肝失疏泄对正常人群和MCI患者认知功能衰退进程的影响及机制研究

The diseases with cognitive disorder caused by accelerated brain aging, such as mild cognitive impairment (MCI) and Alzheimer's disease struck hard at family and society. It has the unique superiority in delaying senescence and improving wisdom of traditional Chinese medicine (TCM), but the mechanism of cognitive function improved by TCM has not yet been elucidated. In the preliminary study of our team it was found that the improved attention orientations difficulties, alleviated neuron damage, and increased excitability of the relevant brain were the parts of the functional mechanism of cognitive function improved by the method of soothing the liver. On this basis, in this subject the early stage of cognitive decline targeted, we plan to do multi-dimensional study for the normal population in different age groups with negative or non-negative emotional traits through the cross-sectional study , with the help of the technologies such as event-related potentials (ERPs) and eye tracker, to explore the relationship between cognitive decline and “liver failing to facilitate the coursing of qi” , and the trend with the aging, directly obtain physical evidences of negative emotions accumulation impairing cognitive function, and focus on the cognitive components such as executive function, prospective memory and so on, to explore further the neurobiological mechanisms of improved the overall cognitive functions. In this research it will provide empirical research support for “liver failing to facilitate the coursing of qi” accelerating normal cognitive aging process and new ideas for intervention of MCI by TCM, and add new connotation for cognitive aging theory of TCM.

由脑老化过速而致的认知功能障碍性疾病如轻度认知功能障碍（MCI）、老年痴呆等，给家庭和社会造成沉重负担。中医药在缓衰益智方面具有独特优势，但其改善认知功能的机制尚未阐明。本团队前期研究发现改善注意力朝向困难、减轻神经元损伤、提高相关脑区兴奋性是疏肝法改善认知功能的部分作用机制。在此基础上，本课题针对认知功能衰退的早期阶段，拟通过横断面研究和病例对照研究，借助ERPs、眼动等技术对不同年龄组的负性及非负性情绪特质的正常人群进行多维度研究，探讨认知功能衰退与肝失疏泄的关系及随增龄的变化趋势，直接获取负性情绪积累对认知功能损伤的生理证据，探索疏肝法改善整体认知功能的神经生物学机制。本课题将为肝失疏泄加速正常认知老化进程提供实证支持，为MCI的中医药干预提供新思路，为中医认知衰老学说增添新内涵。

由脑老化过速而致的认知功能障碍性疾病如轻度认知功能障碍（MCI）、阿尔茨海默病（AD）等，给家庭和社会造成沉重负担。本课题以肝主疏泄调畅情志理论为指导，针对认知功能衰退的早期阶段，围绕认知老化的成因与机理，通过横断面研究，借助事件相关电位（ERPs）、眼动等技术和血生化指标对不同年龄正常人群的高、低神经质被试进行多维度研究，探讨认知功能衰退与肝失疏泄的关系及随增龄的变化趋势，直接获取负性情绪积累对认知功能损伤的生理证据，探寻年老化认知功能衰退的早期客观指标。. 认知量表评估发现，高神经质人群总体认知功能低于低神经质人群。生化指标检测显示，高神经质人群皮质醇水平更高，提示高神经质人群易处于情绪应激状态。ERPs前瞻记忆色词双任务范式研究表明，随年龄增长，前瞻记忆能力逐渐下降；高神经质人群较低神经质人群前瞻记忆年老化趋势更加明显，消耗注意资源更多。执行功能转换范式研究显示，高神经质人群对新异刺激的主动觉察能力下降，且注意资源年老化趋势更加明显。执行功能刷新范式研究显示，年龄和高神经质可能是降低工作记忆绩效的影响因素；高神经质人群注意资源分配能力下降，对目标刺激的评估能力较低。执行功能抑制控制范式研究显示，高神经质人群较低神经质人群的冲突监控和抑制能力下降，高年龄段人群较低年龄段人群冲突监控和抑制能力有减弱趋势。眼动试验研究发现，随增龄执行功能逐渐衰退；高神经质人群比低神经质人群眼跳反应时延长、反向眼跳的正确率降低、任务消耗高、试次转换消耗低，提示高神经质人群的执行功能衰退过速。. 上述结果验证了课题提出的“长期负性情绪积累加速正常认知老化进程，执行功能和前瞻记忆是较早出现衰退的认知成分”的科学假说，为肝失疏泄加速正常认知老化进程提供了实证支持，为认知功能衰退过速的早期诊断和干预提供新思路，为中医认知衰老学说增添新内涵。