Do I Want to Know?

[00:00:02] Elizabeth Wood: We are so much more than our genes, our lifestyle, our health habits, even other medical conditions that we might have. These are also going to have their own impact on increasing or decreasing risk for Alzheimer's disease. [00:00:28] Jake: Welcome to the Age of Aging, a podcast about living well with an aging brain, produced by the Penn Memory center. My name is Jake Johnson, and my. [00:00:36] Terrence: Name is Terence Casey. [00:00:38] Jake: Adults are living longer today than their parents and grandparents did, which is great. But they're also more likely to develop age related diseases like Alzheimer's disease, which is not great in the age of aging. We talk to world class researchers, hear the experiences of patients and caregivers, and find out what aging even means in 2024 and how we can do it well. [00:00:59] Terrence: Each episode will have a theme and a few stories related to that theme. This episode is called do I want to know? Until recently, there were no treatments for Alzheimer's disease or other causes of dementia, and older adults concerned about their loss of cognition had to ask themselves this do I want to know if it's Alzheimer's disease? In our first story, we'll speak to a genetic counselor about making the decision to learn one's genetic risk of developing Alzheimer's disease. In our next well, speak to another researcher who studied how people react to learning about an increase or a lower level of risk. We'll speak to another researcher about stigma or how we or our community responds to us learning this information. And finally, we'll speak to Jason Karlawish, co director of the Penn Memory center, about one such treatment recently approved by the FDA. Nearly everyone knows an older adulthood who has lived with dementia and has asked himself the question, could this happen to me? Between genetic testing and the measurement of biomarkers, it is possible to learn one's risk of developing Alzheimer's disease. But then you have to ask yourself, do I want to know? With more, here's Jake. [00:02:18] Jake: Genetic testing is a growing topic in the medical field as we learn more and more about how genetics play a role in certain diseases. Anyone can get genetic testing, and for some, that's incredibly valuable. Genetic testing can offer a look into the future. But for others, genetic testing just adds unnecessary stress. If you're thinking about getting genetic testing, one of the most important resources available to you are genetic counselors. Genetic counselors are specialized in talking through genetic testing and any of the questions that you might have about genetic testing and what it can mean for you and your family. Lainey Dratch is a genetic counselor at the University of Pennsylvania in the department of Neurology, as well as the penfrontal temporal degeneration center. [00:03:00] Laynie Dratch: One of the questions that I get asked most as a genetic counselor is whether a person who doesn't have any symptoms but knows there's a genetic condition in the family should have genetic testing to learn their own risk status. For some people, they feel like they have to know their genetic risk status to be able to plan for the future. So for some people, if they know they want to have more children in the future, they might want to pursue different ways of having children to avoid passing down a genetic risk in the family. Some people think about planning for the future in other ways, like do they want to stay in the same career? What do they want their retirement to look like? Where do they want to live? What kind of house do they need to live in? What kind of support might they or their spouse need if they develop symptoms? [00:03:41] Jake: Dratch also explained that people may consider getting genetic testing in order to know if they should sign up for clinical trials or studies. If you know you're at a greater risk, you may want to sign up for that new drug sooner rather than later. Sometimes genetic testing can be a way for people to provide information to their kids or other family members, or some people just need to know because it's going to stress them out too much to not know. An important note here is that this kind of genetic testing, where you don't have any symptoms but you think you might have an inherited risk, is called predictive testing, and that's mainly what we'll be discussing this episode. The other kind of genetic testing you can get is called diagnostic testing, which is when you have already been diagnosed with a condition like dementia and are using genetic testing to identify an underlying cause. Dratch said that diagnostic testing is usually the best first step in genetic testing because it can make testing other family members for the same condition much easier. If testers find a genetic cause, they can test other family members for those genes. Diagnostic testing will also not impact your insurability, which is a risk of predictive testing. [00:04:48] Laynie Dratch: It's really important for people to think about what insurances they have in place and what they might want someday because there are some limitations to the protections that exist against genetic discrimination. There's a law in the united states called the Genetic Information Non Discrimination act, or Gina, that says that your health insurance and your employer in most cases, cannot ask for or use your genetic information against you to discriminate. But the loophole is also that life insurance, long term care insurance, and disability insurance groups can ask for your medical information