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Scientists at ºÙºÙÊÓƵ are working to identify early indicators that would identify people with preclinical Alzheimer’s disease. The hope is that earlier detection — before the brain is significantly damaged — would allow for more successful interventions and better outcomes. In this episode, ºÙºÙÊÓƵ psychology professor Charan Ranganath discusses the nature of memory and how he and his colleagues are working to find biomarkers in an area of the brain called the lateral entorhinal cortex.

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The Nuances of Memory with Charan Ranganath

 

[00:00:00] Charan Ranganath Again, the problem is if you're identifying people who already have brain damage, you're not necessarily going to do much better than just slowing the progression of the disease. But if you can get people who are early enough on, you can stop the progression before people even have memory problems.

[00:00:25] Soterios Johnson Early detection of most any disease can help a person get treatment to cure it, or at least slow its progression. Alzheimer's is one disease that remains difficult to spot in its early stages, but researchers at ºÙºÙÊÓƵ are working on ways to do just that. This is The Backdrop, a ºÙºÙÊÓƵ podcast exploring the world of ideas. I'm Soterios Johnson. Charan Ranganath is a professor of psychology at ºÙºÙÊÓƵ, affiliated with the university's Center for Neuroscience and the Center for Mind and Brain. He's also director of the Dynamic Memory Lab. Welcome to The Backdrop.

[00:00:58] Charan Ranganath Thank you.

[00:00:58] Soterios Johnson So how are you and your colleagues at the Center for Neuroscience going about trying to detect these early hidden signs of Alzheimer's disease?

[00:01:06] Charan Ranganath Yeah, it's a good question. So first of all, it's just useful to understand the way the brain changes in Alzheimer's disease. So when you get older, what happens is you start to get this buildup of proteins called amyloid in the brain. And it was pretty controversial as to the role of how much amyloid plays a part in causing the disorder. And it's still unclear. But one thing we know now is that if you scan the brains of people who seem ostensibly healthy, older people and their memory seems to be okay, what you find is, is that a certain proportion of them will have very, very large amounts of amyloid as well as another protein called tau. But they don't seem to have the later stages of brain damage that you see in Alzheimer's. And so they've come to call that preclinical Alzheimer's, meaning that these people are at much, much higher risk to convert to Alzheimer's disease. But it's not yet showing any of the clinical symptoms. So there's a progression that goes from preclinical AD to mild cognitive impairment to full blown Alzheimer's disease. Now, the problem that we have is that if I wanted to make a drug to treat Alzheimer's disease, what do I have to do? I have to find people who have Alzheimer's disease. But the problem is, once people convert to full blown Alzheimer's disease, they have so much brain damage that you can't reverse that brain damage. So what you want to do is prevent the brain damage before it happens. Even in the stage of mild cognitive impairment, though, that's already enough brain damage to cause memory problems. So what you want is you want to intervene in a person who's at risk but does not have enough brain damage to actually cause significant memory problems. And so what we need to do is come up with noninvasive ways because it's just not cost effective to do the kinds of brain imaging measures that would detect amyloid and tau protein in, say, every person over the age of 50. So if we could come up with tests that are better than what the typical neurologist might use in the clinic, that would allow us to identify the people who are at risk and the people who could benefit most from the drugs that could prevent the progression of Alzheimer's disease. So that's why we're doing this. I know you didn't ask that, but.

[00:03:37] Soterios Johnson But I was going to get there. Were you set it all up for us, which is great. So so people who have this amyloid and tau protein, some of them don't present with Alzheimer's disease symptoms necessarily, which is which is caused, I think some researchers to wonder whether there's another factor involved or is it just that they just haven't progressed far enough into the disease to show any kind of symptoms or decline?

[00:04:04] Charan Ranganath Yeah, I think that there's definitely room for debate as to what the mechanisms are. So, for instance, one idea is that inflammation and neuroimmune processes play a role and these aren't independent of each other. And we know there's all sorts of things like metabolic issues like diabetes, dramatically increases the risk of Alzheimer's. But I think that's a separate question from just the fact that we know that people with this significant amyloid buildup are at higher risk for converting to Alzheimer's disease. And so even if the cause is not the amyloid itself, the important thing is to identify those people. And if we want to identify those people again, we want to identify them before they have memory deficits. Because if you have significant memory deficits and you have this buildup of amyloid, say, there's a very good chance you've already progressed to a stage of Alzheimer's, that you can't really turn back the clock on.

