 Good afternoon everybody. My name is Susan Goldberg, I'm the editor-in-chief of National Geographic magazine and editorial director of National Geographic's media efforts overall. I am joined today by an internationally known expert in the world of brain and mind health and scholar of successful aging. Dr. Mirali Duraswamy is with me here and Dr. Duraswamy is also the chair of the Brain Research Council for the World Economic Forum. Thank you so much for being here. It's a pleasure. This is, you know, about the hottest topic that there is. Everybody cares about Alzheimer's, everybody worries about Alzheimer's, everybody knows somebody who has Alzheimer's. You know, there's so many upsides to aging experience and wisdom and knowledge, but it's pretty scary when you look at the figures with 50 million people in the world who have Alzheimer's, one of nine people who are over 65. When I was growing up, grandma just got senile and I'd never heard of this thing called Alzheimer's. What changed in the language or the definition and has that led to this skyrocketing incidence? Yeah, so there are three things that changed. The first is determinology. About 40, 50 years ago, we could only diagnose Alzheimer's in people under the age of 65. Cognitive problems after the age of 65 was considered a normal part of aging. And sometime in the 80s, we realized that the pathology underlying memory problems in someone who's 70 or 80 is the same pathology that causes Alzheimer's in people under the age of 65. So the terminology was changed to allow doctors to now call people over the age of 65 who have significant memory and other cognitive issues also as having Alzheimer's. The second is as we get better with taking care of heart disease and possibly cancer and possibly other infectious diseases, we're living longer. There's been an explosion of aging populations around the world and this is going to be particularly prominent I think in China and India in the coming decades. And so aging is the single biggest risk factor for Alzheimer's. So naturally as we live longer, you see more cases of Alzheimer's. The third thing is as awareness grows, we're getting better at detecting it earlier. So if aging is the single biggest risk factor, I mean that's kind of depressing because we all want to age, we all want to get older, nobody wants to die young. What are the things that people can do as a practical matter to help prevent this if that's even a proper question to ask? No, it's the billion dollar question that I want to know in everybody in this room and everybody in the world wants to know. The sad fact is there is no single magic bullet. There is no proven cure, if you will, or lifestyle strategy that we know for sure can prevent Alzheimer's. There are two things I can tell you. One is a paper and a case series we published about three years ago, a technique that is still somewhat controversial. It's called preimplantation genetic diagnosis. So if you have a very strong family history of Alzheimer's where you've had four generations of people in your family have gotten Alzheimer's and genetic testing has identified one of three families of mutations that has a 100% chance of causing Alzheimer's in you, early onset Alzheimer's. Then you can do what's called as preimplantation genetic diagnosis where as a mother you can select an embryo that doesn't have that particular gene because in a particular woman there could be five or six hundred embryos and each embryo is different in its genetic constituency. So you can do genetic testing of the embryo, select an embryo that doesn't have Alzheimer's, fertilize it in vitro, put it back in, and deliver a healthy child where that gene has been knocked out, has been selected out. Although that child could still get Alzheimer's. Not from that gene, but from other undiscovered genes. And so we've actually done that for two cases now of people with familial Alzheimer's disease. But again, this is a very rare example. Preventing the common form of Alzheimer's, I would say the single biggest risk factor that may be preventable is cardiovascular risk factors. All of the issues that are growing, obesity, diabetes, high cholesterol levels, heart disease, coronary bypass surgery, putting stents, all of those are known to increase your risk for cognitive problems and types of dementia. So anything you can do to keep your blood vessels clean, there are a hundred thousand miles of blood vessels in your brain. So anything you can do to keep those blood vessels clean, exercise, good heart healthy diet could lower your risk. So I have been seeing some stories lately about this, you know, this good, this brain diet, right? And so really what it does is it's good for you generally, and so that helps your... Well, as a bonus, it could be like a triple or quadruple bonus. You know, heart disease, diabetes, obesity makes you feel good, makes you feel light and may help you possibly prevent also. And a glass of wine a day? Well, a glass of wine a day in moderation, you know, because that's everybody's favorite excuse. And it's hard to set limits. One becomes two, two becomes three, and then all of a sudden you're getting alcohol dementia. So what do you personally do? So several things. The