including your genetics, and use that to deny you coverage or charge you a higher premium for a person who already has a diagnosis of some form of dementia or other neurologic condition. Adding on the fact that it's genetic wouldn't really change much for their insurability. So this is primarily an issue to consider if you are someone who's asymptomatic, someone who does not have neurologic symptoms, looking to undergo testing. There are many different ways to access genetic counseling with or without testing, including through clinical care, and also sometimes through research studies. And you should reach out to your care team if that's something that you have interest in. [00:05:53] Jake: This is Elizabeth Wood, a senior genetic counselor at UPenn. [00:05:56] Elizabeth Wood: I think it's really important that people know that by going to speak with a genetic counselor, it doesn't mean you have to get genetic testing. What it means is that you're going to speak with someone who can give you all the facts that you need to hopefully decide if genetic testing is right for you. We never push people to have genetic testing. We very much view genetic testing as a personal decision that's right for some people and maybe not right for others. A fairly typical initial genetic counseling appointment would focus on covering some basic information about whatever the medical concern or the family history concern that the person has. In the case of Alzheimer's disease and other dementias, we'd spend time talking about someone's family history. The genetic counselor will often draw out a family tree to capture those details about your family members who have been affected by Alzheimer's disease or other types of memory problems. And then there would be a pretty detailed conversation to cover some basics about genetics, the type of information that genetic testing may or may not be able to give the person. [00:07:12] Jake: A genetic counselor would then discuss the benefits and risks of getting genetic testing, as well as what kind of genetic testing should be done. Family history is the main way genetic counselors can decide what to actually test for. [00:07:25] Elizabeth: So I think it's important to be very clear that for the most common gene linked with Alzheimer's disease, it is absolutely a risk factor gene. It cannot predict with any likelihood who will or will not get Alzheimer's disease. What it can do is help someone understand if they have a higher than the average person's likelihood of getting Alzheimer's. We are so much more than our genes, our lifestyle, our health habits, even other medical conditions that we might have. These are also going to have their own impact on increasing or decreasing risk for Alzheimer's disease. [00:08:04] Jake: If you decide to get tested, it can be done in one of two ways. [00:08:08] Elizabeth: Most commonly, we do the testing on either a small sample of blood or a saliva sample. The sample would get sent to a lab that does the type of genetic testing that the patient needs, and it usually only takes a couple of weeks for the test results to come back. Oftentimes, the genetic testing, whether it's being done on blood or saliva, can be collected the same day as someone's first appointment with a genetic counselor. Sometimes people want a little bit of time to think, so there's no rush, especially with the saliva kits. We very commonly mail these to people's homes, and they can do that sample collection right at the comfort of home. They don't need to go in and get a blood sample drawn. [00:08:58] Jake: There's another kind of genetic testing available that you may have heard of, which Wood says falls under the category of direct to consumer. She said these services, like 23 andMe, or ancestry DNA, are less regulated in terms of their quality and privacy protection. So your results may be shared with a third party you're not aware of. Of course, you can still use these, but understand the risk before purchasing. [00:09:22] Deia Schlosberg: There was really no question for me that I wanted to know in order to better prepare. [00:09:28] Jake: This is Deia Schlosberg, a documentary filmmaker who faced the question of genetic testing when her dad was diagnosed with frontal temporal degeneration, or FTD. [00:09:38] Deia Schlosberg: In my family, we have FTD and ALS throughout my whole paternal side, so it's something I've been familiar with, and I might have a genetic component to it. My dad has always been really worried about it. He was kind of symptom hunting for a lot of years. My mom would never be like, no. Like, we're not seeing any of these things. We would have just tried to be positive. And then, like, six years ago, we started seeing signs, and finally I came to terms with it. In the last few years, and then early pandemic, he finally got a diagnosis of XUD. And at that point, once my dad was diagnosed and was confirmed to have good gene, I started looking into ways to get involved in research. [00:10:27] Jake: Schlosberg began documenting her experience and eventually ended up in a genetic counseling session with Lainey Dratch. [00:10:34] Deia Schlosberg: I felt from her, everything was very much up to me. Like, the pace of things, making sure I was in the right head space to deal with stuff and work through stuff, and I never felt any bit of external pressure or expectation or anything. Like, I think if I was a little more hesitant about my choice, I probably would have leaned into that counseling a little more. But because I was so sure about what I wanted to, I just appreciated her role. I was like a guide through this. It's