Hey everyone, welcome to the drive podcast. I'm your host, Peter Atia. This podcast, my website, and my weekly newsletter all focus on the goal of translating the science of longevity into something accessible for everyone. My goal is to provide the best content in health and wellness, full stop, and we've assembled a great team of analysts to make this happen.
If you enjoyed this podcast, we created a membership program that brings you far more in-depth content. If you wanna take your knowledge of the space to the next level. At the end of this episode, I'll explain what those benefits are. Or if you wanna learn more now, head over to PeterAtiaMD.com forward slash subscribe.
Now, without further delay, here's today's episode. My guests this week are Lauren Miller Rogan with Richard and Isaacson. Lauren is an actress, screenwriter, director, but also a friend and patient. She's the co-founder of hilarity for charity or HFC, a national nonprofit organization whose mission is to care for the families facing disease of Alzheimer's disease, educate them about living a healthy brain life and activate the next generation of Alzheimer's advocates.
Richard Isaacson should be a familiar name for some of you as he was a guest on a previous episode of the drive in late 2018 when we did a deep dive into Alzheimer's disease. Many of you have requested followup podcasts on this topic among them, this is one. Richard serves as the director of the Alzheimer's Prevention Clinic at Wile Cornell, New York Presbyterian Hospital and is a assistant dean at the office of the faculty of Wile Cornell of Medicine. I've known Lauren for a couple of years.
We actually met through Richard and the three of us been talking about doing this podcast for about a year. Like we were gonna do it last fall and then we put it off until the spring and then COVID got in the way. So this one's been a long time coming. My intuition was that being able to talk about Alzheimer's disease with Richard and Lauren simultaneously would be a beautiful way to discuss the human tragedy of the disease and also to talk about the science of prevention and the pathology of the disease.
And honestly, by the end of this discussion, I felt we had really achieved that. I think Lauren's story is both heartbreaking and uplifting for reasons that will become clear as you listen to this. In this episode, we talk about her journey with her family history, what led her to Richard and ultimately what really changed the course of her life with respect to how she treats prevention. We talk a lot about what preventative measures look like today and how we look at the evolving body of literature to figure out how to modify risk.
So if you have even a slight interest in the prevention of Alzheimer's disease, I think you're gonna find this episode both touching and enlightening. So without further delay, please enjoy my conversation with Lauren Miller-Rogan and Richard I and me. Lauren and Richard, what a privilege to be sort of sitting down with you guys right now. We have been kicking around the idea of doing this for about a year now.
COVID kind of got in our way. We were gonna do this obviously in person last year. So while it's long overdue, I think this is just such an exciting opportunity both to kind of hear from you, Lauren, and kind of understand your personal journey, which you've basically taken on as your life's mission. And then obviously Richard to have you back on and kind of, I don't know, I think bring people up to speed on what's happened in the last couple of years.
So thanks both of you for making time today. Thank you for having us. You might feel like long time listener, first time guest. Very excited to be here.
Long time listener as well. Yeah, I hang on every word of most of the podcast, especially while I had to listen to Tom Days brings podcast like 14 times, I'm still like need to listen to it on repeat. But Lauren, let's start with you. I mean, I want people to really get an understanding of your story.
So I mean, when did you first become aware that there was something going on in your family that was robbing people of this precious thing called their mind? Unfortunately, Alzheimer's has been a part of my life as long as I can have my own memory. My grandfather, my mom's dad had Alzheimer's. My aunt just told me that seems like he showed symptoms maybe in his late 50s or early 60s.
But he was an interesting home, I think from the time I was around eight or nine, maybe 10. And he passed away when I was 12. But when you're young, that age to me, his memory issues were almost funny, right? Like he would take his teeth out at the table and I thought that was hysterical.
And he would, you know, repeat things. And again, like when you're little, that's funny. And I didn't have any concept of the fact that the reason he had to go into an nursing home is because he was wandering and that my grandmother couldn't take care of him. And then after he passed away, my grandmother started showing signs of dementia.
And she was struggling to take care of herself and what clearly wasn't eating. But I was in high school. So again, I wasn't really that aware of the situation and what was happening. But I was aware when they brought her from her home in South Florida up to where we were in Central Florida to put her in a facility and how she was curled over in the seat sleeping and not aware when I was showing her how I could drive for the first time and how she eventually stopped being able to walk or talk or feed herself.
And my senior year, I would go visit her every Friday after school and a few other days during the week. But when she spent the last year of her life curled up in the bed, I'm obviously not talking or being able to care for herself in any way at all. It was a lot at 18. But it was still, I was younger and it was my grandmother.
You know, I think when you're young and you envision your grandparents as like, well, their grandparents there, you know, this happens to them. Even though, you know, I think my grandmother was 76 maybe. So then she passed away. And then at my college graduation, when I was 22, my mom was 52, she repeated a story a few times.
And, you know, my mom, who was this incredibly smart, vibrant woman who was aggressive about the things she wanted in her life. And she didn't take no for answer type of woman. But throughout her life, she'd always say, when I get Alzheimer's, when I get Alzheimer's, stop saying that, don't say that. And then at my graduation, when she repeated a story, a few times, I thought, oh God.
But I didn't say anything, of course. And then, you know, over the next year or two, it became clear that this repetition was becoming a part of who she was. And she was losing control of, you know, her ability to teach and to, you know, do any number of things that someone who is fully functioning in a cognitive way could do. Eventually, we encouraged my dad to take her to a doctor.
And, you know, over the course of a year and a half or so, we got as much as a diagnosis as one could get at that time. You're just out of college, and you're being confronted with the idea that your mom is not even in her mid-50s yet. And she's already in the early stages of Alzheimer's disease, something that's already prematurely taken. Her parents, I'm guessing it's now sort of setting in that there's something going on in your family, right?
Yeah. I mean, there was a lot of denial, I would say, a lot of fear, a lot of anger, and of course, a lot of depression. And I think what was really hard about it at the time was my mom wouldn't let us talk about it. And, you know, at this point, I can only imagine what her identity felt like as a daughter of Alzheimer's herself, what was driving her at this point.
But to me, things were really starting to become clear in a really scary way at that point. I didn't talk to anyone about it, because I didn't, I think, you know, when you talk about something, it seems real all of a sudden, it's really happening. Even your father? Oh, God, especially not my dad, because my dad was the most into an aisle about any of us.
