FOR DEBATE: IS THE EVIDENCE FOR THE EFFICACY OF CHOLINESTERASE INHIBITORS IN THE SYMPTOMATIC TREATMENT OF ALZHEIMER'S DISEASE CONVINCING OR NOT?

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Over 20 years ago the publication of an optimistic report by Summers and colleagues (1986) on the use of the cholinesterase inhibitor tetrahydroaminoacridine (THA/tacrine) to treat patients affected by Alzheimer's disease (AD) started an avalanche of research publications on the use of cholinesterase inhibitors for the symptomatic treatment of the cognitive deficits seen in people with AD. Despite the fact that the Summers et al. study turned out to be very deeply flawed indeed (Division of Neuropharmacological Drug Products, 1991), the juggernaut whose movement it initiated has not yet ceased to roll. Subsequent large studies of tacrine performed on people with carefully diagnosed AD established a plausible methodology for the conduct of clinical studies of drug efficacy in the treatment of AD (Ritchie et al., 2007). These studies suggested that the drug had modest beneficial effects in some patients (Ritchie et al., 2007), and revealed that it had a high rate of adverse effects on the gut (Brodaty, 1996) and liver (Ames et al., 1990).