IRA FLATOW, host:
You're listening to Talk of The Nation: Science Friday, I'm Ira Flatow. Up next, the latest on Alzheimer's disease. As you know, nearly five million people in the U.S. have Alzheimer's disease each year and that number is expected to go up as baby boomers creep towards old age and by mid-century, it is estimated that as many as 20 million Americans could be living with the illness. Alzheimer's is a debilitating disease, it robs people of their memory. Eventually, it leads to death. And if we don't find some effective treatment for the disease, critics say, our aging population could bankrupt our health care system. But this week there has been some good news from the front lines.
Researchers meeting in Chicago at the International Conference on Alzheimer's Disease reported some successes, some baby steps forward in treating the illnesses, and there were some promising news on a couple of fronts, the news that says statin drugs - they're the most widely prescribed medicines used to lower cholesterol - may work against dementia, and also news about a couple of other drugs that may work on the actual plaques in the brain. We've got a lot to talk about this hour with my guests. Let me introduce them. Mary Haan is professor of epidemiology in the School of Public Health at the University of Michigan at Ann Arbor. Welcome to Science Friday, Dr. Haan.
Dr. MARY HAAN (Epidemiology, School of Public Health,University of Michigan, Ann Arbor): Thank you, and thank you for inviting me.
FLATOW: You're welcome. Dr. Ralph Nixon is the vice-chairman of the Alzheimer's Association's Medical and Scientific Advisory Council, he's also a professor of psychiatry and cell biology and director of the Silberstein Institute for Aging and Dementia at NYU's Langone Medical Center. And he's here in our New York studio. Welcome to Science Friday.
Dr. RALPH NIXON (Vice Chairman, Alzheimer's Association's Medical and Scientific Advisory Council; Professor of Psychiatry and Cell Biology and Director, Silberstein Institute for Aging and Dementia, New York University): A pleasure to be here.
FLATOW: Promising news this week?
Dr. NIXON: I think it was quite encouraging. I think this was the first year that we've actually had a chance to see enough clinical trial information to help us guide the next generation of testing. And we had some encouraging and some surprising information as well that wasn't so encouraging. But I think over all, it was good progress and some promise shown.
FLATOW: Let's get to some details. First let me give out the phone number, 1-800-989-8255 if you'd like to call us by telephone or you can send your - you can send yourself over in Second Life over to Science Friday Island, and your avatar can ask a question of me sitting there in Second Life, so to speak. Let's get to the details. There were two different drugs showing promise, having in common the ability to modify the tau protein. Can you give us a layman's idea what that means?
Dr. NIXON: OK. Well, tau has been of interest ever since Alzheimer discovered or defined Alzheimer's disease because it's the component of the tangles that accumulate in the cells that eventually die in the disease. So this approach to therapy has been to try to dissolve these tangles within the cells and it's been of interest for a long time, but this was the first attempt that has been very encouraging that we've seen so far. And one of the - one of the approaches was to actually give a drug that would go in and bind to this protein and help to dissolve these clumps that choke off the nerve cell and keep it from communicating with other cells. And the other approach was to keep this protein functioning in the way that it normally functions so it would prevent the clumps from forming. And both showed some encouraging...
FLATOW: So, would it be safe to say this is the first time we've had something that actually breaks up the tangles, in a medication?
DR. NIXON: That's right. Yes, this is that drug.
FLATOW: It is, but if - was is it in humans or...
Dr. NIXON: This was in humans. This was a clinical trial that was quite extensive in its scope, it's still a phase two trial, so this means that it is needing to go through a much larger jury trial and in a phase three with many more patients. But these results were very encouraging.
FLATOW: Where these seen on autopsy, these results? Or how do we know they broke up the tangles?
Dr. NIXON: Well, there were some imaging studies that were done that showed that the regions that contain these tangles actually showed an increase in blood flow, which is a sign that the cells were somewhat more healthy as a result of the treatment. So that was helpful and then there were some biomarkers that were in the spinal fluid that were also changing in some positive ways.
FLATOW: Was there anything in imaging announced at the meeting that actually, we can look at the brain now without, you know, having to go in with a scalpel, but some sort of imaging technique that we can see the tangles now?
Dr. NIXON: Yes. This is a fast-moving area now, and almost weekly there are some new revelations, and one of them has been the ability to actually detect the amyloid pathology, and to some extent these tangle pathologies in the brain, and to see them develop even before Alzheimer's disease is diagnosable. So this is at a stage that is before dementia sets in, and this is very promising because this might allow us to intervene at an earlier stage in the disease.
FLATOW: 1-800-989-8255 is the number. Dr. Haan, you looked at people who were using statins, these - you know, things we get for cholesterol - I think they're the most widely prescribed drugs in the whole country now, to see what happened to them over time.
Dr. HAAN: It is actually. I want to emphasize that our study is not a treatment study in the sense that - that other people were just describing. We recruited a group of about 2,000 older Mexican-Americans who were living in the community, and they were - and we measured a number of things on them and followed them over seven years to see what kinds of factors predicted the development of new dementia and cognitive impairment cases. So in our study what we're basically looking at is the effect of statin use over a period of an average of five years in people that started out not having dementia or cognitive impairment.
