On Season 7, Episode 7 of The LowDOWN: A Down Syndrome Podcast, Dr. Elizabeth Head gives us the lowdown on Down syndrome and Alzheimer's disease.
The LowDOWN: A Down Syndrome Podcast is produced by the Down Syndrome Resource Foundation. Learn more and support the podcast at DSRF.org.
Follow @DSRFCanada on Facebook, Instagram, and Twitter.
Leave us a rating and review on Apple Podcasts.
On Season 7, Episode 7 of The LowDOWN: A Down Syndrome Podcast, Dr. Elizabeth Head gives us the lowdown on Down syndrome and Alzheimer's disease.
The LowDOWN: A Down Syndrome Podcast is produced by the Down Syndrome Resource Foundation. Learn more and support the podcast at DSRF.org.
Follow @DSRFCanada on Facebook, Instagram, and Twitter.
Leave us a rating and review on Apple Podcasts.
Today on the lowdown in Jasmine podcast talk. Elizabeth Head, kiss us Hello, down on Dancing and Alzheimer MOS Disease. Over to you, Hannah and Mala.
Speaker 2:Thanks, Jodi. On today's episode, we will be featuring a rather complex topic. We know as individuals with Down Syndrome age, they are at increased risk of developing Alzheimer's disease. And there has been some significant research done in this area that can inform how researchers and medical professionals provide interventions. We're very lucky to have a leading expert joining us today.
Speaker 3:Dr. Elizabeth Head received a master's degree in psychology and a PhD in neuroscience from the University of Toronto, Canada. The Motherland Great. Um, she received post-doctoral training at the Institute for Memory Impairments and Neurological Disorders at the University of California Irvine. Dr. Head moved to the University of Conduct Kentucky in January of 2009 and was a professor and associate director of education at the Sanders Brown Center on Aging, now at the University of California Irvine. Since 2019, she's a professor and vice-chair for research in the Department of Pathology and Laboratory Medicine. Dr. Head has dedicated to over 25 years to the study of aging and Alzheimer's disease with a focus on people with Down syndrome and has published over 200 papers. And her research is supported by the N I H. The goal of her research is to contribute to the development of interventions that would promote healthy aging in people with Down syndrome. Welcome to the podcast, Dr. Head. It's great to have you.
Speaker 4:It's a pleasure to be here. Thank you.
Speaker 3:Oh, it's absolutely our pleasure. We've been really looking forward to this discussion today. Yes,
Speaker 4:It's mutual. Trust me,<laugh>. Okay,
Speaker 3:Great. I love that. Um, in our super tradition that we have here on the low down, we would like to start with some secret questions. Are you okay with that?
Speaker 4:I'd love it.
Speaker 3:Okay, super. Um, first question, what is your all time favorite computer game?
Speaker 4:Oh, gosh, right now I am very much addicted to Oxygen Not Included, which is a fun time management game with a little science in it.
Speaker 3:<laugh>. Yeah, it sounds a little bit dire<laugh>, but great. That sounds fun. Um, the second question is, what is one skill that you wish everyone in the world had
Speaker 4:To be able to speak all languages? Ooh,
Speaker 3:Wouldn't that be something? Yeah, that was so great.
Speaker 2:So many things could be resolved if that was a case.
Speaker 4:<laugh>. Exactly. And even just in my own life with the international science community, being able to speak fluently with everybody would be so fantastic.
Speaker 3:Yeah. Yeah. Imagine what we would all learn. It would be just so great.
Speaker 2:Yeah. There's a whole bunch of polyglots everywhere. That'll be awesome.
Speaker 4:Yes.<laugh>.
Speaker 2:Mm-hmm.<affirmative>. Um, okay, I'll take over for the next few questions. Uh, what is your go-to de-stress routine after a busy day of work?
Speaker 4:That would be walking my senior foster fail dog<laugh>. Aw. Aw. Who walks at my pace, which is perfect. Uh, so that usually kind of winds me down for Yeah. 20, 30 minutes, depending on his mood. Right.
Speaker 2:Oh, perfect. Animals have such a good way of de-stressing, so that's such a good idea. Um, okay, question number four. You have your own late night talk show. Who do you invite as your first guest?
Speaker 4:Oh, okay. I would invite Keanu Reeves.
Speaker 2:Oh, okay. Good one.
Speaker 4:He's not only Canadian, which I love, but he just seems to be one of the nice guy celebrities in the world. So yeah, I would do that.
Speaker 2:That's awesome. That's a good one. Um, okay. And then finally, if you could trial another career path, what would it be?
Speaker 4:If I had the skill, I would love to be an opera singer,
Speaker 2:<laugh>. Oh,
Speaker 4:That's true. But I have
Speaker 2:Skill<laugh>. Well, that's,
Speaker 4:So, yeah.
Speaker 2:Do you enjoy listening to opera,
Speaker 4:Though? I enjoy it and I sing with it, but it's just not good. Okay.
Speaker 2:Well, you know, whatever, whatever. As long as you enjoy it, as long as you enjoy it, we, I, I'm right along with you. I can sing along, but not on my own either, so,<laugh>.
Speaker 4:Exactly.
Speaker 2:Um, well thank you so much for indulging in. That was nice to kind for our listeners to get to know you as Marla said, as a person first, and then now we'll kind of jump into the professional side of things. Um, can you talk to us a little bit about how you started working with individuals who have Down Syndrome, and why was this population of interest to you?
