不同抗痴呆药物对阿尔兹海默病认知功能的疗效评价：网络META分析
发布时间：2018-07-17 05:19
【摘要】：目的:应用网络Meta分析(Network Meta-analysis,NMA)方法全面而系统评价不同的抗痴呆药物对于阿尔兹海默病患者认知功能改善的作用,以期为阿尔兹海默病的临床治疗提供临床参考。方法:计算机检索pubmed数据库、web of science数据库、clinicaltrials、embase、cohranne图书馆、中国知网、cbm数据库、万方数据库等数据库中有关于各类抗痴呆药物治疗阿尔兹海默病的随机对照试验(Randomized Controlled trials,RCTs),依据严格的纳入及排除标准,对初步检索出的文献进行筛选,最终纳入文献为33篇,共计8039例患者。其中治疗组共计患者4468例,安慰剂组共计纳入患者3571例。主要评价指标为简易智能评价量表(mini-mental state examination,MMSE)量表,将纳入的33篇文献按照MMSE量表分为轻度、中度、重度3个亚组,AD患者轻度认知功能下降共纳入文献11篇,纳入药物12种(含安慰剂),共计纳入患者3800例,其中治疗组1830例,对照组1970例。AD患者中度认知功能下降组共纳入文献17篇,纳入药物15种(含安慰剂)纳入患者共计3194例,其中治疗组2108例,对照组1086例。AD患者重度认知功能障碍组共计纳入文献5篇,纳入药物3种(含安慰剂),纳入患者共计1045例,其中治疗组530例,对照组515例。根据纳入研究文献的异质性大小,通过R软件采用随机效应模型进行网络Meta分析。对于直接及间接比较结果进行合并,并应用R软件中Gemtc数据包进行异质性及节点分析来检验所纳入文献的异质性,采用Gemtc数据包进行治疗效果的排序。结果与结论:效应量采用MD值及其95%置信区间表示,若MD值0,则证明该药物对于减缓阿尔兹海默病患者认知功能下降成正相关,在AD患者轻度认知功能障碍亚组中,所纳入的药物中疗效最为显著的是多奈哌齐、加兰他敏与石杉碱甲。MD值分别为5.2、2.5与2.4。锂、叶酸、维生素E、辛伐他汀与安慰剂相比,MD值分别为-0.62、-0.16、-0.0021与-1.6。考虑这四种药物对于改善阿尔兹海默病患者轻度认知功能下降无明显作用。在所纳入的12种治疗药物中,多奈哌齐治疗AD患者轻度认知功能障碍疗效最佳,其余药物按疗效大小排序为加兰他敏石杉碱甲褪黑素美金刚雌激素阿托伐他汀维生素E叶酸安慰剂锂辛伐他汀。在AD患者中度认知功能障碍亚组中,疗效最为显著的是多奈哌齐、石杉碱甲与卡巴拉汀。MD值分别为3.8、2.9与3.0。其中雌激素、SB-742457和Dimebon、辛伐他汀与安慰剂相比,MD值分别为-0.31、-0.39、-3.7、-0.035。考虑这四种药物对于改善阿尔兹海默病患者中度认知功能下降无明显作用。在所纳入的15种治疗药物中,多奈哌齐治疗AD患者中度认知功能障碍疗效最佳,按疗效大小排序为多奈哌齐石杉碱甲卡巴拉汀加兰他敏美金刚艾地苯醌N-乙酰半胱氨酸氟伐他汀阿托伐他汀阿立哌唑辛伐他汀安慰剂雌激素SB-742457Dimebon。在AD患者重度认知功能障碍亚组中,多奈哌齐减缓AD患者重度认知功能障碍的作用较美金刚突出。
[Abstract]:Objective: to evaluate the effects of different antidementia drugs on cognitive improvement of patients with Alzheimer's disease by network meta-analysis (NMA) method, and to provide clinical reference for the clinical treatment of Alzheimer's disease. Methods: the pubmed database pubmed of science was searched by computer, and the CBM database was obtained from the library of clinicaltrialsembasecohranne. There are random controlled trialsof RCTs (Randomized controlled trialsof RCTs) in Wanfang database and other databases. According to the strict criteria of inclusion and exclusion, the preliminary retrieved documents are screened, and 33 articles are included. A total of 8039 patients. There were 4468 patients in the treatment group and 3571 patients in the placebo group. The main evaluation index was the mini-mental state examination scale (MMSE). According to MMSE, 33 articles were divided into mild, moderate and severe subgroups with mild cognitive impairment. A total of 3800 patients were included in 12 kinds of drugs (including placebo), including 1830 patients in the treatment group, 1970 patients in the control group, 1970 patients with moderate cognitive impairment of AD patients, 17 papers were included in the study, and 3194 patients were included in 15 kinds of drugs (including placebo). There were 2108 cases in the treatment group and 1086 cases in the control group. The patients with severe cognitive dysfunction in AD group were included in 5 articles, 3 kinds of drugs (including placebo) and 1045 cases were included in the treatment group and the control group, among them, there were 515 cases in the treatment group and 515 cases in the control group. According to the heterogeneity of the literature, the random effect model was used to analyze the meta-analysis of network by R software. The results of direct and indirect comparison were merged, and the heterogeneity of Gemtc data packets in R software and node analysis were used to check the heterogeneity of the included literatures, and Gemtc data packets were used to sort the therapeutic effects. Results and conclusion: the effect was expressed by MD value and 95% confidence interval. If MD value is 0, it is proved that the drug has a positive correlation with the decrease of cognitive function in patients with Alzheimer's disease, in the subgroup of mild cognitive impairment in AD patients. The most effective drug was Donepezil. The values of Galantamine and Huperzine A. MD were 5. 2 and 2. 5 and 2. 4 respectively. The MD values of lithium, folic acid, vitamin E and simvastatin compared with placebo were -0.62U -0.16N -0.0021 and -1.621, respectively. Consideration of these four drugs had no significant effect on improving mild cognitive impairment in patients with Alzheimer's disease. Of the 12 drugs included, Donepezil was the best in the treatment of mild cognitive impairment in patients with AD. The other drugs were Galantamine Huperzine, melatonin, Atto estradiol, vitamin E, folic acid placebo, lithium simvastatin. In AD patients with moderate cognitive impairment subgroup, the most significant curative effect was Donepezil, the values of Huperzine A and carbatin 路MD were 3.82.9 and 3.0, respectively. Among them, estrogen SB-742457 and Dimebon.Simvastatin compared with placebo, the MD values of SB-742457, simvastatin and placebo were -0.31 and -0.39, respectively, and those of simvastatin and placebo were -0.31, -0.39 and 3.7 and 0.035, respectively. Consideration of these four drugs had no significant effect on improving moderate cognitive impairment in patients with Alzheimer's disease. Of the 15 drugs included, Donepezil was the best in the treatment of moderate cognitive impairment in patients with AD. According to the therapeutic effect, the order of efficacy was Donepiperzepine methylcarbaradine plus adenosemide, N-acetylcysteine, fluvastatin, Atto statin, aripiprazole, simvastatin, placebo, SB-742457 Dimebon. In the subgroup of severe cognitive dysfunction in AD patients, Donepezil was more effective in relieving severe cognitive dysfunction in AD patients than in MJ.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749.16
