Alterations in brain activation during cholinergic enhancement with rivastigmine in Alzheimer's disease
Alterations in brain activation during cholinergic enhancement with rivastigmine in Alzheimer's disease
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DOI：
10.1136/jnnp.73.6.665
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发表时间：
2002-12-01
影响因子：
11
通讯作者：
Scheltens, P
中科院分区：
文献类型：
--
作者：
Rombouts, SARB;Barkhof, F;Scheltens, P
背景资料：卡巴拉汀可增强胆碱能活性，临床试验显示可降低阿尔茨海默病的恶化率。目前还不清楚它在大脑中的哪个部位发挥作用。功能性磁共振成像（fMRI）可用于测量脑功能的变化并将其与认知联系起来。目的：使用fMRI研究卡巴拉汀治疗的脑激活。方法：在7名轻度阿尔茨海默病患者中，在面部编码过程中使用fMRI测试了单剂量卡巴拉汀对脑激活的影响，在5名患者中，在参数工作记忆任务中测试了单剂量卡巴拉汀对脑激活的影响。结果：在面部编码期间，卡巴拉汀增加梭状回的双侧激活。在简单的工作记忆任务中，前额叶皮层的大脑激活也得到了增强。当工作记忆负荷进一步增加，不仅是增加激活，但在某些领域也有减少activation.Conclusions：这些研究结果链接先前观察到的增加认知性能在阿尔茨海默病治疗后，胆碱酯酶抑制剂改变大脑激活。尽管这些结果不能普遍适用于阿尔茨海默病人群，但它们提供了证据表明，在轻度阿尔茨海默病中，rivastigmine增强了梭形和额叶皮质的脑激活。这与胆碱能回路的概念是一致的。
Background: Rivastigmine enhances cholinergic activity and has been shown in clinical trials to decrease the rate of deterioration in Alzheimer's disease. It remains unclear where in the brain it exerts its effect. Functional magnetic resonance imaging (fMRI) can be used to measure changes in brain function and relate these to cognition.Objectives: To use fMRI to study brain activation with rivastigmine treatment.Methods: The effect on brain activation of a single dose of rivastigmine was tested in seven patients with mild Alzheimer's disease using fMRI during face encoding, and in five patients during a parametric working memory task.Results: During face encoding, rivastigmine increased bilateral activation in the fusiform gyrus. Brain activation was also enhanced in the prefrontal cortex in a simple working memory task. When working memory load was further increased, not only was increased activation seen, but in certain areas there was also decreased activation.Conclusions: These findings link the previously observed increase in cognitive performance in Alzheimer's disease after treatment with a cholinesterase inhibitor to altered brain activation. Although the results cannot be generalised to the Alzheimer's disease population at large, they provide evidence that in mild Alzheimer's disease, rivastigmine enhances brain activation in the fusiform and frontal cortices. This is compatible with the concept of cholinergic circuitry.