Family Ties: How Family History Affects Alzheimer’s Risk

Intro: I'm Dr. Nathaniel Chin, and you're listening to Dementia Matters, a podcast about Alzheimer's disease. Dementia Matters is a production of the Wisconsin Alzheimer's Disease Research Center. Our goal is to educate listeners on the latest news in Alzheimer's disease research and caregiver strategies. Thanks for joining us.

Dr. Nathaniel Chin: Welcome back to Dementia Matters. Today, I'm joined by two returning guests, Drs. Jessica Langbaum and Sterling Johnson. Dr. Langbaum is the senior director of research strategy at the Banner Alzheimer's Institute. At Banner, she oversees the Observational Research Program, Clinical Trials Program, and Alzheimer's Prevention Initiative departments, as well as directs the Alzheimer's Prevention Registry and its Gene Match Program. She's also the director of the Arizona Alzheimer's Disease Research Center. Dr. Johnson is the Gene R. Finley Professor of Geriatrics and Dementia here at UW School of Medicine and Public Health. He's the associate director of the Wisconsin Alzheimer's Disease Research Center and Wisconsin Alzheimer's Institute, leader of the Wisconsin Registry for Alzheimer's Prevention Study, known as WRAP, as well as the lead principal investigator of the ADRC Consortium for Clarity in ADRD Research through Imaging, known as CLARiTI. They join me today to talk about how one's family history can impact their Alzheimer's risk, particularly focusing on the role of the APOE gene as a risk factor. Dr. Langbaum and Dr. Johnson, welcome back to Dementia Matters.

Dr. Sterling Johnson: Thank you. It's good to be here, Nate.

Dr. Jessica Langbaum: Yeah, likewise, thanks.

Chin: Now I have to confess that I've been looking forward to today's show for some time. The topic of family history in APOE4 is one that impacts many in the community and in the research field. And frankly, there is still much to be understood. Back on September 22, 2024, Darby Peter, a research assistant in Dr. Barb Bendlin’s lab, and I wrote an opinion piece in the Wisconsin State Journal titled, “Family History is Risk, Not Fate.” We made the case that people with a family history of Alzheimer's worry a lot about getting Alzheimer's, but the reality is it's just not as significant as we once thought and it's more complicated because it's a combination of genetics, health conditions, lifestyle factors and environmental exposures. The fear people have prevents evaluations, which is detrimental because not all memory loss is due to Alzheimer's. There are many reversible or modifiable factors that can be addressed, and biomarkers like blood tests, spinal fluid and PET scans can help us understand what's happening in the brain, giving us a better picture. We concluded that we are not our genes and should push through our anxieties to be evaluated and address our cognitive concerns. Now, when I shared that essay with you, Sterling, I recalled you appreciating the sentiment but not fully agreeing because you recognize specifically the risk of Alzheimer's when one has APOE4. You had been a part of a publication in Nature Medicine titled, “APOE4 Homozygosity Represents a Distinct Genetic Form of Alzheimer's Disease,” which made the case that having two copies of APOE4 meant a person was going to have biological Alzheimer's, as defined by the presence of amyloid in the brain. Your feeling was that family history, but specifically APOE4, was more important than ever. Now, Jessica, you and two colleagues just published in JAMA Neurology a viewpoint making the counterargument that the field is not ready to separate this group as distinct and in fact there is more hope than previously thought for those living with one or two copies of the allele. So I want to jump right into this discussion and, firstly, the groundwork of family history and APOE4 or APOE before we talk about having two copies of APOE4. Sterling, can you talk about how having a family history of Alzheimer's disease influences one's risk of developing it as well?

Johnson: Yeah, this is something we've been studying for a long time in the WRAP study, Wisconsin Registry for Alzheimer's Prevention. That registry is actually–its recruiting theme is family history. We've been recruiting people whose parents ostensibly had dementia due to Alzheimer's disease. And I say ostensibly, meaning we don't actually know if their parent had Alzheimer's as the cause of their dementia or not. Family history can be an imperfect construct to study risk because it's kind of a vague risk factor in and of itself. The likelihood that their parent who they think had Alzheimer's–it is likely that that diagnosis was right about 70 or 80 percent of the time, but that means 20 or 30 percent of the time the diagnosis was wrong. In the study, we often rely on self-report of our adult children participants to report on what they think their parent had. That's a long way of saying that the family history of Alzheimer's disease is an imperfect diagnosis. It can be vascular disease. It could have been Lewy body disease or a new disease we're appreciating now called limbic age-related TDP encephalopathy, which is another protein that mimics Alzheimer's disease. It’s an imperfect construct. The other thing I'll just say while I'm droning on here is that when we've looked in our cohort and tried to understand the risk of having a parent with family history on a person's own cognitive decline, we didn't find that family history explains much more of the variance or it didn't explain any more of the variance than did the genetic testing itself, the APOE testing that we're gonna talk about.

