Below is a lightly edited, AI-generated transcript of the “First Opinion Podcast” interview with Jason Karlawish, who writes STAT’s Neurotransmissions column. Be sure to sign up for the weekly “First Opinion Podcast” on Apple Podcasts, Spotify, or wherever you get your podcasts. Get alerts about each new episode by signing up for the “First Opinion Podcast” newsletter. And don’t forget to sign up for the First Opinion newsletter, delivered every Sunday.
Torie Bosch: When a patient is diagnosed with Alzheimer’s, they and their family always want to know: What does that mean for the future? Answering that question is impossible right now. But one thing is for sure: A revolution is happening in dementia care.
Welcome to the “First Opinion Podcast.” I’m Torie Bosch, editor of First Opinion. First Opinion is STAT’s home for big, bold ideas from health care providers, researchers, patients, and others who have something to say about medicine’s most important and pressing topics.
Today I’m speaking with Jason Karlawish, who writes STAT+’s new column, Neurotransmissions. Jason is a professor of medicine, medical ethics and health policy, and neurology at the University of Pennsylvania’s Perelman School of Medicine. He’s also co-director of the Penn Memory Center and executive producer of “The Age of Aging” podcast.
After a quick break, I’ll bring you our conversation about how everything is changing in dementia diagnosis and treatment.
Jason Karalwish, welcome to the “First Opinion Podcast.”
Jason Karlawish: Thank you, Torie. It’s a pleasure to be here. It’s great to reconnect again.
Bosch: Yes, you’re a “First Opinion Podcast” return [guest]. I think this might be your third time on the show, predating me in fact.
Karlawish: Yeah, yeah, I definitely during the notorious aducanumab days I had a few appearances, but there’s been some others, yes, as well. It’s been very satisfying. Yeah, I’ve really enjoyed the opportunity.
Bosch: Yeah, you’re probably our most [frequent] guest, which speaks to how interesting your work is and how timely it seemingly always is. There’s always something happening in your field.
Karlawish: Thank you, there is. My field the field of Alzheimer’s, the field of dementia, is undergoing rapid change, rapid cycle innovation, rapid cycle revolution. It’s absolutely fascinating and wonderful.
Bosch: Now before we get s really get into it, can you maybe talk a little bit about dementia versus Alzheimer’s and how you use those words?
Karlawish: Yeah, I’m a nomenclature perfectionist, but with respect to nomenclature for Alzheimer’s disease, I take words very seriously. Because the nomenclature is in flux. And that’s OK because it represents the flux that’s happening that we’ll talk about in the field in general.
But what I talk about when I talk about Alzheimer’s disease is a pathological process that leads to dementia, meaning pathology is at work causing progressive, disabling cognitive impairments.
In contrast, dementia, and I’ve already sort of gestured to the idea, is progressive, disabling cognitive impairments. And I like that way of framing dementia, to emphasize the focus is disability, ultimately. Like, you’re unable to do things that you used to be able to do, but with accommodations, you might be able to do some of them again.
So there’s the distinction, and of course, what it invites is, well, what are the other diseases that cause dementia? And then of course that brings in diseases like LATE and Lewy body disease, etc. And I think that’s where I think the world will go, is thinking about this just sharp distinction as opposed to the sort of 1980s nomenclature, which pretty much said Alzheimer’s was dementia, dementia was Alzheimer’s, and almost, you know, consanguineous relationship of the two words.
Bosch: Do you find when working with patients that they and their families conflate dementia and Alzheimer’s?
STAT Plus: Tech-enabled caregiving can help dementia patients stay at home — perhaps for too long
Karlawish: Yeah, that’s out there, very much so. Although I have noticed — again, I’m very mindful of where am I coming from, you know, what’s my position. People at the [Penn] Memory Center are pretty savvy to what’s going on and/or get savvy fairly quickly after they come to the memory center. But yes, “What is the difference between Alzheimer’s and dementia?” still remains probably in the top three questions that what is asked.
Bosch: What are the other two, really briefly?