You know, my dad, you know, my parents had, you know, an amazing marriage, and they were best friends and partners, and he admired my mom for her brain, and for how smart she was, and how passionate she was about what she did, and how hard she worked. And so, yeah, he was the last one, I think, to come around. But eventually, a few months after Seth and I started dating, actually, my parents came out to visit. This was in 2005 to meet him, and came up for my birthday, and when I dropped them off at the airport, and I came back to Seth's apartment, it was the first time I'd set it out loud, that I was afraid my mom was developing Alzheimer's.
And it was the first time I cried about it, and he was like, no, no, she was fine. You don't know what's fine. I'm like, you don't know her. You don't know how the person you met this weekend is different than who she was.
And, you know, I guess, around two years from that point of going to visit, and she'd be worse. It was clear, you know, at some point, she shouldn't be driving. Eventually, her school decided she shouldn't be in a traditional classroom anymore. And to the ground of that classroom, it was just who she was, was fading away and changing right in front of her eyes.
She couldn't have these long conversations anymore. She, again, would repeat herself. She would call with the same thing over and over again, and it was devastating. I was in a very dark place at the time.
Do you have any sense that she was aware of some of these things? For example, the idea that she could no longer teach her classes, and to have that taken away from her by her peers, did that register with her what was happening and why? Yeah, you know, I never, I didn't have that direct conversation with her about it. I'm sure my dad did.
I think she took that stuff and strived probably to act like a strong independent person for us, but when she eventually had to retire, I know she wasn't thrilled about it, but she was at a point where, cognitively, she wasn't at full function anymore. And so it became a bit easier to change her life in a way where she didn't question it, which is, you know, really sad to think about. But I think it was, I had one conversation with her. Early on at I read in Team Magazine, if there's ever something difficult, you want to talk to your parents about do it in the car because the drive will eventually end.
And so the awkward conversation will naturally end. So I remember one time I was home in Florida and I was visiting them. It might have been around the time she was forced to retire and we were driving to Target and I asked her if she was scared about getting Alzheimer's. And she told me that she wasn't scared for her.
She was scared for me and my brother and my dad. Cause I think she got that at some point she may not know what's happening and that the weight would be on us. I think she knew that because of what happened with her dad and her mom. And I can only imagine how terrifying that was for her.
But I can't understand where she was at that point cognitively or emotionally even to really know the fear there. So you mentioned that this is around the time when, I mean, it's now hitting you with the full force. And I assume it's much less or maybe somewhat but probably less about what the implications are for you and much more about the loss of her. Yeah, which of course, you know, I was in my early 20s.
So that was only about me. I was at a point in my life where I was just starting to become friends with her. She had, okay, maybe one more shot. She had come out to visit.
I moved to LA in January of 2004 and she came out to visit in March of 2004 during her spring break. And we had such a great time being, you know, I was 22 but you know, a grown up. And we went to dinner, just the two of us like as grownups and like drank wine and like she was a big drinker. She could drink a zebra's.
And like it felt like I was reaching that point where she was my friend, which I think, you know, now I have so many girlfriends who their moms are their best friends and I instantly felt like that was being taken away from me and was so angry about it. And so jealous of all my friends who were having those relationships with their moms and felt so hopeless. You know, I would go online and I would just search like cheer for Alzheimer's, dream for Alzheimer's, gotta be there. I know I can find it.
Like I'm the kind of person who's like, I'm gonna do something, I'm gonna do it, you know, and like, no, there's something out there. I can find something for her. And there was nothing. Like there was nothing.
And so it was a really scary hard time where I felt like I could do nothing and that this train had left the station for my mom and that was it. So I wanna give you a chance to just sort of catch your breath a bit. And Richard, I wanna sort of ask you a couple of questions right now. Not necessarily specifically about Lauren's mom because I wanna come to that in some detail later when you actually, when we get to the part of the story where you and Lauren meet.
But I wanted to ask you a broader question here, which is help a listener understand the context of this type of Alzheimer's disease. And by this type, I mean one that is so clearly familial and also so early in onset. How do you think about that as a neurologist? What's going through your mind as you think about this type of a case in terms of genetic predisposition?
Let's just start with the genetics of this. Sure. So I first have to start with just, I hate this disease. I just like hate it.
I hate hearing stories. Now you're gonna make me cry, Lauren. I'm on a podcast. Come on, record.
No one can see us, that's fine. Okay, good. So I just hate this disease so much because it's so insidious, it's so nasty. It's so just, it just, it just, it robs the person of who they are but it robs the whole family.
I mean, just like you just said, it's like it robbed you of like the good years, like the friendship years. And that's just, so I hate this disease. Alzheimer's disease starts in the brain decades before the first symptom of the memory loss begins. And I didn't learn that in medical school.
I hate to say it, but most doctors don't know that. Still, the new diagnostic criteria have been out now for about a decade. But when I hear it 52, I say, oh my gosh, what was happening in her 30s? What was happening in her 30s?
Like why, why is this happening? And then I hear the family history and I hear, well, her mom and her dad, why, why is this happening? And Lauren, we have some small world coincidences which we talked about later, but my brother, he's an neurologist, he's older than me. He took care of another one of your family members is like on another, so like why, why is this?
And of course the first thing you think about is genetic. And then you think about, well, is this early onset? What is early onset? People think about Alzheimer's disease and older persons' disease.
Greater than 70, 72, 74, what's the average age? But there's a small tiny sliver, a small, small group that I would qualify as having early onset Alzheimer's disease due to a genetic reason where the person usually gets Alzheimer's in their 40s or 50s. But Lauren, your family was different, and we'll talk about this later, but when I hear a family history like this, I say, well, why does certain people in one family get it later? And the other people in the family get it earlier.
This is actually earlier on said Alzheimer's, and I maybe made that up, but what is it? This person should have been affected in the later years, and something is fast forwarding, something is there's a one plus one equals three here. There's a mishmash of things that just, the first thing I think about is why is this happening? And number one, I say, OK, genetics.
There's got to be some genetic something. And then number two is, OK, then I think about, well, could it be lifestyle? Could it be an exposure or something? Could it be head trauma?
Could it be uncontrolled diabetes, high blood pressure cholesterol? These are all things that synergize together to potentially make a late onset Alzheimer's case start earlier. So these are some of the things, detective work things that I think about. But no, it's not typical.
What genes do you think about Richard? What are the suite of genes? I mean, there's the obvious ones, ApoE4. But there are other genes that could be implicated in early cases.
