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a Dementia
Research Laboratory, Neuroscience Research Centre, Guy's, King's and
St Thomas' Schools of Biomedical Sciences, King's College, London,
SE1 9RT, UK, b Cerebrus, Oakdene
Court, 613 Reading Road, Winnersh, Wokingham, RG41 5UA, UK, c Department of Care of the
Elderly, Frenchay Hospital, Bristol, BS16 2EW, UK
Correspondence to: Dr Paul T Francis, Dementia Research Laboratory, Division of Biomolecular Sciences, Guy's, King's and St Thomas' Schools of Biomedical Sciences, King's College, St Thomas Street, London SE1 9RT, UK. Telephone 0044 171 955 2611; fax and answer phone 0044 171 955 2600; email p.francis{at}umds.ac.uk
Received 11 June and in revised form 20 October 1998;
Accepted 30 October 1998
Alzheimer's disease is one of the most common causes of
mental deterioration in elderly people, accounting for around 50%-60% of the overall cases of dementia among persons over 65 years of age.
The past two decades have witnessed a considerable research effort
directed towards discovering the cause of Alzheimer's disease with the
ultimate hope of developing safe and effective pharmacological treatments. This article examines the existing scientific applicability of the original cholinergic hypothesis of Alzheimer's disease by
describing the biochemical and histopathological changes of neurotransmitter markers that occur in the brains of patients with
Alzheimer's disease both at postmortem and neurosurgical cerebral
biopsy and the behavioural consequences of cholinomimetic drugs and
cholinergic lesions. Such studies have resulted in the discovery of an
association between a decline in learning and memory, and a deficit in
excitatory amino acid (EAA) neurotransmission, together with important
roles for the cholinergic system in attentional processing and as a
modulator of EAA neurotransmission. Accordingly, although there is
presently no "cure" for Alzheimer's disease, a large number of
potential therapeutic interventions have emerged that are designed to
correct loss of presynaptic cholinergic function. A few of these
compounds have confirmed efficacy in delaying the deterioration of
symptoms of Alzheimer's disease, a valuable treatment target
considering the progressive nature of the disease. Indeed, three
compounds have received European approval for the treatment of the
cognitive symptoms of Alzheimer's disease, first tacrine and more
recently, donepezil and rivastigmine, all of which are cholinesterase inhibitors.
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