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ALZHEIMER’S DISEASE

THE SCALE OF THE PROBLEM


Approximately 6% of people over the age of 65, rising to as many as 20% of those over the age of 80, are affected by Alzheimer’s disease. As the numbers of people living long lives grows rapidly, so too does the rate of Alzheimer’s disease, and at the present time, it is estimated that more than half a million people in the UK alone are affected.

The costs of Alzheimer’s disease are huge. With millions now affected in the developed countries, the costs of health care are already very large - an estimated £17,000 million per annum in the UK. These costs are set to rise in the developing countries, which will place considerable strain on health services. Costs to relatives are also significant both financially and emotionally. The biggest cost of all though, is to the patients themselves.


MAIN FEATURES OF THE ILLNESS


Alzheimer’s disease is a progressive disorder which begins invariably with memory problems leading to those affected, wandering, becoming lost and eventually being unable to recognise members of their family. Many patients become depressed and some have more frightening experiences - believing that they have been robbed or seeing things that are not there. Often there are personality changes and sometimes patients become aggressive. Early in the illness, the ability to look after themselves is affected. It starts with small things such as difficulties in handling money or using the telephone. Leads on to loss of the ability to look after personal hygiene and dressing. And in the very late stages of the illness to becoming incontinent and finally bedridden. However, many patients with Alzheimer’s disease are largely unaware of the changes brought about by the disease process.

The family or other carers invariably carry a significant burden. Not only are there the tasks of caring for sufferers and gradually having to take over all of the ordinary tasks of living for them, but the family finds that their loved ones are so greatly changed by the disease that the relatives undergo what is virtually a process of mourning. In addition, there is often the added burden of financial difficulties caused by the need to pay for some aspects of care.


TREATMENTS


Treatment for Alzheimer’s disease in the UK first became available in 1997. These first drugs rectify one of the main losses that occur in the brains of people with Alzheimer’s disease – that of the neurotransmitter acetylcholine. One of the first studies to demonstrate that this therapy might be useful was conducted by Professor Levy at the Institute of Psychiatry. Now widely available these drugs treat some of the symptoms but not the actual disorder itself.

For the most part, treatment for Alzheimer’s disease remains the important task of dealing with behavioural disturbance or depression and ensuring adequate support for carers and appropriate services for patients. Research at the Institute of Psychiatry, is examining new therapies for behavioural disorder; is involved in the training of professional carers; and is investigating the best ways in which services can work with families.


PROGRESS IN UNDERSTANDING ALZHEIMER’S DISEASE - WORKING TOWARDS A CURE


Alois Alzheimer, at the beginning of the century, first described the microscopic changes in the brain that are the hallmarks of Alzheimer’s disease. These are the two abnormal deposits called neurofibrillary tangles and amyloid plaques. Rapid progress by researchers around the world has led to a detailed understanding of how amyloid plaques are formed. As a result many of the stages in this process are now receiving intense scrutiny, since it is likely that these are sites where drugs might actually prevent or reverse the process of Alzheimer’s disease.

However, it is the death of neurones, caused by the neurofibrillary tangles, that is probably directly related to the symptoms of the disease and associated disorders. At the Institute of Psychiatry, we have found an enzyme that is responsible for changing the protein that forms tangles (tau) from a normal form to a form that is predominant in Alzheimer’s disease. We have also been able to demonstrate why some genetic changes in the tau gene give rise to dementia. Both of these findings may point the way towards new treatment that might also prevent, slow down or perhaps even reverse the disease itself. The first trials of potential drugs based on these discoveries started in 2010.


GENETIC FACTORS


Some early onset familial forms of Alzheimer’s disease are caused by mutations or changes in a gene called amyloid precursor protein (APP) and in two very similar genes called presenilin-1 and presenilin-2. A closely related dementia is caused by mutations in the tau gene in some families. Together these four genes account for only a tiny proportion of dementia. But even the common late-onset form of Alzheimer’s disease is related to genetic factors.

One gene in particular appears to be responsible for this - the apolipoprotein E (APOE) gene, one form of which increases the risk of Alzheimer’s disease and another form of which might delay the condition. This gene, APOE, does not “cause” Alzheimer’s disease but increases the risk of suffering from it. Very recently, together with collaborators, we have identified two more genes that appear to have a similar, albeit smaller, effect in increasing risk. Calculations suggest that there may be many - perhaps as many as eight or ten genes - that act together to modify the risk of suffering from this condition.

Finding these genes - the ones that cause familial Alzheimer’s disease and those that increase the risk of late onset Alzheimer’s disease - has been one of the most important advances in research into this condition. These discoveries are signposts, pointing the way for biologists and chemists to identify the processes in the brain leading to Alzheimer’s disease, and then to discover drugs which might interrupt this chain of events. However, finding genes also raises other possibilities including the possibility of genetic testing for diagnosis or for other purposes. We are concerned about the implications of this for families and we host a national group which oversees the ethical implications of this research. More research is needed on the impact of these discoveries on the relatives of people with Alzheimer’s disease.


OTHER RISK FACTORS


Of course it is not "all in the genes" and epidemiologists, including a group here, are looking for other causes. So far the search suggests that head injury, heart disease and diabetes are all risk factors. Aluminium was once thought to be important but further research has suggested it does not increase risk. Finding these environmental risk factors is as important as finding genes, since it too signposts ways towards treatments.


THE FUTURE FOR ALZHEIMER’S DISEASE


The pace of research in Alzheimer's disease is fast but not fast enough for those families touched by the disorder. Research over the past 20 years has resulted in the first drugs for the condition - an important start. What is now needed is a greater understanding of the condition itself. We need to find other genes and other environmental factors. We need to understand more about how amyloid is developed and how tangles are formed. We desperately want to understand how amyloid plaques and tangles are related to each other.

Progress on any of these fronts may yield the next generation of treatments; treatments that will affect the disease itself rather than just the symptoms. However if any such therapies are to be used effectively, we need much better ways of diagnosing Alzheimer’s disease which at present is a difficult and not entirely accurate clinical task. A diagnostic test would revolutionise the prospects for treatment of Alzheimer’s disease and researchers here as well as many other groups, are actively looking for such tests. We have had some signs of early success and we are now using computer aided analysis of brain scans to help diagnose Alzheimer’s disease more accurately and are developing a blood test which we hope will be useful to pick up the very earliest signs of the disorder.

We need new ways of treating behavioural disturbance in Alzheimer’s disease, using both drugs and other therapies. We need to understand more about the process of caring.

The last few years of research into Alzheimer’s disease has seen greater progress than in almost any other disorder of the brain. However, although exciting, there is a huge amount still to do.


Professor Simon Lovestone
Professor of Old Age Psychiatry
Institute of Psychiatry at King’s College London
2011

Charity No 284286



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