BrainStorm
Chipping Away at the Crisis - A New Era in Alzheimer's Diagnosis and Treatment with Dr. Jason Karlawish
Chipping Away at the Crisis - A New Era in Alzheimer's Diagnosis and Treatment with Dr. Jason Karlawish
Alzheimer's disease is no longer just a memory problem — it's a biological, cultural, and ethical challenge reshaping how we think about aging, identity, and medicine. In this episode of Brainstorm by UsAgainstAlzheimers, host Meryl Comer sits down with Dr. Jason Karlawish, professor of medicine, medical ethics, health policy, and neurology at the University of Pennsylvania. They explore how Alzheimer's evolved from a rare condition into a full-blown public health crisis. Dr. Karlawish unpacks the science behind biomarker testing and early detection, the promise and complexity of new anti-amyloid treatments, and why so many physicians remain reluctant to diagnose cognitive decline at all. From health equity gaps that leave Latino and African American patients chronically underserved, to the ethical weight of disclosing an Alzheimer's diagnosis to someone still in the middle of their career, Dr. Karlawish brings both scientific precision and moral seriousness to one of medicine's most urgent conversations. It's a candid, wide-ranging discussion about what it truly means to confront a disease that strikes at the heart of who we are. You don’t want to miss this episode!
Produced by Susan Quirk
Transcript - Ep 103
00;00;00;02 - 00;00;21;13
Dr. Jason Karlawish
I am now telling people in life and early in their presentation. Alzheimer's is one of the causes or it is the it is not a cause, etc. and that has absolutely transformed not just how we talk about the disease, but also the illness experience. Because gone is the mystery that sort of surrounded these diagnoses. And you really don't know and really never sure.
00;00;21;15 - 00;00;24;04
Dr. Jason Karlawish
And now is that kind of certainty.
00;00;24;07 - 00;00;43;24
Narrator
Welcome to BrainStorm by UsAgainstAlzheimer's, a patient centered nonprofit organization. Your host, Meryl Comer, is a co-founder, 24 year caregiver and Emmy Award winning journalist and the author of the New York Times bestseller Slow Dancing with a Stranger.
00;00;43;27 - 00;01;20;16
Meryl Comer
This is BrainStorm, and I'm Meryl Comer. Today, Alzheimer's is increasingly defined by biological markers such as amyloid beta and changes serum blood tests or brain scans rather than symptoms alone. This means the disease can sometimes be detected years before memory loss begins or is outwardly evident. Joining us is Doctor Jason Karlawish, professor of medicine, medical ethics, health policy and neurology at the University of Pennsylvania.
00;01;20;18 - 00;01;31;17
Meryl Comer
He is also the author of The Problems of Alzheimer's and STAT's neurotransmission columns. Welcome, Doctor Karlawish. Thank you for joining us.
00;01;31;19 - 00;01;35;06
Dr. Jason Karlawish
Thank you. It's great to be here. Thanks so much for having me.
00;01;35;08 - 00;01;54;15
Meryl Comer
As co-director of the Penn Memory Center, you've written about how Alzheimer's went from a rare disease to a public health crisis. You've also argued that we created Alzheimer's as much as we discovered at. Give our audience a SparkNotes version of what you really mean.
00;01;54;17 - 00;02;20;27
Dr. Jason Karlawish
Sure. Yeah. Yeah. That's the central thesis of my book, The Problem of Alzheimer's. The subtitle is How Science, culture, and Politics turned a Rare disease into a crisis. Yeah. Simply put, you know, the Alzheimer's disease is a real disease. There's real pathobiology going on. But like all diseases, there's aspects of social construction. That is to say, it takes humans to turn this into a disease and therefore have an illness experience at the beginning of the 20th century.
00;02;20;27 - 00;02;39;06
Dr. Jason Karlawish
We were still debating what it meant to be a fully autonomous adult. Well, that all kind of got sorted out by the mid to late 20th century, such that losing one's autonomy became a dreaded event in life. And I think that was one of the cultural events that had us look at aging and say, losing one's mind is pretty awful.
00;02;39;09 - 00;02;58;09
Dr. Jason Karlawish
Science comes along and says, well, in fact, that might be because there's problems in the brain pathology. So maybe we could help. So those were two events in science and culture that really moved what was considered normal aging. And just that's what happens to older adults to something we just didn't really like. And we ought to do something about it.
00;02;58;11 - 00;03;06;10
Dr. Jason Karlawish
So that's how science, culture and politics all work together to take what was a rare disease, turn it into a common one and then make it a crisis.
00;03;06;13 - 00;03;25;24
Meryl Comer
Well, we're now diagnosing Alzheimer's earlier and earlier, as sometimes in people with no symptoms based on biomarkers alone. How early do you think we should be offering biomarker testing to patients, and what safeguards need to be in place around disclosure and follow up?
00;03;25;26 - 00;03;51;12
Dr. Jason Karlawish
Right now, I think the science supports using biomarkers to diagnose Alzheimer's and also some of the other causes of dementia, like Lewy body disease, where we could get biomarkers. I think the science supports it in individuals who are having signs and symptoms of changes in their cognition, perception and behavior that raise the concern of a neurodegenerative disease. I don't think the science is here yet to use that.
00;03;51;12 - 00;04;16;27
Dr. Jason Karlawish
Those technologies in individuals who have absolutely no cognitive problems. We're very close, though, as if potentially within 12, 24 months when they move into that space. The safeguards that are needed for individuals who have symptoms, I think revolve a lot around, getting a proper informed consent, around, the, the knowledge, the uncertainties that surround these tests.
00;04;16;29 - 00;04;23;22
Dr. Jason Karlawish
And how people will use them if they, do get the results, and how they'll impact their lives.
00;04;23;24 - 00;04;35;11
Meryl Comer
What have you learned from your Greenwald Foundation funded work on how people decide whether you should take these new treatments, and what surprises you about their decision making.