first is you need to know your own risk, and fortunately in my family there's nobody with the risk of Alzheimer's. The second is there is a gene that increases the risk for getting Alzheimer's called the ApoE4 gene. But 25% of Caucasians have it. The rates are very low in Africans and in certain Asian countries like India. If you have that gene, it's very risky to eat a high meat diet because a high saturated fat diet has a negative interaction with that gene and increases the risk for certain plaques building up in the brain. Now I'm a vegetarian, and vegetarians tend to have very clean blood vessels by definition, and that's been shown time and time again. The other things I do is I meditate 15, 20 minutes a day in the morning. It reduces your stress level, keeps your brain circuits healthy, and I exercise for 15, 20 minutes minimum three or four times a week. Okay, so it sounds like you are just an overall healthy guy. Well, we still don't know if I'm going to get Alzheimer's or not. Hopefully I won't. Hopefully, hopefully not. You mentioned early on talking about how you thought that rates of Alzheimer's would go up in India and China, you mentioned specifically. Is that just because people there will be living longer or because people in different countries have different rates of getting Alzheimer's to start with? Well, the first thing is the best epidemiological studies to look at rates of Alzheimer's have been largely done in the West because China and India are just catching up with those kinds of studies because infectious disease was a priority for those countries. They're just now turning their attention to Alzheimer's. By and large, the rates suggest that China, the rates are somewhat similar to the rates in the U.S. in terms of the incidence rates. Incidence is the annual rate of occurrence of new cases. In India, the rates seem to be much lower. We don't know because whether their genetic constitution is different, whether their diet is different, or my favorite explanation is curry, but we don't know. But I think the rates are going to increase everywhere because people are living longer. And as I pointed out, age, and the second thing is they are adopting a lot of the unhealthy eating habits. Nobody has time to exercise. Right, and as societies get wealthier and people get wealthier, everybody's eating a meat and not good. So I noticed in a paper that either you or somebody else had published, there were some differences between men and women in terms of memory problems and how it's worse with women. Yes, so this is one of the mysteries that's not fully solved. There's some data emerging suggesting that women, at least in Western countries, constitute a higher proportion of the number of cases of Alzheimer's. I've seen one report say that two-thirds of all Alzheimer's cases are women. There's also some studies suggesting the rate of occurrence of new cases is higher in women. And there's also a study that one of my students published suggesting that if you have mild memory impairment, then women may progress at a slightly faster rate than men. We don't know the explanation for why. Is it hormonal? Is it X chromosome linked? Is it related to how women test on cognitive tests or there's some kind of a bias? So it's not a true difference, it's just maybe that the tests are unfavorable in some way, or it could be something else that we have not discovered. And this isn't just because women are living, live longer. No, this is adjusted. The incidence rates are adjusted for age-adjusted incidence rates at different age groups. So yes, originally it was thought women had more cases simply because they lived longer, but the new evidence suggests that even when you control for that, their difference may still exist. Well, that is something new. What are the other new things that we're learning about Alzheimer's? So probably the most surprising thing that we've learned about Alzheimer's in the last four or five years is that we used to think about Alzheimer's as a disease of old age, right? But what we've learned now is the actual pathology in the brain may begin to build up years, maybe even decades before the actual clinical symptoms become serious enough when someone comes to a doctor. It's like a heart attack, so it's not surprising when you come to an emergency room with a heart attack, it didn't happen that day. There's something that's been building up over years. And I think Alzheimer's we are realizing is a confluence of genetic risks, a silent buildup of plaques and tangles in the brain. So these are the two key core pathologies that are hallmarks. And depending on your family history, if your mother or father had it, you have a much sort of earlier deposition of these plaques and tangles in the brain, perhaps even in your 50s and 60s. So though the full diagnosis may not be made until you're like in your late 60s or early 70s. And just before everybody came in, you and I were talking about this really odd connection or lack of connection between cancer and Alzheimer's. I thought that was so interesting. Yeah, it's not fully proven. Of course, you all heard about the cancer moonshot that's occurring. And I wish at some point there'd be an Alzheimer's moonshot. There