The Dementia Episode

​[00:00:00] Preston: The dumb med student in me and was almost like, why don't just say hemorrhage or bleed out? It's like, yeah, I really, you're like, tell this lady, you're looking a yell, hemorrhage in this room right now. That's, that's probably the only word that they don't want to hear. Welcome back. This is a press and led episode, but Margaret off camera was just giving me permission to do solo episodes. In the future, we'll be covering the whole periodic table and you're res you were resisting my suggestions, which listeners, this is not the first time that I have said to Preston that people love the episode, loved the lithium episode, and I loved the lithium episode. I'm, I'm people you love the lithium episode and I think that you like just I and Margo was bored by the lithium episode. I yeah, I was. She doesn't like talking about hard science, so, so you know what guys may maybe we'll just that do it on her own's not true. That is not true. I don't not like talking [00:01:00] about hard science. Margaret: I just don't like going down divergences that are like. Like, how do I apply this to clinical work? I like hard sciences, like, I like understanding how medicine works, but mind you, in the lithium episode, we didn't even talk about like how to give it in clinic. Yeah. Because you can find anyone to tell you how to give it in clinic, but, but to tie the entire narrative of lithium for how it's made in a star, how you put it in your body. Preston: That's, you need Preston for that. Yes. Well, and people love it to tie that together and people love it. Mm-hmm. And so, well listeners, you should weigh in on why Preston's resisting not steering a ship by himself sometimes. Yeah. Alright, we'll, we'll, we'll see my maiden voyage maybe soon. Um, and, and lest we forget, we actually do have something to talk about today. Um, the episode is gonna be on dementia, which I, I think is, uh, pretty timely and there will be a lot of clinical relevance here. But don't worry, Margaret will be talking about [00:02:00] plenty of basic science. They may not be readily applicable. I just feel like it's sexist when you're like, you don't like basic science. Margaret: Like I feel like you're like, and that's why it pisses me off. Well, I, I just think that, that there's, there is a virtue in liking curiosity for curiosity's sake and not needing it to have some utility in the clinic. Mm-hmm. You know, so I think that's, that's where I push back. I'm like, just, just enjoy learning about how the world works for a little bit. I'm not, I I, I'll let this rest. I'm not gonna argue with, I'm not gonna say what I wanna say, what we say in the ACT episode. We'll drop the rope. Yeah, the rope has dropped. Okay. So we're not gonna do an icebreaker today, but, but because there is a lot that I wanted to cover, but we're just gonna kind of start out with what the definition of dementia is and how we assess cognitive impairment. Preston: Because I think a lot of these, uh, terms kind of exist in the mainstream. People will say like, oh, I have Alzheimer's disease, Alzheimer's, dementia, [00:03:00] frontotemporal dementia. And like, what do those things mean? And are they all the same? So Margaret, how would you define dementia? Um, a stable and possibly worsening loss of different forms of memory that is persistently present and there's no acute, uh, metabolic or other, uh, endocrine body system things going on to make us worried about delirium or a vitamin deficiency. Yeah. So you, you're pointing out that it's, it's has to be something that stands on its own. It's not like related to some other medical illness, which, which is important. And then the other thing that is it's stable or that it's chronic. So chronic and progressive is usually the words we use in chronic meaning, like happen over a long period of time. Um, the one thing you, you pointed out is memory, and it can be related to memory, but [00:04:00] ultimately the definition of dementia is related to function. So I can have deficits in my memory, but not necessarily impairment, my functions, but the ways in which we kind of measure our function are with a couple things called ADLs or I ADLs. Those are like our activities of daily living. Can you think of like any of those? I'm sure, I'm sure you probably talk about these maybe with the children you see sometimes. Yeah. I mean, it's happened, so I've only been six months that I've been away from adults. Uh, I, I still remember, uh, ADLs. I, I feel like, I think I always mess up the ADLs versus IDLs, but I feel like ADLs are the more basic ones of like showering, feeding yourself, doing like more. Margaret: Kind of simpler tasks. And then IDLs are things like paying your bills, like they're slightly more complex parts of like managing life. Mm-hmm. But that could be entirely flipped, so that's totally wrong. No, no, that that's absolutely right. Um, the way I think about it is ADLs, activities of daily living are stuff that like a teenager should be able to do, just survive inside of a house. Preston: Mm-hmm. And the instrumental, [00:05:00] um, activities of daily living are the things that you need to do to make the house function. Mm. So an A DL could be, can you go to the fridge and grab a, a meal and eat it? An IADL would be, can you go grocery shopping and like meal prep and cook a meal? Or can you make sure that you're, like, like you said, your, your bills are paid. Can you, Dr, can you like coordinate where to drive to the store to go execute your job and then come back? Like, those are instrumental activities of daily living. So you need to have some sort of loss of function there, because at the core of it, dementia is a disability. So you need to have loss of ability. So. That loss of ability can be due to memory, but it can be due to a lot of things. So kinda going back to the definition of dementia, it's, it's has to be acquired is one that we didn't mention earlier. But you can't be born with this condition. It has to come on at some point in your life. So it's a, an acquired chronic progressive cognitive impairment leading to [00:06:00] disability and the cognitive impairment. So it has to be of a cognitive nature. It can't be like, like for example, like a LS, um, or like Louw Gehrig's disease. That's not a dementia. Like even though it leads to disability and the inability to complete your ADLs, it's due to muscle degeneration. It's not due to like loss of your cognition. Right. Margaret: Right. Okay. Yeah. So when we think about Alzheimer's disease and Alzheimer's dementia, those are actually two different labels that we're giving for it. Even though, like we say, a lot of those things synonymously. Alzheimer's disease is like the way in which the protein can accumulate over time and Alzheimer's dementia is when it kind of crosses that line to like leading to a disability. Preston: Um, and then for the rest of the episode, I think we're gonna kind of go in and talk about like what are these different types of dementias or what, what are the big three that we were gonna discuss the most? And then how do we actually work these up? What do they look like in the clinic [00:07:00] and how do we approach treating them? Mm-hmm. And then for those of you who are tuned in on Patreon, we're gonna do a couple like practice question clinical vignettes and discuss those. So we are gonna take a quick break and when we come back we will start with Alzheimer's and we are back to discuss the. The titan of all dementia is Alzheimer's dementia, or Alzheimer's disease is how they call it. Neuro clinic. Yeah. We're like, we got another Titan case coming up. Oh. Um, is, it's interesting. So if, if you were to kinda like look at the breakdown of, of the different, like, types of diseases or dementias, how common would you say Alzheimer's is? If, if someone has dementia, what is the likelihood that it's Alzheimer's? Um, 20%. I, that's pulling that outta my head. Yeah. It's much higher actually. It's 60%. Oh wow. 60 to 70% of all dementias are Alzheimer's related. So it's, it's number one by far and away. And then the other [00:08:00] two of the big three that I'm gonna talk about are gonna be, um, Lewy body dementia. Then frontal temporal dementia not mentioned is vascular dementia, which is actually the second highest, but it's a little bit of a different process. Like it still falls under a definition of dementia. It's a acquired chronic progressive neurodegenerative disorder, at least a disability to cognitive impairment. But. It's just through such a different mechanism. It's really just kind of like breakdown of the blood vessels, like delivering nutrients and oxygen to your, your, like meat computer at a function. So it, it kinda follows a different pattern as unique to each person. So we're, we're just kind of gonna acknowledge, gives space for vascular dementia. Yes, it exists. And then we're gonna kinda go back to talking about all these misfolded proteins and everything else that goes wrong, so, got it. So very common type, but like