Can you say a little bit about those? Sure. So there's a typical early onset genes. There's really only three, presinealin1, presinealin2, and amyloid precursor protein gene mutation.
I can count on my two hands. How many patients I've seen with that? I've seen over 1,500 patients easily, probably close to 2,000 patients over the last 15 plus years. Literally two hands.
That's all I got. Lauren, you actually introduced me to one, an amazing person, great individual, and someone that I, whoo. She may have that gene, but I will not say that she will get Alzheimer's. So for the first time in my career, I've not only figured out that someone hasn't early onset gene, which means you're going to get Alzheimer's, but just wait.
Our field is making a lot of progress. So these three genes are just so rare. That's number one. Most people that have earlier onset Alzheimer's have a milieu of things.
So I would call it polygenic risk. So ApoE4, the variant, ApoE4, is the most common genetic risk factor for Alzheimer's disease. Now, the difference between ApoE4 having one variant or two, I'll explain that in a second, means if you get the E4, it doesn't mean you're going to get Alzheimer's. It just increases your risk.
If you get presinealin1, presinealin2, or amyloid precursor protein gene mutation, sorry for the long words there, if you get those genes, you get Alzheimer's. That's what the books say, except in that one person that you introduced me to, Lauren, we've got time. She's in her 20s. We're going to get this up for her.
And those rich at really represent far less than 1% of the total cases are made up of APP, PSEN1, PSEN2. For what it's worth, I've never actually seen one. For me, those only exist in the literature. The interesting aside, by the way, is there's some people speculate that the index case of Alzheimer's disease was actually one of those.
And some of our understanding of this disease may be incorrect as a result of that, but we'll kick that to another discussion. So when you meet a person like Lauren, you're not necessarily thinking one of those three genes. You were just thinking some aggressive combination of other things. Yeah, and it's epigenetics would be the word that I think about.
So the term epigenetics encompasses a person's genetics, plus the environmental impact, the milieu of what a person does in their lifestyle or behavior, or what they were exposed to, for example, whether it was a virus, or if it was a traumatic something, or if it was something that triggered the gene to work in one way or another. And the term polygenic risk means that there are multiple genes that work together, and that some genes can increase risk, and some genes actually decrease risk. So the future of Alzheimer's disease, well, I believe the future of Alzheimer's disease is based in precision medicine, using these types of genetic underpinnings, understanding all the individual genes that impact a person's risk, figuring out what they are, figuring out what their biological function is, figuring out why it puts a person down the path towards Alzheimer's, and then telling that person to do ABC, X, Y, and Z to get them off the path towards Alzheimer's. That's the future of Alzheimer's, and I think in a lot of ways the future is now.
But ApoE is by far the most well understood, most well researched. Every patient that walks through our doors gets an ApoE test. You know, there are commercial, like anyone can basically find out what their ApoE status is, just for the listener out there, you get one for mom and one from dad, either an ApoE2, a three or four, it's called an allele or a variant. A lot of people call it a mutation, but it's not a mutation.
So you get a two or three or four from mom or dad, and a four increases risk a little bit, a three is neutral, and a two actually is protective. So if someone comes in as an ApoE3, three, that's a pretty neutral risk kind of boring, no big deal. ApoE2, three, okay, maybe they have some protection, and one for ApoE3, four, for example, increases risk a little bit, and then two fors, ApoE4, four is increases risk more so, but again, genes are not our destiny. We can absolutely win the tug of war against our genes.
And then, you know, four fors, I have dozens of patients in my practice that I absolutely think that they are not gonna get Alzheimer's disease. They're gonna be able to do some things to delay it. They also have other genes to protect them. So without getting too detailed, ApoE4 is important.
We personalize care, you know, if someone has a four, we're gonna tell them to do certain things. Someone doesn't have a four, we're gonna do other things for them because there are other things that are preferentially effective. But this polygenic risk is what I'm thinking. So when I hear about Lauren's mom, like, what is it, what are he fors, sure?
But what else? There's gotta be something else that devil is in the details there. Richard, I wanna go back to Lauren to continue this right before I do. I wanna explain for folks that want a bit more understanding, what is it about having the E4 variant relative to the E3 variant that increases risk?
So the gene codes for a protein that differs in what way from the, what we call the wild type or the E3 variant. So I guess how to answer that is starting by basic. What does ApoE mean? Apo is Apolipo protein.
That means something related to cholesterol, I guess. People actually who get the gene tested in our practice actually get it through a cardiovascular disease prevention panel. Peter and I have used the same labs. You maybe focus more on cardiovascular disease prevention.
I focus more on Alzheimer's disease, risk reduction, prevention, but it's really a cardiovascular risk gene just as much as an Alzheimer's risk gene. So the way that I think about E4 is it increases vascular risk, increases the likelihood of a bad pathologic protein called amyloid to sticky stuff that builds up in the brain of a person with Alzheimer's. And people with this gene are more likely to have accelerated deposition or accelerated accumulation of this amyloid protein through a, what I would call just in a basic sense, a cholesterol-like vascular-like pathway. There's a ton more I can talk about it, but you know, once you've seen one person with Alzheimer's, you've seen one person with Alzheimer's and different people who can take different roads, Alzheimer's disease.
And the A-B-E-4 road is actually something I kind of understand. I kind of get it. I feel good about it. I know that may sound callous or strange, but like I know what I'm up against.
Like, OK, great. We can do lifestyle things. We can manage cholesterol in a certain way. We can do all these different things.
And I know certain things that work. And I know what I'm up against. It's the person that actually doesn't have the E4 that I'm like, wow, they're either spared or they have another gene lurking. How do I find it?
And what the heck do I do about it? So E4 doesn't bother me. And I feel relieved sometimes when we find it in a person. All right.
Well, I think we'll talk a little bit more about this. But Lauren, I want to kind of hear more from your story. So as you're now kind of coming to grips with the fact that your mom is slowly slipping away, and you're also realizing that unlike, oh, if my mom has premature heart disease, for which there is no shortage of treatments, you're realizing actually your ability to access the best in medical care isn't really going to do much. What's the temporal course of her progression?
So as we get, let's say fast forward to when you and Seth get married, which is 10 years ago, how is she at that point, which is still probably putting her in her late 50s, right? She just turned 60. And so at that point, she could still walk. She was, there were moments where she knew us.
She knew us. She knew that we were her family and that we were her loved ones. But she was, at that point, being fully cared for by my father at that point. But she could still dress herself and bathe herself and use the restroom.
