British Association for Pyschopharmacology. To advance education and research in the science of psychopharmacology
posted on Monday, 19th March 2012
by Professor Paul T Francis, PhD, Professor of Neurochemistry, Director, Brains for Dementia Research, Wolfson Centre for Age-Related Diseases, King's College London
Alzheimer’s Disease International estimate 35.6 million people living with dementia worldwide in 2010, increasing to 65.7 million by 2030 and 115.4 million by 2050. In the UK currently up to 820,000 people are living with dementia.
Dementia can occur from the mid-40s but this is fortunately very rare and more typically occurs after 65 with 1 in 5 people over 80 likely to experience symptoms of dementia. The term dementia refers to a group of symptoms including memory loss, changes in language, thinking and reasoning and is often accompanied by changes in personality, mood and behaviour. Such changes are progressive and interfere more and more with someone’s ability to work, engage in pastimes and socialise. It is often the changes in behaviour such as aggressive outbursts, wandering outside the home and delusions - rather than memory problems that carers find most difficult to cope with.
Diagnosis of dementia in the UK is usually made by a specialist doctor after performing tests of memory, thinking, concentration and language. The tell-tale signs of dementia are poor performance that gets worse between assessments. Sometimes the person may also have their brain scanned to look for evidence that the brain has shrunk.
Different types of dementia and causes
The most common cause of dementia is Alzheimer’s disease (AD), accounting for 50-60% followed by vascular dementia (VaD), Lewy body dementia (LBD) and fronto-temporal dementia (FTD). However, more than one type can be found in a single person for example, AD and VaD commonly co-occur and the exact cause of dementia can only be fully established by a detailed examination of the brain following death. The direct cause of most symptoms of dementia is likely to be damage to nerve cells and the connections between them (called synapses). Particular symptoms will occur depending on which parts of the brain are affected. The varied causes of dementia affect nerve cells and synapses in different ways, for example in the case of AD damage appears to be related to modifications of two proteins called Ab and tau while in VaD the changes are brought about by lack of oxygen supply to areas of the brain. Ongoing research effort will hopefully discover more about the detailed differences between the various causes of dementia and discover molecules that can be measured in people living with dementia and those at risk, so called biomarkers, that will help identify specific types of dementia during life and allow presymptomatic diagnosis.
Only rarely does dementia run in families with a very small percentage of people inheriting diseasecausing gene from a parent. However, a lot of current interest is focusing on variations in genetic code between individuals that may alter the age at which they develop dementia and their overall risk. Recently discovered genes causing small increases in risk (called clusterin and PICALM) seem to link to how the brain gets rid of unwanted proteins. This type of work can be very useful in providing new directions for future research.
How do we treat people with dementia now?
In the 1970s and 80s seminal work identified changes in particular chemicals called neurotransmitters that are involved in communicating between nerve cells in people with AD. The discovery that reductions in acetylcholine and glutamate were related to memory problems inspired huge effort to find drugs based on replacing these lost chemicals and eventually acetylcholinesterase inhibitors (eg Aricept and Exelon) and a glutamate-based drug (Ebixa) were licensed. These drugs, while not a cure, do provide important benefits in some people with dementia. Treating symptoms such as mood, aggression and agitated behaviours has proved more difficult as drugs that are used in people without dementia to treat these symptoms are ineffective (antidepressants) or more dangerous in this older population (antipsychotics).
Considerable research effort needs to be directed to finding new treatments for cognitive and behavioural symptoms that are safe and effective in people with dementia. Most research effort is directed towards AD and in some cases drugs used in AD have some benefit in other forms of dementia but this is not always the case and drug development for these less abundant dementias needs to continue.
How will we treat people with dementia in the future?
Treating symptoms is important and brings much need relief to people with dementia and their carers however, slowing or preventing dementia developing are important targets. For AD, many drugs have been developed that target one of the two proteins that is important as a diseasecausing mechanism, Ab. Drugs that inhibit the formation of this protein and other approaches that use a vaccine against it showed great promise in studies on animals. Unfortunately these drugs have proved ineffective in slowing the course of the disease in people with dementia, possibly because they are being tried too late in the disease course. Now attention has turned to preventing the modification of tau protein that leads to tangles in nerve cells and we wait with considerable interest for the first compounds to come to clinical trial.
How can I get involved?
One way people can help research is to consider donating their brain for research after their death. Brains for Dementia Research is supported by the two major UK charities for people with dementia and was established in 2007 to promote brain donation and establish a network of brain banks to facilitate research into dementia.BDR is interested in hearing from people diagnosed with a memory impairment (or dementia) to participate in monitoring memory, thinking and behaviour prior to brain donation. We also invite those who do not have a memory impairment to take part, as normal brain tissue is essential for comparison.
A UK charity dedicated to people with dementia and their carers and who fund research
Alzheimer’s Research UK
A UK charity dedicated to funding research into dementia
Alzheimer’s Disease International
An international organisation bringing together charities and groups worldwide
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