00;04;35;13 - 00;04;58;20
Dr. Jason Karlawish
I'm so glad you brought that study up. We've got funding from the Greenwald Foundation, which is a foundation, based out of New York, that focuses on bioethics research. And my colleague Justin Clapp at Pandas and medical anthropologist leads the study, and he's embedded himself in our Alzheimer's Center to learn how the clinicians are using these extraordinarily new treatments, the anti-malaria antibodies and the related biomarkers for diagnosis.
00;04;58;23 - 00;05;25;08
Dr. Jason Karlawish
He also interviewed all the clinicians prescribing and, most importantly, interviewed patients and caregivers who chose to take therapy or chose not to take therapy. And we're in the midst of analyzing those data now. So some highlight points. It's a complicated decision. Granted, for some, it's a no brainer, no pun intended. You know, we're going to do this, but once in the group where there's deliberation, there's a host of factors there.
00;05;25;08 - 00;05;45;24
Dr. Jason Karlawish
And what struck me as most interesting is the interrelated interests and needs of both the patient and the caregiver with respect to whether this therapy is the right thing to do. The therapies are a lot of work. They're not a guarantee of success. And they come with risks. And in individuals who, have impairment, it's a tough decision to make.
00;05;45;26 - 00;06;06;09
Dr. Jason Karlawish
And for family members, it's a tough decision to make. Whether now's the right time to want to slow this disease down or not. And for some, that leads to the decision to say, you know, it's too late right now. Granted, most have been wanting to take the therapy, but for concerns about the risks, or it's not appropriate for them after their work done.
00;06;06;11 - 00;06;22;23
Meryl Comer
USA Two's Brain guide recently had its 1 million visitor for its confidential memory questionnaire and resources for doctors. Follow up available clinical trials, brain health supplements are projected to reach about $20 billion.
00;06;22;29 - 00;06;23;13
Dr. Jason Karlawish
Is that all.
00;06;23;20 - 00;06;43;01
Meryl Comer
You 31 and cognition supplements alone? Another variety at 27.4 billion in 2030. So I guess my question is, are younger cohorts likely to have different attitudes about knowing their risk status in particular?
00;06;43;04 - 00;07;12;13
Dr. Jason Karlawish
Yeah, absolutely. And this gets back to the culture point where we're talking about, I think, individuals. I'm just going to put a rough number here 50 and under. They grew up in a world where autonomy, individuality, becoming a person was just part of the culture we lived in. And I think they amplify the threat that is dementia, appropriately, namely, I don't want to lose my ability to be me.
00;07;12;15 - 00;07;42;29
Dr. Jason Karlawish
That doesn't mean a selfish me. It just means me enjoying and being a genitive in the world, perhaps wrapped up in a host of interesting relationships. And I think, for that cohort, especially the threat of dementia is particularly dreaded, not viewed as something to be, well, it's just part of life, etc.. And yes, I think the fact that the industries for supplements, testing are taking off, I think shows the desire for people to get information and do something.
00;07;43;01 - 00;07;59;02
Dr. Jason Karlawish
Now, we could debate whether what they're doing is worth their time and money. But I think that their behavior, their willingness to put their money on these things shows you the interest in wanting to do something about this disease, which is very different. I think you and I can both remember from, say, 30 years ago when it was just indifference and whatnot.
00;07;59;04 - 00;08;18;25
Meryl Comer
You know, there are blood tests for Alzheimer's. There are also genetic tests. I took the genetic test. I know I'm a three for, so I know my risk profile is higher. What does each test tell you as a doctor, and how do you decide when to use them? And what's the difference?
00;08;18;27 - 00;08;51;04
Dr. Jason Karlawish
Yeah, well, the genetic test, you know, your genes where your genes, the moment your zygote was sort of created even before it implanted on your, mother's, womb. And so those are your genes. I'm not discounting their role in risk. I think the more interesting measures together are the biomarkers, namely their measures of pathophysiology. So the dynamic appearance of signs of a disease unfolding in a body, the biomarkers are allowing us to say to someone who has signs and symptoms, whether one of the causes of their signs and symptoms is Alzheimer's or Lewy body disease.
00;08;51;04 - 00;09;12;16
Dr. Jason Karlawish
We're getting close with also with TDP disease, which causes late, that has utterly revolutionized clinical practice. I've been doing this now since basically 1998, since the last century. And, you know, for a long time, diagnoses were probable meaning. Here's what I think it might be. It really looks like this. I'll follow you along. That might firm up the certainty.
00;09;12;18 - 00;09;37;17
Dr. Jason Karlawish
Ultimately, though, the certainty will arrive when I can get your brain tissue. But of course, that means you have to die. Rather gruesome than the neuropathologist will tell us what happened. Well, those days are beginning to fade. I am now telling people in life, and early in their presentation, Alzheimer's is one of the causes, or it is the it is not a cause, etc. and that has absolutely transformed not just how we talk about the disease, but also the illness experience.
00;09;37;20 - 00;10;00;22
Dr. Jason Karlawish
Because God is the mystery that's sort of surrounded these diagnoses. You really don't know, you really never sure, etc.. And now is that kind of certainty. The the test that I think is most interesting is the ability to measure tau using a Pet scan, because there I can actually show you in your brain where the disease is unfolding.
00;10;00;25 - 00;10;07;03
Dr. Jason Karlawish
So it's not just that it's there. It's here it is. And that's why you're having trouble with your mental map.
00;10;07;05 - 00;10;21;13
Meryl Comer
You know, you keep mentioning, signs and symptoms. So men tell me the signs and symptoms that would prompt you to say, it's the right time to take the blood test for Alzheimer's disease.
00;10;21;15 - 00;10;49;09
Dr. Jason Karlawish
Changes in cognitive abilities that are causing either inefficiencies or disabilities in daily life. So what do I mean by inefficiencies? It takes you longer to get things done that you used to do at a quicker, easier pace, finances without cooking, etc.. Disabilities. You're making mistakes, that you might catch or others catch that need to work up. And depending on that workup it may lead to may lead to getting a biomarker test.
