The Ongoing Battle Against Alzheimer's

MS. DIANE REHM

10:06:55
Thanks for joining us. I'm Diane Rehm. Alzheimer's is a devastating disease for both patients and their families. It's also a major public health problem that, given demographic trends, is likely to overwhelm our health care system. Joining me to talk about research efforts underway to slow the progression of Alzheimer's or even stop it before it starts: Dr. Neil Buckholtz of the National Institutes of Health, George Vradenburg of USAgainstAlzheimer's and Dr. Scott Turner of the Georgetown University Medical Center.

MS. DIANE REHM

10:07:37
I know many of you will be interested in this program and will want to call in. That number, 800-433-8850. Send us your email to drshow@wamu.org. Follow us on Facebook or Twitter. Good morning, gentlemen. Thanks for joining us.

DR. NEIL BUCKHOLTZ

10:08:01
Good morning.

DR. SCOTT TURNER

10:08:01
Good morning.

MR. GEORGE VRADENBURG

10:08:01
Good morning, Diane.

REHM

10:08:02
Dr. Buckholtz, let me start with you. As director of the National Institute on Aging, give us a sense of what we know as to who is most at risk for Alzheimer's.

BUCKHOLTZ

10:08:20
Thank you, Diane. Actually, I'm not exactly the director of the institute. I'm the director of the neuroscience division. But with respect to your question, age, we know, is the major risk factor for Alzheimer's disease. In the United States currently, there are over 5 million people, worldwide, about 35. And as you said, demographics is really the driving factor in the increased numbers.

BUCKHOLTZ

10:08:49
Over 65 years of age are at increased risk and especially after 85 years of age, and that is the fastest-growing group of people in the United States. So that's a major driver of why we're seeing so many people with Alzheimer's disease. And by mid-century, if nothing is done, there will be 14 to 15 million people in the United States with Alzheimer's disease.

REHM

10:09:15
So you are literally saying that the only way to avoid Alzheimer's is to die young.

BUCKHOLTZ

10:09:24
Well, we're hoping to find other ways of decreasing our risk for Alzheimer's disease. There are a number of both lifestyle risk factors that investigators are looking at, as well as a major push to try to develop new drugs to slow the course of the disease, to help people who have the disease. And really, what we're hoping for eventually is to be able to delay the onset so nobody will actually get Alzheimer's disease.

REHM

10:09:58
Tell me about those lifestyle risk factors.

BUCKHOLTZ

10:10:03
For example, what we do know from various epidemiology studies is that exercise -- for example, physical exercise, mental exercise, social interactions -- seem to be able to delay the onset of Alzheimer's disease. These are somewhat difficult to look at in what we call controlled clinical trials. But for example, there are a number of trials that are ongoing and that will be started soon that look at physical exercise to see if we can actually delay the progression of Alzheimer's disease.

BUCKHOLTZ

10:10:42
So these are the kinds of factors. Other factors, such as diabetes, cardiovascular disease, these kinds of things also seem to put people at increased risk.

REHM

10:10:53
Dr. Neil Buckholtz, he is director of the division of neuroscience at the National Institute on Aging. George Vradenburg, tell us about USAgainstAlzheimer's, what you hope to accomplish, how you work with research organizations.

VRADENBURG

10:11:17
Well, thank you, Diane. We are committed as a number of individuals who have seen this disease up close and personal and don't want to have other people experience it. It started about 2 1/2 years ago with a commitment to try and stop the disease by 2020, an ambitious goal. But there are a couple shots on goal that seem to indicate that that's a possibility.

VRADENBURG

10:11:40
So we are trying to accelerate that process. We work with the National Institute on Aging. We work with private and academic researchers. We're now working with industry. We clearly work with Congress and the government to the administration to accelerate the pace, to increase the resources devoted to the subject and to increase the focus on this disease.

REHM

10:12:01
And what, to you, seems to be the most hopeful possibility out there?

VRADENBURG

10:12:10
Well, tragically, right now, we have really advanced the science of diagnosing some of the biological markers of this disease fairly early in the process so that we now can diagnose the markers of this disease 10, 20 years before the symptoms appear. But we have not kept up the pace in terms of what you do once you know that you have one of these biomarkers.

VRADENBURG

10:12:35
So what we are trying to do is really threefold to try to increase the amount of resource being applied to the field. It's terribly under-resourced, $500 million dollars a year at the NIA compared to $6 billion a year for cancer and $3 billion for HIV/AIDS. So we're trying to increase the resource devoted to the field. We're trying to get drug companies to change their practices with corresponding practice changes at the FDA to accelerate drug development.