[00:05:03] Soterios Johnson Right. So how do you how do you go about finding these early signs? How do you even start?

[00:05:09] Charan Ranganath Yeah, it's this is what we're trying to figure out. I mean, the beauty of what we're able to do is that, you know, I used to actually test people with memory disorders in the clinic when I was doing my graduate training, and I got really frustrated because a lot of the tests of memory that we would give turned out to be tests that people would develop back in the 1930s or '40s. And really neuroscience has yet to have this major impact in the clinic in the way we identify people with memory disorders. There are some advances. I don't mean to claim there's nothing, but I think we in the basic research community have come up with all sorts of distinctions between different kind of memory. And so one of the things that we're doing is we're trying to switch away from the way people traditionally do memory assessments in the clinic. So, for instance, if you got banged on the head and you went to your neurologist and said, Hey, do I have memory problems? They might say, okay, well, here's a bunch of words I want you to memorize like banana, hammer, you know, truck, something like that. So a whole list of these random words, and then they'll test you on your memory for this list of random words. And you'll make let's say I remember banana, but I didn't remember than you told me hammer. Right? And so, you know, then what we do is we score it relative to all the other people who've taken this test. And so the thing that we can get is a very crude measure of memory, because essentially, let's say somebody is functioning very, very well. They might actually have a memory problem, but it's a subtle memory problem and you can't detect it because what happens is remembering a list of words is just hard for a lot of people because this is not what we do in day to day life. And so what you find is especially, you know, there's all sorts of weird factors that play into it. There's, you know, cultural biases, linguistic biases and so forth. But I think the biggest thing is, is that older people and there's research on this coming out, remember the past through storytelling. And so we've actually done a lot of basic science to understand is there a difference between when people learn essentially a story as opposed to learning a bunch of arbitrary words that we remember? In other words, if we test people on memory in a way that resembles how we remember in the real world, does that make a difference? And so I might show you a movie while we scan your brain, or I might tell you a story while we scan your brain. So it turns out that the network of areas in the brain that are impacted in Alzheimer's and even preclinical Alzheimer's, that whole network is basically online when people are hearing stories. And what you find is, is that let's say there's a particular pattern of activity when there's one scene in a movie and then it'll flip to a different pattern of activity that you see in a different scene in the movie. And so so just to give you an example, I realize this sounds very esoteric. So, you know, let's say, for example, I was talking to you about my science, and then all of a sudden I switch gears and I talk about my dog and I say, Hey, my dog is leaving fur all over the place. That really sucks, right? So your understanding of what I'm talking about fundamentally changes when I switch from science to dog, and we call that shift an event boundary. So the same thing happens just in our day to day life. If you go to the refrigerator and you are sitting in your home office, let's say, or something like that, you walk over to your refrigerator and then you reach the kitchen and you have no idea why you went to the kitchen, right? So this happens to all of us. That happens to us more often when we get older. And the reason is, is that when you cross over to a different room, your mental state changes because now you're in a new room. And so that would also be an event boundary, right? Or you're talking about something, you get interrupted by a text message and then you come back and you're like, Wait, what was I talking about? Salt memory glitches that we have happened because of event boundaries. Now, we've done a study now of three 546 individuals. We didn't collect this data. This was actually a massive study that was done by my colleagues at the University of Cambridge. But they scanned people from ranging in age from 18 to 80 years old. Right. And actually, I think it was even older than that. But anyway, we scanned people's brains while they watched this movie. And what we find is, is that these areas in the brain that are affected by Alzheimer's disease, including the hippocampus, which is thought to be one of the most important areas for remembering events, it turns out that these areas showed spike in activity not throughout the whole movie, but really just at these event boundaries. And so what that tells us, this is something that's very different than what you see when I give you a bunch of words to memorize. What we tend to see is is that a lot of the brain activity that's related to memory is happening at those points where we are shifting gears. Right? So for instance, you are listening to me and then all of a sudden you get a text message about having to pay this overdue bill or something like that, and then you answer that. Then you come back to my conversation. Your ability to even keep up with the conversation depends on being able to pull up what happened right before you shifted gears at that event boundary.