Speaker 4:So it, it certainly wasn't purposeful. Um, I, I don't have anyone in my family or friends, um, with Down Syndrome. And, um, so my background is really in behavioral neuroscience, understanding behavior. Mm-hmm.<affirmative>, and it was more related to actually animals than it was to cool people. Thanks. And it just, in my transition down to the University of California, I started to learn a whole new set of skills, which involved looking at the brains of people with Alzheimer's disease. And while I was learning how to do that, um, I was introduced to a pediatric neurologist, whose name is IRA lot, and Ira became a mentor for me and kind of started asking me questions about aging and Down syndrome, because we had a few lovely brain donors and we had some, um, specimens to look at. And then as we got to talking more and I started reading more of the literature, I realized there was, there was so little information out there for people with Down Syndrome and their families. And, um, so Ira really instilled that passion for me. Mm-hmm.<affirmative>. And it's really fun because in this research area, the people you meet are also super passionate and enthusiastic about the topic, and it's infectious. And, and the next thing you know, you're completely immersed in this world. And it's been an absolute joy for me. Um, not only through the people I get to meet, but it does feel like I can make a contribution.
Speaker 2:Mm-hmm.<affirmative>
Speaker 4:Mm-hmm.<affirmative>. So that's kind of, you know, it, it was, it was a CTU circuitous route. I might have to edit that word out cause I can't say it<laugh>. Um, we get it, but, you know, it wasn't a straight line to where I am now. It kind of just evolved over time.
Speaker 2:Yeah. And I think in the past, a lot of the professionals that we've interviewed have had very similar reasons for kind of focusing on this population. A there's not enough research, and that's an area of interest. Um, or you're right. Anyone who really works in the field of Down Syndrome, they're always so passionate and mm-hmm.<affirmative>, uh, Marla and I included, we just, we love what we do, so mm-hmm.<affirmative>, it just kind of draws you to that as well.
Speaker 3:It is a real community mm-hmm.<affirmative>, um, without some of the competition that you see in other fields. Um, and I, I appreciate that collaboration a lot because I think it's very fruitful mm-hmm.<affirmative> to work together. So,
Speaker 4:And you hit it on, on the nail, there are the Alzheimer's world itself. Mm-hmm.<affirmative>, it is full of wonderful, wonderful people, but it is very competitive.<laugh>. Yeah. And so, um, that another reason it goes with my personality. I am a collaborative person, so mm-hmm.<affirmative>, I just love this area.
Speaker 2:Yeah. Great. Um, so before we kind of delve into the research component, um, for our listeners who may not be familiar, can you define Alzheimer's? And of course, we know that Alzheimer's and dementia can, sometimes those terms can be used interchangeably. So if you would like to set the scene for our listeners,
Speaker 4:It's a common question. And, um, so a lot of people say interchange Alzheimer's disease with dementia. So dementia is a, a clinical set of signs. Mm-hmm.<affirmative>, a loss of memory, a loss of function, a loss ability member where we park the car, that those set of signs can happen for a number of different reasons or different diseases in your brain, the most common cause of dementia is Alzheimer's disease. So that means people have these plaques and the tangles in their brains, and that's what's causing this clinical syndrome. But there's other kinds of dementia that are caused by different diseases in the brain. For example, Lewy body disease looks slightly different. It certainly is a dementia, but it's caused by a different set of proteins that are abnormal in the brain. So dementia is the umbrella term. And then underneath that is all the pieces that kind of go under the umbrella, like Alzheimer's disease, Lew body disease, pheno, temporal dementia. Mm-hmm.<affirmative>, et cetera. Mm-hmm.<affirmative>
Speaker 2:Mm-hmm.
Speaker 4:<affirmative>. But you can use them interchangeably. It's,
Speaker 2:Yeah.
Speaker 4:Totally cool. Mm-hmm.
Speaker 2:<affirmative>. Yeah. Um, and with respect to the Down syndrome population, when they develop dementia, is it always Alzheimer's or has there been other forms of dementia kind of, um, noted in the research in this
Speaker 4:Population? So, that's a great question. In my own personal opinion is it's almost always Alzheimer's disease. I believe there are a few case reports out there suggesting, um, one person with Down syndrome had Lewy body disease mm-hmm.<affirmative>, if that happens, it's probably incredibly rare. Mm. So I think we can be pretty confident when we think about, you know, what, what interventions are we gonna design for future mm-hmm.<affirmative>, it's pretty, it's usually almost always Alzheimer's
Speaker 2:Disease. Okay. Yeah. And what are some of the symptoms or characteristics that you see in Alzheimer's disease? And are they different for people with Down Syndrome?
Speaker 4:Uh, in the general population, usually the, the earliest signs or memory loss mm-hmm.<affirmative>, um, although there can be other profiles that variants of Alzheimer's disease that show up early, looking a little bit different mm-hmm.<affirmative>, but memory losses is the key thing. And then of course, that progresses to language problems, um, difficulty with objects in space and, and placement of things mm-hmm.<affirmative>, and then that transitions into more, um, behavioral problems, psychiatric problems mm-hmm.<affirmative>, and it, it just progressively gets worse. Mm-hmm.<affirmative> until somebody really can't take care of themselves. And in Down syndrome, we, it's essentially some of the same things. Mm-hmm.<affirmative>, you know, uh, families will report memory changes in, and people with Down Syndrome, but the most common thing we hear from families is a change in behavior. Mm-hmm. So that person becomes very withdrawn, not interested in the same hobbies, activities as they used to be. And that's a lot of times when it really triggers for families, something's changing and something's going on. Mm-hmm.<affirmative>, so what we're looking for in everybody is change. Mm-hmm.<affirmative>, oh, a single visit to a clinician will give them a, a good guess at what's going on. But we really firm up that diagnosis when we see that person again after a period of time, and we've seen a decline. Mm-hmm.<affirmative>. So, um, so I think the features are essentially overlapping how they're expressed might be a little bit different for a person with Down Syndrome. And that's why it's great for families to be aware of change. Yeah. Mm-hmm.<affirmative> is the biggest thing.
