Decoding Dementia Prevention with Dr. Richard Isaacson

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Speaker 1: Pushkin. Hi everyone, Doctor Poyter here, I'm popping in to let you know that we're working on a special episode of Decoding Women's Health. We're i'll be answering your questions about one of my favorite topics, hormone therapy. If you've been wondering about the different types of therapy, when it might make sense to start possible side effects are really anything else? This is your chance to ask. You can leave us a voicemail at four FI five two one three three eight five, or send an email to Decodingwomen's Health at Pushkin dot fm and let us know if you'd like to stay anonymous, or if you're up for having your voice featured on the show. I'm so excited for this one. Hormone support is such a misunderstood area of medicine, and there's a ton of new and fascinating research to talk about together. I can't wait to hear what you're curious about.
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Speaker 2: This show is not a substitute for professional medical advice, diagnosis, or treatment. It is for informational purposes. Please consult your healthcare professional with any medical questions.
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Speaker 3: Genes are not our destiny. The field of Alzheimer's disease is changing so rapidly, the things that I can talk about now like I couldn't even dream about ten years ago.
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Speaker 1: Welcome back to Decoding Women's Health. I'm doctor Elizabeth Poynter. Today on the show. We're talking about dementia prevention and long term brain health. If you've ever cared for a loved one with Alzheimer's, you know the emotional toll. You watch someone you care about lose memories, abilities, and pieces of who they are, and somewhere in the back of your mind, a quiet fear grows, what if this happens to me? For women, that fear is statistically grounded nearly two thirds of people diagnosed with Alzheimer's or female. One of the most frustrating realities of the disease is that there is no cure, but what if prevention were possible? Doctor Richard Isaacson has devoted his career to answering that very question and to helping people understand what they can do right now to reduce their risk. Doctor Isaacson is a preventive neurologist at the Atria Health and Research Institute, and he is also the director of the Institute for neurodegenerative diseases, where he is doing groundbreaking research studying brain biomarkers for Alzheimer's and dementia. He is also the founder of the first ever dementia prevention program at wild Cornell. He has been a pioneer in this area for a long time, and I'm so excited to talk with him today about something we both care so deeply about brain health.
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Speaker 3: So I'm a preventive neurologist, and most people haven't heard that term because it's not a common term. It's like a handful of us. We need an army of preventive neurologists because most neurological diseases, brain diseases start silently decades before symptoms, and that's kind of when we should intervene. And just like you know, when a person has a heart attack or a stroke, that problem, the vascular problems and the atherosclerosis and all that it built up over decades, and it's the same thing with brain disease. So I think, you know, instead of being a reactive neurologist, I want to be a proactive neurologist, and that's what preventative neurology is all about.
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Speaker 1: I first heard about doctor Richard Isaacson, and when I came across his research on how nutrition and lifestyle interventions could help protect the brain against Alzheimer's disease. He had a strong personal motivation. Several of his close relatives had developed Alzheimer's and he was determined to find a way to prevent its development. I was immediately intrigued. For the first time, felt like there might be real hope to offer my patients who had a family history of the disease. I reached out and we soon began collaborating. We were both early believers in the potential protective role that hormone therapy could play for the brain, and today we're colleagues. His approach to dementia prevention has gained significant recognition in recent years, but when he began it was anything but mainstream. Many in the medical community were, let's just say skeptical. So you started the first Alzheimer's prevention clinic and preventive brain health clinic. That was revolutionary at the time. It still is a concept that a lot of people don't speak about enough. How did you come up with that idea? Where did that come from?
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Speaker 3: Yeah, so you know, you said revolutionary. I thought the first word you were going to say it was controversial or that was.
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Speaker 1: My next sentence. Yeah, I was like, why was it so controversy? That's my next question.
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Speaker 4: Okay, gotcha.
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Speaker 3: So yeah, what I would say is two thousand and nine was when I saw my first, like my first Alzheimer's prevention patient. And you know, I see people with dementia and I see family members sitting next to them. And one of these family members was a physician, and he said, hey, Doc, this is tough, and I know you've been affected by this, Like is there anything, like what can we do? Because he knew that I have a family history and obviously he has a family history. And I spoke with forty five minutes in the hallway about things that, you know, maybe he could do. Talked about exercise, and talked about nutrition, and talked about Omega three fatty acids, and you know, there was like a list of things, and that conversation just turned into you know what, why don't you come back and maybe we can check some labs and maybe I can help you through this. And then I saw that person's sister. And then later that same week, doctor Arthur Agatson, who was one of the first preventive cardiologists. You know, people know his name because of the South Beach diet. And he referred me a patient whose father had Alzheimer's disease and he didn't want to get it. And that's when everything kind of clicked, you know, three times in one week. I was talking to a person about how to protect themselves potentially from developing Alzheimer's, and I said, this is what I need to do.
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Speaker 1: How do your colleagues react to this? We work in a system of you know, sick care and reactive care and trade a disease, and you're preventing something that we were taught isn't necessarily preventable at the time.
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Speaker 3: Yeah, I mean one person called it hogwash. One person who I love, a really nice guy, like, you know, Isaac's I don't get you, man. You know you're a good guy, But why are you trying to peddle this stuff? Like what are you trying to sell?
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Speaker 1: Man?
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Speaker 3: This is snake oil. You're selling empty promises. And I was like, but I really believe it. And then he said, well, go study it and.
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Speaker 4: Go prove it.
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Speaker 3: And I said, h call the action. Better go study it and go prove it. And that's when I kind of went on this road show to figure out, like where could I go to prove it? Because when I was at the University of Miami, I wasn't able to build a practice for prevention and do all the things that I needed to do. So that's when I started interviewing, and I interviewed in Boston and New York and the Midwest, and honestly, the only place that would allow me to put my kind of flag in the ground with an announcement to say Alzheimer's prevention clinic was at a wild Cornell in New York Presbyterian.
