BrainStorm
When Memory Fades - Rethinking Alzheimer's from Diagnosis to Care
When Memory Fades - Rethinking Alzheimer's from Diagnosis to Care
Host Meryl Comer continues her conversation with Dr. Jason Karlawish, professor of medicine, medical ethics, and neurology at the University of Pennsylvania, about the evolving landscape of Alzheimer's disease. Drawing on his book The Problem with Alzheimer's, Dr. Karlawish explores the promise of early detection, the ethical complexities of disclosing uncertain diagnoses, and why he remains skeptical that an outright cure is on the near horizon — famously comparing it to planning retirement with a lottery ticket.
The conversation moves into the deeply human side of the disease, touching on caregiving as a form of "mind support," the role families play in both enabling and delaying diagnosis, and the exciting potential of smartphones and smart home technologies to transform care. Dr. Karlawish shares a candid reflection on what gives him hope and what keeps him up at night. This episode is a thoughtful, unflinching look at a disease that is best understood as a "complex tragedy."
BRAINSTORM, EP #105
GUEST: DR. JASON KARLAWISH (PART 2)
00:00:00:04 - 00:00:20:24
Dr. Jason Karlawish
There's two categories of what I think are promising technologies. One is and it's right next to me here, my trusty smartphone. It has a host of ways that it can monitor how our brain is working. I just wrote a piece about a patient who didn't like playing Wordle, The New York Times game, but decided to do it because he realized it's a great memory test.
00:00:20:27 - 00:00:40:12
Narrator
Welcome to BrainStorm by UsAgainstAlzheimer's, a patient centered nonprofit organization. Your host, Meryl Comer, is a co-founder, 24 year caregiver, an Emmy Award winning journalist, and the author of the New York Times bestseller Slow Dancing with a Stranger.
00:00:40:15 - 00:01:17:06
Meryl Comer
This is BrainStorm, and I'm Meryl Comer. We continue our fascinating conversation with Doctor Jason Karlawish, professor of medicine, medical ethics, health policy and neurology at the University of Pennsylvania. He is also the author of The Problem with Alzheimer's. Today, we delve into the ethics and challenges of early diagnosis living with uncertainty and the need for a societal reset on the issue of cure versus care.
00:01:17:08 - 00:01:37:05
Meryl Comer
Jason, thank you for joining us. How might early detection influence the treatment options or long-term outcomes for those diagnosed? And I'm really careful not to call them patients. These are people living with the diagnosis in their 40s and 50s.
00:01:37:12 - 00:01:52:05
Dr. Jason Karlawish
This point you made about shouldn't call them patients. You know, I’ll confess as a physician, if you come and see me and I put a billing code on new. You're a patient. But that's just, you know, that's how I that's my world. And I'll just I'll.
00:01:52:08 - 00:01:55:00
Meryl Comer
We're trying to respect the world of advocacy.
00:01:55:03 - 00:02:19:12
Dr. Jason Karlawish
I hear you, I hear you. But that's just I just want to give that away, because I do use the word patient fairly freely and openly. I think what you're envisioning here, though, is a future where this disease, diseases really, are diagnosed in the 40s and 50s. And I think, we have to envision a future where and I'm not sure what the age will be, but at some age, you get some sort of test.
00:02:19:14 - 00:02:38:14
Dr. Jason Karlawish
I'm speaking in generalities here so as to not get people freaked out about what this test will be. And that test says you know what, Jason? You're at risk of developing cognitive impairment in the next ten years or you're not. And if you're in the group that's at risk, here's what we're going to do in terms of the next test or follow up down the road.
00:02:38:21 - 00:03:00:27
Dr. Jason Karlawish
And you only have to look at the progress that's been made in cardiovascular disease to begin to see how you could do this. Because in cardiovascular disease, you know, we've gotten to the point now where at about age 40 or so in LDL and some other tests begin to sort you into the group that does need further testing, follow up, and potentially treatments such as with a statin or not.
00:03:00:28 - 00:03:28:15
Dr. Jason Karlawish
In other words, check you in ten years. And so you could imagine if the approach of anti amyloid therapeutics that we're using now holds up. You could imagine very powerful, much safer, longer acting approaches to targeting amyloid that would prevent its accumulation in the first place. That's a vision. It's not a reality. But I will say it's this is the conversations I have with colleagues.
00:03:28:15 - 00:03:36:24
Dr. Jason Karlawish
This is sort of the way people are beginning to see and think as they sort of, I think, reasonably extrapolate what these technologies are capable of doing.
00:03:36:27 - 00:03:52:03
Meryl Comer
You know, Jason, because we haven't managed that issue of stigma well enough yet. What safeguards do you think need to be in place to minimize the risk or consequences of a misdiagnosis.
00:03:52:06 - 00:04:17:05
Dr. Jason Karlawish
Of a misdiagnosis? So in other words, someone's told you've got all survivors and then later on they're told, you know what, I don't think you do or you don't. But then later on, actually you do. Yeah. You know, both cases raise the need to address when you're doing these tests that there's uncertainty around them. Okay. That just because it's negative now doesn't mean it might not be positive later.
00:04:17:07 - 00:04:46:16
Dr. Jason Karlawish
Or just in the case of a positive test that in fact was negative. You have to think through some of those scenarios. Oftentimes it's because the testing wasn't done. You know, even now, there's no question people are walking around diagnoses who haven't gotten the appropriate testing that could confirm that diagnosis. So in all those cases, you know, I think the obligation of physicians to do one of the most uncomfortable things the doctors have to struggle to do, which is disclose uncertainty, to disclose the fact that this may not be certain.
00:04:46:18 - 00:05:12:20
Dr. Jason Karlawish
And I do think it's wise for a physician to counsel as well, to think carefully about who you're going to tell this information to and why you're going to tell it to them. But I think they have to be very thoughtful about telling it to people who are not very available, reliable and trustworthy. And who might therefore, for number, any number of reasons, exercise acts of, of of stigma and othering on the individual.
00:05:12:22 - 00:05:26:01
Dr. Jason Karlawish
I think this plays out a lot in spaces like the workforce, where, you know, many people might still be in the workforce and therefore, threat, threatened in their ability to perform in their job if other people know.
00:05:26:03 - 00:05:30:13
Meryl Comer
And once it's on your medical record, it's on your medical record. Right.