different and maybe harder to localize sometimes not harder for the neurologist to localize, but like, maybe not as clustered as you would think about the other, like dementias [00:09:00] because it can, I mean, I know it's like more common in small vascular areas, but like, like why are you pulling out vascular? Margaret: I'm not supposed to ask you this. Why, why are you pulling out vascular? No, it's, it's, it's great question. It's, it's because vascular is kinda like a Yes and with all the dementias, so. A lot of people once they go past 80 are gonna probably have some amount of like vascular impairment, not, maybe not to the point of having like isolated vascular dementia, but like there are gonna be some like chronic microvascular changes that are gonna be affecting all the other types of dementia. Preston: The other thing that I think is like less exciting about handling vascular dementia is that a lot of, where's that curiosity you love? Yeah. I guess, I guess it just doesn't exist for this one. A a lot of it is for, um, it's just watching it, it's monitoring. Mm-hmm. The, the main thing you do is manage risk factors and everything that you could do to like prevent this dementia from happening is like everything that you, like your cardiologist was telling you to do for like the 40 years leading up to it and [00:10:00] dealing with blood pressure, not smoking, adjusting like your diet, like those are, it's just kind of, I don't know. It, it ends up being more like an extension of like the other many metabolic chronic diseases that we see. Yeah. Whereas. These other kind of protein is folded. Dementias are unique, they're genetic, and then they, we know less about them, but also the, like, treatments are a lot more dynamic. Got it. So that's kind of why it's like the, it's the only one that's not, it's like on superimposed on any of the other dementias. And it's not like primarily like a protein mis folding. Dementia's a bad saying. You were doing like a tear list of like Preston's dementias and it's like bottom tier, like S I'm like vasculars, F Tier, yeah. TDD 43, like CTE, those, those are like S tiers. Ts B tier, and then yeah, vascular's ft. Just boring. I mean, I'm sure it's plenty guys got its own excitement, but [00:11:00] it's just, okay. Anyways, um, Alzheimer's was discovered in 1906 by AIS Alzheimer. He didn't try to name it himself, but he had this patient, 51-year-old female who was kinda struggling with chronic memory deficits and then, uh, eventually died. He did a brain biopsy and saw these kind of weird plaques everywhere, and I was like, huh, this is strange. And because it's 1906 and he's the first person to describe these strange plaques in someone's brain, they're like, yeah, it's Alzheimer's. Um, but, but functionally it hasn't really changed much, much in the last, like 120 years or so in how we like actually diagnose it with the gross neuropathology. And we still see those like beta amyloid sheets, which is kind of where I wanna start with it. So, um, this is gonna be like a common theme through this episode is starting with the protein that starts, that goes wrong, and then seeing how it manifests like throughout the story of the, the disease. So the most common protein we see building up is [00:12:00] beta amyloid. And if we kind of recall what amyloid is, um, how do you define it? Margaret: Other than like neurofibrillary tangles or something. I don't know. That's not right. Yeah. Amyloids a clumped up protein, like, that's it. That's not helpful. Yeah. It's a, it's a really kinda like nondescript definition, but the beta part can be helpful. It refers to beta sheets. So if you take yourself back to biochemistry, if, if any of you listeners ever did something like this, you remember like the primary, secondary, tertiary structures of proteins. Preston: So there's like the alpha helixes and the beta sheets, those are the secondary structures. So basically when, when you get this like peptide, peptide strung out, you kinda layer it back on itself. Like a little, like, it reminds me of like lasagna. You can imagine like a little hardened lasagna, um, like strip or something, and you just stack those on top of each other. That's kind of how a beta sheet works. They're really stable, but also means they're hard to break apart. [00:13:00] Mm-hmm. So those lasagna, like proteins build up over time and start to stick to certain parts of your brain. They start to impair function. So the, the original thought is like the, the, the protein that contributes to amylin beta has a lot of different functions. It helps with neuroplasticity, it helps with cholinergic firing, it helps with, um, like translocation in the soma. So it was hard for me to kind of pin down what exactly the protein does, but we know that it accumulates over time in the, um, medial hippocampal area, which For everyone, or just for people who will have the illness or for certain people. So most commonly it, it can honestly kind of accumulate anywhere though, because there's, for what population? I mean like is it only people have that who are going to or have Alzheimer's? Or is it like common throughout the general population and a certain amount is people who actually end up with the disease. Yeah, [00:14:00] so great point. So a lot of people can end up with amyloid beta that's mis misfolded and builds up with plaques in their brain, but it has to accumulate enough to start causing impairment for you to actually develop like Alzheimer's disease or dementia. So like if you were to just like look at everyone's brain over the age of 70, you'd probably find amyloid in a decent amount, um, like just amyloid buildup somewhere. But not all of them are gonna have a dementia. It's gonna be in the patients that are like, kind of almost like starting down this track of, of developing like a progressive dementia that you see it building up in the hippocampus area, which is like the most common place for it to build up. It can start in other regions, but it's much more rare. So you can have like a parietal lobe, um, atrophy that starts, or like a posterior cortical Alzheimer's. Those are also possible, but the most common is like in the medial temporal lobes. So what you see first among everything is loss of short-term memory. That's gonna be like the most common thing that starts to go and it's [00:15:00] really slow. Margaret: So what's like something that someone would say, like what are examples of the kind of things you would have like a person come in with their like partner and or like their spouse being like, they don't seem themselves, is this normal memory loss or is this like, what is that short term impairment of memory look or short term memory impairment look like? Preston: Yeah, it's, it's, so, it can be hard to differentiate and there's, you see people come in at different stages of life and different, like steps along the disease. But the most common one I see early on is like trouble with episodic memory or memory, like details from events. So people will say, you know, I, I used to be really functional as my, at my job as a lawyer. I'm this, I'm this independent, high functioning person. And then I started just forgetting details of cases. I couldn't remember small things I needed to email. I couldn't remember what happened on x, y, and Z day. Like, I'll remember that I [00:16:00] went to a wedding the day before, but like I couldn't really tell you like what was on the cake or like what was around the meal, what the forks looked like, like those, those immediate like little sections of these events that they kind of start to disintegrate, it's harder for to hold onto them because it's like, becomes more challenging to register memories. 