VRADENBURG

10:13:02
And we are seeing a couple of companies and a couple of drugs that have demonstrated some ability to modify this disease in mild patients. So Eli Lilly has a drug. Genentech has a drug that have shown some promise. Now, the problem is going out to assure that, in fact, we can verify the efficacy of those drugs, that they're safe to take, and then get them into the hands of -- in the hands of those people who are at risk.

REHM

10:13:32
George Vradenburg, he is co-founder and chair of USAgainstAlzheimer's. Turning to you, Scott Turner, when do you first see patients at Georgetown? Do they come because they feel they have signs? What's the earliest you see patients with Alzheimer's?

TURNER

10:13:59
We see patient at Georgetown in different stages of the disease. Some people are encouraged to come in by their family member who notices a decline in memory, repeating questions, forgetting conversations, losing things at home. And finally the patient realizes that the family member may be correct and agrees to come in for an evaluation.

TURNER

10:14:20
We also see a few people who recognize it in themselves when they start to have more cognitive problems than they used to. We sometimes see patients come in with more advanced stages when they start having behavioral problems such as depression, apathy, anxiety, agitation, delusions, paranoid delusions, and so they're -- so people come in in all different stages.

REHM

10:14:42
Except for the delusions and paranoid delusions, so couldn't you be talking about any one of us?

TURNER

10:14:51
Well, there's a significant change from previous status is what we're looking for and usually a gradual change with Alzheimer's disease. And, of course, our first job is to determine a diagnosis. So people don't come in saying they have Alzheimer's disease.

REHM

10:15:06
How do you do that?

TURNER

10:15:08
So we come in and collect the medical history from the patient and the family. We order diagnostic test such as a blood test and a neuroimaging study such as an MRI scan of the brain. We do an examination, including a cognitive evaluation. And we put all of these things together and come up with a diagnosis.

REHM

10:15:26
Tell me what that brain scan can indicate in either subtle or profound ways.

TURNER

10:15:34
It's done -- for example, an MRI scan of the brain is done mostly to rule out other causes of dementia...

REHM

10:15:41
I see.

TURNER

10:15:41
...and neurologic signs and symptoms such as a stroke or tumor or hemorrhage.

REHM

10:15:46
But other than that, are there any visible signs of Alzheimer's?

TURNER

10:15:54
There is some atrophy or shrinkage of the brain with age. but there's a lot of overlap between normal aging and Alzheimer's. We're trying to get a better handle on this trough the ADNI study, the Alzheimer's Disease Neuroimaging Initiative, trying to better quantitate the shrinkage of the brain in the earliest stages of Alzheimer's.

REHM

10:16:11
So it actually shrinks.

TURNER

10:16:14
It does actually shrink, yes.

REHM

10:16:16
And you can watch that progression.

TURNER

10:16:19
And we can quantitate this and watch it by doing an MRI scan once a year, for example.

REHM

10:16:24
Dr. Scott Turner, he is professor of neurology and director of the memory disorders program at Georgetown University Medical Center. I know that many of you are already waiting on the phone. We'll try to get to your calls as quickly as possible. Join us, 800-433-8850. Dr. Buckholtz, Dr. Turner talked about these biological markers and their importance in Alzheimer's research. Talk about what NIA is doing there.

BUCKHOLTZ

10:17:09
This is really a very important advance, over the past 10 years or so, in our ability to look at changes over time in the living human brain. As Scott said, we can look at the structure of the brain using magnetic resonance imaging. We can look at the function of the brain using something called PET imaging, positron emission tomography, where we can look at how the brain uses glucose as its energy store.

BUCKHOLTZ

10:17:38
And that decreases over time in people with Alzheimer's disease. And really, the -- a major advance that has occurred fairly recently is now our ability to be able to image beta amyloid in the brains of living human beings, which is...

REHM

10:17:53
Now, describe what that is.

BUCKHOLTZ

10:17:55
Yeah. So the two "hallmarks" of Alzheimer's disease in the brain is plaques and tangles. Plaques are made up of a protein called beta amyloid. And until recently, the only way you could determine how much beta amyloid there was in the brain was after somebody died, to do an autopsy and actually measure that. Now, through the use of various PET methodologies, we can actually look at how much beta amyloid there is in the living human brain and track that over time, so...

REHM

10:18:31
And that's going to give you an indication of what's there and what's to come?

BUCKHOLTZ

10:18:39
Yes. And importantly, all of these measures can now be used in clinical trials to be able to see if a drug is working or not.

REHM

10:18:46
All right. We'll take a short break. We'll be right back.

