Brain Health Research: Participate From Your Home

NANCY LYNN: Good morning and good afternoon, folks. OK. We're going to get started. Welcome, I'm Nancy Lynn. I'm Senior Vice President of Strategic Partnerships at BrightFocus Foundation. BrightFocus funds research worldwide for Alzheimer's disease, macular degeneration and glaucoma. And I'm very excited today to bring you the first episode of our Zoom In on Dementia and Alzheimer's Clinical Research.  We've been doing the Zoom In on Dementia and Alzheimer's for just over a year now. And in our second episode, you all were telling me that you wanted to know more about participation in research. And so here we are presenting that today and we should do a minimum of six episodes on this throughout the year. So delighted that you're joining us. I wanted to just mention that these series are supported in part by educational funding from Biogen, Lilly and Genentech. So we thank them very much. So I'm going to jump in and introduce our two speakers. Today we're going to be talking about two research studies that anyone can participate in online from home. And almost anyone, I think if you're over 18. And so we're starting with research that does not involve a drug, that does not involve even riding on a bicycle. These are things that are, I guess we'd call mostly observational. And we're going to talk about the terminology because I think the terminology is very confusing to people. I've been in this field for 15 years and it's confusing to me.  

So we'll talk a little bit about that to start. But first let me introduce our wonderful doctor guests that we're very lucky to get today. I'll first introduce Dr. James Lah. Dr. Lah is currently the Alice and Roy Richards Professor of Neurology and serves as principal investigator of the Emory Healthy Brain Study and the Emory Healthy Aging Study. Clinical Core Leader and Associate Director of the Emory Goizueta Alzheimer's Disease Research Center. I hope I was close on that. That's a hard one to pronounce. Director of the Cognitive Neurology Program and director of the statewide Georgia Memory Net. In his clinical work, Dr. Lah has developed a multidisciplinary team devoted to providing the best possible care for patients and families living with Alzheimer's and related diseases. His current research is focused on improving our understanding of Alzheimer's in its silent, asymptomatic stages and advancing efforts to prevent disease. Welcome, Dr. Lah.  

And I'm also delighted to introduce Dr. John Showalter. Dr. Showalter is the Chief Product Officer and Chief Strategy Officer at Linus health, which is a company that is developing next generation digital cognitive assessment platform to enable earlier detection and intervention in brain health. He is responsible for Linus's integrated strategy for the product, medical and analytics teams. Before joining Linus, John led product strategy and the product, medical and analytics teams as the chief product officer at Jvion, the industry leader in clinical artificial intelligence. Earlier in his career, John served as the Chief Medical Informatics Officer and Chief Health Information Officer for the University of Mississippi Health System, where he also practiced as a primary care physician, which means we know that he can speak in non scientific-ese since he saw patients.  

So welcome, doctors. And I'm going to start, before we actually ask Dr. Lah to start with the Emory Healthy Aging Study and Healthy Brain Studies to go over some terminology because I find it so confusing. So, Dr. Lah, let me start with you. What's the difference between a study and a trial? A clinical study and a clinical trial.  

DR. JAMES LAH: So both of those terms refer to studies that involve people, obviously. The difference between trials and other types of studies is usually you're testing something in a trial. The ones that are closest to patients is clinical trials of medications, whether it's for cancer or for Alzheimer's or anything else. And you're testing different drugs or interventions for a specific purpose, often for treatment, whereas in a observational study or non trial, they can do-- they can encompass different areas. But mainly what you're doing is trying to gather information and learn more about whatever it is that you're studying. So in our discussion today, learning more about brain aging, healthy brain aging and diseases like Alzheimer's disease and related disorders.  

NANCY LYNN: And my next question you mostly answered was, what's the difference between observational and interventional? And that's just a different way of putting it. But is there any further clarification you'd want to add there?  

DR. JAMES LAH: No, I think you're alluding to things that are linked and related. But, you know, interventions and trials can take different forms. Everybody tends to think about drugs, but in the Alzheimer's space, there have been a lot of trials recently looking at lifestyle and exercise. And there are dozens of trials right now looking at exercise as an intervention to promote healthy brain aging and maybe to a slow progression of degenerative brain diseases.  

NANCY LYNN: We actually did get a lot of questions about diet and exercise. And we have done episodes in the regular dementia and Alzheimer's on these interventions. So I'm going to come back to that a little bit later. And Dr. Showalter, I'm just going to ask you because this always comes up. What is eligibility, eligibility criteria and informed consent? Because these are terms you're going to hear always when you're talking about studies and trials.  

DR. JOHN SHOWALTER: Yeah, eligibility criteria really is what are the characteristics of the person that fits into this study. So in the Alzheimer's space, there are studies that we want people that have no evidence of cognitive impairment. We have studies where we want them to have mild cognitive impairment and studies where, you know, it's more of a dementia intervention trial for agitation. And then you're looking for someone who has agitation. So the eligibility criteria is just the characteristics of the person that we either want to watch in that study or that has the problems that we're trying to treat with the medication or another intervention. So that's the eligibility criteria. Just do you have the characteristics and to get a group together that has the same characteristics. And then, sorry, what was the second half of the question again?  

