Predicting Risk for Alzheimer’s Disease Today and Tomorrow

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Dr. Nathaniel Chin: 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.

Today, we have a return guest on Dementia Matters, Dr. Sanjay Asthana. Dr. Asthana is the Dean of Gerontology at the University of Wisconsin School of Medicine and Public Health and the founding director of the Wisconsin Alzheimer's Disease Research Center. Dr. Asthana is a world renowned Alzheimer's disease researcher who has led dozens of Alzheimer's disease clinical trials here in Wisconsin. Dr. Asthana also sees patients with memory disorders at the UW Health Memory Clinic. Dr. Asthana, welcome back to Dementia Matters. 

Dr. Sanjay Asthana: Thank you. It's a pleasure to be back. 

Chin: Now, Dr. Asthana, we like having you on the podcast because you have your finger on the pulse of the latest research findings and clinical trends in the dementia and memory care field. And the topic we want to talk about today, predicting risk for dementia in the doctor's visit, is something I hear my patients ask about often and really one of those topics where clinical practice is changing. So why don't you explain the current tools we have as doctors that can help people understand their risk for Alzheimer's disease?

Asthana: Yeah, thank you. Thank you for that very important question. As you said, as physicians, we see a lot of patients and they really want to know, doctor, what is - what are the odds that I'm going to get this disease or my children's chances of getting the disease. And I think this is very important given the fact that we now know that Alzheimer's - before we see the first symptom of the disease - it's about 20 or 30 years before that symptom that the disease actually had started in that person's brain. So we have a period of two or three decades when, if we know someone's risk and if there are some effective treatments, that could be very helpful for the person and their family. So the estimation of risk is a very important area currently for our researchers and also for clinicians in that area. Unfortunately, at this point we don't have a magic calculator or a magic way of estimating someone's risk. However there is some research that's ongoing here in Madison as well as in other parts of the country where we can measure a certain we can perform some brain imaging tests some genetic tests, some memory tests, and if we can take those findings together to some degree, we can estimate a risk, the ultimate service for someone. However, they're not foolproof at all and did a lot of research that needs to be done.

Chin: So in your clinic as well as mine, can you explain for our audience what are the key components of our memory clinic and how we come to our determination?

Asthana: Yes. So, as you know, we have a very special program here at the University of Wisconsin hospital. We have a very large research program and we have clinics every day of the week, morning and afternoon. So when the person comes to our clinic, most of these visits are quite long because we are very comprehensive and thorough. They are seen by a team - a physician, a neuropsychologist, and a social worker. And each personnel paints very important information and then we combine that information and come to a diagnosis. After the visit - at the visit that we go through detailed history of the person, their family history, what are their symptoms. And then we perform a very extensive  memory test, battery - which takes even a normal person about more than an hour, so it's very, very  comprehensive. And then those results are shared with the team and that the team goes, the physician goes and examines the person and then they discuss what the diagnosis could be. In some people, we may need more than that, and then they are sent either for PET brain scans or MRI brain scans  and even some more special tests including lumbar puncture and  electrical recording of the brain called EEG. So we can really go from the very basic level of testing all the way to very sophisticated state of the art tests. And they all come, they are all done here at University Hospital and it really varies from person to person.

Chin: So while we don't have the research tools in our clinic yet, we do have a fair amount of ways of looking at a person clinically, giving our best clinical judgment as to the cause of their symptoms.

Asthana: Very much so. And I think that once again is a major advancement in the diagnosis of Alzheimer's disease. Just to share that before all these advancements took place, even at the very specialized center where they had experience of diagnosing people with Alzheimer’s disease, their odds of making a wrong diagnosis were about 30%. And now in these special centers, the odds of making a wrong diagnosis are below 10%. So I think these advancements have really helped us diagnose correctly if someone has Alzheimer's disease or not. And the other thing you mentioned,  talking about risk prediction which is very important, is that in the clinic, these tests that we do some memory tests, the brain imaging tests, and in some cases we can do some genetic tests - we are looking for genes like the ApoE4 gene - and once we have all those results, we actually can combine, do some analysis and, to some degree, we can predict even now the risk for someone to get the disease. Although once again, it's not foolproof and even if the risk is high, we know that many of those people will still not develop the disease.

Chin: And that risk is my next question for you, because there are calculators available, even now, and many studies actually into risk scores for people developing dementia. But this is different than providing a risk specifically for Alzheimer's disease. So if you could explain to our audience, you know, what is the difference between these risk scores and calculators?

Asthana: Yes. So - so as you mentioned and people know that Alzheimer's is the most common cause for dementia. There are many other diseases that can cause dementia, like Lewy Body disease, or frontotemporal dementia, or Parkinson's disease. So the risk score relates to risk for Alzheimer's disease and then one can at a different level perhaps predict the risk for dementia. But we are very interested in risk specifically for Alzheimer's disease because our markers that we assess in a clinic are specific for Alzheimer's. And I think the tests that we do to some degree can help us predict what someone's odds are to get the disease right now.

