TREATMENT STRATEGIES OF ALZHEIMER’S DISEASE: DRUGS TO IMPROVE MENTAL FUNCTIONING
The discovery that the brain lacks adequate quantities of important chemicals such as the neurotransmitter acetyl choline resulted in a search for medication that would rectify either the deficiencies concerned or the results of these deficiencies. Traditionally there are three approaches to trying to deal with a situation in which a chemical is missing from the brain.
The first approach is to give the body more of the chemical in the hope that it will be passed to the brain, where it can carry out its normal function, or to provide the brain with other substances that it may be able to convert into the missing chemical. This approach has been tried for Parkinson’s disease and has been very effective in treating the symptoms in many people, although it doesn’t prevent the progress of the disease. For the treatment of Alzheimer’s disease, however, the results have been disappointing. Perhaps the best-known substance to have been tried is lecithin for which there have been many trials, some attempting to show an improvement in intellectual function and others with the more modest objective of showing that it might prevent or slow down further deterioration. There has however been very little evidence that lecithin and similar compounds have been beneficial.
A second approach to help the brain cope with a reduction in the level of an essential substance is to try to ensure that the little that is available lasts for as long as possible. Like most tissues in the body, the brain has the chemical processes to enable it to destroy most chemicals it is designed also to produce. This is essential in biological systems where a balance between production and destruction has to be maintained. We know that there are some drugs that slow down the destruction of acetyl choline and similar compounds, and it was hoped that the administration of these might result in a prolonged life for the small amounts of neurotransmitter produced, with an improvement in intellectual function.
Until recently this technique also seemed to be disappointing, but a new substance called tetrahydroaminoacridine (THA) has proved worthy of further evaluation. Significant improvements in intellectual ability were originally claimed for THA, but although these have failed to be substantiated by subsequent trials, it is beginning to look as if a proportion of patients with Alzheimer’s disease, but not other dementias, may acquire modest improvements in ability and behaviour with this drug. It is, unfortunately, a drug that produces many side-effects which may preclude its ever being generally available on prescription. It may, however, show us the way to development of more effective and safer drugs. Perhaps we have our feet one or two rungs up from the bottom of the long ladder of drug development for Alzheimer’s disease.
The third approach to dealing with a reduction in the amount of a neurotransmitter in the brain is to try to make the brain structures that are switched on by the depleted chemical more sensitive to the reduced amounts available. Although this approach is used in other neurological diseases with a modest degree of success, it has so far failed to be of much benefit to people with Alzheimer’s disease.
Since approaches aimed directly at affecting the missing chemicals have been unsatisfactory, although as mentioned THA is under further evaluation, researchers have turned to other methods of trying to improve brain function. One of the most exciting of these is the attempt to prevent or slow down the rate of cell death of the factory cells that produce the neurotransmitter chemicals. In other words, rather than trying to replenish the brain’s level of neurotransmitters by using tablets or injections that contain the missing chemicals or those that can be made into them, an attempt is being made to see whether it is possible to discover why the factory cells are dying or not working properly, in the hope that they can be made to fulfil their normal function once again. A modest degree of success has been achieved in understanding what is happening to these factory cells although it is not yet known whether this knowledge can be translated into an effective therapy. It seems as if some of the cells in the brain that make neurotransmitters need substances called trophic factors in order to carry out their normal functions and there is a suggestion that in some degenerative diseases of the brain, including Alzheimer’s disease, these trophic substances may be missing. It is hoped that it may be possible to supply the appropriate trophic factors to enable the cells to work properly, so that they in turn may produce the neurotransmitters that are required for normal brain functioning. Although this field of research holds great promise, it is too early yet to know whether it will be an effective form of treatment.
As well as the specific attempts to try to put right the biochemical abnormalities that occur in the brain in Alzheimer’s disease, there have been many other, rather more general approaches to developing drug treatments that may improve dementia, almost irrespective of the underlying cause. All sorts of drugs have been tried. Many of them were originally developed as vasodilators — medicines that would cause dilation of the blood vessels thereby improving the blood circulation to the brain. It is now known that this type of approach is unlikely to be of any benefit since it does not improve any of the conditions that cause dementia. Other drugs were thought to improve the metabolism — the biochemical processes — within cells and these too have proved disappointing. Many other methods have been tried, but so far, with the exception of people who have a treatable cause for their dementia such as a vitamin deficiency, there is no evidence that any medicine that is generally available is of any benefit in improving intellectual performance. This situation may change, however, within the next two or three years.
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NURSING IN THE CASE OF ALZHEIMER’S DISEASE: USING THE TOILET
As a demented person becomes less steady on his or her feet, it is essential to ensure that rails are provided around the toilet area. Most falls occur when a person is in the process of standing up or sitting down; it is possible to get raised toilet seats that make it easier to get on and off.
For night-time use it may be better to have a commode put at the bedside. This is most useful if the bathroom is on a different floor to the bedroom. For men, a bottle-urinal may be helpful not only at night, but also during the day. It can be discreetly placed in a container at the side of the chair in which he is sitting, and regularly emptied.