NANCY LYNN: Informed consent.  

DR. JOHN SHOWALTER: Informed consent. So informed consent is, do you understand what's going to happen throughout this study? Do you understand the risks. So as we're talking about observational studies today, you know, the risks are very low. You know, we're going to know, we're going to call you. Maybe the risk is we might annoy you, right. Or if you have, you know, an invasive procedure like a lumbar puncture, you know, there are some rare risks associated with that we want to make sure that everyone joining the study understands all of the risks and is making a conscious, informed decision to participate despite the risk. And the reason this is such a laborious process is rewind the clock 100 years and we don't have a really great track record with informing people of everything that comes with the study. So this has become a big focus and continues to be a big focus in the trial space is to make sure that you understand all of the risks, are volunteering to participate in the study and making the right choice for you.  

NANCY LYNN: Thank you. I am going to turn now to Dr. Lah and ask you to introduce us. Emory is really doing so much in Alzheimer's trials and Parkinson's and all neurodegenerative diseases. So will you introduce us to the Emory Healthy Aging Study.  

DR. JAMES LAH: Yeah so this is, so you did very well pronouncing Goizueta. So Goizueta-- Mr Goizueta was a former CEO of Coca-Cola. And being in Atlanta, Coca-Cola is a big deal. But there's a foundation, the Goizueta Foundation, that does a lot of great work, philanthropic work in the community here. And a number of years ago, the foundation asked us for a transformative project. They said, we want you to pitch us an idea for something that you think will transform the Alzheimer's space. And this was back in 2014, 2015, now. And the idea that they really liked, there were several that we proposed, but the one that they really liked was we knew that today was going to come, that we were going to get more effective treatments for Alzheimer's disease. But we're not going to win against Alzheimer's disease by treating patients who are already sick. Because what we really want is, it's a horrifying disease because people think of where you might wind up in the later stages of that disease. But what we also have learned is that Alzheimer's disease is really a 30-year process. And with the first half of it being completely silent. And so because of some of the technologies that have developed over the past couple of decades, we can identify individuals who are carrying Alzheimer's pathology. We can do that by either directly visualizing it and using special scans, or we can do that by measuring proteins in the spinal fluid and more recently, in the blood that tell us whether an individual has Alzheimer's changes in their brain. And so the idea was, well, we want to be able to both identify people who have this silent pathology and be able to intervene appropriately. So we talked about interventions and trials. One really important factor is when we look at the brains of people who donate-- people who donate their brains, obviously after they've died, when they're no longer using it.  

NANCY LYNN: Thank goodness.  

DR. JAMES LAH: Yeah. And we take their brains. Take the brains of individuals who are normal, who didn't have any memory issues, no symptoms of dementia, mild cognitive impairment, nothing. And when you look at their brains, about a third of them have abundant evidence of Alzheimer's disease, but they never got sick. So this is really critical because we know that this happens. And so if we can identify the presence of pathology, that's not enough. We have to be able to identify the presence of pathology and know who needs to be treated, and when they're likely to get sick. So that was the whole idea for the Emory Healthy Aging and Healthy Brain Studies. As we wanted to develop a sufficiently large group of individuals who would participate in the Emory Healthy Aging Study, which is a purely online study. You said that you had gone through that process. It's a little annoying. Like John was saying, the main risk associated with it is I'm in the study, too, and so every year they want me to update my damn information. And it's just really annoying. But that's all it is. It's just answering questions, some related to cognition and memory, some related to lifestyle and things like that, and medical and family history. And there are about 30,000 people who've participated in that. And we've used that as a vehicle for identifying individuals who might be appropriate because they provide consent, informed consent for us to both look at their information, but also to contact them about other research that they might be interested in participating in. So we've used that as a vehicle for recruitment into other studies. And really the Healthy Aging Study, one of the main reasons we created that was to support the Healthy Brain Study, which is the study that's really targeting that prediction of Alzheimer's disease. And so using that, John mentioned lumbar punctures. So it's been pretty amazing. We've got over 2,100 people who are healthy, middle aged, I used to be able to say middle age was my age plus ten, can't do that anymore. So we've arbitrarily defined middle age as between 50 and 75. So people who are between 50 and 75 are eligible to participate. They have to not have any diagnosis of mild cognitive impairment or dementia. And not have any reasons why they can't participate in things like brain MRI scans and lumbar puncture.  

NANCY LYNN: Sorry, Dr., I'm just going to stop you for a second because I just want to-- so there's the Emory Healthy Aging Study, which you said about 30,000 people have done. And it's an online not quiz, but questionnaire, let's say. And maybe once a year they come back and ask you to update your information or take a little extra online test. Pretty much anyone can participate. And if someone wants to participate, what website do they go to?  