Speaker 2:Mm-hmm.<affirmative>,
Speaker 3:I, I want to be exceptionally clear here. Um, cause we did get to speak with Dr. Oliva on another episode during this season, who's the, one of the co-authors of the adult healthcare guidelines. Um, if families are seeing a behavior change, please do not jump to the conclusion that it is Alzheimer's. Please ask a doctor to check, check it out. Mm-hmm.<affirmative>, uh, because their behavior changes in this group of people can be caused by a number of things. One of them is Alzheimer's, but there are also other things too. And it is, some of them are very treatable and temporary. So it's worth getting that investigated and, um, maybe getting some treatment for something completely different, um, before you Yeah. Go down the Alzheimer's path and just make that assumption.
Speaker 2:Especially, especially as in adulthood and aging mm-hmm.<affirmative>, there's, it's even more crucial to look at some of the other medical reasons why behavior could be changing. Mm-hmm.<affirmative>. Yeah.
Speaker 4:I'm really glad you mentioned that because I, I am seeing more commonly discussions of regression mm-hmm.<affirmative>, and that typically happens in younger adults. Yes. Mm-hmm.<affirmative>, and it's not in that age range where we start to think about Alzheimer's disease, but the co-occurring illnesses are obviously, thank you, a big deal, I gotta get all that sorted out mm-hmm.<affirmative>, but there could also be environmental changes mm-hmm.<affirmative>, and, and we've seen a lot of that. That's like, sometimes it's hard for us to tease out, is it because of a change in their environment or is it a medical condition that's contributing, or is it mm-hmm.<affirmative> Alzheimer's disease. Yeah. Yeah. And they make co-mingle.
Speaker 3:So. Absolutely. Um, I think from my understanding, and you can correct me, we are not expecting to see Alzheimer's disease in people under 40. So if you're seeing a behavioral change in that younger group, certainly anybody in high school or post high school transition, it's been thrown around like, oh, maybe they're developing Alzheimer's. I'm like, Hmm, don't think so. I think we need to look somewhere else, um, and really dig into that a little bit more. For the younger people,
Speaker 4:The 40, 40 years is a pretty comfortable cutoff. Um, I would even start to think under 50 because what we're really seeing, which I think is terrific, and maybe we can talk about that a little more, is the age of onset of the earliest changes is starting to shift later in age. Mm-hmm.<affirmative> Strange, which is fabulous, because that means there's a lot of things people are doing that is delaying the onset, and it might be related to much better management of health Yeah. And much better enrichment of lifestyle factors, so mm-hmm.<affirmative>.
Speaker 2:Yeah. It's,
Speaker 4:Yeah, I agree. But four days are really Yeah. If it's under 40, ask hard questions of your doctor.
Speaker 3:Yeah. Mm-hmm.<affirmative>. Yeah. Good advice.
Speaker 2:Yeah. And that leads us actually perfectly into my next question, which is US listeners are kind of taking all this information in. Um, can we say that all individuals with Down Syndrome will develop Alzheimer's? Like what are the current incidence rates?
Speaker 4:That's an excellent question. So, um, 90% is the big overall average of what we think. Okay. Um, of people with Down syndrome would develop the, the clinical signs of dementia and Alzheimer's disease. But when I look back at all the different studies of groups of people around the world that, that have been published, looking at incidents and prevalence of dementia, it never quite reaches a hundred percent even in the oldest aged people. Mm-hmm.<affirmative>, and this happens in the general population as well. You get people living out quite old and they have a lot of the risk factors, but they're not developing dementia. Mm-hmm.<affirmative>. So I think if I were to roughly say, based on some of the older literature, and I'm hoping with this other big study we have going, and there's some beautiful studies in Europe too, we're gonna get a better handle on this, but 10 to 15% of people with Down syndrome may get into their sixties and even early seventies without showing change in cognition. And that's despite a background of Alzheimer's disease in our brains mm-hmm.<affirmative>, which is pretty remarkable.
Speaker 3:It is. There must be some protective factors. Ooh, it must be so exciting to be you. Oh
Speaker 4:My gosh. This is the, the fun part of things. There's, there's kind of the what's causing the, the dementia, but then there's also, well, what's protecting these people? Mm-hmm.
Speaker 2:<affirmative>,
Speaker 4:Can we figure it out and then we can bring it to everybody, right? Mm-hmm.
Speaker 2:<affirmative>. Yeah. Yeah. Yeah. And I think that's the thing where I, I found it fascinating that so much research in Alzheimer's is like, they're researchers are using the individuals with Down syndrome as a, a, a gateway to figure out more information. So what is it about the, uh, genetic components and the physiological components of Down Syndrome that are helping Alzheimer's researchers progress?
Speaker 4:So the, the, the most wonderful thing, I think for, you know, and, and working with people with Down syndrome and, um, there's a, an additional benefit, and I'll just throw the word prevention out there, but we'll come back to that mm-hmm.<affirmative> is that in the general population, people develop Alzheimer's disease anywhere between 65 and 125. I'll just make up a number,<laugh>. So there's a huge age range mm-hmm.<affirmative> for when a person might develop decline, plus that decline could be Alzheimer's, it could be Lewy disease, it could be final, you know, there could be many things contributing to that. So when you think about trying to understand, say, um, biomarkers, like fluid measures that tell us someone's developing disease or, you know, neuroimaging brain pictures, it gets really complicated because there's such a huge range. Yeah.
Speaker 2:Mm-hmm.<affirmative>
Speaker 4:For people with Down syndrome because of the genetics and that overexpression of the Chromosome 21, the changes in their brains reflecting Alzheimer's disease are strongly aged dependent.
Speaker 2:Mm-hmm.<affirmative>.