Karlawish: “What is dementia?” [and] “What is Alzheimer’s?” probably, once people sort of begin to get a sense that the two things are different. You know, once upon a time, mild cognitive impairment got mentioned a lot. I notice it’s not so commonly mentioned 1765646289. I think people never really kind of got what it was, no offense whatsoever to the construct. And then probably the most common question once all diagnosis and whatnot is in place is: what to expect in the future?
Bosch: All right, and I wanna come back to that. But first, how long have you been treating dementia patients?
Karlawish: I started practicing at the University of Pennsylvania in 1997, so I am circa 20th century.
Bosch: And what were the first, say, five years of your career like? You know, what sorts of things were you seeing? What sorts of options did you have for patients?
Karlawish: Oh wow. You know, looking back to those early years with my colleague and friend Chris Clark, who sadly is no longer alive, it was so different. It was just him and me and a third clinician who kind of popped in every now and then. And the typical patient presented with a [mini-mental state examination] score of 19.
Bosch: I’m so sorry, and what is that score?
Karlawish: That’s the 0-to-30-point famous, you know, overall omnibus cognitive measure, a little different than the [Montreal Cognitive Assessment], which a current chief executive of the United States is obsessed with. But it’s an omnibus measure that’s been around since the ’70s.
What I’m getting at is that the typical patient presented having lived with, suffered through — as the family as well — dementia for several years. So that was the typical presentation. And our treatments then were a once-a-day pill, and then later on the addition of some other variations on the cholinesterase inhibitors. I started practice just when donepezil was approved as Aricept. That, together with various mood psychotropic-type medicines, you know, from anxiety, depression, etc., was our armamentarium. It was pretty slender. And we had a social worker who did her best to also help people organize a care plan. Looking back, it feels historical.
Bosch: What made you decide to go in into this field that at the time offered so few options for you to share with patients?
Karlawish: Well, like many things that motivate you academically and intellectually, and then deep things about you motivate you deeply and personally. I think many physicians have that kind of chimeric blend of motivations. Academically, professionally, I was, is, and continue to be utterly fascinated with, broadly, the topic of ethics and human values. And certainly that’s right all throughout medicine.
But if you had to pick one field, one area that just amplifies matters of ethics and human values, even what is the nature of being human, having a mind, it’s of course dementia. That together with an interest in geriatrics and gerontology made it a just a wonderful academic, intellectual combination. But, you know, out of a lot of interest, as you know, readers may know, “there he goes again on a tangent” kind of thing. Just after my training, my 92-year-old grandfather fell, broke his hip, and within six months was dead. And, you know, along the way was a poorly diagnosed, not really diagnosed, dementia, absolutely no services and supports. He went to an academic medical center and got the best of care and worst of care. And I just realized, you know, at the time I actually was gonna go into critical care medicine. I was at the University of Chicago in pulmonary critical care medicine. And I just dropped out and switched over to geriatrics. I was the only geriatrics fellow for three years, and I had the best time academically, intellectually, and I’ve never looked back. I have absolute utter respect for my colleagues in critical care. There’s no criticism of them, but I’ve never looked back with regrets on exiting critical care and switching over to essentially a focus in dementia care, initially as a geriatrician.
Bosch: And so when you started, as you said, you had very few things to offer families and patients besides, you know, really being someone who sort of understood these issues and cared for them and this sort of limited repertoire of medication.
Karlawish: I gave them a diagnosis.
Bosch: Right. And care, right? I mean that’s definitely important.
You wrote in your new STAT column Neurotransmissions that there’s a revolution happening in dementia care. And of course you’ve now written four columns about this revolution, so it’s a pretty big idea, but briefly, what are the areas where this revolution is happening and what does it mean?
STAT Plus: All of a sudden, dementia treatment is becoming very exciting
Karlawish: Yeah. So when I think of “revolution,” it means a turning. We were going in one direction, monarchy, the head of state that is the state, to concepts of a liberal democracy. That’s a big turning. That’s the American revolution.
So in science, you know, what’s happening in in medical science, medicine is a revolution in dementia, namely, we now, for some of the diseases that cause dementia, such as Alzheimer’s and Lewy body disease, for example, have the ability to offer somewhat a pathophysiological diagnosis. I can tell you that that pathology is one of the causes of your progressive disabling cognitive impairments. Prior to that, it was essentially always a probabilistic diagnosis, and one essentially had to die until finally my colleague, for example, could do it, perform a brain autopsy and get you a definitive answer. Of course, you’re dead, whatever. Anyway, it’s bleak.