REHM

10:20:04
And if you've just joined us, as part of our mind and body series, we're talking in this hour about Alzheimer's, what we know, what we think we may know and how what we know may lead us to some forms of treatment. Dr. Neil Buckholtz of the NIH is with me, George Vradenburg of USAgainstAlzheimer's, and Dr. Scott Turner of the Georgetown University Medical Center.

REHM

10:20:44
Here's a really thoughtful email, and I think all of you can address this. "Please comment on the application of Alzheimer's research to other forms of dementia. My father was recently diagnosed with vascular dementia. We rarely hear about research for anything other than Alzheimer's. Is the research helpful for all forms of these diseases?" It would seem the first thing you would have to do is separate and define each of these diseases. How easy is it to do that, Dr. Turner?

TURNER

10:21:33
So there is research going on with other dementias, of course. But Alzheimer's is the most common cause, so this is the dementia that focused the most on. The second most common cause that we see in our clinic is Lewy body dementia, which has...

REHM

10:21:46
From Parkinson's.

TURNER

10:21:48
...some overlaps of Alzheimer's with Parkinson's disease. And there are medications that we use typically prescribed for patients with Alzheimer's that are also effective for Lewy body dementia.

REHM

10:21:59
Such as?

TURNER

10:22:00
Such as the cholinesterase inhibitors that are routinely used in our clinic. And then there's a lot of overlap as well of Alzheimer's disease in vascular dementia or multiple strokes. And so there's -- there are treatments as well that help with patients who have vascular dementia or a mixed dementia, a combination of Alzheimer's and vascular.

REHM

10:22:20
But, Dr. Buckholtz, how simple, how straightforward a process is it to define which kind of dementia may be at work?

BUCKHOLTZ

10:22:34
Well, as Scott said, there are ways of determining the differential diagnosis. But getting back to one of the questions that you asked originally, the commonalities among these, many of them have what are called these proteinopathies. That is, there are proteins that are specific to some of these other dementias, in Frontotemporal dementia, for example. It's tau in Lewy bodies. It's the Lewy bodies with another protein called synucleins. So there are efforts going on to look at the commonalities among these various diseases.

REHM

10:23:07
How can you determine the type of protein that's at work here?

BUCKHOLTZ

10:23:13
At this point, it's primarily from autopsy studies. As I mentioned before, in addition to trying to develop ligands for looking at amyloid in the living brain, there are other studies that are going on to try to look at these other proteins to be able to, again, identify these early and follow their progression in living human beings.

REHM

10:23:40
Dr. Turner.

TURNER

10:23:41
I just want to mention that we -- that another reason for developing these biomarkers is that helped distinguish between these different dementias. For example, if someone has a positive amyloid PET scan, they would be less likely to have Lewy body dementia or vascular dementia. So it's helpful in making an accurate diagnosis.

REHM

10:23:57
George Vradenburg, here's a question from Facebook, "Please ask what regular citizens should do to get the president and the Congress to do more to support Alzheimer's disease scientific research."

VRADENBURG

10:24:15
Well, I think I'd direct people to usagainstalzheimers.org. We have one to two messages a month that go either to Congress or to the administration or to industry to urge them to take particular steps that will accelerate the drug development or increase the resource devoted to the disease. But the most important thing is to talk about the disease. People are afraid of this disease. There's a certain stigma around it.

VRADENBURG

10:24:45
So simply talking to your friends and to your neighbors about it and if your family member has it, don't hide it. Talk about it. You rarely see in an obituary anyone dying of Alzheimer's. They'll die of some unknown cause or after a long illness or pneumonia, which is a consequence, in many cases, of Alzheimer's.

REHM

10:25:03
I mean, for a long time, we never even used the word cancer. So now Alzheimer's is sort of in that same category. But here's what I don't understand. If the projections are correct and as many as 15 million people will be suffering from Alzheimer's in the next 10 years, 15 years, why hasn't the country and the government focused more on it?

VRADENBURG

10:25:41
Well, there are a variety of political reasons. But I'll give you one or two important reasons, at least in my view. In other diseases, whether it be polio or it be HIV/AIDS or cancer, usually the victim can speak, and you can see the victim. But when a victim comes in with Alzheimer's and progresses, that victim is hidden out by the family and protected. Social behaviors are awkward.

VRADENBURG

10:26:07
There are a variety of agitations and other behaviors which are embarrassing in public forums or even in social gatherings. So the patient tends to hide out. And then the caregiver tends to pull in their life because they're so devoted to taking care of the victim. And they're exhausted. So who is going to be speaking for the victim and for the caregiver? It has to be the rest of us who've had a family member with the disease or who are themselves fearful of their own -- getting the disease on their own.