And we found that in that case, people who were using statins over that time period had about half the rate of dementia and cognitive impairment as compared to people who were not using statins. So it's more like a simulation of a primary prevention trial for statins and not - it's not a treatment trial. There might be some implications for treatment, but I think there are a number of issues that we were not able to address, for example, what kind of specific statin would be best. And they were changes over time in the types of statins that were being used. So I think there are a number of questions that are still open about how statins might work and whether they are - the benefit that we're showing is really related to early detection.
None of the people that we recruited had ever had dementia - had ever been diagnosed with dementia before we got there. So I guess the final sort of thing I'd like to note about it is that statins do influence cardiovascular risk factors and a major purpose of our study has been to look at the influence of things like Type 2 diabetes and hypertension and other vascular conditions on the development of dementia and Alzheimer's disease. So that's - the statins are really attacking that pathway, I think, by lowering cholesterol and possibly by altering the body's immune response to developing pathology.
FLATOW: A couple of questions for you.
Dr. HAAN: Sure.
FLATOW: When you say dementia that - do I take that to mean that does not include Alzheimer's?
Dr. HAAN: Well, Alzheimer's is a form of dementia. About half of our cases are Alzheimer's cases...
FLATOW: Mm hmm.
Dr. HAAN: Which is fairly typical of other community-based studies that have tried to determine prevalence and occurrence of dementia and Alzheimer's. So it includes Alzheimer's cases. It includes - in analysis that was published, it also includes people with significant cognitive impairment. But we also have some analyses that showed that statin treatment over time reduces the risk of all cause dementia not just the combined - combination of the cognitive impairment and dementia. So, unfortunately, or perhaps fortunately for the participants, we didn't have enough Alzheimer's cases to look specifically at that.
FLATOW: Yeah. Interesting. You know, there are some doctors I've spoken with who think that the real benefits of statins are, is that they're anti-inflammatory drugs and that's...
Dr. HAAN: Yes, I think that's actually another possible pathway. That's what I meant when I was referring to the immune system response. When people are starting, perhaps in early stages of developing disease or even before that when they're just being exposed to certain types of risk factors, their body mounts a defense against that kind of exposure, and those inflammatory factors called cytokines may sort of contribute to the development of disease. And if statins can influence that, can lower inflammatory response, then that might be another possible pathway, but I think most people would agree that we're still not clear about which type of statins would work for this and if any and exactly how they work.
FLATOW: 1-800-989-8255 is our number. Dr. Nixon, are there still things about Alzheimer's that we don't understand? Are we learning more about and finding new ways to attack it and was that addressed at the meeting?
Dr. NIXON: It was and I think this was an important theme, that we've been following one particular hypothesis that's been very compelling and because of the outcomes of some of those clinical trials, it's raised the enthusiasm for exploring some of the other targets that have been known. But we've not had the resources to investigate them and tau...
FLATOW: Such as?
Dr. NIXON: Well, tau is one in particular, and some were touched upon in what you were just talking about inflammation, the role of cytokines, the importance of vascular risk factors and how to address the component of vascular dysfunction that contributes to a significant extent. A lot of the biology of Alzheimer's is still, even though we've come a long way, it's still in its infancy in terms of identifying additional targets, and that's happening as well.
FLATOW: And is there a debate about which way to go, in the community, about which targets to attack?
Dr. NIXON: There is a debate but a healthy debate. It's a plethora of possibilities and it's a complex disease and some things are primary and some things are secondary. So, the debate is really how to prioritize the investigations. But I think what the conference has done is open up the conceptual discussion again.
FLATOW: 1-800-989-8255. We're talking about Alzheimer's this hour. Talk of - see, I almost forgot - on Talk of the Nation: Science Friday from NPR News. Let's go to the phones. Thomas in Independence. Hi, Thomas.
THOMAS (Caller): Hello.
FLATOW: Hi there.
THOMAS: My specific question has to do with something I saw in the news three or four weeks ago, I believe it was and that is a method of detection either in the blood or in the spinal fluid that is as nearly absolute marker for Alzheimer's as one can find. And I would like to know how one can go about getting a test to find out if that marker is one they possess.
FLATOW: Dr. Nixon, does one exist?
Dr. NIXON: There is not a definitive marker. There are several gene variants that are common in the population that can be tested for. It is not something that is definitive in terms of its predictive value for Alzheimer's disease. There is promise for CSF test biomarker substances in the spinal fluid that do help the diagnosis and are starting to be used at least in a research way in the clinic, but by themselves, are not a definitive test. I think one still has to use them in the context of a very thorough clinical evaluation. But many academic centers can make them available. We do it at NYU Langone Medical Center, and there are other places where that type of testing can be done.
FLATOW: Are there lifestyle changes? We hear about exercising your brain. Even exercising your body to help fight off...
