Thirteenth Annual Great Ladies Luncheon Symposium

this is our 25th anniversary or as Howard likes to say we're 25 years young founded by the Lauder family that is Estee Lauder and her two sons Leonard and Ronald we're about three things Diagnostics prevention and treatments and we're going to hear all about prevention today which I know is a favorite subject I always chuckle a little bit too because you know we're about two-thirds filled and by the time 11 30 rolls around will be a hundred percent filled this is a Hot Topic today um the other piece I will say about add app just as a reminder and maybe those of you don't know we don't make grants to academic institutions or to biotechs we make investments so we have a contract with anybody we give money to if they see any kind of positive movement moving from the bench to the bedside with their Diagnostics treatments or preventions we get a piece of that and we immediately put that money back into more science that is the philanthropy part of venture philanthropy so that's us um any of you were here last year it was just brilliant we had two phenomenal honorees and actually both are in the room today first I'll ask if you remember we we honored the Eli Lilly Corporation who sponsored this scientific Symposium today and uh if you want a hot breaking news just last week Eli Lilly announced results from their anti-top line results from their anti-amyloid drug trial and the headline on that is very very very promising so Eli Lilly sponsoring us today and a partner for a long long time thank you you're fabulous the other honoree is our next speaker she is an Emmy award-winning journalist NBC MSNBC we are thrilled she's here with her with us today because we've got all of a sudden yesterday got to be a really busy news day which spilled into today I don't know if any of you noticed she is a fixture uh on MSNBC she's a fixture in the DC political uh circles and media circles and Social Circles but much more than that she is a huge friend and Advocate and supporter of the addf and a very very close friend with the Lauder family ladies and gentlemen I give you the one the only Ms Andrea Mitchell [Applause] so thank you so much it's great to see some wonderful friends here in the audience and Mark and all of our friends with addf this is just a unique organization what the lawners have created here is the only philanthropy that is completely family funded and the investments in promising research are just profoundly important it's wonderful what EI Lilly is accomplished and Dr Philip is going to be talking more about that I was reading about it and excited about the fact that he's going to be here as I understand from Mark you were all at the Milken Forum in LA and Dr Phillip was a featured interview buy Milken about just how exciting this is I mean this is the Leading Edge and all of what we've been hearing for these many years that we've been here in this event about the amyloids and what kind of research could be possible is all coming to fruition and it's coming to fruition In Our Lifetime so um you're all part of that and your support here today means so much to all of us so on behalf of the Alzheimer's drug Discovery Foundation it's it's really my pleasure to be here um as Mark referenced this has been a really busy time as I was leaving the studio this morning to come here my executive producer was saying are you really really sure about the lead of our show at noon we're you know writing it and producing it and choosing the tapes and we were in early this morning to go through a lot of things knowing that I was coming here and this is usually our crunch time of writing and producing the final parts of the show and our studio is now 20 minutes from here on Capitol Hill it used to be much closer when we started this 13 years ago uh so we used to have a little more flexibility I'm not going to be able to stay quite as long as I'd like to but I'll get a full fill in from you all later I hope because what Elise and Mark lefkowitz have done in creating this event is just extraordinary and we want to thank Elise and Mark for their Devotion to this [Applause] in creating this in supportive addf it's really the only charity so focused on accelerating the development of drugs for a devastating disease I don't know anyone in this room who's not in some way been affected a family you know a parent you know some other relative or a friend affected by this terrible disease as Dr Phillip likes to say we've entered an exciting New Era and that's an understatement uh he's being his cautious scientific self but this really is an exciting New Era of research new breakthroughs emerging with drug approvals already happening even more drugs focused on novel targets advancing through clinical trials including many funded through the addf portfolio the biology of Aging approach supported by addf is helping bring to Market a diverse array of drugs that can be used in combination to stop Alzheimer's in its tracks we're seeing as we've said serious progress and that's thanks in large part to the incredible research funds provided by addf gathering together some of the best and brightest Minds in the world leading me naturally to our panelists today our Symposium of course is led by Dr Howard Phillip acknowledged you know well the co-founder and chief science officer but now acknowledge worldwide as the leading research scientist in the field uh Jared geriatrician a neuroscientist he's been involved in Alzheimer's research for 40 years you look too young to have been doing this for 40 years Dr Philip yeah which reminds me I've been at NBC for 44 years can you think of that wow insane [Applause] I know it's hard to imagine I started I was so young when I started and as we talk about aging we'll be joined by Dr Christine yaffe of the University of California at San Francisco and Dr Jose luxinger of Columbia University they are going to talk about all the Innovative research we're seeing on different aspects of Alzheimer's of prevention which is important I know to everyone here and to slowing the progress of this disease and you're going to have the opportunity to ask questions of these renowned scientists and to get these answer directly you know right from the Forefront