Cholinergic enhancement of episodic memory in healthy young adults
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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.
This study evaluated the effects of donepezil, an inhibitor of AchE, on cognitive performance in young and healthy subjects.
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.
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.
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.
KeywordsAcetylcholinesterase Attention Cognition Learning and memory Hippocampus Human
We thank Roman Seidl, Markus Kiefer, Lutz Wendland, Jo Grothe, Bärbel Herrnberger for technical assistance. We also wish to thank Gisbert Farger, Clinic–Chemical Laboratory, University Clinic of Psychiatry and Psychotherapy, Tübingen, Germany, for analysis of the blood samples. This study was in part funded by Eisai, Frankfurt, Germany, and Pfizer, Karlsruhe, Germany. Each author has nothing to disclose as regards any involvement, financial or otherwise.
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