been challenging and painful at times, but it's the kind of challenge and pain that I think leads to growth. And I think it forced my husband and I to have some harder conversations that maybe wouldn't have happened if it wasn't like this imminent thing, the testing and the finding out and just real serious checking in and working about different possibilities and what different outcomes would mean. [00:11:41] Jake: She even felt that the experience made her a better caregiver for her father. [00:11:46] Deia: Before I got tested, it was very hard. It was very hard to see everything my dad was going through and just be hyper aware, like, is this my future? I all of a sudden felt like because there was a decent possibility that I would develop this, I felt like I was at the same stage of life in Sam. And my mom didn't want to lean on me for help as much, just gnawing it really hard for me. So she was a lot more isolated and didn't feel like she could rely on me or lean on me as much. So when I got my result, I do not have the mutation. So in our situation here, it has enabled us to be a much better care team. And my mom can, you know, whatever frustrations or pain or whatever that she's dealing with, she can come to me now without fearing like an extra burden on me. So, yeah, I mean, as a unit dealing with this, it's been pretty night and day. [00:12:54] Jake: If you're considering genetic testing for yourself, genetic counseling is a resource you should definitely utilize. If you're able. You can use the National Society of Genetic Counselors website to search for a genetic counselor near you. The link will also be in our show notes. The Penn Memory center and the Penn Frontal Temporal Degeneration center websites are also great resources for information about genetic testing, diseases and programs for caregivers and those with dementia. [00:13:27] Terrence: This is really interesting because I know I personally want to seek out all this kind of information like this about myself, but there are certainly things that I hadn't considered before we started working on this story, namely the insurance issues and learning information about my family members. I think from a selfish perspective, I want to learn things because I think it is about me and my body, but it also means learning information about my children and my parents. And I think that's an important thing to take away. What about you? Would you have considered genetic testing before or after? [00:14:07] Jake: Yeah, I mean, it's really never something I thought about. I think maybe just for. From being a younger person, it's not something that's on my mind, but it was really interesting to hear Daiya talk about her father and kind of the way in which he became almost a symbol for herself in the future. And it became a very existential way of her thinking about what her future is gonna be like. And it almost prevented her from being a good caregiver. [00:14:38] Terrence: She had this great sense of relief learning that she doesn't have it, and she was able to be a better caregiver. But it makes you wonder, how would she have responded if it had been the other direction? Could this have been potentially more harmful in learning this information? And for her personally, I'm sure this is a tremendous relief, but there is that inherent risk, and I think that a genetic counselor would have certainly laid that out for her. [00:15:05] Jake: Right? Yeah. And in this situation, she definitely got the more positive results. So it's hard to say what that would be like for her if she had found out that she had the mutation. I think also, in approaching this story, and I'm fairly new to the memory center, I always thought of medicine as, like, something very non emotional. And I'm learning more about how the memory center and the Alzheimer's Disease Research center is a lot about dealing with people's emotions, about the diseases and about dementia, and kind of working through these things. So something like a genetic counselor, I never knew that that was even a job or a position or somebody that you could seek out, because I thought of it as, like, genetic testing. You get a test done, and that it was very cut and dry, but, you know, you don't think about it, but there's so many emotions and feelings and questions that go into these decisions that you really need somebody there to help work that through. And at the Penn memory center, we have social workers that people talk to and support groups. [00:16:07] Terrence: Yeah, it's really treatment beyond body and brain and much more treatment of the person. And I agree, that really has stood out to me as something unique and special. The only other consideration in all of this that I remember we had this discussion about, would you have this testing when it was new here? And one of the questions that we had asked around the office is, what would you do differently? And we had a lot of different answers to that. People who would take their health more seriously or come up with sort of a trusted family member who could help manage their finances, different positive health and financial behaviors like that. And then the pushback on a question like that is well, why wouldn't you do that anyway? And so, as someone who took the side of sure, I'd want to learn this information about myself, it makes me wonder, what would I do with more information about an increased risk? Or even worse, what do you do if you find out that you're at a lower risk? Do you suddenly take up smoking and stop exercising? I don't think so. But I think that takes us into our second story, which