are now several studies that suggest there may be an inverse relationship between cancer and Alzheimer's. And to some extent people say, oh, that makes sense because if you don't die of cancer, then you live long enough and you get Alzheimer's. But it appears at a biological level, some of the pathways that are involved that sort of trigger someone towards cancer may be protected towards Alzheimer's and vice versa. So there may be some biological basis for that. If you think of it in a simple way, in Alzheimer's there's something called apoptosis that is cell death that happens. Something makes the nerve cells more vulnerable to dying. If you think of cancer, the factors make the cells immortal. So it's almost, if you can find out what makes the cells immortal, then we can make the nerve cells immortal in Alzheimer's and prevent them from getting Alzheimer's. It's hard to know what to do with that kind of information though, because of course nobody wants to get cancer and nobody wants to get Alzheimer's either. Right, but I think at a fundamental level, if you understand the mechanisms, what I really want is the cancer researchers to start talking to the Alzheimer's researchers. Maybe there are some insights from there that we can learn and vice versa, which really rarely happens. Okay, well that's interesting. Probably you all in your workplaces think of the way I do. We're such a siloed organization in so many ways. We are too. Cases in a different building, brains in a different building. We don't talk to each other. That is totally not encouraging. We should. I'm saying this in an extreme way, but yes, generally they don't. So why do you think that this has been so much more difficult to crack than some of the other medical mysteries where we seem to really be making so much progress? Right. Well, first of all, it's the brain. The heart, you know, you can poke in part the heart. You can put catheters. You can even open up your chest and look at the heart. It's really hard to open up the brain and see what's going on. That's one. The second is only recently we have developed brain scans that allow us to monitor the buildup of Alzheimer's pathology. Until recently, we didn't even have that. So a patient would come to me and say, Doc, I went to my family doctor and said, I have memory problems. The family doctor goes, I have memory problems too. Your memory is better than mine. You know, there's nothing we can do about it. There's no way to look in the brain and sort of map the timeline of how the disease develops. For the first time, we have brain scans that are called PET scans, PET scans that can track the buildup of amyloid plaques and tau tangles in the brain. And so now we have the timeline. Once you have the timeline, you can identify people at risk and you can start targeting drugs and see if the drugs are working or not working. So the drugs, do these drugs actually work? Well, we don't know. We're in clinical trials. The failure rate in Alzheimer's trials has been exceptionally high, almost 90 percent plus. We've not had a single new drug approved in the U.S. or in Europe in the last 10 years. We have three symptomatic drugs that provide some modest benefits. But the good news is there are a number of prevention trials that are now underway. Now that we have these brain scans, we can objectively recruit people who are truly at risk, give the drugs, and truly monitor whether the drugs are clearing the plaques or not. And then we can study the relationship between clearing the plaques and the benefits seen in the trial. So for the first time, we have these objective biomarkers that will help us sort of guide the selection of the best drugs to test. So what's your advice to people for somebody who's feeling like, gosh, I can't remember anything anymore. I'm having trouble remembering words. I'm having trouble remembering names. I mean, what is your practical advice to that person? Well, so the first thing we would do is, is it normal aging? Is it somebody who's stressed out, executive, coming to the WEF? Or is it somebody who's sleep deprived, drunk too much, or is it truly early dementia? And it's hard to tell that just by history. We take the history. We see if it's affecting their functioning. We see if it's progressing increasingly over time. And then we have to do some objective testing, where we have age and gender norms. And we can see if they are substantially below age and gender norms. And then based on that, that's when we would make the diagnosis. And then you can order the brain scans and see if they have the plaques built up in the brain. And then the presence or absence of those plaques in the brain will tell you, is it truly an Alzheimer's type sort of cognitive pathology or is it something else? Are you ever confronted with ethical issues about, you know, somebody brings in their aging parent and should you tell that person if they get a bad answer? Oh, absolutely. It's a huge issue because our ability to diagnose Alzheimer's even 10, 15 years before someone gets it poses all kinds of challenges because you don't want to just diagnose somebody, label and say, I can't do anything for you. So at the present time, we're only doing that for people who are willing