DR. JAMES LAH: So it's the Emory Healthy Aging is the website. And so if you just type in Emory Healthy Aging it will go straight to that study link.  

NANCY LYNN: And we're going to show that link at the end of the program. So never fear. And then, a subset of-- so it's really also something called what is called a registry in a sense, right. So you get all this information on people and their cognitive and lifestyle behavior, how many drinks they have. Just went through it this morning, how many drinks they've had, how much exercise, what do you eat? Are you stressed? How much sleep do you get? All those types of questions. But so it's not an intervention, but it is extremely helpful, I just want to put this in a context, for science, for future generations to be able to study people over time and watch how their cognition changes and how their lifestyles change. So it's really great for science to participate in this. It also, I think, makes people feel a little less helpless and isolated when they can participate in these and have a place they can ask questions to. So it makes people feel like they have a little more engagement and control. And then, what you're saying now, sorry, I just want to make sure then there's a subset of those people who can actually participate in a Healthy Brain Study, which is more hands on, so to speak. So now go into the Brain Study.  

DR. JAMES LAH: Yeah and so, we have people and there are other registries like this. And so there are lots of opportunities for people to participate with what you know, is really a low friction, easy to participate in activities. But it is very valuable because you can draw relationships, when you get large numbers of people, you can draw relationships between people's behaviors. And, you know, the likelihood of them developing certain diseases, things like that, that you really need very, very large numbers to draw some of those relationships. But the Healthy Brain Study, obviously, we have people in the Healthy Aging Study from all over, but the Healthy Brain Study is very much an in-person, much more effort involved in participating in that because it's also a longitudinal study. Longitudinal study, meaning as opposed to a cross-sectional study, meaning that we're following people over time, over many years. So as opposed to taking a snapshot of people at one point in time, we're evaluating people every two years. And so in the Healthy Brain Study, people who are healthy, middle aged individuals, we ask them to do a lot. And amazingly, they do. So everybody that's participated in that study agrees to have visits every two years and was telling you before we started live streaming that usually when people sign up for the study and they come for their first visit, they're the most anxious about the lumber puncture because it's unfamiliar to people and it's invasive. It sounds painful. It sounds terrible. Lumbar puncture, spinal tap. They just sound nasty. But we did some pre and post visit surveys for the first 600 or 700 people and everybody came in anxious about the lumbar puncture but everybody left saying, yeah, that lumbar puncture wasn't so bad but that memory testing really sucked. And my neuropsychology colleagues don't like it when I say that it hurts their feelings. But I'm in this study and I've had probably at this point, I've had five spinal taps and the spinal tap is no big deal. But every time I do the memory testing, it makes me feel dumb.  

NANCY LYNN: I'm sorry. I'm going to jump in again because someone put a question, Dinesh, put a question in the chat and you can chime in if you'd like to ask it directly. But I'll ask it for now since it's in the chat, is a person with a diagnosis of mild cognitive impairment or MCI not eligible? And if not, are there any other studies? How do we help people find studies if they have been diagnosed with MCI?  

DR. JAMES LAH: Many, many studies for MCI. The reason we have to target so many people for the Healthy Brain Study is people in that age group-- the reason so the reason we targeted people 50s and 60s primarily is because most people develop Alzheimer's disease in their 70s and 80s. And we think that there's a 20 year process that goes on before people get sick. And so we wanted to study people in that age group. But when you get into that younger age group, the frequency of silent pathology is much lower. And that's why we have to have such a large group. And the purpose of that really is to see what happens or whether we can predict who's actually going to develop mild cognitive impairment, which for those who may not be familiar, mild cognitive impairment is the very earliest stages of memory loss and cognitive decline. And it doesn't really matter whether it's Alzheimer's disease or something else. If people have an age related degenerative condition that's going to cause progressive decline and dementia, the first stages of that we can detect clinically is in that mild cognitive impairment stage. And in fact, know, today the world is different because we have a treatment for Alzheimer's related mild cognitive impairment that we did not have even a year ago. And so it has actually complicated things because we still need to do a lot of research on people who have very early stage symptoms of mild cognitive impairment. So there are any number of sites if you are in a place where you're close to an NIH funded Alzheimer's Disease Research Center, you can go to the Alzheimer's center's website and find information about clinical trials and studies for people with mild cognitive impairment. The Alzheimer's Association has a clinical trials trial matching group. The Global Alzheimer's Platform is also doing some related activities. So there are lots of opportunities and very important participation needs for people with mild cognitive impairment.  