But planning, I would say planning my wedding was a real emotional turning point for me because it was, I've always was the kind of girl who envisioned my wedding and it was to be this thing. And then my mom and I would do it together. And that is just not what happened at all to the point where I couldn't even have her there when I was getting ready because she would just be wandering. And my dad had to take her to a separate hair appointment because it would just be too disruptive to get everything together to have her there.
But when she walked in, I remember that morning, I'll back up a bit to say we had a bit of a weekend, our wedding. And Friday night was a small thing in Saturday and Saturday night, there was a dinner, and it was not good. We had taken my mom from her home, which for an Alzheimer's patient, for anyone with dementia, is difficult to take someone out of their space, their routine, where they know everything and they are familiar with their world. So that of course had put her in a place where I think she was probably feeling very scared because she didn't understand where she was or what was happening.
And at our rehearsal dinner the night before, I remember her telling me she just wanted to go home, which was really hard to handle. But then miraculously, the day of, she walked in and she called me the bride and she knew that I was the bride and that I think she knew that I was her daughter. But she knew she felt proud, she knew she felt love. And I have an amazing photo of her looking at me and holding my hand and it's just she knows that there's a connection there.
But it wasn't the moment that I had certainly dreamed of and I feel like it was my dad and I that walked her down the aisle instead of him and her walking me down the aisle. And normally in Jewish weddings, the family stands up next to the bride and groom and we didn't do that. We had them sitting next to us because we knew my mom couldn't do that. So at that point she wasn't teaching anymore.
That was a few years earlier and that had ended. So it was for me, it was a really hard thing. But luckily she rose to the occasion that day, which it's interesting throughout this journey with her. I think people that don't understand the disease, trying to find some sort of lightness and hope would always be like, but she must have good days sometimes.
She must remember you sometimes. Does she remember you sometimes? And I'd always be like, no, it's gone. Like that's gone.
Sometimes you remember like, oh, I use my legs for walking. Like once that's gone, that's gone. But for whatever reason, the day of my actual wedding, I will say she was as there as anyone could be in her state and that was an amazing thing. But overall, it was only a few months after that that we encouraged my parents to move out to Los Angeles because my dad, it was clear that it was killing, it was gonna kill my dad before it killed her.
The stress of taking care of her. He always talks about the plane ride home from our wedding. It was like the worst five hours of his life because she had had an accident in her seat on the airplane and was acting out and was screaming. And they had to get help to get off the plane when they landed back in Florida.
It was a pretty horrific time. I mean, these are some of the things that we're gonna talk a lot about, Hilarity, Frigidity, and why the focus is on the family, which I think is part of why I'm so excited about it. And you can ask me a hundred times to do something for it and I'll always say yes. So you always apologize when you ask me.
Don't say that, don't say that. But I'm really so fond of organizations that take that step and appreciate what is being done for the family too often. People think the only way to make a difference is to fund research. And clearly that's important.
But it's too easy to ignore that while we're waiting for these things to happen, people need help in caring for this. And I suppose there's no disease where that's more true than this one. Hopefully. Richard, can you just spend a minute kind of explaining what it is about the deposition of these plaques, the accumulation of the tau?
Why does it lead to this largely predictable set of symptoms that don't just involve almost a folksy, funny loss of memory, right? But also at some of this deeper level of this, what I suspect is fear and confusion on some level, right? Like why would she be upset on the airplane? Well, I'm guessing on some level, there's a sense of fear, right?
If something is wrong, why is she not able to control her bowel or bladder? Like how is this disease wreaking so much havoc on the central nervous system, Richard? Yeah, so there's actually a couple who I believe are both pathologists, Brock and Brock, BRAK, B-R-A-K. And what they did was they kind of came up with a Brock staging of pathology where the amyloid protein and the pathology of Alzheimer's spreads over different parts of the brain.
And when I was in medical school, I always thought that Alzheimer's disease, a progressive neurological disease characterized by changes in short-term memory. And then later on, that includes changes in some behaviors, neuropsychiatric disease, changes in sleep, and then the person as the pathology spreads, they can no longer take care of themselves. What we really now understand about Alzheimer's is it's a much more heterogeneous disease, meaning wherever the pathology goes, those are the symptoms that manifest. So there are newer forms of Alzheimer's and they're newer because they're now published in the literature, but we've seen this for decades.
There's one newer form that has something called a disexecutive syndrome. Well, what does that mean? Executive function is higher order processing, judgment, planning, you know, you find a wallet on the floor, what do you do with it? Right, Peter would take the money out, put the money in his pocket, throw the wallet back on the floor.
You know, Lauren, she's very empathetic, compassionate, she'd look at the license, she'd say, oh, I'm gonna go find this guy, I'm gonna go to the ends of the earth to find this person's wallet. So that's executive function. Maybe depends on this. Depends on how much is in there.
Exactly. That's one form of Alzheimer's. You know, another form of Alzheimer's is part, P-A-R-T, primary age-related, tau apathy. So we've talked about amyloid, but what about tau?
It has another protein. And there's tau and amyloid and neurofibrillary tangles, and then there's glucose, hypometabolism, the glucose, the sugar in the brain, it's just not being efficiently able to be used to power the brain cells. So depending on where the problem is, you have different manifestations, cognitive symptoms, I guess. And part, for example, is primary age-related, tau apathy again, one more time, it's related to age, so it's usually in older people, easily 70s, more likely 80s and 90s, and it's specifically short-term memory, and it's specifically because of that pathology is localized to the memory centers in the brain.
They have a campus, for example. But that person can still have good executive function. The frontal lobe, the front part of the brain, is working. So it just depends.
It depends, you know, for example, when the pathology, when the bad stuff goes to the back part of the brain, that's where the visual fibers are. So the eyes are in the front, but they have visual protections that go to the back. You interpret images. Well, when someone can't interpret images, they get confused, they act funny, they may be weird, they may be, you know, confused.
But it's not exactly a memory problem, it's a visual perception problem. So, you know, I don't wanna be cheeky, but like- I mean, Richard, no, no, this is very interesting, and I never really thought of it this way, but as you probably are aware, we don't really think of cancer as one disease anymore, right? I mean, it's been a while, but nobody's thought of cancer as one disease. So breast cancer and colon cancer have very little in common.