'cause that part of their brain that actively registers those memories is decaying. But everything else will stay the same. Their, their temperament is the same. Their sleep schedule usually isn't changed. They may have like more anxiety or frustration because of these memory changes, but like nothing else is really like affecting them. They don't, they're not gonna have any motor changes and this is like, might be all that happens for years. So it'll. And it's tough because when it starts out it could just be kind of non-specific. Like yeah, you know, I'm just like not as sharp as I used to. Like who's gonna really care if you like, didn't remember all the details of what's going on at the event. You went to the bridal shower you went to last week. If [00:17:00] you're retired now and there's an entire company that's like dependent on you to do things. So while people may still be able to execute their IDLs, they may not have like as many demands on their executive function as they did before when they were working in their life. So it can kind of go unnoticed for a long time. Yeah, it reminds me of like, there's like a saying that I feel like the Jerry people will always say, not always, but. Kind of like social functioning intact. And this is at a point where the memory loss is worse, but just like what people are able to maintain and like the level of challenge in their environment will be the thing that like determines sometimes how quickly, like something is noticed as wrong as you're saying is like presenting to clinic. Well it is really true. Like the, the people that self resent that I see like later in life are people who have really demanding jobs. And that if, if they even start to slip up just a little bit or develop like what we'd normally consider like mild cognitive impairment that could progress to dementia later, they're gonna be like, I'm noticing these deficits and monitor, self [00:18:00] monitor and then correct and go seek out care. Whereas someone who, there are people that without dementia, they Uber eats everything, they just kind of watch TV all day. Like there there's not a lot that if they aren't remembering the TV shows that they're watching as much, that there's gonna be like a noticeable change by other people. You know, like, so for those patients they may. Take another 2, 3, 4, like even five years before a spouse really starts to notice like, Hey, I have to repeat things like five or six times to them. And this, I've noticed this as a departure from their baseline, but we kinda like quickly find that it, it issues probably start out earlier. Mm-hmm. So it really just, it depends on how demanding people's lives are for how quickly it comes out. But it's, it's really common that like, it's just, just that like isolated memory issue. And so if you do like a moca with these patients, um, and MOCA is the Montreal Cognitive Assessment, which kind of takes into account the different, um, neurocognitive [00:19:00] domain. So visual spatial function, language, executive function, you know, like fluency, repetition, um, um, memory registration recall. They will do. The classic one I'll see is almost like a, it's a 25 out of 30 and like the only five points they'll miss will be the five words that they had to remember after five minutes. But everything else looks pretty good. That's like when I see that, I'm like, this is just like, you, like feel in your bones. Like this is gonna be like gonna turn into an Alzheimer's type picture. It's, it's just like that isolated for the memory loss versus like, I guess you'll probably be about to talk about this versus like, what, like you say, it's going to be this from this type of memory being impacted specifically. You don't just think dementia and gen, you don't, your differential narrows just from that. Yeah. My differential, well like, 'cause that person, I'm not neuro, but like yeah. That person who gets a 25 outta 30, they, they may not qualify for dementia yet. They may just have mild cognitive impairment, but my differential starts to narrow for Alzheimer's [00:20:00] specifically. Um, one thing that can be helpful to differentiate that though is looking at. Um, if they can be helped by hints or not, because one thing that really affects this is things like depression or anxiety can affect your memory. And, and actually there's one cause of dementia that I didn't mention earlier, uh, which is pseudo dementia. And that's the only reversible type of dementia we have, which is often caused by a depressive syndrome. Margaret: Mm-hmm. And, and I think this is something we've discussed earlier, um, but to kind of rehash it, if, let's say I, I give you five words, um, leg cotton school, tomato, white, those are the classic ones you'll see on the mocha. And I try to ask you to repeat the words later. And, you know, after five minutes you're like, I got nothing, like zero of them. Preston: Or maybe you remember cotton, but nothing else. If I say one of the words I gave you was a color [00:21:00] and then you immediately say, oh, it was white itm giving you a semantic clue. So I'm telling you, hey. It's within the category of colors. Does that prompting help you go into your memory? And memory Bank can retrieve that, so that helps us differentiate if, is this a consolidation issue? Like is the memory getting stored in a file somewhere or is it a retrieval issue? Is the memory there? But it's just hard for you to pull it out. The other thing you can do to prompt is you could be like, one of them starts with an L, like a Louw sound and you're like, oh, leg could be like another example. If they are able, how does your differential change if they are able to retrieve it versus the one that's not able to, like, do you think more about anxiety or depression? Like mm-hmm. Like exactly. I, I know obviously you're testing everything, not listeners, not nothing ever happens from just the moca, but like in your mind, kind of if we're thinking as good clinicians should of like sharpening the differential with every [00:22:00] piece of data we get. Margaret: Is it the, in a, the ability to retrieve it would lower your. Like, like concern compared for, for like Alzheimer's. Mm-hmm. Yeah. The ability to retrieve it is reassuring because, um, if you think about how you're storing the memory, it's, it's gonna be like consolidated in a neuron in the cortex, and then when you're getting information, you have to kind of travel through your white matter track and then pull it out of the cortex being like the file cabinet. Preston: So if the cortex is degenerating, it's like, think about the file cabinets falling apart. So you went to store the file in the file cabinet and it's just, it's just a giant hole and you just threw it into nothing. But maybe if you're depressed, the, the drawer, the drawers on the file cabinet are a bit rusty and it's harder to open them and you need some assistance opening them, but the whole structure is still intact. So depressed patients maybe will have more issues with retrieval, but they should respond to multiple choice [00:23:00] or semantic queuing. And like, if, if they can, like let's say you got. Three out of five, or remember two out of five. But the other three you recognize quickly or picked up with multiple choice cues, those are all like reassuring. Margaret: Mm. Versus someone who like, there's nothing in the drawer. Yeah, no, seriously. So, so what I could do after that is like, you know, leg school, tomato, white, were the words, um, I could say, okay, between red, white, and blue, which color was it? And you're like, I think it was red. And I'm like, it was white. And you're like, I don't even remember you saying that to me. Preston: Yeah. Like there was, there was like literally nothing to reve. Yeah, yeah. And so, so like that feeling of like, oh, darn it, I did know that, but it was just like harder for it to come back. Those are reassuring signs. And that's why it's actually kind of, we won't get this information from the moca otherwise, like let's say you don't get points for like the multiple choice queuing on the moca anyways. So [00:24:00] two people, someone with like depression or pseudo dementia and someone with like that kind of. Pro dermal Alzheimer's picture, they may score the same. So that's kind of why I do that. They may both get like a 26 outta 30. So that's kind of why I'll do that, like follow up to say like, okay, is this like more of like a white matter track retrieval problem or is this like a true consolidation problem? Got it. And then usually like, we'll go over that again and then my attending will always like ask me like, so then we'll take like 20 minutes of go staff, my attending will ask me the questions again. And then when she comes back in to see the patient, she may ask them like, one more time, like, Hey, you know, do you even have a, like a learning curve with this? So if you're prompted, reintroduce the information and prompted again, can they, can they come back? So, um, the, it's just kind of, we're giving the person's basically hippocampus multiple times to see like how well can it retrieve, like throughout the visit, because we're like zeroing in on like, what type of memory deficit is this? So if someone comes in and we [00:25:00] suspect Alzheimer's is like a couple kind of next steps that you can do. Then they have this kind of like display of like memory loss and, and the first one is you can do something called an AVID PET scan and that's where you literally just look for the amyloid protein. But ultimately it's, it's not amazingly helpful if it's positive because like you said, like a lot of people can just have amyloid anyways. The only way it, it really is like super helpful clinically is if it's negative because it's like, okay, this like can't be Alzheimer's. You can't have all Alzheimer's without amyloid. You like it's, as far as we understand it right now, it's just, it's defining for the illness and how much more, this is maybe not a fair thing to ask you off the top of your head, but like how much more sensitive is like imaging in this case for accurately picking up, I guess sensitivity and specificity accurately picking up a case that the [00:26:00] clinical exam. Margaret: Would have or picking up or like denying it? Like how do you know the difference in those two? Because I think that's, I can comment on the