NANCY LYNN: And I'll jump in on the brightfocus.org website. We have also find a trial widget. That's a little easier to use than the government's version and so on. And you can also write to us and we can help direct you to resources to find the right trial near you. And I want to just say to Carrie, who wrote in the chat, is the treatment you're referring to Leqembi, which I know that is, and potentially, there will be another drug approved soon called donanemab. And we'll just let everybody know that when that is approved, we will immediately do a Zoom Iin to discuss donanemab as we did with Leqembi when it was first approved.  

DR. JAMES LAH: I may have to join that one, because I'm not quite sure how we're going to prescribe donanemab It's a very complicated process, so we'll see if we get some guidance from FDA for that.  

NANCY LYNN: Yeah and since we're talking about this is part of the eligibility criteria. When Dinesh asked if I have MCI, am I eligible or not eligible. Ihor who I see, I hope I'm pronouncing it right, who's on the Zoom sent a question in. When is it considered too late to even consider researching clinical trials? When are there no trials left or it's just not worth it?  

DR. JAMES LAH: Well, I'm not sure that there is a time. The one good example of that is there was a very important study that was done a number of years ago with participants who were enrolled in hospice care. So in terminal stages of disease. And that study was looking at some of the amyloid tracers that we currently can use to visualize Alzheimer's disease in living people. And the reason this study was done enrolling people who are in hospice care is because it's really important-- the gold standard for proving that this tracer actually detects Alzheimer's pathology in the brain in humans is to prove that when you look at their brains after they've died, that the tracers were showing the same pathology that you can see under a microscope. And so these people donated their brains after they died. They had these PET scans during life. And so you could learn about the presence of pathology and how well these tracers work in humans and match it up to what their brains looked like after death. So there's not depending on the goals of the study or the trial John alluded to people who have agitation, which is a terrible problem in our patient population. It tends to be something that occurs later on in the course of dementing illnesses. But there's a really important need because we don't have any good treatments to manage agitation in later stage patients. So I don't know that there really is a limit.  

NANCY LYNN: Thank you. That's wonderful. And there are also places where people can donate their brains after, which is extremely helpful. On this Thursday, we're going to have Steve Salloway, Dr. Steve Salloway on the program, and he runs a brain bank, I believe, at Butler. And I also want to mention to Christie, who's writing in the chat about some genetic situation that Thursday at 1:00 PM eastern, 10:00 PM Pacific, 10:00 AM Pacific, sorry, we will have Dr. Salloway talking about genetics and early diagnosis. And that's exactly the question the person in the chat is asking about. So please, Christie, tune in on Thursday or that program will be available online as well. So, Dr. Lah have about five minutes more if you want to talk any further, before we switch to Dr. Showalter, about the Healthy Brain Study or anybody who wants to ask a question about the Emory study. So you said that-- I have a question, you said that people come in to the office about every two years for these lumbar punctures, and I guess is it an MRI or other. I'm going to ask you what other things they do. But can I fly in if I'm from out of town or do I have to really be local?  

DR. JAMES LAH: You can. We in fact, we do have some people who started in the study and moved and, you know, maybe they're just using it as an excuse to come visit their grandkids in Atlanta or something. But they do they schedule visits to come in from wherever they live. And so it's just we don't expect that to be the norm. But certainly, people can. And you know, two things, and before I give way to John, you mentioned brain donations. And there's a real important misconception. So one of the things that we're doing in the Emory Healthy Brain study is providing information about donating brains. And remember, these are all healthy people. And there's among the Alzheimer's centers around the country, there are thousands and thousands of brains that have been donated from people who are sick. There are very few brains from people who are healthy. And so donating brains from people who are well is really important because we need to know what goes into allowing-- somebody mentioned that 30% of people who are normal have Alzheimer's pathology. Well, what was it that allowed those people to age and be healthy and not have symptoms even though they had this pathology? And that's a really important question. And so something that we're asking our Healthy Brain Study participants to also consider donating their brains when they die. Because unfortunately, with a study this large, people get cancer, people develop heart disease. They have other conditions. And so we're trying to introduce that early. But one of the really key things about that, and that's something that I'll mention, about 10% of our participant pool, 10% to 12% of our participant pool have evidence of silent Alzheimer's pathology. And we know that because we can measure those proteins associated with Alzheimer's, amyloid and tau, these pathologies that are consistently present in Alzheimer's disease, we can measure those proteins in the spinal fluid. And so it increases so people in their 50s overall, it's about 5%, but by the time we get to people in their middle 70s, about a third of those people have evidence of silent pathology. And so this is-- and that was the goal was to identify these people either as they develop this pathology or follow them who have this pathology and the really exciting thing. And so I mentioned the Goizueta Foundation. So they gave us a big gift to launch this project in 2015. It's now funded by $5 million a year, $7 million counting indirect from NIH. So everybody on this who pays taxes is helping us to do this study. And the really exciting thing is, even though this was designed as an observational study, since I know based on the spinal fluid, which individuals actually have silent pathology, in 2029, we're going to get readout from a really important trial of using an intervention, the same intervention, the Leqembi that's now available for clinical use in patients with mild symptoms of Alzheimer's disease. We're testing that drug in people who are healthy to see if we can use that to delay or prevent the development of Alzheimer's disease. And so one of the things that I haven't told NIH because they funded an observational study, but the day after, we have evidence that we can actually do something to intervene, there are going to be hundreds of people in this study that potentially will benefit from that treatment. And at that point, the study becomes something completely different because I want all of those people to actually get treatment.  