I mean, about the only thing they have in common is unregulated cell growth, but thereafter, they're very different diseases, not just in the ability to impact a different organ. And it sounds like what you're saying is, Alzheimer's is not really one disease. It's kind of an umbrella term that encompasses many different diseases of the brain that have some common features in the way that cancers, all cancers have some common features that, you know, cells don't respond to normal signaling, but this notion that someone could have a form of Alzheimer's that largely spares their frontal cortex and therefore preserves some higher-order functioning versus another person that has something that's not- I mean, listening to this story of Lauren's mom, just hearing what we've heard so far, how would you think about the etiology or the insult? Well, I'll try not to bias my answer because I know a lot about Lauren's mom and Lauren's whole family, but if I just took her face value, what Lauren said, that symptoms began with little repeating of stories and memory glitches around 52 to 54 to where she had to have then a modified work schedule to then six years later, she's having trouble caring for herself, maybe not recognizing her daughter and then having emotional behavioral psychiatric components.
I mean, that sounds like Alzheimer's disease. That sounds like progressive short-term memory loss plus behavior changes plus other things. So it sounds like she started in the mild cognitive impairment phase with a symptom. So there's just three phases of Alzheimer's, three stages, maybe we should take a step back for listeners.
The first stage is actually the preclinical phase, the pre-sympathetic phase where Alzheimer's disease has started in the brain, but there are no symptoms yet, no clinically apparent symptoms. Believe it or not, there are 46 million Americans with Alzheimer's disease in their brain right now, but no symptoms. That's crazy. I've never heard that before.
Yeah, I try to keep that close to my vest because- How do we know that, Richard? That's what the studies say, you know. You're the critical appraiser of studies. I'll have to send you the study and you can tear it apart, Peter.
You're gonna bring this one to Journal Club next month. What a great idea. I love those Journal Clubs. That sounds like the nerdiest club of all time.
Oh my, and we've discussed you and we've discussed now. It is pretty freaking dirty and we record it and then we watch it and we- Oh my God. I was captain of my math team at Comac High School. Well, there you go.
Nevermind, it sounds really cool then. Thank you. Thank you. Also the Alma Mater of Lauren's mom.
I've got Comac and Lauren's uncle and some others. Anyway, so this preclinical, pre-symptomatic phase is by far the most important phase, I think, well, maybe to focus on because that would be prevention of Alzheimer's. You can call it either treating preclinical Alzheimer's or secondary prevention of Alzheimer's because you're trying to prevent the dementia from happening. So stage one is preclinical Alzheimer's.
Stage two is mild cognitive impairment due to Alzheimer's where there are enough memory glitches and other changes to where it's noticeable. It's greater than a standard deviation and a half below the norm, but the person can still take care of themselves. So I think Lauren when your mom started having symptoms she was easily in the borderline preclinical to MCI stage. And then people have roughly between a 12 and 16% per year, depending on what study you read, a chance of converting from MCI mild cognitive impairment due to Alzheimer's to dementia due to Alzheimer's.
And the only difference is they still have the symptoms. They're just worse and they can no longer take care of themselves. So Lauren, many people would be very pleased and thankful that if symptoms started at 52 and she was able to attend your wedding at 60, I mean, that's horrible, but better than it could in the grand scheme. At least she was there.
I have friends who unfortunately had weddings without parents there. So because they've lost them already. So, absolutely. So these are the stages.
OK. It's a staggering number. And whether it's 46 million or 36 million or whatever the number is, you know, it's not surprising in the sense that if when you look at how many people are prediabetic and you think about how that is one of the pathways to Alzheimer's disease, sort of the energy dependent pathway, it's very plausible, especially when you consider the other pathways. Richard, one thing I want to park with you to come back to is some thinking around how many different variants of the disease there are, right?
Sort of the lipid variant of the disease, the toxin variant, the potentially an infectious variant if such if one such exists. And maybe we'll let you think about that for a minute. So, Lauren, I want to talk about how you made your way to Richard, because that's how you and I met you and I met through Richard. But I want to know how you and Richard met.
Sure. So, OK, I'll try to keep this somewhat brief. I feel like it might be long. This is a hilarious story.
I'm sorry. I remember this like a video in my mind. But anyway, I don't want to interrupt. So in 2011, it was the year that I got married.
It was the year I shot for a good time. Paul, and it was the first year that we planned the first Hillary fraternity event, which was January 2012. So 2011 was a pivotal year for me. Up until that point, like I said, I had been really dark and depressed and I had been trying to work in the screenwriter and I was writing.
But I just spent a lot of time just being pretty dark and pretty upset. And then a friend came to me and was like, let's learn an event to raise money for Alzheimer's. And I was like, no. But then he wore me down.
Thank God. And we did. And so in January 2012, we threw our first variety show to raise money for the Alzheimer's Association. And that was incredible.
Then we raised a few hundred thousand dollars. But the most incredible part of that was that we were contacted by young people who felt seen for the first time, because they were seeing me in my late 20s and my husband and his late 20s talk about Alzheimer's, which, you know, even for me up until that point, every image of Alzheimer's I had seen was of someone who was old and gray and not at all related to me in any way that I could understand. So we felt like we had an opportunity to continue talking and to continue hopefully gathering people and helping them feel like they too had a place in this disease, which is considered a disease for old people. And so that's when we kind of decided to form our own little organization, which was a fund within the Alzheimer's Association for many years in 2017, became our own 501c3.
But during that time, of course, we became Alzheimer's advocates. And I met many smart people and doctors and scientists and other advocates who were doing all sorts of incredible work. We became friendly with Maria Shriver, who of course has always used her platform to raise awareness about Alzheimer's and it's so incredible. And I had really sort of gotten to know the Alzheimer's community a bit.
So then my uncle, who was my mom's brother, who was five years older than her, was starting to show symptoms. Now, my uncle, who was an athlete his whole life, he was, and his later life started when he was, I don't know, I think in his 40s riding a bike and was an obsessive bike rider. And he was in great shape and he's a big, strong, muscular guy. And we'll get into some of the other things while Alzheimer's happened to my mom earlier than I did with him, but he started showing symptoms.
And I wasn't allowed to talk about that publicly at the time. Unfortunately, he passed away in March this year, only a month after my mom and his family, my aunt and my cousins have fortunately now given permission to tell his story so it can potentially help. So he was starting to show symptoms and they were on the East Coast. So they came to me and said, what do we do?
What do we do? What do we do at this point? And this way, by the way, my mom was very advanced at this point. They were out here.
I was in the West Coast and I was like, oh, I'm not going to talk about Richard. It was 2014, 15, 16, even, 17. And basically I reached out to a doctor that I knew and was like, you know, my uncles on the East Coast, I want to get him into the best of the best. Who is it?
