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Neurological Disorders Channel
Reported September 21, 2012

Catching Alzheimer's Early -- In Depth Doctor's Interview

Randall Bateman, M.D., at Washington University, discusses the DIAN trial and how they are trying to find a way to discover Alzheimer’s disease while it is still in the early stages.

What is DIAN?

Dr. Bateman: DIAN is the Dominantly Inherited Alzheimer's Network; it’s a research study that was established in 2008 by the National Institutes of Health and specifically the National Institute of Aging. The lead principal investigator is John Morris here at Washington University. Each DIAN site studies a very rare form of Alzheimer's disease called Dominantly Inherited Alzheimer's disease, hence the name Dominantly Inherited Alzheimer’s Network.

How rare is it? Is it more than ninety nine percent?

Dr. Bateman: There are over five million people in the United States that have Alzheimer's disease. We estimate that less than one percent of those people have this form of the disease that’s caused by a mutation.

Why do you think this is such a big study?

Dr. Bateman: For a few reasons. One is that it’s inherited at fifty percent risk. If someone has the disease it means that their descendants have a fifty percent chance of inheriting that mutation in the gene, and that mutation invariably leads to Alzheimer's disease. So it’s very important for the people in the family who have the disease, even though it’s very rare. Scientifically though, it’s very important because the mutations have taught us a great amount about what are the likely causes of Alzheimer's disease in everybody. More specifically, it was the discovery of these mutations that have led to many of the research tools and much of the understanding about how Alzheimer's disease starts and how it progresses. Another aspect of this is that the mutation allows us to predict whether someone will get the disease and about when they’ll get it. We can’t do that yet for the rest of Alzheimer's disease, but we can do it in people who have the mutation. Since a person is born with the mutation, at any point in their life they can be tested and they can know whether they have the mutation or not. If they do have the mutation, as I said, they would get the disease and they would get it at about the same age that their parent had the disease.

What are the different phases of the study?

Dr. Bateman: The aim of the DIAN study is to determine what changes and when, in multiple assessments. The goal there is to really figure out in people who have these mutations, what’s the first thing that changes, how much does it change by, and then what happens next. The way that’s done is people from all different ages, from eighteen to upwards of fifty, are enrolled in the study and then they undergo a battery of assessments, which includes a clinical evaluation. So that means going in and talking with the doctor, describing any changes in memory or thinking which have occurred, doing a neurologic and a physical exam, and they take specialized tests that test their memory and their thinking processes. They also have a series of brain scans that measure the structure of the brain and deposits that are associated with Alzheimer’s disease, beta amway deposits, as well as how the brain uses energy and how it consumes glucose. Then the person also contributes blood samples and cerebral spinal fluid, and those undergo biochemical measures to look for these proteins and other changes that occur with Alzheimer's disease. All of that data for that individual is then combined with all the other people in the study and we compare those people that have the mutation to their family member and the counterparts that don’t have the mutation and look for changes. Some of those first changes have already been discovered and are now being described that they occurred years before, even decades before, people have the first symptoms. So that’s perhaps one of the largest initial findings from the DIAN study; that the process of Alzheimer's disease really starts many years before the early symptoms.

Why is it so important to get that early intervention before the actual symptoms begin to show?

Dr. Bateman: With that knowledge we can design prevention studies. Since we know that the person has the mutation and they’ll get the disease and there are already changes occurring that lead up to that disease that gives us the opportunity to go in and test drugs at a very early stage of the disease, even before people have symptoms. We refer to that as secondary prevention, meaning the disease process has started but the person doesn’t have symptoms from it and we want to go in and prevent that from happening. The reason that’s important is because in almost all diseases that we treat, un-prevention modes are much more effective than treatment modes. An example of this would be if a person has a heart attack and you give a drug that lowers cholesterol. Once the heart attack has occurred and the damage has occurred, lowering cholesterol, even though it will help prevent future damage and future heart attacks, doesn’t do much good for the heart attack that’s already occurred. However, if we’re able to treat someone with a drug that lowers cholesterol before a heart attack occurs, we can actually prevent that heart attack from occurring. So by the same token, we think that treating Alzheimer's disease at an earlier stage will give us an opportunity to actually prevent a person from having cognitive decline.

What are you hoping that ten years from now you will have gotten from this study?

Dr. Bateman: A few things. From the DIAN study we hope to really understand many of the processes that lead to Alzheimer's disease and be able to compare and demonstrate whether those changes also occur in the more common, what we call idiopathic, Alzheimer's disease. In ten years-time we hope to really have several trials of drugs already completed telling us whether prevention and treating is beneficial, and by how much it’s beneficial. Frankly, in ten years I really hope that we have some much more effective therapies for Alzheimer's disease and that’s the point of doing the trials in the DIAN network.