NANCY LYNN: That's fantastic. And I want to point out that when I ask about can we fly in every two years to Emory to see Dr. Lah is not really for you guys at Emory but for us and one of the reasons why I'm such a big proponent of participating in these trials is imagine having Dr. Lah to ask all of your questions to as you're going through this journey with your family. And so one of the huge benefits of participating in research is having the connection to a doctor like Dr. Lah, or Dr. Showalter, who are going to where you can ask your questions all along the way. Because one of the things about dementias, as we know, is that it's a long journey most of the time, and things are constantly changing. And so you really it's not possible to have a 90 minute program and know everything there is to know. So participating in research is really an excellent way to be able to get better care and more information. So thank you. And I'm going to now reintroduce or re invite Dr. Showalter, who is about to launch with Linus Health and a couple of other organizations, a brand new online-- it is a study, but it's a quiz. And it's quite unusual, which is why I asked him and Linus to come on and talk about it. It's not actually available for another week, but it will launch in a week, I believe, on June 27 online, and we'll all be able to participate in it then. So welcome, John, Dr. Showalter. And can you just give us a basic overview of NeuroQuest and the neuro types.  

DR. JOHN SHOWALTER: Yeah so, you know, we're really excited to be launching the NeuroQuest study in conjunction with Not Impossible Labs and their Mind Neurotype Initiative. And the goal of this study is to really understand the lifestyle and behavioral choices that people are making from 18 and up. So there's increasing data, increasing literature that lifestyle and behavioral choices impact the overall risk of cognitive decline, impact the risk of dementia. But the vast majority of those studies have been in the 45 plus, and many of them in the 55-60 year-old plus. But as Dr. Lah said, you know, we know this starts at least 30 years before. So that's pushing us back to 45. If the first signs show up 30 years before the activities preceding that are very likely contributing to whether or not you begin to have signs 30 years ahead. But we don't really understand what that behavioral piece is across the ages. So this is targeted at getting what we refer to as behavioral clustering, but an understanding of which behaviors go together and which behaviors need intervention and how do they look across the overall lifespan. And, you know, to pull out particular examples, you know, there's just a longitudinal study out of Barcelona that showed poor sleep and excessive drinking was associated with an increased likelihood of cognitive impairment and dementia. Well, we also know that the college students tend to suffer from excessive drinking and decrease quality sleep. But how does that know, how many 30 year olds, 35 year olds have that cluster? Is this a cluster that weakens? And people really developed it when they were in college and it sticks with them until they're 70, and that's the driving factor? Is it something that waxes and wanes and there's some evidence that alcohol intake increases after retirement, so just understanding across the ages what these behaviors are that we compound because, poor sleep and excessive sleep and looks in the study like that's a worse cluster than just poor sleep or excessive drinking if the other one's fine. So the goal here is to gather you know, the initial tranche we're going for is 20,000. If we get 20,000, we're going to expand it to 100,000. But the initial tranche is just to get people to come in and provide lifestyle information. Now, to make this fun, because that sounds very boring, right, to just go online and take a quiz and tell us your behavior sounds very boring and doesn't bring you a lot of benefit. So we've worked with a couple other groups to bring it into this neurotype where you'll come in, you'll take some questions about your preferences, your likes, you'll get a sign, you'll find out, you know, one of eight neurotypes like how do you approach the world, you know, some personality insight. And then that personality insight will actually drive being given a personal brain health action plan. So what can you particularly do to protect your brain and giving that to everyone down to 18 and telling an 18-year-old knowing they're 18, you know, this is what you can do for the rest of your life to protect your brain while we're collecting the data, because we want to make sure that you're getting benefit from this study as well. So everyone that comes and takes it will end up with a better insight into their personality, their psychology as well as, 3 to 5 specific actions that you can take to improve your brain health. And I think it's incredibly important that we emphasize the improve your brain health. There was just it was a small trial, but it was just published last week that showed people with mild cognitive impairments if they make lifestyle changes. 75% either improve their cognition or stabilize their cognition over five months compared to those that did not make lifestyle changes where it actually continued to decline. So having, I mean, it seems like it's a very easy quiz, but that 3 to 5 things can be very powerful for your brain. And we want to make sure that everyone has access to it. So this is free. It's online. It's available to everyone in the US that's over 18. The website is myneurotype.com. You could go to it today, we'll say under construction, but you can bookmark it. And have it there for the 27th to tackle it. But this is really about, again, that observational understanding what are people doing what activities that other research show are, bad for your brain when you're over 45 are already occurring when you're 27 or 30. And how do they flow across the generations, is a really powerful piece of information for us to know how to target behavioral change across the ages. So that's the overall goal.  