00:05:30:16 - 00:05:37:03
Dr. Jason Karlawish
Which plausibly should not be viewed by, you know, people in your job.
00:05:37:06 - 00:05:45:23
Meryl Comer
In your writing, you've compared the idea of a cure for Alzheimer's to planning your retirement with lottery tickets.
00:05:45:26 - 00:05:46:11
Dr. Jason Karlawish
Yeah.
00:05:46:14 - 00:05:58:15
Meryl Comer
Tell me, how should clinicians, advocates in the public, how do we recalibrate our expectation around cure versus care and risk reduction?
00:05:58:17 - 00:06:19:11
Dr. Jason Karlawish
You know, when I wrote that, I still stick with it, although maybe I might be willing to say, you know, there's there's a there's a greater than iota chance that we might be able in some of the presentations and forms of Alzheimer's, to block further progression such that if, you know, it becomes a non-issue, for the remainder of your life.
00:06:19:14 - 00:06:53:12
Dr. Jason Karlawish
But, yeah, I mean, the point I was getting at was these are complicated diseases. Oftentimes people have more than one other words. It's not uncommon. I just looked at a postmortem on a patient of mine who had Alzheimer's pathology, and also Lewy body pathology and TDP pathology. And so, you know, if you take all these pathology seriously and let's include vascular, the idea that we'll get to our 90th decade, 90th year, ninth decade, free of any cognitive problems is just an expectation that doesn't hold up to rational reasonableness.
00:06:53:14 - 00:07:22:07
Dr. Jason Karlawish
I think a lot of this really comes down to money. If you feel that the funds are tight, you get into a fight of care versus cure. If you feel that the funds are there, you're beginning to willing to take risks and grow. And certainly that was the case with cardiovascular disease and cancer. You know, those diseases had robust have robust business models that bring in the support needed to build the kind of infrastructure at cancer centers that allow people to get palliative care, along with curative treatments.
00:07:22:09 - 00:07:27:14
Dr. Jason Karlawish
I think we could we should envision the same thing for the problems that cause neurodegenerative diseases.
00:07:27:17 - 00:07:32:08
Meryl Comer
You've also written about undiagnosed a patient with dementia.
00:07:32:11 - 00:07:32:21
Dr. Jason Karlawish
Yeah.
00:07:32:29 - 00:07:38:29
Meryl Comer
What does undiagnosed mean in practice and when is it the right thing to do?
00:07:39:01 - 00:08:17:01
Dr. Jason Karlawish
Well, as you know, dementia, starts to become, risk as one enters their 60th, 70th year of life. It takes off after the 85th year. And, excuse me, after the 75th year. And what's what's been discovered in the last several years, is that one of the common causes of dementia in the 7580 plus group is limbic associated, age related TDP encephalopathy, otherwise known as late, late caused by a distinct pathology, TDP 43, distinct from Alzheimer's pathology, namely amyloid plaques and tangles.
00:08:17:03 - 00:08:43:17
Dr. Jason Karlawish
And I have several patients who I diagnosed with Alzheimer's disease, who I ran subsequently, biomarkers for Alzheimer's, as well as the imaging that gives supports a diagnosis of of late. And I undiagnosed them of Alzheimer's disease that they instead have late. And it's a rather incredible moment to say to someone based on this more definitive test than what I had before.
00:08:43:19 - 00:09:06:07
Dr. Jason Karlawish
You don't have Alzheimer's. You have this different, separate disease. I've had some people say to me, oh, well, why does it matter? You know, it's just dementia. And this gets back to the sort of 1990s, 1980s attitude. First of all, you're giving people facts that no longer mystery and people don't like uncertainty. Humans don't. Markets don't like uncertainty.
00:09:06:09 - 00:09:31:16
Dr. Jason Karlawish
It's called a bear market. What they like is facts that are certain. What's the answer? And once you know what's causing your problem, it lets you come to terms with it. Put a name on it. Moreover, there's a different prognosis for late versus Alzheimer's disease. They progress much slower. There's subtle but important differences in their phenotype, and also in the kind of care they need to receive because of the nature of their memory impairment.
00:09:31:18 - 00:09:58:17
Dr. Jason Karlawish
So it isn't just a fetishistic biomarker label. You know, it's a very relevant giving someone a clear diagnosis to why you're short of breath. It's not emphysema. It's actually pulmonary fibrosis. You know, we have this weird, like, cynicism about diagnostic specificity for causes of dementia, which I just don't follow because the fundamental role of a physician is answering a patient's problem.
00:09:58:19 - 00:10:10:00
Dr. Jason Karlawish
I know I'm short of breath. I'm fatigued. I'm forgetting whatever it may be, and I'm going to try and do the best I can to get you an answer for why you're short of breath, fatigued, losing weight, forgetful, whatever it may be.
00:10:10:03 - 00:10:30:12
Meryl Comer
Unfortunately, this becomes a family disease attached to the care. Does the spouse get in the way of an early diagnosis? As as we try to normalize things. What gets in the way from the familial side?
00:10:30:15 - 00:10:57:00
Dr. Jason Karlawish
Yeah. You're raising a very, very fascinating point. It's one I just finished an essay that's going to drop a little bit on stat called who Will Take Part in Your Care, namely, who's the person who's available, reliable and trustworthy to be around you. And you know, one of the points I make is, yeah, once upon a time, we just assumed caregivers came out of the woodwork or out of the trees, like like you know, leaves just appear in the spring.
00:10:57:02 - 00:11:18:15
Dr. Jason Karlawish
But, you know, that's not the case. They have to choose to take on the role. They have to choose to sort of figure out why there's a problem. And you're right. For many patients, a sort of normalization occurs, you know, as things are unfolding in the world around them, such that it's only when someone from the outside steps in and says, oh my God, what the heck's going on here?
00:11:18:18 - 00:11:40:05
Dr. Jason Karlawish
That, you know, action is finally taken. Having said that, I think, you know, for another cause for family members to sort of hesitate is fear the same fear that the patient's feeling, albeit in a different way, which is, I don't want this to be what's happening. So I'm just going to pretend it's not there. And this gets back to what we've been talking about, which is the need for this.
