Prime Time Replay:
Dr. Marcelle Morrison-Bogorad
on New Research into Alzheimer's Disease
MsgId: *breakthrough(1)
Date: Wed Jun 11 20:45:05 EDT 1997
From: moderator At: 206.80.182.219
Hi, I'm Madeleine Lebwohl, moderator of Breakthrough Medicine. Tonight I'll be speaking with Dr. Marcelle Morrison-Bogorad, Ph.D., the associate director of the National Institute on Aging's Neuroscience and Neuropsychology of Aging Program. Welcome, Dr. Morrison-Bogorad.
MsgId: *breakthrough(4)
Date: Wed Jun 11 21:04:26 EDT 1997
From: Dr_Morrison-Bogorad At: 206.80.182.219
Hello, Madeleine. I'm very pleased to be on your program tonight. I'm looking forward to it. It's a first for me.
MsgId: *breakthrough(5)
Date: Wed Jun 11 21:06:20 EDT 1997
From: moderator At: 206.80.182.219
Dr. Morrison-Bogorad, why don't we begin with the area that you're working on now: Alzheimer's disease, and the clinical research going on.
MsgId: *breakthrough(6)
Date: Wed Jun 11 21:08:11 EDT 1997
From: Dr_Morrison-Bogorad At: 206.80.182.219
Alzheimer's Disease (AD) is a major public health problem. A person with AD loses their memory and eventually all signs of personality. This impacts not only the patient, but also relatives. What we're trying to do is develop drugs to slow the progression of AD. If we slowed progression by 5 years, then we could cut the number of persons with AD by 50%.There are two drugs approved so far for treating AD by the FDA. These drugs were developed through research that has taken place over the last 20 years. They are the first generation of drugs. Unfortunately, while they increase levels of a missing chemical in the brain which helps people think, they do not do anything for slowing AD itself. The changes go on in the brain.
What we're trying to do now is to identify drugs that would slow down AD progression in the brain. And the first studies suggesting that drugs to slow progression might work have recently been completed.
MsgId: *breakthrough(9)
Date: Wed Jun 11 21:11:22 EDT 1997
From: moderator At: 206.80.182.219
How do these drugs work? What aspect of the disease are they attacking?
MsgId: *breakthrough(10)
Date: Wed Jun 11 21:13:21 EDT 1997
From: Dr_Morrison-Bogorad At: 206.80.182.219
The drugs are a class of drugs called antioxidants. And one of them is a very familiar compound, vitamin E. Oxidation in the brain produces harmful free radicals. And vitamin E might slow the production of these free radicals. So what the studies did was conduct a clinical trial which is the only way to really determine whether a drug works or not.So in clinical trials you collect several groups of people who are as identical as possible. So this trial compared groups of people who had moderate AD. Some took the drugs and some did not. And the researchers studied how long it took the patients in the different groups to reach certain very practical end points. These included loss of ability to perform such functions as eating, dressing, combing your hair, or another one was whether they had to go in to a nursing home because their families could no longer look after them. Or whether they died.
The results showed that Vitamin E and the other anti oxidant drug they tested slowed the progression of the patients to one of these practical endpoints. They took longer to lose ability to look after themselves, or to enter a nursing home, for example. However, their cognition was not improved. So it is possible the drugs were working just to increase the general health of the people.
Persons should not take the high doses of vitamin E used in the trial without consulting their physician.
MsgId: *breakthrough(14)
Date: Wed Jun 11 21:19:12 EDT 1997
From: moderator At: 206.80.182.219
Are there any drugs available to improve cognition?
MsgId: *breakthrough(15)
Date: Wed Jun 11 21:24:00 EDT 1997
From: Dr_Morrison-Bogorad At: 206.80.182.219
We have tantalizing hints in two directions. They come from both basic molecular studies and also from studies on human populations--epidemiology. Two classes of drugs offer hope. Epidemiology studies suggest that anti-inflammatory drugs and female hormone estrogen could delay the onset of AD. In these studies, people who take anti-inflammatory drugs seem to have half the risk of getting AD, than people who did not take them. Similar results were found for estrogen in separate studies. And basic research shows us there is inflammation in the brain of a person with AD. The combined studies suggest that reducing the inflammation might slow the progression of the disease.The bottom line is that these results are tantalizing but we need to test them in clinical trials to see if they really work or not. And that takes time, of course.
MsgId: *breakthrough(17)
Date: Wed Jun 11 21:25:54 EDT 1997
From: moderator At: 206.80.182.219
If someone gets tested and discovers they have a gene for AD, how worried should they be? Can they affect whether they get it or not?