really answers that question of now what? How do people react to learning about increased risk, and what do they do with that information? How do they behave differently? [00:17:31] Jake: So, in this segment, we spoke to a researcher who studied exactly that, how people respond to learning their risk for Alzheimer's disease. And just a note for this segment, you're going to hear mostly Emily Largent talking about the Socrates study. But interspersed throughout, there will also be some quotes. The quotes are from the actual study, from participants, but the people saying the quotes are actually some of our colleagues here at the Penn memory Center who we asked to record for this episode. So it might be a little jarring at first. There will be a sound cue in between doctor Largen and the quotes, and then doctor Largen is going to talk about the individual quotes. Okay, that's it. Enjoy. [00:18:16] Emily Largent: Hi. My name is Emily Largent. I am on the faculty at University of Pennsylvania in the Department of Medical ethics and Health Policy, and I am also part of the Alzheimer's Disease Research center. Scientists have found that when people have Alzheimer's disease, they also have certain characteristic changes in their brain. One of these, and one that people often talk about, is the accumulation of amyloid plaques. These are abnormal molecules that collect and form between neurons that can actually affect how the brain thinks and functions. In the last decade or so, investigators have been able to develop a number of different ways that we can test for amyloid in individuals. This can be through a spinal tap. We can do it through various PET scans and imaging. And the newest way that you may have heard people talking about is through blood tests. You can actually go to a lab, have your blood drawn as it normally would be drawn, and then there are tests now that can say something about whether or not you have amyloid in your brain. For people who are cognitively unimpaired and have an increased level of amyloid in their brain, that puts them in an increased but really uncertain risk still of developing cognitive impairment caused by Alzheimer's disease in the future. This has been a focus of research, really trying to understand even better at an individual level, what it means when we say that somebody has elevated amyloid. So a team of us at the Penn Memory center conducted the Socrates study. And Socrates stands for the study of knowledge and reactions to amyloid testing. And what we were able to do was actually interview 80 adults who are 65 and older who had undergone an amyloid PET scan and learned their results. We interviewed them shortly after they learned the amyloid PET scan results, and then again about a year later. The purpose of these interviews was really to understand what it's like to be cognitively unimpaired on testing, and also to find out that you have amyloid plaques that put you at increased risk of developing impairment caused by Alzheimer's disease in the future. And some of our interviewees learned that they did not have elevated amyloid, and so they were at average or perhaps decreased risk of developing cognitive impairment in the future. At the time we conducted the Socrates study, amyloid disclosure was still quite new within the field of Alzheimer's disease research, and there were. There were a lot of efforts to understand whether or not it was safe to communicate this information to participants, whether they would understand it once we shared information with them. So we've been able, through this and other studies, to answer some really key questions. So we do know that it's safe to disclose these results. Participants have an emotional reaction, of course, as we would expect, but we don't see any sort of increased depression, anxiety, or suicidality, which were concerns that people had about disclosure. We also have seen that people can understand these results. Now, importantly, in Socrates, we made sure that participants had solid pretest education, and so they understood what they were agreeing to when they underwent testing, and we gave them some context for possible results and what they might mean. But what we saw was that with this education, people do understand the implications of their amyloid PET scan results. And then we got a host of very interesting information about what people think and feel after getting these results. [00:21:41] Participant 1: A colonoscopy isn't going to change who I am. This is my brain involved. The results speak to who I am. My brain is a very critical part of me. [00:21:50] Dr. Largent: Participants indicated to us that learning an amyloid PET scan result was somewhat different than learning other medical test results. And this really had to do with the idea that Alzheimer's disease can, through the process of cognitive and functional impairment, affect their sense of who they are as a person. And we saw participants speaking to this in their results, talking about how important their brain is to making decisions and living their life as they want to. [00:22:19] Participant 2: The result made me think that any memory problems I was having was just. Normal age related rather than Alzheimer's. [00:22:29] Dr. Largent: So one of the things we wanted to understand is how learning that you have elevated amyloid might affect how you perceive your own thinking and memory, because we know that amyloid is linked to an increased, again, but uncertain risk of developing cognitive impairment in the future. What we saw is that participants had various responses. Some who had elevated amyloid