00:11:40:11 - 00:12:06:28
Dr. Jason Karlawish
And I think the emerging cultural transformation, because once I think you change the narrative around these diseases from out of fear to what I call a complex tragedy, and by that I mean these are not pleasant diseases. And you can't pretend that they are. But what you can do is say, there are ways out there now to get you answers to deliver care and treatment, to make this something that we can figure out how to live with.
00:12:07:00 - 00:12:28:01
Dr. Jason Karlawish
And this is what we're seeing in our study that you mentioned earlier that doctor, Clapp is leading around the decisions patients and caregivers make to take therapy. Many of those who take therapy explain. This gives me something to do. This gives me hope. This gives me a sense that I'm taking charge. And there's a tremendous feeling of self-control that they gain from that and empowerment.
00:12:28:04 - 00:12:49:28
Dr. Jason Karlawish
And I think as those narratives get out in culture, like the physician who was the yesterday that was recent, the Wall Street Journal, who talked about him, his being on treatment, it's going to begin to make the reluctant spouse, the reluctant adult child, typically a daughter. As you, though, go from saying, I'm going to pretend there's nothing wrong to saying you know, we really need to look into this.
00:12:50:01 - 00:12:53:27
Dr. Jason Karlawish
And so I do think that, those attitudes will start to change.
00:12:54:00 - 00:13:16:01
Meryl Comer
As, caregivers. And because I was one to both my husband and my mother. The goal is to protect a loved one's dignity. How do you measure dignity and autonomy? I would play to whatever strength my husband had as long as he had it. And then I want to move with the disease.
00:13:16:04 - 00:13:45:06
Dr. Jason Karlawish
I think the fundamental role of what you were doing for your husband, what I did for my father, was supporting his mind. And. And at once you do that and do it well, you then the support, dignity to the best of possibility. Your supporting agency, which is the vehicle through which people exercise their autonomy, agent of behavior, being able to make decisions, being able to make choices, etc..
00:13:45:09 - 00:14:05:20
Dr. Jason Karlawish
And so thinking about what you do as a caregiver is mind support, I think is a very helpful way to sort of capture the essence of all those many quotidian activities you do. And so it begins, I think, with a caregiver asking a very basic question of the person they're caring for. You know what is it like to be you?
00:14:05:22 - 00:14:25:27
Dr. Jason Karlawish
How can I remove the negative parts of that? Like he's very afraid. What do I need to do to keep them from being afraid? What sort of supports does he need? And so I like to kind of think of what a caregiver does is mind support. Like he's not able to drive anymore to the gym. I have to get him to the gym somehow.
00:14:26:00 - 00:14:48:17
Dr. Jason Karlawish
I recognize, though, that it's embarrassing for him to give up driving. So I need to find someone whose job is to take him to get food. So again, in summary, what you did, what I did. What caregivers do is they constantly ask you to answer the question. What is it like to be my relative? And based on what I'm perceiving, how can I support them?
00:14:48:19 - 00:15:06:17
Dr. Jason Karlawish
That the challenge, the tragedy, I think, is there comes a time often where it's very difficult to answer that question. I just don't know what it's like anymore to, you know, because it's just so difficult to perceive what she's feeling and thinking. And that captures the tragedy of being a caregiver, particularly as the disease advances.
00:15:06:19 - 00:15:42:06
Meryl Comer
Let's move into, some areas that have excited me as a former caregiver. The idea of wiring us up along with our. Yeah, spouse or patient. And so let us be part of the clinical trial because, excuse me, we're six times more likely to get dementia ourselves because of the intensity of care. So which ones do you see that are being used that really can sort of leap over that barrier to broader adoption?
00:15:42:09 - 00:16:07:01
Dr. Jason Karlawish
There's two categories. What I think of promising technologies. One is and it's right next to me here, my trusty smartphone. God love it. My little peripheral brain, my caregiver, which, you know, is it, has a host of ways that it can monitor how our brain is working. And you can throw in some gamified apps that are essentially testing your cognition as well.
00:16:07:04 - 00:16:29:27
Dr. Jason Karlawish
I just wrote a piece about a patient who didn't like playing Wordle. The New York Times game, but decided to do it because he realized it's a great memory test, and he started making mistakes on it, and he realized what he was feeling about his memory was real. The rest is a diagnosis. So I do think there's a role for these gamified ways to measure cognition patients and caregivers.
00:16:30:00 - 00:16:55:27
Dr. Jason Karlawish
I think the other, more, even more promising technologies are these unobtrusive in the home systems that monitor how you're functioning in your home. How you're using your stove, your refrigerator, etc.. This is a very hot area in the world of home appliance manufacturing. So the leading home appliance manufacturers have clearly doubled down on smart home based technologies.
00:16:55:29 - 00:17:18:27
Dr. Jason Karlawish
And they allow two things. Number one detection and monitoring. And number two, essentially delivery of care because the technologies can be controlled. You can remotely see how someone's using something and potentially also manipulate and use the technology. Will it be used in clinical trials as ways to measure endpoints? You know, it's incredibly attractive to see how they could.
00:17:18:29 - 00:17:41:11
Dr. Jason Karlawish
But the rigors of trials in terms of the need for consistent, valid data and, you know, the risk that's inherent when you change, you know, to adopt new endpoints. I think this these innovations are going to unfold outside of the realm of clinical trials and more in the realm of of care spaces and care delivery, frankly, even outside the medical infrastructure.
00:17:41:13 - 00:17:57:09
Meryl Comer
I was very excited by the idea of the technology because don't trust what I have to say or my observations or my characterizations. There's a collection of real world data. Now, there might be some, privacy issues.
00:17:57:11 - 00:18:20:25
Dr. Jason Karlawish
I agree, asking someone to look back over the last six weeks and say, so rate your relative on the scale. Probably is missing a host of signal and bringing in a lot of noise. And, you know, I don't want to overhype the, the, you know, in-home, unobtrusive monitoring, but, it gets to the heart of the individual and how they're doing.
00:18:20:28 - 00:18:45:14
Dr. Jason Karlawish
I, I think the obtrusive this issue needs to be addressed. I think once these are out in clinical practice, who will look at the data, how they will interpret it and how they will act on it, all need to be sorted out. I think it very interesting conversations unfolding in our culture. Silicon is starting to step up and to help care for us.