Dr. NIXON: This is the new mantra of the Alzheimer's Association, really. Things that can be easily done by everyone, for which the science now is well developed enough to really show a scientific basis, and exercise is probably at the top of the list as something that can reduce the risk of Alzheimer's disease and will actually increase and slow the decline once someone has symptoms. There were some reports at this meeting showing that you could see changes in the brain with imaging as a result of physical exercise. So, this is a no-brainer.
FLATOW: Wow. Dr. Haan, where do you go with your statins research now? What's your next step?
Dr. HAAN: Well, I think one of the things that we need to do is as a scientific community is to try to figure out why these are working the way they are. We're certainly - what's happened up until recently is most of the statin studies that have been in randomized clinical trials have been focused on people with the disease in hopes that it would be a treatment that might slow down progression or possibly even cure disease. So, those have not worked. I think Dr. Nixon would agree with that, and so I think what our study and probably the bulk of other observational studies on this suggests is that primary prevention is important. As Dr. Nixon was just alluding to, physical exercise is being looked at as a kind of something that you could do if you're in early stages. But in fact, it points toward lifestyle factors that should be really practiced throughout life. And one of the things that we're trying to work on now is to establish a large study that will look at the early effects of some of these risk factors on the brain and on cognitive change, in people who are actually much younger than most Alzheimer's cases are. So, I think the statin study has a couple of implications. One of them is clearly that there's an important role for vascular factors in the development of dementias. Secondly, if that's true that vascular factors have an important role, and I would add metabolic factors to that like diabetes, then it would mean that...
FLATOW: I'm going to have to interrupt because we have to take a break, but hold that thought, Doctor. We'll come back talking with Mary Haan and Ralph Nixon after this break. Stay with us. We'll be right back. I'm Ira Flatow. This is Talk of the Nation Science Friday from NPR News.
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FLATOW: You're listening to Talk of the Nation: Science Friday. I am Ira Flatow. A brief program note. Talk of the Nation moves next Wednesday back to the ever popular Newseum in Washington D.C. and if you want to be in the live audience there, you want tickets to join the audience, you have to send an email. Send an email to tickets@npr.org. We're talking this hour about Alzheimer's disease with my guest Mary Haan, professor of epidemiology, University of Michigan in Ann Harbor and Dr. Ralph Nixon. He is the director of the Silberstein Institute of Aging and Dementia at NYU's Langone Medical Center. And when I rudely interrupted Dr. Haan, she was telling us, she was working on the second thought about prevention.
Dr. HAAN: Well, I think I'm sure Dr. Nixon would agree and everyone who works in this field would agree that if we could prevent dementia and Alzheimer's disease that would be great, of course. We're not doing that right now, and we may never completely get there. But all of the evidences gathering now about physical activity, vascular factors, and a growing interest in early and midlife risk factors and how they affect the brain points toward, strongly toward at least the possibility that we could mount a more effective prevention campaign that we have so far.
So, for example, actually at the congress there were a few people that presented results showing that if you measure - if you have high cholesterol, let's say at age 50 or you have hypertension or you have midlife obesity, that those factors are associated with a higher risk of late-life dementia. And this has been shown from some studies in Finland, from some studies in Kaiser Permanente, and there's a growing body of evidence that points that things that you do or conditions that you have in midlife actually are related to your late-life risk.
So, if that's true, then it points toward intervention at an earlier age - reduction in weight, control of blood pressure, better control over diabetes. And I'm concerned because we see increases in most of those factors now in the population. And as a public health professional, that's really where I have to put most of my focus. But I think there's hope there, and there's growing evidence that could help us in trying to do a better job of preventing the development of dementias and Alzheimer's.
FLATOW: Dr. Nixon, in the closing minutes that we have, what would you like to see? What would be a great breakthrough or some tool or technology or technique or something that might tell us more about Alzheimer's?
Dr. NIXON: Well, I think more research into early diagnosis.
FLATOW: Could - better imaging so we can actually image the brain and see it happening, growing there?
Dr. NIXON: Yes, in fact, the Alzheimer's Association is putting out a request for applications for innovative new imaging techniques exactly to achieve this. We have some progress now with the amyloid imaging but there's potential to really start looking at the process back when Dr. Haan was referring back in the 50s and to be able to see some manifestation of the disease at a point when you could really say, you better start changing your lifestyle. Here is what you can expect if you don't.
FLATOW: And hopefully having offering somebody some medication that might work at that.
Dr. NIXON: That's right. And certainly, there are things, lifestyle changes - changing one's diet where the science is already there to show that you can delay the onset of Alzheimer's disease to some extent. So, these are things that don't hit the news as much as they should.
FLATOW: We'll try to do that for you. Thank you for taking time to be with us today. Dr. Mary Haan, professor of epidemiology, School of Public Health, University of Michigan, Ann Arbor. You're welcome. Dr. Ralph Nixon, who's a member of the Alzheimer's Association's Medical and Scientific Advisory Council and professor of psychiatry and cell biology at NYU's Langone Medical Center.
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