In this episode, Matt & Donovan speak with University of Michigan School of Public Health Professor, Dr. J. Scott Roberts, who investigates the psychological and behavioral impact of genetic risk disclosure for Alzheimer's disease.
In addition to being a professor in the Health Behavior & Health Education department at the School of Public Health, Dr. Roberts is also a core lead of the Michigan Alzheimer’s Disease Center. Dr. Roberts’s research interests focus on the process and impact of risk assessment and disclosure for adult-onset disorders, as well as the ethical, legal, and social implications of advances in genomic science & technology.
Related Links
- Faculty Profile: https://sph.umich.edu/faculty-profiles/roberts-j.html
- Michigan Alzheimer’s Disease Center (MDAC): https://alzheimers.med.umich.edu/
Transcript
Matt Davis:
He was People Magazine's sexiest man alive, which is not surprising considering his handsome physique, excellent bone structure and flowing hair. He looks fantastic when his face is clean shaven, and even better when it's not. In fact, Robert Downey Jr. just came out and said it, "We've got to take this guy out. He's too good looking, too tall and too charming." You may be thinking that I'm describing my co-host, Donovan, but I'm actually referring to actor Chris Hemsworth, perhaps best known for playing the character Thor on the immensely popular Marvel Superhero series.
The Thor character is the epitome of physical strength and power. The guy runs around smashing things with his huge magical hammer, crushing his enemies, defending the universe, all while maintaining is witty sense of humor. So when something comes out that reveals the human side of Thor, it can get some attention among us mere mortals. Recently Chris announced that he's taking some time off from acting because he tested positive for a genetic risk factor for Alzheimer's disease.
Alzheimer's disease, the most common cause of dementia has a genetic component which can actually be tested for. For some individuals who may have a family history, the genetic test may be a welcome tool to assess their personal risk, while others may not want to know whether they're at higher risk, especially considering there is no cure for the disease.
In this episode, we'll speak with a researcher who investigates the psychological and behavioral impact of genetic risk disclosure for Alzheimer's disease. I'm Matt Davis.
Donovan Maust:
And I'm Donovan Maust. You are listening to Minding Memory, a podcast devoted to exploring research on Alzheimer's disease and other related dementias.
Matt Davis:
We're joined today by Dr. Jay Scott Roberts. Dr. Roberts, who's a professor in the Department of Health Behavior and Health Education at the University of Michigan's School of Public Health. There he serves as the co-director of the dual degree program in Public Health and Genetic Counseling, and is a core lead of the Michigan Alzheimer's Disease Center. His research interests focus on the process and impact of risk assessment and disclosure for adult onset disorders, as well as the ethical, legal and social implications of advances in genomic science and technology.
Since 2001, he has served as the co-principal investigator of the REVEAL Study that stands for Risk, Evaluation and Education for Alzheimer's Disease. REVEAL is an NIH funded series of clinical trials that examine the psychological and behavioral impacts of genotype based risk disclosure. He's here today to speak with us about genetic testing for Alzheimer's disease. Scott, welcome to the podcast.
Scott Roberts:
Thanks so much, Matt. It's great to be here.
Matt Davis:
So we have a lot to talk about today, and I would say perhaps learn. So why don't we jump right in. When we talk about diseases such as Alzheimer's, it's pretty rare probably that they're caused by just one factor. So to what degree is Alzheimer's disease attributed specifically to genetics?
Scott Roberts:
Well, that's a great question. Alzheimer's is what we refer to as a common complex disease, meaning that genetics is just one part of the picture, but it's a pretty important part of it. There have been some studies that try to create an estimate of what's called heritability. So some of those studies suggest that the heritability of Alzheimer's is over 50%, meaning that genetic factors are pretty important in the development of the condition. Another way I think of looking at that, the flip side of the coin is the Lancet Group that's done a lot of focus on modifiable risk factors for Alzheimer's and other dementias. They've suggested that if we took care of all of the modifiable risk factors that are out there that are important, we would still only be preventing or delaying onset of 40% of dementia. So I think those are indications that genetics is an important driver of Alzheimer's and why there's been so much attention over the past decades in genetic research.