00;10;49;11 - 00;11;10;03
Dr. Jason Karlawish
And the reason why I say May is there are a host of reasons, particularly for the inefficiencies in daily life caused by cognitive problems that are not neurodegenerative, poorly treated sleep apnea. I saw someone who was on a regular daily dose of, Benadryl for sleep and out of and, and, frankly, also a little bit too much hooch.
00;11;10;05 - 00;11;17;20
Dr. Jason Karlawish
You know, all those behaviors taken away, the cognition improved, etc.. But that part of the workup.
00;11;17;22 - 00;11;28;14
Meryl Comer
Is there a direct correlation between a positive result on a blood test and a timeline for a formal Alzheimer's and mixed dementia diagnosis?
00;11;28;17 - 00;11;49;21
Dr. Jason Karlawish
Well, that's getting to the, the way the variability is in clinical practice across America. You know, you can get some of these blood tests through the direct to consumer route is at least six companies offering it. I do not recommend folks pursuing that avenue. I've looked at the websites. I'm not confident, in in the, in the cut points they're using.
00;11;49;23 - 00;12;12;04
Dr. Jason Karlawish
Moreover, you know, they're not terribly well attached to, the kind of additional workup one needs. But, you know, once it's prescribed by a physician, it ought to be coupled to a clear plan for follow up and etc. warning to your listeners. The Cures Act, the act of Congress that did a whole host of modifications to Medicare.
00;12;12;10 - 00;12;31;23
Dr. Jason Karlawish
One of its requirements is all test results. All medical records are available to patients the moment they're created. So here's a heads up to to listeners. You get an Alzheimer's blood test. It's going to pop into your medical record. And you're going to get that ping on your, email. You know, you've got test results in your My Penn Medicine account.
00;12;31;23 - 00;12;48;02
Dr. Jason Karlawish
Log in and look, I strongly counsel my folks. You're welcome to look, but I would I would urge you simply to wait until we have our follow up visit to go over the results. And let me help you interpret them, as opposed to just seeing this cut point and what it says.
00;12;48;05 - 00;13;17;05
Meryl Comer
You know, different communities have different risks for Alzheimer's. I mean, the Latino population begins showing symptoms perhaps seven years earlier than non-Hispanic whites. African Americans twice as likely to develop dementia, but 35% less likely to be diagnosed at all. How do we ensure equity in getting to a timely diagnosis and then everyone's being screened appropriately?
00;13;17;07 - 00;13;53;12
Dr. Jason Karlawish
Well, I think, the inequities around timely diagnosis that you're showing reflect larger inequities in our health care system. Where access is often limited based on income, etc.. And, I think the big challenge that all of America faces, which is amplified in this topic of, that you've raised, is we do not have the adequate infrastructure set up to properly address the challenge of diagnosing and treating the many, frankly, millions of Americans who, I have cognitive impairment.
00;13;53;14 - 00;14;19;18
Dr. Jason Karlawish
And, I'll give you one very focused problem. If you finish a medical residency, if you finish a neurology residency in the United States, the odds are you did not get any substantial training in cognitive neurology. You got great training in stroke, epilepsy, neuro critical care, but very little with any training in cognitive urology, which is the field that is skilled in the diagnosis and treatment of Alzheimer's disease.
00;14;19;18 - 00;14;42;15
Dr. Jason Karlawish
And other diseases. If you finish a geriatrics residency, you're pretty good at dying of fellowship jerks. Fellowship. You're pretty good at diagnosing dementia, but that's about as that's often for many. That's about as far as they get. So there's a real need to train a workforce competent to do this. And the problems you raised around, inequities of diagnosis only amplify the need to address this.
00;14;42;17 - 00;14;57;27
Meryl Comer
You know, you've written about the reluctance of among doctors to diagnose for Alzheimer's or related cognitive disorders. What factors do you believe contribute most to the hesitation within the medical profession is here.
00;14;57;27 - 00;15;22;20
Dr. Jason Karlawish
I reached to the Bible, to the book of Genesis, where once dinosaurs roamed the earth, there are some dinosaurs roaming the medical hallways, namely physicians who just don't get it. They don't feel the need to do this. I think it reflects a couple things explicit and a couple implicit. Explicit. They don't think there's anything you can do, nothing to do, and they're of the view.
00;15;22;20 - 00;15;29;16
Dr. Jason Karlawish
Well, in the end, just the women will take care of these people that do it anyway. So what's the point in diagnosing? It's a view locked in about 1984.
00;15;29;16 - 00;15;30;23
Meryl Comer
Don't depress them.
00;15;30;26 - 00;15;49;00
Dr. Jason Karlawish
I think a lot of it though is they don't have the skill and doctors do not like to admit two things uncertainty and lack of skill. At other words, it's very hard for doctor to say, you know what the problem you're telling me is? One that I don't really feel confident working up, and I need to find someone else who can take care of it.
00;15;49;02 - 00;16;12;08
Dr. Jason Karlawish
You know, early stage assessments are often haunted by uncertainty about whether or not there's a problem here until you really do a good workup. Doctors don't like to admit those things, so I think there's a host of physicians out there who have these implicit and explicit biases, and we see this in our own health system. We are attempting to transform, my friend and colleague, Doctor Cara O'Brien, Penn Medicine.
00;16;12;08 - 00;16;27;26
Dr. Jason Karlawish
And we're making great progress. But in doing this, we are encountering some physicians who will write back to us and say, I don't understand why we would do this. There's nothing you can do. It's not very accurate. All we're going to do is depress these people. But the good news is we've got plenty of physicians who are like, thank you.