difference. Yeah. I'll say like it, like it is not that specific, but it's very sensitive, so Okay. It, it can be helpful that if, if there's a suspicion that this could be Alzheimer's based on like the moca on our assessment, like the, the kind of memory testing that we're doing, then it can help rule it out if that's up to question. Preston: So I'd say how common is it for people to not have any Yeah, that's a, that's a great question. So this is, I feel like that's like, one of the things that's like a blank spot in my mind is like, is this actually better or is, and I mean, granted, it's like who is the clinician like doing the assessment, right? Margaret: Like you're mm-hmm. Neuropsych attending who did a fellowship, did whatever, like their ability to catch things and use imaging well to support what they're mm-hmm. Like well informed clinical judgment is, is one thing. [00:27:00] And so. Yeah, that's why I'm just curious of like, if it's positive, it doesn't necessarily say, yes, this is definitely what it's going to be. So then it would depend on how often it's negative outside of like beyond the clinical judgment in terms of adding to healthcare costs and usefulness. Mm-hmm. So, um, this is me on the fly right now. Just, I'm just using open evidence to look this up. Yeah. That, so like a negative amyloid pet or an amyvid, um, is about 92 to 96% sensitive. Preston: So that's, that's actually pretty helpful. Um, and I couldn't tell you like how frequent it is in, in patients that don't have Alzheimer's pathology, but it, it'd be, it's very common for, um, people to not have these avid pets if they don't have any Alzheimer's pathology. I think I, I'm kind of like maybe over emphasizing the. Like non specific specificity of it in older individuals. But if you were to look at like, [00:28:00] kind of any like healthy, younger population, a hundred percent of them would ha would be amyloid negative. Oh, okay. And then even in patients with, um, a memory clinic, there's, look at this cohort, 34% of the patients in the memory clinic had negative amyloid pets. Wow. So it, it can be helpful for like that differentiation. That makes sense. And then it's not just kind of like our own self insistent pedantics that ends up like not contributing to the differentiation is the point of differentiation. Point of standard of care. Now I'm not sure what I would like to define as like the standard of care for like, the workup of Alzheimer's. I think I'm just like hesitant to say Absolutely. Gotcha. Um, one way or the other. So I think does something, does everyone in the clinic like get one? Uh, essentially, yeah. Hmm. I, I think it's, it's weird. Like, I, I dunno if you, if you come across this too, maybe I'm being like, um, a bit too cavalier here, but I feel like. When I think about like what standard of care is a lot of, it's kinda like monkey see, monkey do in medicine and then you're like, wait, wait a second. We've been kind of doing all these things like I need to like consult the gods or like the, the [00:29:00] sacred texts to be like, what are we like considering like the consensus standard of care. Margaret: I mean, I think of like, my best friends in training are the like clinical recommendation guidelines that usually the societies have put out and they tell you like what year it's updated. And so I guess I mean like that, um, like if, what level of evidence it has been recommended for by the like neurology or like memory academy type of bodies. Um, so that's what I mean when I say standard of care. And I know, I know that like dementia and Alzheimer's in specifically has changed like it's a rapidly. Evolving field in terms of like advances and like when people should get treatment and things like that. So maybe there isn't anything, and I work with kids now, so I dunno. Mm-hmm. So I may be asking you pedantic questions is also the problem, and I apologize if I am. Yeah. So I, I just like on a brief [00:30:00] search, like amyloid PET is not like the standard di like standard of care for like, diagnosis of Alzheimer's. I mean, like ultimately the best way and the only definitive way you can diagnose like any of these diseases is via autopsy, which is just not helpful in a lot of these cases. Preston: So, so much of it is kind of empirical, but giving people like more answers and reassurance if the resources are available. Yeah. I mean, I'm gonna like push back a little bit on you there. Not, like, I don't, I don't think doing more, I think this falls into this category, right, that we're stuck in, but like at a like larger level in healthcare that like, it's. Margaret: It can be comforting, I think, for clinicians and for patients to have like more imaging and more answers. But does it actually improve outcomes or improve care? And like if an imaging like it, I think of like mild to moderate lower back pain for the first three to six months in a [00:31:00] relatively healthy adult with no other signs of anything. We used to say like, oh, they should get an MRI or they should get this. And now like the governing bodies of like chronic pain and back pain. Like, do not recommend that imaging because it doesn't actually improve clinical outcomes. And so that's part of, I guess why I'm just pushing this. 'cause I think there's a lot of talk right now culturally of like, we should always order everything we can and I don't, you know, like if it's not helping clinical outcome, so you're saying, well why order an amyvid if it's not gonna help with the outcome at all? We, uh, yeah. And it, and it probably does. Let's, like, I'm not a Jerry person so I don't know, but like. That's, well, no, I think that like a lot of people do disagree with that and a lot of people think that it, ultimately, what I'm gonna do for this person anyways is probably start donepezil, which is uh, like a acetylcholine aase inhibitor inhibitor. Preston: So like it promotes acetylcholine in the brain. So honestly, based on the, a lot of their clinical assessments, whether [00:32:00] or not they got the amyvid, they're probably gonna start to neol the person on the patient, which is like ultimately like the best thing that you can do for them. There are no reversible definitive treatments for Alzheimer's. So there, I, I guess the way I would put it with things like the amyvid is that it, I don't think it's analogous to this kind of the back pain imaging in that it's doesn't actually like help change any outcomes. I think it can help with diagnostic clarification, but the problem is the treatments that we have right now are so limited that being more granular about the diagnosis. At this point in time doesn't always necessarily change the treatment that much. That being said, as more treatments come out like us practicing, defining and being very specific about how to differentiate these diagnoses may pan out into being able to give outcome changing or very definitive treatments in the future. So, you know, maybe in 10 [00:33:00] years when we do have like a more definitive, um, like treatment for Alzheimer's that maybe is revers reversible now, like the fact that we're able to like have this infrastructure to use an amyvid pet and like actually can like rule out who's gonna get it and who's gonna not get it. Margaret: Yeah, yeah. That's really helpful. And that, that's actually one the biggest reason why we use the OV it is to see if you'll qualify for this medication called Kinumab. Is that the new, that's like the new guy on the scene, right? Yeah, yeah. He's, so, he is the, the new guy in town only came out in the last couple years. Preston: And so what this medication does is it, it literally binds to those amyloid beta plaques and then. Like removes them. So it, it's an antibody that binds to the plaques and then the macrophages come by, see the antibodies, tag them, and they're like, oh, you know, I'm gonna, I'm just gonna like, eat these plaques. So there's no point in giving someone kinumab if they don't have amyloid in their brain. Mm. Okay. So if you wanna see if someone's like a good candidate for like, getting kinumab in the future, like that's what like the amyvid would be useful for. So, [00:34:00] I'm sorry for not like mentioning that earlier, but I thought that's, that's actually one pathway where like you would see that going forward, where otherwise you're like, okay, we'll just do drazil anyways. Got it. And this isn't gonna change it. The the problem though is that like, as we thought that like Kinumab came on the scene and was gonna like change everything because we're like, oh, like we managed to knock out this protein that causes Alzheimer's. So like we're It's cured. Right? Wrong actually. Like we, it's not funny. Margaret: I'm sorry, listeners. I'm sorry. No, no. It's so underwhelming. Um. If you, if you're already in like the moderate to severe stage of Alzheimer's, like, it's not even like helpful to start kinumab because you have to be like really early in the prodrome or in the mild cognitive stage, identify you have Alzheimer's disease and then you have amyloid