And this person recommended Richard. The best of the best looking, I hope. The best looking, all the best doctor. Okay, perfect.
Yes, exactly. Thankfully, this is a podcast. That's what my uncle was hoping for. It was the best looking doctor.
The one with the best phones, I think is what it was doing. Definitely the best phone. Well, I mean, certainly I listened to that episode where we talked about where you guys talked about Richard's phones. Oh, God, he's showing one.
My stones and a horse on the back at the top are those not my stones? Diamonds, hello. Oh, no, excuse me. Those are diamonds.
It's a diamond pillow. Come on. Anyway, so gave me Richard's name and I went on his website and I found his email. It's direct email because of course I was, again, I'm not the kind of person who's like, I'm going to be polite and give me my stuff and follow the rules to get to where I need to go.
Like I'm going to do what I got to do. So, so I found his direct email address and was like, hi, here's who I am. This is what I've done. My uncle has Alzheimer's and needs your help.
And so he wrote me back right away. And then of course, then we connected that he was from Comac and that my mom and my uncle had gone to the same high school as Richard, which is, you know, what a small world. He, of course, got my uncle in their right away and they went on the journey that they went on. So then I was in LA and then I, once I connected them, I came to New York, you know, a few months later or something and I, you know, said, I'm coming to New York.
I want to come see the clinic, come at you. And then of course, you know, I'm seeing the clinic and talking to him and I was like, I want to be a patient. I want to prevent Alzheimer's. Lemian, help my brain.
You literally like, I don't know how to do this, but like, like, shout out your arm and said, like, take my blood now. Let's do it. And literally you walk into the clinic, we like literally stuck a needle. You signed a consent form and then like, it was the quickest, most rapid Alzheimer's prevention consult in the history of our program.
So lucky for me. Lucky for me. Lucky for me. What kind of shape was your uncle in at that point in time?
I actually didn't realize this part of the story that the initial connection with Richard was actually a consultation for your uncle. Is that presumably because at that point you felt your mom was just advanced enough that it. Yeah. No, at that point, my mom was, she was fully bedridden.
I'm pretty sure at that point, getting everything fed to her fully cared for. There was her train had long left the station. So your mom at that point would have been in her early 60s, I guess. And your uncle is a little older, did you say?
Yes. He's five years older than her. And he was, you know, I would say in that MCI, in that mild cognitive impairment space, right, Richard? Even almost a little before that it was, he was a very functional guy, you know, with both my mom and my uncle.
And you know, and you guys can speak to this more about other people. They could both like rise to the occasion in a way. And so, you know, I knew that what my aunt was seeing with my uncle was different than what I saw, that he could somehow dig deep and put on a show, if you will, and act like he was still in control. But there were little things, little hints that wasn't happening.
My mom, we were far past that point. Richard, let's talk a little bit about now the beginning, you go down this path of kind of being a detective. So you're never going to get to meet the parents, the grandparents in this case, but the parents of your first patient. But you know enough about their story.
You're meeting Lauren's uncle. You know about Lauren's mom, though you haven't met her. How are you now starting to piece together this family first, for the standpoint of trying to understand if anything can be done to help Lauren's uncle, but ultimately to really figure out what to do to help Lauren and her brother. Yeah, this is detective work.
This is a spelunking mission down the deepest darkest cave with no light and, you know, instead of a pickaxe, I don't know, maybe with a plastic fork and knife. Let me take a step back. Lauren, before I met your mom, I saw a video of your mom, which kind of changed things for me. This was a video of a movie, actually, that you can maybe talk about he'd worked on.
And I had actually watched, I don't know if it was a clip online or maybe it was something you sent me. And seeing the video of your mom from the, I don't know, you can tell me eight something years before the present, that was so instructive. I mean, I, I don't know how to explain this, but like, I'm not psychic or anything like that, but I trust my gut. And when I see people sometimes, this is going to sound weird, but I think it's true.
I see jeans. I see, I don't know, my gut just feels something and I can, I don't know if it's just because I've seen the pattern so many times. There's genotype and the genes and the phenotype, which is the, you know, the physical real world manifestations of genes. But there was something about your mom, her behavior, her mannerisms, her, I don't know her shape or her face.
I mean, I don't get too like kooky and weird, but like there was something. That my gut where my subconscious just saw and your mom was a little confusing to me because I saw something consistent with Alzheimer's, but there was, you know, my gut said there's something else. This is, this is just strange. This is not clearly Alzheimer's.
This could be something else. And then when I talk to you, Lauren, about, and really talk to, you know, your aunt and your uncle and I learned all the intricate details, I just learned that this was, this was more complicated than Alzheimer's. Maybe there's Alzheimer's on one side, but there's Alzheimer's plus something else on another. And I don't know if I ever told you the story, but your uncle brought in his Komak High School Yearbook.
I don't know if you were talking about that. And then I don't know. And then when I was actually at your place in LA, your, I think your dad found your mom's Komak High School graduation, your book, and this is going to sound even cookier, but you can tell in the handwriting, your grandparents signed your mom's your book and your uncle's your book. And there were five years apart.
And I could tell in the handwriting, there's like research to support this, but you know, you could just tell by the change in the handwriting over the years and just the, you know, like Alzheimer's is a neurological disease or other neurological conditions, like Parkinson's disease, dementia with Lewy bodies. And in Parkinson's disease, when you start writing, as you write more and more that the writing gets smaller and there's like a shaky nature to the writing. This is really hard to explain. I don't know.
Something about the handwriting was just different and about the word choice. Like, you know, there was a study that looked at nuns and the nuns wrote their autobiographical sketches in like their late teens. And then depending on analysis of their autobiographies that they wrote, you could predict which nuns were going to get dementia 60 years later. So there's a lot, you know, I believe Alzheimer's is a life course disease.
Literally people with the 8.4 variant, one or two copies has smaller brains when they're born. So I know we say Alzheimer's starts 20 to 30 years before in the brain. Well, that may be because of the biomarkers of Alzheimer's that we can detect are noticeable in the brain. But I believe Alzheimer's is a life course disease.
And sorry for the long story here, but I learned a lot about your family from the clues that I got from those videos and the handwriting samples of your grandparents. So I guess I would start with that. And then I think I just said earlier, my brother ran completely randomly cared for another one of your family. Your grade uncle.