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Speaker 1: So how long did it take you to say I'm really onto something here with what I'm doing.
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Speaker 3: Well, I'll start by saying the fact that people could come to see a doctor and talk to someone that was a net positive for a lot of people. They felt like they had agency, they felt like they had some control. Now, you know, I have a saying that I say a lot promise, not to overpromise. Back then, you know, I made no promises, But what I said is, you know, if we can improve your heart health, improve your vascular health, improve your metabolic health, and later down the road turns into better brain health, than that's worth it. And back then I didn't have blood tests biological markers like we do now. We had cognitive tests, and these were early days, and you know, took us a long time to prove that these cognitive tests were right. But we were showing in like the late you know, twenty ten, nine, ten, eleven, twelve, that people that took the baseline cognitive tests and then came back after they controlled these risk factors actually had improved cognitive function.
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Speaker 4: And to me, that was it.
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Speaker 3: That was the thing where I said, Aha, their blood pressure is better, there's all these vascular measures that are better, and their cognitive functions better. Maybe this is real. I want to go try and study this improve it. Initially, eighty percent had dementia and twenty percent of my clinic was for prevention, and then little by little its switched. Then it was twenty percent dimension, eighty percent prevention. Then I switched to prevention full time in twenty thirteen.
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Speaker 1: I sent you a lot of patients when you first opened.
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Speaker 4: Co managing patient. I learned a lot from you.
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Speaker 1: I was like a big believer. I'm gynecologist who loves brain help and so appreciated your care of our patients.
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Speaker 3: And honestly, if it wasn't for that, I wouldn't have made a pivot. We did brain imaging in women. We in a structure way, like focused on women's brain health. And you know, women get Alzheimer's more likely than men. Right, two out of three brains affected by Alzheimer's or women's brains.
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Speaker 4: We don't know why.
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Speaker 3: I always said it was age, women live longer, right, Well, no, that was wrong. And basically because of all these questions, half of my time was spent, which it should be half the population, but half of my time more than yeah, more than half of my time was spent on trying to figure out the answers to these questions.
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Speaker 1: Just for our listeners, let's talk a little bit about, like what are the risk factors for dementia and Alzheimer's disease?
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Speaker 3: Sure, so, the number one respector for Alzheimer's disease and dementia's age advancing age and as we get older. You know, it's not exactly like fine wine. Things do happen as we age. Our brains age too, and when it comes to women's brains, women's brains, age at I would say different rates than men. I think that has to do with in part this estrogen drops during the perimenopost transition. I think that triggers accelerated brain aging. And I believe that one of the most powerful things that we can do during the perimenopaust transition for these women is to consider hormone replacement therapy. I think that age and the perimenopaust transition are the two biggest risk factors in some ways, plus obviously having a gene that increases risk. Obviously you can't change your genes, can't choose your parents necessarily, But what you can do is you can change your lifestyle when it comes to modifiable risk factors. I believe that the majority of the negative effects of the life that we live can overcome that risk, and genes are only part of the story. The femal biological sex is only part of that story. And I believe through living a brain healthy lifestyle, we can attenuate or neutralize most of those other risks.
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Speaker 1: Actually, I want our listeners to understand a little bit about apoe four, like what is apou four and who should be tested? Should everybody be tested, or just if you have a family history.
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Speaker 3: Talk to us about that great question. So, for everyone out there that has not heard about apo e, a poe is a gene. You get either a two, a number three, or a number four from Mom, and you get a two, A three, or four from Dad. Apoe three is neutral, Apoe two is protective, and a pox four increases risk. So everyone out there, everyone is either a most commonly three three, which is about fifty five percent of the population. Three three is neutral risk. So if a person has one copy of an eight POE four variant from Mom or Dad, that increases risk a little bit of Alzheimer's disease. If a person has two copies of the a POI four variant, so one four from Mom, one four from Dad, then that risk is higher. But but, but please, genes are not our destiny. We can win the tug of war against our genes. And what I mean by that is this is not a genetic combination that definitively leads to Alzheimer's. Does it increase risk?
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Speaker 4: Sure?
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Speaker 3: Can you neutralize or negate or you know, account for a lot or most of that risk by doing brain healthy things and living a brain healthy lifestyle. I absolutely believe that to be the case, whether it's sixty percent, seventy percent, eighty percent, or ninety percent of that dad Apoi four risk. I think most of that risk can be neutralized by brain healthy living, modifying risk factors. And I believe that people with this genetic combination should kind of follow a different path on the road against Alzheimer's disease. You know, forty five percent of dementia cases may be preventable if that person does everything right. And that's based on the twenty twenty four Lancet Commission. So I believe passionately, yet in a controversial you know, want to be clear that this is not maybe the exact accepted you know framework. I think it's really important for people that want to know to know and to find out. And if a person has an Apoi four, okay, let's do it, let's fight, and let's go. For example, women with one or more copies of the Apoi four variant, I start looking at their estra dial levels or estrogen levels in the blood. If that starts dipping even sometimes before perimenopausal symptoms, maybe we need to start doing something about it. And then do something about that. On the early side, if a woman has perimenopausal symptoms and they have an Apoi four variant, I'm really, really really gonna want to treat, and I'm gonna obviously work very closely with uns or are there treating clinicians to try to navigate that. Women or men with apoe also need to drink alcohol in a much less way like alcohol plus apoe is bad, Smoking plus apoe is bad. A sedentary lifestyle plus apoe is bad. There are so many things that I tell patients to do differently if they have one or more copies of the Apoe four variant of the gene. For example, Omega three fatty acids, So Omega three fatty acids are a brain healthy type of fat. If a woman wants to reduce their risk of Alzheimer's disease and they have an Apoi four variant and they're eating lots of fatty fish or a couple times a week fatty fish like lake trout, mackerel, herring, Alba cortuna, wild salmon, sardines, and they can't get the Omega three fatty acid levels up from eating a brain healthy, you know, fatty fish diet. Then potentially using an Omega three fatty acid supplement is preferentially beneficial for people with the APOI four variant. So the take on point with APOE is, I believe it's important to be tested. I believe it's important to then personalize a care plan based on APOEE, and we've published on this. You know, the instruction manual is at least there, But I would say most doctors and most of the public are totally unaware. I think the other thing is if there is someone out there listening that's reluctant and doesn't want to know because they think that if they find out that they have an APOI four you know their life is going to be ruined and they're going to be sad and anxious. I'd first say, I don't agree that that's the case. When you get a genetic result like that, it does not mean you're going to get Alzheimer's disease. You can have one or two copies of apo BE four and never get Alzheimer's, and you cannot have any.