Chin: Okay, so that's a pretty powerful piece of information right at the end there, Sterling. Having the family history didn't add any more explanation than just the APOE alone.

Johnson: Right.

Chin: And I'm going to add–before I move on to you, Jessica–I am going to add that in clinic, when patients tell me they have a family history of Alzheimer's, I do try to clarify and ask, “Well, do you mean you have a family history of dementia?” Because oftentimes people will use those terms synonymously. Many times they'll correct me and say, “No, no, Dr. Chin, I mean Alzheimer's.” And then I'll ask politely, “Well, did they have an autopsy? Or how do you know it was Alzheimer's?” More often than not, it's word of mouth. And so, of course, I'm here at Wisconsin and so I work with you, Sterling, but I do see this word of mouth and this idea of a record that is really just based on verbal history or oral history and that can be misleading.

Johnson: Yeah. Our physicians don't yet have the tools they need in specialty care to make this diagnosis as accurately as they could if they had access to amyloid PET imaging and the new blood markers and the CSF markers that are available. That wasn't available five years ago or 10 years ago when a lot of our participants enrolled. So it's true that it's a very imperfect diagnosis, and that's similar to what you're experiencing in the clinic.

Chin: But you did mention APOE. So Jessica, can you tell us more about the APOE gene and how much does that impact one's risk of Alzheimer's?

Langbaum: The APOE gene, which stands for apolipoprotein E– everybody has this gene, right? It comes in three types, or we call them alleles. You get one copy of the gene from mom and one copy of the gene from dad. The three types, we call them APOE2, APOE3 and APOE4. You can get a copy of the APOE3 gene from dad and a copy of the APOE4 gene from mom, and then you’re an APOE3-4 or an APOE4 heterozygote, meaning you have one copy of the gene. If you happen to get a copy of the E4 allele from both mom and dad, that means you're an APOE4 homozygote. And for quite some time, researchers including us here in Arizona have been studying individuals with zero, one or two copies of this APOE4 gene, following them over time. We know that having one or two copies of APOE4 increases your risk or susceptibility of developing Alzheimer's in later life, but this is really quite different than hereditary autosomal dominant gene, like a mutation on the Presenilin-1 or Presenilin-2 or APP genes, in which that genetic mutation is passed down from generation to generation to generation. If you have that genetic mutation, it causes, with nearly 100 percent certainty, that you will develop Alzheimer's disease and typically at a younger age. APOE4 increases your risk or susceptibility of developing Alzheimer's disease at older ages. There's sort of an age relationship with APOE4 such that if you have two copies, your age of risk is in your mid to late sixties; one copy, mid-seventies, early to mid-seventies; and no copies, late seventies, early eighties. And I just want to say that age is actually the best established risk factor for developing Alzheimer's disease. As we age, we are all at risk. Having one or two copies of APOE4 just happens to increase your risk, but really it's moving the needle through age, right? Your age of onset is at the younger age spectrum versus older. APOE itself is really just known for influencing how our brain influences lipid metabolism and so it's related to cardiovascular health. How APOE and why it increases our risk of developing Alzheimer's disease– it’s far outside of my area of expertise. Others have really dedicated their whole careers and we could have a whole other podcast developed to actually what APOE does and why APOE, particularly the APOE4 allele, exerts such an increased risk.

Chin: But this level of risk will vary though based on certain background factors, right, Jessica? So based on race in particular?

Langbaum: Yeah, so this is really interesting and why we need a lot more studies on this topic and really increasing the representation of participants in our research studies. While we know that APOE–most of our research has been done on non-Hispanic white individuals of European ancestry, majority of longitudinal studies and in our field. There's some research out there that the strength of the association between APOE4 and Alzheimer's disease really might differ based on race and ethnicity so that the association of APOE4 might be lower in some Black or African-American and Hispanic Latino communities. While these groups often will report a higher prevalence of Alzheimer's disease, perhaps is it Alzheimer's disease or other forms of dementia or are there other risk factors at play here in addition other than APOE? This is a really active area of research, but one that's going to require more longitudinal studies in representative populations.

