补肾化痰祛瘀中药治疗遗忘型轻度认知损害的随机、双盲、平行对照临床研究

背景：阿尔茨海默病（Alzheimerdisease,AD）的早期诊断和干预十分重要。作为AD的早期阶段,遗忘型轻度认知损害（amnesticmildcognitiveimpairment,aMCI）逐渐受到关注。研究表明多奈哌齐可以降低轻度认知损害患者的AD评定量表认知分量表（ADassessmentscale-cognitiVesubscale,ADAS—Cog）得分,改善患者的注意力和反应速度,但是具有一定的副作用,因此,有必要进一步探讨中医药对于aMCI的作用。目的：观察补肾化痰祛瘀中药治疗aMCI的临床疗效和安全性。设计、场所、受试者和干预措施：本研究为随机、双盲、平行对照临床试验。根据随机、双盲的原则,将aMCI患者分为补肾化痰祛瘀中药组和盐酸多奈哌齐组。补肾化痰祛瘀中药组予补肾化痰祛瘀中药颗粒,1袋／次,2次／d;盐酸多奈哌齐组予盐酸多奈哌齐5mg／d。另外58例患者不接受任何治疗,作为对照。在用药第12周对所有入组的aMCI患者进行随访。主要结局指标：ADAS—Cog和简易精神状态检查表（mini～mentalstatusexamination,MMSE）得分。结果：补肾化痰祛瘀中药组和盐酸多奈哌齐组治疗12周后的ADAS—Cog得分较基线均有显著改善（P=0．001,P=0．000）,而未治疗组MMSE得分和ADAS—Cog得分较基线无显著变化（P=0．151,P=0．125）;中药组与盐酸多奈哌齐组比较,差异无统计学意义（P=0．105）,两组患者的ADAS-Cog得分均低于未治疗组（P=0．000,P=0．000）。补肾化痰祛瘀中药组治疗12周后的注意力得分较基线显著改善（P=0．015）,盐酸多奈哌齐组较基线无改善（P=0．085）。盐酸多奈哌齐组在用药过程中出现失眠、多梦5例（20．8％）,恶心3例（12．5％）,腹泻5例（20．8％）,分别显著高于补肾化痰祛瘀中药组（P=0．002,P=0．005,P=0．000）。两组药物对于患者的生命体征和实验室检查无显著影响。结论：补肾化痰祛瘀中药和盐酸多奈哌齐治疗12周均可以提高aMCI患者的总体认知功能,两种药物疗效相当。此外,补肾化痰祛瘀中药可以较好地改善患者的注意力以及头痛、四肢发凉、腹胀和大便溏泻等临床症状,而且补肾化痰祛瘀中药用药安全、不良反应少,优于盐酸多奈哌齐。有必要进行进一步的研究以评价中药的远期疗效。

Effects of Chinese medicine for tonifying the kidney and resolving phlegm and blood stasis in treating patients with amnestic mild cognitive impairment: a randomized, double-blind and parallel-controlled trial

BACKGROUND： It is important to detect and prevent Alzheimer disease （AD） at its early stage. Constituting the early stage sign of AD, amnestic mild cognitive impairment （aMCI） has drawn much attention. Studies have shown that donepezil could reduce the AD assessment scale-cognitive subscale （ADAS-Cog） score in MCI patients and improve the patient＇s attention and speed of response; however, it also has many side effects. Therefore, the authors aim to explore the effects of Chinese herbal medicine for treating aMCI. OBJECTIVE： To explore the clinical efficacy and safety of Chinese medicine for tonifying the kidney, and resolving phlegm and blood stasis in the treatment of aMCI. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： This clinical trial used randomized, double-blind, double-dummy and parallel-controJled design. According to the randomized, double-blind principle, some aMCI patients were randomly divided into Chinese medicine group and donepezil group. Other patients who did not receive any treatment were enrolled as the control. Patients in the Chinese medicine group received oral administration of Chinese medicine, 1 bag/dose, two doses per day, while patients in the donepezil group received donepezil hydrochloride, 5 mg/day. Twelve weeks were allocated as the trial period. MAIN OUTCOME MEASURES： After 12 weeks, the Chinese medicine group patients, the donepezil group patients and those patients who did not receive any treatment were accessed using the scores of ADAS-Cog and mini-mental status examination （MMSE）.RESULTS： The ADAS-Cog and MMSE scores of the Chinese medicine group and the donepezil group were both improved from baseline （P=O. 00], P~0.O00）, but the non-treatment group showed no change from baseline （P~ O. 151, P= 0. 125）; furthermore, there was no significant difference between the Chinese medicine group and the donepezil group. The attention function of the Chinese medicine group was better than baseline （P=O. 015）, but no change was seen in the donepezil group （P=0. 085） at the 12th week. Safety data showed that the occurrence of insomnia, nausea and diarrhea was greater in the donepezil group than in the Chinese medicine group （P=O.OO2, P=0.005, P=-O.O00）, and both treatments had no influence in participants＇ vital signs and laboratory examination results. CONCLUSION： Both Chinese medicine and donepezil can improve global cognition in patients with aMCI after 12 weeks of treatment. Chinese medicine can also improve attention function and some clinical symptoms in patients with aMCI. Furthermore, Chinese medicine is safe for aMCI patients. Further study is necessary to explore the long-term effect of Chinese medicine for aMCI.