That being said, as we'll talk about, it's certainly not the entire picture and that there are things one can do to reduce risk, and even if one does have the genetic risk factors, the ones that Thor and others have, those aren't kind of going to be destiny necessarily.
Matt Davis:
Wow. So it's not direct, but it implies that perhaps even half of it you think is maybe genetics?
Scott Roberts:
Yeah. Again, some people can maybe quibble with some of these heritability estimates that I was referring to, but those suggest that if you did try to quantify it probably would be slightly over half of the variability is explained by genetic factors. Not all of these are identified though, and we can talk about that, that there are certain known genetic risk factors, and then there's still other factors that are presumed to be genetic in nature that we haven't quite pinpointed yet.
Donovan Maust:
When you think about lifestyle risk factors that influence development of dementia, to what extent do those apply if you have genetic risk factors as well? Does it mean if you're at genetic risk, it doesn't matter if you smoke or not? Or how do you think about the overlap between lifestyle and these genetic factors?
Scott Roberts:
Yeah, I think there's certainly, even if you're at elevated genetic risk, I think we should still be encouraging the positive health behaviors that we talk about with brain health, whether it's exercise, stopping smoking, healthy diet, remaining socially and cognitively engaged, those kinds of things. I think they're relevant no matter what your genetic profile. And I think also they're just important for outcomes beyond dementia risk. As you know, Donovan, they're important to mental health and other aspects of physical health. So I certainly would not want to give anybody the message that, hey, if you have a family history of the condition, or even if you learn you're at genetically high risk from AOE or other types of testing, that you shouldn't still, in fact, maybe it's even more important than ever that you attend to some of these health behaviors that I think you're alluding to.
Donovan Maust:
And is it right, so I think that there are some specific, say very rare, essentially like a dominant risk factor where if you have this gene, you will develop Alzheimer's. Is that the case?
Scott Roberts:
Yes. Yeah, and we've actually known this since the 1990s. There are these rare mutations that are located on chromosomes 1, 14 and 21. So there have been three that have been identified that if you have one of these mutations, you'll almost inevitably get Alzheimer's, and usually with pretty early onset, so maybe even in one's 40s and 50s. Fortunately, they're very rare, so they only account for maybe 1 to 2% of all Alzheimer's cases. But in those situations, the genetic determinants of Alzheimer's are very prominent. And we do have specialty clinics, including here at Michigan, where if you have a family history that suggests that autosomal dominant form of the disease, that you can get tested because it might inform your life planning. But if you ever saw the movie Still Alice with Julianne Moore, who won an Oscar, she was an example of that. She was in her 50s, and she did have this rare mutation that caused the disease, but over 90% of cases, like I alluded to earlier, are not caused by those rare mutations.
Matt Davis:
So genetics can be confusing, and I even get confused by some of the terms people use, and my undergrad degree was in biochemistry. So I'm curious, I've heard you use this term and I've heard other people talk about APO, APOE.
Scott Roberts:
Yeah.
Matt Davis:
What are they referring to specifically?
Scott Roberts:
So the, yeah, APOE stands for Apolipoprotein E. So it's a specific gene found on chromosome 19 that we all have, but we all have different forms of it depending on what we inherit from our parents. And so we each inherit what's called an allele from our parents. So we have two copies of this APOE gene, and the different forms are known as E2, E3 and E4. It's the E4 allele that's the risk allele, that elevates risk for Alzheimer's. And so Thor, who you alluded to earlier, he has what's called an E4 E4 genotype. So he inherited one risk allele from each of his parents. So he has even more risk than someone who just has one E4 allele, if that makes sense.
Donovan Maust:
But so then is it right, so even one copy of the E4 raises your risk somewhat, and then two is even further?
Scott Roberts:
Correct. Yeah. And what's interesting about this is that the E4 allele is relatively common. So those other mutations I was just talking about are very rare in the general population, but I think about one in four adults in the US are E4 carriers. So that's a pretty common genetic risk factor. Luckily, the E4 E4 specific genotype is only maybe about 2 to 3% of the general population, but still compared again to some of these genes that cause other diseases, like Huntington's, you may have heard about. Those kinds of mutations are very rare usually in the general public.