Chin: Now, one of the tools that you've mentioned, which we don't in general use in clinic, is genetic testing, specifically that ApoE test. And we have a prior interview on our podcast with Dr Corinne Engelman, who talks about ApoE and she really emphasizes it's a susceptibility gene, which means it's not a guarantee that you develop Alzheimer's, but rather it increases your risk. So as a clinician, knowing that risk is important particularly if it motivates you to make healthy changes, but if I don't have a specific targeted treatment, you know, I'm cautious to tell patients to go out and pursue this kind of testing as what would it do for them? And so I'd like to hear from you, why don't we offer genetic testing right now? And do you see us doing that in the future?

Asthana: Yes. That's such an important question, Nate, because I think this test - as we know this gene, the ApoE gene, after years and years and decades of research now, it is one of the genes which has the most confirmatory evidence that if someone has the one form of this gene, called E4, just one copy, then the risk for getting Alzheimers is increased about fourfold. If someone has two copies of the ApoE4 gene, their risk of getting Alzheimer's has increased ninefold. So we know that this is at least one of the most proven genes that increases the risk for the disease. However, we also know that even people who have two copies of this gene, they still don't get Alzheimer’s. So there's no hundred percent risk of getting Alzheimer's, even if someone has two copies of this gene. So if you do the test in the clinic and tell the person that you have the E4 gene, there’s still a decent chance, if they resorted to a healthy lifestyle and did all the other preventive measures, that they will not get the disease. So by sharing the results we may cause undue anxiety and stress for people which may not always be good, so we try and avoid that situation. I think in the future, yes, we will be able to come up with a collection of tests which will certainly include, in my opinion, ApoE4 gene along with grain imaging findings and the cerebral spinal fluid findings and some other tests that may come very close to being definite if that, if someone has those risk factors, that they will get Alzheimer’s. We are not there yet, but I think in the future there is a good chance that that'll happen.

Chin: And then in the research world where we are able to collect these proteins through spinal fluid or imaging, it seems to me that we would have the ability to put together a risk score for healthy people with Alzheimer's disease in that 20 to 30 years of not having symptoms - 

Asthana: I agree with you.

Chin: -and predict when they might develop. 

Asthana: Yes, I agree with you. I think that the way the field is moving and I think that's going to happen one day and it’ll be so beneficial because my hope also is by then - in the next 10 or 15 years - there'll be some very effective treatments that are going to come along. So if someone is young, has a strong family history, and we know that they have some changes in their brain on the imaging scans and CSF examination that, and we know that the risk is high, we might be able to give them very effective treatments and either delayed their risk of getting the disease or perhaps, one day, stop it.

Chin: And we have to be careful when we start talking about these risk factors or predictive tools. And at our center we're about to begin a disclosure study where we are going to discuss with some of our healthy research participants, having only one of the proteins that we identify and really trying to understand, what are the consequences, how do we improve the process of doing this? And so we're hoping to use this study really to help provide perspective before it's actually done in a standardized research way as well as in a clinical way in one of our clinics. From your perspective, what do we need to learn from studies like this so that we do this in the best way possible?

Asthana: You know, Nate, this is one of the very unique studies that we are doing and as you know, you are a key investigator in that study. And I'm really waiting for the results of those studies. The reason being that they, at least so far, we don't know the best way of how to share the results of the abnormal tests that we find on PET brain imaging or the spinal fluid examination and your study is going to tell us really what the best way to share those findings with people and their families. And there's no single best way. I think it really depends on the person's background, how prepared they are to hear the results. Also we want to make sure that that does not cause undue anxiety or stress for the person. In the past, as you know, there are some studies that have shown that, in fact - unlike what we physicians think, that sharing this result can cause stress - in fact, the studies have revealed that most of the people and the patients and their families took it very well when we shared the results of ApoE4 gene. So the answer - the best answer is not available yet as to how to disclose the results. And I think your study will be a breakthrough study which will inform us here and across the country and beyond how best to share the results.

Chin: Now, another point that is very important to mention is that we cannot create a one-solution-fits-all test. So for instance, African Americans and American Indians are up to twice as likely to develop dementia as non-Hispanic whites. Women have a higher risk for dementia and people of different socioeconomic statuses carry different risks for the disease. How are we ensuring our discoveries for risk prediction and early diagnosis will work for a diverse population?