of research so that is the wonderful opportunity and then for dessert you of course have a wonderful lunch all of your friends and the great actress Fashions I am for one devoted to actress myself so I um I'm a loyal actress supporter so without further Ado it's my great pleasure to introduce our friend the chief scientist the co-founder of addf Dr Howard Phillip at his colleagues I want to welcome all of you thank you for coming we really appreciate your support and being working with us here I hope we have a great day we're really focused on prevention today um I I would say that it's amazing that we can really even talk it intelligently about prevention from the perspective that when I started in the field 40 years ago we knew almost nothing about Alzheimer's disease and over the 40 years some of these two scientists and doctors have made a great contribution to our understanding about how to prevent this disease and so if somebody asks you I hope whether or not we can actually prevent Alzheimer's I think you'll find very interesting information that today it is possible as Andrea mentioned we've been at this at the foundation for about 25 years and we've seen finally after all these years of research breakthroughs as was mentioned I mean we have two drugs on the market now through accelerated approval we're going to have a third I believe over the summer coming to a full approval application with the FDA and some really interesting results from Lily and Biogen and Eastside and actually I found out last week that I could even start prescribing one of these monoclonal antibodies to slow down the disease in Manhattan in my little practice these kinds of results are the result of 40 Years of research in the field from a time when I remember that we knew basically nothing about the disease to where we are today and some of the breakthroughs that enabled us getting to where we are today were actually either by Serendipity or intelligence developed by the Alzheimer's drug Discovery Foundation one of the first things we did was actually to start developing the Pet Scan the pet amyloid scan at the University of Pennsylvania back in the year 1999 and it the basis of the current approvals of the drugs for for removing the amyloid from the brain are really very much based on that test that we developed and it was the reason and why we developed that test or funded development of that test was to accelerate drug development so you know we went all the way from very earliest stages of developing the test all the way through its use not only in in drug development as as we've seen today but also in clinical practice it's amazing the change in clinical practice that's occurring right now if I see a patient with memory problems and I'm not really sure what they have or they're thinking about going into a clinical trial where a positive pet scan would be required I can send them down to the radiology office down the block from my office and within 24 hours I can tell them with about 90 95 certainty if they have Alzheimer's disease that's a big breakthrough not only that but with companies like c2n that we've invested in out of the Washington University in St Louis there's a blood test on the market now it's available in 49 states New York is the last Hangar on because they have the most strict regulatory for these blood tests but it will come to New York and I can already order a blood test and the blood test correlates with the brain scan so this markedly reduces the cost of clinical trials it markedly reduces the cost to patients and it's convenient it's part of the normal workflow of a doctor's office to order a blood test and there are better blood tests that are coming down of the pike that are going to be even better than the ones that are on the market now and these tests are going to become increasingly complex and and novel because as as Andrea mentioned we finally have this first generation it's such a huge breakthrough in the history of the world the first generation of treatments for Alzheimer's disease monoclonal antibodies to amyloid but they're based on this framework that aging is the leading risk factor for Alzheimer's disease we are funding several approaches to translating the knowledge about aging into new drugs for Alzheimer's disease so just as evidence of that about five years ago 75 percent of the drugs that were being developed for Alzheimer's disease these were mono were antibodies against the amyloid protein which is the pathology of the disease and the tangles which is also part of the pathology today 75 percent of the drugs and development are non-amyloid non-tau novel approaches like inflammation in the brain of Alzheimer's patients which is a Hallmark of aging and Hallmark of Alzheimer's disease now recognized that way and it's seven or eight other Pathways that I won't talk about I don't want to take up too much time here but I will say that you know people say well you've been at the sporty years aren't you discouraged no I've never been more excited about what we're doing than I am today and I think we all share that it's really amazing what's what's come about just in the last few years so with that I want to turn it over to a subject that I know is really near and dear to all our hearts and we really have we really and truly have two of the world leaders in the science of prevention for Alzheimer's disease here today we're very fortunate and the first speaker is going to be Dr Christine yaffi she's a professor of biology and Psychiatry and epidemiology at the University of Southern California at San Francisco Houston yeah right University of California San Francisco and um conducted one of the first clinical trials of prevention for Alzheimer's and has been at this uh I I like to think that I have a lot of papers published in the literature with 350 and when I read Christine's bio she's got over 600 so she's really busy sure um thank you Howard I'm really happy to be here I uh I've known Howard I think we met actually at an addf physical activity Symposium um in your offices a while ago so it's just amazing to see how much it's developed and how much you've done and and um thanks to all of you really um so you know you know Alzheimer's is a huge deal it's it's