Donovan Maust:
And so does APOE testing happen in clinical care? Should it happen in clinical here?
Scott Roberts:
Well, there's been a lot of debate over that. I think the concern is kind of twofold. One is that even though APOE is an important risk factor, it's not as nearly as predictive as some of those other genes I was talking about earlier. A phrase I like to use is the E4 allele is neither necessary nor sufficient to cause Alzheimer's. So you could have an E4 E4 genotype and never get the disease. You can get the disease with an E3 E3 genotype. So it's not super highly predictive. And that combined with the fact that we don't have proven prevention options. Like in heart disease, we would put somebody on statins, for example, or we have perhaps more confidence in the risk reduction recommendations as opposed to Alzheimer's where you can in theory modify your risk, but it's not as tried and true as in other conditions.
So I think that combination of the lack of predictive value of the test and the limitations in what we can recommend lead most medical groups to say, "We should not be generally doing this routinely." And I think part of that too is the concerns of the harms. And here's where a lot of our research has been trying to look at how likely are these harms and to what extent might they occur. I think the fear has been, hey, you have bad news about this terrifying disease like Alzheimer's, are you going to become depressed or anxious? Or if this information got in the hands of your insurers or employers, could they use the information against you? So I think there's been fears about that the harms might outweigh the benefits. And so there's generally been reluctance in the medical community to do this testing on a widespread basis.
Matt Davis:
Do we have estimates of the risk, like what your risk is if you have one allele or both for this?
Scott Roberts:
Yeah. And they can vary from study to study, but the statistics I like to use, the general population lifetime risk of Alzheimer's is about 10 to 15%. If you have an E4 allele, I think we could say maybe your risk is roughly double, so maybe 20 to 25% lifetime risk. And if you have two alleles, then you have several times the risk. And some of the estimates I've seen range from maybe like 45 to 60% lifetime risks in the E4, what we call homozygotes, they have two copies. So again, important but it's not like if you have the E4 E 4, you have a 90% chance like some of these cancer genes you hear about where it's really high risk if you're a carrier.
Donovan Maust:
Sometimes when we think about other kinds of tests in clinical care, you think about false negatives where somebody really has it, but the test doesn't show up or false positives where they don't have it, but the test shows up. For this kind of test, is that an issue at all or is it, it's accurate and if you have it, it shows up?
Scott Roberts:
I think it's pretty easy to have a correct call of your genotype. So I don't think the concerns of like, oh, we're misidentifying people who are E4 E4 as E3 E3. That is not a concern, but the test is not, it's just more of what we call a susceptibility test. An analogy might be like, hey, if you have high cholesterol, it puts you at higher risk for heart disease or if you smoke, but it's not like we use those tests as, you're going to get the condition if you test positive for it.
Matt Davis:
How expensive is it?
Scott Roberts:
It's not super expensive, and I think an interesting development has been, it's now available through these direct to consumer tests, which themselves are like, what, $99 through 23andMe? Or they have a holiday sale now, maybe it's even less. So in 2017, 23andMe got FDA approval to offer APOE testing as part of, you're probably familiar, they do all kinds of genetic tests in one fell swoop. You just spit in a tube, you send your sample in and they can tell you about everything from risk of Alzheimer's to Parkinson's to, I think they test for BRCA mutations for breast and ovarian cancer. They test for ancestry and all kinds of things.
So I think that development has raised a lot of concerns, I think, in the medical community where our preference is you get the genetic test as part of a formal medical consult, maybe you meet with a genetic counselor even. And then this is a very different approach where, hey, you're just logging onto your personal website and learning all this information about yourself. They have some educational materials on the website, but it's not in the context of discussing it with a medical professional. So that's been an interesting development, and there's been a lot of debate over is it even appropriate to allow this information to be disseminated that way.
Matt Davis:
That's probably such an interesting area for you to look at in terms of how people receive the information via these two different routes. I think that's really interesting, to think about how they respond to that.
Scott Roberts:
And I think there's certainly been anecdotal reports of people having pretty strong reactions to being blindsided by this information. Like, "Hey, all I wanted to do is learn my ancestry. Am I as Italian as I think I am? Lo and behold, oh my gosh, I wasn't even thinking about Alzheimer's, but this test shows I'm..." So I think there are concerns that people aren't properly prepared for the kinds of information they might get.