NANCY LYNN: I'm so happy you're here today because this is such an unusual study. What Linus and Not Impossible Labs have basically done is turned a study into almost a game. It's almost like a game app. So when you go on and it asks you questions, some of those questions, as Dr. Showalter was saying, are about your personality. Do you like to be a lifelong learner or are you more interested in people? So it asks behavioral questions as well as things about your anxiety and your lifestyle and how many times you exercise and so on. And at the end you're assigned a neuro type based on your answers. That can be, I haven't looked at them, but it could be a cheetah or a wolf or they have much more clever names than that. But so for young people, they can then put their neuro type icon on social. And while this is fun, it's also really important for our kids and our grandkids. And that's what I want to emphasize here, is that this idea of learning about brain health and how effective lifestyle interventions at any age are is becoming much more a part of the conversation. You know, these diseases have been stigmatized for so long that certainly kids haven't been encouraged to learn about brain health and how their lifestyle affects their is going to affect them in their older age. So I think this is a brilliant and creative way to try to do this. And I had in my notes, I think you've had 13,000-- here it is, 13,000 people over 55 take this quiz already. And so this next cohort of 20,000, or this 20,000, you're wanting to see if you're learnings from the 13,000 that took the quiz hold true, let's say across all ages from 18 to 98, let's say.  

DR. JOHN SHOWALTER: Yeah, absolutely. I mean, that's correct. This is a follow up study for us. So we do have 13,000 people who have already taken the lifestyle assessment. We understand how they're clustering and how those clusters are related to their cognitive performance. So how they do on testing. So not necessarily their diagnosis, but, you know, are they performing well on memory task? Are they performing well on planning tasks? And have really deep insight from those 13,000. The two outstanding questions that leaves is how do those clusters look like when you're less than 55? As well as those are all patients that came into a doctor and took a test. So how does that look in the general population if you're over 55, if you're not worried enough to be in your doctor taking a test? That's huge, because as Dr. Lah said, the biggest challenge in almost all health research is what is healthy, what is normal, what is average? We get a lot of people that are participating because they have a concern, they have a problem, they have an issue, or they have, you know, increased risk factors because the parents, you know, but that what is normal is a real challenge in research. And you know that the number of healthy brains donated to brain banks is a perfect example. Where do we cross from normal to disease is a big challenge in health care. And, we have cutoffs for diabetes. You know, there's a blood test and it has a cutoff. And yes, we get a little smudgy around that cutoff. You know, if your 0.1 over that cutoff, do you really have the disease. But if you're well above it, you clearly have the disease. And we don't necessarily have that for how much amyloid in your brain, you know, actually, you know, causes cognition or is it the location of the amyloid in your brain that really matters. Because we don't have that normal piece at the level that we need it. So these observational studies, these participations in healthy cohorts, the, you know, coming and taking the neurotype and then letting us even just understand what the behavior is of your age group really does allow us to advance science, even though it seems like it's not nearly as sexy as I have a problem, I have a drug. Did the drug fix it? But it that basic science understanding is super important to coming up with the next generation of interventions and therapies.  

NANCY LYNN: Well, I can say your quiz is shorter and sexier than Dr. Lah's quiz, but they're both actually fun to take. And I wondered if we talked for a long time about this idea of behavioral clustering. And I thought it was really fascinating because especially when you're talking about young people, but it's really true throughout one's life that people who may have mood disorders or anxiety and depression, in addition to other types of clusters that you're looking for may actually need a different type of advice in terms-- or different instructions on how they can help their own brain health. So I wonder if you could just go a little bit deeper into the things-- what we're really talking about is the development of precision medicine over time, right. Being able to say this person has an issue with sleep and exercise. They seem to be depressed. We should tell them to do this and we should tell them to do in this particular way. It's also how we tell people. So there's a whole-- it seems to me, a whole psychological aspect here. Am I right in terms of what you guys are trying to do?  