to be enrolled in trials. We counsel them and say, look, you're just at risk for Alzheimer's because of this build-up of pathology. You know, it's like having a family history. You may be at two to three-fold higher risk for getting it, but it doesn't mean you're going to get it. And we want to enroll you in this trial so that if it works for you great, if not, you're helping others, you know, in the future. Well, recently Dr. Doriswamy did a Q&A in the New York Times and there were so many questions that came in from readers that they had to break the Q&A into a couple of different parts. So I don't want to hog all the good questions. I'm sure that you all have wonderful questions for him as well and why don't we just open the floor? If you could just say who you are. Gary Cohen with Bechton Dickinson. I've heard called speculation that statins could be effective because of their impact on not building up, allowing the build-up of plaque. Is there any research on that to date? Is there any anecdotal evidence or empirical evidence on that? So the question is statins. Statins are the cholesterol-lowering drugs. In animal models, the statins work wonderful in curing Alzheimer's and clearing the brain of plaques. In humans, the trials that have been done have failed. We don't know why they failed. And there's also anecdotal evidence that people taking statins sometimes complain of memory problems because cholesterol is a vital ingredient for nerve cells to function and signal messages from each other. So we don't know the optimal level of cholesterol needed for the brain versus the arteries and the rest of the body. So that's one of the issues. But statins are currently not being pursued for Alzheimer's that I know of. The current drugs that are being pursued are mostly focusing on the immune system. They're sort of boosting the body's immune response so that the body itself can fight the plaques and tangles. So there are antibodies that are being tried against the plaques and tangles. Most of the drugs, leading drugs in prevention trials. Yes? How do you differentiate between dementia and Alzheimer's? So dementia is an umbrella term. So dementia is the equivalent of a car. Alzheimer's is just one type of dementia. So dementia is any condition where from previously high normal functioning someone has declined substantially in two or more cognitive abilities. Their functioning has gone down. They're not able to independently do things they used to do. That's called dementia. And there's objective criteria and there are many causes of dementia. So about 200 to 300 causes. Alzheimer's is generally considered the most common cause of dementia in western nations and older people. In younger people there are all kinds of other causes, infectious diseases. And, you know, mad cow disease can cause dementia. Alcohol, as I mentioned, can cause dementia. And there are many reversible causes of dementia, such as metabolic deficits, thyroid problems, vitamin deficiencies, sleeping pills. A variety of these things have to be looked for in the history to make sure that we can sort of correct those imbalances before we call someone as having Alzheimer's. Given the incidence rate is so high and given we're in the political silly season, do you think that presidential candidates should have to have a brain scan? So I wrote an op-ed for the New York Times on this, by the way, so I would encourage you to read it. I don't think so. And the reason I say that is I think we can judge candidates fairly well by their speeches, by their television appearances, and if they appear to be cognitively with it in their Q&A session, in their memory, at the time of their election, then it's highly unlikely that in the next four years they're going to develop Alzheimer's disease, unless they have a significant family history. So if they have a significant family history of early onset Alzheimer's disease, then there's a good chance. That's one. The second is, of course, if someone is fairly old, I mean, I think when I last in many western nations, there are tens of thousands of centenarians. Let's say if a 100-year-old person were to run for Alzheimer's disease, run for president or vice president, then I probably would ask some questions. That seems perhaps unlikely. But they do disclose their physical health results, and so if they have had a cognitive testing done, it would be great if they could disclose it. But I think what's going to happen in the future is we have automated speech analytics that are coming out that can look at how many times you repeat the same words, how many times you use, ah, when you can't find the right word, and with those speech analytics, they've already gone back and shown that using speech analytics with Reagan, they could predict when he was deteriorating and when he would develop dementia. They've done the same thing with Winston Churchill. So I think that's what's going to happen in the future, so we don't need anything. So automatically you're going to have the presidential candidate speaking, and then the speech analytics at the bottom are going to say 40% chance of developing dementia in the next three years. Is anybody doing that with the current candidates? Not that I know of. That