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Speaker 4: Copies of apo BE four and still get Alzheimer's.
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Speaker 3: So to me, getting tested for the APOI four variant is something that can help personalize care, but not predict if someone's going to get the disease.
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Speaker 1: So the estimate is about forty five percent of dementia cases can be prevented. What about the other fifty five percent.
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Speaker 3: Some people can do everything right and still get Alzheimer's disease, And in a very small number of cases, like a few percent, there's a gene, an early onset gene where if they get it, and these are usually people that get Alzheimer's symptoms in their forties or fifties, we just don't have the best tools for or many tools at all. There are other people that have different genetics and different lifestyle factors and different things that maybe we haven't figured out yet, where maybe they do everything right and they can delay Alzheimer's by six months here, two years, or five years, but no matter what they do, they're still going to develop. So what I would say is based on the best available evidence, there's a reasonable number of people that can get off the road to Alzheimer's, but there's a lot of people that may only be able to delay it. But to me, that's a glasses have full thing. If we can delay Alzheimer's by six months, a year, two years, or five years, and in that time period, that new blockbuster drug comes and something comes.
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Speaker 1: Out, right, figure it out.
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Speaker 3: Then through the person's own you know, behavior change in adopting brain healthier habits than that person was able to make a difference. But no, I think within a few years will be at fifty percent, fifty five percent, sixty percent because the evidence will evolve. But I think we're pretty close to the majority of people. And that's not what I was taught in metopal.
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Speaker 1: Yeah, that's just kind of like the cancer predisposition genes, right, like ten percent is hereditary. So talk to us a little bit about those imaging studies that you did, because I thought they were so profoundly impactful.
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Speaker 4: Yeah.
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Speaker 3: So, and this is you know, led by doctor Lisa Mosconi and Holly Hurstov at the Alzheimer's Prevention Clinic and Women's Brain Initiative. And what we did was we looked at basically brain imaging of women during various time periods, so premenopause, perimenopause, and postmenopause, and we looked at women's brains in terms of MRIs MRIZ or magnetic resonance imaging, which is brain imaging that can look at the size of the brain like if they're shrinkage or if it looks normal. You could also look at something called white matter disease, which is evidence of vascular issues and strokes and mini strokes and silent strokes. And then we looked at a type of imaging called the PET scan. We use a marker that actually bound to amyloid amoloids, that sticky protein, a plaque that builds up in the brain of a person with Alzheimer's disease. And basically we tracked women. We also then had a men's brain imaging study that kind of tailed on later, and we tried to compare the two. But women who were treated with hormone replacement therapy had less amoloid accumulation and their brains looked better. At least one or two, probably three of these women were your patient, So you were a big part of this. And I mean I had a sixty sixty one year old woman who sho had two copies of the APRILI four variant. She should have done worse. Her brain looked pristine. Her brain looked like a fifty year old woman or a four five year old woman. Why she had been on harmone replacement therapy the whole time. And I remember another woman was on harmone replacement therapy and it's seven years because it was some magic number. They told her to come off and the woman's like, but I don't want to, but the doctor said, you have to because this study and this research and you can't be on it for more than seven years. And the woman came off, and like, aside from feeling worse, her cognition got worse.
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Speaker 1: Her hormones scary stuff.
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Speaker 3: Clearly went down, her estrogen went down, her cholesterol went wackado, I mean, everything got worse.
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Speaker 4: And then she had to fight with her gyn to go back on hormone.
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Speaker 1: Replacement therapy an better education.
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Speaker 3: Yeah, so she finally did, and she felt better, but she probably lost like six months of I think brain protection and she ended up okay. But you know, I think where we are today, hopefully that happens less.
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Speaker 1: I think it does happen last, but it's still happening.
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Speaker 4: I there is so much, my gosh, just garbage out there.
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Speaker 3: I'm worry about estrogen and it saddens me because estrogen is what I believe to be among the most if not the most protective like chemicals. A woman's brain can be protected by we just see better brain outcomes, like brain size is larger, amyloid is less or not there, a cognitive function is better, memory function is better. So to me, estrogen is a brain protective hormone.
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Speaker 1: Late start estrogen women in their sixties. We're being told kind of by our guideline makers, right, don't start after sixty or after ten years of menopause. So talk to us about that. Are we okay to use estrogen in older women over sixty?
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Speaker 4: Yeah?