That being said, the studies we've done, and I think the broader literature does not suggest that this has been a widespread occurrence of catastrophic reactions where people are becoming clinically depressed or anxious. And so I think given that, we haven't seen the FDA modify its approach to regulating these kinds of tests or requiring that people have to meet with a genetic counselor before they learn the information, that kind of thing.
Matt Davis:
We've been asking about this APOE thing because it comes up a lot and you see it out there in the media, but it's not the only way that you can test for potential risk factors for Alzheimer's disease. There's other things like biomarkers. I'm wondering, how does it compare to those in terms of, from your perspective, I don't know, how good of a test is it compared to the biomarker tests?
Scott Roberts:
Yeah, so when you talk about biomarkers, I think you're usually referring to the two cardinal features of Alzheimer's are these amyloid plaques that can develop in the brain and how it tangles. It used to be that we could only see if those were present upon autopsy, but now we are able through neuro imaging or the spinal tap, what's commonly referred to cerebral spinal fluid, lumbar puncture. So you can get information that way, but now you can even get information through just a simple blood test that can detect, hey, are these amyloid plaques starting to develop in the brain? So to me, they're probably going to be ultimately more useful than a susceptibility gene test like APOE.
But some of the same issues arise, so you could be amyloid positive from one of these tests and never go on to develop the condition. A lot of older adults do have some amyloid plaques, but their thinking is fine, and they never get clinical manifestations of Alzheimer's. But I think there's a lot of excitement though in the field about these biomarkers because, not just could they identify people who are at high risk, but they can identify people who might be appropriate for some of the emerging therapies that are starting to come on board. We just had a, it's controversial, but there was a new FDA approved drug last year for treatment of mild Alzheimer's. There's another one that seems on its way to approval.
So I think these biomarkers are going to be ways that maybe identify people who might be appropriate for some of these new therapies, but I think some of the same sensitivity needs to be kept in mind in terms of how do we communicate because it can be pretty overwhelming for people and make sure people understand, again, this message of just because the test is positive doesn't necessarily tell us a whole lot about if and when you're going to develop full fledged dementia of the Alzheimer's type.
Donovan Maust:
So on a little bit of a tangent, occasionally on some other episodes, we've talked about the idea of cognitive reserve or protective factors, education, cognitively challenging activities that can be protective in aging. Is there any sort of evidence that in any way that factors that there's an overlap in risk factors for Alzheimer's disease? Are they in any way related to cognitive reserve? Is there any overlap there?
Scott Roberts:
Yeah, that's a good question. I don't know if this gets exactly at what you're asking about, Donovan, but there are some genetic factors that are protective. So I mentioned APOE 4, but the E2 allele, which is a pretty rare one, if people have an E2 E2 genotype, it actually seems to lower their risk of Alzheimer's. So maybe, and again, we don't know the mechanisms exactly by which this occurs, but I think in theory it's possible that maybe they could play into some of the resilience you're talking about.
I think my understanding of cognitive reserve is that oftentimes it's really a way to compensate for pathology that might be happening. So it's like a parallel process that allows someone, let's say they do have some of these plaques develop or tangles, their neural networks are developed enough that maybe they can still function even in the presence of this pathology that maybe the genes are helping to drive, if that makes sense.
Donovan Maust:
Yeah. Thanks.
Matt Davis:
So now we got some of the basics out of the way. I was wondering if we could shift gears a little bit and start talking a little more about the patient perceptions and some of, I suppose, the ethics around genetic testing for Alzheimer's disease. Something that I know that you and your team has thought a lot about.
So we have a devastating disease for which there is no formal cure, although there's some, like you mentioned, a couple promising things perhaps in the pipeline, and we're talking about a person finds out perhaps they're at higher risk, and that's probably pretty chilling information to receive. I was wondering, could you tell us just a little bit about what you've been doing with the REVEAL Study?