VRADENBURG

10:26:38
We have to speak out, and we have to urge change about this. The second thing that I think has hung up is that we've tended to look at the costs of health care as a zero-sum game. Either we have to cut back on benefits, or we have to cut back on payments to hospitals and doctors and to drug companies. That's not the only way to get at the health care cost of this many people.

VRADENBURG

10:27:03
With polio, you don't hear about polio health care cost today because we, in fact, innovated a solution to that disease. We need focus on innovations in the treatments for Alzheimer's and for the care of those people who have Alzheimer's today. And innovation is a third way to get at the cost of health care. We haven't yet persuaded our politicians to think that way.

REHM

10:27:26
How did you begin to focus on Alzheimer's?

VRADENBURG

10:27:32
Well, we point to the numbers that you laid out. Not only are we going to have 15 million victims, but over that same time spent, 10 million people, 10 million baby boomers will have died of the disease. So we're talking about 10 million deaths in the coming decades, and we're talking about 15 million in the aggregate still with the disease. We're talking $200 billion a year as of now in health care cost associated with this disease.

VRADENBURG

10:27:56
Seventy percent of that is Medicare and Medicaid. Talking to the VA, they have $3.5 billion in health care cost today for veterans with Alzheimer's disease. So we're trying to point out the cost of this disease, the ability to project the cost of the disease and therefore, how it is that we ought to attack this as a problem of our fiscal debt and deficits, not just a health issue as important as the health issue is.

REHM

10:28:21
Dr. Turner, would you agree with George Vradenburg's assessment that there is no one to speak for the person who has Alzheimer's?

TURNER

10:28:34
I would agree with that, and I think there's another factor at work in that there's often what -- this disease is sometimes considered normal aging when it absolutely is not normal aging. But there's a certain amount of question for many people. Is it normal aging or is it Alzheimer's? And we, of course, think that it is a disease that needs a treatment and can be treated, and new treatments can be developed. And it's not just normal aging.

TURNER

10:29:00
We would encourage people to seek evaluations -- medical evaluations when they have memory problems. We encourage them to get a diagnosis, avail themselves to current treatments and learn about research studies that are available. Another rate-limiting step in making progress is finding volunteers. We need patient and family volunteers to join us and partner with us in discovering these new treatments. And that would be something that the public could do when someone has Alzheimer's disease.

REHM

10:29:28
Give me an idea of the kinds of testing that you'd like people to participate in.

TURNER

10:29:36
So we're also now moving to earlier and earlier stages of the disease. So we're looking for older people who are beginning to have memory decline as they get older. And we will then do our investigation to come up with a diagnosis, Alzheimer's disease. But we're also now increasingly diagnosing mild cognitive impairment or MCI, which is a precursor to Alzheimer's disease often.

TURNER

10:29:59
And some of our treatments are targeting this group instead of already having the disease, having the earliest stage of the disease or even finding people who are asymptomatic but have a positive amyloid PET scan, and now we're beginning to recruit those volunteers.

TURNER

10:30:14
So I think less than 1 percent of people with Alzheimer's volunteer for studies. Many of them don't even know that there are research studies available to them to discover these new treatments. So we would encourage people to seek evaluation, learn about research and perhaps participate if they have the interest to participate.

REHM

10:30:33
Give me that website. We'll put that up on our website.

TURNER

10:30:39
Memory.georgetown.edu is the website here at Georgetown. And there's a national website, adcs.org.

REHM

10:30:46
Adcs.org.

TURNER

10:30:49
Alzheimer's Disease Cooperative Studies.

REHM

10:30:51
And to you, Dr. Buckholtz. Are you also looking for volunteers?

BUCKHOLTZ

10:30:59
We are helping all of these sites, including the ADCS, find volunteers. The website for the Alzheimer's Disease Education and Referral Center at which people can find out which clinical trials are ongoing is www.nia.nih.gov/alzheimers, and people can go on that website to find out what clinical trials are being done and where they're being done.

REHM

10:31:25
All right. And we'll have those websites linked to ours, drshow.org. George, you wanted to say something.

VRADENBURG

10:31:37
There is now, as part of the annual wellness exam that Medicare is offering for free, a cognitive assessment that is part and parcel of that annual wellness exam, and people should take advantage of that, and Medicare is recommending a variety of testing tools. Patrick Kennedy has put it so well. He said we need to make a checkup from the neck up as common and understandable and as accessible as a checkup from the neck down. And I do think we have to be more attentive to the state of our brain health, much as we're attentive to the health of other parts and organs of our body.