00;16;28;02 - 00;16;40;14
Dr. Jason Karlawish
Get me these tools, get me the training. I really want to make this part of my practice. And I think again, back to Genesis. Once upon a time, dinosaurs roamed the Earth. I think over time, these dinosaurs will no longer roam the earth.
00;16;40;16 - 00;16;48;28
Meryl Comer
I attributed it to paternalism, which really always upset me. Just tell me what it is. If you know or tell me you don't know.
00;16;49;05 - 00;17;05;06
Dr. Jason Karlawish
Dan Gibbs, the physician who has Alzheimer's, admits that the patients he least liked working up were the dementia patients when he was neurologist. And it was part of it was there's nothing you can really do with the uncertainty. That's surrounded. That's a big that's a step a doctor has to take when it comes to, a dementia workup.
00;17;05;06 - 00;17;25;07
Dr. Jason Karlawish
I'm not very good at working this up. I need to have someone to refer to. But then that gets to our other problem. Who do you send them to? And this is the wait list that we have at the memory center. At six months. We had a whole new patient appointments because we had such a backlog. We said if we don't just stop taking in new patients, we'll never get through this backlog.
00;17;25;12 - 00;17;51;10
Meryl Comer
You mentioned stigma. The greatest concern for many advocates is that it's just trending younger with earlier diagnosis. So my question is what ethical considerations arise when clinicians must disclose uncertainty to individuals diagnosed with Alzheimer's in midlife, compared to those diagnosed later in life?
00;17;51;13 - 00;18;12;15
Dr. Jason Karlawish
I think the diagnoses in individuals under the classic ages of retirement, 6570 have some unique challenges, and they relate to aspects of the 55th six decade of life for many or decades, a very important.
00;18;12;18 - 00;18;36;26
Dr. Jason Karlawish
Acceleration of bringing in income. And so it's a tough diagnosis to give someone who's 58 and now very well is going to have to step out of the workforce. And, and if they're in the workforce, which many are, the other challenges, if they went back to the job and said, oh, I've got some news.
00;18;36;29 - 00;18;51;07
Dr. Jason Karlawish
You know, the employment discrimination that they are going to face is real and vivid. This gets back to the stigma. This is a public stigma issue. And so these matters are intense important. So I think and a huge social policy issue that we're going to need to face.
00;18;51;09 - 00;19;07;29
Meryl Comer
Do you think that our current labels, mild cognitive impairment, MCI, dementia, Alzheimer's? I mean, when you label someone, you label them and does it help or harm patients, families, clinicians?
00;19;08;02 - 00;19;34;13
Dr. Jason Karlawish
Well, you know, the nomenclature in this field is really in a big flux. You know, once upon a time, Alzheimer's and dementia were synonymous terms because if you didn't have dementia, you couldn't have Alzheimer's. And that lingers still in some of our nomenclature. And I could go on. I will with Alzheimer's has at least three meanings synonymous with dementia a path, a physiologic entity defined by tau and, plaques, tau tangles and amyloid plaques.
00;19;34;15 - 00;20;01;25
Dr. Jason Karlawish
And it's also used as an umbrella term to describe all causes, if you will, of dementia. So, you know, and then you put MCI in the mix and it only gets more complicated. Having said that, dementia is the problem. Okay? I mean, if we didn't have disabling cognitive impairments, this wouldn't be so bad. I'm not trying to say MCI is not a problem, but you know, one can figure out how to live with MCI as well as dementia for most patients.
00;20;01;25 - 00;20;23;19
Dr. Jason Karlawish
We should not stop at a label of MCI or dementia. The next question is what's causing what's the disease or diseases? And in some cases, the answer is I'm not sure. The tests I've done are are indeterminate or negative. But I think we owe people that final as close to final answer as what disease or diseases might be causing this.
00;20;23;23 - 00;20;47;16
Dr. Jason Karlawish
I do think the MCI term, it has a historical problem to it, namely, it was a risk factor for Alzheimer's back when to have Alzheimer's meant you had to have dementia. And so it's sort of caught in this kind of weird historical moment when I remember telling people, you've got MCI, it's a risk factor for Alzheimer's. Well, that's just not the case anymore.
00;20;47;23 - 00;21;07;24
Dr. Jason Karlawish
I can tell you that you have MCI caused by Alzheimer's based on the results of biomarker tests and really good phenotyping. And so I'm kind of left with what's the value of the MCI label? And because the other problem I have with is it the very name kind of makes it sound like a kind of nothing burger, you know?
00;21;07;26 - 00;21;18;17
Dr. Jason Karlawish
And it also just says back to the patient what they've told you. Anyway, I've got cognitive impairment and it's sort of mild. And so it just it's a quirky term that I'd like to kind of see replaced and retired.
00;21;18;20 - 00;21;23;06
Meryl Comer
There are groups out there trying to get rid of the term dementia, which is a medical term.
00;21;23;08 - 00;21;53;15
Dr. Jason Karlawish
Yeah. I'm not ready to retire dementia. I think we can learn to live with it because we'll as we change the mystery that surrounds dementia. I think there's a larger thing going on here that the mystery and the horror that surrounds Alzheimer's and dementia is beginning to be chipped away at the ability to diagnose people and explain what's wrong in the case of Alzheimer's, the ability to treat it with their time with therapies, the ability of our, the beginning to provide better services and supports the things like the guide program.
00;21;53;17 - 00;22;23;12
Dr. Jason Karlawish
So that's why I think this like, let's stop using the word dementia is a kind of a language police solution to a larger cultural problem, which will work itself out. Now, it doesn't help when politics politicians use dementia as a cudgel against their opponents, which was done in the last election. And so there's some need for a little more mature behavior, if it's possible, in some of the spheres of culture which enjoy using, dementia as a political cudgel.
00;22;23;15 - 00;22;54;00
Meryl Comer
You've been very generous with your time. Our guest 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. Essays in STAT that looks at the vast problems of dementia.
