创新表达认知干预对老年轻度认知障碍的中枢机制研究及治疗方案的评价

Mild cognitive impairment (MCI) is a kind of unstable clinical state between normal aging and dementia. At present there is no effective drug treatment of patients with MCI, especially in the long-term effects. Our study found that cognitive intervention model of creative expression(timeslip) which focused on encouraging imagination and creative potential instead of memorizing could improve mild to moderate MCI patients the status of cognitive decline, communication skills, emotional state and quality of life etc, but the mechanism is unclear at present. This project aims to combine the methods of neuropsychological tests, electrophysiological measurement and enzyme-linked immunosorbent assay (ELISA), social cost benefit evaluation to make clear the content changes of GAP-43 and Aβ1-42 to explore the change rules of the above indicators and the effects before and after the interventions of cognitive intervention model of creative expression (timeslip), and to further clarify the mechanism of MCI and provide objective basis for prevention and control of non-drug. Hippocampal changes in network connection before and after interventions were observed by Resting state functional magnetic technology, the central receptor mechanism of cognitive recovery in patients with MCI were described from the aspects of brain structure and function by the seed point connection methods.

轻度认知障碍（MCI）是介于痴呆与正常衰老之间的一种不稳定的临床状态，目前尚无有效药物治疗，已有的非药物干预缺乏严格随机对照、疗效的生理学评价以及机制探索。我们前期研究创建了符合中国轻中度痴呆患者的创新表达认知干预模式，并证实了通过鼓励想象、发挥创造性潜力可改善痴呆患者认知衰退、沟通交流、生活质量等状况。为进一步明确创新表达的干预效果，本项目拟结合神经心理学测量、电生理测量，酶联免疫吸附试验(ELISA)测定患者CSF中GAP-43、Aβ1-42含量的变化，社会成本和效益分析，探讨MCI在创新表达认知干预前后上述指标的变化规律，临床综合评价创新表达认知干预对MCI患者的治疗效果，进一步阐明MCI的发生机制；利用静息态功能核磁技术和扩散张量成像，观察创新表达认知干预前后静息状态下海马脑网络连接的变化,采用种子点功能连接方法，从大脑功能探讨创新表达干预对MCI患者认知改善的中枢效应机制。

轻度认知障碍（MCI）是介于正常衰老与痴呆之间的过渡阶段，已被公认为是痴呆前期有症状的阶段。目前尚无有效的药物治疗，已有研究表明创新表达能够改善认知功能但机制不明。本项目采用行动研究法创建了中国MCI患者的创新表达认知干预的标准路径，并采用了严格的随机对照试验（试验组进行创新表达认知干预，对照组采用一般社会活动）开展为期16周，共25次的活动。于干预前、后及随访6个月后，采用神经心理学量表以及定量脑电图(qEEG)、事件相关电位(ERP-P300)等多元评价机制证实了创新表达认知干预在改善MCI患者的总体认知功能和日常生活能力中的有效性和可行性。利用静息态功能核磁共振(fMRI)技术，深入探索了创新表达认知干预对改善MCI患者认知功能的中枢效应机制。静息态fMRI功能连接组间比较结果显示，以海马为种子点全脑功能连接负激活差异脑区为右角回、扣带回、楔前叶，正激活差异脑区为辅助运动区；以基于体素的形态学分析其差异脑区为左右角回。任务态fMRI组间比较结果显示，有显著差异的正激活脑区为右额叶、双枕叶、楔前叶及后扣带回，负连接激活脑区无显著差异，揭示了创新表达认知干预活动对MCI患者认知相关脑区的作用和特点。本项目的研究成果不仅为今后医疗机构、社区服务、老年中心等场所开展活动提供了参考依据，同时也为今后开展MCI非药物干预提供了新的证据和观点。