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Brought to you by the Alzheimer’s Therapeutic Research Institute (ATRI), The Alzheimer’s Research Podcast offers an inside look at the science, stories, and people driving progress in the fight against Alzheimer’s disease. Through engaging conversations with researchers, study participants, and leading experts, we explore the latest discoveries, ongoing clinical trials, and the real-world impact of groundbreaking studies.
Welcome to the Alzheimer's Research Podcast, a show reshaping and leading the conversation around Alzheimer's prevention, brought to you by the Alzheimer's Therapeutic Research Institute at Keck School of Medicine of USC. Whether you're a clinician, a researcher, or someone who wants to change their mind, these conversations explore the possibilities within reach to prevent and effectively treat Alzheimer's disease. I'm your host, Shelley Moore.
Mickenzie Vought:And I'm your cohost, Mickenzie Vought. Hey, everyone. Welcome back to another episode of the Alzheimer's Research Podcast. Today, we had the incredible honor of sitting down with Dr. Cecily Jenkins.
Mickenzie Vought:Cecily is an Associate Professor of Clinical Neurology and USC's Alzheimer's Treatment Research Institute, ATRI. And in this conversation, she talked all about the role that she plays as the director of neuropsychology at ATRI. And if you're wondering what is neuropsychology, don't worry, we asked her right off the bat, to really get an understanding of what she brings to the research process and what she has seen the entire landscape of Alzheimer's research change over the last thirty years that she has been in this field. And so it was such a fascinating conversation. And I really, really enjoyed getting to know her a little bit more.
Shelley Moore:Yeah. I think you're really gonna enjoy meeting Cecily today and learning about how she's just excited about the future as well as the most recent changes, which are really exciting. So let's dive in. In this episode of the Alzheimer's research podcast, we will be speaking with doctor Cecily Jenkins. Cecily is an associate professor of clinical neurology at USC's ATRI and is licensed neuropsychologist with expertise in cognitive assessment of older adults.
Shelley Moore:In her role here as director of neuropsychology, doctor Jenkins plays a key role in the conduct of the NIH funded Alzheimer's Clinical Trial Consortium. Cecily is an immensely, caring individual, and she brings that to all of her work here at ATRI. And I'm really excited to to be talking with you today. Cecily, welcome.
Cecily Jenkins, PhD:Happy to be here, and and nice to talk with you both.
Mickenzie Vought:We are excited to chat with you. The first question that I have and maybe our audience will have is, what is neuropsychology? And how did you particularly get into this field?
Cecily Jenkins, PhD:Yeah. Good good question. A lot of people, even people internal to the Alzheimer's Therapeutic Research Institute, are often a little confused about what it is that the neuropsychology team does. So neuropsychology is really a branch of psychology that is really interested in looking at brain behavior relationships. And so specifically in this field of Alzheimer's disease, the neuropsychology team is looking at identifying and using the best kinds of assessments, the best tools to capture things that are changing in people's thinking and memory that will reflect what's happening in the brain, the brain changes that are happening in Alzheimer's disease and preclinical Alzheimer's disease now.
Cecily Jenkins, PhD:We have instruments that actually can capture what's happening in someone's brain before they begin to have symptoms but may be at high risk. So looking for the relationship between things that we see when we assess their memory and other thinking skills and what's happening in the brain itself.
Shelley Moore:So talk about that a little bit more and how you came to have interest in this field and and your path here to the Alzheimer's Therapeutic Research Institute?
Cecily Jenkins, PhD:I graduated from undergraduate the year that the first NIH funded ADRCs came to be. So the Alzheimer's Disease Research Centers were funded in 1984, the first group of them. It was recognized that Alzheimer's disease was something that was going to be beginning to be a real problem, was going to only become more of a problem as the population aged. And at that time, the center focus was on observational studies. Meaning that the studies were all looking at what is Alzheimer's disease.