had changes in how they thought about themselves, and some who learned they had not elevated amyloid also had changes in how they thought about themselves. This quote comes from a participant who learned that they had not elevated amyloid. They had been quite concerned before testing that they were likely to develop Alzheimer's disease at some point in the future, and when they got a not elevated result, they found it reassuring and actually were reinterpreting changes that they had been thinking of as Alzheimer's related, as normal age related changes. What we might think that people would overall be reassured that they did not have elevated amyloid, and this was often the case. Some people actually left feeling a little bit frustrated. They were experiencing what they perceived as changes in their thinking and memory, and we're hoping that the amyloid PET scan result would offer them some sort of explanation. But when they got a not elevated result, they were left wondering the changes that they were sensing, what was causing those? [00:23:46] Participant 3: It has taken more emotional energy than I ever thought it would when I first got into the study to make these kinds of decisions. I mean, it's been an ongoing decision, as it were. I mean, I never really appreciated how much energy, psychic energy, that process might take and whether there might be unintended consequences. It just has taken much more emotional energy than I ever imagined it would. [00:24:11] Dr. Largent: One of the things we really wanted to explore with the Socrates study was whether people shared their test results with others and really their reasons for sharing it with other people. One of the things we heard from participants who had elevated amyloid PET scan results was that it was actually somewhat complicated for them to make a choice to choose to share information with others. Everybody in the study did share with at least one other person, often a very close family member or a dear friend. But sharing beyond those one or two key people in their life could be difficult for them, and their reasons for not sharing, as this quote suggests, often had to do with worries that people would stigmatize them or discriminate against them as a result of having elevated amyloid. Now, these were individuals who were not cognitively impaired. They were just at increased risk for impairment at some point in the future. But they still felt like other people might misunderstand and start to treat them differently. And they worried about discrimination in the workplace, in purchasing long term care insurance, and in other settings where people might want to use that information in ways that could ultimately harm them. When we dug a little bit deeper into why people did or did not choose to share an elevated amyloid result with others in their life, we saw that there were some obvious reasons for not sharing. This included not feeling close to a person so they didn't need to know the information, or perhaps worrying that that person was a gossip or somebody who would share that information more broadly than the individual wanted it to be shared. But in terms of the reasons for sharing, we saw some very core reasons that came up over and over. People often shared their elevated amyloid PET scan result with somebody that they thought would be their caregiver in their future. So a spouse or an adult child who would have that role in providing. Providing assistance with activities of daily living. [00:26:02] Participant 4: At some point, I may need to count on other people to tell me if I'm changing in a way that I'm trying to deny. She's someone I would trust with that. [00:26:11] Dr. Largent: So individuals who found out that they had elevated amyloid and so were at an increased risk for developing cognitive impairment caused by Alzheimer's disease in the future. In some instances, not all. Certainly, they were interested in having others monitor them and help them look for changes that might be related to the onset of Alzheimer's disease. The Socrates study was conducted several years ago. Really? When, as I've mentioned, we were at the outset of disclosing amyloid PET scan results to research participants. But in the time since, we've only seen growing interest in disclosing amyloid results, both to participants and also to patients who are being seen clinically. And our hope has been, and I'm reassured that it's happening, that the Socrates results would help inform how disclosure is occurring across a variety of settings. We've had the fortune at the memory center to be able to use these results to help other investigators in other studies develop their disclosure techniques. Currently, amyloid scans may be available to some individuals through seeing a physician, but right now, they really are only recommended for people who have some measurable cognitive impairment. And that has to do with availability of therapies. Insurers won't cover scans for people who are cognitively unimpaired. So if you're unimpaired and interested in learning about your amyloid PET scan results, I would suggest that you look for research opportunities as many studies include some sort of biomarker testing. [00:27:43] Terrence: There's a lot of overlap with genetic testing and counseling when it comes to learning amyloid pet results. But for me personally, amyloid scans just feel so much more urgent, more pressing, whereas genetic counseling is sort of the book that's laid out for you, but may happen, may not, and may happen in ten years, 20 years, who knows what amyloid scans feel like. You're in progress here. And so