Objectives: Clinical trials of the cholinesterase inhibitor donepezil have used standard psychometric tools to evaluate treatment efficacy. These trials, however, appear not to capture clinically demonstrable, but otherwise unmeasured, beneficial treatment effects. We sought to identify and categorize clinically recognizable effects of donepezil treatment in Alzheimer's disease.
Methods: A list of potential effects was developed using clinical trials data and the experience of an expert panel. These were incorporated in a questionnaire, which was tested with a focus group, revised and then used in a postal survey of physicians. Data were classified by cognitive domain, and reviewed by a second panel.
Results: Items that were most often rated as being improved were related to frontal systems function, including attentional capacity and initiative. Behavioral symptoms that were among the highest rated items were apathy, mood, and agitation. The top two other items were social interactions and involvement in domestic activities. Of the top ten symptomatic treatment effects, only four appeared to be readily identified by current standard measures.
Conclusions: Physicians recognize as important several treatment effects that are not well captured by current standard measures. New methods are needed to capture such effects, which also have the potential to offer insight into the neurobiology of the human cholinergic system.