PMID- 26086183 OWN - NLM STAT- MEDLINE DCOM- 20160923 LR - 20220317 IS - 1552-5279 (Electronic) IS - 1552-5260 (Linking) VI - 12 IP - 2 DP - 2016 Feb TI - 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. PG - 89-99 LID - S1552-5260(15)00193-4 [pii] LID - 10.1016/j.jalz.2015.04.010 [doi] AB - 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 /=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 to NBP 200 mg three 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 = .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. CI - Copyright (c) 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved. FAU - Jia, Jianping AU - Jia J AD - Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China; Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China. Electronic address: jjp@ccmu.edu.cn. FAU - Wei, Cuibai AU - Wei C AD - Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China. FAU - Liang, Junhua AU - Liang J AD - Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China. FAU - Zhou, Aihong AU - Zhou A AD - Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China. FAU - Zuo, Xiumei AU - Zuo X AD - Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China. FAU - Song, Haiqing AU - Song H AD - Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China. FAU - Wu, Liyong AU - Wu L AD - Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China. FAU - Chen, Xiaochun AU - Chen X AD - Department of Neurology, The Affiliated Union Hospital of Fujian Medical University, Fuzhou, Fujian, China. FAU - Chen, Shengdi AU - Chen S AD - Department of Neurology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China. FAU - Zhang, Junjian AU - Zhang J AD - Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China. FAU - Wu, Jiang AU - Wu J AD - Department of Neurology, The First Teaching Hospital of Jilin University, Changchun, Jilin, China. FAU - Wang, Kai AU - Wang K AD - Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China. FAU - Chu, Lan AU - Chu L AD - Department of Neurology, The Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou, China. FAU - Peng, Dantao AU - Peng D AD - Department of Neurology, Beijing Hospital, Beijing, China. FAU - Lv, Peiyuan AU - Lv P AD - Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei, China. FAU - Guo, Hongzhi AU - Guo H AD - Department of Neurology, Qilu Hospital of Shandong University, Jinan, Shandong, China. FAU - Niu, Xiaoyuan AU - Niu X AD - Department of Neurology, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China. FAU - Chen, Yingzhu AU - Chen Y AD - Department of Neurology, Northern Jiangsu People's Hospital of Yangzhou University, Yangzhou, Jiangsu, China. FAU - Dong, Wanli AU - Dong W AD - Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China. FAU - Han, Xiujie AU - Han X AD - Department of Neurology, Anshan Changda Hospital, Anshan, Liaoning, China. FAU - Fang, Boyan AU - Fang B AD - Department of Neurology, The First Affiliated Hospital of Liaoning Medical College, Jinzhou, Liaoning, China. FAU - Peng, Mao AU - Peng M AD - Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China. FAU - Li, Dan AU - Li D AD - Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China. FAU - Jia, Qian AU - Jia Q AD - Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China. FAU - Huang, Liyuan AU - Huang L AD - Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China. LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20150615 PL - United States TA - Alzheimers Dement JT - Alzheimer's & dementia : the journal of the Alzheimer's Association JID - 101231978 RN - 0 (Benzofurans) RN - 0 (Neuroprotective Agents) RN - 822Q956KGM (3-n-butylphthalide) SB - IM MH - Aged MH - Benzofurans/*therapeutic use MH - Cerebral Small Vessel Diseases/*complications MH - China MH - Cognition Disorders/*drug therapy/etiology MH - Double-Blind Method MH - Female MH - Humans MH - Male MH - Middle Aged MH - Neuroprotective Agents/*therapeutic use MH - Neuropsychological Tests OTO - NOTNLM OT - Cerebral small vessel disease OT - DL-3-n-Butylphthalide OT - Multicentre study OT - Randomized controlled trial OT - Vascular cognitive impairment without dementia EDAT- 2015/06/19 06:00 MHDA- 2016/09/24 06:00 CRDT- 2015/06/19 06:00 PHST- 2014/06/19 00:00 [received] PHST- 2015/02/27 00:00 [revised] PHST- 2015/04/06 00:00 [accepted] PHST- 2015/06/19 06:00 [entrez] PHST- 2015/06/19 06:00 [pubmed] PHST- 2016/09/24 06:00 [medline] AID - S1552-5260(15)00193-4 [pii] AID - 10.1016/j.jalz.2015.04.010 [doi] PST - ppublish SO - Alzheimers Dement. 2016 Feb;12(2):89-99. doi: 10.1016/j.jalz.2015.04.010. Epub 2015 Jun 15.