00:18:45:21 - 00:19:04:02
Dr. Jason Karlawish
To date, carbon humans have been doing all the care. And I think we're in a very interesting conversation about, you know, how much and in what ways can silicon based technologies do this, and when is a human needed? You know, and I play with these things of carbon and silicon to emphasize there's always going to be a role for humans.
00:19:04:02 - 00:19:14:04
Dr. Jason Karlawish
But we have to negotiate what that role is and where the appropriate places for silicon and AI to kind of an exciting future, that, that we face here.
00:19:14:06 - 00:19:23:28
Meryl Comer
All right. So how do you define a good life for someone living with dementia? And what do health systems have to do differently to support that?
00:19:24:04 - 00:19:54:05
Dr. Jason Karlawish
I think a good life for someone living with dementia is a life where they're allowed to, to where they receive having received adequate mind support. That individual is is is is being them. It's being you. That they have their is high up in their ability to have agency and and experiences they can possibly be. And by agency I mean the ability to think choose to side make decisions.
00:19:54:08 - 00:20:15:04
Dr. Jason Karlawish
And by experience I mean the ability to have experiences in the world to enjoy coffee with sugar or no sugar, as it were, etc., you know, get out and be amongst people, etc.. I mean, that to me is the good life for someone living with a diagnosis of Alzheimer's and Lewy body disease that's causing, say, mild stage dementia.
00:20:15:07 - 00:20:36:15
Dr. Jason Karlawish
And the responsibility, therefore is a health care system. And I do mean a health care system, as opposed to just a medical system that delivers the necessary mind support that they need to be themselves. That's my vision. I think it's attainable. I think it's the I think one of the right limiting steps is the health care.
00:20:36:15 - 00:20:53:07
Dr. Jason Karlawish
The medical system has to catch up. And it's not just doctors. There's a whole profession out there that's waiting to be created. It's sort of there, which is that person who can help you set up and monitor and change the technologies you need to monitor being you.
00:20:53:10 - 00:21:19:00
Meryl Comer
Do you think with early diagnosis, I have found that those with early diagnosis are the ones that are most deliberate about working on brain health and what they can do, and that 40% that's supposed to help you in terms of your daily living, sleep, all the things that that that are listed, along with the ordering. Right.
00:21:19:02 - 00:21:19:16
Dr. Jason Karlawish
Yeah.
00:21:19:18 - 00:21:21:10
Meryl Comer
But you track, you.
00:21:21:12 - 00:21:47:29
Dr. Jason Karlawish
Well, I think when you and I are saying early diagnosis, what we mean is a diagnosis before, say, solid, mild stage dementia. Certainly moderate. That's correct. Because by the time you label someone who's solid, mild stage, they're particularly, reduced in their age until abilities, you know, they're still good with experiences of joy, pleasure, pain, sadness, etc. although apathy oftentimes is a problem.
00:21:48:01 - 00:22:16:16
Dr. Jason Karlawish
The earlier a diagnosis is made, oftentimes the more subtle things are, and therefore there's some uncertainties around some of the tests, etc.. More importantly, these individuals are out in the world, oftentimes working etc.. And so you have to really be savvy and make sure they, have the service supports and, and particularly supports counseling to be able to handle this label and integrate, integrated their life and carry on as the person that they are.
00:22:16:18 - 00:22:26:11
Meryl Comer
So when you look at where we are now and diagnostics, strokes and care, what makes you most hopeful and what keeps you up at night?
00:22:26:13 - 00:23:06:19
Dr. Jason Karlawish
Yeah, I'm most hopeful about, the simultaneous advances in creating, accessible, accurate, diagnostics and, access to care through programs like the federal government's guide program. That gives me great hope that we're beginning to pivot from the neglect of, the the system that that that gives me hope, adding the therapeutics that we were just talking about and the innovations there, the hope amplifies what keeps me up at night is, kind of why I wrote the book.
00:23:06:21 - 00:23:32:07
Dr. Jason Karlawish
The Problem with Alzheimer's, which is the influence of politics and culture in this, you know, we're in a fraught conversation still in America about how are we going to care for people who are, older and disabled from dementia? We we we in the last 12 months, made changes to Medicaid that will be harmful to older Americans.
00:23:32:07 - 00:23:56:14
Dr. Jason Karlawish
Access to the services, the supports they need. We haven't had a mature conversation for years in this country about designing and necessary long term care services that supports the people need. And, I'll, I'll conclude with, the need to think thoughtfully about care for people at the very advanced stages is going to also keeps me up at night.
00:23:56:16 - 00:24:22:22
Dr. Jason Karlawish
I, I get bothered, by a kind of, attitude of death that surrounds, living with these diseases. I understand, that along the spectrum of the disease of dementia, it's it's it it's unpleasant and it's particularly unpleasant in the advanced stages. But I think we have to enter to a more mature conversation about when are we dying and how do we die of these diseases?
00:24:22:24 - 00:24:56:28
Meryl Comer
Listening to you, it it strikes me that, if you've seen the disease up close, you're somewhat changed forever. And as you look at what the prospects are, I think you look at them in a slightly different way. And, that's where the advocacy comes in. It sort of saves your life. You have to level the playing field in some way and fight it because, you know, it's the disease will ultimately win.
00:24:57:00 - 00:25:22:06
Dr. Jason Karlawish
That's why I call it a complex tragedy. You know, I realize a little high falutin, it sounds like you're in a graduate English class, but, you know, I mean, think of tales like Lear or or hamlet. Not Macbeth, but you know, where it's understood. This is not going to end pleasantly, you know? But how are we going to make sense of it?
00:25:22:06 - 00:25:27:23
Dr. Jason Karlawish
Live with this and that? That is why I appeal to the idea of complex tragedy.
00:25:27:28 - 00:25:58:15
Meryl Comer
You've been very generous with your time. Our guest has been Doctor Jason Karlawish, professor of medicine, medical ethics, health policy and neurology at the University of Pennsylvania, co-director of the Penn Memory Center. You can catch his podcast, The Age of Aging, dedicated to living well with an aging mind and neurotransmission and his essay in STAT that looks at the vast problems of dementia.
00:25:58:17 - 00:26:04:17
Meryl Comer
That's it for this edition. I'm Meryl Comer. Thank you for brainstorming with us.
00:26:04:19 - 00:26:13:15
Narrator
Subscribe to BrainStorm through your favorite podcast platform and join us for new episodes on the first and third Tuesday of every month.