Chin: And just to confirm for our listeners too, the APOE2 is thought of as a protective gene?

Langbaum: Yeah, thank you. Yeah, APOE2 is thought of as protective, so if you happen to have two copies of APOE2 that's thought to be very protective. I think this is a really active and interesting area in terms of drug development. Like how can we, through medications, mimic the effects that APOE2 has through a medication? Similarly, the Christchurch mutation on APOE3– this is a rare variant–it is also protective. Our colleagues discovered this woman in Columbia, South America, who happened to have the autosomal dominant mutation on the Presenilin-1 E2ADA gene. She should have developed Alzheimer's disease. She had a head full of amyloid but yet no tau. As they started to figure out why this was, what's going on here? Why hasn't she progressed to clinical symptoms in her seventies? Well, it turns out she had two copies of this really rare variant on the ApoE gene called this Christchurch mutation. So the APOE gene, I think, is just really fascinating and there's a lot to learn here.

Chin: Well, so those who carry the APOE4–two of those copies–have a lifetime risk for Alzheimer's disease dementia that can reach 60 percent by the age of 85. I got that from the article in Nature Medicine, Sterling, that you were a part of. That was really looking at five large cohorts with Alzheimer's biomarkers that were being analyzed. The study compared people with two copies of APOE4 to people with two copies of APOE3. If you don't mind sharing with us, our listeners, what were the findings that were so important in that paper?

Johnson: Yeah, thanks. It's an exciting paper that has sparked debate and I've never been part of a paper that has sparked as much debate as this one, which is really great. That's, I think, important to bring more emphasis and attention to this topic. What we found in that paper was that–first of all, there were two levels to that paper. One is looking at the actual brain and seeing how much amyloid was in a person's brain, amyloid and tau and all the hallmark signs of Alzheimer's disease. This is kind of our gold standard approach. So we looked at that, and then the second phase of that paper was to look at the biomarkers. They're less direct than looking at the actual protein levels and the amyloid plaques in the brain itself. When we looked at the brain itself–this is from the National Alzheimer's Coordinating Center. All the ADRCs, including Arizona, Wisconsin, and everybody else, we all contribute to this national database. What we found was that I think it was by age 65, there was something like 90 percent of the E4 carriers were already amyloid positive and that by age 85, it was near universal. And then when we looked at the biomarkers, 75 percent of the folks who had E4 homozygote status were positive for the fluid biomarkers by age 65. I think it was something like 88 percent were positive by age 80, either the fluid biomarkers or PET scans. It showed us that there was maybe something more to the story than we had previously thought. It seemed to show that there's a pretty strong likelihood of having the amyloid side of the Alzheimer's pathology in your brain if you have if you're homozygous for APOE4.

Chin: Yeah, Sterling. Looking at the paper, age 65, nearly every person who had two copies of APOE4 had the abnormal spinal fluid levels and 75 percent had abnormal PET scans for amyloid. And you're right, at age 80, they said 88 percent had abnormal amyloid and tau biomarkers. You're right; those are the indirect findings, but they also show they also talked about symptoms in your manuscript or your paper. This is speaking to something that Jessica was saying too, that symptom onset was seven to 10 years earlier. What do you make of that? Perhaps you can speak to the WRAP study too when it comes to APOE amyloid onset and symptoms.

Johnson: This is such an exciting topic, and it's one that I'm really enjoying. Let me back up to say that we've been doing amyloid imaging in the WRAP study since 2009. We've done a lot of amyloid PET scanning in this cohort, as have other cohorts–ADNI, the Baltimore Study of Aging, the Harvard Aging Brain. There's several cohorts that have been doing this longitudinally. What we found in WRAP in a different paper–one published by Tobey Betthauser in 2022–was that in the ADNI study and in our study, WRAP, and in the Baltimore Study on Aging, we found in each of those studies an APOE4 effect on the age at which we estimate that a person became amyloid positive. And E4 homozygotes are about, they develop amyloid in their brains–detectable amyloid in their brains–about 10 years before E3 homozygotes. And this, I think, makes sense with the Nature Medicine paper that you're going to get it earlier. The other thing that this Betthauser paper showed us was that the range of amyloid onset age is quite large. E4 homozygotes, yes, the average age of amyloid onset was in their, I think, late fifties or early sixties, but the range, the minimum and the maximum that was a span of about forty years. Some people can get this disease in their forties, some people may get it in their eighties is what that's telling us. And that the genetic component of this is telling us about the average, but we still need that personalized approach to understand each individual in our studies and that's sitting across from us in the doctor's office.