this felt so much more real and heavier than the story on genetic counseling for me. I don't know. How did you feel about that? [00:28:22] Jake: Yeah, I mean, I completely agree. I think it's an interesting way to put it, because it feels like something is developing in a part of your body, but that part of your body is this very essential piece to you. And you can hear the people in the study talking about that, being like, this isn't just, you know, something happening in my leg or my arm or, you know, this is my brain. This is, like, who I am, my personality. What is that going to mean down the road? And I think that it's a huge question what you're supposed to do with that information. And, honestly, one thing that really stood out to me was hearing about people who were actually frustrated that they didn't have amyloid plaque. Like they had this conception about themselves. Something is happening to me that is out of my control. I'm developing this disease. And to hear that they didn't, it's like, oh, it completely throws into question what's been happening to them or how they even see themselves and how they see themselves aging. [00:29:17] Terrence: Yeah, absolutely. I mentioned earlier that I'm a total sucker for just information about myself and my body. And I totally understood where these people were coming from at how frustrating it would be to go back to, why is this happening to me if this is not the answer? And one of the other things that I thought about in the comparison between this and the genetic counseling, I thought earlier with genetics that learning information about myself meant learning some information about others, and that feels like prying. But here it's not just learning information about other people. You're learning what their responsibilities might become to me, learning about how my genetics may impact half of my children's genetics. But learning that I've elevated amyloid may mean that my children have a caregiver burden in their future, and that feels so different, so heavy, so important, and like a decision that would need to be made together with the people who would bear that burden moving forward. But what I haven't given a great deal of thought to is beyond that, who else needs this information? And who else could I trust with this information? And there are a lot of reasons to hesitate on that, and I think we get to that in our next piece. [00:30:42] Jake: Yeah. So a lot of participants in the Socrates study worried about facing stigma from their results. In our next story, contributor Meg McCarthy spoke to a researcher who specializes in stigma related to Alzheimer's disease and other dementias. [00:31:05] Meg McCarthy: As our team discussed podcast topics, stigma was an instant yes amongst the group, and I think it's because it's a topic that clicks even outside of our field. Facing stigma based on identity or circumstances, whether it's mental health or racial backgrounds or sexual preference, it's extremely common. But for patients with Alzheimer's disease or related dementias, these experiences can affect identity and also the quality of care received. Doctor Shana Stites is a clinical psychologist and researcher at the Penn Memory center, and her research focuses on the lived experience or what it means to live with Alzheimer's disease. She is particularly interested in how sociocultural diversity can impact this, and so much of her research revolves around stigma. Naturally, I turn to her for information about the topic. [00:32:04] Shana Stites: Stigma is associated with a negative attribute or hallmark. In this case, it would be Alzheimer's disease, and whether that's the diagnosis itself or clinical symptoms that we associate with the disorder. But those associations build out to negative thoughts, beliefs, and behaviors. And so when we see this hallmark or this signal, then people may treat an individual with that marker more negatively or have negative thoughts or beliefs about them. There's different types of stigma. The stigma in terms of how we treat others, that's a public stigma. So we might meet somebody with Alzheimer's disease and make a lot of assumptions about how their memory does or does not work. Then there's internalized stigma. Let's say we have Alzheimer's disease and we feel shame and guilt and turn a lot of those negative beliefs about what we can and cannot do against ourselves. There's spillover stigma, and that's when we experience stigma because of our close association with somebody who in this case, has Alzheimer's disease or has that detrimental mark. And then there's vicarious stigma. It's actually, we're not really involved at all, but we watch someone being stigmatized because of this mark. Right. They have Alzheimer's disease. Someone else is treating them poorly, and we're watching that happen. And that can be damaging to how we think, feel, and behave, and potentially how empowered or disempowered we feel in that moment stigma often refers to the misattribution or the over attribution of the severity of symptoms. So really helping patients not catastrophize or over attribute how severe their impairments are, helping them understand exactly sort of where they land on the continuum. One of the big benefits of going in and getting a diagnosis is then creating the space to have the conversations, to name those things, to find out actually where you stand and get some of the support that you need, but also maybe put to bed some of those overarching fears that maybe keeping you up at night. I think those clinical conversations, particularly for the caregivers when they're in those