Acetylcholinesterase inhibitors for Alzheimer's disease

Papers p 633 The development of effective treatments for Alzheimer's disease has been vigorously pursued over the past few decades. Most recent developments have focused on drugs which inhibit acetylcholinesterase and thus increase the availability of acetylcholine within the brain. In this week's issue a pivotal clinical trial of rivastigmine shows, on average, modest benefits for older people with Alzheimer's disease in cognition, clinical global assessment, and quality of life (as assessed by a carer) (p 633).1 What does this add to the evidence for these cholinergic treatments? The evidence to date is that treatments based on the cholinergic hypothesis are essentially symptomatic. No substantial data support the hypothesis that these medications modify the disease—that is, delay its progression. The first drug in this class to show a beneficial effect was tacrine. An early report of dramatic clinical response2 was not confirmed, and documented hepatotoxicity3 severely curtailed its use. More recently developed drugs in …