Dr. Richard Isaacson, Director of the Alzheimer’s Prevention Clinic at Weill Cornell Medicine, shares the just-published results of his groundbreaking clinical trial which show that a personalized prevention plan can dramatically lower the risk or progression of Alzheimer's. Also joining the discussion is one of Dr. Isaacson’s patients who is living proof that this new approach works.
Dr. Stieg: Dr. Richard Issacson, one of the leading authorities on Alzheimer's disease joins me today to talk about Alzheimer’s disease and the results from his groundbreaking clinical trial. I'm also especially pleased to welcome one of Dr. Isaacson's patients from the trial, Karen Segal. Karen became a leading advocate for Alzheimer's prevention after her mother was diagnosed with early onset Alzheimer's. Currently a board member of Us Against Alzheimer's, she is focusing our efforts on increased awareness of the critical need for Alzheimer's prevention. Welcome to you, Richard and you Karen, and thank you so much for being here.
Dr. Isaacson: Thank you.
Karen Segal: Thank you.
Dr. Stieg: Richard, I was hoping that you could go into a little bit of detail. You've established the Alzheimer's Disease Prevention Clinic at Weill Cornell Medicine, and as a result of that, you've been following, I believe, over 100 patients and published your results with what we can do to prevent and improve cognitive function. Can you go through that?
Dr. Isaacson: Sure. So back in 2013 we started the Alzheimer's Prevention Clinic and we've been recruiting patients ever since. We've actually seen over 600 patients, just over 300. I actually have a clinical diagnosis of, of dementia due to Alzheimer's. And the other two to 300 are really in this, uh, prevention phase or early treatment. And what we've just done actually is finally published all the results and in this study actually included 174 patients. The title of the study is called “Individualized Clinical Management of People at Risk for Alzheimer's Disease.” And the key here is the title: individualized care. And I'm really excited, Karen, thanks so much for joining today and being willing to share your story. Each person has to get a different personally tailored plan for them. I think a lot of people say, well, first of all, there's nothing you can do about Alzheimer's. I'm going to get it or I'm not. And that's just not the case. A one out of three cases of Alzheimer's disease may be preventable if that person does everything right, but what is that “everything right?” In our program we hone in on the details. We really try to understand the individual risk factors that each person has. If they're going to be on that road to Alzheimer's disease, we're going to get them off of that road by using evidence-based generally safe interventions and we're going to personalize care for these patients.
Dr. Stieg: I guess I want to understand in order to do a balanced scientific study, one would think that you would measure the full battery of everything in every one of the patients and then try to hone that in as it relates to specific patients. So I'm presuming that's what happened in your study. Tell me what you've learned.
Dr. Isaacson: Sure. So we've learned that when we recommend a targeted personalized intervention plan for patient, you know, and the cornerstones of care for specific types of exercise, nutritional changes, stress reduction, sleep hygiene, as well as potentially certain vitamins or supplements if that person is deficient or maybe if their genes require additional fuel to make their genes work better for them. So on average we recommend 21 different personalized interventions per patient and those people will follow the plan over an 18 month period. And what this study has shown really for the first time is that after 18 months of following this individualized clinical recommendation plan, not only can we stabilize brain function, but actually we can improve brain function and we can not only improve how the brain works, but it can actually lower Alzheimer's risk, lower cardiovascular disease risk, and also correct blood levels of markers of Alzheimer's, these risks. So the take home point here is that whether the person had no symptoms whatsoever or the person actually had symptoms that were the earliest manifestations of Alzheimer's disease, those people improved. Now, when you already have symptoms, you need to comply, meaning follow graded and 60% of those recommendations when people earlier on in the process before symptoms, whether you had lower compliance or higher compliance, both groups responded.
Dr. Stieg: Let's assume that this becomes the standard of care or a lot of doctors believe these results. What can the listeners expect that they would be tested for? Can you give an overview of, you know, is it x-rays, cat scans, MRIs, blood tests? Where are they going to be stuck with needles and what kind of unusual tests will they have?