Chin: I think that's something you and Jessica share there. I'll wait for a few minutes when I ask Jessica a follow-up question. In this study, you compared the biomarker changes with APOE4 to the autozonal dominant Alzheimer's disease, and Jessica explained that. That's the Presenilin-1 and 2 and the APP mutation, and also to adults with Down syndrome. The study found similarities in this timeline of biomarker development. Why is that important in this paper?

Johnson: It's really important because that gives us the context of this autosomal dominant penetrance. The penetrance is if you have this genetic background, what is the likelihood of this phenotype occurring. And with autosomal dominant Alzheimer's disease, it's nearly one hundred percent penetrance. If you have the genetic mutation, you're going to get the eventual symptom or the eventual disease. I think that's why it was so important to compare it to those, to compare these E4 homozygotes to that, because it showed a similar level of penetrance. People with the E4 homozygotes pattern had a very high likelihood of being amyloid positive.

Chin: And so, Jessica, in your most recent article in JAMA Neurology, you say it's too soon to conclude that APOE4 homozygotes who live to older ages are destined to develop biological Alzheimer's and the subsequent symptoms. Why do you say that?

Langbaum: Yeah, that's a great question. We looked at some of our own data from our ongoing longitudinal studies, again, in people with various APOE genotypes, as well as our studies from other researchers and the API Generation Program. There are still plenty of APOE4 homozygotes who do not have evidence of amyloid pathology at these ages. We think that there's such a need to, first, continue to unravel and unpack what are some of the protective factors that might be in play here that might be accounting for the lack of amyloid pathology. Like if somebody has made it to age 70 and they don't have amyloid pathology, yet are APOE4 homozygotes, that's telling us that there's some protective factors at play. To conclude that APOE4 homozygosity is akin to some of these autosomal dominant mutation mutations where, again, for the most part it's very, very rare for somebody to avoid developing the disease and having the pathobiology associated with the disease, we felt that it's really too soon to say that APOE4 homozygosity is this unique and akin to these autosomal dominant mutations, that they are destined to develop Alzheimer's disease, frankly.

Chin: And so you made a comment too about cross-sectional data versus, and even longitudinal data, and that we need to be careful about conclusions that we're making. Can you go a little bit further into that?

Langbaum: Yeah. Well, some of the cross-sectional studies, like the original studies looking at APOE4, were based on cross-sectional neuropathologic. These are looking to oftentimes–either it's a moment in time or they're looking backwards. And so particularly like case-control studies and where you find that, let's say, 90 percent of homozygotes are destined to develop Alzheimer's disease. Frankly, when you enroll individuals in longitudinal studies, we see much lower rates of either a diagnosis of Alzheimer's disease or some of the–now of course we have biomarkers that we didn't always have, but we do see a much lower risk. You know, we're trying to develop genetic counseling materials for telling people their APOE results. We really wanted to look at longitudinal studies that enrolled people before the age of risk or the potential age of onset, so enrolling people in their fifties, and then following over time to see what's the likelihood of developing Alzheimer's disease in later life. What we find is that, even for APOE4 homozygotes, we estimate that the chance of developing mild cognitive impairment or dementia due to Alzheimer's disease is really 30 to 55 percent, not 90 percent as based on some of those cross-sectional studies, because there are other factors at play, Nate, that you talked about early on. There are environmental factors, there's protective factors. There's other things going on that might actually be influencing their risk of developing Alzheimer's disease in life. So we really do look to those longitudinal studies instead of those cross-sectional studies for really understanding risk.

Chin: It makes a good case for why it's so important for people to participate in research and these longitudinal studies so that we can get a better sense of individual and even risk over time, Jessica. Right?

Langbaum: Yeah, we really do need participants in research studies and like the WRAP program is a really great example of the community coming together and participating in research. I think what we now need in addition are representative cohorts. Again, I mentioned earlier that a lot of our risk estimates and our understanding of the biological changes and the biomarker changes that we're developing and we have all these PET scans and blood samples. Well, they're still taken from individuals, non-Hispanic white individuals of European descent. And what we, I think, continue as a field to really need are really representative studies,good representation for men and women, races and ethnicities to really fully understand the role of APOE in the different populations, the biomarker changes that occur, again, following people over time. It's really important.