[00:10:53] Soterios Johnson So the event boundary is almost like a distraction.

[00:10:56] Charan Ranganath The event boundary happens when you get distracted. That's right.

[00:10:59] Soterios Johnson Okay.

[00:11:00] Charan Ranganath It can happen even when you're paying attention, but you're just shifting gears between what you're paying attention to, if that makes any sense. Right?

[00:11:09] Soterios Johnson Right. And so the inability to switch back to what you were doing before you crossed the boundary, that's where the disconnect happens with with people who have Alzheimer's?

[00:11:20] Charan Ranganath Well, so there's two things that could happen. One is you have trouble shifting gears. The other is you try to shift gears, but you have no memory for what happened at the event boundary. Does that make sense?

[00:11:32] Soterios Johnson Yeah, I think so. Yeah.

[00:11:33] Charan Ranganath Yeah. So you cross the doorway, you get into the kitchen and you're you remember that you try to go back and mentally time travel back to when you're in your bedroom or your office or whatever. But the problem is you didn't form a memory at the event boundary and so you can't pull up what you were just doing before what you wanted to get in the kitchen.

[00:11:53] Soterios Johnson Right? So that takes us to two to memory, how memory works. And so. So can you talk about how memories are formed in the brain and how they are retrieved just kind of in lay terms as far as like how those mechanisms are disrupted in Alzheimer's disease?

[00:12:11] Charan Ranganath Yeah, absolutely. Absolutely. So, I mean, this is really the revolution I think that we're starting to see in my field. We thought we knew a lot of the answers to this. But I think I'm actually at least part of an emerging vocal group that's saying that we might need to change the way we think about it. So, used to be the traditional thought, and it still is. I think the dominant thought is that the hippocampus is always forming memories, right? So every word that we hear, it's forming a memory of it. Right. And that idea was it's like memory is like a tape recorder that's always on or, you know, you're recording like right now we're recording this podcast and every world is being recorded, right? But if you look at the way people remember events, they don't remember a ton of the details of what they experience. They remember some details, but nobody has a photographic memory. I mean, we can talk about that more. That's a fascinating topic in and of itself. But on average, nobody has a photographic memory. And most memory researchers don't believe in a photographic memory that it could exist. So what do we do then, if we're really not remembering everything? Maybe this question's a whole way in which we're conceptualizing memory. And so another school of thought says, Well, really what we do is you might form memories at particular moments like an event boundary, but then you fill it in with the knowledge that you have, right? So as we get older, our memory for events goes down. But our memory, our knowledge about the world actually stays the same or it goes up. So, for instance, if I'm remembering, let's say if I'm remembering a picnic that I had with the people in my lab, right? So I know what happens in a picnic. I know everything about people in my lab. And so if I can just pull up enough detail that pulls my brain back to that moment and allows me to say, Hey, there was a picnic taking place and hey, these people in my lab were there and it was Maureen and Frank and so forth. All these people who used to be in my lab, I can fill in the blanks from there. Right? And this is what we do a lot is when we remember you sort of pull up the cast of characters, you pull up a little information about where it happened and you pull up some details that are just innocuous things, things you were hearing, things you might have been smelling. But then you start to tell a story and you elaborate on that. And so the storytelling that you see in memory is pretty intact with aging. And in fact, it's pretty. If anything, people rely on the storytelling part more and more and more. But that ability to get those details and the ability to find have a memory for exactly where it took place and exactly when it took place and exactly what you were seeing and smelling. Those are the things that go down with age. And so we think that what is happening is, is that the hippocampus is really giving you these snapshots of our memory when our brain says, hey, this is really important. Grab this. So rather than getting quantity and just hoarding memories our brain is really taking snapshots and prioritizing quality over quantity. Does that make sense?