Dr. Isaacson: So I'm a brain doctor. I'm not a fancy neurosurgeon like you. I'm just a simple brain doctor, not a brain surgeon. So I'm going to try to keep this answer simple. And what we've published on and what we've tried to, you know, spread in terms of education as the ABCs of Alzheimer's prevention management. The A stands for — it's a big word: Anthropometrics. Anthropometrics means body composition, body fat, muscle mass. Where the body fat is, is around, is it around the belly? As the belly size gets larger, the memory center gets smaller. What about the B? The B is blood biomarkers. We're going to look at cholesterol. We're going to look at metabolism like blood sugar, nutrition markers and genetics. We're also going to look at the C: cognitive function. We're going to get a cognitive baseline and we're going to check memory, function, attention, language processing speed. We're going to follow all these three metrics every six 12 and 18 months and at each intervention time point we're going to give a person an individualized plan based on the data that we get from the A, Bs, and Cs,
Dr. Stieg: And that's what you did and published in this study. And with that you've demonstrated that you can not only preserve but improve cognitive function.
Dr. Isaacson: And that was honestly, I'll be very frank. That was a surprise to me. In people without symptoms, I was hoping that was going to be the case that we would either maintain or possibly improve. That was, that was the reach goal, but with people in this study that had mild cognitive impairment due to Alzheimer's disease, these are people, there's no drugs. There are no FDA approved drugs for mild cognitive impairment due to Alzheimer's. These, there's nothing most doctors say, I come back in a year, there's nothing we can do. Well, our study showed that individualized clinical management based on this framework of some ways what we call precision medicine can absolutely improve cognitive outcomes even in these patients, but they had to follow greater than 60% of the recommendations.
Dr. Stieg: You mentioned 21 interventions or specific things. I don’t know if it's easy to list all those 21. So that means out of those 21 I've got to follow at least 15 of them. If you're telling me now, is it 21 for everybody? Or is it's 21 possible interventions that I might only need five so that means I've only got to do three or four.
Dr. Isaacson: Great. So 21 was actually the average per patient. We actually recommended just over 50 different recommendations on the whole to the whole group of 174 patients. Now about 15 of those recommendations were only recommended once or twice. So the whole universe of recommendations that we give to patients is roughly around 40 and of those on average, each person gets an individualized list of about 21 different things.
Dr. Stieg: And as you go along, obviously you can modify those interventions. And as I understand it, Karen had some control of her blood sugar and you had to tweak or modify that in her care. Yep.
Dr. Isaacson: So when I met Karen, um, we had this conversation and we took a deep dive, we wanted to find exactly what could potentially put Karen on the road to Alzheimer's disease and we wanted to set up a detour and get her off of that road. And, and Karen, um, did it, Karen took the bull by the horns. She really made some active changes with that. Really mostly anyone can do if they put their mind to it. Um, and she really fixed her problems and is now off that road.
Dr. Stieg: I was actually really surprised to see about the prevalence of Alzheimer's disease in women versus men. Can you go into that a little bit and some possible reasons why that may be taking place?
Dr. Isaacson: Sure. So two out of three people affected by Alzheimer's are women and we don't exactly know why. However, I think we've learned a lot in the last five years. Now, when I was in medical school we were taught, more women have Alzheimer's than men because they live longer than men. That's just not the case. Um, women actually are predisposed for a variety of reasons. First of all, women that have the APOE4 gene, which is a gene that that a lot of people get tested cause you can send away in different commercial tests that you can, you know, anyone can do right now. People who are women that have the APOE4 gene are at a higher risk than men with that gene. So that's one potential interaction. The other part where I think is really important is the menopause transition. The peri-menopause transition of women changes energetics — energy in the brain. And sometimes when people are on that perimenopause transition, they can fast forward down on the path to Alzheimer's disease. And I think we're just starting to understand why and what the goal is of our program and, and, and our research is to not just help patients as a whole, but also specifically hone in on women and try to understand what we can do during the peri-menopause transitioneto be protective. And with Karen, that was also one of the important parts of the plan.
Dr. Stieg: Karen, I'd like to bring you in on this conversation. In the introduction we noted that your mother had early onset Alzheimer's disease. Can you give us an idea as to why you got involved with this trial? And it must be difficult since you don't live in New York to be involved with the trial. Describe that for us.
Karen Segal: My maternal grandfather had Alzheimer's and my mother has Alzheimer's and I was a caregiver for her for a year in living in my home. And once we got her involved in some clinical trial work, I thought to myself, why am I not participating in a clinical trial? Well, I don't have a diagnosis first of all, but what could I do to sort of track myself? And so I actually did some research and found Richard Isaacson in New York and I thought, you know what, this is really important to me to be able to be able to be driving this bus versus chasing the bus, which is what you know we were doing with my mother.
