轻度认知损害临床研究指导原则(草案)

轻度认知损害（mildcognitiveimpairment，MCI）是指一个有轻度认知缺损但没有痴呆的疾病分类单元，是痴呆发病的预警信号和新的治疗靶点。欧洲MCI诊断标准及其诊断程序更加符合MCI综合征的异质性特征，基于此，首都医学发展基金MCI联合攻关组提出MCI的诊断方法，包括临床、神经心理、机能、神经影像和遗传检测，诊断程序分为三步。第一，确定MCI综合征，必须符合下列条件：（1）来自患者和（或）家庭成员的认知主诉；（2）患者和（或）知情者报告在过去一年内相对于先前的认知功能有所下降；（3）认知障碍由临床评估证实，在记忆和（或）其他认知领域出现损害；（4）日常生活活动保存，复杂的工具性机能未受损或有非常轻微的损害；（5）无痴呆。第二，辨认MCI亚型，即记忆型MCI、单个非记忆区域MCI以及多个区域MCI。第三，尽可能明确亚型的发病原因，潜在原因有阿尔茨海默病、血管性痴呆和其他神经变性痴呆，如额颞叶痴呆、路易体痴呆、语义型痴呆以及创伤、感染、中毒、营养或内分泌缺乏等。推荐的特异性检查包括血清维生素B12、叶酸，血浆胰岛素、胰岛素降解酶、Aβ10、Aβ12、类性因子，CT（最好是MRI）是强制性的神经影像学检查。其疗效观测指标有（1）主要结果：痴呆或AD转化的可能性；（2）次级结果：认知和机能；（3）补充结果：中医证候；（4）APOEε4携带者：携带状态对痴呆进展率或AD转化率的影响，并比较治疗效果。

Guiding principles of clinical research on mild cognitive impairment (protocol)

Mild cognitive impairment (MCI), as a nosological entity referring to elderly people with MCI but without dementia, was proposed as a warning signal of dementia occurrence and a novel therapeutic target. MCI clinical criteria and diagnostic procedure from the MCI Working Group of the European Alzheimer's Disease Consortium (EADC) may better reflect the heterogeneity of MCI syndrome. Beijing United Study Group on MCI funded by the Capital Foundation of Medical Developments (CFMD) proposed the guiding principles of clinical research on MCI. The diagnostic methods include clinical, neuropsychological, functional, neuroimaging and genetic measures. The diagnostic procedure includes three stages. Firstly, MCI syndrome must be defined, which should correspond to: (1) cognitive complaints coming from the patients or their families; (2) reporting of a relative decline in cognitive functioning during the past year by the patient or informant; (3) cognitive disorders evidenced by clinical evaluation; (4) activities of daily living preserved and complex instrumental functions either intact or minimally impaired; and (5) absence of dementia. Secondly, subtypes of MCI have to be recognized as amnestic MCI (aMCI), single non-memory MCI (snmMCI) and multiple-domains MCI (mdMCI). Finally, the subtype causes could be identified commonly as Alzheimer disease (AD), vascular dementia (VaD), and other degenerative diseases such as frontal-temporal dementia (FTD), Lewy body disease (LBD), semantic dementia (SM), as well as trauma, infection, toxicity and nutrition deficiency. The recommended special tests include serum vitamin B12 and folic acid, plasma insulin, insulin-degrading enzyme, Abeta40, Abeta42, inflammatory factors. Computed tomography (or preferentially magnetic resonance imaging, when available) is mandatory. As measurable therapeutic outcomes, the primary outcome should be the probability of progression to dementia, the secondary outcomes should be cognition and function, and the supplement outcome should be the syndrome defined by traditional Chinese medicine. And for APOE epsilon4 carrier, influence of the carrier status on progression rate to dementia and the effect of treatment should be evaluated.