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Cholinergic enhancement of episodic memory in healthy young adults

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Abstract

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.

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Acknowledgements

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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Authors and Affiliations

  1. Department of Psychiatry, University of Ulm, Leimgrubenweg 12, 89075, Ulm, Germany

    Georg Grön, Matthias Kirstein, Axel Thielscher & Manfred Spitzer

  2. Department of Psychiatry Mental Health and Old Age Psychiatry, Charité Medical University, Eschenallee 3, 14050, Berlin, Germany

    Matthias W. Riepe

  3. Transfer Center for Neuroscience and Learning (ZNL), University of Ulm, Beim Alten Fritz 2, 89075, Ulm, Germany

    Manfred Spitzer

  4. Department of Psychiatry, Neuropsychological Section, University of Ulm, Leimgrubenweg 12–14, 89075, Ulm, Germany

    Georg Grön

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  1. Georg Grön
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Correspondence to Georg Grön.

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Grön, G., Kirstein, M., Thielscher, A. et al. Cholinergic enhancement of episodic memory in healthy young adults. Psychopharmacology 182, 170–179 (2005). https://doi.org/10.1007/s00213-005-0043-2

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  • DOI: https://doi.org/10.1007/s00213-005-0043-2

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