Dr. Stieg: You found Richard on the internet, somebody recommended him.
Karen Segal: I do a lot of Alzheimer's advocacy and on different researchers and through, I guess through Us Against Alzheimer's, Richard had been one of our on one of our panels and I cornered him and started talking to him and started coming up to New York about four years ago and I go every six months and I've been very adamant about following his protocol because it is basically precision clinical medicine and I don't think people should be scared when they think there's 50 things that you think you have to do. A lot of them are very straightforward and pretty easy to follow. For example, he wanted me to play a musical instrument, speak a foreign language. You know you can use Duolingo online and you can play, you can even play a piano on the iPad if you would like to. So I'm always looking for the Spanish speaking piano instructor so I could do two at one time. But it's not that difficult to follow his protocol and it's figuring out what you're at risk for and modifying your risk. And I am very athletic, have a very good diet and am not overweight. But thinking about sleep, thinking about meditation, thinking about lowering the stress in your life, taking a deep breath are all things that can affect your overall health.
Dr. Stieg: The way you were describing yourself is this perfect candidate you exercise, you eat right, you do all the right things. So what specific interventions did you and Richard come up with that would help improve your cognitive scores?
Karen Segal: So for me, believe it or not, whenever I would do a fasting blood draw, my glucose levels, fasting glucose where at the high end of the normal range, which meant that I was kind of a pre-pre- diabetic, and diabetes, as you may or may not know, is a track to Alzheimer's. And so basically Dr. Isaacson suggested I cut out sugars and carbs and that I take a supplement or two and we did and tracked me. Six months later it was a little better, but when I came back a year later, I was actually in the middle of the normal range. So one could say, by reducing my carbs and sugars, that I have modified my risk for diabetes, which has therefore modified my risks for all time.
Dr. Stieg: So then at six months, because Dr Isaacson, Richard tells us that every six, 12 and 18 months he evaluates patients. This is a question to both of you, Karen. First, what changes did you see at six months, 12 months, if any? And then I'll let Richard answer that from both a clinical and a scientific perspective,
Karen Segal: The first six months, you know, it takes time. Things don't happen overnight. So you have to, you know, it's hard to turn away all carbs and all sugars all every single day — I'm not going to say that I, you know, don't have one or two, but I have Mo made it a priority to me to say, look, I don't want to unfortunately be my mom and have to live what she's unfortunately gone through and she's — my mom is still surviving today, which is unbelievable that she has had this disease for 17 years now. And I really would like to be able to modify my risk and I want to be able to be brain healthy.
Dr. Stieg: So your message then is, which is very real, is that somebody starts as, they shouldn't expect to see in the first week, something's going to happen. It's a slow, healthy living process. And Richard, maybe you can expand on that.
Dr. Isaacson: Sure. So different people respond differently and just like we talked about earlier, different people with different genes can respond differently. So Karen did what we told her to do. She did great. Um, she followed most of the suggestions and when she cut her sugar, it took her body a little bit of time to start responding and, and that was based on a variety of things. First of all, you know, Rome wasn't built in a day. If you change your sugar intake today, it's going to take several months, if not longer for your body fat and your metabolism to really respond. The other part is depending on a person's genetics. Um, in our study, um, certain people took longer to respond that actually some people needed the year. Other people really, at 18 months was, was kind of the time where basically everyone started to respond. But whether it's six, 12 or 18 months, that's not a lot of time when you compare it to a 30-plus year disease.
Dr. Stieg: Karen, given the fact that Richard's message is that prevention is actually a treatment, when you're out and you do a lot of awareness and philanthropy in this area and you hear from somebody,” Why would I want to know? There's nothing I can do.” How do you respond to that or what do you say to them?
Karen Segal: Well, knowledge is power and the more that you know than you can actually act on the information that you would be information that you have. If you just dig your head in the sand and don't have the information and just choose to disregard it, even though there is no treatment for the disease currently, there is no drug, there is no magic pill. The first person cured of Alzheimer's is going to be somebody who's in a clinical trial. So if I were to find out tomorrow that my cognitive testing baseline has taken a nosedive when I go in for my next six month checkup and I and I would put myself in a clinical trial because at least I'd be doing something proactive versus reactive. I think it's really important. I think we don't think enough about what's good for your brain is what's good for your heart and that we need to be cognitive and vital and thinking forward about how to take care of our brain.