DR. JOHN SHOWALTER: Yeah, so understanding the behavioral change and the need to message in a way that causes behavioral change is huge, so I crack up when people talk about AI can replace doctors and, not until the AI can on the fly figure out how to motivate people to change. Because that's-- when we're prescribing a medication. It's not about prescribing the medication itself. It's about getting someone to understand and agree to take the medication and coping with the side effects and continuing that change, you know, getting somebody to, to exercise, overcoming the challenges that they particularly have with exercise. So we do a lot of, you know, particularly in primary care, you know, things are called motivational interviewing and behavioral change and, you know, measuring whether someone's ready to change their behavior or moving them through the behavioral change process. And there's a lot of personality and understanding that goes with that. And the greater insight we can have into saying like you're a high achiever. You're going to be motivated by me talking about how this is going to get you to the next level. You're a much more, laid back type B person to be generic, how are we going to talk about identifying what matters the most to you and maybe a conversation about maintaining more engagement with your grandchildren's what's going to motivate you. But understanding that personality is really important. And understanding, you know, these personality preferences across the ages and generations from the neurotype is also going to be very insightful and understanding like, wow, you know, there's a whole bunch of, you know, young high achievers that are still really pushing. They're looking for that messaging about, how they're going to advance in their career or how they're going to, you know, conquer the world. And on the retirement side, it is more about, you know, messaging on and, you know, these are all individualized. But, we're expecting to see on the retired side, it's going to be less about that high achieving and more about life and experience. Participation with people just from other studies. But we don't know, that's the awesome part about this is we don't really to our knowledge, this is the first time that we are in a single study trying to get all of this across all of the ages and really focused on understanding the lifestyle and the personality side of this and clustering. Because what we do know is that things when they go together are worse. So if you're depressed and excessively drinking that is worse than if you're just depressed. If you're depressed and not exercising, that's worse than if you're just depressed. If you're depressed, not exercising and excessively drinking, that's worse than the other two. So there is a negative synergy. Things get worse when bad things travel together and understanding how to break that cycle cycle, how to help people. So I practiced in Jackson, Mississippi, which is one of the most challenging environments in the country to practice. Getting people to exercise when it's not safe to walk around the neighborhood is very, very difficult. Getting people to eat healthy when the only thing on the bus route is a 7-eleven. It's very challenging. So understanding how to deal with those individual circumstances and, move people forward. It's very important to this concept of prevention, right. But first and foremost is what is our baseline, what are people doing today? And not necessarily that lifestyle is normal, but what is average? Is really important. And we're not, working from a fountain of knowledge. With that, again, we're pretty good. Lots of studies on impact of cognition on lifestyle for people that are older. But understanding what are those brain healthy behaviors in a 19-year-old is just not there's not a lot out there today.  

NANCY LYNN: Yeah, and it's interesting because I know the Emory Healthy Aging Study, not the Healthy Brain Study, but the Healthy Aging Study applies not only to Alzheimer's or dementia, but across-- they're looking at all diseases. And I think even though this is the NeuroQuest study, it seems more focused in. It seems to me it really could apply to your overall health, right. Or your overall brain health. But your brain health and your heart health are so connected. So it seems to me that even though this seems sort of light and fun, you're actually in a very important area collecting data that has just hasn't been looked at before. Is that fair?  

DR. JOHN SHOWALTER: And that's definitely how we're looking at it. We believe that to bring in particularly the 18 to 25 range this needed to be entertaining and something they were used to doing, like a Facebook quiz or an Instagram quiz or, you know, something that they would experience on the internet that would be. Quick and easy and fun. Because their brain health isn't their primary motivation at 19. But also, if it's engaging in fun, it'll bring in the rest. But there's, very serious scientific question behind all of this on what are those lifestyles as we continue to see the benefit of lifestyle intervention and the risk that lifestyle has in these longitudinal studies. And, I'm sure when the Healthy Aging Study and the Healthy Brain Study from Emory are analyzed, they're going to show that there were lifestyle risk factors that contributed to cognitive decline or contribute to diabetes, contribute to heart disease. And, I'm a proponent that the brain as an organ is an end pathway for these lifestyle. You know, so if you end up damaging your kidneys, that's going to affect your brain. If you end up damaging your heart, that's going to affect your brain. If you aren't able to control your glucose, that's going to affect your brain. So our most important organ, the one that lets us think is negatively impacted by all of the other diseases that come before it, like hypertension.  

NANCY LYNN: And hearing loss and vision loss and, yeah. We have about five minutes left. The time always flies by on these things. So if anybody has a burning question they want to ask, I encourage you to put it in the chat or raise your hand or give us some other indication. I will at the end put the websites back up again. For the next-- I think it's really been great actually, that you've been talking so much about lifestyle interventions because I was going to pull folks for the next episode of clinical research. We obviously will be wanting to talk about donanemab at some point, but I think for this program, I'd like to know if you would like the next, if you the visitors, would like the next episode to be on maybe highlighting a few trials that are on lifestyle interventions. And you can put either your preference into the chat box or Yes, or just a yes, I'd like that. But there's a lot of studies for diet and exercise and I did receive a lot of questions, as I said, about diet and exercise. And I think somebody just asked in the chat. Whether either of you can comment on the work of Dr. Richard Johnson connecting fructose in the diet with Alzheimer's. Do either of you have anything particular you would want to say on that?  

DR. JOHN SHOWALTER: I'm not directly familiar with his research. But generically speaking, highly concentrated sugar is not good for a lot of chronic diseases. And I mean, that's all I'm comfortable saying. But absolutely. Anything where you were spiking your glucose because of high concentrated sugar is nothing your PCP is ever going to recommend that you do.  