plaques that are positive on your Avid, then you can do kinumab and it might give you a certain amount of like extra like function per year or might slow down the progression of the [00:35:00] disease by like 20% per year or something. Preston: I dunno the exact numbers on this, but over time, you know, let's say if you get an extra 10% per year, uh, you may, after 10 years, it may turn into 11 years. So you, you can buy someone almost like another year with their loved ones to do these, these infusions frequently. So for a lot of people it can be worth it to do that. Yeah. The problem with Kinumab is it has, its its own issues and side effects. So it can cause brain swelling and brain bleeding. And because the politics around this, they actually don't like call it that. They call it aria. Which is am, this is pretty funny, is amyloid related imaging abnormalities. R-A-R-I-A and there's A-R-I-A-E, so for edema and A-R-I-A-H for hemorrhage. So are the abnormalities without the E or the H? Just like they's there, but it okay. It's just heh, it's just brain bleeding. Oh. But it's like, we're didn't call it aria h, you know, because [00:36:00] that's like a little bit, it's a little, it's a little bit more, um, socially acceptable, you know, it's, it's not gonna like, cause as much of a fuss to be like, oh yeah. Brain hemorrhage. It's like, you know, you have a case of aria. It's, yeah. That's really gonna scare people also, when you tell 'em, like, so this brain illness you have, we may make you bleed, like, like in, um, labor and delivery. Mm-hmm. I remember like the ob GYNs would say like, oh, the, the, the mother's gonna exsanguinate if this happens. Or like, there's a risk of ex exsanguination. I was like, like the dumb med student in me and was almost like, why don't just say hemorrhage or bleed out? It's like, yeah, I really, you're like, tell this lady you're looking yell hemorrhage in this room right now. That's, that's probably the only word that they don't wanna hear. Margaret: I like, but please do not, can we get the male med student out here? Why don't you just say she's bleeding out. So like, like, and to be fair, like words do matter. So, so it can be helpful to say like, yes, there, there is this kind of like, um, [00:37:00] small, but they're like risk of, of bleeding that we need to monitor. Preston: And then, and it's, and honestly if there's any like sniff of aria, then immediately people stop the medication. Um, we need to, to kind of seek treatment. So like, it's pretty common that like, um, a lot of, like the attendings I'm within clinic will just kind of get these potential aria cases to like review continuously. Um. But I, I actually, um, couldn't speak to like the incidents of Aria with Kinumab. I'm not sure. But essentially that, that's kinda like where we're at. Mm-hmm. The interesting conclusion though is that if Kinumab is so good at taking out the amyloid plaques, which it is, when we do like follow up scans with it, we find that it removes almost like 99% of the plaques. So, so it did its job in taking away the plaques, but the disease continues to progress despite that. So that's actually like what's kind of challenging our like, primary hypothesis around Alzheimer's. [00:38:00] We thought that it was all due to this plaque building up over time, but we remove the plaque and it's still happening. So now there's like just more questions and answers, I think. And we don't know like really what the primary driver is. Um, I think there's some thought that amyloid may play a role, but it's more like a bystander or a byproduct of like what's actually happening. That it's essentially just kind of like dunk or rust that's building up, but it's, it's not the core culprit. Margaret: So it's like kind of, it's the like possibly a correlation versus causation mistake. Like when people are like healthy, like breakfast makes you lose weight. If you eat breakfast, you'll be healthier and have less heart disease. And it's like people who eat regular breakfast have more routine and other health behaviors. And so that was, it wasn't the breakfast. And so in this situation, the amyloid might be the breakfast. Yeah. Yeah, exactly. I, I guess the way I think about it is like, [00:39:00] let's say you're trying to stop trees from being chopped down or something, and you notice that there's like a ton of wood chips around all the trees that have been chopped down. Preston: And like the core issue is that like there's a lumberjack going out there and chopping down the trees, but you don't know how to find the lumberjack. So you just think like, Hey, let's just make these really interesting ways to pick up the wood chips. That are left behind by the lumberjack after he is like chopping everything up. And like, we have nothing to stop the wood chipper that he's using, but we're like cleaning up after it, you know, it's like, ah, you know, I go by here and this whole place is cut down. There's always one chip server. Huh. And look, we spent billions of dollars developing truck to remove wood chips and like, maybe the forest grows back a little bit better because there's not like a layer of wood chips on top of it. Mm. But overall, it doesn't, like they're still going buck wild deforesting. And we're, we're not like getting to the core of this. Huh. That's interesting. And a little depressing. Uh, yeah. Yeah. It is. Um, the, [00:40:00] the only like real ways that we can determine someone's risk factors. I, I mean, among other things are like a P OE testing, right? So we all have different variants of the a P OE gene. Um, but like a P oe, um, four is the one that's most associated with Alzheimer's. Then what do you do with it if you like? I guess you maybe get this medicine earlier, which sounds like it still can be meaningful, but is there, or maybe it motivates people to like do other, like brain health promoting things that mm-hmm. Margaret: But I feel like I've seen like a lot of health podcasts that are kind of like, optimize your health, be like, people should be tested for this. And if it's like you have super early onset, like family condition, like certainly getting genetic testing and things make sense. I think the ways in which it makes the most sense is like family planning. Mm. Yeah. End of life planning, like philosophically what you wanna do with the rest of your life. It doesn't, like if you don't have dimension now and you have, like, if you're homozygous [00:41:00] for the high-risk, a OE variant, that also doesn't guarantee that you're gonna get Alzheimer's. So it's not helpful to start donepezil now. Preston: Like you just, it, it's, it's like kinda like, what do I do with that information? So actually when we do genetic testing. Clinic, we'll often have people meet with Julia, who was the genetics counselor here earlier, and we're back. That's where she would say, like, I do more counseling than genetics at that point. Yeah. Because a lot more of it is having a conversation with someone about like, what benefit do they even get from this information? How will like modify their life in a positive way? And a lot of people ultimately choose that. They don't wanna know. I mean, that's fair. It's kind of like that question of like mm-hmm would you wanna know when you're gonna start to get sick or when really bad things might happen to you in your life? Margaret: Like, do you want to know that in advance so that you know how much time you have? And I think if I remember from that episode you said, yes, you would like that information yourself. Uh, and I think I said no, but [00:42:00] so is that, but it's that kind of question. Mm-hmm. Yeah. So, and that's, that's ultimately a very personal question. Preston: But it could be helpful to say like, okay, if, you know, if I have these a OE variants, like what likelihood, likelihood that my kid's gonna have it and how do, how do we like approach it from there? So that, that's kind of all I really had for Alzheimer's right now. I know like we could spend entire podcast episodes. We've already spent almost like 40 minutes talking about, um, this one already. And, and it goes be, be way beyond my un understanding, um, if you get into the translational science. So I, that's why I find it interesting. I'm doing a fellowship in these types of disorders. Um, but that's kinda like kind of the cursory, like look at it right now. So moving on to the next, um, kind of big hitter of the big three, we're gonna talk about Lewy body dementia. So [00:43:00] that one is related to the protein alphas and nucleon, which. Is normally, um, helpful for kind of basically neurotransmitters firing or moving across, um, neuronal cell membranes. That one's a little bit more specific for neuron movement. And so it's the same, same situation. There's like a misfolding of the protein causes, like neuronal mis firing, and then you start to see symptoms develop in a chronic progressive way. So one thing that's interesting about Lewy body dementia or like basically alpha-synuclein issues is that they have a much earlier prodrome. So there's pathologically not really a difference between Lewy body dementia and Parkinson's. It's the same protein that's misfolding and going awry. It just happens to be where it's located in the, in the brain where it's depositing. Hmm. And so where are the two positing? So like Parkinson's is more likely gonna be in the, like in the brainstem.