Interview with Dr. Jeffrey L. Cummings.
"Dementia is a disease of the family as it affects the caregiver as much as the patient," says Dr. Jeffrey L. Cummings, vice-chairman, Department of Neurology, University of California, Los Angeles (UCLA). According to him, dementia patients are best taken care of at home, even though they cause tremendous stress to the family.
As Professor of Neurology and Psychiatry and Biobehavioural Sciences, Dr. Cummings played a key role in setting up the Alzheimer's Disease Core Centre at UCLA in 1991, which he converted into a Research Centre in 1998. Since then he has built up an active clinical trials programme.
Apart from being a member of the Alzheimer's Disease Cooperative Study, Dr. Cummings is a consultant to some pharmaceutical companies. He is also director of the UCLA Behavioural Neuroscience and Dementia Research Fellowship, funded by the National Institute on Aging (NIA). Of the 40 Fellows he has trained under the programme, several head dementia research programmes in other parts of the world.
A prolific writer, Dr. Cummings has authored and edited 13 books, over 300 peer reviewed papers, over 150 chapters in books, and several hundred abstracts. Dr. Cummings is particularly interested in neuropsychiatry and the interface of neuroscience and society in Alzheimer's Disease and related dementias.
While in Chennai to deliver the 23rd T.S. Srinivasan Oration on "Dementia - From Science to Patient", he spoke to Asha Krishnakumar on various aspects of dementia, including its causes, diagnosis, treatment and care. Excerpts from the interview:
What is dementia? Is it only an age-related problem?
Dementia refers to a syndrome of memory and intellectual impairment. The word dementia is very general. It applies to any condition that leads to the impairment of memory and intelligence - to all the conditions of the aged, to the kind of problems that follow a brain injury or to the AIDS (Acquired Immune Deficiency Syndrome) patients when the virus enters the brain and so on.
Does the risk of dementia vary across age, sex, social and economic conditions, ethnic groups, environment and genetics?
The prevalence of dementia increases greatly with age, particularly with Alzheimer's Disease (AD). Only 1 per cent of people are affected at the age of 60, at 85, nearly 40 per cent are affected. But dementia can occur at any age.
For the most part, it does not vary across ethnic groups. But if the disease runs in the family then one is more likely to get it than if there is no family history. There is a genetic component to it, but it is only partially understood. Women are more likely to get AD than men - there is a 1.5:1 possibility. Those who have had a head injury in the past are more likely to get AD. We know only some of the facts that predict who is more, or less, likely to get AD.
Does the prevalence of dementia vary across countries?
In Western countries, roughly 10-15 per cent of those over the age of 60 will suffer some degree of abnormal memory loss. This percentage increases with age. In India, studies show a lower prevalence of dementia than in the West. This is an important clue that something in India may be reducing the overall rate of dementia in the country.
We suspect that the Indian diet - the general low-fat food, which is very high in Vitamins E and C which are also good antioxidants; crocumin in turmeric (used in the preparation of curries) is also a very powerful antioxidant - may be responsible for this.
We are trying to figure out the reasons for the lower rate of AD in India compared to the United States. If a diet component is the reason, then we can encourage the intake of that to lower the rates further in India and, of course, apply it worldwide to help prevent the disease. We are very excited about this Indian result.
So, can you say that the problem of dementia is lower in India than in the U.S.?
Although the rate in India is lower than in Western countries, it is still going to be a major problem unless an effective intervention is managed. Of India's population of one billion, about 60 million are over 65 and at least 2.5 million have dementia. That is a huge number of individuals who are suffering the progressive loss of cognitive functions.
It is estimated that by the year 2020, eight million individuals in India will be affected by dementia. This is overwhelming.What are the causes of dementia?
There are several important causes for dementia in older individuals. The two most important ones are AD and stroke. An important distinction has to be made between normal aging and dementia, as the latter is a disease of the brain, while the former, although there can be some changes with memory, is not a disease. The changes that one sees with normal aging are the slowing of the ability to recall things and so on. People worry about it, as they know AD begins with memory impairment. But that is not what we are talking about when we refer to abnormal memory loss in the elderly. This happens because a disease has affected the brain.
What happens to the brain of a person with AD?
In AD, which is the single most common cause of memory loss in the elderly, an abnormal protein, amyloid, accumulates in the brain. Most of our research is concentrated on how to reduce the protein's accumulation or how to stop the injury that the protein inflicts.
What causes amyloid accumulation in the brain?
We are not quite sure as yet why some people accumulate the protein and why others do not. Active research is on in this area.
How do you distinguish memory impairment during the normal course of aging and when one has dementia?
The major challenge is to distinguish between normal aging and AD. The loss of memory that accompany normal aging are milder, they are not disabling and do not impair one's daily activities such as eating, dressing and so on.
The memory of a person with dementia is found to be severely impaired. In particular, such people have difficulty in learning new things and accumulating new memories. They may be able to talk about their childhood fairly accurately but when you ask them about what they did that morning, they have much trouble recalling that. One of the most common complaints of the patient's families is that they repeatedly ask the same question. Other intellectual faculties such as judgment and so on are also impaired. Behavioural changes such as depression and agitation are also common.
