Cholinesterase inhibitors in Alzheimer‘s disease: sooner or later or both?

Abstract

Evaluation of: Winblad B, Kilander L, Eriksson S et al.: for The Severe Alzheimer‘s Disease Study Group: Donepezil in patients with severe Alzheimer‘s disease: double-blind, parallel-group, placebo-controlled study. Lancet 367, 1057–1065 (2006). At the time of the original introduction of cholinesterase inhibitors it was intuitively suggested that these drugs should be targeted to patients with mild-to-moderate Alzheimer‘s disease who had a useful enough degree of cholinergic reserve to provide a substrate for the drugs‘ mode of action. Clinical studies and economic modeling supported these propositions and national guidelines groups, such as the National Institute for Clinical Excellence (NICE), endorsed this approach. More recently, other work has suggested that cholinesterase inhibitors may, after all, be useful in later phases of the disease. The most recent advice from NICE has shifted its emphasis towards moderate disease and the paper evaluated here represents a definitive study on this topic. This raises intriguing questions as to other mechanisms of actions for this class of drug.

Keywords: :

• acetylcholinesterase
• Alzheimer‘s disease
• cholinesterase inhibitors
• donepezil
• National Institute for Clinical Excellence