What has been the biggest surprise and the thing that stand out the most?

Dr. Bateman: I think the biggest surprise is how similar dominantly inherited Alzheimer’s disease is to regular later onset Alzheimer's disease. People with this disease get it in their thirties, forties, and fifties and it’s a terrible disease that affects half the family members. Many of us for a long time thought, well if it’s caused by a mutation it’s somehow different, but as we look at all these different measures of the amyloid, the brain, the cerebral spinal fluid, and the cognitive performance we see how similar it is to sporadic Alzheimer’s Disease.

How long have you been working with Alzheimer's research?

Dr. Bateman: I guess it’s going on more than fifteen years now.

Why in your opinion is this such a big study for both the volunteers and for other families out there?

Dr. Bateman: For the volunteers it’s their opportunity to do a few things. One is to help contribute towards advancement and understanding of their disease and the more it’s known about it, the more likely we are to develop therapeutics which can really help. The second advantage is the opportunity to participate in the treatment trials themselves. Many of the participants indicate that they want to have access to drug trials, they want to participate, and of course they want to receive the active drug in the trial.

How does it work?

Dr. Bateman: This hasn’t formerly been launched yet, but the current design is to try to start with three different drugs. What that would enable us to do is instead of having half the people on a placebo and half the people on the drug that allows us to have three out of four people on drugs and only one out of four people on placebo. That increases the number of people who are on active drugs and improves the efficiency of the trial; it means that we can test more drugs with fewer people and the participants also get the opportunity to be on an active drug which is something that they almost universally request.

When is that part of the study set to begin?

Dr. Bateman: We plan to start it fairly soon. We’re thinking that within the next six to twelve months it’s likely to start.

Would you describe Alzheimer’s as an epidemic?

Dr. Bateman: I would. I think it’s actually an unrecognized epidemic in large part. When we talk about epidemics, a spread of a disease through a population, we get very concerned about things like the flu and other things because they’re communicable, they are transmitted. However, Alzheimer’s affects so many people; there’s over five million people in this country alone that have the disease and that number is expected to go up quite a bit because the population is aging. It’s an epidemic in the sense of how many people are affected by it and the fact that it’s going to grow. It’s a disease of aging that we now have an opportunity to intervene in, but if we don’t do it soon enough a great number of people will suffer Alzheimer's disease and die from it. It’s universally fatal, which is quite different than most other diseases and so we really need to have an effective way to go in and treat the disease.

So for volunteers like Robert, will they at some point find out if they have the actual gene if they want to?

Dr. Bateman: If they want to. They can find out at any point if they have the gene. They would put in a request then they would see a genetic counselor and receive some counseling about the results before receiving them, and as a part of the study we would help pay for that as well.

What have you heard from different volunteers so far?

Dr. Bateman: Most don’t want to know. I would estimate that maybe about ten percent of people want to know or find out, but most people don’t want to know when they don’t have symptoms.

Who is eligible for it, just anyone that wants to participate?

Dr. Bateman: You have to be at risk for having one of these mutations and there are some simple rules that we apply, but the basic one is that we have to know the mutation is in the family. That usually means that they’re the descendent or the child of someone who had the disease. So those people can enroll and whether they have the gene or not, it’s a fifty percent chance that they would have the gene, they can come in to the study. There’s a website, Someone who is at risk for having one of these mutations is eligible for the DIAN trial. There are additional eligibility rules, but the basic one is that we have to know the mutation is in the family. That usually means the participant is the descendent or sibling of someone who had the disease. The website, www.DIANExpandedRegistry.org has a description of eligibility and a person can provide contact information if they’re interested in the DIAN trial.where it has a description of what likely makes someone eligible and a person can put in their information if they’re interested.

Are you still enrolling?

Dr. Bateman: Yes.

What would you say to families that maybe have someone that is on the edge and they don’t know if they want to be a part of this study?

Dr. Bateman: I would say ‘check it out’. Go to the website (www.DIANXR.org ), contact the study, and talk to family members who have already done the study. There’s now more than two hundred and sixty people who are enrolled in the study and more than ninety five percent of those people come back. I think that says something; participants are very interested in the study and want to continue in the study. Contact the local DIAN site research coordinator (www.DIAN-info.org ), to ask about the study and talk with the people who are doing the study. Being a part of the research and the solution is an individual decision – with information, people should make their own decision.
 

END OF INTERVIEW

This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.

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If you would like more information, please contact:
Judy Martin
Washington University School of Medicine
martinju@wusm.wustl.edu
(314)286-0105
www.DIANXR.org

To read the full report, Catching Alzheimer's Early, click here.

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