I mean, like just completely strange and bizarre, but you know, I actually talked to my brother about him and we just start to put the clues together. So first we do the detective work and kind of the investigative part. And then we just do a clinical history. We ask about all sorts of things from medical history to what are the risk factors or parent.
We did some genetic testing, which was critical. So we just try to put together lots of different pieces to the puzzle and do as best as we can with the information we have to personalize or individualize a person's care. So Richard and Lauren, I don't know if you don't, if you don't have permission to talk about Lauren's uncle's case, then we don't need to talk about it at all. But if we do, so I'm curious, Richard, you have this clinical history that is, at least for me would be very overwhelming.
I realize that a lot of people walk into your clinic with stories as tragic and as complicated as this. But what are the things you most want to see come back out of that blood work? Once you have a very detailed clinical history, at this point you've probably established that brother and sister are on the same pathway, those sister is moving much quicker in Lauren's mom versus uncle. The apoegenotype comes back.
What does it show and what does that tell you? All I can say is my brain kept asking why, why, why, why, why? Why did Lauren's mom have symptoms of 52? But Lauren's uncle, five years older, started having symptoms in his late 60s or maybe it was early 70s.
Why, why, why, why, why was there this 15 something year old? What is going on here? So the first thing I think about is, and this is also because of a genotype phenotype thing, I felt or smelled or whatever it was that there was some e4 something, a poe4 something. Lauren, when I saw that video, your mom, I don't know, again, this is weird, but your mom was the four.
I actually thought she was the four four. I'll just be frank. She was four four. Yeah.
Exactly. Yeah. From the video. Yeah.
And again, I was weird talking about when it's being recorded, but like, I don't know. I've seen a lot of patients. So I can just, you know, I can, I don't know something subconscious. When your uncle walked in for four, but just to be clear, Richard, did you think that Lauren's mom was four four because of how early it affected her or because of the fact that she had such a clear history of disease on both sides of the family?
Honestly, I guess what I'm saying now is I saw her on video and the phenotype that I saw that the, her body makeup, her habitus, her structure, again, sounds weird, but I saw four four. I felt four four plus, of course, in my subconscious mind, I knew she got it early. I knew the parents, I knew her parents, Lauren's grandparents got it later. So it's just fit.
And also big, big, big, big, you heard it here first. No, this is common knowledge. I hope it should become knowledge. Women with the e4 variant, much higher risk.
I mean, women with e4 are very different than men with e4. And I think most people just completely are not aware of that. And then Lauren, I forget when this came up, but I don't know if I asked you this, but I said, when did your mom go through menopause? And then you told me about this direct to me and they took the ovaries out.
And I said, oh, my goodness, my goodness. I said, wow, e4, four, even though I don't think we had the genetics at the time or maybe we did, plus the, you know, surgical menopause taking out, you know, immediate withdrawal of estrogen and taking out the ovaries back then we had no idea relationship to all times or anything else. Plus she's a woman and there's a synergistic, you know, impact on risk. So it kind of was the perfect storm, but but still a four four plus a woman plus a hysterectomy, there had to have been something else.
And then we went on a spelunking mission to find something else. Lauren, how old is your mom when she had a hysterectomy? Was she in her 40s, late 40s? I want to say she was 46, maybe 47, but I'm pretty sure 46.
All right. You've alluded to this just in passing a moment ago. I want you to expand on it a little bit. You basically created a little bit of a contrast between your uncle and your mom in terms of lifestyle, your uncle being exercising constantly.
Tell us a little bit about your mom. Obviously you've spoken about her intellectually and you mentioned she didn't consume much alcohol. What other lifestyle factors do you know about her? Did she sleep well?
Was she under a lot of stress? What was her diet like? How much did she exercise? She was in her smoke.
She told me once she tried to smoke a cigarette and had school and threw up and never did again. So that's why I never smoked a cigarette. But she did not exercise. We were a big sugar house who had dessert every night.
She probably had cookies most nights after dinner. She used her brain every single day, but was she constantly learning new things? A little. She taught first grade for 15 years.
And so, you know, sure, could she have been learning things? Yes, but was she recycling information that she had already learned, potentially? But I think, you know, knowing what I know now, she got almost no cardio exercise. And she ate a lot of sugar.
And combining those things with, you know, her family history, of course. And then, of course, the hormonal issues that arose from her hysterectomy, you know, seemed to really put her on the path that she eventually went down. Do you know if she had any difficulty sleeping prior to the hysterectomy? I can only imagine afterwards it was devastating, but yeah, I mean, it's funny.
She and my uncle and my grandfather were similar sleepers, I would say, and that they would fall asleep on the couch every night and then wake up super early. That's as much information that I got from her. I like, you know, of course, less. It's like an older, but like, kind of person who loves sleep and is very happy to sleep, whereas like she wasn't a big sleeper.
She definitely did herself no favors with her sleep habits, especially again, knowing what we know now. She did not use her sleep to help her brain at all. I just want to comment one thing. And I talked to your dad about this at some point.
Your mom was not, you know, when you looked at your mom when she was in 80s and 90s, your mom was not unhealthy by any means. No, I don't want to paint the picture of hers being this like disgustingly, you know, unhealthy person who didn't care about herself. But wasn't that? It just she didn't make the effort that is needed that we know now to, you know, as Richard said, you take control of the genes that she had been given.
And prevention in the prevention space and preventative medicine and preventative health. At least the way I think about it is there's normal and then there's optimal. You know, your mom for the time, that was kind of the typical, you know, what I would call your mom now is, you know, maybe, you know, the term skinny fat, right? Skinny on the outside.
I was in the inside. You know, I don't know what your mom's waist circumference was in high school versus her waist circumference in her, you know, 40s and 50s. But I can guarantee you, it was larger based on, you know, my understanding of the pathology of this disease. And but back then that wasn't really talked about or thought about, you know, in the 80s, it was like, you know, I was like, when 10,000 steps came about, you know, like, who came up with 10,000?
Well, sorry, I know who came up with it. But I understand that there's some better than nothing and calculating, but 10,000 steps is like so antiquated. It's like, you know, literally the 80s compared to now, we truly understand physical fitness and how to optimize physical performance. Your mom was not unlike most middle aged women at the time.
You know, and the difference we heard in my uncle or even, you know, me and my brother is like, my mom was never an athlete. Like, I was a gymnast growing up. My brother was a baseball player. My uncle ran track and then he got into cycling and was always a physically active person.