Scott Roberts:
Yeah, so the REVEAL Study, as you alluded to earlier, is a series of clinical trials we've done over the years, but they've all kind of been united by this basic premise. We're offering people the chance to learn risk information for Alzheimer's. Most of it has been focused on APOE testing, and then we're following people afterwards to see how do they respond to learning that information in terms of psychologically, behaviorally, et cetera. And so, one of the good news set of findings is that some of these feared psychological reactions, we haven't really seen happen too often.
And again, there's some caveats to our studies. This is a pretty selected, these are people who are signing up for this. They tend to be on average, higher educated than the general public, and they usually meet in our studies with a genetic counselor. So we do have a lot of things in place that might not generalize to direct to consumer testing or other context, but even given those caveats, it's been reassuring to see that even when people learn they're at elevated risk, they typically have not responded by becoming clinically anxious, clinically depressed, a lot of rumination or worry. That has not typically been how people have responded or if they've responded in that way, it's been in the immediate aftermath of learning it, and then by six weeks or so, they're back to their baseline levels of psychological functioning. So that's been one aspect that's been, I think, a positive.
It's been interesting to see what people do with the information. Some people do things like you might expect. They're starting to do the Sudoku puzzles more frequently, or maybe they do attend to their diet and exercise more closely. Some have added nutritional supplements or vitamins. There's this whole world out there of nutraceuticals, and some of them are explicit. If you go to a health food store, you'll see these things on the like, supports memory or these more vague statements that to me, are concerningly misleading in some respects. It's not totally irrational. I think there have been some epidemiological studies that suggest things like vitamin E, vitamin C, can maybe have some benefits for brain health, but a fair amount of our participants said that they did something like that. And so that's one area where I think we should keep an eye on because that's a much more unregulated industry than our pharmaceutical industry.
To me, it also fits into these broader concerns even beyond genetic testing of, as our population gets older, what kind of quick fix products, whether it's cognitive training or other kinds of things are being marketed to older adults to capitalize on this fear of developing dementia. So that's been an interesting element of what we found.
Another thing that we've found that sometimes people do that I think all raises some broader ethical issues is one rational response might be, "Hey, I'm going to think about getting some long-term care insurance if I'm at high risk, because that might help if I do develop Alzheimer's, might help me and my family down the line." But interestingly, there are laws on the books that protect against genetic discrimination. So you may have heard of this legislation called GINA, the Genetic Information Discrimination Act. So that prevents health insurers or employers from using genetic information against you, but it does not cover long-term care, life or disability insurance. So there are these gaps in that protection against genetic discrimination that some have said, "Well, maybe we need to expand GINA to cover those." I don't mean to suggest that genetic discrimination is rampant in the long-term care. I don't think we know that, but it's, in theory, it's something I think people worry about if APOE testing becomes more commonplace, could long-term care insurers or life insurers start trying to factor it into their premium decisions or coverage decisions?
Donovan Maust:
As part of the study, do you report test results to participants' clinicians?
Scott Roberts:
Not as a routine matter of fact, but we try to give them information that would be useful if they want to take that to their physicians, but we try to leave it in the hands of the participant.
Donovan Maust:
And I'm curious if you ever hear back then from participants about how that conversation with a clinician goes, because my guess is most clinicians would feel totally unprepared to discuss these results and wouldn't really know how to talk about the risk or what the results really mean. So just curious if you've gotten any feedback on that front.
Scott Roberts:
Yeah. Well, I guess I'm thinking of a broader study. We had a study where we looked at people who had used direct to consumer genetic testing more broadly. And so we surveyed consumers of both 23andMe in this company called Pathway Genomics at the time had a DTC model going. And we found that over one in four of our respondents said that they had divulged their results to their primary care physician, which we thought was a pretty high number. And I think a lot of them... We didn't go in great detail as to how did that go and what happened, but some of this issue of you're talking about the potential lack of preparation or self-efficacy on the part of their physician, they were, I think, we did find that a lot of them were saying the physicians didn't really know how to respond.
And I think some of the patients felt frustrated by that. But to be fair to primary care docs, this is not part of their training because a lot of these tests are not in routine use in clinical care. They don't have that clinical utility where they would be warranted. And so I think it does create this interesting dynamic. Some of the ethicists like to call this phenomenon rating the medical commons. They feel like that they get frustrated with the companies that punt to the doctors, "Oh, if you have any concerns, go ask your doctor." And they don't have to worry about it. And then the doctors are like, "I don't want to be dealing with this information that's arguably not of direct benefit to my patients."