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Speaker 3: So I can tell you if we had this conversation a few years ago, I would say I have no idea. I would say that the best I could do is women that were on estrogen for between seven to ten years or greater than ten years in our cohort, and what I saw had better brain outcomes. But I didn't have like definitive evidence. Now and again I wouldn't say this is definitive evidence. And we haven't fully published this. We've presented this at a conference, but not published. We have women between the ages of forty two and sixty seven in our research coulport where we track brain biomarkers, we track hormones, and we track Oh there is something I want to talk to you about We've done six blood draws during the menstrual cycle just to figure out like what happens to these brain markers as estrogen and progesterone change during the natural mentrol cycle. So between the ages of forty two to sixty seven we've studied hormone replacement therapy and on a whole on the women that we've studied hormone replacement therapy with estrogen and or progesterone, depending on with the gin and or primary care and or endrocronologists we have helping too. We have shown significant improvements reductions in tau protein, which is a bad protein that builds up in the brain of Alzheimer's, and maybe a little bit of familoid too, but more on the TAW side, and women have higher baseline taws than men, and that's a whole different discussion and we haven'tgured out exactly why that is. But on the whole harm and replacement therapy throughout, whether you're forty two, we have a forty five year old, we have a forty seven year old, we have a forty nine, multiple forty nine, fifty and fifty one, so we have a cluster obviously, right around there. And then we have a sixty year old woman and a sixty seven year old woman. And in these individual women, when we look at like how were their numbers, they got more normal. Some of these women were borderline optimized yep, and they got optimized it. But basically we're building up a cohort of women to study this in and so far in our IRB approved research study, we've shown better brain protein outcomes after starting harmon replacement therapy, even in women at age sixty and above.
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Speaker 1: Coming up, when it comes to Alzheimer's, what are the biggest risk factors outside of hormones and genetics and what are the best possible actions we can take to mitigate them. We'll be right back. Let's talk a little bit about the other risk factors for women. Actually, we've talked about hormonal risk factors. You hear a lot like heart health is brain health, cardioc health is brain health. Talk to me about the other risk factors for Alzheimer's STU sure.
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Speaker 3: So you know, in terms of lifestyle factors, there's many A hugely important bucket is vascular health and vascular brain health. So things like diabetes. When a person has diabetes, they have twice the risk of developing Alzheimer's disease. High blood pressure, hypertension, Does it cause Alzheimer's, Well no, I don't think it causes Alzheimer's, but it fast forwards cognitive decline. High cholesterol. Oh boy, same sort of thing. You know, people say, oh, your cholestero's borderline. Go you know, eat less this or go exercise more. No, A lot of that's genetic and like a lot of times, most of the time someone's going to need a medicine if the general lifestyle things don't work. So when I think about the big buckets blood pressure management, cholesterol management, and diabetes management, what I would say here is borderline is not normal and borderline cholesterol, borderline blood pressure. You know all these numbers that are borderline. See you back in a year. Like the difference between normal and optimal and normal and borderline is a big difference when it comes to preventive brain health. So what I would say here is know your numbers. Everyone out there should know what their blood pressure is. And there's a study called the Sprint Mind Study. The Sprint Mind study looked at two different blood pressure ranges and the effects of these blood pressure targets on brain health. And I would say a lot of doctors think that one forty eighties is like okay, But this study looked at how do people do one forties versus a lower target of one twenties or below. And I actually stopped the trial early. The results were so good. After three and a half years of just lowering the blood pressure from one forties to one twenties, not a big drop, people were able to reduce their chances of developing the earliest symptomatic phase of dementia called mild cognitive impairment by nineteen percent, well nineteen percent, just by optimizing blood person. So again the concept here is normal versus optimal. Same thing with cholesterol. I see so many people out there with ldl's that's you know, the bad cholesterol LDL cholesterols one thirties, one forties, one fifties, on sixties, one seventies, And doctors will say, eh, I don't know, let's.
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Speaker 4: See it back in the year.
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Speaker 3: Go eat less fast food and the person's like going on any fast food. The take on point with cholesterol is you can eat everything right and still a high cholesterol. So what we try to do fundamentally is if a person is doing everything right from a nutrition perspective and their cholesterol is still high, then we may need to use a pharmacologic agent, a drug, a prescription drug. And when we don't know what to do, we may look at the heart because the calcium score in the heart basically predicts what your heart risk is for the following ten years. And if person has elevated calcium in their heart vessels, they are at a much higher risk of vascular cognitive impairment or vascular dementia twenty years later. And what we can look at in the heart potentially as a proxy for brain is if a younger woman is at risk and their calcium score is zero, but they have soft plaque building up in their heart that hasn't turned hard yet, and they're in their forties or fifties or sixties, then that's someone If they have borderline cholesterol, I'd rather treat them, and as a clue that we should treat earlier rather than later. Now, there are some women and some men that just their vessels are clean, their brain looks clean, there's no soft plaque, there's no hard plaque, and they have borderline or elevated cholesterol. And maybe those cases are okay not to treat, but there's so much nuance here, and you know it's an evolving story.
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Speaker 1: Yeah, that's tough one. So talk to me about statins a little bit, because you know, I have a few patients that will come to me saying I'm not going to take that statin because it actually causes dementia because it impacts my mitochondria, the powerhouses of the cells.
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Speaker 3: Yeah yeah, okay, my favorite topic, I'm so go advertised is being recorded. Hop Yeah, it's the same, right, I'd love to do this again. Don't get me wrong if there's a glitch. But okay, let me start by saying the totality of evidence is extremely strong, that the net positive effects of statins are absolutely net positive and protective on brain health, and the lion's share of studies, the vast majority of studies where people have been on statins, and these are epidemiological studies and they follow them over time. People that take statins are at a lower risk of dementia and Alzheimer's disease. That's what I would say. There are certain cases. This goes back to the whole personalized care and precision medicine there are certain cases, and I would say this is a small number of cases, but there's a lot of internet chatter about this where people who take statins feel that they have brain fog. People that have statins can also have muscle soreness, and there's all sorts of things that can happen from statins. But I would say, on the whole, the vast majority of people that take statins will be most likely to benefit from statins on the overall net effects. So I guess what I would say is, I don't have all the answers. I don't have the perfect answers, but the totality of evidence suggests that statins are protective. You know, I don't have the perfect answer for precision based cholesterol treatment, but this is something we're studying in our research.
