中医辨证治疗轻中度阿尔茨海默病的随机对照试验

背景：阿尔茨海默病（Alzheimer disease,AD）是一种进行性发展的神经退行性疾病,目前对本病的发病机制尚不清楚,也无有效的治疗方法。随着全球人口老龄化程度的提高,AD的患病率不断增加,严重影响老年人的生活质量。目前中医药对AD的研究正逐渐深入。目的：观察中医辨证治疗方案改善轻中度AD患者认知功能的临床疗效,并通过静息态功能性核磁共振技术观察治疗前后AD患者的脑功能变化。设计、场所、受试者和干预措施：在上海徐汇区凌云等5个社区街道与上海市第一福利院等7个福利院,采用国际公认的美国国立神经病、语言交流障碍和卒中研究所-老年性痴呆及相关疾病学会AD诊断标准,纳入轻中度AD患者131例,随机分为中药组66例,西药组65例。中药组每月1次中医辨证对证用药。心气虚证用调心方,肾精虚证用补肾方,2次/d;对夹痰、夹瘀的患者分别加用礞石滚痰丸和血府逐瘀胶囊进行治疗。西药对照组采用盐酸多奈哌齐5mg/d进行治疗,疗程为48周。主要结局指标：治疗前后分别用简易精神状态量表（Mini-Mental State Examination,MMSE）、物体记忆测验（Fuld Object-Memory Evaluation,FOM）、积木测验（Block Design,BD）、数字广度测验（Digit Span,DS）量表进行评定,以评价患者的认知功能;采用静息态功能性核磁共振成像观察患者治疗前后的脑功能变化。结果：中药和西药盐酸多奈哌齐均能够改善轻中度AD患者的认知功能。两药治疗后与治疗前相比MMSE量表总分均有提高（P〈0.05或P〈0.01）。治疗48周,中药组的MMSE有效率为70.91%,恶化率为20.00%;西药组的有效率为55.77%,恶化率为34.62%。两药均能提高患者FOM分母、BD量表分值,中药治疗还能提高FOM分子、DS量表分值（P〈0.05或P〈0.01）。静息态功能性磁共振检查发现,治疗后两组患者后扣带回与脑功能区的连接性均不同程度改善。中药组的作用范围比较局限,主要作用于左侧的顶叶,西药组的作用范围则相对较大,主要作用于双侧的额叶。结论：中医辨证治疗方案能够改善轻中度AD患者的认知功能,且能够提高后扣带回与脑功能区的连接性,改善脑功能,是治疗AD有效的方法。

Chinese herbal medicine for patients with mild to moderate Alzheimer disease based on syndrome differentiation: a randomized controlled trial

BACKGROUND：Alzheimer disease（AD）is a chronic neurodegenerative disease that is characterized by its gradual progression.At present,the cause and mechanism of AD are yet unclear,and there is no effective therapy for treating it.With development of global aging,the prevalence rate of AD is increasing.The life quality of elderly people is affected severely by AD that is ultimately life-threatening.Recently,study on treating AD with traditional Chinese medicine（TCM）has deepened. OBJECTIVE：To explore the therapeutic effects of a syndrome differentiation-based TCM regime in treating patients with mild to moderate AD for improving cognition,and to evaluate the changes in brain function of AD patients observed by resting-state functional magnetic resonance imaging（fMRI）technique. DESIGN,SETTING,PARTICIPANTS AND INTERVENTIONS：Adopting the internationally recognized criteria developed by National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer’s Disease and Related Disorders Association,the clinical trial was conducted on 131 patients with mild to moderate AD from5 communities and 7 social welfare institutions.Participants were accepted after informed consent was received,and laboratory tests and a head imaging study were conducted.The patients were randomly divided into Chinese medicine group（CMG）（66 cases）or Western medicine group（WMG）（65 cases）. Patients in the CMG were treated monthly with Chinese medicine according to syndrome differentiation. Patients in the WMG were treated with donepezil at a dose of 5 mg once daily.The therapeutic course lasted 48 weeks. MAIN OUTCOME MEASURES：The scores of Mini-Mental State Examination（MMSE）,Fuld Object-Memory Evaluation（FOM）,Block Design（BD）and Digit Span（DS）were used to evaluate the cognitive function; resting-state fMRI was used for observing brain function.The questionnaires and fMRI were performed before and after treatments. RESULTS：The cognitive functions of the patients in the CMG and WMG were improved after treatment. MMSE score was improved significantly in both groups（P0.05 or P0.001）.After 48 weeks of treatment, 70.91%patients in the CMG had an improved MMSE score and 20%got worse,however,55.77%patients in the WMG were improved in MMSE score and34.62%got worse.Scores of FOM denominator and BD increased significantly in both groups;scores of FOM numerator and DS were also increased in the CMG（P0.05 or P0.01）.The results of fMRI suggested that both Chinese medicine and donepezil treatment improved the connectivity between posterior cingulated gyrus and specific areas in the brain.The influence range of Chinese medicine primarily impacted on the left parietal lobe,being less than the influence range of donepezil, which primarily affected both sides of frontal lobes. CONCLUSION：TCM treatment based on syndrome differentiation is effective in improving cognitive function of patients with mild to moderate AD and increasing the brain function by increasing connectivity between posterior cingulated gyrus and specific areas in the brain.