Speaker 4:So that means we have a really good understanding by 40, we typically have full-blown Alzheimer's disease in the brain, but that doesn't necessarily reflect in their change of function mm-hmm.<affirmative>. And that means in their, and we know in their thirties, they're starting to develop the earliest signs, but in their twenties, they, they seem to be okay. So we can understand better what's coming first in the order of events that mm-hmm.<affirmative> leads to disease mm-hmm.<affirmative>, and it's really hard to do that in the general population. In fact, almost impossible. Mm-hmm.<affirmative>. So this is where understanding these age related changes in people with Down syndrome tells us a huge amount about how Alzheimer's disease develops and what are the markers in blood or in M R I, for example, that are telling us that person's on that trajectory. And, uh, so that's why we can take a lot of what we learned from people with Down syndrome and take it to the general population. And it also, this is my more positive take on things. Yeah.<laugh> is sand speed. No. That age dependency. So, well, we have a really good shot at prevention mm-hmm.<affirmative> for people with Down Syndrome, a far better chance to do that for people with Down syndrome than for people in the general population. Hmm. So I hope by the time I retire, that's, that's gonna be in play.
Speaker 2:Yeah. Mm-hmm.<affirmative>. Yeah. It would be wonderful. Yeah. Um, so
Speaker 3:I wanna come back to one thing that you said, um, which might be encouraging for families, which is the brain of an individual with Down syndrome might look one way on an M R I and it may not be reflected in that person's behavior. And this is one of those tricky areas of medicine where you look at symptoms and you look at, you know, imaging and they don't match up. Um, do you have any speculation at this point that you can share with us as to what is going on there?
Speaker 4:So we don't know specifically for people with Down Syndrome. There's a lot of really great researchers looking at that question, um mm-hmm.<affirmative>, and it, it really revolves around, um, genes and environment. And there are some genes, you know, just like for everybody that are protective mm-hmm.<affirmative>, and, but they're playing against a very strong genetic background for people with down syndromes mm-hmm.<affirmative>. So they might be a little more muted, although there's lots of data, for example, the apo, lipoprotein egen, there's a variant of that that is drives Alzheimer's disease and, and everybody, and there's a variant that protects you. Mm-hmm.<affirmative>, the same factors are in play for people who with Down syndrome, against that background mm-hmm. Of extra chromosome 21. But most of the areas seems to really be focused on lifestyle factors and the whole idea of cognitive resilience, um, or protection mm-hmm.<affirmative>. So, um, beautiful, beautiful literature. And there's a group, uh, Segan Hartley and Victoria Fleming at the University of Wisconsin are doing a lot of work on these lifestyle factors like physical exercise, for
Speaker 3:Example. Yeah.
Speaker 4:Mm-hmm.<affirmative> and how that alters the trajectory of a person with Down syndrome in terms of when their cognitive changes happen. Because, you know, that would be a beautiful intervention.
Speaker 3:Absolutely.
Speaker 4:There, there's nothing but good things that come. It's complicated scientifically.
Speaker 3:Yeah.
Speaker 4:We can figure that out later.
Speaker 3:<laugh>. Yeah. But so simple but easier to implement. Yeah. Right. From a family perspective, it's actually something doable. Right.
Speaker 4:Very doable. It's, it's not going into a clinic for an injection or, and it has so many complicated pieces to it that all come together and improve your brain's function, like the social aspects, right? Mm-hmm.<affirmative> mm-hmm.<affirmative>. So, um, so that's why I think there's this huge buffer in time of at least 10 to 15 years where, uh, people with Down syndrome, and I'm sure people in the general population have all this stuff going on in their brains, but they're buffering. Yeah. They're buffering a lot because they're managing their hypertension, they're managing their cholesterol, they're exercising, eating well, and Ma, that has a huge impact on your brain. Yeah. Um, at a molecular level. And we've seen a lot of that. So those are things to look forward to, and that's why a lot of the field is talking about the best way right now to, to slower prevent Alzheimer's disease is controlling your risk factors. Mm-hmm.<affirmative> mm-hmm.<affirmative>. And that means controlling your co-occurring illnesses, hypothyroidism for people with Down syndrome, stay on top of that one actually, that drifts a little bit. Yeah. And that can have a real impact on cognition. Mm-hmm.<affirmative>. So I think that is, in my mind, the biggest explanation right now. Mm-hmm.
Speaker 3:<affirmative> interesting. Mm-hmm.<affirmative>. And when we think about the group as a whole, and obviously there's individual differences within that, um, the idea of, of favor favoring of routine is very strong, right. People with Down syndrome are kind of well known for preferring things to happen predictably. And so what that would indicate then is that including, as Met much variety and as many components mm-hmm.<affirmative> into a healthy routine as possible, would be a really good way to go. Right. So that there Yeah. Is space for exercise, space for socializing, space for employment, space for, you know, healthy eating and a, a well-rounded life. Yeah. Um, that's something that's hard to do often, um, because it does involve change for people who might feel a bit inflexible, um, but very worth it and kind of has a knock on effect of bringing further benefit to the person and their family in terms of health and wellbeing.
Speaker 4:And, and we can do this in baby steps
Speaker 2:Mm-hmm.
Speaker 4:<affirmative> mm-hmm.<affirmative>, right? We, we all know that trying to start a new diet or a physical, you know, an exercise, um, routine, if you start with those baby steps of five minutes mm-hmm.<affirmative>, I'm gonna do five minutes and work your way up, that's a great way to introduce a new routine, right? Mm-hmm.
Speaker 2:<affirmative> mm-hmm.<affirmative> mm-hmm.<affirmative> and the baby steps help that person accommodate and get used to the new routine, right. So it's not this sudden and change, and, and Marla, what Marla was mentioning, there's an actual term for that now called a, like our, our adults with syndrome fall into what's, what's called grooves, right? Mm-hmm.<affirmative>, they kind of get in these repetitive patterns of the same routine. And I mean, of course the more you do that routine, the harder it is to get out of it. So it's mm-hmm.<affirmative> one of those things where you're trying to find a balance with supporting their need for structure, but also being flexible within that structure
Speaker 3:Yeah. Routine as healthy as possible.