Matt Davis:
Clinicians, in my opinion, are some of the most practical people I've ever met. And I'm just curious, in your work, do you ever come across clinicians who even question the value of early detection?
Scott Roberts:
Of dementia in particular?
Matt Davis:
Yeah, Alzheimer's.
Scott Roberts:
Yeah. I think certainly, I think it does depend on specialty. I'm sure Donovan has a lot of thoughts here too. I think a lot of more generalists are going to wonder, is this really worth going down this road that might be very laborious, time intensive, costly, when at the end of the day, what we can offer has so many limitations in terms of we don't have the magic bullet cure. Whereas I think the specialist, like the neurologist might say, "Well, it's still an early diagnosis, can help the family plan. We do at least have some therapies that can maybe in the short term help improve symptoms." So I think there are disciplinary differences among physicians into how useful they think an early diagnosis is. And Donovan, I'm sure you can add on here.
Donovan Maust:
Yeah, I guess I also think, I definitely think of the timing of the diagnosis as distinct from learning about genetic risk. So for sure, I think a diagnosis generally is useful information for people and for their families. The learning about your genetic risk I think is trickier because, as we discussed, a lot of the things you would do related to lifestyle would be the same regardless of what your level of risk is. And so if you're a clinician working with a patient in their 40s or 50s say, there are potentially so many other things that you and that patient are trying to address and think about and worry about.
So then learning about genetic risk for dementia where there's not a definite preventative intervention and the general lifestyle counseling would be pretty much the same regardless of what the test result is, I do think that that's kind of a hard sell for your average clinician to really think that that's worthwhile for the patient.
Scott Roberts:
In our work, we talk a lot about this distinction between clinical utility and personal utility of information. And I think clinicians are understandably very focused on clinical utility, but it's harder to know what to do with these "personal utility reasons". A lot of our participants have said, "Well, yeah, maybe I should be doing these things, but I'm going to be more motivated if I know I'm at higher risk." Or a lot of our participants have said, "Well, I don't know exactly how it might be useful, but I would just rather know that not know. Knowledge is power." And so how do we value that sentiment in these decisions? I do think interestingly though, we are seeing APOE is now becoming relevant in other ways as well. There are some prevention trials for Alzheimer's where eligibility might be determined in part by genetic risk.
So if you're at high risk, maybe you become eligible for a prevention drug trial, then you otherwise would not. And some people find that appealing. And then once someone has symptoms, these new class of drugs, I don't know, have you guys talked about on other podcast episodes, like Aduhelm or-
Donovan Maust:
Season one, we talked to Ken Langa.
Scott Roberts:
Well, Aduhelm is an example, but even Lecanemab or some of these other anti amyloid therapies that are in the pipeline, they all seem to carry this side effect known as ARIA, which refers to symptoms that can include swelling or bleeding in the brain that are usually not a major concern but can present some problems for the patient. Well, it turns out that E4 carriers, not only are they at elevated risk for Alzheimer's, but they're also at elevated risk for side effects from these medications.
And so there's some recommendations that, hey, if you're going to prescribe one of these medications to someone with mild cognitive impairment or early Alzheimer's, you should be doing APOE testing concurrently because then that might help someone know their chance of side effects. So maybe people, it might even inform their decision whether or not to go on the medication to begin with, if they feel like, "I was kind of on the fence and now I know it's likely I'll have these ARIA side effects that maybe I don't want to go that route.È
Donovan Maust:
So if this is too personal, you don't have to answer, Scott, but I'm curious, have you been tested and would you recommend your own family members get tested?
Scott Roberts:
I have. I just feel like being in the field, I thought it would be interesting to learn my, not just a APOE genotype. So yes, I have been tested. Fortunately I'm not an E4 carrier, but it wasn't major news. It wasn't like, oh my gosh, what a sigh of relief. But I did find it moderately helpful to know that I do not have a strong family history of Alzheimer's or dementia. So it also maybe made some sense in that context. But yeah, I feel like otherwise it's kind of a personal choice. I don't recommend it. On the other hand, I don't actively dissuade it. I do have some colleagues who I think would say, "Oh, it's a bad idea to get direct to consumer genetic testing," because some of these risks we talked about earlier. I tend to think that most people are decent judges of their own ability to handle this kind of information. And so I'm kind of a centrist, I guess on the issue.