REHM

10:32:16
Go ahead, Dr. Turner.

TURNER

10:32:17
I just wanted to add something to the very first question that you asked about, risk of Alzheimer's disease. Obviously, I agree that aging is a major risk factor, but another risk factor is family history. Anyone who has an affected parent with Alzheimer's disease or an affected sibling with Alzheimer's disease has a much higher risk. And there's a certain gene called apolipoprotein E or ApoE that has different varieties, and one variety is a higher risk for Alzheimer's.

REHM

10:32:44
So you're saying that with the process of genetic mapping, one could determine whether one is at risk.

TURNER

10:32:54
So we do know there's a certain gene that increases your risk for Alzheimer's, and this explains part of the increased risk with family history.

REHM

10:33:00
Pretty scary stuff to subject oneself to that kind of test and know what's out there waiting for you.

TURNER

10:33:09
Right, right.

REHM

10:33:11
And you're listening to "The Diane Rehm Show." We have many callers. We'll open the phones now, 800-433-8850. Let's go first to Vermilion, Ohio. Hi there, Barbara.

BARBARA

10:33:32
Hello. How are you today?

REHM

10:33:33
Fine. Thank you. Go right ahead, please.

BARBARA

10:33:36
Yeah. I have -- I tried to combine this all in one question, so it's going to be pretty quick here. I'd like to know how aluminum, cholesterol-lowering drugs, which reduce the cholesterol in the brain, and systemic yeast, which usually isn't tested for, I'd like to know how these three affect the brain and if they're going to ever be studied.

REHM

10:34:03
All right. Dr. Turner.

TURNER

10:34:07
Well, aluminum theory has been essentially discarded, and I don't think there's really any validity to the systemic yeast theory.

REHM

10:34:17
And cholesterol?

TURNER

10:34:19
And the cholesterol, we do know that cholesterol-lowering drugs decrease your risk for stroke, and multiple strokes can cause dementia. So we would certainly encourage evaluation of cholesterol levels and treatment of high cholesterol if this is discovered.

REHM

10:34:32
I hope that answers it. To Sarah in Manchester, N.H. You're on the air.

SARAH

10:34:40
Hi. Thanks for taking my call.

REHM

10:34:42
Sure.

SARAH

10:34:42
I -- I'm trying to -- I have lots and lots of thoughts and questions on this topic that...

REHM

10:34:48
Just one, please.

SARAH

10:34:49
I know. I understand. My mom, who is 82 years old, has dementia, and it's pretty significant and pretty far advanced. My question kind of goes back to the earlier email with respect to the type of dementia. And I guess my real question is -- I've been given a number of different ideas over -- you know, they said -- one person has said Lewy body, someone else said it's just vascular, but it's pretty significant. How important is it that I know, as a daughter and as a caretaker, what type of dementia it is and what's the implication for her treatment?

REHM

10:35:21
I think that's a first great question. George, any thoughts?

VRADENBURG

10:35:27
I think this is probably a better question for Dr. Turner.

TURNER

10:35:32
Well, I think it's very important to get a diagnosis. There are treatments that are specific to Alzheimer's and different treatments that are specific...

REHM

10:35:40
You know, you've said that a couple of times.

TURNER

10:35:44
Yeah.

REHM

10:35:44
I want you to talk about the different treatments available for different types of dementia.

TURNER

10:35:53
So there are three drugs that we commonly prescribe.

REHM

10:35:55
And use their generic names, please, or their popular names.

TURNER

10:36:00
So they're -- Aricept, Exelon and Razadyne are the three. They're fairly equivalent. We prescribe these medications once someone is diagnosed with Alzheimer's disease. They do have some benefit for Lewy body dementia as well as vascular dementia, but there are other specific treatments to these other dementias. And obviously if we want to investigate a new drug, we need to make an -- as accurate a diagnosis as possible. It also has implications for prognosis and implications for family members who may be at risk as they get older.

REHM

10:36:30
And, Dr. Buckholtz, what kinds of drugs are out there in the testing process?

BUCKHOLTZ

10:36:39
There are a lot of drugs that are currently being developed and tested. Many of them focus on beta amyloid. But there are other things that are going on as well -- for example, looking at tau as a potential target for Alzheimer's disease, other kinds of things. There is a clinical trial that's just getting started -- for example, an intranasal insulin, which had been shown in a smaller trial to be able to help people with mild cognitive impairment and early Alzheimer's disease.