Cecily Jenkins, PhD:How do we characterize it? How do we describe it? When someone recognizes a change in their loved one's memory, what exactly does that mean? Does that mean that they can't remember new things? They can't remember old things?
Cecily Jenkins, PhD:They don't recognize? What aspect of thinking is impacted. So we were at that point developing the tools to test all the different aspects of thinking, language, attention, visual spatial ability, memory and learning. We wanted to really cover the entire gamut to see what is affected and when. So I got very excited in that very early period as I heard that the NIH was funding these research centers.
Cecily Jenkins, PhD:And that's at that's the point at which I decided to actually go to graduate school in neuropsychology. I've had a pretty straight career path since then. It's a little unusual. A lot of times professionals do a bit of zigging and zagging before they find their place and their passion, but I've kind of been on a straight path And I've been passionate about the work that I do and excited to see the changes that have happened over the years. And I've seen a lot of them.
Mickenzie Vought:Yeah, I think I would imagine that maybe your straight path is also because so much has happened in this field. And it has not looked like those observational studies of, we're just trying to understand what Alzheimer's disease is to, we're trying to diagnose it before someone even shows symptoms, that's such a huge swing in that short amount of time. So I think that's so fascinating and how it has changed so rapidly in the last thirty years. And that may not feel to maybe someone who's been diagnosed with Alzheimer's thirty years ago that is that rapid, but in my mind, in thirty years, how much progress has been made is very fascinating.
Cecily Jenkins, PhD:Absolutely.
Mickenzie Vought:Yeah, what are some of those changes that you've seen? How has the field evolved? And how is our thinking and approach evolved as well?
Cecily Jenkins, PhD:When we first started off, the focus was really on observational characterization of the disease. What is it? The goal was to find out what's causing these changes in memory leading to memory decline in people's loved ones, find a way to either halt it or slow it down.
Cecily Jenkins, PhD:And before you can figure out how to intervene, you need to know what it is. Right? So once you've identified the things that are changing, then you can say, well, how can we go in and and maybe modify that? The first sort of kind of change that happened is that researchers began to take those observations and to look at what the actual pathway of deterioration or negative change that was happening in the brain and then to find pharmaceutical or non pharmaceutical products to try out in clinical trials and to see if they worked. The way that they could see if they worked at that time was largely based on how people performed on the cognitive tests that neuropsychologists had developed.
Cecily Jenkins, PhD:So are they improving? Are we seeing that their memory performance is actually getting better? Or is it just holding steady and we're not seeing the same decline in someone who is taking the medicine versus someone who is not. So that was kind of the first level of change is moving from observational to interventional. The earliest interventional studies were for symptomatic treatment.
Cecily Jenkins, PhD:So people actually had to have symptoms of memory decline and memory change in order for us to look and see whether or not their memory improved or stabilized. A much later shift and gradual involved the identification it sort of paralleled the identification of biomarker evidence of the changes in the amyloid cascade or the pathway from earliest Alzheimer's changes to later Alzheimer's changes. And so once biologists actually began to identify those things that are happening biologically in the brain that are underpinning memory and other cognitive changes, Then the cognitive tests began to be used at much earlier and earlier stages. And this has really just happened within the last several years. So this is fairly recent.
Cecily Jenkins, PhD:That biomarkers are associated with the cognitive tests. And we can now identify people who have biological markers of Alzheimer's disease but don't yet have symptoms. So we know that they are at high risk for developing Alzheimer's changes but they don't yet have symptoms. And we are at this point working on finding interventions that can actually modify the disease pathway. Not just treat symptoms, but actually modify the trajectory of the disease and potentially slow, even stop.
Cecily Jenkins, PhD:So cognitive tests have kind of gone from taking a front seat in Alzheimer's research to riding alongside. It's still in the front seat, but in the passenger seat, maybe to biomarker evidence. And we have now a couple of therapeutics that have been FDA approved for individuals in the early stage of Alzheimer's and even the mild cognitive impairment stage, which is just before an individual might be diagnosed with Alzheimer's disease. And we have FDA approved medications, treatments that help to slow the pathway by about thirty percent over what's been studied today. It is over a fairly short period of time.