[00:15:36] Soterios Johnson Yeah, I think it does. I mean, I kind of feel like, you know, in my own personal experience, I feel like there are times where, you know, you like, I'll remember something and I can't believe I could remember that detail, whether it was like a song lyric or something like, you know, how how, how was that in there all this time? And how was I able to come up with it at that moment? So I wonder if there's like, maybe both things are happening in a way.

[00:16:01] Charan Ranganath Well, yeah. So I mean, we don't know. What I'm telling you is just a theory, right?. It could be the case that what our brain is doing is kind of turning up the sensitivity in memory, and maybe we really prioritize the important stuff, but then the unimportant stuff, it's still little bit recorded. We don't know for sure. It's almost certain, though, that there is some kind of a way of saying, Hey, this person pointed a gun at me. This is really important. Whereas, you know, this person shook my hand, not so important. But this idea that you brought up about a song, bringing you back to a place in time, that's actually that point that I was making about the hippocampus, is that what the hippocampus is doing for you is giving you how all of the details of your experience kind of came together at one point, one place and time. And that's what allows you later on you hear some innocuous song, but you hadn't listened to that song, you know, in 20 years or something like that. That song will basically provide a great cue for the hippocampus to pull up all these other details that take you back and give you that feeling of being in the past. And that also allows you to pull up all of this information that you couldn't have before. But it turns out if you do a computer model of memory, you can get a lot of that information just by recording memory at particular points like event boundaries. So the ability to go back in time could be a memory that actually isn't being recorded by the hippocampus for very long. And yet that's enough to give you the feeling of being in the past and give you access to all the place information and the people information who, what, when, where and how. So imagine if you had like a little index card or an index in the brain that says, okay, this is what happened now and then, you know, an hour later, this is what happened now.

[00:18:04] Soterios Johnson So getting back to kind of your work and trying to and trying to find early signs of Alzheimer's disease. So from what I understand, you're trying to find what are called biomarkers. Right? So can you explain what a biomarker is? And also and how are you going about trying to find these biomarkers?

[00:18:23] Charan Ranganath Yeah, Yeah. So what is a biomarker? A biomarker -- that translates to biological marker, which means is there some index of biological function that marks people for being at risk for a particular thing? So for instance, if I wanted -- or allows you to diagnose a particular condition, right? And so in the case of Alzheimer's, what we want is a simple, easy physiological marker that reliably gets people who are at risk for Alzheimer's disease. Right? So, for instance, if I had a blood test, a blood test in theory could give me a biomarker for Alzheimer's disease. If if I said I've got a blood test that identifies people at risk, that could be a good biomarker. In the ideal world, you'd probably want more than one biomarkers so that you can be more and more precise because no biomarker would be perfect. But what we want to do is be able to you know, I've been doing MRI in my lab to record brain activity related to memory. I've been doing this now for, I would say, almost 30 years and so maybe 25 years. Okay. So we have a lot of experience in identifying what a typical pattern of brain activity looks like when people remember. And so we can actually use that knowledge to say, hey, maybe if we scan people's brains while they're trying to learn or remember something, maybe we can identify those markers. And the key thing that we're trying out is to say, well, what if we give people just we give people natural stuff that they naturally remember and we look at what the hippocampus is doing at these event boundaries? And so we have a computer model that tells us how the hippocampus might be supporting learning, and it involves this -- the newest model we have is really cool because it captures the ground zero first point of atrophy in Alzheimer's, which is this little population of cells in the entorhinal cortex, which is a big part of the system that the hippocampus is working in. So we got a model that tells us essentially how do all these cell assemblies come together in the entorhinal cortex in the hippocampus, to help us form memory, and we can make predictions about what the brain activity should look like at these event boundaries. And when we've looked in this very, very large scale study that my post-doc Zachariah did, he's now a professor at Washington University, St Louis. And Zach did an analysis of this big, big data set and found that hippocampal activity spiked at the event boundaries. But people who are older showed less of a spike than people who are younger. Okay. So if we just look at these event boundaries,there might be in a five minute movie, there might be ten of these event boundaries or 20 of these event boundaries, and a lot of them. But it turns out that at these boundaries, you see these reliable spikes in hippocampal activity. We've seen this in study after study. But what's really cool is. They go out of the scanner and they're asked to memorize a story, kind of like again, what we would do in the real world. And what we found is, even irrespective of age, the more people activated the hippocampus during a movie, while these event boundaries were happening, the more they were able to remember from these stories on a completely different test that had nothing to do with what they did in the scanner. So what that tells us is the hippocampal activity at these event boundaries is a biomarker for individuals' ability to remember things out in the real world, or we think it is right? If we have the sensitive marker that is explaining actually quite a chunk of variability in how people might remember in the real world. Now we have something that we can say maybe this is more sensitive because the brain activity might even index risk for memory problems even before it's really obviously apparent to anyone in the real world. And that's what we're going after now, is to see -- we're collaborating with a very, very large scale study that's going to be happening in Germany through this coalition of Alzheimer's research centers. And the idea there will be to get people who we know are at risk, as well as people who we think are low risk, track them over time and see if our measures of hippocampal activity of these event boundaries, which we've designed in experiments and given it to them, see if those little spikes in activity in the hippocampus at just these precise moments in time are going to be telling us who's at risk and who's at low risk for Alzheimer's disease.