00;22;54;02 - 00;23;00;03
Meryl Comer
That's it for this edition. I'm Meryl Comer. Thank you for brainstorming with us.
00;23;00;06 - 00;23;09;03
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
Alzheimer's disease is no longer just a memory problem — it's a biological, cultural, and ethical challenge reshaping how we think about aging, identity, and medicine. In this episode of Brainstorm by UsAgainstAlzheimers, host Meryl Comer sits down with Dr. Jason Karlawish, professor of medicine, medical ethics, health policy, and neurology at the University of Pennsylvania. They explore how Alzheimer's evolved from a rare condition into a full-blown public health crisis. Dr. Karlawish unpacks the science behind biomarker testing and early detection, the promise and complexity of new anti-amyloid treatments, and why so many physicians remain reluctant to diagnose cognitive decline at all. From health equity gaps that leave Latino and African American patients chronically underserved, to the ethical weight of disclosing an Alzheimer's diagnosis to someone still in the middle of their career, Dr. Karlawish brings both scientific precision and moral seriousness to one of medicine's most urgent conversations. It's a candid, wide-ranging discussion about what it truly means to confront a disease that strikes at the heart of who we are. You don’t want to miss this episode!
Produced by Susan Quirk
Transcript
Transcript - Ep 103
00;00;00;02 - 00;00;21;13
Dr. Jason Karlawish
I am now telling people in life and early in their presentation. Alzheimer's is one of the causes or it is the it is not a cause, etc. and that has absolutely transformed not just how we talk about the disease, but also the illness experience. Because gone is the mystery that sort of surrounded these diagnoses. And you really don't know and really never sure.
00;00;21;15 - 00;00;24;04
Dr. Jason Karlawish
And now is that kind of certainty.
00;00;24;07 - 00;00;43;24
Narrator
Welcome to BrainStorm by UsAgainstAlzheimer's, a patient centered nonprofit organization. Your host, Meryl Comer, is a co-founder, 24 year caregiver and Emmy Award winning journalist and the author of the New York Times bestseller Slow Dancing with a Stranger.
00;00;43;27 - 00;01;20;16
Meryl Comer
This is BrainStorm, and I'm Meryl Comer. Today, Alzheimer's is increasingly defined by biological markers such as amyloid beta and changes serum blood tests or brain scans rather than symptoms alone. This means the disease can sometimes be detected years before memory loss begins or is outwardly evident. Joining us is Doctor Jason Karlawish, professor of medicine, medical ethics, health policy and neurology at the University of Pennsylvania.
00;01;20;18 - 00;01;31;17
Meryl Comer
He is also the author of The Problems of Alzheimer's and STAT's neurotransmission columns. Welcome, Doctor Karlawish. Thank you for joining us.
00;01;31;19 - 00;01;35;06
Dr. Jason Karlawish
Thank you. It's great to be here. Thanks so much for having me.
00;01;35;08 - 00;01;54;15
Meryl Comer
As co-director of the Penn Memory Center, you've written about how Alzheimer's went from a rare disease to a public health crisis. You've also argued that we created Alzheimer's as much as we discovered at. Give our audience a SparkNotes version of what you really mean.
00;01;54;17 - 00;02;20;27
Dr. Jason Karlawish
Sure. Yeah. Yeah. That's the central thesis of my book, The Problem of Alzheimer's. The subtitle is How Science, culture, and Politics turned a Rare disease into a crisis. Yeah. Simply put, you know, the Alzheimer's disease is a real disease. There's real pathobiology going on. But like all diseases, there's aspects of social construction. That is to say, it takes humans to turn this into a disease and therefore have an illness experience at the beginning of the 20th century.
00;02;20;27 - 00;02;39;06
Dr. Jason Karlawish
We were still debating what it meant to be a fully autonomous adult. Well, that all kind of got sorted out by the mid to late 20th century, such that losing one's autonomy became a dreaded event in life. And I think that was one of the cultural events that had us look at aging and say, losing one's mind is pretty awful.
00;02;39;09 - 00;02;58;09
Dr. Jason Karlawish
Science comes along and says, well, in fact, that might be because there's problems in the brain pathology. So maybe we could help. So those were two events in science and culture that really moved what was considered normal aging. And just that's what happens to older adults to something we just didn't really like. And we ought to do something about it.
00;02;58;11 - 00;03;06;10
Dr. Jason Karlawish
So that's how science, culture and politics all work together to take what was a rare disease, turn it into a common one and then make it a crisis.
00;03;06;13 - 00;03;25;24
Meryl Comer
Well, we're now diagnosing Alzheimer's earlier and earlier, as sometimes in people with no symptoms based on biomarkers alone. How early do you think we should be offering biomarker testing to patients, and what safeguards need to be in place around disclosure and follow up?
00;03;25;26 - 00;03;51;12
Dr. Jason Karlawish
Right now, I think the science supports using biomarkers to diagnose Alzheimer's and also some of the other causes of dementia, like Lewy body disease, where we could get biomarkers. I think the science supports it in individuals who are having signs and symptoms of changes in their cognition, perception and behavior that raise the concern of a neurodegenerative disease. I don't think the science is here yet to use that.
00;03;51;12 - 00;04;16;27
Dr. Jason Karlawish
Those technologies in individuals who have absolutely no cognitive problems. We're very close, though, as if potentially within 12, 24 months when they move into that space. The safeguards that are needed for individuals who have symptoms, I think revolve a lot around, getting a proper informed consent, around, the, the knowledge, the uncertainties that surround these tests.
00;04;16;29 - 00;04;23;22
Dr. Jason Karlawish
And how people will use them if they, do get the results, and how they'll impact their lives.
00;04;23;24 - 00;04;35;11
Meryl Comer
What have you learned from your Greenwald Foundation funded work on how people decide whether you should take these new treatments, and what surprises you about their decision making.