a big big deal the numbers are increasing we think that the numbers are going to Triple in this country who has Alzheimer's worldwide triple maybe quadruple this is a problem it's a big deal uh of course it's it's a devastating disease um you know huge toll on families emotionally financially so we've got to do something about this and you know we've heard that that um you know the the the well the other thing the important is you know affects women more which maybe we'll talk a little bit about we think interesting reasons we don't completely understand why affects minoritized Elders more we really need to get to the bottom of some of this and as we've heard you know the last few last couple decades were kind of disappointing we just kept saying if I heard one more time you know oh in the next five or ten years we'll figure this out it kept going another five or ten years another but you know what I think we're really here it's just amazing how much has changed just in the last year or two the the drugs um finally are coming to fruition and very exciting we've been using the same drugs for 20 years in clinical practice and now you know we and they were okay they weren't great but they were okay and now we really think we've got some much more effective drugs so really exciting uh there's a little controversial some of them but but we're going to get there uh the biomarkers that that Howard alluded to are incredible I mean I imagine we now have a blood test you can see if somebody has Alzheimer's it's going to revolutionize the field and and the clinical practice really um and and I'm going to talk also about prevention you know so we really have to get it the this is what we all want we want to prevent the disease we don't want to you know treat the disease so um I think one of the most exciting things that we've discovered and I'm happy to say we were we were the first to to my group was the first to show this we think that about 40 of Alzheimer's could be prevented now there's a big genetic part of Alzheimer's right that's harder to you can't pick your parents uh it's hard to do um but but you know we do think that there's about 40 percent that could be prevented and that's because we know that Alzheimer's has a lot of risk factors and I'm going to talk a little bit about them and if you could modify those risk factors you know not even change them completely but modify them 25 50 you could have a big Downstream effect on Alzheimer's from a public health point of view but also hopefully from from a an individual point of view so that's what we're really excited about now you all know it's hard to change Behavior you know I need to probably eat a little better and exercise a little more but but you know we we think that we can actually move the needle and have a big effect what are the things we're talking about physical activity cognitive activity using your brain improving your sleep very very interesting uh a risk factor cardiovascular risk factors what do I mean by that high blood pressure diabetes obesity smoking you know and Dr luxinger is going to talk quite a bit about this this this adage what's good for your heart is good for your brain I think is really really important and we're discovering it's not just because of vascular Pathways it's also a direct effect on amyloid and Tau the proteins that accumulate in the brain to cause Alzheimer's so it's really interesting and I think we need to get much more down to the mechanisms of this but these are some of the the most promised things things also traumatic brain injury I was actually at a National Academy of Medicine Forum we're looking at traumatic brain injury it turns out this is a really important risk factor getting dementia there's some other things that we talk about but I don't think the evidence is quite as good and maybe we'll talk a little bit about how you how you know whether something really works or not you know I don't think it's going to be blueberries but you know we we need to figure out you know what what's the science telling us what are the mechanisms what are the studies show so there's some promising but not less clear I think with um I'd say diet social engagement sensory changes like hearing and vision and depression I think those are those are areas that we need more research on but are looking good I don't think quite as clear as as the other ones I mentioned so if these things are preventable and we know they're very common right A lot of people have sleep issues a lot of people have hypertension how can we move the needle how can you get people to to change their behavior there was a very important trial called the finger trial um gosh a while ago now seven years ago or so and this was a colleague from Finland who ran this study it was finished it was all white Finnish um adults who were they didn't have Alzheimer's but they but they were older they had maybe some risk factors and they were half of them got the usual control group and and half of them got interventions looking at cardiovascular risk factors they had diet changes they had physical activity and cognitive stimulation and at the end of two years the group who got the intervention actually did better than the group who had the usual education so that really tells us you can actually if you change these behaviors you could actually change the slope of of the cognitive trajectory and so we're really really interested in that and now a number of different countries are are having these kind of Trials the U.S interestingly has been a little behind why I think because we're we're um you know we're much more interested in Pharma and biotech and which are all really great but we don't we haven't invested as much as I think we should in some of these risk factor changes and risk reduction and lifestyle changes but that's changing so we're now having some of these trials I think Dr lutzinger will talk a little bit about this and we just finished the trials that I really want to tell you about um it's I can't even say it's hot off the press because we haven't even published it yet but but it's we're working at it we're about to publish it um what we did was we took people who had uh increased risk of of having Alzheimer's based on these risk