[00:23:22] Soterios Johnson So it's not necessarily a blood test or anything like that. It's more like how their brains perform at these event boundaries.

[00:23:30] Charan Ranganath That's right. How much parts of their brain are just working. Essentially, they're showing an increase in technically, it's an increase in metabolic activity, which means they're using more energy. But we think that's also related to lots of neurons kind of coming together and doing something and supporting learning. And so that's what we're looking for, is that marker of when's the brain really coming in and popping in to support learning. And the reason we think that these event boundaries are so powerful is, like I said, if I give you a bunch of words to memorize like justice and, you know, clouds and things like that, it's the kind of arbitrary, weird stuff that you really have to use a lot of weird strategies to try to memorize all this stuff, right? But those strategies are separate from the--  in the brainn the areas that help you use those strategies are separate from the areas of the brain that just encode memories. And so what we think is, is that if we give people a kind of a natural memory test that resembles how older people remember, in the real world, you remove a lot of the stuff that is really unnatural and you focus specifically on what is a healthy brain doing when people are trying to remember things in the real world.

[00:24:51] Soterios Johnson So how close do you think this is to actually being used in like a clinical setting?

[00:24:57] Charan Ranganath Um, we don't know. We still haven't actually validated that it is something that we can really identify people at risk with Alzheimer's disease. And, you know, doing a study like this is very expensive, time consuming, requires a lot of people, which is why right now we've been relying on collaborations with groups that have those resources. I mean, in an ideal world we would be able to have the infrastructure to do something this big because, you know, if you really want to predict something in the real world, you want to have a diverse group of people who you're studying and you want to be able to track that range of just what's what's the typical range of memory functioning in the real world. And so that's the challenge, right? But the technology is already there. The technology is there to basically identify brain activity related to memory. And it's in every hospital. And doing MRI's in hospitals is routine thing. And so you could potentially do this in a 20 minute scan session. You could tack it on to all any other clinical MRI's that you'd want to do and it should be doable. So we think that it's it's very like feasible to implement it and it would not cost that much, you know, be sort of like, you know, it's a little bit more costly say than doing a mammogram or something, but it's something that in theory you could scale up and you could have, you know, everybody over the age of 60 does one of these scans. So that's I think a good target for us is something that involves a sophisticated way of measuring memory. And, you know, and that's actually a whole nother interesting thing that we're working on, which is can we actually use the words that people use when they remember things? So the way in the order in which they remember things as another marker. And so we're exploring how computational methods like the kinds of tools that people are using in these language models like ChatGPT. Can we use those like tools to dissect how people tell a story about a memory and identify those markers that are really indicative of memory problems? Right. So, for instance, if you look at people with memory problems, they might be less likely to say. "And so the the detective picked up "the knife," because "the knife" implies that you are kind of referencing some knife that we already told people about, right?  And so that's just a simple example of the kind of thing where memory is just incorporated into the way we act and talk in the real world, right? Because if you didn't know that there was a knife in this scene of the movie, you would just say, well, the detective picked up a knife, you know? And so these are little bits that we think might be able to pull out and give us additional information through computational methods. And so that's a really exciting frontier.