00;04;35;13 - 00;04;58;20
Dr. Jason Karlawish
I'm so glad you brought that study up. We've got funding from the Greenwald Foundation, which is a foundation, based out of New York, that focuses on bioethics research. And my colleague Justin Clapp at Pandas and medical anthropologist leads the study, and he's embedded himself in our Alzheimer's Center to learn how the clinicians are using these extraordinarily new treatments, the anti-malaria antibodies and the related biomarkers for diagnosis.
00;04;58;23 - 00;05;25;08
Dr. Jason Karlawish
He also interviewed all the clinicians prescribing and, most importantly, interviewed patients and caregivers who chose to take therapy or chose not to take therapy. And we're in the midst of analyzing those data now. So some highlight points. It's a complicated decision. Granted, for some, it's a no brainer, no pun intended. You know, we're going to do this, but once in the group where there's deliberation, there's a host of factors there.
00;05;25;08 - 00;05;45;24
Dr. Jason Karlawish
And what struck me as most interesting is the interrelated interests and needs of both the patient and the caregiver with respect to whether this therapy is the right thing to do. The therapies are a lot of work. They're not a guarantee of success. And they come with risks. And in individuals who, have impairment, it's a tough decision to make.
00;05;45;26 - 00;06;06;09
Dr. Jason Karlawish
And for family members, it's a tough decision to make. Whether now's the right time to want to slow this disease down or not. And for some, that leads to the decision to say, you know, it's too late right now. Granted, most have been wanting to take the therapy, but for concerns about the risks, or it's not appropriate for them after their work done.
00;06;06;11 - 00;06;22;23
Meryl Comer
USA Two's Brain guide recently had its 1 million visitor for its confidential memory questionnaire and resources for doctors. Follow up available clinical trials, brain health supplements are projected to reach about $20 billion.
00;06;22;29 - 00;06;23;13
Dr. Jason Karlawish
Is that all.
00;06;23;20 - 00;06;43;01
Meryl Comer
You 31 and cognition supplements alone? Another variety at 27.4 billion in 2030. So I guess my question is, are younger cohorts likely to have different attitudes about knowing their risk status in particular?
00;06;43;04 - 00;07;12;13
Dr. Jason Karlawish
Yeah, absolutely. And this gets back to the culture point where we're talking about, I think, individuals. I'm just going to put a rough number here 50 and under. They grew up in a world where autonomy, individuality, becoming a person was just part of the culture we lived in. And I think they amplify the threat that is dementia, appropriately, namely, I don't want to lose my ability to be me.
00;07;12;15 - 00;07;42;29
Dr. Jason Karlawish
That doesn't mean a selfish me. It just means me enjoying and being a genitive in the world, perhaps wrapped up in a host of interesting relationships. And I think, for that cohort, especially the threat of dementia is particularly dreaded, not viewed as something to be, well, it's just part of life, etc.. And yes, I think the fact that the industries for supplements, testing are taking off, I think shows the desire for people to get information and do something.
00;07;43;01 - 00;07;59;02
Dr. Jason Karlawish
Now, we could debate whether what they're doing is worth their time and money. But I think that their behavior, their willingness to put their money on these things shows you the interest in wanting to do something about this disease, which is very different. I think you and I can both remember from, say, 30 years ago when it was just indifference and whatnot.
00;07;59;04 - 00;08;18;25
Meryl Comer
You know, there are blood tests for Alzheimer's. There are also genetic tests. I took the genetic test. I know I'm a three for, so I know my risk profile is higher. What does each test tell you as a doctor, and how do you decide when to use them? And what's the difference?
00;08;18;27 - 00;08;51;04
Dr. Jason Karlawish
Yeah, well, the genetic test, you know, your genes where your genes, the moment your zygote was sort of created even before it implanted on your, mother's, womb. And so those are your genes. I'm not discounting their role in risk. I think the more interesting measures together are the biomarkers, namely their measures of pathophysiology. So the dynamic appearance of signs of a disease unfolding in a body, the biomarkers are allowing us to say to someone who has signs and symptoms, whether one of the causes of their signs and symptoms is Alzheimer's or Lewy body disease.
00;08;51;04 - 00;09;12;16
Dr. Jason Karlawish
We're getting close with also with TDP disease, which causes late, that has utterly revolutionized clinical practice. I've been doing this now since basically 1998, since the last century. And, you know, for a long time, diagnoses were probable meaning. Here's what I think it might be. It really looks like this. I'll follow you along. That might firm up the certainty.
00;09;12;18 - 00;09;37;17
Dr. Jason Karlawish
Ultimately, though, the certainty will arrive when I can get your brain tissue. But of course, that means you have to die. Rather gruesome than the neuropathologist will tell us what happened. Well, those days are beginning to fade. I am now telling people in life, and early in their presentation, Alzheimer's is one of the causes, or it is the it is not a cause, etc. and that has absolutely transformed not just how we talk about the disease, but also the illness experience.
00;09;37;20 - 00;10;00;22
Dr. Jason Karlawish
Because God is the mystery that's sort of surrounded these diagnoses. You really don't know, you really never sure, etc.. And now is that kind of certainty. The the test that I think is most interesting is the ability to measure tau using a Pet scan, because there I can actually show you in your brain where the disease is unfolding.
00;10;00;25 - 00;10;07;03
Dr. Jason Karlawish
So it's not just that it's there. It's here it is. And that's why you're having trouble with your mental map.
00;10;07;05 - 00;10;21;13
Meryl Comer
You know, you keep mentioning, signs and symptoms. So men tell me the signs and symptoms that would prompt you to say, it's the right time to take the blood test for Alzheimer's disease.
00;10;21;15 - 00;10;49;09
Dr. Jason Karlawish
Changes in cognitive abilities that are causing either inefficiencies or disabilities in daily life. So what do I mean by inefficiencies? It takes you longer to get things done that you used to do at a quicker, easier pace, finances without cooking, etc.. Disabilities. You're making mistakes, that you might catch or others catch that need to work up. And depending on that workup it may lead to may lead to getting a biomarker test.