Cecily Jenkins, PhD:But we hope that they will be much longer lasting and the and the research continues.
Mickenzie Vought:I loved how you put that the role of cognitive tests have been leading the charge to now joining it to being often secondary and just a confirmation piece with the biomarkers in tandem. So very cool. What do you wish participants or potential participants knew about the research process? From your point of view?
Cecily Jenkins, PhD:I guess first and foremost, I would hope that anyone listening to this and considering research participation but wondering exactly what the value is, I would hope they would recognize that we can't do this without We absolutely cannot do this without you. And the individuals that we're now trying very much to connect with and to help understand their value in this research are people who are at risk but don't necessarily have any symptoms. And this is a tough crowd because they may be still working. Maybe they've had a family history, a loved one in their own their own family that they have watched decline. It's it can be scary.
Cecily Jenkins, PhD:And maybe they're fearful about that in their future. And to think about participating in research, maybe gets them a little closer to that condition and what's happening in that field. We need to study these kinds of treatments in people who do not yet have the disease and to follow them and see whether or not the changes that might be anticipated down the road are slowed or halted. So I guess the biggest message is you are not just a number. It may feel like that if you're deciding to participate in a large clinical trial, but we need every single one of you in order to get to that preventive treatment.
Mickenzie Vought:You kind of spoke out some of the barriers that someone might have to leaning in and taking part in research. I loved hearing some of the ways that your department is advancing your processes to really increase access and equitability within this research process. What does that look like? And how is your department really making some bold changes and shifts in the way that you've traditionally done research?
Cecily Jenkins, PhD:Yeah. I'm so glad you asked that, Mickenzie. So I think everybody on the various teams at ATRI are taking making efforts and taking action to try to find ways to touch and to interface and to meet the needs of those people who we really need to be a part of our work. Specifically in the area of neuropsychology and cognitive testing, we have realized that in the past, research participation often required that people come into a clinical institute, an academic institute or a clinical research center in order to take tests of memory and participate answer, engage in interviews, answer questions, and specifically to do paper pencil tests of memory and thinking. And that can be a burden.
Cecily Jenkins, PhD:It's a big ask sometimes. Yeah. It's a big ask, especially a big ask for people who are in their midlife who are still working Yeah. Who can't take off a half a day to come into a center and have memory testing and answer questions. And so one of the big ways in which my field of neuropsychology is changing is that we are developing assessments that can actually be administered remotely.
Cecily Jenkins, PhD:So administered via the web rather than in person can be done over the phone, also rather than in person. And we are just in the process. We're we're nearing the launch of introducing a cognitive assessment battery. And I I hate that word battery. It means it means like a a collection of tests of all different thinking skills.
Cecily Jenkins, PhD:But we are we are introducing this into our APT web study registry. So the APT web study registry Registry that ATRI has, developed is a large registry of individuals who are potentially interested in participating in research. But for the time being, they've just signed on to engage in some question answer type activities remotely online. So they don't actually come into a center at all, but they are part of a group and a group that we hope we recognize as being highly important to this work. We'll be launching a new cognitive assessment grouping that people can take online.
Cecily Jenkins, PhD:And we will ask them to do it every six months. It takes about ten to twelve minutes to do the whole thing, and we will ask them to take the same set of tests for ten to twelve minutes, five days in a row, and to do that every six months. The reason that we're asking people to do that five days in a row is because the most recent research shows that the earliest changes in people who are not yet aware of any thinking changes but who biologically can be identified as people who are at risk for that in future. The earliest changes are actually a little bit of diminished ability to learn new information with repeated presentation. So usually, when everything's working perfectly, if you repeat the same information over several sessions, people will actually improve.