About This Episode
Host Meryl Comer continues her conversation with Dr. Jason Karlawish, professor of medicine, medical ethics, and neurology at the University of Pennsylvania, about the evolving landscape of Alzheimer's disease. Drawing on his book The Problem with Alzheimer's, Dr. Karlawish explores the promise of early detection, the ethical complexities of disclosing uncertain diagnoses, and why he remains skeptical that an outright cure is on the near horizon — famously comparing it to planning retirement with a lottery ticket.
The conversation moves into the deeply human side of the disease, touching on caregiving as a form of "mind support," the role families play in both enabling and delaying diagnosis, and the exciting potential of smartphones and smart home technologies to transform care. Dr. Karlawish shares a candid reflection on what gives him hope and what keeps him up at night. This episode is a thoughtful, unflinching look at a disease that is best understood as a "complex tragedy."
Transcript
BRAINSTORM, EP #105
GUEST: DR. JASON KARLAWISH (PART 2)
00:00:00:04 - 00:00:20:24
Dr. Jason Karlawish
There's two categories of what I think are promising technologies. One is and it's right next to me here, my trusty smartphone. It has a host of ways that it can monitor how our brain is working. I just wrote a piece about a patient who didn't like playing Wordle, The New York Times game, but decided to do it because he realized it's a great memory test.
00:00:20:27 - 00:00:40:12
Narrator
Welcome to BrainStorm by UsAgainstAlzheimer's, a patient centered nonprofit organization. Your host, Meryl Comer, is a co-founder, 24 year caregiver, an Emmy Award winning journalist, and the author of the New York Times bestseller Slow Dancing with a Stranger.
00:00:40:15 - 00:01:17:06
Meryl Comer
This is BrainStorm, and I'm Meryl Comer. We continue our fascinating conversation with Doctor Jason Karlawish, professor of medicine, medical ethics, health policy and neurology at the University of Pennsylvania. He is also the author of The Problem with Alzheimer's. Today, we delve into the ethics and challenges of early diagnosis living with uncertainty and the need for a societal reset on the issue of cure versus care.
00:01:17:08 - 00:01:37:05
Meryl Comer
Jason, thank you for joining us. How might early detection influence the treatment options or long-term outcomes for those diagnosed? And I'm really careful not to call them patients. These are people living with the diagnosis in their 40s and 50s.
00:01:37:12 - 00:01:52:05
Dr. Jason Karlawish
This point you made about shouldn't call them patients. You know, I’ll confess as a physician, if you come and see me and I put a billing code on new. You're a patient. But that's just, you know, that's how I that's my world. And I'll just I'll.
00:01:52:08 - 00:01:55:00
Meryl Comer
We're trying to respect the world of advocacy.
00:01:55:03 - 00:02:19:12
Dr. Jason Karlawish
I hear you, I hear you. But that's just I just want to give that away, because I do use the word patient fairly freely and openly. I think what you're envisioning here, though, is a future where this disease, diseases really, are diagnosed in the 40s and 50s. And I think, we have to envision a future where and I'm not sure what the age will be, but at some age, you get some sort of test.
00:02:19:14 - 00:02:38:14
Dr. Jason Karlawish
I'm speaking in generalities here so as to not get people freaked out about what this test will be. And that test says you know what, Jason? You're at risk of developing cognitive impairment in the next ten years or you're not. And if you're in the group that's at risk, here's what we're going to do in terms of the next test or follow up down the road.
00:02:38:21 - 00:03:00:27
Dr. Jason Karlawish
And you only have to look at the progress that's been made in cardiovascular disease to begin to see how you could do this. Because in cardiovascular disease, you know, we've gotten to the point now where at about age 40 or so in LDL and some other tests begin to sort you into the group that does need further testing, follow up, and potentially treatments such as with a statin or not.
00:03:00:28 - 00:03:28:15
Dr. Jason Karlawish
In other words, check you in ten years. And so you could imagine if the approach of anti amyloid therapeutics that we're using now holds up. You could imagine very powerful, much safer, longer acting approaches to targeting amyloid that would prevent its accumulation in the first place. That's a vision. It's not a reality. But I will say it's this is the conversations I have with colleagues.
00:03:28:15 - 00:03:36:24
Dr. Jason Karlawish
This is sort of the way people are beginning to see and think as they sort of, I think, reasonably extrapolate what these technologies are capable of doing.
00:03:36:27 - 00:03:52:03
Meryl Comer
You know, Jason, because we haven't managed that issue of stigma well enough yet. What safeguards do you think need to be in place to minimize the risk or consequences of a misdiagnosis.
00:03:52:06 - 00:04:17:05
Dr. Jason Karlawish
Of a misdiagnosis? So in other words, someone's told you've got all survivors and then later on they're told, you know what, I don't think you do or you don't. But then later on, actually you do. Yeah. You know, both cases raise the need to address when you're doing these tests that there's uncertainty around them. Okay. That just because it's negative now doesn't mean it might not be positive later.
00:04:17:07 - 00:04:46:16
Dr. Jason Karlawish
Or just in the case of a positive test that in fact was negative. You have to think through some of those scenarios. Oftentimes it's because the testing wasn't done. You know, even now, there's no question people are walking around diagnoses who haven't gotten the appropriate testing that could confirm that diagnosis. So in all those cases, you know, I think the obligation of physicians to do one of the most uncomfortable things the doctors have to struggle to do, which is disclose uncertainty, to disclose the fact that this may not be certain.
00:04:46:18 - 00:05:12:20
Dr. Jason Karlawish
And I do think it's wise for a physician to counsel as well, to think carefully about who you're going to tell this information to and why you're going to tell it to them. But I think they have to be very thoughtful about telling it to people who are not very available, reliable and trustworthy. And who might therefore, for number, any number of reasons, exercise acts of, of of stigma and othering on the individual.
00:05:12:22 - 00:05:26:01
Dr. Jason Karlawish
I think this plays out a lot in spaces like the workforce, where, you know, many people might still be in the workforce and therefore, threat, threatened in their ability to perform in their job if other people know.
00:05:26:03 - 00:05:30:13
Meryl Comer
And once it's on your medical record, it's on your medical record. Right.