That’s changed. I can now tell someone, “You have the pathology of Alzheimer’s causing your disease.” There may be other pathologies — mixed pathology is very common in in dementia — but it’s unlimbering the inherent uncertainty that laced it. And that matters a lot to patients. It gives them a different illness experience. “I know what’s causing my problem.”
The second innovation, which is part of this revolution, is the arrival of effective treatments for Alzheimer’s, namely the anti-amyloid therapies, the monoclonal antibodies, lecanemab and donanemab. Which, you know, went through not two, but one adequate, well-controlled Phase 3 trial with good, solid methods and produce results that I think are definitive: The drug was greater than placebo.
And there’s still a lot to work out about whether, you know, do they really slow the disease? But they certainly change the slope of decline, which is one way to represent the pace of a disease.
So for many patients, I can give you a definitive diagnosis. And for some patients, I can do that and give you a therapy that slows the progression of disease. So what’s the consequence of this revolution? Simply put, and the argument I make across the three essays is dementia is being democratized. And what do I mean by that clever play on, alliterative play on words, is that each patient’s illness experience, I’m noticing, is quite different than the illness experiences that I narrated and wrote about and thought about in the early, late 20th, early 21st century. There are experiences that are more or less inflected with sort of the horror story. “There’s nothing you can do,” a kind of hopeless hopelessness, if you will, to a tragic story of, you know, “This is a disease, you can’t cure it, but we know what it is, and we’re gonna figure out how to live with it, and I’m doing something that might slow it down.” And out of those very different illness experiences, I would argue that culture will change, that what we think about when we hear words like Alzheimer’s and dementia will change. It’s not gonna go from a horror story to a fairy tale, but it will become, as I’ve already mentioned, I think, more thought of in the way of a human tragedy, something we’re going to figure out and we’re going to live with. And I think that will transform culture. And one of the points I make in the essays, and I’ll pause after this monologue, is I don’t think it will just be acceptable to use dementia as this sort of stigmatizing term that has nothing to do with dementia. As, for example, in the last election, dementia was tossed around willy-nilly is a way to insult one of the candidates. And I think those kind of activities are going to fade.
Bosch: Can you talk a little bit about, you know, on a practical level, how do these new diagnostics, these new medications change the experience for a patient? What’s different for a patient today versus in 1997 in terms of their day-to-day life?
Karlawish: Yeah, what’s different for a patient now is they in many cases now know what is causing their mysterious mental phenomena. And one patient explained this to me, I thought in a way that was really quite vivid. And I do find that patient stories really are the ultimate sort of arbiter of what is the truth. If you have to tease out the truth from the story. And this gentleman told me, “You know, in my family, I had a relative who had chronic mental illness, depression with substance use issues. And it just always sort of haunted the family, like, why does he have this?” And you know, family members and various clinicians had all kinds of theories, you know, and explanations: genes, childhood, lack of motivation, not enough serotonin, too much serotonin, whatever. And he said, “You know, when I developed my symptoms, this mysterious mental phenomena, I kind of began to feel like him, like, well, what’s causing this?” And it was this mystery that was very unsettling. Humans do not like uncertainty. It is hidebound, tied up with anxiety. But he said, “Look, I didn’t like getting the elevated amyloid result and the positive, albeit mildly elevated, tau result. But that told me that’s what’s going on here. This is what the problem is.” And it just gave him meaning as opposed to mystery. And I think humans like meaning. They like to and I and colleagues have re-endorsed the same experiences with their patients.
Bosch: And what do these new medications mean for, say, how long someone is able to keep working or be involved with care or live at home?
Karlawish: Yeah, all constructs which seem easy to talk about, but ultimately really are kind of hard to measure and whatnot. And, you know, I’m gonna go on a slight tangent, but here’s where I think my field looks to fields like cardiology and oncology, also orthopedics in some sense. They’ve got hard endpoints, you know, death or not, clear stages of progression. In our field, we are struggling to have a coherent language of benefit, and that’s been the case since the cholinesterase inhibitor days.