Speaker 2:Yeah.
Speaker 4:Yeah. Exactly. Yeah.
Speaker 2:Yep. Yeah,
Speaker 3:For sure. Um, I'm gonna take us in a controversial direction. Mm-hmm.<affirmative> heads up to everyone. Um, so there has been some controversy around drug companies excluding people with Down Syndrome from clinical trials. And this has led to some public outcry, a movement from advocates about allowing individuals with Down syndrome who arguably would hugely benefit from clinical therapies, um, to be included in these clinical trials. And I'm sure you have some thoughts on this, so I'm interested to hear those.
Speaker 4:I'm glad you brought that up. Um, this has been something I've been watching for all the years that I've been kind of involved in this. And every time we look at clinical trials and how they're recruiting, cuz we do run a lot of clinical trials in our Alzheimer's center here mm-hmm.<affirmative>, and yes, people with Down Syndrome are excluded from all these opportunities. And it's heartbreaking. I, I I don't like it either. Um, I understand it from a, a, a scientific basis because, um, you know how a person with Down syndrome might respond to an intervention might be different from the general population and drug companies would have difficulty interpreting that data, let alone not having enough people enrolled mm-hmm.<affirmative> to make some really clear, get some really clear answers. Mm-hmm.<affirmative>. So, um, and you know, we've, in the community, we've talked about this an awful lot and I'm, I'm, there's definitely a shift coming
Speaker 3:Mm-hmm.
Speaker 4:<affirmative>, I think in the pharmaceutical companies. But one of the first things that probably will happen, which I kind of like better anyways, is there's gonna be dedicated clinical trials for people with Down syndrome. And I really like that for a number of reasons. One is that how we assess benefits in a clinical trial is gonna be very different for people with Down syndrome than it is for people in the general populations. So even if a pharmaceutical company did include people with Down syndrome, are they gonna do the right assessments for that person? I'd rather have the experts who know how to design those outcome measures, work on that mm-hmm.<affirmative>. Um, so I really like that part of it. And the second part I really like is we do make a big assumption that everything's the same.
Speaker 3:Yes.
Speaker 4:And it isn't, you know, in some, in some parts of Alzheimer's, people with Down Syndrome, there's a lot of overlap mm-hmm.<affirmative> and that's why they, we can crosstalk a lot, but we learned from Alzheimer's in the general population, we could take to people with Down syndrome. I mean there is a lot of crosstalk, but we do have a chromosome 21 extra copy and there's 300 plus genes. And depending on what that drug is and how it works, it might affect a different part of a pathway that is different in people with Down syndrome mm-hmm.<affirmative>, which could mean extra benefits. That would be the best case scenario. Sure.
Speaker 3:Right. Or it doesn't guarantee that, but that would be great.
Speaker 4:<laugh> It would be, or it could mean there's gonna be a side effect mm-hmm.<affirmative> that we wouldn't see and people without Down syndrome. Mm-hmm.<affirmative>. And so having dedicated clinical trials in my mind is probably the best way to go about doing this. Yeah. The safest way mm-hmm.<affirmative> and it will give us interpretable data so we can really go back later and say to families, yes, this is definitely something we suggest, or Mm, not sure it's up to you mm-hmm.<affirmative> or a definite no.
Speaker 3:Yeah. Mm-hmm.<affirmative>. Yeah. But the option is still there, which is great. Yeah.
Speaker 4:Yeah. But I would, you know, those that are gonna be F few mm-hmm.<affirmative>, there's not gonna be as many trials for families to access. So I still think there's a huge benefit from any of these clinical trials to open this up.
Speaker 3:Mm-hmm.
Speaker 4:<affirmative> to people with Down syndrome
Speaker 3:Mm-hmm.<affirmative>. Mm-hmm.<affirmative>, I think, I think it's interesting, it reflects sort of a, a broader population shift from including a very, very limited group in clinical trials mm-hmm.<affirmative>, which we could call adult males, um, to<laugh>, um, a much broader consideration of the people who would be receiving the therapy. Um, also being included in the clinical trials so that we understand medications and their effects and side effects better. Um, this is, this is interesting and I think it sounds like it's moving in a positive direction from your perspective.
Speaker 4:I, I think so too. And when, and you know, the other issue we need to consider is the clinical trials that have been conducted for Alzheimer's disease and have led to these new vaccines. If you look at the makeup of the people who participated, not only only are they they male, they're white. Hmm. They're highly educated. Mm-hmm.
Speaker 3:<affirmative>. Yeah.
Speaker 4:Yeah. So this is not speaking to everybody.
Speaker 3:Yeah, absolutely. Yeah. Oh yes. We have a ways to
Speaker 4:Go. We do. But I guess it right now it's fantastic cuz people are very focused on it. They are really making big efforts to broaden our reach to everybody.
Speaker 3:Mm-hmm.<affirmative>. Um, let's talk a little bit, a little bit more about the research. I think there has been some news about dementia and Alzheimer's in the popular media. Um, may there's been some discussion of p hacking, there's been some debunking of research going on. Um, can you tell us a little bit about the current state of Alzheimer's and Down syndrome research and how research with people with Down syndrome is leading to some breakthroughs in the population?
Speaker 4:Sure. Um, so there's a whole bunch of kind of areas actively going on and interacting through a number of consortiums. And that's the other beautiful thing about this research world is it literally is a research world. Everybody talks to everybody. And, um, so I think a big focus certainly in the space of working with people is getting ourselves to a point that we are ready to engage in clinical trials mm-hmm.