Matt Davis:
What percentage of the population actually even want to get tested? I was just curious. There's got to be some avoidance among some people that just don't want to know, even people with a family history.
Scott Roberts:
Yeah, for sure. My wife would fall in that category. The health psychology literature has this concept of health monitors and health blunters. Some people, they want to know every possible piece of information that's out there, even if it's not directly beneficial. Whereas others, the blunters are more like, "If I really absolutely need to know something, then maybe yes, I'll learn, but otherwise I don't want to cast a pall on my day if I have to think about these things." So I think there are some really interesting individual differences.
What's been interesting to us though is when you ask questions about interest in genetic risk information for Alzheimer's versus other conditions, the level of interest in Alzheimer's is pretty close to conditions that you could do much more about, like the cancers and heart disease. So we've been surprised at the level of Alzheimer's interest when we do these broader surveys of public interest in this information.
Of course, saying on a survey you're interested is one thing, and then signing up for testing is another. We saw that in other conditions where some of these pretest surveys suggested, oh, everybody's going to want Huntington's testing who's eligible. And then only a small proportion came forward. But there does seem to be a broad interest in... Because it's a common disease. I think there is some sense that even if we don't have a cure, maybe there's things you can do. And then again, these personal utility reasons, I think a lot of people just feel like, "Hey, I have this general sense that I want to know what's my relevant risks, and it may or may not be useful down the line."
Matt Davis:
Yeah, it's very different from saying on a survey that you're interested versus taking a deep breath and actually doing it.
Scott Roberts:
Yeah.
Matt Davis:
So you alluded a little bit to some of the effects that you've observed in your studies on how people change their behavior a little bit. And you said start doing more puzzles and those types of things. What do we know downstream, long term consequences? Do we have evidence that people that were tested for it way ahead of developing symptoms, any differences in terms of end of life care and advanced planning and all that kind of stuff?
Scott Roberts:
Yeah, it's a great question. I don't think we have much literature on these longer term impacts. Our studies have tended to follow people from maybe six months to a year after they learn the information. So we don't really have a great feel.
Some folks are learning this information, in our early studies, some of them, people in their 40s and 50s where, again, if they were going to develop it, it would still be likely decades away. So I think it's still an open question as to what are the longer term impacts of this kind of information.
One thing that's interesting is the genetic counselors I work with have told me that a lot of people put a lot of credence, understandably if they have a family history, when did my parent or grandparent develop the disease? And so that's a time where I think people's anxieties might resurface. Like, "Hey, I got this result in my 50s, but now I'm in my 70s and I know my mom started showing symptoms when she was 75." And so you might speculate that maybe the reemergence of some of these concerns might be many years after the fact of learning your genetic risk or these early signs of subjective concerns or things... Everybody has memory lapses or they lose where their keys are, can't find their car in the parking lot. But you could imagine that someone who, hey, if I know I have a family history and I'm this E4 carrier, the meaning of those kinds of symptoms might be more dramatic when they're in their 70s and 80s.
Donovan Maust:
Are there some say, new trends on the horizon for dementia related testing and disclosure?
Scott Roberts:
The biomarkers we were talking about earlier, I think, are really going to be a big deal and are already. We already have commercial companies marketing blood biomarker testing to aid in diagnosis, and I think that's only going to expand dramatically. Again, if we see Lecanemab, for example, getting approved next year, people seem to think it's going to happen. I think we're going to see a real explosion of marketing of blood biomarker tests and they're going to be marketed for use in cognitively impaired patients. But you can see how then older adults, "Hey, I'm not formally impaired, but I'm not as sharp as I used to. Can't you just give me that test, Doc?" You could see the expansion of this because if it's a blood test as opposed to I have to go get a PET scan, the cost and access issues will be dramatically different.