visits, is a key opportunity to get everybody on the same page. What are these symptoms that we're talking about? How severe are they? What types of impairments and abilities are happening in this room? And so there's a shared understanding of the symptoms. Unconditional positive regard would be the top thing that a family member could do, which is sometimes easier said than done, but really is one of the most important things that we could do. Reassuring, especially during moments where maybe there's a difficult symptom or a difficult interaction, that that fundamental act of caring and love that we share with our family members is intact and unchallenged, can make the dealing with other lesser important, but still problematic aspects of the disease easier. I think one of the consequences with stigma, or one of the key features that happens is that it's not directly addressed or talked about or said. It comes across almost like microaggressions or just subtly poor treatment towards a person or things that we choose not to say. That space of what's not said then becomes more harmful or harmful to begin with. One of the ways that's really important for addressing stigma is leaning into the initial inclination to go into silence or quiet and let those negative beliefs or attitudes prevail. It's a short leap to think about other cognitive biases as well. And some of the work that I've been doing more recently is looking at the intersection of racism and Alzheimer's disease stigma to try to understand whether there are people or certain groups, rather, that feel the compounded effects. Right. Not only are you contending with racism, but now you're contending with Alzheimer's disease stigma, that now you're contending with the genderism or sexism. Right. And ageism and all these things. And how does that work for a person? And again, barriers that once we understand them, are, I'm going to hope, are addressable. Which brings me to the thing I'm actually increasingly interested in, how do we get a good intervention? Because it's easier said than done. A stigma is very tricky in that, as one example, the language we use can perpetuate stigma. The language we use can mitigate stigma. And so if you design an intervention that's focused around language, we have to be very careful whether you're perpetuating or mitigating stigma. Since it could go either way. There's a lot of nuance there that has to be understood. [00:36:53] Terrence: There are so many layers to doctor stite's work, it's almost hard to imagine where you begin. You can imagine stigma playing a role in community relationships and family relationships, close friends. But I think one thing people don't think about is stigma in the relationship between patient and clinician and how a clinician may approach a patient as soon as a visit starts. I think one thing that we hear in general in the Alzheimer's care community is of physicians who come in and immediately start speaking to a caregiver rather than the patient themselves. Just the assumption that this person is not going to be able to speak clearly about the work that they're doing. Stigma, at least when I think about it, I think of a public stigma of people being sort of outwardly rude and aggressive or belittling and things like that. And doctor Stite's commentary forces me to think more about what she called unconditional positive regard. That was a particularly touching phrase because I think that that is a general positive rule in life that can translate well into the Alzheimer's space. It goes back to one thing that we talked about earlier, of treating the personhood in this space beyond clinical care, how we treat the human being. And unconditional positive regard really sums it up quite nicely, I think. [00:38:21] Jake: Yeah, I mean, I completely agree. You know, I said earlier in the episode that you asked me if I had considered genetic counseling or genetic testing, and I said, well, I haven't really thought about it. And I think that's something that I'm realizing about Alzheimer's disease and dementia, is that it's simultaneously about older people and people that we just don't really think about in general. I think for a lot of the population, older people are just kind of, like, forgotten about. They're a little bit on the margins, and then same for people with disabilities or differently abled, they're also kind of on the margins. And Alzheimer's disease and dementia is almost this combination of the two of these two kind of groups that we don't really want to think about or accommodate. And so Shayna stites says that it's a lot of the things that are not said, and that's what I've been thinking about. It's when we are trying to not think about them, it's when we're trying to avoid people with dementia or just go straight to the caregiver when we're talking. These people can be kind of invisible, and I think trying to make them visible is a huge part of addressing this kind of stigma, because it can really all add up and degrade somebody's quality of life. [00:39:34] Terrence: Yeah, I think that whereas people typically think about the outwardly aggressive forms of stigma, I think doctor stites points out different ways of stigma where it is possible to stigmatize others while trying to do good, because you may be acting to help an individual, but if your reason for doing so is a pile of assumptions about this person's inability to function, then this is stigmatizing language and stigmatizing efforts. Back when we first started planning this podcast and this episode particularly, we settled on the title do I want to know? Because at the