Cholinesterase inhibitors and memory
Cholinesterase inhibitors and memory
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DOI：
10.1016/j.cbi.2009.11.018
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发表时间：
2010-09-06
影响因子：
5.1
通讯作者：
Giovannini, Maria Grazia
中科院分区：
文献类型：
--
作者：
Pepeu, Giancarlo;Giovannini, Maria Grazia
胆碱酯酶抑制剂（ChEI）对轻度至中度阿尔茨海默病（AD）有效，这是一个共识。不幸的是，无反应者的数量很大，而且治疗效果通常是短暂的。在实验动物中，ChEI发挥三个主要作用：抑制胆碱酯酶（ChE），增加脑乙酰胆碱（ACh）的细胞外水平，改善认知过程，特别是在AD模型中被破坏时。在这篇综述中，我们将讨论通过ChEI治疗改善的认知过程，因为它们依赖于脑胆碱能通路的完整性及其激活。胆碱能系统在认知中的作用可以用不同的方法来研究。微透析实验表明胆碱能系统参与注意、工作、空间和外显记忆、信息编码、感觉-运动门控、技能学习。长期记忆尚未得到证实。相反，低胆碱能活性促进记忆巩固。尽管对年龄、剂量和不同的记忆测试提出了警告，但对健康人类受试者的实验证实了动物实验的结果，并证明胆碱能系统的刺激有助于注意力、刺激检测、知觉处理和信息编码。目前尚不清楚是否可以提高信息检索，但记忆巩固减少胆碱能激活。ChEI在AD患者中的作用已经使用评估认知和行为反应的评定量表进行了广泛的研究。很少有人试图确定哪些量表项目更好地响应ChEI，因此，据推测，取决于胆碱能系统的活动。据报道，注意力和执行功能，沟通，表达性语言和情绪稳定性有所改善。高水平的乙酰胆碱可能会损害记忆的巩固和提取。因此，考虑到AD中胆碱能系统的退化与其他神经递质系统的改变和弥漫性突触丢失相关，应该预期ChEI对记忆过程的有限功效。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
A consensus exists that cholinesterase inhibitors (ChEIs) are efficacious for mild to moderate Alzheimer's Disease (AD). Unfortunately, the number of non-responders is large and the therapeutic effect is usually short-lasting. In experimental animals, ChEIs exert three main actions: inhibit cholinesterase (ChE), increase extracellular levels of brain acetylcholine (ACh), improve cognitive processes, particularly when disrupted in models of AD. In this overview we shall deal with the cognitive processes that are improved by ChEI treatment because they depend on the integrity of brain cholinergic pathways and their activation. The role of cholinergic system in cognition can be investigated using different approaches. Microdialysis experiments demonstrate the involvement of the cholinergic system in attention, working, spatial and explicit memory, information encoding, sensory-motor gating, skill learning. No involvement in long-term memory has yet been demonstrated. Conversely, memory consolidation is facilitated by low cholinergic activity. Experiments on healthy human subjects, notwithstanding caveats concerning age, dose, and different memory tests, confirm the findings of animal experiments and demonstrate that stimulation of the cholinergic system facilitates attention, stimulus detection, perceptual processing and information encoding. It is not clear whether information retrieval may be improved but memory consolidation is reduced by cholinergic activation. ChEI effects in AD patients have been extensively investigated using rating scales that assess cognitive and behavioural responses. Few attempts have been made to identify which scale items respond better to ChEIs and therefore, presumably, depend on the activity of the cholinergic system. Improvement in attention and executive functions, communication, expressive language and mood stability have been reported. Memory consolidation and retrieval may be impaired by high ACh levels. Therefore, considering that in AD the degeneration of the cholinergic system is associated with alteration of other neurotransmitter systems and a diffuse synaptic loss, a limited efficacy of ChEIs on memory processes should be expected. (C) 2009 Elsevier Ireland Ltd. All rights reserved.