Cecily Jenkins, PhD:They will learn over time. That's the natural way. For those who are at risk, they will still learn over time, but they will learn a little more slowly, a little less deeply than those who don't have those early signs. So we are wanting to use this new test battery to study learning. And for anyone who may be identified as showing a little bit shallower learning curve who also has some other indicators of risk, which may be biological risk from imaging of the brain.
Cecily Jenkins, PhD:It may be family history, sociocultural background, variables, factors that we have identified with risk. Anyone who is identified as having kind of that configuration of risk may be invited to participate in a research study of prevention. So it's exciting to go from having requiring people to come into an office. Yeah. Take paper, pencil tests to go to remote.
Cecily Jenkins, PhD:And also, we give you a little bit of feedback so you can sort of get immediate feedback about how you did.
Mickenzie Vought:Yeah. And that's something we've been hearing across the board in these interviews is that participants really want access to their results and how are they performing and how can I digest this information? And so I love that you've already built that into the study, and in a way that will give them back some agency in their participation. Very fascinating.
Cecily Jenkins, PhD:We've been very thankful to hear feedback from the participant advisory board Yeah. Which our colleague, Sarah Walter, really spearheaded that effort. And it allows those who participate in our research to actually tell us what they want, and we try as best we can. We can't always provide that. There are sometimes where sharing will actually impact the research data itself.
Mickenzie Vought:Yeah.
Cecily Jenkins, PhD:And so sharing has to wait or has to be modified in a certain way that can be both accommodate what our participants want to hear and also respect the validity of the research itself, the data itself. But we're very thankful to have a voice to let us know what we can do better.
Shelley Moore:In your opinion, what do you think is the most important milestone in the last ten years that ATRI has been in existence?
Cecily Jenkins, PhD:The most important development has clearly been the identification of biomarker evidence of Alzheimer's disease. And our collaborative work and with Dr. Robert Rissman's large research group able to sort of take biological samples at the same time that a person is also being assessed through interview and through cognitive assessment to see how our blood related biomarkers associated with different levels of change in cognition, also imaging findings. So looking at the amyloid burden in the brain, how that is associated with the changes in cognition. We are now moving into kind of a new era where we are beginning to investigate sort of tau biomarkers and tau plus amyloid biomarkers. So we're we're combining the biomarker evidence and looking for combination treatments.
Cecily Jenkins, PhD:It may not be one treatment. It most likely won't be a single treatment that really is best at modifying this disease pathway. It'll probably be several and maybe several at different stages. Can you explain more about you've used that word tau a couple times. I'm exactly sure what that is.
Cecily Jenkins, PhD:It's been known for a very, very long time back to the beginning of of Alzheimer's research. So plaques and tangles have always been associated with Alzheimer's disease. Plaques later came to be understood as a deposition of a protein, a toxic protein. When it accumulates in overabundance, if it can't be cleared from the brain and if it's overproduced, it actually leads to depositing of these protein plaques in the brain. And then at a later, a slightly later stage, those plaques become also associated with a disintegration of microtubules and those tubules begin to break down because of tau, another protein that actually impacts the infrastructure of those cells.
Cecily Jenkins, PhD:It starts to just break down the ability for those cells to transport nutrients. It's a cascade.
Mickenzie Vought:That was great. Thank you so much for simplifying that. That was a fantastic answer. Oh, I really felt like I understood it. I was like, oh, okay.
Mickenzie Vought:Because I've been in these conversations, and I feel like those are words that get thrown around. So that was super, super helpful.
Mickenzie Vought:I've heard a lot about the processes that you and your team go through just the way that you've been able to, like, streamline it across multiple research sites. You've seen so much change in the last thirty plus years in this industry. So I'm just wondering, reflecting on your time at ATRI like, what are you most proud of and the contribution that you and your team have been able to bring?