Asthana: Yeah, another critical area for Alzheimer's disease. As you mentioned, populations like African American, Native Americans, and Asians, we really don't know how this disease behaves in those populations. What are the likely major causes of this disease in those populations? So our center is the ADRC, the Wisconsin ADRC, here at University of Wisconsin, is one of very few centers in the country that - with expertise of people like Dr. Carrie Gleason and yourself and others are actually engaging the African American and Native American populations in Wisconsin and doing very unique research in those populations and finding out whether the disease progresses or differs in each population. When the results of those studies are available, we will have a better informed idea of how the disease differs in these races and ethnicities. Does it really differ from a white population or not? My gut feeling is, it certainly does. And when we have those results, I think we will be able to inform those communities much better. Perhaps there may be some specific genes that we will discover that only relate to those populations more than other populations. And based on that, there may be new forms of treatment that will only apply to those populations. So research here at Wisconsin ADRC is highly likely to reveal some breakthrough findings in Alzheimer's disease in different races and ethnicities. Until that happens, I think we have to do the very best to inform the population and also convey to them the best ways to reduce the risks while we are doing more research.

Chin: One of the things that I've learned from our center is that we really need people from all walks of life to volunteer for research. But people aren't - they're busy and it's a difficult thing to do. And so one of the things that I'm appreciative of our group is that we've gone into the community, and I know other centers around the country do that as well. It's so important to meet people where they are and still provide education, reassurance, but have them come to our centers that we can conduct these studies.

Asthana: Very much so. And I think these outreach community activities from, once again, people like yourself and other people in our center are so important for us to inform those populations as to what's going on here, inform them about the disease. If there are any misconceptions, then we help them get rid of those misconceptions. And I must say that I'm so excited and driven by the fact that those communities have shown so much interest in being a part of the Wisconsin ADRC research and in large numbers they are coming to our center and enrolling in our studies. Having said that, we need many more participants from those communities to come to the center, contribute to the research, because the returns will be best for them. Clearly the feeling is that the disease differs between different races and ethnicities. The more we learn, the better application we'll have for those populations, so the returns go both ways. For the Wisconsin ADRC, we learned so much more about Alzheimer's in minority communities and in return people of different races and ethnicities will learn more about disease in them and perhaps different ways of treatments.

Chin: And I think the ultimate goal would be for doctors to have a simple low cost test, maybe like a blood test or a pen and paper cognitive tests that can predict the risk for developing dementia. Something like a blood pressure reading or a cholesterol test that can tell us if a person shows risk for Alzheimer's disease. How close do you think we are to something like that?

Asthana: Yeah. You know, this is another area of research where we are involved in many of the centers in the country. So the blood-based biomarkers, we call them, is advancing rapidly. In fact, there are some tests that are being developed which just measure those abnormal proteins, Amyloid and Tau proteins, in the blood and we calculate that ratio and there's increasing evidence that just doing that simple blood test can, in some way, depict the presence of amyloid in the brain. So we don't need the costly PET scans anymore one day, or even doing a lumbar puncture because the blood test may help us or tell us whether there's abnormal protein in the brain or not. I think they will let - they'll be very important. They'll be scalable. They will be low cost. They could be done literally in just about every lab where blood can be drawn. When those techniques are widely available, I think it will be a major breakthrough and we are moving rapidly in that area to diagnose - if not diagnose, at least estimate - the risk of Alzheimer's disease by doing these simple blood tests. Whether it’ll diagnose the disease, I think some more work needs to be done.

Chin: And again, knowing risk is important if it helps motivate you to make healthy lifestyle changes or changes that are needed to prevent the development of dementia. So in closing, I'm going to ask you the same thing I asked most of my guests, which is what do you do in your personal life to help reduce your risk of developing Alzheimer's disease?

Asthana: Yeah, thanks Nate. You know, that reminds me, I need to lead a much more, healthier life than I do right now. But, as you know, my own father had the disease and he died from Alzheimer's disease. So my own risk just through my family history is high. What I've been doing for the past many years is what we preach to everyone. That is, I do regular exercise a few times a week, I do watch my diet. I control my blood pressure, if that needs to be, and I screen myself for other medical diseases that can cause Alzheimer's disease. And really trying to have good sleep. We know that poor sleep can increase the risk for Alzheimer's disease. So a healthy lifestyle, healthy diet, and I try and stay informed about what is the latest going on in the field so that I could use those strategies and reduce my risk.

Chin: Well, that's wonderful. I think that's a very complete answer for our audience. So I'd like to thank you again for being on our show and I anticipate we'll have you on in the future.

Asthana: Thank you. It's really a pleasure talking to you and being a part of these shows. They're so successful and so important for the public and for the center as well.

Outro: Dementia Matters is brought to you by the Wisconsin Alzheimer's Disease Research Center. The Wisconsin Alzheimer's Disease Research Center combines academic, clinical, and research expertise from the University of Wisconsin School of Medicine and Public Health and the Geriatric Research Education and Clinical Center of the William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin. It receives funding from private university, state, and national sources, including a grant from the National Institutes of Health for Alzheimer's Disease Centers. This episode was produced by Rebecca Wasieleski and edited by Bashir Aden. Our musical jingle is "Cases to Rest" by Blue Dot Sessions. Check out our website at adrc.wisc.edu. You can also follow us on Twitter and Facebook. If you have any questions or comments email us at dementiamatters@medicine.wisc.edu. Thanks for listening.