STAT Plus: The word ‘dementia’ is about to lose its value
Having said that, you know, they do slow down the progressive, disabling cognitive impairments, the progressive disabilities and doing daily day-to-day function, like preparing a meal, etc., progressing to the next stage, which of course is very difficult. … If you look at the different staging criteria, how they describe mild stage sort of differs a bit across the stages in ways that can be rather frustrating. But that’s what they do. And I do notice families struggle to understand, well, what will it mean to slow things down? And what I say is “Well, it just will take longer for disability to occur.”
Bosch: Does that make sense to them, or do they continue to struggle with it?
Karlawish: Yeah, they get that idea. Granted, it’s very interesting, and we’re studying this at Penn, led by work done by my colleague at Penn, Dr. Justin Clapp, who’s an anthropologist in the medical ethics and health policy department I’m in. And Justin and Emily Largent and myself are doing a study funded by the Greenwall Foundation to examine how people make the decision to take or not take these treatments. And it’s interesting, you know, there’s this sort of “I get what you’ve told me, they slow the disease” but then they’ll talk about after being on therapy, “I think that she’s better.” And I’m not contesting that, like “you’re wrong.” And in some sense, and we actually have a a story about this on our podcast, “The Age of Aging,” of a patient who started therapy and got better. And what I mean by that is she felt hope, she felt motivation, she reclaimed friendships, and most importantly, she started painting again. She’s a very accomplished artist, Neesa Procaccino, and actually even transformed her art from hyperrealist works to abstract, expressionist-type surreal works. So there’s almost two kind of ways that we talk about these treatments. In the professional role, it’s about slowing, etc. And it’s a much more varied conversation about benefit in the patient and caregiver world.
Bosch: And so these medications are changing the experience for you, for your colleagues, and for patients and their families, but they also do come with some risks. Can you talk a little bit about them?
Karlawish: Yeah, anti-amyloid therapies cause microscopic bleeding in the brain as a result of breakdown of micro, of tiny blood vessels. And if left unchecked, that can lead to leakage of fluid and swelling or edema. I recognize the term out there is ARIA. I just don’t find that term helpful. I’m not trying to be difficult, but I don’t think naming something as an abbreviation for amyloid-related imaging abnormalities, so it’s an abbreviation of a term that almost sounds like the imaging is the abnormality. I just find that so opaque. I get it in the professional community, it’s a simple abbreviation. And in many professional spheres, we take things down to abbreviation so that it becomes this sort of secret, private language.
But for patients and caregivers, it’s called microscopic bleeds and swelling. And that’s what it is. And so that’s how I think we should talk about it. And that’s how I explain it.
Anyway, that’s what the drugs cause. The great thing, good thing, good thing, great, is an MRI scan can pick up the microscopic bleeds and swelling. And both drugs’ labels have very scheduled MRI scanning sequences to try to pick those up before they become a problem, particularly the edema. Moreover, you can do a genetic test, the APOE test, and based on that result, you can inform someone of what their risk is in addition to other factors like uncontrolled high blood pressure. So if someone can get a real good sense of, so if I take this drug, A, what’s my risk, and B, how are you going to minimize that risk?
Bosch: What role do you think that the potential downsides of these medications are playing in the revolution? Is it holding it back or are people maybe going full force faster than they should?
Karlawish: Definitely not full force. If anything, you know, they slow the disease and they’re slow to get out there into therapy. Because they’re not easy drugs. I mean, they’re intravenous infusions, either every two or every four weeks, the frequent MRIs, the workups to get to the drug. It’s a lot of work, and it’s a lot of work to take the drugs as a patient and family. And I think that has led to slower than desired adoption, which you could argue is ironic because we so lack a health care system to deliver care to people with dementia that maybe there’s sort of a cruel irony there. This is just the kind of drug to ease into the system, as opposed to a widely available drug that, you know, would just inundate the system with demand, such as say a GLP-1 agonist to treat Alzheimer’s, which at the time of we’re talking we just found out is not effective. We’ll learn more later.