Cecily Jenkins, PhD:I've been very excited about the fact that the Alzheimer's Clinical Trial Consortium, which consists of sort of three powerhouse academic institutes, including USC's Alzheimer's Therapeutic Research Institute as one of those three powerhouses. It recognized the importance of selecting the right measurements, the right instruments to measure change in cognition for various clinical trials providing a resource to investigators who are wondering what should what tests should I use if any in my study. And so the Alzheimer's Clinical Trials Consortium as part of its structure includes what's called the clinical outcome instruments unit. And we are a team now of five neuropsychologists and one behavioral neurologist, very well known professionals in our field. And we get together biweekly.
Cecily Jenkins, PhD:And we can meet with investigators, that are in process of developing their protocols for new studies, and they may have questions about what instruments they should be using and what are the pros and cons. I mean, there are there are often many options. There are many, many memory tests. How do we pick one that's that's good? How do we know what's good?
Cecily Jenkins, PhD:And so they come to this group of experts and I'm I'm one of that team and very proud to be one of that team. They can come and ask questions and we can actually help them to pick the best tests. So in that way, we have an impact on what measures are being used in the research studies.
Mickenzie Vought:And so incredible how just the heart of ATRI and the ACTC is just to share knowledge to share research, to find a solution and so much collaboration. I know that's not necessarily always the case.
Cecily Jenkins, PhD:So You're absolutely right. It has not always been the case, but it is an overarching mission Yeah. For the Alzheimer's Therapeutic Research Institute is to share what we learn so that we can learn more and not start from square one. And others don't have to start from square one. They can take what has been learned and then use that as a stepping stone.
Cecily Jenkins, PhD:And that's so important.
Shelley Moore:So as we celebrate the ten year anniversary and look to the future at ATRI, what is your hope for the future of Alzheimer's research, Cecily?
Cecily Jenkins, PhD:Well, given all of the progress that we have made so far, I'm hoping that we will kind of continue to improve our outreach, really help people to see the value in their participation in our research studies, people from all corners of The US and international sites that we partner with, people who maybe have not known a lot about research, but I'm hoping that we will find ways to help people open their ears and listen and not feel threatened or, you know, not feel I'm not smart enough. I'm not I'm not a good fit to to give a chance and to realize no matter who you are, you are valuable. So that is a big hope. It's just that we are better at reaching more people. And I'm also hoping that we'll be able to meet with people in ways that they are able and to reduce the burden in their lives as best as possible.
Cecily Jenkins, PhD:And these remote assessments are one way in which we're trying to do that.
Mickenzie Vought:That's what I walked away from kind of a conversation before we hopped on this interview with you was just your passion and the importance of having diverse research and having diverse research participants so that you are creating solutions and prevention methods and therapeutic interventions in a way that is applicable to multiple different populations. And so I'm so grateful that you put that out there that that is your wish. And that's also so much of the heart behind ATRI and create a space that is approachable and equitable and almost enticing, almost like how could I be a part of something bigger than just me?
Cecily Jenkins, PhD:So yeah, yeah, sharing some of our findings, I would hope is going to be helpful to that effort. So just within the last year, I believe Doris Molina Henry, one of our faculty members, was really instrumental in kind of demonstrating that amyloid deposits are different in African American communities. And so therefore, cutoffs that we may be using to include people in clinical trials for Alzheimer's therapeutics may not be so appropriate to African American populations that we don't see the same amyloid burden. There's less of an amyloid burden. And so what's that about?
Cecily Jenkins, PhD:And how can we modify what we're doing in order to make sure that we include people who should be a part of our research and don't use a cutoff that may be appropriate to one group and not another.
Mickenzie Vought:As we kinda round this out, Cecily, is there anything that we didn't ask you that we should have?