would be a very good story. You can analyze all kinds of other things with speech analytics, by the way, not just dementia. Nancy Burke. Would taking hormones after menopause abort the onset of Alzheimer? So hormones have had a mixed history. So we went through a phase where we thought estrogen was really good for the brain, and that both estrogen and progesterone would prevent dementia, and then in the U.S. they did a number of trials. The Women's Health Initiative was the name of the trials, and the trials actually found contrary to our hypothesis women taking hormones actually developed cognitive impairment and dementia at higher rates, not at lower rates. So that kind of set the field back a little bit. Studies have been done of testosterone as well, and they've not shown benefit. So at the present time, we don't know. There may be a hormonal relink, but we haven't found the right answer yet. You know, I don't... Are you all studying, and I'm sure you are, how technology is affecting the brain? You know, everybody's using technology for everything. There's so many kinds of problems you don't have to solve anymore, whether it's remembering a phone number, or now given, you know, GPS devices, you never have to get lost anymore. So what does it mean that your brain doesn't have to function in those ways, and what does that have to do with Alzheimer's? It's a great question. I don't think we know all the answers yet. Of course, it's good and bad of technology. On the one hand, I think technology has great potential to help those with memory problems, because you don't have to remember as much. You can outsource all your information to the phone. You know, and soon we'll have an artificial intelligence butler who will go shopping for you, who will... You know, in the Fourth Revolution, you could be essentially a dementia patient, but you might have a smart machine that would do a lot of your tasks for you, which would be a boon in nursing homes and lots of other places. It might help you live in your home longer. At the early end, I think technology is helping us detect people sooner, because soon you're going to have cognitive testing on your phone. In fact, at the loft, there's a technology exhibit, there's a company called Anthrotronics that is exhibiting a mobile self-assessment cognitive tool. So you can take the test yourself and see where you stand in relationship to peers in your age group. And if you score low, it doesn't mean you have dementia, but maybe you could forward that report to your doctor and say, hey, give me some advice, and maybe it's anxiety, maybe it's whatever. So people will be able to diagnose themselves earlier, whether they want it or not. For research purposes, I think it's going to be a boon, because we are trying to create a registry of 60 million people in 180 countries who are interested in research. So you have all these people, and let's say they take all these online tests. We know exactly who to recruit for a trial. If a new drug comes up, you send this email to all these 60 million people, and you could get 30 million people ready to do a trial, and the trial could be done as half as much time in a fraction of the cost. So technology will help in that area. I think it's important to keep our brain active, but I don't think technology is going to reduce that, because every time you upgrade your iPhone, you're working your brain, you're learning new things. Well, that's for sure. So when you stop learning new things, that's when you age. I don't think technology by itself is going to cause you to age. I'm just curious, asking the audience here, how many people would want to go over to the loft and take that test and know where they stacked up? Okay, so the vast majority of people, that's very interesting. I'm not sure. It's one of those things where it's a little bit scary to know that, right? It is, but I think you have to treat these as a number. It's not a diagnosis, so don't feel bad. It's just a number, and numbers fluctuate all the time. Your cognitive test results can fluctuate if you're having a bad day, a good day, so don't panic just because you did well. And we all have a learning curve, and the true test of dementia is how you change over time. It's the slope of change that matters. It's not a single time point test. So I'm just going to keep talking here then. Every so often you'll say early onset, and other times you'll just say Alzheimer's. What does that mean, and what are the ages, and what's the difference? So typically early onset is before the age of 60 or 65. Late onset is after the age of 65, and the reason we call that is early onset forms are thought to have a stronger genetic predisposition. And there are at least three families of genes that have been identified where if you inherit that, then you have a 100% chance of getting Alzheimer's. We have not identified such a gene for people who develop it in the late onset variety. So, you know, we've had the war on cancer, and now we have sort of a new war on cancer. We've heard all over many years about massive amounts of research involving the heart. Do you think we've paid enough attention? Are we spending enough time and money and effort on Alzheimer's? I don't think