00:05:30:16 - 00:05:37:03
Dr. Jason Karlawish
Which plausibly should not be viewed by, you know, people in your job.
00:05:37:06 - 00:05:45:23
Meryl Comer
In your writing, you've compared the idea of a cure for Alzheimer's to planning your retirement with lottery tickets.
00:05:45:26 - 00:05:46:11
Dr. Jason Karlawish
Yeah.
00:05:46:14 - 00:05:58:15
Meryl Comer
Tell me, how should clinicians, advocates in the public, how do we recalibrate our expectation around cure versus care and risk reduction?
00:05:58:17 - 00:06:19:11
Dr. Jason Karlawish
You know, when I wrote that, I still stick with it, although maybe I might be willing to say, you know, there's there's a there's a greater than iota chance that we might be able in some of the presentations and forms of Alzheimer's, to block further progression such that if, you know, it becomes a non-issue, for the remainder of your life.
00:06:19:14 - 00:06:53:12
Dr. Jason Karlawish
But, yeah, I mean, the point I was getting at was these are complicated diseases. Oftentimes people have more than one other words. It's not uncommon. I just looked at a postmortem on a patient of mine who had Alzheimer's pathology, and also Lewy body pathology and TDP pathology. And so, you know, if you take all these pathology seriously and let's include vascular, the idea that we'll get to our 90th decade, 90th year, ninth decade, free of any cognitive problems is just an expectation that doesn't hold up to rational reasonableness.
00:06:53:14 - 00:07:22:07
Dr. Jason Karlawish
I think a lot of this really comes down to money. If you feel that the funds are tight, you get into a fight of care versus cure. If you feel that the funds are there, you're beginning to willing to take risks and grow. And certainly that was the case with cardiovascular disease and cancer. You know, those diseases had robust have robust business models that bring in the support needed to build the kind of infrastructure at cancer centers that allow people to get palliative care, along with curative treatments.
00:07:22:09 - 00:07:27:14
Dr. Jason Karlawish
I think we could we should envision the same thing for the problems that cause neurodegenerative diseases.
00:07:27:17 - 00:07:32:08
Meryl Comer
You've also written about undiagnosed a patient with dementia.
00:07:32:11 - 00:07:32:21
Dr. Jason Karlawish
Yeah.
00:07:32:29 - 00:07:38:29
Meryl Comer
What does undiagnosed mean in practice and when is it the right thing to do?
00:07:39:01 - 00:08:17:01
Dr. Jason Karlawish
Well, as you know, dementia, starts to become, risk as one enters their 60th, 70th year of life. It takes off after the 85th year. And, excuse me, after the 75th year. And what's what's been discovered in the last several years, is that one of the common causes of dementia in the 7580 plus group is limbic associated, age related TDP encephalopathy, otherwise known as late, late caused by a distinct pathology, TDP 43, distinct from Alzheimer's pathology, namely amyloid plaques and tangles.
00:08:17:03 - 00:08:43:17
Dr. Jason Karlawish
And I have several patients who I diagnosed with Alzheimer's disease, who I ran subsequently, biomarkers for Alzheimer's, as well as the imaging that gives supports a diagnosis of of late. And I undiagnosed them of Alzheimer's disease that they instead have late. And it's a rather incredible moment to say to someone based on this more definitive test than what I had before.
00:08:43:19 - 00:09:06:07
Dr. Jason Karlawish
You don't have Alzheimer's. You have this different, separate disease. I've had some people say to me, oh, well, why does it matter? You know, it's just dementia. And this gets back to the sort of 1990s, 1980s attitude. First of all, you're giving people facts that no longer mystery and people don't like uncertainty. Humans don't. Markets don't like uncertainty.
00:09:06:09 - 00:09:31:16
Dr. Jason Karlawish
It's called a bear market. What they like is facts that are certain. What's the answer? And once you know what's causing your problem, it lets you come to terms with it. Put a name on it. Moreover, there's a different prognosis for late versus Alzheimer's disease. They progress much slower. There's subtle but important differences in their phenotype, and also in the kind of care they need to receive because of the nature of their memory impairment.
00:09:31:18 - 00:09:58:17
Dr. Jason Karlawish
So it isn't just a fetishistic biomarker label. You know, it's a very relevant giving someone a clear diagnosis to why you're short of breath. It's not emphysema. It's actually pulmonary fibrosis. You know, we have this weird, like, cynicism about diagnostic specificity for causes of dementia, which I just don't follow because the fundamental role of a physician is answering a patient's problem.
00:09:58:19 - 00:10:10:00
Dr. Jason Karlawish
I know I'm short of breath. I'm fatigued. I'm forgetting whatever it may be, and I'm going to try and do the best I can to get you an answer for why you're short of breath, fatigued, losing weight, forgetful, whatever it may be.
00:10:10:03 - 00:10:30:12
Meryl Comer
Unfortunately, this becomes a family disease attached to the care. Does the spouse get in the way of an early diagnosis? As as we try to normalize things. What gets in the way from the familial side?
00:10:30:15 - 00:10:57:00
Dr. Jason Karlawish
Yeah. You're raising a very, very fascinating point. It's one I just finished an essay that's going to drop a little bit on stat called who Will Take Part in Your Care, namely, who's the person who's available, reliable and trustworthy to be around you. And you know, one of the points I make is, yeah, once upon a time, we just assumed caregivers came out of the woodwork or out of the trees, like like you know, leaves just appear in the spring.
00:10:57:02 - 00:11:18:15
Dr. Jason Karlawish
But, you know, that's not the case. They have to choose to take on the role. They have to choose to sort of figure out why there's a problem. And you're right. For many patients, a sort of normalization occurs, you know, as things are unfolding in the world around them, such that it's only when someone from the outside steps in and says, oh my God, what the heck's going on here?
00:11:18:18 - 00:11:40:05
Dr. Jason Karlawish
That, you know, action is finally taken. Having said that, I think, you know, for another cause for family members to sort of hesitate is fear the same fear that the patient's feeling, albeit in a different way, which is, I don't want this to be what's happening. So I'm just going to pretend it's not there. And this gets back to what we've been talking about, which is the need for this.