factors and we said okay we're not going to just tell you what to do we're going to ask you what you want to do what do you want to work on it was personalized what what risk factors do you have and what do you want to work on and how do you want to work on it and even though it was covid and everything sort of got crazy and remote and you know it was it was a mess lo and behold we finished the trial um uh over in the in the fall and we found huge benefits with the group that actually worked on the risk factors compared to control and these were people with Alzheimer's disease no these were people at risk but it was really primary prevention they didn't have Alzheimer's they were older with risk factors so we're extremely excited about this we want to do a bigger trial we're going to talk hopefully more about this but I'm really excited and the effects by the way were as big as the drug trials if not bigger so this is a big deal no side effects cheap you know so I'm very very excited about it um and I think you know we're ready now I just want to end by saying I think not only have we made great discoveries but I think we're at a place now where we can combine drugs and risk factors why is it either or it should be like cardiovascular disease you go to the doctor and they say okay we want you to lose some weight try and exercise change your diet take this drug you know for cholesterol take this drug for hypertension we're going to be in the same boat I I would bet in five or ten years my five or ten years we're we're going to say here's a drug for inflammation here's a drug for maybe Tau but but please work on your sleep and try and exercise more and reduce your hypertension you know so we're coming I think it's really exciting it's going to really change this terrible disease from prevention and from treatment [Applause] just let me say that um Christine you know we could we can talk about these risk factors but what we need is data and I think Christine has been generating the data over the many years to to really put the science behind prevention so that we can come out here publicly and speak about it with great credibility based on the research that Christine and others have done over the last few decades I guess um and and one more thing you know when we talk about these lifestyle interventions like let's say exercise um let me just ask that one question about how strong is the evidence that exercise can prevent Alzheimer's disease and what have you thought about in terms of the mechanism like what is exercise if it's effective for preventing Alzheimer's disease what is it telling us about how you go from exercise to reducing the number of plaques and tangles in the brain yes so I think I think the question of evidence you know how do you know how do you know if blueberries are good or not how do you know it's hard to it's hard to know I mean you know Andrew Mitchell knows well you know you you have to know you know you have to be a Savvy reader right you can't just read or believe everything you read or hear you have to try and dig a little deeper and um trust your sources but also I think what we do is we try and look at you know okay are there good mechanisms so is there good biology underlying this that suggests that that this makes sense turns out with physical activity well obviously it's good for your heart you know it's you know it's good but it turns out it also has a big role in in the brain it actually physical activity causes new neurons and to neurons to grow and to connect wow that's pretty profound right it causes all kinds of other changes in the brain uh probably some changes with amyloid and Tau so you can look at the mechanisms that we have to be based in biology that's our bedrock and then you look at the quality of the studies the gold standard are always these trials where you take people and you say you know eeny meeny miny mo you know you're going to be in the control you're going to get the intervention that way you get rid of those annoying people who you know who only drink one glass of red wine a night not two not zero and they cross their teeth every they've lost their teeth every night because we know they're the people who do healthy behaviors are different right so you want to get rid of that bias by doing these trials and that's the that's the gold standard yeah so two comments one I have my story about bread oh yeah by my tail so so just to illustrate some of the problems with evidence um I can prove to you that bread causes felonies and the way I can do that is that 95 of all felonies are committed within 24 hours of eating bread so there's fallacies there are other jokes I can tell you but the other thing I want to say when we presented we funded one of the first of these clinical trials of exercise for Alzheimer's disease and cognitive aging and showed the the investigator that we invested in showed that uh a very simple exercise of three times a week going to a gym actually increased the volume of the brain particularly in areas where Alzheimer's starts and actually reduce what's called um or improve cognitive function over a six-month period so that was one of the first evidences when I presented that to my board one of my board members said Howard I'm a couch potato can't you develop a pill that would mimic the effects of exercise and I said we're already doing that because we are investing in a company that's currently out of Stanford University in California that's developing a pill that mimics the effects of exercise it's on a molecule called bdnf which actually is as Christine mentioned increases the number of neurons and is what we call neuroprotective and could be revolutionary so let me turn now to um a focus Jose luxinger Dr luxinger is a professor of Neurology and medicine right I saw my medicine and epidemiology at Columbia University and has focused his career on Diabetes uh as a risk factor but we'll also talking talk to us about cardiovascular risk factors and especially metformin which I know we're all interested in and had its role in in the prevention of Alzheimer's disease sure thank you it's a pleasure to be here I mean before I I began talking about that I just want to say I'm very grateful personally to addf ADF uh gave me