00:27:26
Speaker 1: Let's talk about sugar. Most people will go the doctor and hemoglobin a one ce by point six, it's okay, you don't have diabetes. By point eight it's okay, you don't have diabetes. But it's insulin resistance absolutely, And so talk to us about that. What should be our target for our measurements of our glucose metabolism?
00:27:45
Speaker 5: Yes?
00:27:45
Speaker 1: Why?
00:27:46
Speaker 4: Yeah?
00:27:46
Speaker 3: So I think I mentioned earlier that people with diabetes, and it's a frank diagnosis of diabetes where hemoglobin a one cee as much higher, is two times the risk of Alzheimer's. But insulin resistance just really fast forwards amyloid accumulation and amyloid isn't that bad protein the pathological protein that builds up in the brain of a person with Alzheimer's disease and insulin resistance, I think fast forwards brain aging. As the belly size gets larger, the memory center in the brain gets smaller. Fat around the mid section, around the visceral organs, especially for women, Women that have increased belly fat are at an increased risk of dementia.
00:28:23
Speaker 1: That's huge because it's such a problem for perimen apostle women.
00:28:28
Speaker 4: Stubborn area to get rid of it.
00:28:29
Speaker 3: And women could do everything right and still have trouble getting rid of that fat. And you know, there's some you know stuff which I'm sure we're going to talk about GLP ones, which is.
00:28:37
Speaker 4: A very interesting topic, hot button.
00:28:39
Speaker 3: That's our big hot button topic which you and I have both talked about and implemented in our clinical practices. But women and men need to gain muscle mass, and the more muscle you have, the better your metabolism. Women and men need to lose belly fat and that can be hard, and that's you know, through a targeted exercise, lower intensity zone to training that some people talk about. Through nutrition changes obviously sometimes these new drugs that can help, but yeah, insulin resistance, just fast forwards brain aging and fast forwards amyloid and you know, as one of the most critical things that we need to optimize in the fight against Alzheimer's disease.
00:29:15
Speaker 1: Give us your exercise prescription. Is it zone two cardio? Is it strength training? Three times a week? Like? What is the exercise prescription to prevent dementia?
00:29:26
Speaker 3: Everyone that I see gets an individualized exercise prescription based on what I would say are three factors. We call it the ABC's of Alzheimer's Protection. My next question, so A, is anthropometrics. Anthropometrics is a big fancy word for body composition. Body composition is percent body fat and muscle mass, and to me, the percent of lean mass is the most important. And it's not just about what the percent body fat is, but where it is in a woman that has stubborn belly fat, especially perry or postmenopausal. We recommend really a multi prong attack. So number one, zone two training, which is about steady state cardio where a person is exercising walking fast, for example, but the person can still carry on a conversation. This is not, you know, high intensity interval training, This is not sprinting. This is lower intensity steady state or zone two means zone two of your cardiovascular rate where you can take your maximum heart rate and you multiply that by point six or point sixty five, so at sixty to sixty five percent of what your maximum heart rate is and try to stay in that heart rate zone for forty five to sixty minutes to burn the carbs that are in your blood and basically lose body fat. And I think most people are unaware that. Like high intensity interval training, for example, where someone's either on a peloton bike at a hit class or an orange theory or berries, that's a great way to get a great workout and sweat a lot and make your heart stronger. But a lot of the times you're just not being efficient at burning body fat. You actually burn body fat more efficiently when you're at a lower steady state. The zone two cardio, where again this could be walking fast with a weighted for forty five to sixty minutes and you do that three times a week and if your doctor says, okay, you know, I can't give anyone individual medical advice here, but the doctor says, okay, even doing it fasted in the morning, and that's another way to jump start body fat loss. So if a woman is trying to lose fat around the midsection, we recommend at least a few times a week, two to three times a week of Zone two training. We absolutely, absolutely, absolutely recommend strength training. Strength training is tricky in women during the peri and postmenopause because many women have trouble gaining muscle mass after the perimenopause.
00:31:43
Speaker 1: You gotta lift heavy, yep.
00:31:44
Speaker 3: But like there are certain women that just cannot gain muscle, And then what do you do? Is it protein? Is it creatine? Is it testosterone?
00:31:52
Speaker 4: Hormones? Hormones and hormones exactly, And that's what I thought you were going.
00:31:55
Speaker 1: To say, persistence, lift heavy yep, safely yep, and hormones and hormones.
00:32:00
Speaker 3: And I agree with that, and I had to put nutrition and protein and all that kind of stuff. But you can't just do zone two, and you can't just do strength training, and you can't just do high intense interval training. If a woman is muscled, then you want to do more strength training.
00:32:14
Speaker 1: For brain health, what should we aim for in terms of percent body fat, percently muscle mass.
00:32:19
Speaker 3: These are tricky things, so we recommend dex's scans. So DEXes are a little bit of radiation, but it's like less than a chest X ray minimal, and you look at body fat, muscle mass, and you look at bone density. So to me, when I'm giving a woman recommendations for brain health, I'm also very interested in their bone health. And if a woman has osteoporosis or low bone mass, I'm going to prioritize strength training, maybe more so than would otherwise. You know, obviously I'm trying to prevent someone from getting dementia, but when it comes to women, I also want to prevent them from having like a fracture. You know, my mom, when she was eighty two, fractured her femur, her hip.
00:32:57
Speaker 4: She broke her hip.
00:32:58
Speaker 3: And like you learn in medical school that once a woman breaks their hip, they usually die within six months. And six months later, my mom passed away, So you really taken the whole picture.