Johnson: I agree with that so much, Jessica. And I think that as we get more confidence in these blood biomarkers and collect these in population-based studies, that maybe we'll be able to get the kind of coverage we need of the full population to really understand this. The other sampling, in addition to the paucity of our race and ethnicities in our studies, is that we also have a paucity of studying the very oldest olds. The older you get and the fewer data points you have, the more unstable the point estimates become in these research studies. We need to replicate this. We need to look at this in different race and ethnicity backgrounds and certainly see what we can find in the general population rather than in these big samples of convenience that we've been studying.

Langbaum: Yeah, and I'll just add one more thing, right? I talked about race and ethnicity, but there's other factors at play, right?Where you grew up, where you live and where you live now, so urban, rural, the area deprivation index. There's so many factors at play here, right? Participating in research often tends to be a privilege and we, as researchers, don't make it easy for participants by only running our studies Monday through Friday from nine to five. And so making research more accessible for individuals who work during the day and can't come into our studies and from different socioeconomic backgrounds. I think that it goes beyond race and ethnicity here, but we really need that representation of participants in our studies.

Johnson: Nate, I wanted to also say that the effect that we saw in that Nature Medicine paper was about-it was the predominant focus there was about amyloid plaques or evidence of amyloid plaques in the brain. One way that we think about Alzheimer's is if you have that particular biomarker, you're in the lane of Alzheimer's disease. Most of the inference in that paper was around that particular feature of Alzheimer's disease. Symptoms are another matter. I agree completely with what Jessica said. It was that when in these longitudinal studies, you don't often see these really high rates of conversion. We are seeing the same thing in WRAP. We're not seeing high rates of conversion to clinical symptoms and so we need to keep following people and understand why that is or isn't the case. I just wanted to raise that point, that the biomarker evidence of the disease and the clinical manifestation can be disambiguated and one is certainly going to predict the other but there's a lot of variance there. The average age from amyloid onset to symptom onset may be 20 years or so. That's kind of what we're finding in our study, but there's a big range there. Some people develop symptoms fairly soon, some people much later than 20 years. And then I also want to just go back to the amyloid onset idea I mentioned earlier. In these autosomal dominant cohorts, there's still a range of amyloid onset age, like in Down syndrome. There's not one particular age that people become amyloid positive. There's a 20, 30, 40 year span. Same in autosomal dominant disease, there's a range of amyloid onset age that if we can harness that and understand that, I think we will be able to treat our patients in a much more customized way to their own disease journey that they're on.

Chin: And Jessica, in your study, speaking to what Sterling's talking about, what do you say to individuals who have two copies of APOE4 that are not having symptoms but you're sharing this information to them? You've shared that they're at higher risk of having Alzheimer's disease. Do you give them–are there a certain lifestyle recommendation, certain clinical trials, certain treatments that are unique to them, or is it more of a holistic approach for brain health and for the general population as well?

Langbaum: When we're disclosing APOE genotype to individuals, we share what their risk is. And again, for APOE4 homozygotes, based on the longitudinal data we put their risk of developing MCI or dementia due to Alzheimer's disease anywhere from 30 to 55 percent by age 85 and then we talk about factors that might decrease their risk or increase their risk. Those factors are–those are the same protective and risk factors that we share with everybody irrespective what their actual APOE genotype is. We share things, for instance, being a woman might increase your risk, and there are modifiable risk factors and non-modifiable risk factors, right? We know that being a woman, lower education, those are things that might increase your risk. Things like heart disease, having high blood pressure, things of that nature may also increase your risk. Then we talk about the importance of getting regular physical exercise, aerobic exercise, a proper balanced nutrition diet, sleep, all of the things for overall brain health. What's really interesting, we find, is that we follow up with people after we've told everybody what their APOE results are– and I think this gets back to some of the family history things–even if we tell a non-carrier, “Your risk is 10 to 15 percent by age 85 that you will develop Alzheimer's disease,” if you ask them afterwards, “What's your risk?” It's always higher. On average, people report a higher risk, what they feel their risk is, compared to what we told them. That is true for APOE4 non-carriers, heterozygotes and homozygotes. I think that these are opportunities actually for us to really rethink how we communicate information, let them know that, again, there are things that they can do to improve their brain health. Everything that we talk about, nothing is going to 100 percent prevent developing Alzheimer's disease if you're homozygote, heterozygote, non-carrier, but there are things that we can just generally do for brain health. So I think that there's opportunities, I guess again, to say or to rethink how we communicate APOE information to participants so that they feel that this doesn't define them entirely. We had the opportunity to lead a particular trial for APOE4 homozygotes and one for heterozygotes with elevated brain amyloid. Right now, there's not a particular trial for APOE just based on APOE but that's not to say there won't be one in the near future. There are clinical trials and prevention trials out there right now and individuals can always contact one of their local ADRCs or look on clinicaltrials.gov because I think this is–people might be listening to this podcast in six months and the landscape could really change.