[Abstract]:Objective: to evaluate the effects of different antidementia drugs on cognitive improvement of patients with Alzheimer's disease by network meta-analysis (NMA) method, and to provide clinical reference for the clinical treatment of Alzheimer's disease. Methods: the pubmed database pubmed of science was searched by computer, and the CBM database was obtained from the library of clinicaltrialsembasecohranne. There are random controlled trialsof RCTs (Randomized controlled trialsof RCTs) in Wanfang database and other databases. According to the strict criteria of inclusion and exclusion, the preliminary retrieved documents are screened, and 33 articles are included. A total of 8039 patients. There were 4468 patients in the treatment group and 3571 patients in the placebo group. The main evaluation index was the mini-mental state examination scale (MMSE). According to MMSE, 33 articles were divided into mild, moderate and severe subgroups with mild cognitive impairment. A total of 3800 patients were included in 12 kinds of drugs (including placebo), including 1830 patients in the treatment group, 1970 patients in the control group, 1970 patients with moderate cognitive impairment of AD patients, 17 papers were included in the study, and 3194 patients were included in 15 kinds of drugs (including placebo). There were 2108 cases in the treatment group and 1086 cases in the control group. The patients with severe cognitive dysfunction in AD group were included in 5 articles, 3 kinds of drugs (including placebo) and 1045 cases were included in the treatment group and the control group, among them, there were 515 cases in the treatment group and 515 cases in the control group. According to the heterogeneity of the literature, the random effect model was used to analyze the meta-analysis of network by R software. The results of direct and indirect comparison were merged, and the heterogeneity of Gemtc data packets in R software and node analysis were used to check the heterogeneity of the included literatures, and Gemtc data packets were used to sort the therapeutic effects. Results and conclusion: the effect was expressed by MD value and 95% confidence interval. If MD value is 0, it is proved that the drug has a positive correlation with the decrease of cognitive function in patients with Alzheimer's disease, in the subgroup of mild cognitive impairment in AD patients. The most effective drug was Donepezil. The values of Galantamine and Huperzine A. MD were 5. 2 and 2. 5 and 2. 4 respectively. The MD values of lithium, folic acid, vitamin E and simvastatin compared with placebo were -0.62U -0.16N -0.0021 and -1.621, respectively. Consideration of these four drugs had no significant effect on improving mild cognitive impairment in patients with Alzheimer's disease. Of the 12 drugs included, Donepezil was the best in the treatment of mild cognitive impairment in patients with AD. The other drugs were Galantamine Huperzine, melatonin, Atto estradiol, vitamin E, folic acid placebo, lithium simvastatin. In AD patients with moderate cognitive impairment subgroup, the most significant curative effect was Donepezil, the values of Huperzine A and carbatin 路MD were 3.82.9 and 3.0, respectively. Among them, estrogen SB-742457 and Dimebon.Simvastatin compared with placebo, the MD values of SB-742457, simvastatin and placebo were -0.31 and -0.39, respectively, and those of simvastatin and placebo were -0.31, -0.39 and 3.7 and 0.035, respectively. Consideration of these four drugs had no significant effect on improving moderate cognitive impairment in patients with Alzheimer's disease. Of the 15 drugs included, Donepezil was the best in the treatment of moderate cognitive impairment in patients with AD. According to the therapeutic effect, the order of efficacy was Donepiperzepine methylcarbaradine plus adenosemide, N-acetylcysteine, fluvastatin, Atto statin, aripiprazole, simvastatin, placebo, SB-742457 Dimebon. In the subgroup of severe cognitive dysfunction in AD patients, Donepezil was more effective in relieving severe cognitive dysfunction in AD patients than in MJ.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749.16
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