Zaven Khachaturian, Ph.D., and Teresa Radebaugh, Sc.D., are Alzheimer's disease experts who have significantly advanced the research into this debilitating disease. Dr. Khachaturian, former director of the Office of Alzheimer's Disease Research, coordinated all Alzheimer's disease activities at the National Institutes of Health and established the national infrastructure for Alzheimer's disease research. Dr. Radebaugh, a psychiatric epidemiologist trained at the Johns Hopkins School of Hygiene and Public Health, spent many years at the National Institutes of Health. Together they have recently edited a comprehensive volume, Alzheimer's Disease: Causes, Diagnosis, Treatment, and Care, available from CRC Press. Read more about Dr. Khachaturian and Dr. Radebaugh.
Dr. Khachaturian and Dr. Radebaugh were chat guests on PlanetRx.com on November 2, 1999. The following is an edited transcript of the chat.
PRx Host :
Welcome to our PlanetRx.com special event chat. Tonight we'll be talking about Alzheimer's disease with two primary researchers in the field, Zaven Khachaturian and Teresa Radebaugh. Welcome, both of you, we are so pleased to have you here!
Khachaturian :
Thank you very much!
PRx Host :
First off, could you tell us something about Alzheimer's disease -- what exactly is it and how prevalent is it now?
Khachaturian :
Alzheimer's disease is a neurodegenerative disorder, which means that the cells in the brain are gradually deteriorating and gradually will die. It's one of the most prevalent forms of dementia. Dementia is a generic form of the disease, which means loss of cognitive functioning. That means loss of memory, language, the ability to reason. The person gradually loses social functioning. It's a process that starts in a very benign way but progressively gets worse and eventually gets so severe that the person will no longer recognize family members, will not be able to recognize common words. Eventually the person loses their ability to function properly. Right now, Alzheimer's disease involves 5%-6% of people in the 65 and older age group. The prevalence rises with age, although aging does not cause it. In the 85 and older age group, 35%-40% of individuals are at risk for this disease.
PRx Host :
It sounds so frightening. What causes Alzheimer's disease -- do we know yet? Dr. Radebaugh, maybe you can take this question?
Radebaugh :
The simple answer is that scientists do not yet know what causes Alzheimer's disease, but there are many clues.
PRx Host :
What are those clues?
Radebaugh :
Dr. Khachaturian do you want to take that?
Khachaturian :
During the last 20 years, several theories have emerged about the cause of Alzheimer's disease. These include theories on the genetic basis of the disease. There have been several things discovered that are linked to the disease. Other theories involve the abnormal processing of certain proteins in the brain, which have been associated with the lesions that are associated with the disease. There are some other theories concerning the lack of energy being available to the brain, due to metabolic deficiency in using sugar, which is a main supply to the brain. There are theories concerning the presence of certain toxins.
Each one of these theories focuses on leading to or explaining why brain cells become dysfunctional and why they die. The theories may appear to be in contradiction to each other or in opposition to one another, but in reality, they are dealing with parts of the whole fabric of the puzzle. What's happening during the last few years is that these different theories are converging. We're beginning to solve the puzzle, and that's very exciting. Once we understand what's causing the disease, we're going to be able to have treatments that will offer strategies for helping patients and their families.
PRx Host :
I'd like to present a question from the audience, since it relates to what causes Alzheimer's.
Patricia King :
Does aluminum poisoning have anything to do with causing Alzheimer's?
Khachaturian :
The idea of aluminum playing a role in Alzheimer's has been around a number of times. There have been numerous studies but the evidence is not conclusive. There are many studies showing that aluminum accumulates in those parts of the brain where the lesions appear. Scientists do not know if the aluminum gets there because of the lesions or if the aluminum gets there because there is a pathology in the first place. The prevailing scientific view is that aluminum does not play a direct or major role. That's the current thinking.
PRx Host :
If you are diagnosed with Alzheimer's disease, is there anything you can do to slow its spread?
Khachaturian :
Currently, we do not have any treatments that would alter the course of the disease; that is, treatment that has been approved. Although there are many clues indicating that in the near future, it will be possible to change the clinical course of the disease, these clues come from epidemiological studies from small-scale trials with compounds, such as the use of estrogen, the use of nonsteroidal anti-inflammatories, and the use of antioxidants. These have all been tried, and they have shown that they play a role in delaying the onset of the disease.
There are many formal clinical trials underway to explore these clues. These are not yet ready for direct prescription by physicians. We do not yet know how much to prescribe the dosages, under what conditions they should be prescribed, what might be the side effects. In order to address those issues, there have to be formal clinical trials. Those are underway. The end theory is that, although there is nothing yet that could be taken on a routine basis to alter the course of the disease in the near future, the prospects are very good that we will have several options for achieving that goal. Meanwhile, people can, as a practical matter, keep a healthy lifestyle, keep eating the right foods, keep getting exercise, keep the mind busy. These activities may help slow the progression of the disease, although there is no direct scientific evidence.