Speaker 3:<affirmative>
Speaker 4:And to get to that part, which we're literally about a year away, um, is we have to understand what changes are happening in the blood, what are happening in, in with the neuro imaging or PET scans, what are changes happening in cognition over time so we understand the natural progression mm-hmm.<affirmative> and then when we go into a clinical trial, we know which outcome measures to use mm-hmm.<affirmative>, which is really important,
Speaker 3:Very important.
Speaker 4:And then, um, if we see a, a certain amount of change in those outcome measures, is that important too for a person? I mean, changing a, a score on a test by two points Yeah. Is that, do we care? Significant?
Speaker 3:Yeah. Right.
Speaker 4:Mm-hmm.<affirmative>, right? Yeah. I mean, is that a big impact for that person on a functional daily day basis? Mm-hmm.<affirmative>. So that's the kind of stuff we're trying to get poised and, and we're doing great. I mean, there's huge data studies coming out and they're, they're rolling out like crazy this year. So I think we're all, um, internationally feel pretty good about where we're on track so that we know when it's time to start a clinical trial. We, we know how to design it, we know how many people we need to enroll, we know what measures we need to take mm-hmm.<affirmative> and we could do a really good job. Mm-hmm.<affirmative>. So that's one part of it. And that's running the other part of it is what intervention, right? Yeah.
Speaker 3:Mm-hmm.
Speaker 4:<affirmative> and that piece of it is being fed by a couple of different roads. Um, one is some very basic science on the bench that might be looking at, uh, the brains of donors, of people with Down syndrome mm-hmm.<affirmative> to look at what protein changes are happening that maybe we should try to change oxidative stress or you know, something else that we're finding in the brain. Then there's people working with mouse models, taking that information and saying, Hey, does it, let's try it first. Preclinical mm-hmm.<affirmative> and if it looks promising, you know, maybe now we need to think about taking it to people. So, um, so there's all this area of which intervention mm-hmm.<affirmative> and then there's all this, let's get it ready and poised to do the clinical trial. Mm-hmm.<affirmative>, these longitudinal studies also help us understand what is the best age to target intervention mm-hmm.<affirmative> or what is the profile of a person that would best respond to this kind of treatment, precision medicine types of approaches. Right. So it's really so exciting right now, when I first started this field, there were just a handful of people kind of working on this question and everybody was working with little, little groups of people and getting, you know, sometimes very biased outcomes because all those people recruited from Chicago. Right. I'm just making a thing up and doesn't translate to everybody Right. Right now. But this international community is built up so beautifully now that mm-hmm.<affirmative>, I can understand how people in Barcelona, Spain, with Down syndrome are aging and I know how they look in California mm-hmm.<affirmative> and, uh, so it's, it's great right now and it's only getting, it's only accelerating cuz the N NIH also invested a huge amount of money specifically and dedicated to people with down syndrome called the include program. Mm-hmm.<affirmative> that's galvanized and really accelerated the research.
Speaker 3:I wanna back up just in case people who are listening aren't super familiar with, um, clinical trials and research. So when you are talking about longitudinal studies, you're looking at people for quite a long period of time. And when you're talking about outcome measures, essentially what you're deciding is do we know if it worked or not? And how do we measure what success is when we've provided a something therapeutic, a medication or some other adjustment or some kind of therapy for a person, how do we know that that is successful? What's enough to be considered success? Um, yeah. And those things are difficult to do, like you described because the population of people with Down syndrome is a little bit different. So we can't just take everything that we would use for your highly educated white males and apply it to the group of people with Down syndrome. It's not relevant. Um, so, and that decision of what a good outcome measure is, we'll tell you if your data is meaningful or not. So it's very, very important to get those things right. And that's why you guys are so focused on mm-hmm.<affirmative> spending time there,
Speaker 2:<laugh>.
Speaker 4:Yeah. Just, just getting to know the natural history. I mean think it, another analogy would be, um, say a statin and cholesterol. Yeah. Mm-hmm.<affirmative>. Right. What we're trying to do is figure out what is the statin we would use, for example mm-hmm.<affirmative>, what is the treatment would use, and then the cholesterol in the blood is the measure that tells us it's working. Yeah. We want the cholesterol measure. Yeah. Mm-hmm.<affirmative>, but it's gonna be a cognition measure, it's gonna be, you know, yeah. Mm-hmm.
Speaker 3:<affirmative> and the group of people with Jan syndrome is a very, very diverse group. Not everybody has the same cognitive baseline. Not everybody was doing the same things prior to the clinical trial and intervention. So it's very difficult to measure. Um, and that's where the precision medicine comes in and all of those details. Oh, I'm so excited for you, Dr.
Speaker 2:You mentioned a little bit earlier about the outcome measures and how we have to kind of, can you talk a little bit more about like what you would use as an outcome measure and why it is difficult to figure that kind of thing out for a population with Johnson syndrome?
Speaker 4:Right. So one of the outcome measures, you know, is, is looking at ch change in cognition. I mean, if, if we have a treatment that doesn't change your memory Yeah. When you have that memory problem, then it's not working. Right? Mm-hmm.<affirmative>. Yeah. So then some of the questions are how do we measure memory in people with Down syndrome mm-hmm.<affirmative> and Marley, you just pointed out, I mean, we have different levels of intellectual disabilities, so we have a different background. Yeah. And actually there's a huge amount of research in that area, by the way, trying to figure out how level of ID affects aging. Mm-hmm.<affirmative> not good, but it also gives us a, you know, some challenges, um, not insurmountable of how do we measure improvement. Yeah. Because they're either very high or very low on that test, just, you know mm-hmm.<affirmative>. So getting that sort out, it's really important because if our measures are not super specific or precise, that means we have to enroll a lot more people mm-hmm.<affirmative> to see changes. Mm-hmm.<affirmative>, if we can get some really nice precise measures that tell us about memory ability or, you know, that means we, we, we don't need to enroll as many people to get a better, to get an answer to our question. Mm-hmm.<affirmative>. And, um, so another way that the, the whole Alzheimer's world is, is dealing with this because the cognitive outcome measures in any Alzheimer's clinical trial are, are less sensitive Yes. Than we hope
Speaker 2:Mm-hmm.