MsgId: *breakthrough(18)
Date: Wed Jun 11 21:28:38 EDT 1997
From: Dr_Morrison-Bogorad At: 206.80.182.219
It depends. In early onset disease, the rare kind, sometimes AD is inherited, being caused by a defective gene. So a parent can pass the defective gene onto their child, and both the parent and the child will get AD. However, most AD is late onset, occurring after the age of 65. A risk factor gene has been identified for this population. The gene is called apoE, and the form of apoE which is the risk factor, is called apoE4.If a person inherits one or two apoE4 genes, then their risk of getting AD is increased. However, this is not a test, because a person can have the apoE4 form and not get the disease, and a person with no apoE4 risk factor disease can get AD. So it is not a definite test.
MsgId: *breakthrough(21)
Date: Wed Jun 11 21:31:01 EDT 1997
From: moderator At: 206.80.182.219
What work is being done by your program on apoE?
MsgId: *breakthrough(22)
Date: Wed Jun 11 21:32:30 EDT 1997
From: Dr_Morrison-Bogorad At: 206.80.182.219
Scientists funded by our program are working on why apoE4 is a risk factor: how does it work? And they are also working on the other genes identified for early onset disease. The genes give us valuable clues as to where the disease starts in some people. And scientists are rapidly following up these clues.
MsgId: *breakthrough(23)
Date: Wed Jun 11 21:33:05 EDT 1997
From: moderator At: 206.80.182.219
Does what you eat or medications you take, or other environmental conditions, affect your developing AD?
MsgId: *breakthrough(24)
Date: Wed Jun 11 21:35:50 EDT 1997
From: Dr_Morrison-Bogorad At: 206.80.182.219
Unfortunately, nothing is so simple yet. Epidemiology studies are being conducted all over the states and the world to try to identify other risk factors. We hope we can identify risk factors which will be easily used to reduce the risk of AD. One risk factor found already is obvious, it's aging, and we can't do anything about that. Another is head injury. That's bad, that seems to increase the risk of getting AD in some people. What we hope to find are protective factors. Studying different populations, we hope will allow us to find people who are at lower risk for AD, compared to others. Then we have to find out what might have made the difference.
MsgId: *breakthrough(25)
Date: Wed Jun 11 21:37:26 EDT 1997
From: moderator At: 206.80.182.219
When your developing these drugs, are you following the results from each study, kind of step by step in your progression through finding out what's behind AD?
MsgId: *breakthrough(26)
Date: Wed Jun 11 21:39:46 EDT 1997
From: Dr_Morrison-Bogorad At: 206.80.182.219
One of the ways we're searching for effective drugs is by developing animal models of AD. Transgenic mice, where the mouse is given a human mutant gene that causes AD in persons. After several fruitless years, our mouse model was developed last year, that with age developed the brain changes of AD, and also developed memory problems. These mice are being used to look at how the disease develops as the mouse ages, and are also being used to test the ability of drugs to slow the development of AD in the brain. Other mice are being developed with the other gene changes that cause AD, and the results from these studies are awaited with great interest.
MsgId: *breakthrough(28)
Date: Wed Jun 11 21:42:05 EDT 1997
From: moderator At: 206.80.182.219
If someone feels that they're losing their memory, should they worry that they're getting AD?
MsgId: *breakthrough(29)
Date: Wed Jun 11 21:46:02 EDT 1997
From: Dr_Morrison-Bogorad At: 206.80.182.219
No, not really. Memory problems are a part of being human. What you have to worry about is if memory problems get worse over a certain period of time, and if, for example, you suddenly find you cannot find your way back from the grocery store. This is in a different class of problem from misplacing your car keys. If the memory problems are getting worse, and if the person is older, then our advice is to talk to their physician. There are simple memory and other tests that a competant clinician can use to accurately diagnose AD about 85% of the time. So along with medical tests and tests to make sure that the memory loss is not due to, for example, lack of B vitamins or taking too many brain-altering drug.Older people metabolize drugs slower than younger, and so a medication appropriate for their younger days might be inappropriately slowing them as they get older. So it's important to find out if a progressive memory loss is perhaps AD or not. As we develop drugs to treat the disease, we hope to develop tests to identify persons who will get AD before onset of symtoms. Ideally, we want to get the preventative drug before the disease starts.
We have great excitement about the near future for AD. For more information on AD there are several resources. One is in my institution, the National Institute on Aging, which funds AD research taking place across America. We fund about 240 million dollars a year. We have a referral center called ADEAR. The number is 1-800-438-4380, and it can provide literature on AD. For help with coping with the illness of a loved one, practical help can be obtained from the Alzheimer's Association. 1-800-272-3900. These groups along with pharmaceutical companies are working to educate physicians on how to identify AD in their patients, and to help patients and families cope with this progressively debilitating disease.
MsgId: *breakthrough(33)
Date: Wed Jun 11 21:54:25 EDT 1997
From: moderator At: 206.80.182.219
I understand that there are groups working with medications that ordinarily are prescribed for diseases other than AD, and yet seem to help AD patients. How are these working?