00:11:40:11 - 00:12:06:28
Dr. Jason Karlawish
And I think the emerging cultural transformation, because once I think you change the narrative around these diseases from out of fear to what I call a complex tragedy, and by that I mean these are not pleasant diseases. And you can't pretend that they are. But what you can do is say, there are ways out there now to get you answers to deliver care and treatment, to make this something that we can figure out how to live with.
00:12:07:00 - 00:12:28:01
Dr. Jason Karlawish
And this is what we're seeing in our study that you mentioned earlier that doctor, Clapp is leading around the decisions patients and caregivers make to take therapy. Many of those who take therapy explain. This gives me something to do. This gives me hope. This gives me a sense that I'm taking charge. And there's a tremendous feeling of self-control that they gain from that and empowerment.
00:12:28:04 - 00:12:49:28
Dr. Jason Karlawish
And I think as those narratives get out in culture, like the physician who was the yesterday that was recent, the Wall Street Journal, who talked about him, his being on treatment, it's going to begin to make the reluctant spouse, the reluctant adult child, typically a daughter. As you, though, go from saying, I'm going to pretend there's nothing wrong to saying you know, we really need to look into this.
00:12:50:01 - 00:12:53:27
Dr. Jason Karlawish
And so I do think that, those attitudes will start to change.
00:12:54:00 - 00:13:16:01
Meryl Comer
As, caregivers. And because I was one to both my husband and my mother. The goal is to protect a loved one's dignity. How do you measure dignity and autonomy? I would play to whatever strength my husband had as long as he had it. And then I want to move with the disease.
00:13:16:04 - 00:13:45:06
Dr. Jason Karlawish
I think the fundamental role of what you were doing for your husband, what I did for my father, was supporting his mind. And. And at once you do that and do it well, you then the support, dignity to the best of possibility. Your supporting agency, which is the vehicle through which people exercise their autonomy, agent of behavior, being able to make decisions, being able to make choices, etc..
00:13:45:09 - 00:14:05:20
Dr. Jason Karlawish
And so thinking about what you do as a caregiver is mind support, I think is a very helpful way to sort of capture the essence of all those many quotidian activities you do. And so it begins, I think, with a caregiver asking a very basic question of the person they're caring for. You know what is it like to be you?
00:14:05:22 - 00:14:25:27
Dr. Jason Karlawish
How can I remove the negative parts of that? Like he's very afraid. What do I need to do to keep them from being afraid? What sort of supports does he need? And so I like to kind of think of what a caregiver does is mind support. Like he's not able to drive anymore to the gym. I have to get him to the gym somehow.
00:14:26:00 - 00:14:48:17
Dr. Jason Karlawish
I recognize, though, that it's embarrassing for him to give up driving. So I need to find someone whose job is to take him to get food. So again, in summary, what you did, what I did. What caregivers do is they constantly ask you to answer the question. What is it like to be my relative? And based on what I'm perceiving, how can I support them?
00:14:48:19 - 00:15:06:17
Dr. Jason Karlawish
That the challenge, the tragedy, I think, is there comes a time often where it's very difficult to answer that question. I just don't know what it's like anymore to, you know, because it's just so difficult to perceive what she's feeling and thinking. And that captures the tragedy of being a caregiver, particularly as the disease advances.
00:15:06:19 - 00:15:42:06
Meryl Comer
Let's move into, some areas that have excited me as a former caregiver. The idea of wiring us up along with our. Yeah, spouse or patient. And so let us be part of the clinical trial because, excuse me, we're six times more likely to get dementia ourselves because of the intensity of care. So which ones do you see that are being used that really can sort of leap over that barrier to broader adoption?
00:15:42:09 - 00:16:07:01
Dr. Jason Karlawish
There's two categories. What I think of promising technologies. One is and it's right next to me here, my trusty smartphone. God love it. My little peripheral brain, my caregiver, which, you know, is it, has a host of ways that it can monitor how our brain is working. And you can throw in some gamified apps that are essentially testing your cognition as well.
00:16:07:04 - 00:16:29:27
Dr. Jason Karlawish
I just wrote a piece about a patient who didn't like playing Wordle. The New York Times game, but decided to do it because he realized it's a great memory test, and he started making mistakes on it, and he realized what he was feeling about his memory was real. The rest is a diagnosis. So I do think there's a role for these gamified ways to measure cognition patients and caregivers.
00:16:30:00 - 00:16:55:27
Dr. Jason Karlawish
I think the other, more, even more promising technologies are these unobtrusive in the home systems that monitor how you're functioning in your home. How you're using your stove, your refrigerator, etc.. This is a very hot area in the world of home appliance manufacturing. So the leading home appliance manufacturers have clearly doubled down on smart home based technologies.
00:16:55:29 - 00:17:18:27
Dr. Jason Karlawish
And they allow two things. Number one detection and monitoring. And number two, essentially delivery of care because the technologies can be controlled. You can remotely see how someone's using something and potentially also manipulate and use the technology. Will it be used in clinical trials as ways to measure endpoints? You know, it's incredibly attractive to see how they could.
00:17:18:29 - 00:17:41:11
Dr. Jason Karlawish
But the rigors of trials in terms of the need for consistent, valid data and, you know, the risk that's inherent when you change, you know, to adopt new endpoints. I think this these innovations are going to unfold outside of the realm of clinical trials and more in the realm of of care spaces and care delivery, frankly, even outside the medical infrastructure.
00:17:41:13 - 00:17:57:09
Meryl Comer
I was very excited by the idea of the technology because don't trust what I have to say or my observations or my characterizations. There's a collection of real world data. Now, there might be some, privacy issues.
00:17:57:11 - 00:18:20:25
Dr. Jason Karlawish
I agree, asking someone to look back over the last six weeks and say, so rate your relative on the scale. Probably is missing a host of signal and bringing in a lot of noise. And, you know, I don't want to overhype the, the, you know, in-home, unobtrusive monitoring, but, it gets to the heart of the individual and how they're doing.
00:18:20:28 - 00:18:45:14
Dr. Jason Karlawish
I, I think the obtrusive this issue needs to be addressed. I think once these are out in clinical practice, who will look at the data, how they will interpret it and how they will act on it, all need to be sorted out. I think it very interesting conversations unfolding in our culture. Silicon is starting to step up and to help care for us.
00:18:45:21 - 00:19:04:02
Dr. Jason Karlawish
To date, carbon humans have been doing all the care. And I think we're in a very interesting conversation about, you know, how much and in what ways can silicon based technologies do this, and when is a human needed? You know, and I play with these things of carbon and silicon to emphasize there's always going to be a role for humans.