[00:44:00] So in like the ventral mentum where you house a lot of your dopaminergic neurons, it is gonna start to wear those down, which is gonna cause like those motor symptoms and dysfunction in like the basal ganglia where Lew body dementia can have like, more diffuse deposition of these like alphas and nucle entangles or Lewy bodies. Margaret: Got it. We'll, okay, we'll try to put a picture of it, like what a Lewy body is over the camera. So if you're watching on video, Jason. Yeah. Yeah. But it, it's super interesting. So these, like, Lewy bodies can kind of deposit anywhere in your, um, body that has nerves because it, they just kind of go along your, your nerve endings. Preston: Um, and so if you remember like a lot of part of your like skin cells come from like the neural ectoderm. Mm-hmm. And that can actually, like one of the early ways in which we diagnose it. So kind of taking, taking a step back, there's. The early prodrome that I was mentioning is something called REM behavioral disorder.[00:45:00] Is that something that, that you've seen or heard of? Yeah. Oh, it runs in my family, yeah. Oh, awesome. Yeah. Yes. Yeah, I'm aware of it. So for, for those who aren't familiar or kind of listening, um, REM is like rapid eye movement, so that that's the portion of sleep when you're kind of paralyzed, but your brain is really active and you're, and you're experiencing dreams most commonly. You can experience dreams in other sleep stages, but we won't get into kind of those details right now. The the point is like your brain is very active and you, your body wanna, wants to act out on its dreams, but it kind of paralyzes your entire body while that happens. So as certain of certain neuro circuits start to break down, that paralysis function also starts to break down. So you're, you're not able to shut off the basal the, like basically input to the basal ganglia in the same way you were before. So you actually start to sleepwalk and act out your dreams. So like, I'll, I'll ask people like, do you ever wake up [00:46:00] and it's like, your dream was like happening, or you're already on the edge of the edge of the bed doing something for your dream? And they'll, they, they'll be like, oh yeah, like, how'd you even know to ask that? Or like, the easiest way to be like, to ask a partner if they're like yelling and swinging around in their sleep. I think it's a, it's a little bit more than just like mumbling in your sleep and going in and out. It's like, Hey, you know, like, you know, get outta here. I'm gonna do this. And you're like getting up on the edge of the bed, but like still in your sleep. Those are all like bigger signs of, of REM behavioral disorder. And I don't know the exact data on it off the top of my head, but about a good portion of people that have REM behavioral disorder. Early on in life can go on later to develop Lewy body dementia or Parkinson's 20, 30, 40 years later. So like people with REM behavior disorder in their thirties are at a much higher risk of developing Lewy body dementia at age like 60 or 70. And a lot of these patients you can follow them and like kind of see how [00:47:00] they like convert. Um, so one thing that you can do in patients with brain behavioral disorder, and this is what they're, um, there's a lot of new research coming out on to like how effective this is or, or the sensitive sensitivity and specificity of these like tests are. But you can take a biopsy of someone's skin, it's called the syn one biopsy, and you can look for alpha-synuclein proteins like in their skin. And if that's positive, that that really increases the likelihood of it being lube body dementia. Wow. Or eventually like turning into that because it's kind of hard to have lube body dementia without lube bodies. So. Then kind of going forward, when, when we see, when we see it starting to affect people, um, more thoroughly or having become more diffuse, like progressive of dementia, it's not gonna be like Alzheimer's where it's isolated to like those memory issues. It's, it's gonna spread across more domains. [00:48:00] So, so you're gonna see like some orbital frontal generation, uh, degeneration or like parts of the medial frontal lobes, which commonly manifests as like apathy or lack of interest. Abolition. You can also see a lot of hallucinations and they're more commonly like visual hallucinations. So that can cause from like breakdown the occipital lobe and the parietal lobe. So it's, it's not really like psychosis necessarily. Sometimes it can be psychosis, but sometimes it's really just disruptions of the like occipital or like the visual frontal visual pathways. Margaret: Isn't this a little push in? Hallucinations. Little like Lili lilipu ones, they're like little tiny, cute. Yeah, exactly. They're not, I'm sorry. So, so those, those like little animals that they're seeing in their yard mm-hmm. That's, that's from the Lewy body is basically causing disruptions to how you're, how you're your [00:49:00] eyes, take in information sent to your occipital lobe and send it back to your frontal lobe. Preston: Like that's where the disruption is. It's not because you're having some kind of like hijacking of your meso Olympic system like you would in psychosis. So, and then the other thing that you see a lot more commonly is like motor symptoms. So someone may not, when someone has Parkinson's, the first primary symptoms they have often are like motor related. They'll have like a lot of muscle weakness. They'll start to develop a tremor, they'll have issues swallowing. They have this like kind of shuffling ga and they're hunched over as they're walking. Someone with Lew body dementia, like their cognitive issues may come out first, but they'll still have the motor symptoms after. So that's why kind of when someone's coming in, they're, you're not sure if they're like, uh, like, are they depressed? They're having trouble memorizing stuff because that apathy, like lack of volition, that can also be very common in, in depression. So you can see how a lot of these can start to like run together really fast. Margaret: Yeah. Yeah. If you're, if you're [00:50:00] not like doing a, like a thephysical exam and, and like, like you said, sharpening the diagnosis. So one thing to look out for is, is cogwheeling, which I memorized cogwheeling so much in like med school, but, but it was like so hard for me to, to ever really articulate what it was or what it felt like. Preston: And 'cause, because I would picture like co, co, co like the cogs are like big and they're moving like this, but, but they're, they're tiny. When you actually feel 'em, it's, it's kinda like, so. The easiest way to test for cogwheeling that I, that I do with patients is, um, you tell 'em, you distract them. So you tell 'em with your other hand to like tap. Mm-hmm. Like, I want you with this hand to tap on your leg. And then with the other hand, you passively move their arm around and then you move their wrist around and it's like, you're gonna feel it best in the wrist. It's most sensitive there. Hmm. And it should move passively, but it, it's gonna, it's gonna have these like catches and releases. Margaret: Yeah. [00:51:00] And this is where like, I guess I, I can get better if someone has a resting tremor. It is really hard for me to differentiate that from cog wheeling. Mm-hmm. So like, I'll hold their hand out until they don't have a In your population. No. No. Seriously, it, it's, it's hard because if they hold their hand out and it's not tremulous, then you kind of feel it and you're like, okay, well, like I'm having the catching and releasing while I'm moving their hand around. Preston: But they don't have a tremor when they're like, or an intention tremor when they're holding their hand out and it's like, okay. Like I'm pretty sure this is cogwheeling, but yeah. Just because you have a tremor doesn't mean you don't have cogwheeling either. Right. So you can have both. You can have tremor and cogwheeling and then that's where PGY three Preston has trouble. We're like, I, I don't, I don't know. There maybe you say tune in two years from now. Lemme know. Find out what he has to say. Yeah. And then we, we won't get too much into like the other aspects of the physical exam, but like walking is really helpful. You can see if someone's like turning, like able to turn on their own or if they're turning in block. So, and, and block is like when [00:52:00] you kind, you kind of go slowly around like this instead of going, we being able to, to turn around really easily. So it's actually really common in Lew body dimension that dementia, that we, we would also treat this with donepezil. Really it can help someone with the cognitive function. Margaret: Oh. 