00;10;49;11 - 00;11;10;03
Dr. Jason Karlawish
And the reason why I say May is there are a host of reasons, particularly for the inefficiencies in daily life caused by cognitive problems that are not neurodegenerative, poorly treated sleep apnea. I saw someone who was on a regular daily dose of, Benadryl for sleep and out of and, and, frankly, also a little bit too much hooch.
00;11;10;05 - 00;11;17;20
Dr. Jason Karlawish
You know, all those behaviors taken away, the cognition improved, etc.. But that part of the workup.
00;11;17;22 - 00;11;28;14
Meryl Comer
Is there a direct correlation between a positive result on a blood test and a timeline for a formal Alzheimer's and mixed dementia diagnosis?
00;11;28;17 - 00;11;49;21
Dr. Jason Karlawish
Well, that's getting to the, the way the variability is in clinical practice across America. You know, you can get some of these blood tests through the direct to consumer route is at least six companies offering it. I do not recommend folks pursuing that avenue. I've looked at the websites. I'm not confident, in in the, in the cut points they're using.
00;11;49;23 - 00;12;12;04
Dr. Jason Karlawish
Moreover, you know, they're not terribly well attached to, the kind of additional workup one needs. But, you know, once it's prescribed by a physician, it ought to be coupled to a clear plan for follow up and etc. warning to your listeners. The Cures Act, the act of Congress that did a whole host of modifications to Medicare.
00;12;12;10 - 00;12;31;23
Dr. Jason Karlawish
One of its requirements is all test results. All medical records are available to patients the moment they're created. So here's a heads up to to listeners. You get an Alzheimer's blood test. It's going to pop into your medical record. And you're going to get that ping on your, email. You know, you've got test results in your My Penn Medicine account.
00;12;31;23 - 00;12;48;02
Dr. Jason Karlawish
Log in and look, I strongly counsel my folks. You're welcome to look, but I would I would urge you simply to wait until we have our follow up visit to go over the results. And let me help you interpret them, as opposed to just seeing this cut point and what it says.
00;12;48;05 - 00;13;17;05
Meryl Comer
You know, different communities have different risks for Alzheimer's. I mean, the Latino population begins showing symptoms perhaps seven years earlier than non-Hispanic whites. African Americans twice as likely to develop dementia, but 35% less likely to be diagnosed at all. How do we ensure equity in getting to a timely diagnosis and then everyone's being screened appropriately?
00;13;17;07 - 00;13;53;12
Dr. Jason Karlawish
Well, I think, the inequities around timely diagnosis that you're showing reflect larger inequities in our health care system. Where access is often limited based on income, etc.. And, I think the big challenge that all of America faces, which is amplified in this topic of, that you've raised, is we do not have the adequate infrastructure set up to properly address the challenge of diagnosing and treating the many, frankly, millions of Americans who, I have cognitive impairment.
00;13;53;14 - 00;14;19;18
Dr. Jason Karlawish
And, I'll give you one very focused problem. If you finish a medical residency, if you finish a neurology residency in the United States, the odds are you did not get any substantial training in cognitive neurology. You got great training in stroke, epilepsy, neuro critical care, but very little with any training in cognitive urology, which is the field that is skilled in the diagnosis and treatment of Alzheimer's disease.
00;14;19;18 - 00;14;42;15
Dr. Jason Karlawish
And other diseases. If you finish a geriatrics residency, you're pretty good at dying of fellowship jerks. Fellowship. You're pretty good at diagnosing dementia, but that's about as that's often for many. That's about as far as they get. So there's a real need to train a workforce competent to do this. And the problems you raised around, inequities of diagnosis only amplify the need to address this.
00;14;42;17 - 00;14;57;27
Meryl Comer
You know, you've written about the reluctance of among doctors to diagnose for Alzheimer's or related cognitive disorders. What factors do you believe contribute most to the hesitation within the medical profession is here.
00;14;57;27 - 00;15;22;20
Dr. Jason Karlawish
I reached to the Bible, to the book of Genesis, where once dinosaurs roamed the earth, there are some dinosaurs roaming the medical hallways, namely physicians who just don't get it. They don't feel the need to do this. I think it reflects a couple things explicit and a couple implicit. Explicit. They don't think there's anything you can do, nothing to do, and they're of the view.
00;15;22;20 - 00;15;29;16
Dr. Jason Karlawish
Well, in the end, just the women will take care of these people that do it anyway. So what's the point in diagnosing? It's a view locked in about 1984.
00;15;29;16 - 00;15;30;23
Meryl Comer
Don't depress them.
00;15;30;26 - 00;15;49;00
Dr. Jason Karlawish
I think a lot of it though is they don't have the skill and doctors do not like to admit two things uncertainty and lack of skill. At other words, it's very hard for doctor to say, you know what the problem you're telling me is? One that I don't really feel confident working up, and I need to find someone else who can take care of it.
00;15;49;02 - 00;16;12;08
Dr. Jason Karlawish
You know, early stage assessments are often haunted by uncertainty about whether or not there's a problem here until you really do a good workup. Doctors don't like to admit those things, so I think there's a host of physicians out there who have these implicit and explicit biases, and we see this in our own health system. We are attempting to transform, my friend and colleague, Doctor Cara O'Brien, Penn Medicine.
00;16;12;08 - 00;16;27;26
Dr. Jason Karlawish
And we're making great progress. But in doing this, we are encountering some physicians who will write back to us and say, I don't understand why we would do this. There's nothing you can do. It's not very accurate. All we're going to do is depress these people. But the good news is we've got plenty of physicians who are like, thank you.
00;16;28;02 - 00;16;40;14
Dr. Jason Karlawish
Get me these tools, get me the training. I really want to make this part of my practice. And I think again, back to Genesis. Once upon a time, dinosaurs roamed the Earth. I think over time, these dinosaurs will no longer roam the earth.
