Grön Georg, Kirstein Matthias, Thielscher Axel, Riepe Matthias W, Spitzer Manfred
Department of Psychiatry, University of Ulm, Leimgrubenweg 12, 89075 Ulm, Germany.
Psychopharmacology (Berl). 2005 Oct;182(1):170-9. doi: 10.1007/s00213-005-0043-2. Epub 2005 Sep 29.
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.
已知乙酰胆碱酯酶（AchE）抑制剂可改善阿尔茨海默病的症状。然而，关于胆碱能治疗对正常受试者认知功能影响的系统性数据很少。
本研究评估了AchE抑制剂多奈哌齐对年轻健康受试者认知表现的影响。
我们采用随机双盲平行组安慰剂对照重复测量设计，对30名年轻健康男性受试者（平均年龄23.9岁±2.24标准差）应用多奈哌齐或安慰剂30天，以研究认知功能的变化。使用广泛的神经心理测试组合来研究注意力和执行功能、视觉和言语短期及工作记忆、语义记忆以及言语和视觉情景记忆。
时间×组间交互作用显示出显著的药物效应，这在言语和视觉领域的情景记忆中具有特异性。此外，多奈哌齐显著改善了长期视觉情景回忆。在其他所研究的功能中均未观察到任何显著的治疗效果。
鉴于这种特定的药物效应以及海马区对情景记忆的众所周知的相关性，我们得出结论，由于长期抑制AchE，该区域似乎是健康受试者中胆碱能增强的主要靶点。