So in that sense, democratizing dementia has not been democratized. Namely, another sense of the meaning of democratizing is wide availability of something. So certainly like the automobile went from being a luxury item to a democratized technology out in the world. I’m not trying to say everyone’s got a car, but cars are fairly widely available. TVs, radios, those are all democratized technologies for good reason, because they really do allow people to flourish. Alzheimer’s disease treatments have not been democratized. They are not widely available. They are they are still aristocratic, to play on some political terms, if you will. Yeah, available in the specialty centers in some sense that have the adequate equipment to do it.
Bosch: Is it particularly different, I would imagine, in, say, rural areas?
Karlawish: I don’t have those data. I’m sure those data are there. I can’t say with facts, like with citing a study. But, you know, if you think about it, it’s come into a space, get a diagnosis. That diagnosis requires a careful clinical assessment, MRI imaging, amyloid PET imaging, and then come to an infusion center every two or four weeks with frequent MRIs in between. If you live where travel is a challenge, well, your access is a challenge. And we know from our study that I talked about, that Dr. Clapp leads, that matters of the hassles of treatment enter into people’s decisions whether they’re gonna take that treatment or not. They do. They do, as does their cost, by the way, [that] the treatments do come with, depending on one’s magnificent insurance plan and whatnot. Pardon my cynicism, but, you know, I don’t know whose benefit a pharmacy benefit manager is managing.
STAT Plus: The way we talk about dementia is about to change completely
But anyway, putting that aside, some people can face hundreds of dollars a month copay, which also for some is just not gonna be possible. And some insurers don’t offer them. Some of the commercial insurers do not pay for these drugs.
Bosch: And are you in your office having to spend a lot of time sort of navigating the availability?
Karlawish: As a whole group we are. One of many great things about Penn Memory Center and Penn Medicine — and this is not an ad, I’m just speaking my experience compared to my colleagues — we really stepped up and put together the necessary administrative and other systems to be able to deliver these drugs. It’s been really magnificent. In contrast, when I talk to colleagues at other centers, peer centers, you know, they’re slower with the uptake because the investment that has to be made by the institution is not insignificant. Not just money, but human resources, people, brains.
Bosch: Yes, it always comes back to brains here.
Karlawish: It does. It takes humans to take care of humans.
Bosch: One thing you wrote about in your column Neurotransmissions that’s really stuck with me is that you’re getting far more fellowship applicants than usual recently. Is that right?
Karlawish: It’s great.
Bosch: What are those numbers going from to?
Karlawish: Zero or one to five to nine, even more. The tragedy is we don’t have the funds to pay for. We could take more, but we just don’t have the funds. We can’t, you know. And I’m waiting for America to wake up and say, “We gotta build this workforce. We need this.” And these young people are really excited. It’s, again, back to my early days at the Memory Center with Chris Clark. You know, it’d be him and me and our staff at our consensus conference. That’s it. We’re the two doctors. And that has totally changed. You know, it’s eight clinicians and fellows and medical students popping in. I mean, I’d be with a medical student for two weeks in my clinic who just can’t wait to become an Alzheimer’s doctor. I’ll tell you, as old man Karlawish, it reminds me of when I was young. You asked someone who wanted to go into medicine, “Why do you want to go in?” and they say, “I want to cure cancer.” And I myself talked about curing cancer. I remember that. And I’m beginning to hear these, I get emails from high school students like, “I want to go into Alzheimer’s. I want to cure Alzheimer’s.” And I appreciate the enthusiasm. The naivety is touching. But that’s good because that’s exactly the emotions you need to have when you’re 16. You’ll work your butt off.
Bosch: And what do you tell a 16-year-old who’s interested in in going into this field?
Karlawish: Go into it. Yeah. I mean, go into the brain. There is so much opportunity in the space of the brain. And a lot of it, not all of it, is obviously, but one big reason is the advances that have been made in the ability to measure the brain, to get into the skull, get through the skull and into that organ. And those spectacular advances in neuroimaging, biomarker measures, remote, unobtrusive continuous monitoring, brain-computer interfaces, are all sort of unlocking that. And I think one of the most exciting areas is consciousness science, you know, the science of mind. I hope, I think, that it will intersect with dementia. We’re part of a group that actually that’s one of our agendas. So this is a selfish PR promotion for our interests.