00:33:10
Speaker 1: Talk to me about other prevention maneuvers that you can do. Social engagement, neuroplasticity, cognitive reserve, keeping your mind nimble, and learning new things.
00:33:19
Speaker 3: Yeah, so if you don't use it, you lose it. I mean, the list goes on and on. You know, forty five percent of cases of dementia maybe preventable. There are so many modifiable risk factors, you know. For example, hearing loss is something that people just they hear and they're like, wait, what what do you mean treating hearing loss? At like eight percent of cases of dementia may be attributable to hearing loss, And that's confusing, like why would that be well, less socialization, less interaction, less verbal whatever. So hearing loss is key. Vision screening is key. Socialization is absolutely critical. Learning something new, a new language, musical instrument. Stay engaged. It's not just you can do all the sodoka you want and you're just going to get better at sodoku, but learning something new, socializing with friends, staying engaged. Stress reduction is key. Stress mitigation something called mindfulness based stress reduction NBSR. It's tied to better brain health outcomes.
00:34:14
Speaker 1: So you do a lot of work in biomarkers. Oh yeah, right, So tell us the utility of biomarkers, what they are and when does Alzheimer's start? Does it start in our forties and we just don't know that it's starting and biomarkers can help us with that.
00:34:30
Speaker 4: Or talk to us. Yeah.
00:34:31
Speaker 3: So, you know, I've been talking about trying to develop and create and prove a cholesterol test of the brain to fruition. And what I mean by that is just like everyone goes to their doctors and hopefully starting in their thirties and forties, they get a cholesterol test where you look at your total cholesterol, your HDL, your LDL which is the bad cholesterol, and triglycerides, and then doctors know how to treat it. There's going to be what I colloquially call the cholesterol tests for the brain, and instead of those markers, you're going to have the amyloid and the TAO and this and the that. And currently in our lab we have over one hundred and fifty markers that we're looking at and that we're tracking over time. So what I would say is, you know, it's still early days. There are blood tests that are available today that if a person has symptoms and the person's doctor thinks that the symptoms could be related or due to Alzheimer's disease, then there are blood tests out there today. They can be used to basically say, aha, this is a good screening test, these symptoms are probably due to Alzheimer's. I think when it comes to prevention and risk reduction and doing a risk assessment, our work has shown that you can't just order one test. You can't just order a handful of tests. You have to order a panel of tests and really interpret them within the context of each other. So I hope and I believe that people in the coming years will go to their doctors in their thirties, forties, fifties, sixties, seventies, eighties and beyond before they have symptoms and get this cholesterol test for the brain, this risk assessment panel to figure out are they at risk? And then not just are they at risk, but based on the markers, what you can do about it. If a person has high tau before symptoms, what do you do. If a person has high amyloid before symptoms, what do you do? It's the same thing like what do you do if you have an LDL cholesterol that's high, Well, you take this medicine or that medicine, or you do a scan. We kind of understand that for preventive cardiology. We're just starting to understand that now for preventive neurology, and you know, I hope that very soon we'll be able to offer these tests to people. I think the challenge with blood tests for Alzheimer's disease one, sometimes you can have elevated levels and they're not really elevated. They could be a false positive. What we've seen in our in our work is that people with active viral illnesses. I've seen people with you know, for example, herpes lesions or herpes herpie simplex one. I've seen someone who just had COVID and their markers were off the charts, and then a few weeks later we retest and the markers came down. I've seen people that looked like they had elevated brain biomarkers worrisome for Alzheimer's disease triggered by things that were transient. I had someone going through a divorce, sleep deprived, terrible like situation, really rough, and one of these brain markers was through the roof, came back six months later. I was pretty worried about the person. Divorce was over the person that slept. We repeated the markers and everything was normal.
00:37:24
Speaker 1: It's time for a quick break. But when we return, doctor Isaacson and I will get into some of the biggest hot button issues around long term cognitive health, and we get into what the future of diagnostics and treatment will look like for Alzheimer's and dementia. Decoding women's health will be right back. Let's do some hot button topic. Sure, of course, talk to me about testosterone in women's brain health.
00:37:59
Speaker 3: So I was for both women and men a decade ago, like I would say anti testosterone, I would say, what are these people doing or reving up the system? Like why are we using testosterone? That's my performance enhancing drugs? Like I would say, that's the way I was a decade ago. I was wrong what I've seen clinically, and this is a shotal shift for me. I mean, there's probably ten men and women that have started on testosterone that I mean one more muscle mass or sustained muscle mass. Two felt better clinically, you know, was tired yet.
00:38:35
Speaker 4: Yeah, exactly.
00:38:36
Speaker 3: People don't even realize how bad they feel until they start taking testosterone, and like that was really surprising to me. I didn't really understand that. And what I would say is when I say estrogen replacement plus progesterone like slam dunk, better brain outcomes on the whole. With testosterone, I would say a lot of people on testosterone, I don't see much of a brain health brain biomarker change, but some people I do, it's just less robust of a change. So please don't take this as fact. Then we haven't studied this, but I've never seen brain biome marker worsening in the ten or so people that have started on.
00:39:15
Speaker 1: Testosterroen important because yeah, some some women with lower testosterone levels have fatigue. And it's interesting because we always asked this question like how do you feel? And it really speak could you feel better?
00:39:24
Speaker 4: Right?
00:39:25
Speaker 1: You know, let's get really controversial. Okay, I'm ready microdosing GLP ones for brain help. Yeah, my favorite topic.
00:39:32
Speaker 4: Yeah, this is the whole.
00:39:32
Speaker 1: Thing lands me in hot water all the time.
00:39:35
Speaker 4: Oh you're telling me forget it? Okay.
