基于静息态功能性磁共振探讨中医辨证治疗重度阿尔茨海默病脑功能改变的临床研究

Clinical study on TCM pattern differentiation and treatment of brain function change in patients with severe Alzheimer’s disease based on resting-state functional magnetic resonance imaging

目的结合静息态功能性磁共振,观察中医辨证治疗方案对重度阿尔茨海默病(Alzheimer’s disease,AD)患者脑功能改变的干预作用。方法采用国际公认的语言交流障碍和卒中研究所-老年性痴呆及相关疾病学会(NINCDS-ADRDA)有关阿尔茨海默病的诊断标准,纳入重度AD患者50人,随机分为中药组25人和西药组25人。中药组每4周进行中医辨证1次,心气虚证予调心方,肾精不足证予补肾方,挟痰者,加用礞石滚痰丸,挟瘀者,加用血府逐瘀胶囊;西药组予盐酸多奈哌齐5 mg治疗。疗程均为48周。观察并比较2组患者治疗前后简易精神状态检查量表(MMSE)、临床痴呆评定量表(CDR)疗效变化,通过静息态功能性磁共振观察并比较2组患者治疗前后脑功能改变。结果治疗48周,中药组MMSE有效率45.00%,西药组38.89%;中药组CDR有效率30.00%,西药组22.22%。静息态功能性磁共振检查发现,治疗后2组患者后扣带回与脑功能区的连接性均有不同程度改善。中药组的作用范围主要分布在左侧额顶叶、左侧颞叶、枕叶;西药组的作用范围主要分布在右侧海马、左侧额叶和颞叶。结论以调心、补肾法辨证施治能够有效提高重度AD患者的认知功能,减轻病情程度,且不同程度提高后扣带回和多个脑区功能活动的连接性,改善脑功能。

Objective To explore the effects of TCM pattern differentiation and treatment on brain function of patients with severe Alzheimer’s disease(AD)using resting-state functional magnetic resonance imaging(fMRI).Methods According to the internationally recognized NINCDS-ADRDA Alzheimer’s Criteria,fifty patients with severe AD were enrolled in the study and were randomly divided into Chinese medicine group(CMG)(n=25)and Western medicine group(WMG)(n=25).Patients in the CMG were given TCM treatment based on pattern differentiation:patients with heart-qi deficiency received Tiaoxin Fang(Heart-regulating Formula),patients with kidney-essence insufficiency Bushen Fang(Kidney-supplementing Formula)and patients with patterns complicated by phlegm and blood stasis were additionally given Mengshi Guntan Wan(Chlorite Phlegm-Removing Pill)and Xuefu Zhuyu Jiaonang(Blood Mansion Stasis-Expelling Capsule)respectively.Patients in the WMG were treated with donepezil 5 mg once daily.The course of treatment lasted 48 weeks for both groups.Therapeutic effects were observed and compared using Mini-Mental State Examination(MMSE)and Clinical Dementia Rating(CDR).Changes in brain function of the AD patients before and after treatment were also examined and compared with resting-state fMRI.Results After 48 weeks of treatment,45.00%and 38.89%patients scored higher in MMSE and 30.00%and 22.22%scored higher in CDR in the CMG and the WMG respectively.The results of fMRI demonstrated better connectivity between posterior cingulate gyrus and other brain regions in both groups of patients.In CMG,the improved regions involved primarily the left frontal and parietal lobes,left temporal lobe and occipital lobe,while in WMG,the improved regions included primarily the right hippocampus,the left frontal lobe and the temporal lobes.Conclusion The heart-regulating and kidney-supplementing TCM treatment based on pattern differentiation is effective in improving cognitive function and reducing disease severity of patients with severe AD and enhancing their brain function by increasing connectivity between posterior cingulate gyrus and specific regions in the brain.