Speaker 4:<affirmative>. Yep. Is they're turning to the quote unquote the biomarkers mm-hmm.<affirmative>, which is getting a blood sample from somebody and measuring different proteins, metabolites or the, the neuro imaging is huge. I mean, it's terrific. Mm-hmm.<affirmative>, you can look for changes in metabolism in the brain. You can see plaques in the brain, you can see tangles in the brain. So those, those outcomes might be far more sensitive. Mm-hmm.
Speaker 3:<affirmative>
Speaker 4:And, um, so if we hit a mark on a blood measure for example, but we're not seeing a change in function, there are some in the field that would argue that's a positive outcome and we're still missing that little piece.
Speaker 3:Yeah.
Speaker 4:Of does it really tell us that person is gonna stay Okay. Stay. We don't know yet.
Speaker 3:Yeah. Okay. Interesting. Yeah. Thank you. That's really helpful. Interesting. Helpful. Yeah. Mm-hmm.<affirmative>, um, I wanna change track a little bit here and ask you if you have any advice for families who are navigating an Alzheimer's diagnosis now with their loved one with Down syndrome?
Speaker 4:Yeah. So the advice I would give is always keep the positive attitude. And sorry if that's a little Pollyanna, cuz I know for families going through this process, it's really hard. Yeah. It's really hard and, and there's not a lot of resources out there mm-hmm.<affirmative> and there's, I know a lot of, we're all trying to help with that when we have a better idea of what guidance we can provide mm-hmm.<affirmative>. So, um, so the, you know, I think the important thing is don't, don't give up on trying to manage any of the behavioral changes. Keeping that routine is really great. There's gonna be disturbing behaviors that are gonna be challenging to deal with. And I think it's really important to, to let families know that caregiver re respite is, should be a part of the whole treatment plan. Yes. Mm-hmm.<affirmative>. Yes. So a, a break for the person taking care of that person with Down syndrome is critically important. Yeah. Mm-hmm.<affirmative>, it, it's, it's, we're treating the family, it's not just the person who has the disease. Right. Yeah. So those would be things I would suggest. And keeping, you know, there's, it's never too late to introduce, even though it may be challenging these kind of healthier lifestyle things. Mm-hmm.<affirmative> mm-hmm.<affirmative>, um, you know, that walk that trying new food. Yeah. Um, you know, music all and social mm-hmm.<affirmative> as much as possible. And, you know, the, the way the, the Alzheimer's disease world has moved, as you can see in the clinical trials listings, there's more and more movement to prevention and less and less movement to treating people with a disease mm-hmm.<affirmative>. And, um, you know, which hurts my heart a little bit, I understand it, but there's still so many things we can do. There are, uh, there is help with medications to help with the behavioral changes, making sure that person's getting sleep is a big deal too. Yeah. So, um, yes, I, I do have a bit of more optimistic outlook on it, but I recognize the challenges are just huge and the biggest problem is the lack of support mm-hmm.<affirmative>. And so I would love to see more grassroots movements of families coming together for support groups mm-hmm.<affirmative> mm-hmm.<affirmative>. So at least they can share their experiences.
Speaker 3:Mm-hmm.<affirmative>. Yeah. I'm so glad that you mentioned respite as one of the first things. Um, Hannah and I and our whole clinic actually advocate for respite sort of all the way through from pediatrics onward. Um, because the caregiver burden is very high and the societal support is very low. Mm-hmm. Um, and it is a big hustle to get that in place for any person. Um, but it's very, very important to do so when possible.
Speaker 4:Yep. And certainly in in the, in the Alzheimer association, um, there are so many resources, there's so much family support, there's so many programs and I would, I want to see more of that for people with Down Syndrome.
Speaker 3:Yeah. Yeah. And some of it's a little bit easier now we've had some families tell us that, oh yeah, I just found my people on Facebook. So that's, it's worth trying for sure. Mm-hmm.<affirmative>, um, especially if you live somewhere remotely, um, maybe that's the easiest way to connect with other families who have a similar experience because Down Syndrome is fairly rare and you might be the only person where you live who's in your situation. So that's Yeah. Worth trying as well.
Speaker 2:Dr. Head, do you also find in your conversations with families that a lot of physicians are not very well aware of how to support a family that may have somebody aging with Alzheimer's syndrome?
Speaker 4:I think that is one of the biggest challenges right now. Mm-hmm.<affirmative>. And what we've been seeing is families will call the, their, their family, family physician will say, yes. You know, your loved one has Alzheimer's disease, the Alzheimer's Association has resources. They reach out to the Alzheimer's Association. They say, well, you can use to talk to the Down Syndrome Association mm-hmm.<affirmative> and then people into this kind of circle. Right. Yeah. But everybody's getting, everybody's now aware of this problem and is connecting up better. And, um, you know, there's, there's some beautiful organizations. I'll just point out the National Down Syndrome Society mm-hmm.<affirmative>, um, who is really trying hard to come up with kind of a directory of doctors that have experience with this and with telemedicine, things are a lot more accessible. Although the healthcare system in the US is very different, as you know. Yeah.
Speaker 3:Yeah.
Speaker 4:<laugh>, this would work way better in Canada. Yeah.