NANCY LYNN: You concur, Dr. Lah? 

DR. JAMES LAH: Absolutely.  

NANCY LYNN: And it's not just for brain health, but I think for I, as a layperson, associate intake of sugars with inflammation, and inflammation in the brain is not good. Maybe, Dr. Lah, you want to just talk about that for a second and whether that's something that you have a way of looking at or measuring in the research Emory's doing?  

DR. JAMES LAH: Yeah so, you know, and I'm glad you brought that up because people don't tend to think about brain disease as being associated with inflammation. But that's it's also true in heart disease and other conditions. In fact, part of the problem with obesity is that it increases the set point in terms of the level of inflammation and immune function. And there's some really great technologies now that allow you to measure thousands and thousands of proteins and what are called metabolites. And so people are more familiar with the genetics and the Human Genome Project and sequencing. But now, really there are technologies that allow us to look at proteins and chemicals, there's something called the exposome. So everything that we're exposed to, both internally and externally in our environment, all of those things that can converge on different mechanisms, different systems that wind up causing, disease. And so inflammation is one of those ones that tends to be fairly universal, whether we're talking about heart disease or degenerative brain disease.  

NANCY LYNN: Thank you so much. I'm quickly going to ask April's question.  

APRIL: Hey there. It was magnesium 3 and 8. The supplement I just was reading a lot about it had been taking it magnesium 3 and 8.  

NANCY LYNN: Anyone, Dr. Lah, do you want to comment on?  

DR. JAMES LAH: It's not something that I'm specifically familiar with. And my general approach to supplements is to downplay them. So, when you look at all we're as Americans, we've gotten so accustomed to you know, taking supplemental pills and omega 3 and blah de blah de blah, all of those things have come from dietary studies. So, you know, when we talk about something like omega 3 and don't know where the magnesium 3 and 8 comes from specifically, but when we talk about omega 3 fatty acids and to my knowledge, there's never been a study that has demonstrated taking omega 3 fatty acids from GNC does anything to your risk of dementia. It came from studies where they looked at populations diets and said, well, this group here appears to have less dementia than this group here. What's different? And they narrowed it down to intake of fish and then specific types of fish appear to have more beneficial effects. And then that led to identifying particular types of fats in those fish fatty acids. And so now we take omega 3 fatty acids in a pill from GNC. We have no idea whether that's beneficial or not. So eating healthy, eating healthy diets, exercising, and then, you know, for a good multivitamin with minerals is generally the only thing I tend to recommend.  

APRIL: Thank you.  

NANCY LYNN: And I will also encourage we did an episode with, I believe it's Dr. Laura Baker, on vitamins and supplements which was really interesting. And she has run like 55 studies on different types of supplements or cocoa or, all those. And so that episode is available online. OK. Yes. Do you have that link? I don't know, Amanda or Sharyn, if you could put it-- if you Google, Zoom In on dementia and Alzheimer's. It will bring you to the-- or go to brightfocus.org/ZoomIn. There is an episode, Dr. Laura Baker. And also because several people in the chat today asked genetic questions. There is an episode with Dr. John Hardy on genetics and Alzheimer's in general. And then as I mentioned, this Thursday, we're doing another episode on genetics and early detection. So if some of your questions about genetics were not answered today, please tune in on Thursday. And we're a bit over time, but I think I'm going to have to move these to two hours soon, because I never I always feel like there's so much more to ask, but I want to ask everyone to thank Dr. Lah, and Dr. Showalter for taking time out of their research to talk with us. We really appreciate it, and I hope you'll come back. So I know a lot of questions were not answered that were submitted ahead of time or on today. So please visit the Zoom In website to see if one of those episodes will answer your questions. But if there's something that we didn't answer that you really need us to please email us at reply@brightfocus.org. And let's go to the next slide. Here are websites for the Emory Healthy Aging Study and the NeuroQuest study, again, with note that NeuroQuest study is not active yet. We've got a week to go on that and share that with all of the children and grandchildren in your life. And let us know how they like it. Because it's just being launched and it should be really fun. And any of our episodes can be found at brightfocus.org. And here's where all those other episodes are stored. And the last slide is to tune in Thursday. As I've mentioned, The Role of Genetics in Early Diagnosis and Treatment of Dementia with Dr. Steve Salloway. And on August 1, is when we'll do the next episode and we'll announce ahead of time, which interventional trials are there. So I just want to say again, how much we appreciate everyone joining us. And if your questions weren't answered, please, please re-ask them or write to us. And on behalf of BrightFocus Foundation and Emory and Linus, thank you so much for participating today and have a great day and be healthy.

• Emory Healthy Aging Study: https://healthyaging.emory.edu/
• NeuroQuestStudy: www.myneurotype.com