As the disease progresses, they lose the ability to talk and walk, and eventually die. So AD is a fatal illness.
Apart from behavioural changes, are there any diagnostic methods to identify dementia?
The diagnosis of AD is exclusively a clinical one. No blood tests. No specific scan findings assist us in making the diagnosis. On the other hand, the clinical picture is relatively distinctive. With a careful examination of memory, language, judgment and a good neurological and medical examination, one can be over 90 per cent accurate in making the diagnosis.
What are the treatment and management methods available?
The treatment is multi-pronged. First, general nutritional measures, fitness, getting adequate water and food, taking care of the skin during advanced stages of the disease and so on are critically important. All these are important not only for survival but also for comfort. We have specific treatments for behavioural changes. We use drugs when necessary, to treat depression or agitation.
Of the specific treatments for AD, one involves using high doses of Vitamin E (because it is an antioxidant), which appear to make the brain more resistant to the effects of the accumulating amyloid. There are also drugs that help restore a chemical, acetylcholine, which is lost by the brain of AD patients. We have three drugs that raise the level of that chemical and therefore help to compensate for the symptoms of AD. They do not cure or stop it, but help to compensate for the absence of the chemical.
How expensive are these drugs in the U.S.? Can people affected by dementia afford them in India?
They are relatively expensive. The drugs cost $100 a month. That would be excessive, I am sure, for many Indian families. There are alternatives that are being looked into, which may be relatively cheap. There is a Chinese herb that can raise the level of acetylcholine in the brain. If that turns out to be a safe drug, which is now being investigated, it could be a very cheap alternative.
How expensive do you think the cheap drug would be?
I cannot say for sure. But, I think, it could be around $10-15 a month. It may still be out of the reach of some, but within the reach of more families.
What is the name of the herb? Where is it found? Is it found in abundance to be able to cater to the increasing population of the old in developing countries?
Huperzine is the name of the herb. It is available, I believe, in relative abundance in China. Studies in China have shown that it has a remarkable effect on dementia patients. But more studies are being done from the safety point of view before it is accepted.
What are the other medicines you use to treat dementia?
Apart from the already mentioned specific treatment, we use a whole lot of anti-depressants and anti-psychotic medications to control behaviour. Working with the family is critically important. It is one of the most important reasons for making the diagnosis because the family needs to be educated about what is going to happen. They need to know how to protect the patient. They need to be given assistance for help in managing AD patients. Tremendous psychological distress is caused while taking care of patients with AD. So, working with caregivers is a critical part of working with dementia patients.
Considering the genetic component of dementia, would the human genome project offer any treatment options to patients with dementia?
There are two known ways in which genetics is important in AD. There are a small number of patients - fewer than 5 per cent of all patients with AD - in whom a mutation of the genes directly causes AD by increasing the amount of amyloid in the brain. These patients in general have a very aggressive course. It starts early in life and kills the patient in about five or six years.
There are also genetic influences in the late onset cases that increases the risk even if there is no mutation. We have evidence that these people are inheriting a genetic risk factor for AD. But it does not mean necessarily that they get the disease. Only, that they are more likely to get it.
Also, there is probably a gene-environment interaction, which means that if you inherit a risk factor but have a diet with high antioxidants, maybe then you would not get it. On the other hand, if you had a risk factor and a diet low in antioxidants, then you would get it.Have you identified any risk gene?
Yes. We have identified one risk gene. There is preliminary evidence of about at least two other risk genes.
What are the research trends in understanding dementia? Are treatment methods improving with better understanding of the disease?
The exact way in which amyloid is produced in the brain is well understood. There are two enzymes that appear to be critically involved in the production of amyloid. And so we are systematically studying drugs that will inhibit those enzymes and therefore reduce the production of amyloid. If we can do that, we could either prevent AD by administering the drug early or greatly slow down the progress of the disease by preventing the protein after the diagnosis is made. There is some continuing work such as on crocumin that are good agents in reducing the amount of injury that amyloid produces in the brain. Thus, there are two major approaches to research now - how to keep the amyloid out of the brain and how to reduce the injury it produces.
Has pharmacological development kept pace with the research on dementia?
Most of the research is linked to a pharmacological outcome. The idea is to understand better the amyloid or the injury it causes to the brain so that a pharmacological treatment can be found.
What is the state-of-the-art research in the area your group is working on?
We are working on the effects on crocumin on mice with AD. We have already found that crocumin reduces amyloid accumulation in the brain. We are also looking at ibuprofen as it is also found to have some protective effect against amyloid.
Other researchers are working on a vaccine. It is possible to vaccinate people against amyloid and make their own cells keep amyloid out of the brain. Unfortunately, trials on people led to unacceptable side-effects. So, the researchers are back in the laboratory trying other vaccination possibilities.
My own work is to find out why some people get depressed or agitated while others do not.
Are you confident of a cure emerging for dementia?
I am optimistic that within a decade we will discover drugs that would meaningfully alter the course of AD treatment.