BUCKHOLTZ

10:37:09
This goes back to the issue of the brain's utilization of glucose as a fuel. There's an idea that there may be a deficit in this and that getting insulin directly to the brain intranasally may be helpful.

REHM

10:37:24
Dr. Neil Buckholtz, he is director in the division of neuroscience at the National Institute on Aging. Short break here. More of your calls, your email when we come back.

REHM

10:40:05
And welcome back to our Mind and Body discussion of Alzheimer's. Here's an email, which says, "According to a Sept. 12, 2010 New York Times article, Alzheimer's could well be a form of diet-induced diabetes suggesting a diet of fats and junk food including sugar could be the cause of Alzheimer's." Any comment, Dr. Buckholtz?

BUCKHOLTZ

10:40:47
I don't think it's clear at this point that that's actually the case, although as I mentioned before, diabetes is a risk factor for Alzheimer's disease.

REHM

10:40:58
So in connection with sugar.

BUCKHOLTZ

10:40:59
Yes. And there may be, as I -- as, again, I mentioned before the break, there is a clinical trial going on currently looking at intranasal insulin because there may be ways that the brain can't handle sugar and that insulin getting directly to the brain may help. So although that particular idea may or may not be correct, we're looking at the general idea of glucose or sugar being involved some way in Alzheimer's disease.

REHM

10:41:29
All right. And, George Vradenburg, here's one for you: "My lovely mom," says Corey, "was diagnosed at 55 with early onset Alzheimer's. There's no family history. Her PT scans are consistent with Alzheimer's. She's now 59. The disease has progressed quickly and cruelly, leaving very little of her. What portion of the current research efforts are expected to be focused on early onset? And you have seen that kind of Alzheimer's in your own extended family."

VRADENBURG

10:42:17
Yeah. My mother's wife died of Alzheimer's, although later in life, and, as I say, once you see this disease up close, it is not a long, sentimental goodbye. It is a cruel experience for the victim and for the caregiver and for the family members. So my heart goes out to every family member and every victim of whom there are many. This is a disease that is not just of aging if you really do think that, in fact, we can diagnose the hallmarks of Alzheimer's 20 years before symptoms appear. This is a disease of people in their 50s generally.

VRADENBURG

10:42:53
Normally, you don't see symptoms that early. But there are several hundred thousand people in this country at least -- 'cause we don't keep tabs on this -- that have Alzheimer's in their 40s and 50s and early 60s. So we call that early onset, and there's no question that looking at those people to understand why it is that they are getting the symptoms of Alzheimer's early in life is an important element of the research.

REHM

10:43:24
But what do you mean you don't keep tabs on them? How do you know there are that many out there?

VRADENBURG

10:43:30
I think there are estimates based upon looking at small populations and then extending it to the rest of the country through extrapolation. But, quite frankly, this is not a disease that's typically diagnosed and then reported like other diseases. And indeed, we think that the death certificate information which now, according to the CDC, is -- estimates about 75,000 people a year dying in this disease. We have some studies that are soon to be published which suggest this is way underestimated, that, in fact, the actual deaths attributable to Alzheimer's are into the several hundred thousands.

REHM

10:44:09
Dr. Buckholtz, considering these numbers, why do you suppose -- as George Vradenburg talked about earlier, why do you suppose that such a small amount of our health care resources have been focused on Alzheimer's compared to other diseases? Is it public relations? Is it lobbying? What is it?

BUCKHOLTZ

10:44:41
Actually, Diane, unfortunately as a government employee, I can't speak specifically to the funding issue. I can say that with respect to the grant applications that we get to look at this, we have many more excellent grant applications than we have funds for. But I think George Vradenburg can address the policy issues a lot better than I can.

VRADENBURG

10:45:05
Well, I'll say this. We started with the war on cancer in 1971 under Richard Nixon. So we have had a 40-year run of annual increases in the budget against cancer. The attention maybe started being paid much more significantly to cardiovascular disease in the '80s and HIV/AIDS in the late '80s and the '90s. Congress decided in its wisdom in the mid-'90s no longer to look at investing in particular diseases but to double the entire NIH budget instead, a very productive thing to have done.

VRADENBURG

10:45:39
And we went through the doubling through the early parts of 2000 to 2003 that was completed. Since then, it's been flat for NIH, and in real dollar terms, it's been down almost 20 percent. So NIH itself is, I think, underfunded against the whole disease states that we're confronting. But that means that diseases whose importance or significance or whose scientific understanding has come later in this cycle have been left out.

