Cholinergic enhancement of episodic memory in healthy young adults

Rationale: Acetylcholine esterase (AchE) inhibitors are known to remediate symptoms of Alzheimer's disease. However, only few systematic data exist on the effects of cholinergic treatment on cognitive functions in normal subjects: Objective: This study evaluated the effects of donepezil, an inhibitor of AchE, on cognitive performance in young and healthy subjects. Methods: We used a randomised double-blind parallel group placebo-controlled repeated measures design to investigate changes of cognitive functions in a group of 30 young healthy male subjects (mean age 23.9 years +/- 2.24 SD) upon application of donepezil or placebo for 30 days. Attentional and executive functions, visual and verbal short-term and working memory, semantic memory, as well as verbal and visual episodic memory were investigated using an extensive neuropsychological test battery. Results: Time-by-group interactions demonstrated significant drug effects that were specific to episodic memory in both the verbal and visual domain. Additionally, donezepil significantly improved long-term visual episodic recall. In none of the other functions under investigation any significant treatment effects were observed. Conclusion: Given this specific drug effect and the well-known relevance of the hippocampal region for episodic memory, we conclude that this region appears to be the major target of cholinergic enhancement in healthy subjects due to long-term inhibition of AchE.