seed money to start a clinical trial open Foreman approximately 16 or 17 years ago wow and uh time flow and I you know I don't I don't have the budget in front of me but it was probably between 200 000 and 300 000 and that has led directly to over 40 million dollars in in funding to continue the program and indirectly actually over a hundred million dollars so you know I think I'm a testament to the power of the Investments that addf do and so I appreciate you being here and thank you and supporting addf so I I will anchor my my conversation the following way uh uh we're in a very exciting time because we have proof finally that Alzheimer's disease can be treated with these monoclonal antibodies but I think that there is proof as well that Alzheimer's disease and cognitive disorders in general can be prevented and the one I think one of the most important observations that have been has been made in studies in the last few years is that it's been observed that the risk of Alzheimer's disease and dementia at the population level has actually been decreasing although the numbers have been increasing simply because the population is larger and the older population is larger but actually the risk has been decreasing and when the first study that came out reported this there was a little bit of a skepticism but then there's been several studies that have shown that over the last 40 or 50 years all across the world the risk of Alzheimer's has decreased now how how can this be and I think that the the what's been happening in parallel with that phenomenon is that in the last 40 or 50 years the treatment of heart disease has improved the treatment and prevention of stroke has improved the treatment of you know high cholesterol high blood pressure treatment and prevention or diabetes has improved and you know as Christine said what's good for the heart is good for the brain and particularly there's been a a dramatic decrease in Strokes you know when when there's death of brain cells basically which clearly makes uh you know Alzheimer's you know more likely to happen so uh you know to me that is proof uh not a hundred percent but eighty percent at least I believe it I'm convinced that uh Alzheimer's is not only treatable but it's preventable as well so uh you know when I was a resident uh 30 years ago uh there were no statins you know there wasn't you know uh things like a Lipitor and things of this sort I'm sorry if I'm mentioning a uh a commercial name it just started at that time uh there were very few treatments for um for diabetes and uh and then the treatment of heart disease were just being revolutionized at that time with you know catheterization and doing you know procedures in the heart and such without the need to uh to to do uh outright uh surgery and since then there's been a huge uh Improvement in the number of drugs but also preventive strategies for things like high blood pressure diabetes and cholesterol so I'm gonna go a little bit one by one those things because I think it's important I'll try to do it in an efficient way because we we have time constraints but anyhow high blood pressure is without a doubt the um you know I think the greatest risk factor for stroke there's others like high cholesterol and diabetes as well but uh without a doubt uh um high blood pressure is is the greatest one and when I was a resident uh you know uh 30 years ago we used to you know we used to tolerate things like systolic blood pressure of 160. you know I think we all kind of know our numbers with blood pressure that's the high number and since then we've learned that uh no you actually have to go lower you know that uh you know first it was said 140 now we're talking about levels of 130 120 being better and so now with uh hitting those targets and also with improved availability of medications for high blood pressure we've seen a dramatic decrease in stroke which we believe that it's improved uh um uh you know the the risk of cognitive impairment in general and I I think Christine I think we collaborated in a report from the national academies actually that sort of reported uh the the likely benefits of blood pressure reduction so the the other one is cholesterol you know we uh um you know again 30 years ago so when I was a resident the first clinical trial proving that a medication for cholesterol was beneficial for heart disease simvastatin at that time it was a trial called the forest trial came out before that you know it was very rare to have anybody on these cholesterol lowering medications uh and since then a very large proportion of the population is on these medications particularly if they're at high risk if they have diabetes or if they have high blood pressure they're on these medications and some of you may be on these medications as well and this has resulted also in a dramatic decrease in heart disease and and uh in stroke as well and then I've been particularly interested in diabetes throughout my career as Howard mentioned diabetes doesn't occur alone you know diabetes is probably you know is an elevation of blood sugar that is abnormal by the way I'm talking about type 2 diabetes not type 1 diabetes which is a different type of disease but type 2 diabetes is also accompanied by high blood pressure and by high cholesterol and by high inflammation which is called the metabolic syndrome and I think Christine was I think the first person to report on the importance of the metabolic syndrome and inflammation for for cognition I think you published that in Jama a bunch of years ago but so anyhow all these things happen together so I I was very interested in the potential relationship between diabetes and Alzheimer's disease I'm an internist I'm a primary care physician I'm an internist like Howard so I treat diabetes in my clinical practice and you know so I wanted to know whether diabetes was causing uh what we were calling Dementia or Alzheimer's disease at the time through amyloid and the mechanisms involved in Alzheimer's disease or through other mechanisms and so a lot of my research has been in trying to establish uh whether the high risk of cognitive disorders and dementia and diabetes is due to amyloid or not because now that we have treatments for for the amyloid we need