00:39:38
Speaker 3: So I did not wake up one day and say I'm gonna try to advance the narrative on microdosing. What happened was I had a patient that needed a GLP one for insulin resistance that did not seem to benefit from lower carb diets, exercising out to wazoo, you know, doing the zone two, doing the strength training, was still insulin resistant eight POE four. Just too many risk factors and I just did not feel comfortable. Was the person diet No is this off label by the FDA? Yes, but their doctor put them on tr zeppetide, which is, you know, one of the GLP ones two point five milligrams, and that person felt really sick, lost some body fat, which is good, also lost a little muscle mass which wasn't as good. And basically the recommendation was try half of the dose. And in that one case, that's what kind of like changed it for me. The person did better, felt better, their insulin resistance went away, and their brain biomarkers improved. And this was using less than the FDA approved regular dose of the drug. So the drug companies will say, oh, that's never been studied, you can't use it. I mean people use drugs off label all the time, like blood pressure medicine, can't tolerate it, get lightheaded. Use less pain medications. Oh boy, getting lightheaded, but you're still in pain. Use less some people it works for right. So I think, you know, using drugs off label is controversial, and I think you know, obviously the doctor has to talk to their patient about this and make informed decisions. But in our data set, you know, we have a subset of people that have taken less than the lowest dose recommended or FTA approved of glp ones, the injectables. And also I want to say that there is twenty years of data on glp ones, the oral ones that show that people that are on these glp ones for long periods of time have a lower likelihood of developing dementia. It's not like we're trying these things willy nilly. I mean, there's like many studies that have shown this. There's also a study that's going to be published sometime later this year to look at is the oral dose of semaglutide and commercial name is Rabelsis, but semiglutide is the generic name, and a fourteen milligram pill is being studied in two studies called Evoke and Evoke plus and people with mild cognitive impairment, which is the earliest symptomatic phase of Alzheimer's to see. You know, does it improve symptoms? Does it delay progression? Like?
00:42:02
Speaker 4: How do these people do?
00:42:03
Speaker 1: These are people without diabetes or without insulin resistance crack. These are just like all comme. So how much of the effect do you think is a direct effect of the gl maybe as an anti implammatory And how much of the effect of this microdose sing do you think? Is it just change in body comp and decrease of visceral fat.
00:42:19
Speaker 3: Yeah, I don't know. I think there's more to it than just the body fat loss. I think there's some sort of direct effect. I think something happens with inflammation. I also am very you know, I'm an advocate that if people are on glp ones and they're losing muscle mass or losing a majority of their weight is due to muscle mass, I tell their doctors or or I advocate, because I'm not usually prescribing these, please stop, or please go on a lower dose, like we don't want to lose muscle mass. And you know, I guess what I would say is in the right person, at the right dose and for the right duration of time, as long as the person's doing strength training, eating enough protein and carbs around their workouts so they don't lose muscle mass, and eating brain healthy and otherwise, I really think GLP one's at lower doses if possible, when possible, maybe one one of our most like helpful things for dementia.
00:43:14
Speaker 1: Prevention keytnes keto.
00:43:17
Speaker 4: Yeah.
00:43:19
Speaker 3: I spent a lot of my time earlier in my career, like probably fifteen years ago on keytnes and ketosis, and I really do think that there's something to this and lower carbs and ketogenic diet, time restricted eating, intermittent fasting. There's what I would say, is this The answer here is personalized medicine and precision nutrition. And I haven't figured out like the exact algorithm I think, but I'm not certain that people without an apoe four variant may benefit more from keytnes and ketosis.
00:43:47
Speaker 1: And that's because you can use them as an alternate energy source for the brain. Right. This is like tapping into the brain's energy production exactly.
00:43:53
Speaker 3: So the brain can only use two things as fuel. Sugar, which is, you know, the stuff that we don't want to overload the brain with because it causes inflammation, insulin resistance and key tones. KEYTNES is like, you know, a cleaner burning fuel. It's like the hybrid car model, Like you have the hybrid battery, which is the KEYTNES, and then you have the gasoline, which is the sugar. And of course what do you want to do? You want to use the keytones right if you can. I think there is probably a role for ketogenic diet maybe and if someone can handle it, but I don't fully have it all worked out.
00:44:21
Speaker 1: Yet looking forward to that answer. And some of these interventions, like lifestyle interventions impact women more than men. Actually, is that correct or yeah?
00:44:30
Speaker 3: So you know, we actually published a paper on this. We took our Alzheimer's Prevention Clinic cohort and we actually showed that the interventions, the lifestyle interventions in our Alzheimer's Prevention Clinic actually on the whole worked better in women than in men.
00:44:44
Speaker 1: So like some good news for women.
00:44:46
Speaker 4: It's really good news. And you know, we're not powerless.
00:44:51
Speaker 3: And our data shows that while yes, on the whole for everyone, it work, meaning lifestyle interventions and managing risk factors. On average, the people in our study got twenty one different interventions, so This wasn't like, you know, eat a magic blueberry and think you can prevent Alzheimer's disease. But between the synergies you have the exercise, the brain healthy nutrition, the olive oil, omega three fatty a acids, the stress reduction, the staying engaged and modifying your blood pressure, cholesterol, diabetes. Like you do all of these things together, socialization making sure someone gets adequate sleep. Doing all these things together works, and it works better in women. And it worked regardless if a woman had either one, zero or two copies of the Apoi four variant.
00:45:33
Speaker 1: What have I not asked you about today? Do you think is important for especially for midlife women, in their brain health.
