Effects of donepezil on cognitive performance after sleep deprivation

Objectives To identify tasks that were sensitive to a temporary decline in cognitive performance after sleep deprivation and to investigate the ability of the acetylcholinesterase inhibitor donepezil to reverse any sleep deprivation-induced impairment. Methods Thirty healthy volunteers were administered either a 5-mg daily dose of donepezil or placebo for 14-17days, in a double-blind parallel group design, then underwent either 24h sleep deprivation or a normal night of sleep in non-blinded crossover, and were subsequently tested on a battery of cognitive tasks designed to measure different components of memory and executive function. Results Sleep deprivation selectively impaired performance on several memory tasks whilst also impairing non-memory function on these tasks. Performance on other tasks was spared. Despite partially reversing the decline in subjective alertness associated with sleep deprivation, treatment with donepezil failed to significantly reverse the decline in cognitive performance on any of the tasks. Conclusions The results demonstrate the sensitivity of certain tests, particularly those that measure memory function, to cognitive impairment after sleep deprivation. The inability of donepezil to reverse this performance decline suggests that the sleep deprivation model of cognitive impairment may not be suitable for detecting pro-cognitive effects of cholinergic augmentation.