so. I think the amount of research spending on Alzheimer's is a fraction of what it deserves, given if you're in a knowledge economy. What's more important than cognitive abilities? And if Alzheimer's is striking people increasingly in their 50s and 60s, that's at the peak of our cognitive abilities. You know, people are in leading organizations, the prime ministers, ministers, politicians. I really think we need a concerted international effort. Plants are underway. There are many large brain projects that many countries are doing. In the U.S., there's something called the Human Brain Project. There's the Brain Project. Europe has a Brain Initiative. China is the China Brain Project. I think we need sharing of data, but we also need, I think, out-of-the-box thinking. Sometimes if it's just government doing it, I don't think you will get the biggest innovators and the biggest contrarian thinkers jumping in. You're going to get a lot of academics for contrarian thinking. So one of the things that we posted a blog, myself and Peter Diamandis, is the founder of the X Prize. I don't know if people have heard of the X Prize. So we posted a blog on the web agenda that you could look up where we are proposing the creation of an X Prize for Alzheimer's that would bring out-of-the-box thinkers where anybody working, a single inventor working in a garage somewhere may be able to propose a solution. One thing we want to do that is sometimes these kinds of challenges, you know, contrarian multidisciplinary out-of-the-box thinking, solves the problem that sort of group think may not be able to solve. Two quick questions based on two things you said. First, you mentioned strengthening the immune system as a potential preventative measure. This is a long shot, but there's an increasing, I think, well, there's a lot of investment in probiotic therapy for autoimmune disorders. Is there any potential that bacteria in the gut can have anything to do with plaque buildup and deterioration of the brain? They probably do. We don't know enough about it. Bacteria in the gut have a lot to do with the brain in general. Lately we've been discovering they're involved in depression, they've been involved in obesity, they control what we eat. And so I think there's a very good chance that the gut is related to the brain because amyloid plaques are also found in the lining of the gut. So that's one. The second is a broader question that you're asking is could Alzheimer's be an infectious disease? Even though you didn't imply it. And increasingly there's some belief in the field there is an infectious-like propagation of the pathology in the brain. So could it be a form of sort of a pre-on dementia like mad cow disease? So if you think about mad cow disease, you know, it's slowly propagating, there's an infectious particle, you get it from eating contaminated meat. And there are species of wild animals where amyloid plaques are transmitted through the feces. So we don't know. So the field is now starting to recognize that as a potential and they're starting to study it. Second quick question that thinks something interesting you said that you start aging when you stop learning. I'm not sure if that was based, it was an evidence-based statement or it's a logical statement, but has there been either for aging in general Alzheimer's in particular, thoughts about learning therapy, if you will, more reading when you reach a certain age or coursework for seniors. Has that been incorporated into any research or activities that you're aware of? Yeah, it's a huge interest in that space. So the underlying hypothesis is the brain has plasticity. It's called neuroplasticity. So the more new experiences we expose the brain to, the more connections it can make and the more connections it makes, the more damage it can withstand. So the more resistant it can become. So that's called cognitive reserve. So it's almost like you're building up a reserve capacity. Now the best way to do it of course is the free way to do it. New hobbies, new books, attending events like this. Sorry. But the more formal way to do it would be like going to a gym. You have a trainer who systematically trains your different muscle groups and the equivalent of that is an online brain training game where you systematically train your frontal lobe, your parietal lobe, your reasoning, logic, whatever. We have not had enough evidence-based large trials of brain training to conclude whether or not it can prevent Alzheimer's. Just in the last couple of days, the Federal Trade Commission in the U.S. imposed some fines on a number of brain training companies for making false claims. So which is good, because now it will trigger those companies to do the kind of rigorous clinical trials we need. So we are conducting some trials and a number of others are. So we believe there is some promise there, but it's premature to conclude it will help. Okay, so we are out of time. Unfortunately, like three-word answer, if there's one thing that you can do, what is it to help not get Alzheimer's? Three words. Vegetarian diet? That's two. Meditation? Don't worry. Oh, don't worry. Be happy. There you go. All right. Well, thank you everybody for coming. Fascinating. Thank you so much.