But fundamentally, dementia is a disorder of the mind. That’s what it is. And we need to integrate the way so we think about, talk about, study, and care for people with dementia with the advances that are occurring in consciousness, the science of consciousness.
Bosch: One thing that you’ve talked about a bit is that you have some complicated feelings around the word “dementia.” Can you talk a little bit about that?
Karlawish: Well, I’m gonna let culture work this out. I mean, right now it is a stigmatized word, although there’s some people that are so happy they only have dementia and not Alzheimer’s, because that’s stigmatized, so both words have troubles. I get the desire to rid the world of the term “dementia.” And in some cultures the word is incredibly stigmatizing. In French, for example, they just don’t say “dementia.” I actually had occasion to listen to a French-language documentary. No, it was English language translated into French. Anyway, when the French said “Alzheimer’s,” the English translation said “dementia.” Because they just won’t say “dementia” in French. It’s so stigmatizing. Everything’s “Alzheimer’s.” You have to respect these cultural differences.
But I understand why we would like to rid ourselves of the of the word “dementia” and replace it with something else. But what that something else will be, I don’t know. And we need “dementia,” like we need “cancer.” Like we need “heart disease.” We need, like, so what if Alzheimer’s didn’t cause dementia, if limbic associated age-related TDP encephalopathy didn’t cause dementia, these wouldn’t be a problem. They would, I don’t know what they would do. They would just be sort of, I don’t know, annoyances, like you know, acne. But they do, and we can’t lose sight of that is the problem. You know, if we can prevent that, slow it down, etc., we’ve achieved our goal.
Bosch: Do you find that patients struggle with the word dementia?
Karlawish: Yeah, they do. Just like people struggle with any label of any disease or any syndrome. I mean, does anyone like, “Oh, I’m so happy, I’ve got Covid. That’s great.” I mean, no disease label is, but [my patients are] very worried about how people will treat them when they learn they have these labels. So there is a very legitimate concern about stigma. Namely not just self-stigma, what you how you feel about yourself and how you then minimize your abilities: “Oh, I can’t do that.” But what’s called public stigma, namely, when people know something about me, they will treat me differently. There’s no question that persons living with dementia experience that. That, you know, the slightest mistake, the slightest slip-up is, you know, the beginning of the end, etc. And, you know, just today I had a word-finding moment and I thought, “Oh boy, you know, that was really embarrassing.” But imagine if I had that word-finding moment and you knew that I had Alzheimer’s or that I had dementia. And boy, that is extremely harmful. And this gets back to the cultural transformation that needs to occur. And it will occur.
Bosch: You wrote in Neurotransmissions about a lawyer you worked with who was practicing was noticing essentially that she wasn’t as sharp as she once was and came to you. Yeah, I imagine you don’t want to open a meeting as an attorney saying, I have recently been diagnosed with mild cognitive decline.
Karlawish: Mild cognitive impairment. Yeah, no, you don’t. You don’t.
This is one of the ground zero public policy issues we’re gonna have to deal with, which is, you know, as I mentioned back in the late 20th century, by the time I saw people at the Memory Center, they were long out of the workforce with tragic stories to tell me about how they got out of the workforce. But now we’re diagnosing this disease where people are still in the workforce. And you’re right, you do not want to walk into the office and say, “Oh, by the way, guys, just yesterday I saw my doc,” and you know, for just the reasons of you know we’ve been gesturing to, which is no, they’re going to treat you differently. So this is an enormous issue that we need to begin to address as a matter of public policy, which is how to make sure that employment practices are in place to obviously address two — at least two — competing interests or potentially conflicting interests, I think. One is the employee’s ability to continue working for the basic issue of “I need my job, I need my income.” And two, the employer’s ability to get the work they need for the money that they’re paying you for salary. And this is an area that has not been worked out and that we need to work out.
Bosch: I think we’re gonna have to ask you to write a column about that.
Karlawish: Yeah, it’s on the list.