to know if that particular risk group needs that treatment or a completely different type of treatment so around diabetes the other important observation that was made was that many of the mechanisms or phenomena that occur in diabetes are important in Alzheimer's disease for example diabetes is is associated with a high inflammation in general a high inflammatory state in the body and that's very important in Alzheimer's disease we believe in the in the brain but also under the neck if you will uh also oxidative stress which is what we try to take vitamins for vitamin C and vitamin E although that's controversial or blueberries and strawberries like like uh Christine was saying that's also that's important in Alzheimer's disease and it's observed in the brain of people with Alzheimer's disease but uh and it's also very high in people with diabetes actually and with a metabolic syndrome and people with pre-diabetes as well so um uh so there's medications that are very good at targeting this you know so there are some medications and diabetes that what they do is they simply make you pump more insulin you know in the pancreas us to bring the glucose down okay but there's other medications that don't make you pump more insulin they actually make you more insulin sensitive make make the the insulin work better if you will and uh and then they uh um also reduce inflammation reduce oxidative stress uh improve cholesterol actually can improve high blood pressure as well and so there's several medications uh that can do that and I focus particularly on Metformin uh because it was a very it's a very cheap medication it caused you know sense per pill uh it's been out of patent for a while so it's it's what's called an orphan medication if you will so one of the few ways to study these medications is with support whether Alzheimer's disease drug Discovery foundation in addition to the National Institute on aging and NIH uh and so uh I I I I I was used to using Metformin I was not afraid of using it because it doesn't it doesn't cause bottoming of of your blood glucose even if you don't have diabetes so it's very safe to use the side effects are usually gastrointestinal meaning that people can get bloating gassy it can get diarrhea at worse and if that happens then you know maybe they cannot take the medication so and and again metformin has all these benefits it decreases inflammation it decreases on oxidative stress and can improve it can improve high blood pressure not on its own but it helps it can improve uh cholesterol and so I said let me give it a try and see if this helps for uh the prevention of Alzheimer's disease in in people at risk and so uh you know we did a small pilot clinical trial supported by the Alzheimer's disease Discovery foundation and the National Institute on aging and that clinical trial gave a signal it was a small clinical trial in 80 people it showed some some evidence or promise because people their memory were better after 12 months so on the basis of that we applied for uh for a larger clinical trial of Metformin which is currently underway covid has not been helpful for the completion of the trial but things are now back to normal and I'm confident they're going to be able to finish it in the next few years and and then we're also collaborating with Mia kivipelto investigators in Sweden and Finland and the UK to do a trial of the intervention that that uh Christine mentioned uh in addition to metformin and I believe addf is is supporting uh that as well so anyhow that's the gist of the question sure you're you are a practicing doctor like I am um and maybe many people in the audience don't have diabetes but they've heard about metformin and we know metformin from the biology of Aging is like the leading anti-aging drug and aging is the leading risk factor for Alzheimer's disease and I know you have a practice too Christine let me ask you in the context of a drug like metformin um would how do you prescribe it off label like if somebody doesn't have diabetes but they want to ask the question should I take metformin today to prevent Alzheimer's disease would you prescribe it and if you would like wonder what conditions would you do that how would you mind yeah that's a great question I would be cautious because you know we we've been burned before and getting ahead of ourselves and thinking that something helps and then it doesn't but I think if if there's evidence of the metabolic syndrome okay if there's evidence of what we call insulin resistance uh if if there is what we call pre-diabetes which is not necessarily you know an elevation of that of glucose where you would give uh you know diabetes medications uh then I I would say that there's there's likely to be a benefit for the metformin uh not uh even if there's none for the for for cognition but there's likely to be a benefit in producing a little bit of weight loss if you want to get a little bit of weight loss if to improve the cholesterol to get the glucose levels from the pre-diabetes level to being a little lower and the worst thing that can happen is that if if you cannot tolerate the metformin then you stop it but I I so I I would have a conversation with with the person who's considering this who does not have diabetes and uh first I think identify do they have risk factors that would benefit from from metformin because I think it then it becomes I don't want to say a no-brainer but but then there's there's a likely benefit uh uh there's likelihood of benefit uh uh and and the engines just see how it goes I mean I think one of the most powerful things that one can do uh when when one is treated with this medication says see what happens to your glucose see what happens to your cholesterol uh see what happens to your blood pressure because if you see that it improves then you know something beneficial must be happening Yes actually biomarkers yeah correct Christine you mentioned sleep um why is sleep important I mean it's hard to go from like um understanding okay sleepy we found sleep is a risk factor or ABS sleep problems or risk factors but what happens during sleep that you know makes it a risk factor good question so you know up until recently no we didn't know why do we spend a third of our life