'cause I guess 'cause de nil is a colones a colones inhibitor. Mm-hmm. Is it pro. Cholinergic function or anticholinergic? It's pro cholinergic function. Okay, great. Yeah, we're giving back some acetylcholine. Great. Which, which means like the thing you're gonna most expect when you give it is other sides of hyperactive acetylcholine. Preston: So the thing you're gonna worry about most in, in an older population is diarrhea. So you give someone, so these pro cholinergic, they just get the runs and then honestly, that's usually not to say like, it's not worth it. The other thing to worry about is like if they already have a really slow heart rate or have like a heart block or something, [00:53:00] a lot like pro cholinergic medicines are gonna slow the heart even more. That could increase their fall risk. So like heart stuff and diarrhea, that's which, which you gotta look out for the most when for Parkinson's. So like, it surprises me that you say that that versus like going into the dopaminergic. Yeah. So this is for Lewy body dimension necessarily like Parkinson's. So, oh, sorry. Margaret: Duh. Yeah, sorry. Okay, got it. Yeah, so like we would, if it was Parkinson's, we'd absolutely start with like Levodopa Carbidopa. I wouldn't be titrating that from there. Um, but if this is with someone who has like primarily cognitive symptoms, they have rem behavior disorders, they're seeing the small animals, um, in the driveway or in their backyard and they have like a little bit of cogwheeling, but outside of that they're like function. Preston: Their motor function is pretty normal. Mm-hmm. So, so then they wouldn't necessarily need like carbidopa levodopa yet, but you would start to kinda mess with their cognition. But, but, but, but if they have like comorbid depression or like mood symptoms with that serline can be a great option for them. [00:54:00] So serline not only like promotes brain drive neurotropic factor and is like pretty protective, but it also, uh, has a lot of dopaminergic activity. Mm-hmm. So you can get like a little bit of a wind there in, in both giving people some like get up and go and some like volition while also like hopefully returning some of their like dopamine activity. Gotcha. Gotcha. Okay. So. All that being said, if you're treating someone who, who you suspect to have lead body dementia and, and are co comorbid depression, serline is, is like one of the better SSRI options. Gotcha, gotcha. And then the other one that can be helpful with patients that have like mood behaviors or, um, kind of difficulty in the evenings where kinda like that sundowning that we see is mementine. Hmm. So that one's, um, an anti NMDA medication. And this is again, more so with like primarily Lewy body dementia rather than mm-hmm. Combined. It can be helpful with [00:55:00] Alzheimer's too, but that's when we, we use it in most often or that, that I see at least. And then now we, we'll kind of cover really quickly. The last one with, which is frontal temporal dimension. We'll, we'll probably give it the same amount of energy, um, as its incidents. So, so 2% or, we'll, we'll give it, we'll give it 10%. Guys, listeners, we don't you, I'm, I'm fading. It's 8:10 PM in Boston right now, and I teach Pilates at six in the morning, and I at five. So my sleep schedule is like grandma level at this point. So that is, I'm not trying to be rude to you. I'm just, my sleep is bad. Margaret: Oh, no, don't, don't worry, grandma. We're, we're almost done. And, and, and the thing is like, there's not a lot of like treatments that, that we can do for frontal temporal dementia. So it's really just kinda like, how does this happen? And, and it's, it's this protein tau that goes wrong. It's a, it stabilizes microtubules and that's everywhere in the brain. Preston: Mm-hmm. [00:56:00] The, the biggest reason I can't understand why it targets the frontal and temporal lobes when it starts to misfold. And, and we don't know exactly why it misfolds, but it has a lot of like genetic predisposition. So like the map T gene or the CR nine gene can be things that people are born with autosomal dominant. And then like around age 50 or 60, these micro tubial proteins start to misfold. They probably deposit in the frontal temporal lobes because they have such high metabolic activity that they're just like constantly sucking in different proteins that they're using because it's like, you know, whether you like it or not, you should be using your frontal lobe a lot and you should be, you hear that brain rock community, you're always making new memories. You should, your temporal lobes constantly firing. So in frontal temporal dimension, we can see a lot of different like sub variants though, because there's different spots in your frontal lobe where it can like localize more. And that's gonna translate into like the different behavioral variants that you're gonna see and also the different types of, um, dimensions you get for the temporal lobes. So. One that we've talked about earlier in the aphasia [00:57:00] episode was like the frontal temporal dementia with primary progressive aphasia. So the frontal lobe, basically where the proteins end up landing is in the bro area. So it can cause like logopenic aphasia or it lands in the temporal lobe so it can cause like a semantic aphasia, but it's basically like, okay, is it like a verus area issue? Is it frontal lobe issue? Does it like affect my impulsivity in the frontal lobes? And then I start kind of running around and spending a ton of money everywhere I should. It's like everything else about me is the same except like someone just took off the the rationale switch. So you could see how that you could get a misdiagnosis of like, ideally you wouldn't get a misdiagnosis here 'cause it like shows up suddenly and someone's like in their forties and wouldn't have a manic episode for the first time necessarily then. Margaret: But you could see how this could be missed for a while in terms of just like accurate diagnosis. No, and, and it's actually really common that people will, will confuse this for mania. Yeah. So I've had a lot of, not a lot, but I've had several [00:58:00] patients, like on the site consult service that someone is, they're impulsive, they're irritable, they're angry, they're yelling, they're getting in fights with people, they're spending a ton of money. Preston: Um, and they come into the hospital for a lot of those reasons. And then you get head imaging and you're like, oh, I think this person has frontal temporal dementia. Like this is, like this profound deterioration of the frontal temporal lobes. But they might've, this patient might've carried a history of bipolar two disorder and they're like, oh, you know, he was stable on his bipolar medications for like 30 years and now like age 55 or 60 or something. This new, you know, version of it's happening and then you, you have to really dig in with the wife or with the family members and say like, does this even look like a normal manic episode for this, this patient? And like, there's been times where like, no, like his manic episodes are like, they're positive. He has a lot of religious delusions. He always wants to do stuff with the gospel. And then here he's like spending money. He, he, like he would, him and [00:59:00] man and manic state would think that he's sinning right now. Like this is a, he's acting totally different than I would expect him otherwise. Yeah, no, it's, you, you could, it, especially when being seen in the hospital, I feel like oftentimes people who have a psychiatric diagnosis, any mental considerate change or consideration, especially 'cause in the hospital, like, we don't know you in the same way your outpatient people do, or your primary care does that, like, I feel like it can be very easy for anyone with a psych history to just be like, oh, well this is their schizophrenia. Margaret: Like, oh, this is their, mm-hmm. Bipolar. Certainly that can be, it can be a d difficult diagnosis like skill wise too. But also there can be that stigma where it's like, oh, they're acting like this in the ICU because they have schizophrenia. It's like they've been delirious for three days. Like this is not that. Yeah, this is front of, this is not a manic episode. Like, and like, and this has been like building up slowly for a long time. Like it started with them like falling for like phone [01:00:00] scams earlier or being more likely to kind of buy stuff that they wouldn't on Amazon. And now it's like, now it's kind of like snowballed into this other big issue, but it's been like kind of coming and building up other things to like look out for that can help you kind of differentiate those is, um, eating or being hyper oral. Preston: So people with frontotemporal dementia will just like, eat tons of food. That, that same kind of, um, patient scenario that I had on consults. Um, patient got in trouble because they were ordering pizza to the hospital. You've all been there, like kept or kept ordering pizza to the hospital. And