00:19:04:02 - 00:19:14:04
Dr. Jason Karlawish
But we have to negotiate what that role is and where the appropriate places for silicon and AI to kind of an exciting future, that, that we face here.
00:19:14:06 - 00:19:23:28
Meryl Comer
All right. So how do you define a good life for someone living with dementia? And what do health systems have to do differently to support that?
00:19:24:04 - 00:19:54:05
Dr. Jason Karlawish
I think a good life for someone living with dementia is a life where they're allowed to, to where they receive having received adequate mind support. That individual is is is is being them. It's being you. That they have their is high up in their ability to have agency and and experiences they can possibly be. And by agency I mean the ability to think choose to side make decisions.
00:19:54:08 - 00:20:15:04
Dr. Jason Karlawish
And by experience I mean the ability to have experiences in the world to enjoy coffee with sugar or no sugar, as it were, etc., you know, get out and be amongst people, etc.. I mean, that to me is the good life for someone living with a diagnosis of Alzheimer's and Lewy body disease that's causing, say, mild stage dementia.
00:20:15:07 - 00:20:36:15
Dr. Jason Karlawish
And the responsibility, therefore is a health care system. And I do mean a health care system, as opposed to just a medical system that delivers the necessary mind support that they need to be themselves. That's my vision. I think it's attainable. I think it's the I think one of the right limiting steps is the health care.
00:20:36:15 - 00:20:53:07
Dr. Jason Karlawish
The medical system has to catch up. And it's not just doctors. There's a whole profession out there that's waiting to be created. It's sort of there, which is that person who can help you set up and monitor and change the technologies you need to monitor being you.
00:20:53:10 - 00:21:19:00
Meryl Comer
Do you think with early diagnosis, I have found that those with early diagnosis are the ones that are most deliberate about working on brain health and what they can do, and that 40% that's supposed to help you in terms of your daily living, sleep, all the things that that that are listed, along with the ordering. Right.
00:21:19:02 - 00:21:19:16
Dr. Jason Karlawish
Yeah.
00:21:19:18 - 00:21:21:10
Meryl Comer
But you track, you.
00:21:21:12 - 00:21:47:29
Dr. Jason Karlawish
Well, I think when you and I are saying early diagnosis, what we mean is a diagnosis before, say, solid, mild stage dementia. Certainly moderate. That's correct. Because by the time you label someone who's solid, mild stage, they're particularly, reduced in their age until abilities, you know, they're still good with experiences of joy, pleasure, pain, sadness, etc. although apathy oftentimes is a problem.
00:21:48:01 - 00:22:16:16
Dr. Jason Karlawish
The earlier a diagnosis is made, oftentimes the more subtle things are, and therefore there's some uncertainties around some of the tests, etc.. More importantly, these individuals are out in the world, oftentimes working etc.. And so you have to really be savvy and make sure they, have the service supports and, and particularly supports counseling to be able to handle this label and integrate, integrated their life and carry on as the person that they are.
00:22:16:18 - 00:22:26:11
Meryl Comer
So when you look at where we are now and diagnostics, strokes and care, what makes you most hopeful and what keeps you up at night?
00:22:26:13 - 00:23:06:19
Dr. Jason Karlawish
Yeah, I'm most hopeful about, the simultaneous advances in creating, accessible, accurate, diagnostics and, access to care through programs like the federal government's guide program. That gives me great hope that we're beginning to pivot from the neglect of, the the system that that that gives me hope, adding the therapeutics that we were just talking about and the innovations there, the hope amplifies what keeps me up at night is, kind of why I wrote the book.
00:23:06:21 - 00:23:32:07
Dr. Jason Karlawish
The Problem with Alzheimer's, which is the influence of politics and culture in this, you know, we're in a fraught conversation still in America about how are we going to care for people who are, older and disabled from dementia? We we we in the last 12 months, made changes to Medicaid that will be harmful to older Americans.
00:23:32:07 - 00:23:56:14
Dr. Jason Karlawish
Access to the services, the supports they need. We haven't had a mature conversation for years in this country about designing and necessary long term care services that supports the people need. And, I'll, I'll conclude with, the need to think thoughtfully about care for people at the very advanced stages is going to also keeps me up at night.
00:23:56:16 - 00:24:22:22
Dr. Jason Karlawish
I, I get bothered, by a kind of, attitude of death that surrounds, living with these diseases. I understand, that along the spectrum of the disease of dementia, it's it's it it's unpleasant and it's particularly unpleasant in the advanced stages. But I think we have to enter to a more mature conversation about when are we dying and how do we die of these diseases?
00:24:22:24 - 00:24:56:28
Meryl Comer
Listening to you, it it strikes me that, if you've seen the disease up close, you're somewhat changed forever. And as you look at what the prospects are, I think you look at them in a slightly different way. And, that's where the advocacy comes in. It sort of saves your life. You have to level the playing field in some way and fight it because, you know, it's the disease will ultimately win.
00:24:57:00 - 00:25:22:06
Dr. Jason Karlawish
That's why I call it a complex tragedy. You know, I realize a little high falutin, it sounds like you're in a graduate English class, but, you know, I mean, think of tales like Lear or or hamlet. Not Macbeth, but you know, where it's understood. This is not going to end pleasantly, you know? But how are we going to make sense of it?
00:25:22:06 - 00:25:27:23
Dr. Jason Karlawish
Live with this and that? That is why I appeal to the idea of complex tragedy.
00:25:27:28 - 00:25:58:15
Meryl Comer
You've been very generous with your time. Our guest has been Doctor Jason Karlawish, professor of medicine, medical ethics, health policy and neurology at the University of Pennsylvania, co-director of the Penn Memory Center. You can catch his podcast, The Age of Aging, dedicated to living well with an aging mind and neurotransmission and his essay in STAT that looks at the vast problems of dementia.
00:25:58:17 - 00:26:04:17
Meryl Comer
That's it for this edition. I'm Meryl Comer. Thank you for brainstorming with us.
00:26:04:19 - 00:26:13:15
Narrator
Subscribe to BrainStorm through your favorite podcast platform and join us for new episodes on the first and third Tuesday of every month.