Cholinesterase inhibitors for Alzheimer's disease

Background ** This review is awaiting update with a new protocol. The methods used for the review were acceptable when the review was published but do not meet contemporary standards, and the review is also considerably out of date. Therefore, readers should note that the review may not represent a reliable basis for decision making. ** Since the introduction of the first cholinesterase inhibitor (ChEI) in 1997, most clinicians and probably most patients would consider the cholinergic drugs, donepezil, galantamine and rivastigmine, to be the first line pharmacotherapy for mild to moderate Alzheimer's disease. The drugs have slightly different pharmacological properties, but they all work by inhibiting the breakdown of acetylcholine, an important neurotransmitter associated with memory, by blocking the enzyme acetylcholinesterase. The most that these drugs could achieve is to modify the clinical manifestations of Alzheimer's disease. Cochrane reviews of each ChEI for Alzheimer's disease have been completed. Objectives To assess the effects of donepezil, galantamine and rivastigmine in people with mild, moderate or severe dementia due to Alzheimer's disease based on evidence summarised in three existing Cochrane Reviews Search methods The Cochrane Dementia and Cognitive Improvement Group's Specialized Register was searched using the terms 'donepezil', 'E2020' , 'Aricept' , galanthamin* galantamin* reminyl, rivastigmine, exelon, "ENA 713" and ENA‐713 on 12 June 2005. This Register contains up‐to‐date records of all major health care databases and many ongoing trial databases. Selection criteria All unconfounded, blinded, randomized trials of at least six months in which treatment with a ChEI at the usual recommended dose was compared with placebo or another ChEI for patients with mild, moderate or severe dementia due to Alzheimer's disease. Data collection and analysis Data were extracted by one reviewer (JSB), pooled where appropriate and possible, and the pooled treatment effects, or the risks and benefits of treatment, estimated. Main results The results of 10 randomized, double blind, placebo controlled trials demonstrate that treatment for 6 months, with donepezil, galantamine or rivastigmine at the recommended dose for people with mild, moderate or severe dementia due to Alzheimer's disease produced improvements in cognitive function, on average ‐2.37 points (95%CI ‐2.73 to ‐2.02, p