Beyond the cholinergic hypothesis: the effect of metrifonate and other cholinesterase inhibitors on neuropsychiatric symptoms in Alzheimer's disease.

Preliminary studies suggest that non-cognitive behavioural and personality alterations in Alzheimer's disease may benefit from agents which inhibit central acetylcholinesterase (AChE). A double-blind, placebo-controlled, 26-week study of the AChE inhibitor metrifonate using the NeuroPsychiatric Inventory (NPI) to assess the effects of treatment on neuropsychiatric symptoms observed statistically significant mean change differences favouring treatment in the total NPI score and in symptoms of depression, apathy and hallucinations, as well as a nearly significant difference in aberrant motor behaviours. These data are consistent with previous studies and are believed to represent the first large prospective, controlled study demonstrating a beneficial effect of AChE inhibitor therapy on neuropsychiatric symptoms in Alzheimer's disease. The nature of non-cognitive symptom responses to AChE inhibitor therapy and their potential impact on caregivers is discussed.