time, there were no clinically available treatments for Alzheimer's disease or other causes of dementia. That has changed as we worked on this episode. For more on how Penn Medicine is responding to the approval of lecanumab marketed as Leqembi, we turn to doctor Jason Karlawish, a geriatrician and co director of the Penn Memory center, where he sees patients clinically. [00:40:53] Jason Karlawish: Beginning in mid November of 2023, Penn Medicine began delivering leucainumab to patients. This is a big event. It took us several months to get a pathway organized to move people from interest to drug delivery. And I'm proud to say that in the region, we were probably the first to be doing this. And in subsequent months, I've learned from colleagues that the progress we've made since mid-November is pretty good. We've infused now up to about 30 some odd people, and the program's growing. We began focusing on individuals who are patients in the memory center because we knew them well. They've been learning about the drug, and now we're beginning to expand access to patients coming through the primary care and other Penn medicine networks. Next steps for this drug, we're awaiting the potential approval at some point of a subcutaneous delivery of the drug. It's like the way you get insulin. A little skinny needle is delivered right under the skin. And after you wipe off your skin with alcohol and make the injection, obviously we need to see the data on that and FDA approval, most importantly. But assuming it's shown to be as effective as the intravenous drug, and it's very promising opportunity for patients given the ease of delivery of a subcutaneous injection compared to intravenous. By the time you are listening to this, it's possible that dynam will also be FDA approved and available. But at the time that this is being recorded, remains under FDA review. We're very excited about that drug as well. I, along with my colleagues, are prescribing this. We've set up a very, I think, thoughtful process. It begins with education between the provider and the patient and the patient's family. We've prepared a variety of materials that summarize the key points available on our website, pemmercenter.org dot. We emphasize the drug's benefits, the risks related to microscopic hemorrhages and brain swelling, the need for genetic testing to make sure an individual gets a more precise estimate of their risk of developing those side effects. And the conversation about genetic testing, of course, emphasizes that learning about your aPOE four gene is information that doesn't just inform what your risk of developing microscopic bleeds might be, but also the risk within the family, then, of developing late onset Alzheimer's. Because, of course, apoe four gene raises an individual's risk of developing late onset dementia. So these conversations unfold over time, and I think a key decision people need to make is a very fundamental one, which is, do I value slowing this disease down at this point? That's a very personal decision. And once people arrive at that answer that says, yes, I do, and then it's about thinking through the risks and hassles of the drug, et cetera. The other great innovation that we've made is once a week we meet and review patients who have moved along the process. It's a great learning exercise for us as a group. This is a very new drug, very new space, and it's been a great exercise on the part of the clinicians to review patients, discuss why they're candidates or why they may not be candidates. And now, as we're delivering the drug, to learn from the experience of the drug, the infusion related side effects and how to manage them. Had a few cases of ran learned as well from how to manage those. If an individual is interested in Lekembi and not a patient at the Penn memory Center, I think the first step is to talk to their provider about the drug. Penn Medicine and Penn Memory center have put together materials for primary care providers for the steps they would take to determine whether a patient is a candidate for the drug. We think they're accessible to primary care providers and would allow for people to have an upfront assessment to know whether it's worth going forward. Just as important as though working with your primary care provider is reading about the drug and deciding, is this right for me? And again, on our pennmemorycenter.org website, we've assembled a variety of materials, print, as well as a 1 hour long discussion between David Wolk and myself to help people think through whether this is the drug that they want. Do they value slowing the disease? And if they do, to the hassles and risks and degree of benefit of this drug rise to levels that they think are acceptable or unacceptable, that becomes a very personal decision. I think overall, I'm very optimistic about what Penn medicine has set up, the potential for growth, and optimistic about the addition of new drugs coming down the pipeline. It's a new day. It's a new era in Alzheimer's disease diagnostics and therapeutics. [00:45:17] Jake: Thanks for listening to this episode of the Age of Aging. The Age of Aging podcast is supported by the Penn Memory center, the University of Pennsylvania Alzheimer's Disease Research Center, Institute on Aging, and the Penn Ftd center. [00:45:30] Terrence: Contributors include myself and Jake Johnson, as well as Nicolette Calcavecchia, Marie Ingeneri, Jason Karlawish, Cait Kearney, Emily Largent, Meg McCarthy, and Olivia Vozzella. [00:45:41] Jake: More information on the stories you heard today can be found in our show notes and on the penmemorycenter.org.