[00:27:56] Soterios Johnson So I guess the the ultimate goal of a lot of this work is to be able to, you know, intervene when somebody is at risk. So right now, there is no known cure for Alzheimer's disease. So what does a successful intervention look like right now if you're if you are able to detect it early?

[00:28:13] Charan Ranganath Yeah. So one of the things that a lot of the drugs --  this is, again, very controversial, but a lot of the drugs that are being used in Alzheimer's trials are these drugs that stop the accumulation of amyloid. And in particular, you want them to stop the accumulation of amyloid in the cells themselves. There's another approach that my colleague Menno Witter is just really he's at this incredible research group and helped contribute to a Nobel Prize leading discovery about the entorhinal cortex. And so he is an anatomist and can identify that the cells that are part of this Ground Zero reaction in Alzheimer's disease have another protein called reelin. And so he's trying to target that. But basically, I think no matter how you slice it, there's some kind of garbage being accumulated in these neurons that eventually becomes toxic to the neurons. And then that garbage sort of spreads to other neurons. And so one of the things we find is we can use MRI methods to identify networks in the brain. And what you can see is this pathology in Alzheimer's, as people get worse and worse, worse just sort of runs rampant through these particular networks. Right. So it's just like, you know, you're on Facebook and you have a regular social network and somebody starts spreading all this fake news. Next thing you know, it's sort of proliferating all through that network. And the same way we start to see this in the brain where once this junk starts to accumulate, it starts to spread through networks in the brain. And so a good pharmacological target would be to say, hey, let's stop the spread of those proteins in the brain before it becomes neurotoxic. So again, the problem is if you're identifying people who already have brain damage, you're not necessarily going to do much better than just slowing the progression of the disease. But if you can get people who are early enough on, you can stop the progression before people even have memory problems. But if you already have significant memory problems and I try to stop the progression, by then, you're really trying to --  it's kind of like you've got a wild fire and you're trying to put it out after it's already taken out several acres. Right? And I mean, ideally you want to put out that fire before it's had a chance to do much damage. So that would be the idea is you could use a drug intervention, for instance, but you don't want to give these drugs to everybody. You want to give these drugs to the people who need them, because there are often side effects that can you know, there's interactions with other health conditions. And so that's why you wouldn't necessarily want to give a drug to just everybody.

[00:30:58] Soterios Johnson So what's the next step in your research?

[00:31:00] Charan Ranganath So the next step, the next steps are kind of a multi-pronged approach. I mean, one is to really get at whether or not this event, boundary activity, can be tied to risk for Alzheimer's disease and to really conclusively show it. We know already that it can be used as a biomarker for just the range of memory functioning in people. But the next step is then to see can it be used as a indicator of risk for pathology. Another thing, though, that we want to do is build up really nice technical models to track what happens in single cells and relate those to how memory works in the real world. And what I mean by this is that a lot of the mechanistic work on memory or the development of drugs is being guided by work in mice, let's say, or in rats. And there you can get into single neurons and find out how all these neurons are working. But a mouse or a rat's not going to tell you, Oh yeah, Last week I went to a picnic and they were giving these like Coors lights and I wanted a real beer or something like that. Right? That's not going to be the kind of thing that you can measure in a mouse or rat. So what we want to be able to do is say, Hey, here's what we know or here's what we think is happening in the cells. How does that relate to something that we can scan in a brain in a person? Because we can't get to those cells in a living person, but we can scan a brain that has those cells in it and get what's happening in the hippocampus or what's happening in a little slice of the entorhinal cortex. And so computer models are a really valuable tool to bridge the gap between what's happening in individual cells or even individual cell assemblies and these markers that we can get in the real world. And so.