in sleep like you know must be doing something good right I mean evolutionarily what what did it do that made it something we do so much of and it turns out it's really interesting I I think some of the most you know interesting science has come out about the brain in the last 10 years have been around sleep it turns out when we sleep the brain gets quiet and it allows the the spaces in the brain to flow out some of the toxic proteins that have accumulated in the day like amyloid and Tau are two friends that that seem to be very involved in Alzheimer's so what happens is if you sleep you know it's like a Clearinghouse the the the toxins get removed if you don't sleep very well or if you're you know you have sleep apnea and you're you know up and down without even knowing it or you have you have um low oxygen that happens sometimes in sleep apnea that disrupts the clearing mechanism and so it looks like you get more buildup you get more buildup of the amyloid and Tau and sure enough this has been shown in in rodent models and in flies and now in people using these biomarkers if you if you take people and and you don't let them sleep you see greater Tau and amyloids so it's really interesting and so we're we're very interested in if you can improve sleep can you prevent Alzheimer's and other dementia and uh there haven't been a lot of Trials but it's a really great area now yeah okay I want to open it up to audience for questions we have a lot of questions here please could you come in on as a factor with Alzheimer's sure I I get this question a lot and and the the I think we don't really know so what I tell people is in the short term a sleep Aid's probably helpful you know if if you really have not been sleeping well and you need to get a good night's sleep for something or you know you're flying internationally I use a sleep aid when I fly internationally because I you know I want to get sleep um but so I think short term it's probably okay uh there are two caveats to that one long term we think it's probably not helpful you don't want to be on a sleep aid indefinitely because it probably causes some other issues but the second caveat is there's some classes of sleep drugs that are are more benign than others so some of the sleep drugs even some of the over-the-counters you know you you pick up something and it says PM or a lot of it has um some pretty heavy drugs that can affect your cognition so you become careful that you don't you know you know think you're helping your cognition when you might even be harming it with these other drugs so be careful with what they are and maybe talk to your doctor but again short term probably okay long term I would avoid yeah speaking of sleep aids could you talk about belsama yeah I don't know much about it really do you do you either I don't have any real clinical experience I guess there was a report that it might be protective or something but there's also reports that Ambien is bad for you and these benzodiazepams are bad for you but these are just associations and we don't have a clinical trial so to speak of of these drugs so um I agree with what you said but I I don't think there's a lot of clinical experience in terms of belsomra and the risk of Alzheimer's disease or cognitive impairment but I know you can't have side effects from that drug just like you can from the other sleep aids yes yes while we're still talking about sleep how about naps that's the other question I get all the time so so this is fantastic so um great question right should you do a power nap you know where you you know go and climb under your desk and sleep for 15 minutes uh you know I I don't know so so we did the study actually a few years ago a colleague of mine and I looked at the and and we we showed that um that napping in this was an older people they didn't have Alzheimer's they're older normal people and we looked and we found that using um objective measures you know measuring the sleep with these uh after graphs we found that actually people who napped had higher risk of cognitive decline and dementia so we were we thought ah but wait but wait wait wait wait wait wait wait so then so then we said this let's look at the group let's divide them into two groups who are the ones who actually had a good night's sleep the last few nights because we had that data right from the from the actor versus who wasn't sleeping well and what we found was really interesting if you're not sleeping well the Naps were were helpful so you know they're you they're catching you up but if you're sleeping well napping was not a good thing meaning you're you know you're probably maybe it's you're sick from something else or maybe it's a medicine or so it was really interesting so the answer is you know kind of both but but I think it depends it depends right but I think if you're sleeping if you're not sleeping well a nap's a good thing yes hi um many people take anti-inflammatory drugs whether for an autoimmune disease uh colitis or rheumatoid arthritis have you looked into what effect the um anti-inflammatory biologics might have on future Alzheimer's yeah I'll take that one years ago there were there was a lot of epidemiological data that people that took non-steroidals had a 40 or 50 reduced risk of Alzheimer's Motrin the typical drugs and then there were clinical trials of vioxin Celebrex and other ibuprofen for Alzheimer's disease and they didn't work now that was in an era when I think we didn't we definitely didn't have the biomarkers to find out which Alzheimer's patients were inflamed in their brain and which weren't one of the things we're trying to do now is develop the biomarkers to identify people that not only have amyloid and plaques but have inflammation in their brain around the plaques because it's been shown that people that just have amyloid without inflammation don't progress address or they progress very slowly whereas people that have inflammation in their brain progress much more rapidly so the idea now is how do we reduce this inflammation we funded a clinical trial at the University of Southampton in the UK several years ago of a drug the most common drug used for these inflammatories disease is Enbrel and actually there was preliminary results already