PRx Host :
What do you recommend for someone newly diagnosed with Alzheimer's disease? What can they do to prepare themselves?
Khachaturian :
First of all, the person who has been newly diagnosed with the disease should get all the information they can about the disease. The Alzheimer's Association has an 800 line that one could dial and get information. There are over 250 chapters of the Alzheimer's Association that are staffed by professionals or family members who have gone through the process of dealing with the disease. They have a lot of very helpful information. I would urge such individuals to make an effort to join a chapter.
In addition, there are sources within the federal government, such as the National Institute on Aging, which maintains an 800 number and an education and referral center that has publications. In addition to these kinds of activities, a person should keep active, keep doing things that would keep the mind busy. No matter how much the disease progresses, keeping the mind active can help and can retard the progression of the symptoms. Besides that, unfortunately, there's not much that can be done in terms of medication and treatment immediately. As I indicated earlier, such treatments are likely to be available within the next 3-4 years.
PRx Host :
Many people I know who become forgetful say things like, "I must be getting Alzheimer's." What should we look for as a symptom? Is memory loss alone an indicator?
Khachaturian :
Loss of memory by itself is not a sign of Alzheimer's disease. One forgets things for a variety of reasons. One reason is that a person may not have learned the task properly in the first place, or may not have paid enough attention or may not be motivated to remember, or could be distracted. There are a variety of reasons why individuals may forget things. None of these by themselves are signs of Alzheimer's disease. However, having said that, one should take forgetfulness in a chronic status, one that persists and progressively gets worse, as a sign of something being wrong. The person should immediately get an evaluation by a competent physician, a neurologist, or a psychologist, who can evaluate the person's cognitive dysfunctioning.
The practical way to tell if someone has Alzheimer's disease is to examine whether a change in memory is occurring in a way that's progressively getting worse. The way to tell that is this: normally, if I forget where I put my keys on a particular day, the next day I would remember. If I forget where I put something or if I forget a word, the next time or on another occasion, I would not forget. In the case of Alzheimer's, that forgetfulness progressively gets worse. That's the key indication. More items get forgotten. It's very common that people will not remember names. If besides not remembering names, one is forgetting events, items, numbers, those are signs that there is a problem. The key indicator is that the forgetting keeps getting worse.
PRx Host :
Is there a support group for people who have Alzheimer's?
Khachaturian :
Yes. The Alzheimer's Association is the major national organization that has support groups. The Alzheimer's Association has over 250 chapters across the country. It's practically within reach of every community in the country. It's a very good source of information and help. Each chapter has professional staff who are knowledgeable, as well as family members who have experience with the disease. I would urge anyone and everyone who has problems to get to know their chapter.
PRx Host :
We have a question from the audience I'd like to ask you now.
EJSW :
A client is in stage 6. How can you get them to do things without upsetting them, like taking a bath or shower, changing clothes?
PRx Host :
Dr. Radebaugh, would you answer this one?
Radebaugh :
It is helpful to know the preferences of the person, how he or she would do things before developing Alzheimer's disease, so that plans and approaches can be designed with the person's wishes in mind, such as privacy and temperature. One needs to approach the person gently and try to gauge what the upsetting triggers about the activity might be and avoid them.
EJSW :
Where can one get more training in working with Alzheimer's clients?
Radebaugh :
There are now many, many sources of information. These include many of the health care professional organizations, the Alzheimer's Association as well as the ADEAR Center, (the Alzheimer's Disease Education and Referral Center mentioned earlier).
PRx Host :
When you recommend that people who are diagnosed with Alzheimer's keep their minds active, what specifically may help?
Khachaturian :
There is some epidemiological evidence showing that people who have higher education or are involved in challenging occupations tend to get the disease much later. There is also anecdotal evidence that dementia patients in nursing homes, when they're kept active and given challenging stimulation like puzzles, the opportunity to learn a different language and even physical activities, such as exercise, appear to improve their cognitive function. There are some studies being done at the University of California-Irvine showing that exercise actually helps cognitive functioning.
At the present, we do not yet know the exact mechanism by which such activities enhance brain functioning. From animal studies, we know that in animals that have had a good environment, where they get a lot of stimulation, there are many more connections. The theory is that such stimulation, or the use of the brain, decreases the number of contact points between neurocells. But again, I want to emphasize that the exact mechanism by which such effects come about is not known. The knowledge we have is derived from animal studies and from anecdotal reports. Those studies are underway.
PRx Host :
What is the research you are doing now?