00:45:39
Speaker 3: I've seen so many women over the last fifteen years that are concerned about their brain health, and women are more likely to be affected. The Apoi four gene affects women, you know, more in a negative way. There's so many individual risk factors for women that are really confusing, complicated, and I would say, in some way scary, and the best thing that I could do is just tell women to just just pause, take a deep breath, and it's going to be okay. Genes are not our destiny. The field of Alzheimer's disease is changing so rapidly. The things that I can talk about now, like I couldn't even dream about ten years ago. I went from like seeing patients and you know, doing all these like cognitive tests and some blood draws to now like running a comprehensive blood biomarker lab where we have multiple pieces of equipment and we like finger prick techt Like I have a fingerprint card and my backpack over there, Like we're going to be doing finger print card testing soon. It's not there, it's not one drop of blood, but it's like with nine drops of blood, we can detect one hundred and twenty brain proteins. Like things are getting better. And what I would say to women out there, regardless if you're premenopausal, perimenopausal, or postmenopausal, there are things that you can do today to improve your brain helth tomorrow. You know, we have agency. We can take control of our brain health. Talk to your doctor, get online, learn there are resources out there we can win the fight against Alzheimer's disease.
00:47:02
Speaker 1: Where can we find information, Like because a lot of doctors don't talk about this and it's not well recognized but where can we get the real information?
00:47:09
Speaker 3: Yeah, so back in twenty fourteen, you know, we created the first I believe kind of evidence based curriculum about Alzheimer's prevention. We studied it in a randomized controlled trial, and we published on it and we put coursework out there. We've then updated that and now we have two different resources. So one people can go to id dot org. I in D stands for the Institute for Neurodegenerative Diseases i ND dot org and if you go to the learn page i ind dot org backslash learn, you can watch video after video after video. There's over fifty videos interviews about brain healthy nutrition and the latest on blood testing and exercise and all sorts of information. It's all available for free. The other website is also a randomized controlled study that we've done. It was funded by the NIH and National Students of Health, where people can go to Retain your Brain dot com and basically using a software platform that gets to know you from the comfort of your own cell phone. You can do a risk assessment, you can do cognitive activities and then the software will learn about you. You can actually type in your APO if you know it, if you checked it on twenty three and meters and basically the SOFTWARELD then put you on a kind of a risk education plan to try to get you to adopt brain healthier habits. So what we've tried to do is take everything we've learned in our research studies, take everything that we've learned from other people's research studies, and we've tried to put it out there.
00:48:31
Speaker 4: And I think that's going to be the way to It's pretty cool.
00:48:34
Speaker 1: That's kind of a model for like a lot of issues that we can prevent, right, not just brain health. But it's like a great paradigm.
00:48:41
Speaker 3: Yeah, I mean, access to care is so difficult, and you've said this before. We're a sick care system. Were not a healthcare system. There's no diagnostic code that a doctor can bill an insurance company for the term Alzheimer's prevention. We lost so much money at the Alzheimer's Prevention Clinic. It was like impossible. We were collecting twenty eight cents on the dollar, and we had to get grant funding and donations and all this kind of thing. Preventive care is like it doesn't pay, doctors can't build for it. So we've decided to just put it out there online for free.
00:49:09
Speaker 1: Yeah, that's great. I mean to really focus on preventative care. Thank you so much for joining us today. So appreciate it. It's, like I said, such an honor to have you.
00:49:17
Speaker 4: I appreciate it. Thank you.
00:49:22
Speaker 1: The landscape of Alzheimer's prevention is changing. Leading neurologists like doctor Isaacson are proving through robust research that evidence based strategies can delay and even in some cases, prevent the disease from ever taking hold. And there are meaningful steps that you can start today. First, know your genetic risk. A simple test can tell you which APOE variant that you carry. Even if you have one or two copies of the APOE for variant, it does not mean that you're destined to develop Alzheimer's. Understanding your risk helps you take action early. Talk to your doctor about hormone support. Estrogen is a brain protective hormone. Beginning therapy around menopause is ideal, but even later into your sixties and beyond may still offer cognitive benefits, and I look forward to that research in the future. Monitor your numbers, keep an eye on blood pressure, cholesterol, and hemoglomina ONEC borderline isn't optimal, and there is a big difference between optimal and borderline, so it's not something to shrug off. Even small improvements in metabolic and vascular health can positively affect brain function. Understand your body composition. A DEXA scan can help you track visceral fat, which is linked to cognitive decline, as well as bone density and muscle mass. Zone two. Cardio and strength training are really powerful tools for shifting body composition. And if insulin resistance is severe, talk with your doctor about whether a golp one medication might help protect your mental well being. Chronic stress is neurotoxic. Find practices that help you slow down, breathe, and enjoy your life, and finally, stay hopeful. We are living in a moment of unprecedented progress. Do what you can today, knowing that even more effective tools are coming tomorrow. Coming up on the next episode of Decoding Women's Health, I speak with a pioneer and weight loss surgery about his own experiences not only as a clinician, but also as a patient.
00:51:37
Speaker 5: Society, including a lot of doctors, think people are taking the easy way out because there's this absolute myth and it's a myth that you can do this sort of weight loss on your own and keep it off.
00:51:55
Speaker 1: Decoding Women's Health is a production of Pushkin Industries and the Adrea Health and Research Institute. This episode was produced by Rebecca Lee Douglas. It was edited by Amy Gaines McQuaid, mastering by Sarah Burguier. Our associate producer is Sonia Gerwitt. Our executive producer is Alexandra Garreton. Our theme song was composed by Hannes Brown. Concept creative development and fact checking by Shavon O'Connor. A special thanks to Alan Tish, David Saltzman, Sarah Nix, Eric Sandler, Morgan Rattner, Amy Hagdorn, Owen Miller, Jordan McMillan, and Greta Cohne. If you have a question about women's health in midlife, leave us a voicemail at four f five two oh one three three eight five, or send us a message at Decoding Women's Health at Pushkin dot Fm. I'm doctor Elizabeth Pointer, and thanks for listening. Until next time.