that Enbrel would slow it down completely if patients got Enbrel This was um Clive Homes at the University of Southampton and we funded another study of that and we're also funding other studies to directly affect what's neuroinflammation we want to directly reduce the amount of neural inflammation so there's a lot of interest in it we're trying to develop biomarkers like ykl40 as one blood tests and spinal fluid tests to identify these people that have inflammation with Alzheimer's so we can Target them and enrich those patients in clinical trials and develop novel drugs I mean one other company that we're supporting out of the clinical uh Cleveland Clinic is called Neurotherapy and they have what's called a CB2 receptor Agonist which is a small molecule pill that binds to the cannabinoid receptor in the brain which is actually inflammatory so it reduces the amount of inflammation in the brain and they're going into phase two now they've shown that the drug is safe there's been a lot of animal model data so I will say that that years ago inflammation was totally underfunded and nobody really believed that inflammation was important in this disease and I think that's changed almost 180 degrees now I think we there's a lot of interest in in developing inflammation elector and Denali are another two biotech companies that have inflammation drugs and development against the gene risk factor called trim two that's a short answer well that would come out of a large scale like kind of what we call real world data to see you know if people with rheumatoid arthritis who get actually I was involved in this study like that and and people with rheumatoid arthritis were at greater risk for getting Alzheimer's disease and um you know there was Data there is there is ways of looking at that but I think again we need to randomize control trials ultimately as I said before the the date originally showed that use of non-steroidals reduce the risk by 40 50 but then when they ran through trials it didn't work at all yeah questions um the first is at what age can you get a brain scan for Alzheimer's and the second is in terms of physical activity are there certain types of activity that are better than others yeah let me ask you the first one so um anybody can get the brain scan but I think what what the point you're raising is really interesting with the Advent of the brain scan for people with Alzheimer's we could actually see the Alzheimer's disease in the brain for the first time and then scientists like recess Sperling and others at Harvard and elsewhere started screening people in the community who were in their 30s 40s 50s 60s and it turns out that Alzheimer's is a disease of middle age not just of old age and that people in their 20 years before they develop symptoms they start developing the disease we start seeing the plaques on the amyloid scans and what that led to is prevention trials so these anti-amyloid monoclonal antibodies have been used in early Alzheimer's disease but there are also studies of prevention where we're finding these people that have very minimal amyloid they're in their 40s and 50s or they have very minimal cognitive symptoms with the amyloid in the brain and giving them the monoclonal antibodies to see if we by preventing the occurrence of amyloid and people that are not symptomatic as a secondary prevention study if we could prevent or delay the onset of Alzheimer's disease in late life 20 15 20 years later and it has been modeled that if we could delay the onset of Alzheimer's Disease by just five years we would reduce the number of people that get symptoms from it by 50 percent so I do think this is an achievable goal today very much in line with what we're what we're hearing about prevention what we're learning about it and combining drugs along with lifestyle and comorbidity management and I forgot the second question physical activity okay yeah so I you know I I don't think that um we don't know for sure it looks like it's probably cardiovascular disease cardiovascular aerobic exercise but um I'm not sure we know for sure some Studies have shown that actually weight lifting and stretching could be beneficial but it's it's controversial I think you're the the safe answer is aerobic would you agree that that's what the evidence shows yes I think the other interesting thing is whether you have to continue doing the exercise to get the benefit and I think it looks like that's the case yeah we have time for one more question yes you mentioned that traumatic brain injuries can contribute to alzheimer's um I worked for non-profit for eight years at the height of the Iraq Afghanistan war and met many into service members with tbis I wonder if there have been any studies in conjunction with the military to work on this and you know help these ninja service members um yes there have been quite a few studies some of which are ongoing we've done quite a bit of work uh you with veterans and and Veterans Health Data showing that um veterans are at a greater risk of developing dementia who have TBI so we've done a lot of work in that space and there's a big big study now underway looking at veterans or active duty who have a blast injury you know so unfortunately in in Iraq and Afghanistan there were a lot of blast injuries and so people had a lot of head injuries um and now they're being carefully followed looking at biomarkers looking at Imaging so I think we'll know that answer in a few years there are young people by and large they're in their 30s and 40s so it may be a little early but but those studies are underway a couple of things just to wrap up number one we can detect 20 years in advance number two we can prevent and decrease the incidence by 40 percent and note to self I think I need a nap a couple of things we're going to break down but our speakers are here if you want to ask some one-on-one questions they're happy to do that and then outside of this room is the aforementioned Saks Fifth Avenue actress pop-up store as well as the Aaron's scent bar so enjoy we'll see you at lunch

Channel: Alzheimer's Drug Discovery Foundation

Views: 146

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Id: lt90WERT8rA

Length: 56min 6sec (3366 seconds)

Published: Tue May 30 2023