to be in an environment where we can try to do our best each day.

Melanie Avalon: Well, I love that so much. I am so grateful for the work that you're doing. It's really, really incredible. All listeners. get The Age-Proof Brain. If any of this even remotely interested you, there's so much more information in there. So, thank you so much for what you're doing. Are you writing any future books?

Marc Milstein: I hope so, I hope so. Yeah, I think hopefully, hopefully down the road, yeah.

Melanie Avalon: Awesome. Well, hopefully, you can come back in the future. How can people best follow your work?

Marc Milstein: Oh, thanks. Either my website, drmarcmilstein.com. I'm starting to do more things on Instagram too @drmarkmilstein.com. On my website, there's a sign-up if you want to get a once every few weeks newsletter with tips. I always like to give take-home tips. I like to say little things that make a big difference based upon the research that's there for you too.

Melanie Avalon: Awesome. Well, we will put links to all of that in the show notes. Also, I'll have to send you my supplement serrapeptase. Have you heard of that?

Marc Milstein: I'm not that familiar with that, no.

Melanie Avalon: Okay, I'll send it to you. It's my supplement and it's been shown to break down amyloid plaque at least, I think, in vitro studies. Awesome. Well, thank you so much for your time. I so appreciate this and I really, really do. And enjoy the rest of your day.

Marc Milstein: Thank you. Thanks for having me.

Melanie Avalon: Thanks.

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