Khachaturian :
We no longer do research. Both Dr. Radebaugh and I have been involved in supporting research; that is, administering research. We spent the last 20 years or so building national programs of research at universities and medical centers. We have not done any direct research during the last several years.
PRx Host :
What is the focus of what you are doing now, then? What research are you funding and do you think is hopeful?
Khachaturian :
The primary role we play is to be something analogous to conducting an orchestra rather than being a musician. The main function we serve is to connect people from different areas of research, people with different ideas, get them together and create synergism between them. We connect people from basic science with clinical research or different areas of science to look at the problem from many different perspectives.
During the last several years, we put together Alzheimer's research centers, which were instrumental in making most of the advances that you read in the press. Those advances came about because we created a connection between basic scientists such as geneticists and neurochemists to work side-by-side with clinicians, neurologists, psychiatrists. Through that kind of teamwork, advances were made. We specialize in putting such teams together.
The future where you see the most promising work that's likely to come is from understanding the basic biology; that is, how mutation errors in genes transfer into clinical symptoms that one sees. By understanding the connection between genetic mutations and the disease, we are trying to find targets for treatment. It's through that effort that we're going to be able to find the clue for prevention. We're very hopeful that's going to be achieved in the lifetimes of many people alive today.
PRx Host :
How exciting! And how hopeful. Is there any research indicating any environmental connection to genetic mutations?
Khachaturian :
There is always the possibility that certain environmental exposures would influence how our genes are expressed, such as radiation or strong stimuli. However, in the case of Alzheimer's, there is no specific environmental culprit that one could pinpoint as being the guilty party. In the complex disease process of Alzheimer's disease, what is likely is that many genes interact. The disease is not caused by a single gene, but by many genes working together. Some interact with environmental or lifestyle experiences. A person may have a gene that makes them susceptible for the disease, but the gene may not be sufficient to cause the disease. Exposure to environmental toxins, industrial solvents, or some other toxins may trigger the disease. But we do not yet have those environmental toxins. We haven't identified them. That will come through epidemiological studies, and epidemiology is an area of science where Dr. Radebaugh is the expert. They are the detectives of medicine. These detectives are looking for such interactions between genetic and environmental factors.
Perhaps Dr. Radebaugh could talk about some of the types of studies that are being done with different populations in different parts of the world, trying to find these complex interactions between genetic, environmental, social factors. We don't know enough about them.
PRx Host :
Dr. Radebaugh is temporarily unable to access the screen, unfortunately. When she returns, we will ask her. Meanwhile, we have another audience question.
Elska :
My grandfather had Alzheimer's, and I would like to know if there are statistics on the genealogy of the disease? What are the chances that my father or I will get it? Is it genetic, and if so is it paternal or maternal?
Khachaturian :
The chances of someone who has a close blood relative getting the disease increases by several fold. It's not a 100% guarantee that the person who has a close blood relative is going to get the disease. There are many individuals who have large numbers of members in their family with Alzheimer's disease, yet they survive to very old age without getting the disease. On the other hand, there is always a greater risk of someone with a family history vs. one without the family history. The best advice one could give is to be acutely aware of the risk and to be evaluated constantly at the first sign of any memory or cognitive problem -- and to go on with life.
PRx Host :
Dr. Radebaugh is back on now, so I'd like to ask her to speak about research in different populations and the connections she is finding with environment, location, etc.
Radebaugh :
Research in unique or special populations has the potential to provide insights about exposures or experiences that may increase or decrease the risk of developing the disease. For instance, some investigators have found very low rates of illness in populations in Nigeria as well as in the Cree Indians in Manitoba.
PRx Host :
Is Alzheimer's a recent disease or one that has been around but not identified? Is there a hope that if someone already has Alzheimer's disease, that some of the research could reverse or halt it?
Radebaugh :
I think the answer to that question is that Alzheimer's has always been part of the human condition. We know that from the writings of Greek and Roman physicians. Even Shakespeare has written about conditions like Alzheimer's. In several of the plays, he describes symptoms that were very similar to Alzheimer's.
The problem, until the turn of the century, was that very few people in the population survived beyond age 65. Since the disease starts appearing about that time, it was not recognized as a major medical problem. During the last three decades or so, the number of individuals who survive beyond age 65-70 has increased dramatically. One of the reasons we know that is that we have legislation like the Older Americans Act, which came about in 1961. The National Institute on Aging was created in 1971.
The tendency for the population to survive into very old age is going strong. Since the prevalence of the disease starts rising with age, we are going to see more and more people at risk for it as the Baby Boomers come of age. It is not a new disease. It's always been around. It's becoming a large number simply because people are living longer.
