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Abstract：
Acetylcholine is critically involved in modulating learning and memory function, which both decline in neurodegeneration. It remains unclear to what extent structural and functional changes in the cholinergic system contribute to episodic memory dysfunction in mild cognitive impairment (MCI), in addition to hippocampal degeneration. A better understanding is critical, given that the cholinergic system is the main target of current symptomatic treatment in mild to moderate Alzheimer\'s disease. We simultaneously assessed the structural and functional integrity of the cholinergic system in 20 patients with MCI and 20 matched healthy controls and examined their effect on verbal episodic memory via multivariate regression analyses. Mediating effects of either cholinergic function or hippocampal volume on the relationship between cholinergic structure and episodic memory were computed. In MCI, a less intact structure and function of the cholinergic system was found. A smaller cholinergic structure was significantly correlated with a functionally more active cholinergic system in patients, but not in controls. This association was not modulated by age or disease severity, arguing against compensational processes. Further analyses indicated that neither functional nor structural changes in the cholinergic system influence verbal episodic memory at the MCI stage. In fact, those associations were fully mediated by hippocampal volume. Although the cholinergic system is structurally and functionally altered in MCI, episodic memory dysfunction results primarily from hippocampal neurodegeneration, which may explain the inefficiency of cholinergic treatment at this disease stage.
摘要：
乙酰胆碱与调节学习和记忆功能密切相关，这两种神经变性都下降了。目前尚不清楚胆碱能系统的结构和功能变化在多大程度上导致轻度认知障碍（MCI）的情景记忆功能障碍。除了海马变性。更好的理解是至关重要的，鉴于胆碱能系统是目前轻中度阿尔茨海默病对症治疗的主要目标。我们同时评估了20名MCI患者和20名匹配的健康对照者的胆碱能系统的结构和功能完整性，并通过多元回归分析检查了它们对言语情景记忆的影响。计算了胆碱能功能或海马体积对胆碱能结构与情景记忆之间关系的中介作用。在MCI中，发现胆碱能系统的结构和功能不太完整。较小的胆碱能结构与患者功能更活跃的胆碱能系统显着相关，但不是在控制中。这种关联不受年龄或疾病严重程度的调节，反对补偿过程。进一步的分析表明，胆碱能系统的功能或结构变化都不会影响MCI阶段的言语情景记忆。事实上,这些关联完全由海马体积介导.尽管MCI中胆碱能系统的结构和功能发生了改变，但情景记忆功能障碍主要是由海马神经变性引起的，这可以解释在这个疾病阶段胆碱能治疗的低效率。