so I remember, I remember like, we like going back and forth, the attending, I was like, yeah, and I think this is FTD. And they're like, are they hyper oral? And I was like, let's pull this nursing note right now about patient ordering pizza to the room. Like six Dominoes has been here. I was like, I was so vindicated. Did you feel like house at that point? Yeah. Yeah. [01:01:00] I was like, oh crap code. You each from your white pocket. It's all coming together. You just had one receipt for his pizza order and you said, you tell me Doc, I've got, I've got Papa John's to weigh in on that. He'll, he'll let us know. Dr. Papa John's to you. Yeah. The uh, the other thing that you can see too outside, like the hyper oral stuff is, is loss of disgust. This is, this is a really fascinating symptom to me. So we don't know exactly where you can localize disgust to in the brain. I think it's a little bit more complicated, um, than we could modularize it to be inside. Has this fully Yeah, she was in the board position at the, in the brain. Just controlling. Yeah. Right. Just outside of your core memories. Um, but think somewhere in the anterior insula is where we, where we think about it related. So, so it candid the anterior insula can definitely generate in frontotemporal dementia, but [01:02:00] it, it is fascinating. Like the patients will stop showering and they'll stop cleaning their house and, and they'll be able to function in like all these other areas, right? So like you'll do the mocha and the memory will still be intact. Executive function's like still doing pretty well. It, you know, the, it's still around like 25 out of 26, maybe some issues of like repetition or fluency, but then they're just like, yeah, just, I just don't care about showering anymore. And the family member is like, yeah, like it's a fight to get them to shower. Or like they used to be this meticulous, meticulous, militant, cleaner of their household, and now they just, just don't care. And that, that can also be another thing that's hard to differentiate from depression, because right, in depression you'll see anhedonia, which is loss of the ability to experience pleasure, that that can, and you, and you feel guilt and worthlessness. So the thought process is, I don't deserve to have a clean body. I don't deserve to have a clean floor. Like I'm so worthless, and [01:03:00] I don't, and I wouldn't even get any joy from cleaning. It'll just feel like a chore if I did it anyways. But, but I still don't like these things. Mm-hmm. I don't like, I'm disgusted by the clean floor, but I think I deserve to be disgusting. You know, like, I hate myself, but this patient is like, no, I don't, I don't hate myself. Right. I'm fine. Like, I, I just don't care. Like, I literally don't care if I stink or, or not. Like I'm, I am, I am apathetic to it. And I just, I just don't feel like that sense of disgust like I did before. I do think that like apathy can be kind of a hard thing to delineate. Margaret: That's like apathy can be a part of more of the like neuro vegetative, de like severe depression. But I agree with you and I feel like my neuropsych attendings have kind of have a like fine delineation between like apathy and severe depression and apathy and like something has is either a, a lesion has happened or there is like FTD going on or something else that like, this is [01:04:00] rare for even severe depression to make them appear like this much. Mm-hmm. And also it sounds like there, they don't have the adverse experience with disgust is what you're saying too, so they don't care that way either. Mm-hmm. The, I think the easiest way, like it, it's really hard to differentiate, for me at least. I think there are a couple nuggets that can be helpful. Preston: One is socializing. So apathetic patients will still socialize. They just don't, they don't care either way. Hedonic patients or like neuro vegetative depressive patients will really detach and isolate. Um, the other thing is like, you can have, you could have apathy without, like melancholic depression, without any other of like the emotional symptoms. It, it's like really strange to see like apathy alone. So I think it can be like hard to differentiate like depression and Parkinson's symptoms, depression and Lewy bodies because like they'll [01:05:00] have apathy mixed in there. But I think it can be really helpful when you see someone who just has apathy and like those frontal different frontal temporal dementia cases to be like, oh, this is what this is. And it is separate and distinct from these other like clusters of symptoms that I see in depression. The word I was looking for that the neuropsych people, which you'll be familiar with this word, Preston, but the bulia. Being like lack of motivation will drive. Mm-hmm. Is what we're talking about. No, I wasn't, I wasn't familiar with Bulia. Margaret: I wasn't either. And then we went and they were like, that's what this is. And I, this is someone who I want us to have on the show. Who to like, give us the like, like tiny, tiny details of everything and why they ask what they ask on the neuropsych thing. And his vocab is expansive in terms of this. But, uh, there's like a whole chapter on, on this like neuroanatomy, uh, text that he gave me to read and I did read it, but Bulia, that's the [01:06:00] word. Preston: Bil. Yeah. I think, I guess I use a volition, but maybe I should use bulia. It's a little bit shorter. We should have mine then my syllable. You can, you can sound very smart and be like, yes, there's a profound, um, presence in the room of Bulia and you take the tweet off. Yeah. It's all about celebrating your own petit tree. Right. Exactly. You can catch the next part of this on Patreon. It's patreon.com/happy Patient Pod. Well, thank you Margaret, for surviving with me as we kind of went into more of like the weeds of this episode. I, I think it's, it's fun and important to talk about the different dementias and I think, you know, for a lot of like clinicians or residents listening, I, I hope this was mostly just to review and kind of going over stuff that we've, like talked about in the past. And hopefully this is kind of a centralized way to, to organize some of the information that just kind of sounds like a disease or dementia to you. If you, if you're not familiar with any of these things, we hope it jogs your memory. [01:07:00] Yeah, exactly. And hopefully you can retrieve the memory too. Yeah. That it registered somewhere. Margaret: Hopefully you don't feel like you'll like about it. Yeah. We, we will be covering, um, some like practice cases and vignettes on the Patreon, but as far as today goes, that's gonna conclude our show. So thank you again for listening. We really appreciate all the comments that you've been leaving. Um, we're also, uh, shout out to the speech language people from. Speech. Like we recognize we need to have an SLP on after the aphasia episode. That was our bad the shout out. You guys. We love you guys. We love speech language people. Thank you for letting us know. We're aware. Yeah. We should have a, a speech language pathologist. That would be, that would be a really good episode. Preston: We could practice doing some of the like speech pathology stuff they do. We could, yeah. Baseball. And we can ask them about aphasia. They do, you know, the main treaters of aphasia. We could ask them what they actually do mm-hmm. To treat [01:08:00] it. Um, if, if you are a speech language pathologist and want to come chat with us, you can find us on Instagram and TikTok at Human Content Pods. I'm always on Instagram at it's prerow. And you can also find video versions of the podcast on my YouTube. Margaret's at Badar every day. She's also on Substack. Where you can spend, you could buy her an overpriced latte $8 and get behind that paywall. She's can, yeah. They, they're featuring her on local radio stations now for her, her mythical whimsy of winter. It's, it's incredible. It's winter mysticism, but close enough. Whi Sorry. Yeah. Snowflake, whimsy, whatever. We're your host, Preston Roche and Margaret Duncan. Our executive producers are me, Preston Roche, Margaret Duncan, Wolf Flannery, Kristen Flannery, Aron Korney, Rob Goldman and Shanti Brook, our editor and engineers, Jason Portizo. Our music is Bio Benz V. To learn more about our program, disclaimer and ethics policy submission verification, licensing terms on our HIPAA release terms, go to how to be [01:09:00] patient pod.com or reach out to us at how to Be patient@humancontent.com with any questions or concerns. How to be patient as a human content production. Thank you for watching. If you wanna see more of us or if you wanna see, this is lilac. She's my cat. She's gonna be waving her hand at one of the floating boxes, which will lead to more episodes. Lilac Point to the other episodes. Lilac doesn't know what the internet is, but I swear they're there. They, they probably exist for real. But in the meantime, I'm just gonna pet lilac and then I'm gonna go dance in the [01:10:00] background.