The effects of DL-3-n-butylphthalide in patients with vascular cognitive impairment without dementia caused by subcortical ischemic small vessel disease: A multicentre, randomized, double-blind, placebo-controlled trial

被引：183

作者：

Jia, Jianping ^{[1
,2
]}

Wei, Cuibai ^{[1
]}

Liang, Junhua ^{[1
]}

Zhou, Aihong ^{[1
]}

Zuo, Xiumei ^{[1
]}

Song, Haiqing ^{[1
]}

Wu, Liyong ^{[1
]}

Chen, Xiaochun ^{[3
]}

Chen, Shengdi ^{[4
]}

Zhang, Junjian ^{[5
]}

Wu, Jiang ^{[6
]}

Wang, Kai ^{[7
]}

Chu, Lan ^{[8
]}

Peng, Dantao ^{[9
]}

Lv, Peiyuan ^{[10
]}

Guo, Hongzhi ^{[11
]}

Niu, Xiaoyuan ^{[12
]}

Chen, Yingzhu ^{[13
]}

Dong, Wanli ^{[14
]}

Han, Xiujie ^{[15
]}

Fang, Boyan ^{[16
]}

Peng, Mao ^{[1
]}

Li, Dan ^{[1
]}

Jia, Qian ^{[1
]}

Huang, Liyuan ^{[1
]}

机构：

[1] Capital Med Univ, Xuan Wu Hosp, Dept Neurol, Beijing, Peoples R China

[2] Beijing Inst Brain Disorders, Ctr Alzheimers Dis, Beijing, Peoples R China

[3] Fujian Med Univ, Affiliated Union Hosp, Dept Neurol, Fuzhou, Fujian, Peoples R China

[4] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Neurol, Shanghai, Peoples R China

[5] Wuhan Univ, Zhongnan Hosp, Dept Neurol, Wuhan 430072, Hubei, Peoples R China

[6] Jilin Univ, Teaching Hosp 1, Dept Neurol, Changchun 130023, Jilin, Peoples R China

[7] Anhui Med Univ, Affiliated Hosp 1, Dept Neurol, Hefei, Anhui, Peoples R China

[8] Guiyang Med Coll, Affiliated Hosp, Dept Neurol, Guiyang, Guizhou, Peoples R China

[9] Beijing Hosp, Dept Neurol, Beijing, Peoples R China

[10] Hebei Gen Hosp, Dept Neurol, Shijiazhuang, Hebei, Peoples R China

[11] Shandong Univ, Qilu Hosp, Dept Neurol, Jinan, Shandong, Peoples R China

[12] Shanxi Med Univ, Hosp 1, Dept Neurol, Taiyuan, Shanxi, Peoples R China

[13] Yangzhou Univ, Northern Jiangsu Peoples Hosp, Dept Neurol, Yangzhou 225009, Jiangsu, Peoples R China

[14] Soochow Univ, Affiliated Hosp 1, Dept Neurol, Suzhou, Jiangsu, Peoples R China

[15] Anshan Changda Hosp, Dept Neurol, Anshan, Liaoning, Peoples R China

[16] Liaoning Med Coll, Affiliated Hosp 1, Dept Neurol, Jinzhou, Liaoning, Peoples R China

来源：

ALZHEIMERS & DEMENTIA | 2016年 / 12卷 / 02期

关键词：

DL-3-n-Butylphthalide; Vascular cognitive impairment without dementia; Cerebral small vessel disease; Randomized controlled trial; Multicentre study; ALZHEIMERS-DISEASE; NO DEMENTIA; L-3-N-BUTYLPHTHALIDE; PREVALENCE; EFFICACY; DONEPEZIL; CHINESE; RATS; RIVASTIGMINE; MEMANTINE;

D O I：

10.1016/j.jalz.2015.04.010

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

100204 [神经病学];

摘要：

Introduction: Vascular cognitive impairment without dementia is very common among the aged and tends to progress to dementia, but there have been no proper large-scale intervention trials dedicated to it. Vascular cognitive impairment without dementia caused by subcortical ischemic small vessel disease (hereinafter, subcortical Vascular cognitive impairment without dementia) represents a relatively homogeneous disease process and is a suitable target for therapeutic trials investigating Vascular cognitive impairment without dementia. Preclinical trials showed that dl-3-n-butylphthalide (NBP) is effective for cognitive impairment of vascular origin. Methods: In this randomized, double-blind, placebo-controlled trial, we enrolled patients aged 50-70 years who had a diagnosis of subcortical Vascular cognitive impairment without dementia at 15 academic medical centers in China. Inclusion criteria included a clinical dementia rating >= 0.5 on at least one domain and global score <0.5; a mini-mental state examination score >20 (primary school) or >= 24 (junior school or above); and brain magnetic resonance imaging consistent with subcortical ischemic small vessel disease. Patients were randomly assigned toNBP200mgthree times daily or matched placebo (1: 1) for 24 weeks according to a computer-generated randomization protocol. All patients and study personnel were masked to treatment assignment. Primary outcome measures were the changes in Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) and clinician's interview-based impression of change plus caregiver input (CIBIC-plus) after 24 weeks. All patients were monitored for adverse events (AEs). Outcome measures were analyzed for both the intention-to-treat (ITT) population and the per protocol population. Results: This study enrolled 281 patients. NBP showed greater effects than placebo on ADAS-cog (NBP change -2.46 vs. placebo -1.39; P = .03; ITT) and CIBIC-plus (80 [57.1%] vs. 59 [42.1%] patients improved; P 5.01; ITT). NBP-related AE were uncommon and primarily consisted of mild gastrointestinal symptoms. Discussion: Over the 6-month treatment period, NBP was effective for improving cognitive and global functioning in patients with subcortical vascular cognitive impairment without dementia and exhibited good safety. (C) 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

引用

页码：89 / 99

页数：11

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