So I think that'll be an interesting area to monitor. In terms of the genetics, I think where the field seems to be moving is these polygenic risk scores that you may have heard about, where APOE would be just one of a whole panel of tests where then your predictive value might be more powerful if you can combine looking at many genetic risk factors at once. Most genes aren't going to be as powerful as APOE, but if you add up 20 to 30 others, you could start to see the predictive value of these polygenic risk scores being greater than just APOE alone. So I think we'll start to see, potentially... Right now they are being used heavily in research, but we might see some greater application of those.
Matt Davis:
So I must say one of my goals today was to try to segue back into Chris Hemsworth. He has a series now on National Geographic series looking at different therapies and strategies to prolonging health and all this. And he actually has a whole episode on memory and another one on healthy aging where he wears... I was struck by this last one. Where he wears an aging suit. You guys ever seen this? It mimics aging and it restricts your motion and blurs your vision and all stuff was quite fascinating. I do wonder though, how much that entire series may have been partially... Maybe he's just interested in health or maybe it was partially driven by his-
Donovan Maust:
So actually it was totally because of this, Matt. When I read your introduction, I googled it. And so he, as part of one of the episodes for this series, he was tested for APOE and got the results as part of that testing. And then they actually, apparently the series consulting doctor had a whole conversation with him because the plan was to present the results live in front of the camera.
Matt Davis:
Oh, wow.
Donovan Maust:
And so when he saw these results, they had a whole conversation about, "You should know this. Do you want to talk about it on the show?" So that's how this all actually happened was because of that series.
Matt Davis:
Wow. I have to watch that one episode.
Scott Roberts:
Well, I'm glad you brought it up though, because although my Entertainment Weekly subscription has lapsed, I'm a big pop culture person and a believer in the importance of pop culture in sending messages for better or for worse about health and medical options. Angelina Jolie was very public about her BRCA testing experience for risk of hereditary breast and ovarian cancer. And I think that really drove a lot of interest in the field and created a lot more referrals and inquiries. So it'll be interesting to see what this does for APOE testing.
What was interesting to me was that I haven't looked really closely at the media coverage yet, but my cursory glance was, there wasn't a lot of discussion of... Genetic information has implications for other family members as well. And so when you learn you're an E4 E4 carrier, any of your children will be what we call obligate carriers. Just the laws of genetics are any of your children won't then automatically inherit one E4 allele from you as the parent. And then we know also by deduction that his parents are each at least E4 heterozygous because he had to inherit one.
So him revealing that, whether his relatives know it or not says something about their status too. And maybe they already knew that or maybe they didn't care. But I think we do need to think about genetic information differently than some other types of health risk information because of these ripple effects.
From an ethics standpoint, I think the rule of thumb in medical genetics is we don't like to disclose genetic information to children or adolescents unless there's something that's medically necessary to do so. The fact that his kids would now have this information about them public.
Matt Davis:
How interesting, yeah.
Scott Roberts:
Some might say, "Oh, that's inappropriate," because does it saddle them with information that they would maybe rather not have.
Matt Davis:
All really important things to consider. Scott, thanks so much for joining us today.
Scott Roberts:
Yeah, thank you guys. It was great.
Matt Davis:
As we wrap things up, I also want to thank Chelsea Cox for her help behind the scenes putting this episode together. Chelsea is a graduate student in Dr. Robert's lab and an emerging scholar in this space.
If you enjoyed our discussion today, please consider subscribing to our podcast. Other episodes can be found on Apple Podcasts, Spotify, and SoundCloud, as well as directly from us at capra.med.umish.edu, where a full transcript of this episode is also available. On our website, you'll also find links to our seminar series and data products we've created for dementia research.
Music and engineering for this podcast was provided by Dan Langa. More information available at www.danlanga.com. Minding Memory is part of the Michigan Medicine Podcast network. Find more shows at uofmhealth.org/podcast.
Support for this podcast comes from the National Institute on Aging at the National Institutes of Health, as well as the Institute for Healthcare Policy and Innovation at the University of Michigan. The views expressed in this podcast do not necessarily represent the views of the NIH or the University of Michigan. Thanks for joining us, and we'll be back soon.
Listen to more Minding Memory podcasts - a part of the Michigan Medicine Podcast Network.