[00:32:51] Soterios Johnson That's really cool.

[00:32:51] Charan Ranganath Yeah. And so we have a great guy who's going to be joining our team from Stanford, and he's been specializing -- his name is Tyler Bonnen, and he's just won the UC Presidential Fellowship. So I'm really excited about that. And he's trying to bridge the gap between the world of artificial intelligence like these, the models that are used in things like ChatGPT or and Stable Diffusion, all these things that are just getting a lot of attention right now in the press. But taking these models that can really relate to words or pictures that a human can understand and use to communicate and tying them to our models of what neurons are doing when people remember. And so the hope will be is that we can actually get a computer simulation that says, Hey, I'm going to feed it a bunch of words or I'm going to feed it a movie, or I'm going to feed it a story and simulate how that actually gets translated into something that the brain can later on reconstruct as a real memory. And we think if that works, then we can really identify all sorts of other markers that we can use, because once we have a model that takes us from cells to memory in the real world, I mean, you've reverse engineered one of the biggest mysteries of life, right?

[00:34:14] Soterios Johnson Yeah. And, I mean, this work is so important. I mean, it's so it's a it's affecting so many people, as you know, as as human beings live longer. It's just it's affecting so many people nowadays.

[00:34:27] Charan Ranganath It is. It's and it's a growing problem. The costs are staggering. And the projected costs in the future are just enormous. And the projected prevalence of the disorder, I mean, if you talk to anyone over the age of 60, I bet you -- everyone knows someone who's had a memory disorder and probably multiple people, you know, I mean, it's just amazing how many lives it impacts in addition to the people who have the disorders. But they're your mothers, your sisters, your brothers, you know, even in some cases, you know, with early Alzheimer's, it could be your children. You know, it's it's just frightening.

[00:35:06] Soterios Johnson Yeah, I know we're running out of time. So I just wanted to ask you, what drew you to the fields of psychology and neuroscience and cognition? Was there anything, any person in your life or what kind of like, you know, drew you to the fields?

[00:35:19] Charan Ranganath Yeah, I guess I would say that, honestly, what drew me to psychology is we my parents immigrated to this country when I was very, very, very young, like less than one year old. And, you know, I grew up in a neighborhood that was, suffice it to say, not very friendly to people who didn't look like them. And so I was always a little bit of a I mean, I was always quite a bit of an outsider when I was growing up feeling like nobody really understood me or I didn't really understand how other people worked. And so when I discovered psychology, it was fascinating because the way the brain actually works and the way people's minds work is very different than how we think it does work in how we think it should work. And so once they started to get into that, it really drew me in to this idea that maybe we're all a little bit out of it and we all really don't understand the way each other are behaving. And, you know, so that was really, for me, very valuable in thinking about, you know, how I can relate to other people and how I can understand myself better.

[00:36:28] Soterios Johnson That's really interesting. And I mean, the work that you're doing is so great. I'm sure a lot of us are just waiting to find out what you discover in the near future.

[00:36:37] Charan Ranganath Well, thank you. Yeah, I can't wait either. So we just have to get the people and the resources and things will happen. So stay tuned. I hope to be back not too long from now, telling you about -- giving you some feedback about how it's going.

[00:36:53] Soterios Johnson That's great. And thanks so much for coming on to The Backdrop.

[00:36:56] Charan Ranganath Thank you.

[00:36:58] Soterios Johnson Charan Ranganath is a professor of psychology at ºÙºÙÊÓƵ, affiliated with the university's Center for Neuroscience and  Center for Mind and Brain. He's also director of the Dynamic Memory Lab. You can find out more about his work on our website, ucdavis.edu/podcast. If you like this podcast, check out another ºÙºÙÊÓƵ podcast, "Unfold." Season four explores the most cutting edge technologies and treatments that help advance the health of both people and animals. Join Public Radio Veterans and unfold hosts Amy Quinton and Marianne Russ Sharp as they unfold stories about the people and animals affected the most by this research. I'm Soterios Johnson and this is The Backdrop, a ºÙºÙÊÓƵ Podcast Exploring the World of Ideas.