MsgId: *breakthrough(34)
Date: Wed Jun 11 22:04:13 EDT 1997
From: Dr_Morrison-Bogorad At: 206.80.182.219
These groups are together called the Alzheimer's Disease Cooperative Study. And this group of 35 institutions tests drugs for efficiency against AD, and tests drugs which are used for other conditions, or which pharmaceutical firms are not interested.The Alzheimer's Disease Cooperative Study (ADCS) performed the clinical trial on vitamin E that we talked about earlier. They have a number of clinical trials ongoing, including anti-inflammatories and estrogen, but the results will not be known for some time. Such studies are made easier by the long-term investment of monies for setting up AD center across the country, by the National Institute on Aging, and by Federal funding of basic science.
MsgId: *breakthrough(36)
Date: Wed Jun 11 22:09:16 EDT 1997
From: moderator At: 206.80.182.219
Has the incidence of AD changed in the past thirty or forty years? Has awareness of it made any difference in degree of onset?
MsgId: *breakthrough(37)
Date: Wed Jun 11 22:11:44 EDT 1997
From: Dr_Morrison-Bogorad At: 206.80.182.219
Possibly not. But it's difficult to say, because before about 20 years ago, AD was thought to be normal aging and inevitable. It has only been recently that we have become aware of its being a distinct disease. And of how common it is. After the age of 65, the number of persons with AD doubles every five years. With population of the USA becoming more elderly, and the baby boomers themselves getting old, we know that the numbers of persons with AD are going to increase.
MsgId: *breakthrough(38)
Date: Wed Jun 11 22:12:50 EDT 1997
From: moderator At: 206.80.182.219
Has there been any correlation between how you behaved in your youth, in regard to drinking or drugs, and the onset of AD?
MsgId: *breakthrough(39)
Date: Wed Jun 11 22:14:28 EDT 1997
From: Dr_Morrison-Bogorad At: 206.80.182.219
No, but some studies suggest that the amount of education that you receive could influence getting AD.
MsgId: *breakthrough(40)
Date: Wed Jun 11 22:15:05 EDT 1997
From: moderator At: 206.80.182.219
How is the education factor helpful?
MsgId: *breakthrough(41)
Date: Wed Jun 11 22:17:19 EDT 1997
From: Dr_Morrison-Bogorad At: 206.80.182.219
Scientists speculate that a person who is highly educated has more brain cells and more connections between them, busy thinking, and AD finds it more difficult to rob these people of their thoughts. This theory is called Brain Reserve. One possibility, not yet tested, is that we could protect ourselves a little by keeping our brains active throughout life. It's sort of like the health club of the mind.
MsgId: *breakthrough(43)
Date: Wed Jun 11 22:20:09 EDT 1997
From: moderator At: 206.80.182.219
Talking about health clubs, how does generally keeping in shape help ward off AD. If you have the gene, will keeping up your health help lower the risk?
MsgId: *breakthrough(44)
Date: Wed Jun 11 22:22:28 EDT 1997
From: Dr_Morrison-Bogorad At: 206.80.182.219
I'm glad you asked that question, because a recent study suggests that having strokes in certain parts of the brain can exacerbate the clinical symptoms of AD. So a person with a relatively small amount of AD pathology in the brain could be quite demented if they also had strokes. The hope here is that by persuading people to avoid risk factors for strokes, such as smoking and high blood pressure, might not only decrease the risk for stroke, but also delay clinical symptoms of AD if they were getting it.We don't know this for sure yet, but scientists will be studying this possibility. And in general terms, keeping fit can't hurt. The ultimate aim of the National Institute on Aging is for people to age successfully. Not only as far as mental function, but physical functions as well. We should be able to enjoy the last part of our life free from some of the diseases that now afflict us.
MsgId: *breakthrough(46)
Date: Wed Jun 11 22:27:39 EDT 1997
From: moderator At: 206.80.182.219
Thank you for joining me, Dr. Morrison-Bogorad. Let's hope the cure for AD will be there if we need it.
MsgId: *breakthrough(47)
Date: Wed Jun 11 22:28:30 EDT 1997
From: moderator At: 206.80.182.219
Dr. Morrison-Bogorad: I certainly hope so, and we're working hard to make sure it happens.
MsgId: *breakthrough(48)
Date: Wed Jun 11 22:30:02 EDT 1997
From: moderator At: 206.80.182.219
Dr. Morrison-Bogorad: Thanks for letting me share with you our excitement.
MsgId: *breakthrough(49)
Date: Wed Jun 11 22:31:45 EDT 1997
From: moderator At: 206.80.182.219
Thank you for joining me on Breakthrough Medicine. Goodnight.
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