Bosch: Because it’s something that I’m incredibly interested in. Yes, the very, very long list. One other thing you wrote about that really stuck with me was undiagnosing a patient. Can you talk really briefly about that?
Karlawish: Yeah, this has been fascinating. And this gets to the power of these revolutionary technologies. The case that stood out to me was Barbara who had a diagnosis of Alzheimer’s, just classic case, you know, amnestic disorder, some troubles with executive function, temporal limbic atrophy on MRI, just, you know, classic, like, you know, hello, let’s move on, something more interesting. Excuse my tone. But what I’m getting at is she doesn’t have Alzheimer’s disease. And how do I know that? Because I did both amyloid and PET imaging on her, which are the gold standard for in vivo detection. And hers were totally negative. She has limbic associated age-related TDP encephalopathy, or otherwise known as LATE, a very common cause of dementia in the 75-plus-year-old crowd in particular, which is the fastest growing group of people at the highest risk of delving dementia, which suggests that LATE is actually an extremely common cause of dementia that for many people has not been diagnosed and they carry around the label of Alzheimer’s.
My tone is a little flippant, but what I’m getting at is that’s revolutionary. And so I undiagnosed her. I said to her and her daughter, “You don’t have Alzheimer’s. You have this other disease.” And for them, that was transformative for kind of two interrelated, intersecting reasons. One, the uncertainty was gone. It was always probable Alzheimer’s, not certain. And number two, when it was certain, it was a different disease and with a different prognosis. And that meant a lot to the family, like because the family said to me, “Every time I looked at her, I was afraid it’s gonna be the last time she’s gonna know who I am” because of the rapid decline in Alzheimer’s that can occur, etc. Whether that’s true or not isn’t the issue. But LATE is alone is less likely to cause that. It’s a dense amnesia with troubles with social cognition, executive function, but relative preservation of semantic memory, which is why patients who are well cared for with LATE can kind of seem quite undisabled as long as they’re in an environment that they really know because they’re not reliant on their immediate memory and having to learn new geospatial things. In contrast, they’re tapping into their well-learned memories and their semantic memory. And they in that kind of setting, they actually do quite well comparative to someone with where it’s amyloid, tau causing Alzheimer’s.
Bosch: Now, as we start to wrap up, I want to go to something you talked about early in our conversation, which is that patients want you to tell them their futures, or families want you to tell them their futures. Are you better able to tell the future now, do you think?
Karlawish: No. That’s my one thing. So I stopped answering that question with an answer, but with instead I would ask a question, which is: “What is it that you’re concerned about in the future?” … And often there’s a long pause. … But then they kind of begin to articulate various states of mental impairment, maybe loss of experience the world or act with as an agent in the world, the agency and experience, or states of profound disability, oftentimes invoking impairments in performing life’s basic activities of daily living, the morning routine. So at least they’re getting me to what they’re worried about, and to the extent that I can talk about when those problems might happen, or I can’t, we at least have a conversation about those matters as best as I possibly can.
We need better ways to tell someone the trajectory of their disease and to measure biologically, is their disease getting worse? We don’t have these. We’re the cusp with the advances that I narrated earlier. To be able to say to someone, you know, based on measures of nerve generation, neurofunction, you know, “This is slowing down, speeding up, changing, not changing, etc.” I’d love to see better markers of conscious experience incorporated into how we think about this as well, in order to give people a sense of how they’re changing and also when those kinds of problems emerge from data gathered in cohort studies. So this is the future. This is why the 16-year-olds need to go into this field.
Bosch: Well, Jason Karlawish, I think that’s a great place to end it. Thank you so much for coming on the show today.
Karlawish: You’re welcome, Torie. I had a great time, and I’d love to come back sometime.
Bosch: I’m sure you’ll be back very soon. You’re our repeat guest.
And thank you for listening to the First Opinion Podcast. It’s produced by Hyacinth Empinado. Alissa Ambrose is senior producer, and Rick Berke is executive producer. You could share your opinion on the show by emailing me at [email protected]. And please do leave a review or rating on whatever platform you use to get your podcasts. Until next time, I’m Torie Bosch, and please don’t keep your opinions to yourself.