VRADENBURG

10:46:07
And so we are at $500 million. I say we, the research against Alzheimer's, at $500 million a year from NIA and $6 billion for cancer and $3 billion for HIV/AIDS. So in the end, this is going to be politics. In the end, the Congress will bend, and the facts of the numbers of people affected and the cost of the care of people affected will cause a change in this. We're not sure where, we're not sure when. And that's why it's important for people to join the movement and to articulate their desire to see a change in that structure.

REHM

10:46:41
What about private laboratories around the country perhaps not even connected in any way with government research?

VRADENBURG

10:46:52
No question that private philanthropy has been a significant contributor to research and to buildings in various centers around the country, and that has been a great supplement. And thus tying together those academic research institutions through a national research plan is important to assure that that flows philanthropic dollars actually supplement what is being done by government.

VRADENBURG

10:47:15
Industry itself invests two times as much in research as the NIH, $50 billion a year compared to NIH's $30 billion. So industry, figuring out targeted incentives for industry to continue to stay in the game of Alzheimer's even though these trials take much longer with respect to this disease to show results is going to be an important inducement for continued research investment by industry.

REHM

10:47:41
All right. To Flint, Mich. Good morning, Patrick.

PATRICK

10:47:46
Good morning. How are you?

REHM

10:47:46
Fine. Thanks.

PATRICK

10:47:48
Thanks for taking my call. I had a question. I seem to remember reading a trial a few years back regarding TZD therapy reducing the onset of Alzheimer's by 35 to 40 percent. I was wondering if either of your guests had any ideas. Or is there any further research being done with those types of drugs?

REHM

10:48:10
TZD for diabetes.

BUCKHOLTZ

10:48:14
So I can answer that question. Now, this is one of our strategies that we're investigating in Alzheimer's. It has not been as promising as we had liked. We've had several negative trials in recent years. I don't want to say it's all doom and bloom because we've had -- also had reason for optimism in developing the biomarkers for additional outcomes from our studies are suggesting that we are finally maybe turning a corner and finding more encouraging results in some of our trials.

BUCKHOLTZ

10:48:47
And that's leading to the next set of trials and helping design the next set of trials, which we think may be more successful. And part of this strategy is, again, focusing on earlier stage of the disease that we think will be more effective then.

REHM

10:48:58
All right. Jonathan in Washington, D.C. asks, Dr. Buckholtz, the story behind a Colombian family with Alzheimer's.

BUCKHOLTZ

10:49:13
Yes. There is a rare form of Alzheimer's disease which is caused by specific mutations in one of three genes. And in Colombia, South America, there is a very large kindred group of people who have a specific gene mutation. And these people get Alzheimer's disease at a very early age, in their 30s and 40s. So one of the strategies is to look at these groups of people, understand, again, using biomarkers how the disease progresses in the brain.

BUCKHOLTZ

10:49:49
But very recently, the National Institute on Aging at NIH in cooperation with a pharmaceutical company has initiated a clinical trial to look at a specific -- what's called a monoclonal antibody, a drug that inhibits this beta amyloid protein in these people with the hopes that we'll be able to give the drug at an earlier stage before symptoms develop in this people. And we know because they have the gene mutation that they are absolutely going to get the disease. So we will be able to tell if this drug actually works in delaying the onset of Alzheimer's disease in these individuals.

REHM

10:50:34
And then another question: How does Alzheimer's affect other cultures around the world? Does the U.S. have a worse problem than other countries? Do we know the answer, Dr. Buckholtz?

BUCKHOLTZ

10:50:51
Now, again, one of the recent estimates is that there are up to 35 million people around the world who have Alzheimer's disease, so it's in every culture. Again, in cultures in which there is -- people are aging much faster, for example, Japan, China, increasingly in South America, I think we're going to see more and more of this. So it's not an American disease.

REHM

10:51:16
George.

VRADENBURG

10:51:17
Yeah. I'd say that this is a global disease. And since we know that the global health care costs of the aging are driving deficits around the world, it is part of the cause of sovereign debt crisis around the world. China will have more Alzheimer's victims in 2040 than all of the developed world combined. Because of their 4-2-1 policy, they will have fewer people to support those people. Women have this disease at a significantly higher rate than men for reasons we don't really understand, some obviously because they live longer, but in fact, the incidents of disease in women is greater than it is for men.

VRADENBURG

10:51:58
Blacks are twice as likely to get this disease as whites, Hispanic 1 1/2 times as likely to get the disease as non-Hispanic whites, so there are cultural and environmental factors that I don't think we truly understand. And the research has been difficult across the -- with blacks and Hispanics because they have not participated in clinical trials at the same rate as whites. And so part of the current efforts to get volunteers for clinical trials that both Neil and Scott have mentioned is heaving up on, hopefully, African-Americans and Hispanics.