Speaker 3:<laugh>. Oh
Speaker 4:Boy. But I mean, with telemedicine and remote access to specialists I think is gonna be great. The other things that I'm, I'm starting to see, I'm gonna try and do this a little bit on my end too, is going back to medical school education mm-hmm.<affirmative> and, and starting to introduce that whole concept to the medical students. And I have medical students come work in my lab Great. And get it on their radar. Yeah. Mm-hmm.<affirmative>. Um, and so I think that's gonna be the biggest solution in the long run. It's the long haul solution mm-hmm.<affirmative>. Yeah. Mm-hmm.<affirmative> in the meantime. Yes. My sense is that, um, your family physician is, does not have all the skills and referral to a a neurologist is very, very helpful, but if that neurologist also doesn't have experience with a person with Down syndrome, you end up in the same boat. Yeah. Mm-hmm.<affirmative>. So this is where the families and these guidelines are so important mm-hmm.<affirmative> that you can go to the doctor and say, can you check for
Speaker 2:Yeah.
Speaker 4:These things mm-hmm.<affirmative> and then all of us as educators put information out Yeah. To say, you know, here's other people you can talk to. Here's the support group you could join virtually, you know
Speaker 2:Mm-hmm.<affirmative>, yeah. Mm-hmm.<affirmative>. And I think with medical students also that the same goes for therapists. Any allied health team member that is on your, on your loved ones team. Right. OTs, SLPs, PTs. Mm-hmm. We should all become more familiarized with, with, with this topic so we can mm-hmm.<affirmative> also provide some of that supplemental support as
Speaker 3:Well. Absolutely.
Speaker 2:Yeah.
Speaker 4:And, sorry, go ahead.
Speaker 3:Oh, I was gonna say, your therapist is a good person to ask as well. We're all trained to watch behavior, really mm-hmm.<affirmative> carefully. Mm-hmm. Yeah. Um, and really notice some of the subtle things. And so if you have concerns, you can talk about it with your therapist and they might say, oh yes, I've also noticed that it's a good time to talk to your doctor about that<laugh>. Or, oh, have we considered, you know, maybe they need, I'm an S L P. So maybe, you know, there's a just a communication breakdown that we could look at first or Yeah. Something that might be causing a behavior. Um, so there's, there's a lot to consider there. And I also wanna bring up, if you are not in this situation and you have a loved one with Down Syndrome who's doing great and you feel like advocating right now, then please, please, please contact your local medical school and see if they have a day. Often they do, um, where they invite people with Down Syndrome to come in and talk and get to know these medical students. That's the way to make it personal. That's how, you know, our group gets included. Yeah. And, you know, people take interest at that level.
Speaker 4:Yep. It's, um, it's just so important to expose people
Speaker 2:Mm-hmm.<affirmative>
Speaker 4:So that it, you know, they're aware of it. It's on their radar. The, and the other group of people that I think are really, are gonna need this kind of support are people with autism mm-hmm.<affirmative>. Because when those folks start to get older, and they will probably have the same rates of developing dementia as in the general population. Mm-hmm.<affirmative>, how do you take care of that person? Yeah. How do you need to plan? And of course we have the mixed diagnosis in people with Down Syndrome, right. So, yeah. Yes,
Speaker 2:Yes. Mm-hmm.<affirmative> makes the picture a lot more complicated for sure. Yeah. Mm-hmm.<affirmative>. Yeah.
Speaker 3:Absolutely. Um, so we talked a little bit about resources that you would recommend. I have the National Down Syndrome Society, talking to your specialist, talking to your therapist. Were there any further resources that you would suggest? Uh, the Alzheimer's Association's very active and by your description more involved now with the group of people with Down Syndrome. Um, is there anything else that you'd like to include on that list?
Speaker 4:Yep. I think I'm really happy. The Alzheimer's sensation is now does have a lot of focus on Down syndrome. It has some support on, on their website. Uh, the N I H also has some, uh, a good website for education purposes. And, um, of course D S R F is fantastic, so I'll, I'll have to say that too.<laugh>. Uh, so, you know, any national or even local organizations, your local Down syndrome association, um, even their local Alzheimer's associations, um, you know, those are places you can go and look for information. Mm-hmm.<affirmative>. Um, and you know, if you're interested, there's these longitudinal studies that are happening, like our Alzheimer's biomarker consortium for Down Syndrome, which involves many sites, including in Cambridge, uh, uk. There are websites that we all have these different studies that are trying to keep families updated with what are we learning? Mm-hmm.<affirmative>, what's the latest and greatest. So, uh, that's another place to kind of look, uh, for information. And, and one last, uh, group I think is really fantastic is Lu Mind.
Speaker 2:Oh yeah.
Speaker 4:Yes. Um, they're just a fabulous organization. They're also engaged in, in research and they have a great Facebook family page and a website.
Speaker 2:Yeah. Mm-hmm.<affirmative>. We're gonna also put the link to Dr. Chico's, um, adult clinic in Chicago, cuz I know they have tons of really great resources on supporting loved ones with Alzheimer's as well.
Speaker 4:He's, he's amazing. He's one of my absolute favorite clinicians.
Speaker 2:He's pretty awesome. Yeah. Mm-hmm.<affirmative>. Great. Well thank you Dr. I just wanted to make sure we kind of got all those in there. Thank you so much for taking the time to, um, chat with us today. We really appreciate it. It's, I learned a lot today as well. Um, it, it is an area that I personally also feel like, you know, as an OT I need to, to do a little bit more. Cuz we're starting to see more and more adults, especially post pandemic, we're noticing a lot of our adults we're struggling. So it's, whether it's Alzheimer's, whether it's preventative model, either way, it's really great to be able to have that information out to our families and to our listeners. So thank you so much for taking the time. We appreciate it.
Speaker 4:Thank you so much for having me. And those were really great questions. Thank you. Thank you.