When a man with dementia begins to forget to go to the bathroom and when, having got there, he has difficulty in remembering the routine, it may be easier for him to sit on the toilet to pass water than to stand up. This can be less problematical and less embarrassing for a wife or other carers.
Problems with using the bathroom and toilet, and many others such as dressing, are an area where the occupational therapist can give invaluable support and advice. This can usually be arranged through the general practitioner or health visitor.
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BEHAVIOURAL AND PSYCHOLOGICAL PROBLEMS IN THE CASE OF ALZHEIMER’S DISEASE: PROBLEMS AT NIGHT
Those suffering from a dementing illness may well disturb other people’s sleep. Sometimes it is because they have a tendency to wander; sometimes they are disorientated and think that it is time to get up; sometimes they are frightened at night. Often, having gone to the bathroom they are unable to find their way back to the bedroom or have their attention diverted to something else with which they then become involved.
Many people with dementia are less active than they used to be during the daytime and may take more daytime naps than before. Try to make sure that they get adequate physical and mental activity during the day, to help promote sleep. It is also a good idea to try to ensure that they go the bathroom last thing before going to bed; restricting fluids during the evening, say after supper if this does not cause distress, can also help. Leaving a light on in the bathroom and having a low-wattage bulb on the landing can assist a confused person in getting around at night.
The bed needs to be comfortable and some relatives find that continental quilts are easier for a person with dementia to manage than blankets and sheets. It is probably best not to use cot-sides as they rarely manage to deter a wanderer and can be irritating. Sometimes, however, they can be helpful in preventing a person from falling out of bed if this is a problem.
If sufferers decide to get dressed and you have difficulty dissuading them, don’t worry — let them get on with it. They may well be prepared to go back to bed, even though fully clothed. Sometimes a warm drink works as it is often associated with the going-to-bed routine.
Finally, there are two important points. First, if wandering at night is a real problem, make sure there are no hazards to safety, like gas taps that could be turned on. Secondly, a step that can be taken is to ask the doctor to prescribe some sleeping medicines. These should be avoided except as a last resort and should only be tried for a few weeks at a time. Sometimes it can be left to the carer’s discretion to administer them intermittently, perhaps after having had two or three bad nights in a row. All medicines have side-effects and you must ask the doctor what to watch out for if they were to affect the person you are looking after.
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DEVELOPMENT OF DIAGNOSTIC TESTS OF ALZHEIMER’S DISEASE: MONITORING THE CSF
Many of the diseases that afflict mankind can be diagnosed with relative ease by examining the blood for abnormal changes or looking for specific diagnostic indicators in other body fluids, for example the urine and, particularly for diseases that affect the nervous system, the cerebrospinal fluid (CSF). There are currently many studies seeking such ‘peripheral’ markers of the presence and severity of Alzheimer’s disease. If identified, not only might they help with diagnosis, but they might also assist in monitoring the effectiveness of treatment when this becomes available.
Some of the earliest attempts at isolating diagnostic markers involved examining the CSF for changes in its biochemistry that would reflect the biochemical abnormalities that we know occur in the brain. Although there have been some reports of differences between people with Alzheimer’s disease and normal people of the same age without any intellectual deficit, there has been too much overlap between the two groups to enable the biochemical differences in question to indicate reliably the presence or absence of the disease. Similar attempts have been made to examine the changes in the blood and again the results have been disappointing.
More recently, and in many ways more hopefully, researchers have been trying to identify changes in the CSF and the blood that relate not to the biochemical changes within the brain, but to the structural abnormalities that develop in Alzheimer’s disease. Attempts are in hand to try to make the diagnosis by proving that the blood or CSF contains substances which indicate that the brain, in its turn, contains more senile plaques or neurofibrillary tangles than it should. At the time of writing this seems a much more logical approach and several tests have arrived at the point of clinical trial. It will probably be a year or two, however, before we know whether they are going to live up to expectations.
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UNTREATABLE CAUSES OF DEMENTIA: CEREBRAL TUMOURS
A cerebral tumour can cause dementia. Such tumours can be divided into two types – primary and secondary. Primary cerebral tumours are those that arise within the brain itself whereas secondary tumours spread there from a site somewhere else in the body, usually arriving via the bloodstream. Secondary tumours arise when a few cells from a tumour, say a cancer of the breast, are taken by the bloodstream and planted as seeds in the brain, where they grow and destroy brain tissue. Sometimes there are many small secondary deposits. They may cause all sorts of other symptoms and side-effects and don’t always cause dementia.
Since most brain tumours are unsuitable for X-ray therapy or surgical removal, it is usually only possible to treat the symptoms, such as headache. However, some primary tumours, especially one called a meningioma, can often be completely and safely removed. A meningioma can grow to a very large size and still be removed. It is therefore another of the treatable conditions that can be diagnosed from a brain scan. In most tumours, unfortunately, although treatment can be given to improve the quality of life of the person concerned, the tumour will eventually be responsible for the patient’s death.
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