REHM

10:52:31
Dr. Turner.

TURNER

10:52:32
I think the biggest growth in Alzheimer's is going to be in countries such as India and China.

REHM

10:52:36
Why?

TURNER

10:52:37
Partly linked to increasing life expectancies, so it's...

REHM

10:52:41
Life expectancy is going to see...

TURNER

10:52:42
Life -- as life expectancy increases, we see more and more Alzheimer's.

REHM

10:52:47
Here's an email from Greg, who says, "My concern is that testing might affect my insurability or hireability. I have to put my family first." Any thoughts?

TURNER

10:53:07
I'm not sure if this testing is physical exam testing or genetic testing. If it's genetic testing, there has been a law passed that if you have a high-risk gene, that you should not be discriminated for the purposes of medical insurance.

REHM

10:53:23
Should not but?

TURNER

10:53:25
But exactly. And it also left out life insurance, disability insurance and long-term care insurance.

REHM

10:53:31
All right. Let's go to Walpole, N.H. Good morning, Jennifer.

JENNIFER

10:53:36
Good morning. Thanks for taking my call.

REHM

10:53:38
Sure.

JENNIFER

10:53:39
I have a comment. I'm a palliative care social worker who works with many dementia patients. And I just wanted listeners to know that there are many resources in hospitals and clinics and adult daycare center, social workers and palliative care professionals who are there at every phase of the illness to help patients and families get the emotional support they need to figure out resources, and most importantly, discuss their own personal goals of care so that no matter what stage of illness they're at, the treatment plans are made with the patient's specific personal goals and values in mind.

JENNIFER

10:54:15
Really, palliative care is about putting the patient first and also giving them support and care throughout the trajectory of the illness, not just the end of life.

REHM

10:54:25
Thank you, Jennifer. George Vradenburg.

VRADENBURG

10:54:27
I think this caller makes an excellent point. And why is it important to know whether or not you -- your cognitive or functional impairments are the result of Alzheimer's or something else? Because there are things that you can do. There are things beyond the availability of immediate disease-modifying treatments in terms of legal planning, financial planning, health care planning.

VRADENBURG

10:54:46
Well, one the companies we worked with, U.S. Trust, says the first question that people ask as they're beginning to plan their retirement or their lifetime savings plan is, how much should I set aside in the event that I get Alzheimer's? And so people can plan differently. They will live their life differently. You'll live life, perhaps, more time with your family than you will in work if you have that option, if you know that you have this disease.

REHM

10:55:11
Finally, caller here in Washington, D.C. Ahmed, (sp?) can you make it quick it, please?

AHMED

10:55:18
Sure. My father has Lewy body dementia, and I myself have an (word?) disease called familial Mediterranean fever. It's rare in the U.S. I am 32. I wanted to know -- I've done a genetic test through one of the commercial services, 23andMe. I haven't gotten the results yet. I know I'm not going to see good results. But I want to know when is the good time for me to plan for my future if the results are, in fact, positive?

REHM

10:55:47
Dr. Turner.

TURNER

10:55:49
I'm assuming that you sent the genetic test for the ApoE gene. The ApoE gene is not completely determinative, meaning that if you're ApoE4 positive, it's not 100 percent that you're going to get Alzheimer's. It just greatly increases your risks. So I would say, if you're ApoE4 positive, you're at higher risk at a younger age of getting Alzheimer's and to plan accordingly.

REHM

10:56:14
And that goes back to what you were saying, George Vradenburg, that each of us at no matter what age as we begin planning for our future, the longer we live, perhaps, the more likely we are to get it.

VRADENBURG

10:56:37
That's certainly true. And I must say that we now have persuaded the Obama administration to set a goal of stopping this disease by 2025. And I think we are now organizing research of the governments and private industry in a way that will do that. So knowing what your risk is and knowing the course of the disease is vitally important.

REHM

10:56:58
George Vradenburg, co-founder and chairman of UsAgainstAlzheimer's, Dr. Neil Buckholtz of the National Institutes of Health, Dr. Scott Turner of the Georgetown University Medical Center. All of the information we've talked about this morning, the websites are on our website, drshow.org. Gentleman, thank you so much.

TURNER

10:57:30
Thank you.

BUCKHOLTZ

10:57:30
Thank you, Diane.

VRADENBURG

10:57:31
Thank you, Diane.

REHM

10:57:31
And thanks for listening, all. I'm Diane Rehm.
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