Chin: To end today, I want to end on a future outlook. And I'm going to start with you, Jessica. What do you think the field will look like? What do you hope the field will look like in the next five years, next 10 years? Knowing how important APOE is and Alzheimer's disease, where do you see this area of research?

Langbaum: I would love to see this as basically the field, and maybe not, where we're getting to clinical care. I think my hope is a personalized medicine approach where we have–we're using blood tests to, particularly if somebody knows their APOE genotype or even if they don't, we have regular blood tests as part of your annual wellness exam that is looking at like plasma p-Tau 217, really monitoring an individual over time. Because depending on whether we have a treatment out there for–depending what's approved–maybe there's a prevention, primary prevention or a secondary prevention therapy that's approved and we can get somebody on treatment really early on before they are experiencing perhaps even significant measurable amounts of brain amyloid and certainly preventing clinical symptoms from manifesting. I think, that is our hope and the way our field has progressed over the past even past five years, certainly 10 years, I'm really optimistic about the next five to 10 years.

Chin: Well, that is a tough answer to follow. Sterling, where do you see us in the next five to 10 years?

Johnson: Well, I just mainly agree with Jessica. This is such an exciting time for our field, having these biomarker tools to tell us who has the disease and now we can really leverage these tools to see when they got the proteinopathy of the disease. That's going to really help us make these decisions about clinical care and enrolling in clinical trials. I'd love to see more clinical trials happen in our field, especially the prevention trials that Jessica and her team at the Alzheimer's Prevention Initiative are doing. They're leading the field in this area and it's so exciting to see the prevention trials happening. We're really focused on these trials and launching them and hoping that they work for our patients. I just feel like there's a lot of optimism right now for where we're going to be. With regard to this particular topic, I think it's also important to know that the APOE4 homozygotes, they're 2 percent or so of the population. And so by sheer numbers the APOE 3/3–which is by far the most common form of APOE–by sheer numbers, there's gonna be more Alzheimer's even among that group of people. And the tools we're developing and the clinical trials we're seeing, we wanna make sure that these are representing and and incorporating all of these people, especially the E4 homozygotes because they're the ones who are gonna really need this.

Chin: Well, with that, I'd like to thank both of you for being on Dementia Matters. I know you're both repeat guests, and so I intend to have you on again in the future.

Johnson: Thank you. Great to be here.

Langbaum: Thanks for the opportunity.

Outro: Thank you for listening to Dementia Matters. Follow us on Apple Podcasts, Spotify or wherever you listen. Or tell your smart speaker to play the Dementia Matters podcast. Please rate us on your favorite podcast app. It helps other people find our show and lets us know how we're doing. If you enjoy our show and want to support our work, consider making a gift to the Dementia Matters Fund through the UW Initiative to End Alzheimer's. All donations go toward outreach and production. Donate at the link in the description. Dementia Matters is brought to you by the Wisconsin Alzheimer's Disease Research Center at the University of Wisconsin-Madison. It receives funding from private, university, state and national sources, including a grant from the National Institutes on Aging for Alzheimer's Disease Research. This episode of Dementia Matters was produced by Caoilfhinn Rauwerdink and edited by Eli Gadbury. Our musical jingle is Cases to Rest by Blue Dot Sessions. To learn more about the Wisconsin Alzheimer's Disease Research Center, check out our website at adrc.wisc.edu. That's adrc.wisc.edu and follow us on Facebook and Twitter. If you have any questions or comments, email us at dementiamatters@medicine.wisc.edu. Thanks for listening.