Cecily Jenkins, PhD:I guess one of the other things and and this may be of less importance, less on people's minds who are listening to this, but one of the other things that neuropsychology team does and has done is that we help to standardize the gathering of the cognitive data across sites and across individuals within the sites who are collecting the data. We lead a very rigorous kind of training and certification program in the instruments that are used in the various studies and that often involves meeting with raters online one on one, having them demonstrate, giving a test. If it's going to be the what's called a primary outcome measure, meaning this is how we decide whether or not the study is effective or not based on this particular cognitive test, we have to make sure that everybody around the country and around the world who's administering this test in this study is doing it exactly the same way, scoring it exactly the same way so that we see consistency and we reduce the variability in things that could affect the actual statistical findings in the data. So Yeah. It's it's a fair amount of work And sometimes we go back in and listen to audio recordings of test administrations so that we can make sure that the raters are giving it in a consistent fashion, and we give them feedback.
Cecily Jenkins, PhD:We we let them know when they need to adjust and modify. So there's a lot of stuff that happens in the in the back. And
Mickenzie Vought:Yeah.
Shelley Moore:I'm glad you brought that up, Cecily, and I wanna put it in context for everybody because I don't think people understand the numbers of tests that might be giving what's the scale and scope of that just in a single trial if you can just put into context for the listener?
Cecily Jenkins, PhD:Well, I I'm not sure I can give it as an average, but I can say that in our larger studies, both the number of tests that are given and the number of sites and number of raters, sometimes it's more than we can manage through our internal team. Yeah. And we sometimes have to work with an outside vendor that we partner with. They are the ones to actually they have the the breadth of resources in order to to manage it. But the the number of tests can be, you know, 20 or even more than that for a large trial.
Cecily Jenkins, PhD:The number of sites also varies depending on how big the study is. But it could be 50 to 100 sites that we partner with. And at each site, we really expect them to have two raters so that now says, okay. Now we've got a 100 people out there who are giving these tests that we need to make sure they're all doing it exactly the same way. So it is it's a pretty big effort.
Shelley Moore:Yeah. I think it's important to see the big context and and how important that standardization is when you've got that many. And that's really driving the force of making sure that we meet our outcomes with rigor and, scientific care for the participants and that they can feel confident that what I'm getting here in California is the same as what somebody might be getting in Georgia or Washington or Boston or any of the locations where they're participating.
Cecily Jenkins, PhD:And that the answer somebody gives to a question in one location is scored, rated exactly the same as it is in another location. It's free from kind of bias that might be introduced just by the individual who's giving the test. That Yeah. That answer is gonna be scored the same way for everybody at all sites.
Mickenzie Vought:And I would make up that the push behind that has also really come from the role of cognitive testing for so long. Like we need to make sure that if this is the main marker, we have a lot of validity and we have really limited the variability. So that is such an undertaking for your team.
Cecily Jenkins, PhD:It hasn't always been done so rigorously in the earlier days of cognitive research. I think there was probably a lot more sloppiness in that data. And it only kind of began to be recognized the importance of rigor really probably in the early to mid 2000s, especially for the A four clinical study. If any of you watching this know about that very first trial in individuals with preclinical Alzheimer's disease conducted here at ATRI. And that was really, I think, the first large study that was done by our group that had the regular listening to audio recordings of test administration, providing feedback.
Mickenzie Vought:I wonder for those who are listening saying, Okay, I hear it, and I want to take a part. What are the ways that they can get involved? Whether it is through the branch study, whether it's through the larger web study, or just wanting more information about ATRI, where would you send people?
Shelley Moore:So I think it's important for people who want to get involved to visit us at our website. The Alzheimer's Therapeutic Research Institute is found at atri.usc.edu. And there you can find our studies, including the one that Cecily shared with us, which is the aptwebstudy.org. So I hope you'll get involved, and, we do have support for those folks interested through our website, and we have a email, and you can subscribe. You can also get involved by getting in touch with our call center if you have questions.
Shelley Moore:So thank you so much.
Mickenzie Vought:Thank you so much, Cecily. This has been really informative and so encouraging. We're grateful for all the work that you do.
Cecily Jenkins, PhD:Thank you, Mickenzie. Really glad to be a part of this podcast series.
Shelley Moore:Thank you, Cecily. It was so great to see you today. Thanks for listening today. If you'd like more information, please visit us at atri.usc.edu. Thank you.