Dr. Stieg: Short of eating that chocolate souffle after dinner. This is number one, a painless thing. There virtually is as I can see it no downside to it. And as Karen just stated, it's beneficial for the heart. It's beneficial for the brain, it's beneficial for your body index, body mass index and how heavy you are. So it's good for your joints, it's good for you all over. So I would suspect that you're going to have, um, a rather large following. Are you prepared to handle that?
Dr. Isaacson: Good question. So we're now actually, I'm really applying for the next phase of our work and it's really great. And you know, what we did was we started the program in New York. We then expanded to Puerto Rico and you know, we, we started the nearly the first phase of this work, but, but the next phase is to expand and we're now applying for NIH funds to fund a five clinical centers in the United States that, you know, some at major academic institutions, other at smaller institutions. And then also to see if we can replicate this outside the United States. And we have a site in the United Kingdom, and Jersey, on the Island of Jersey, in the UK. Resources are not as great there and, and things are different there. So we're trying to replicate — can, the clinical practice of Alzheimer's prevention, can it be successful in multiple different environments and also by different practitioners. I'm a neurologist, but a family nurse practitioner also cares for patients in our clinic. We have geriatric psychiatrists involved. We have family practice doctors. I hope that one day this is going to be practiced by different specialties, not just, not just neurologists as well.
Dr. Stieg: Karen, as you've indicated both between your mother and your grandfather, this is a family disease. And by that I don't mean genetic family — I mean that the family has to live with this. How has this affected your husband and your children and how you're going to have them treated and how you interact with them.
Karen Segal: My children as a result of having a grandmother that they were very attached to as babies and that she took care of them, they now have had to take care of her for so many years. And it definitely has affected them, and in a positive way, all of them are very involved in starting events at their high schools: Dunk Alzheimer's, they raised several thousands of dollars for medical research and they also are concerned about their own health and their own brain health as well. So I mean it's something we talk about.
Dr. Stieg: Can you go into the emotional and intellectual factors that play in your life in regard to the disease management?
Karen Segal: Of course. I wake up every single morning and I think about my mom and I think about the fact that she's here, but she's not here. She's kind of living in a fog, but it makes me sort of live each day and appreciate each day and my family and my health and that, I think it's really important to me to educate others. So I do a lot of talking to friends and I do a lot of seminars and things talking about brain health and the work that I'm doing because everyone wants a Richard Isaacson here in Chicago. It's kind of like what organic food was 20 years ago. This is all —this will be commonplace for kids today because as they are born right now, they are, they are being genetically tested right away from the get-go of what they're allergic to or what they're not allergic to. And people today my age are afraid to get their genetic testing and thinking that they will find out something that they don't know. But you're going to know everything. And so you're going to want to be able to deal with it throughout your lifetime.
Dr. Stieg: I can only hope that you and the Alzheimer's universe have better luck than we in the American Heart, American Stroke Association have had with trying to get people to modify their diets and their behavior patterns. It's, it's so common sensical, but yet it's so hard. And in that regard, Richard, for those people that are so motivated, where do you recommend that they go and get more real but good information?
Dr. Isaacson: Sure. So we've created a course online that's free for everybody. And, you know, the things that we're learning in the clinic, we literally put out on the internet the next day that we learn it. So the website to go to is alzu.org, the website is called Alzheimer's universe. There's six courses on there now. We have courses for college students, high school students for practicing doctors, for medical students. But the main course that most of the people listening want to take is the prevention course. There's now 12 lessons. It's over two and a half hours of content lessons, they range, five to 15 minutes each. You can take them on a computer, a cell phone, whatever, um, you can listen to them on the go. And it's really anything and everything that you need to know about Alzheimer's prevention.
Dr. Stieg: Dr. Richard Isaacson and Karen Segal, thank you so much for spending this time with us. We can only hope that artificial intelligence and telemedicine will bring Dr. Isaacson and his message to people beyond New York City. And to you, Karen, in your hometown. I want to thank both of you again for reviewing from a medical perspective, but also from a personal and patient-centered perspective how to go about managing this complex disease process. Thank you for being with us.
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