At present, the answer to the second question is, we cannot halt or reverse Alzheimer's. The objective of most of the research being done in the last 3-4 years is to find ways to slow the progression or halt it. That's going to be the Holy Grail, to find a way in which we can detect the disease very early, while the person is still cognitively able to function, and stop the disease at that point. Ideally, we would want to reverse the course of the disease, but that will probably happen 10 to 20 years from now, as we learn more about the genetic basis of the disease and develop the technology for increasing the functionality of nerve cells, such as growing new nerve cells and restoring their functioning.
These technologies are being used in animals. There were studies showing it was possible for individuals to grow new nerve cells. These are very exciting and promising scientific advances which are going to find applications in the future, but in the meantime, we have to solve a number of very important technical and ethical issues that are involved with such research.
Elska :
Thank you for answering my question previously. However, I would like to know if there is any evidence that the disease is passed paternally or maternally?
Khachaturian :
We do not know that yet. We haven't got enough information to make that kind of fine dissection. As we learn more about genetics and as genetic technologies become available, it should be possible to make such determinations.
mlsten :
Assuming there is no genetic Alzheimer's factor in a person's family history, is it known whether there is still a risk of acquiring it from purely environmental factors?
Khachaturian :
The genetic factor can never be totally ruled out. We do not know the impact of many, many genes that may play a role. We have, in my view, only begun to scratch the surface of the genetic basis of the disease, I think. To rule it out, to say, "Without genes, does environment play a role?" -- the answer is unlikely, but yes, there could be certain conditions which may trigger Alzheimer's-like symptoms.
A few years ago, there were cases in Montreal, Canada where people ate some seafood that was contaminated with certain algae. They developed Alzheimer's-like symptoms because the algae produced toxins that killed nerve cells in the same way Alzheimer's disease does. There are toxins produced by the body and brain, certain chemicals produced by the nerve cells, that at times can become toxic and kill the cells. The toxicity of these chemicals in the brain are neurotransmitters. They become toxic if the nerve cell is deprived of glucose. A chemical that's normally functioning properly all of a sudden becomes energized because of some other condition. Genes are always playing a role. We simply do not know enough about that.
PRx Host :
What is the longest you are aware of that someone diagnosed with Alzheimer's disease has been able to continue functioning adequately enough to hold a job, and continue his or her life pretty normally?
Radebaugh :
The difficulty with answering that question is that people seek diagnosis at different stages in the illness. We do know that it will progress steadily and deprive people of the ability to carry out those activities, but an exact dating is not possible.
PRx Host :
I thank you both for such an informative and also hopeful chat. We unfortunately have come to the end of our hour. I hope we can have you both back in the future.
Radebaugh :
Thank you very much for inviting us.
Khachaturian :
Thank you very much!
PRx Host :
Could you give us the name of your organization and the contact info, please, before we close?
Khachaturian :
We are Khachaturian and Radebaugh and Associates, Inc. Our website is located at www.kra.net.
PRx Host :
Thank you, and good night to you both!
More About Zaven Khachaturian & Teresa Radebaugh
Alzheimer's disease experts Zaven Khachaturian, Ph.D., and Teresa Radebaugh, Sc.D., have spent decades researching this debilitating disease, which currently affects approximately four million Americans. Together they have recently edited a comprehensive volume, Alzheimer's Disease: Causes, Diagnosis, Treatment, and Care, available from CRC Press.
Zaven Khachaturian, former director of the Office of Alzheimer's Disease Research, received his undergraduate degree from Yale University, his doctorate from Case Western Reserve University, and his post-doctoral training at the College of Physicians and Surgeons, Columbia University. He is the former associate director for the Neuroscience and Neuropsychology of Aging Program at the National Institute on Aging at the National Institutes of Health. While there, Khachaturian coordinated all Alzheimer's disease activities at NIH and established the national infrastructure for Alzheimer's disease research. He has made significant original scientific contributions to the development of brain aging and Alzheimer's disease as distinct areas of investigation. As an international lecturer, he translates research for lay audiences, publishes seminal reviews and theoretical papers, and serves on the editorial boards of several papers.
Teresa Radebaugh, a psychiatric epidemiologist trained at the Johns Hopkins School of Hygiene and Public Health, spent many years at the National Institutes of Health. Her positions include serving as Chief, Dementias of Aging Branch, Neuroscience and Neuropsychology of Aging Program, National Institute on Aging. She was also the director of the Division of Extramural Research, National Institute of Nursing Research, where she had responsibility for the scientific program and review of activities of the Institute. Radebaugh has substantial experience in other major aging-related research areas, including falls, hip fractures, osteoporosis, and urinary incontinence.
The two experts have formed an international consulting firm, Khachaturian, Radebaugh and Associates, which handles the planning, developing and managing of science- and technology-based programs devoted to Alzheimer's disease.
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