00;16;40;16 - 00;16;48;28
Meryl Comer
I attributed it to paternalism, which really always upset me. Just tell me what it is. If you know or tell me you don't know.
00;16;49;05 - 00;17;05;06
Dr. Jason Karlawish
Dan Gibbs, the physician who has Alzheimer's, admits that the patients he least liked working up were the dementia patients when he was neurologist. And it was part of it was there's nothing you can really do with the uncertainty. That's surrounded. That's a big that's a step a doctor has to take when it comes to, a dementia workup.
00;17;05;06 - 00;17;25;07
Dr. Jason Karlawish
I'm not very good at working this up. I need to have someone to refer to. But then that gets to our other problem. Who do you send them to? And this is the wait list that we have at the memory center. At six months. We had a whole new patient appointments because we had such a backlog. We said if we don't just stop taking in new patients, we'll never get through this backlog.
00;17;25;12 - 00;17;51;10
Meryl Comer
You mentioned stigma. The greatest concern for many advocates is that it's just trending younger with earlier diagnosis. So my question is what ethical considerations arise when clinicians must disclose uncertainty to individuals diagnosed with Alzheimer's in midlife, compared to those diagnosed later in life?
00;17;51;13 - 00;18;12;15
Dr. Jason Karlawish
I think the diagnoses in individuals under the classic ages of retirement, 6570 have some unique challenges, and they relate to aspects of the 55th six decade of life for many or decades, a very important.
00;18;12;18 - 00;18;36;26
Dr. Jason Karlawish
Acceleration of bringing in income. And so it's a tough diagnosis to give someone who's 58 and now very well is going to have to step out of the workforce. And, and if they're in the workforce, which many are, the other challenges, if they went back to the job and said, oh, I've got some news.
00;18;36;29 - 00;18;51;07
Dr. Jason Karlawish
You know, the employment discrimination that they are going to face is real and vivid. This gets back to the stigma. This is a public stigma issue. And so these matters are intense important. So I think and a huge social policy issue that we're going to need to face.
00;18;51;09 - 00;19;07;29
Meryl Comer
Do you think that our current labels, mild cognitive impairment, MCI, dementia, Alzheimer's? I mean, when you label someone, you label them and does it help or harm patients, families, clinicians?
00;19;08;02 - 00;19;34;13
Dr. Jason Karlawish
Well, you know, the nomenclature in this field is really in a big flux. You know, once upon a time, Alzheimer's and dementia were synonymous terms because if you didn't have dementia, you couldn't have Alzheimer's. And that lingers still in some of our nomenclature. And I could go on. I will with Alzheimer's has at least three meanings synonymous with dementia a path, a physiologic entity defined by tau and, plaques, tau tangles and amyloid plaques.
00;19;34;15 - 00;20;01;25
Dr. Jason Karlawish
And it's also used as an umbrella term to describe all causes, if you will, of dementia. So, you know, and then you put MCI in the mix and it only gets more complicated. Having said that, dementia is the problem. Okay? I mean, if we didn't have disabling cognitive impairments, this wouldn't be so bad. I'm not trying to say MCI is not a problem, but you know, one can figure out how to live with MCI as well as dementia for most patients.
00;20;01;25 - 00;20;23;19
Dr. Jason Karlawish
We should not stop at a label of MCI or dementia. The next question is what's causing what's the disease or diseases? And in some cases, the answer is I'm not sure. The tests I've done are are indeterminate or negative. But I think we owe people that final as close to final answer as what disease or diseases might be causing this.
00;20;23;23 - 00;20;47;16
Dr. Jason Karlawish
I do think the MCI term, it has a historical problem to it, namely, it was a risk factor for Alzheimer's back when to have Alzheimer's meant you had to have dementia. And so it's sort of caught in this kind of weird historical moment when I remember telling people, you've got MCI, it's a risk factor for Alzheimer's. Well, that's just not the case anymore.
00;20;47;23 - 00;21;07;24
Dr. Jason Karlawish
I can tell you that you have MCI caused by Alzheimer's based on the results of biomarker tests and really good phenotyping. And so I'm kind of left with what's the value of the MCI label? And because the other problem I have with is it the very name kind of makes it sound like a kind of nothing burger, you know?
00;21;07;26 - 00;21;18;17
Dr. Jason Karlawish
And it also just says back to the patient what they've told you. Anyway, I've got cognitive impairment and it's sort of mild. And so it just it's a quirky term that I'd like to kind of see replaced and retired.
00;21;18;20 - 00;21;23;06
Meryl Comer
There are groups out there trying to get rid of the term dementia, which is a medical term.
00;21;23;08 - 00;21;53;15
Dr. Jason Karlawish
Yeah. I'm not ready to retire dementia. I think we can learn to live with it because we'll as we change the mystery that surrounds dementia. I think there's a larger thing going on here that the mystery and the horror that surrounds Alzheimer's and dementia is beginning to be chipped away at the ability to diagnose people and explain what's wrong in the case of Alzheimer's, the ability to treat it with their time with therapies, the ability of our, the beginning to provide better services and supports the things like the guide program.
00;21;53;17 - 00;22;23;12
Dr. Jason Karlawish
So that's why I think this like, let's stop using the word dementia is a kind of a language police solution to a larger cultural problem, which will work itself out. Now, it doesn't help when politics politicians use dementia as a cudgel against their opponents, which was done in the last election. And so there's some need for a little more mature behavior, if it's possible, in some of the spheres of culture which enjoy using, dementia as a political cudgel.
00;22;23;15 - 00;22;54;00
Meryl Comer
You've been very generous with your time. Our guest 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. Essays in STAT that looks at the vast problems of dementia.
00;22;54;02 - 00;23;00;03
Meryl Comer
That's it for this edition. I'm Meryl Comer. Thank you for brainstorming with us.
00;23;00;06 - 00;23;09;03
Narrator
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