Whereas my mom was an intellectually active person. She read, you know, like I said, she was a great student. She loved to learn and then to teach, but she didn't use her body in a way that perhaps could have at least delayed what, you know, her genes were leading her toward. When someone meets me at a cocktail party or I think you asked me that question, Peter, what are the three things that you tell someone when they...
Yes, it was in your podcast. I refused to answer it. I was like, walking the dogs the other day and someone asked me the same question. I'm like, well, but the number one thing by far is exercise and physical activity.
But it's not just like, you know, going for a walk. It's physical activity and there's physical exercise and the difference is key. So, there's a lot of cardiovascular and strength training. There's just so many degrees, high intensity interval training, specifically for this case, high intensity interval training is probably the only thing that can move the needle in terms of certain aspects of cognitive function in people with the able to be for variant and like knowing any of that even a few years ago, a little long, a decade ago.
So, optimization of physical activity is key. And your uncle, just so we can paint the picture, your uncle was like, he was a machine. He was a beast. Yeah.
He was a, I mean, I'm, you know, he put... I don't know him and Peter next to each other be close, I'm scrawny or whatever compared, but he was ripped. He just looked great. His leg muscles were like.
Oh, my word. Yeah. all these different things. Richard, was he three four or four four?
He was four four also. I see. Okay. So this is very interesting, right?
Because until you have that information, you could say, well, maybe the reason everything came to him so much later is he was the three four, his sister's the four four, and that explains the 15 year gap. But to have them both be four four, you're basically looking at gender inclusive of the removal of hormones, lifestyle factors, it's some probably some combination of those things that's explaining it. Can you explain a little bit the gender issue? Again, most people who follow the research will be very well aware that Alzheimer's disease disproportionately affects women.
The answer that used to be thrown about was, well, that's because women live longer. Anybody who understands even first order mathematics will realize that the increase in expected lifespan of women does not fully explain that. So there must be something else. Do you think that it's the loss of hormones that explains the remainder of that gap?
Or do you think it's even something beyond that? Yeah. So I would have answered that question just like you did with the age thing, you know, even five, six, seven years ago. And then it was one day on some television, something where someone kept elbowing me.
Someone named Maria, our friend, Maria's driver, it's like, no, no, you got to figure it out. Why do women? No, no, two out of every three brains of all timers or women's brains. And we don't know why Isaac's single figure it out.
And I said, yes, ma'am, I'll go do it. I think I understand much better now. And in the category of likelihood is during the perimenopause transition, there are bio energetic shifts in the brain that absolutely can predispose a woman to accelerate Alzheimer's mythology. And we call it the window of opportunity during the perimenopause transition.
If we can intervene the right way at the right time in the right woman, I believe that we can negate a reasonable amount, if not much of, careful with my words, of the negative impact of this precipitous drop of estrogen, which I believe is neuroprotective, again, the right type of estrogen, the right, whatever, the natural estrogen, I believe is protective, whether we get into harm and replacement, that could be a different part of the conversation and which types and what this and what that. But the bio energetic shifts during the perimenopause transition, you know, why do people have perimenopause? What are the symptoms? They get hot flashes, right?
Night sweats, talk about that. Oh, boy, my sweat. I don't know what you're talking about. No, no, no, no.
Irritability never. Never. So all of these different things, it's a brain disease. Perimenopause is a brain condition.
Those are manifestations of the hormone withdrawal in the brain. And those are the symptoms that brain fog. I used to think I was completely dead wrong. Like women that have perimenopause and they have this brain fog thing, maybe they're just not sleeping, right?
Maybe, well, no, they're not sleeping right. And their sleep is interrupted because of this bio energetic shift. And heck, yeah, you're going to have brain fog. And now we know what it looks like.
I hate that term brain fog. It's so non-specific, it's probably processing speed and attention. And that's how I think of it. But perimenopause is a brain disease.
So I think that's really important. And this bio energetic shift is like, it's like, if you want to fast forward brain aging, like in a woman, in a susceptible woman, because not all women are created equal, an E44 woman, a surgical menopause, meaning taking out the ovaries with it with the uterus. Wow, that's, that could do it. Now, I don't want to say this in all cases.
It again, depends on the individual person, but perimenopause transition is a huge, unrealized risk factor for progression to dementia and Alzheimer's susceptible women. And just be careful and listen to those words, because just because you're going through perimenopause does not mean you're going to get Alzheimer's, but it's susceptible people. It is. And I really believe that from a precision medicine perspective, we can intervene with specific hormones in specific ways.
Is it a patch? Is it a gel? Is it a, you know, all these different things you need? It's estrogen, what type of estrogen from horses, from, you know, from natural, from progesterone.
And we added, these are things that I talk to an OBGYN every other week now. I'm a neurologist. What the heck? So, so I could talk about this for a long time, but just know that this hormone thing is real.
That's where you think the bulk of it is, then Richard, it's less about the age gap or the age advantage, likely, you know, the sort of life span of men, and you think it's the elephant in the room is this enormous hormonal shift. I think that's the most under recognized slash largest impact in a lot of women, but I have to take a step back. And age is the number one risk factor for Alzheimer's. Women plus age, so a 65 year old woman with the eight, four, with at least one or two, eight, four variants.
That's like the perfect storm. Plus you add in this, you know, the perimenopause transition. But you know, there's individual things when it comes to a woman's life. So for example, there's more widows than widowers and widowhood is a astronomically important risk factor for cognitive decline and dementia.
Also women specifically with abdominal obesity, what's all it's all right, sorry, enlarged a waste or conference visceral fat is as the belly size gets larger, the memory center of the brain gets smaller. And we now know that in women specifically, women have a 39% increased risk of dementia when they have, you know, enlarged waste or conferences over a certain degree and they're impacted more so than men. When I think of a woman, and I think of body composition, I'm really paying attention to body fat. And I'm not just paying attention.
I don't like weight. I don't care about for women. I care about what's percent body fat and where is the fat? Is it visceral or otherwise cellulite on the thighs?
I don't care. Oh, thank God. Belly fat. Thank you.
Great. You don't have cellulite in your eyes. You're on the ITI, Isaac's in program. Thank goodness.
This is a podcast. No, you beat me in the spin club. You were you were a person there. I did.
That was impressive. I was dying. So where the fat is key, like in men, I really believe in, I think evidence is coming around to support this, but muscle mass and men is more important as opposed to body fat, especially visceral fat and women as a specific individual sex specific risk factor. So I was going to ask you about that, Richard.