Jianping Jia1, Cuibai Wei2, Junhua Liang2, Aihong Zhou2, Xiumei Zuo2, Haiqing Song2, Liyong Wu2, Xiaochun Chen3, Shengdi Chen4, Junjian Zhang5, Jiang Wu6, Kai Wang7, Lan Chu8, Dantao Peng9, Peiyuan Lv10, Hongzhi Guo11, Xiaoyuan Niu12, Yingzhu Chen13, Wanli Dong14, Xiujie Han15, Boyan Fang16, Mao Peng2, Dan Li2, Qian Jia2, Liyuan Huang2. 1. 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. 2. Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China. 3. Department of Neurology, The Affiliated Union Hospital of Fujian Medical University, Fuzhou, Fujian, China. 4. Department of Neurology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China. 5. Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China. 6. Department of Neurology, The First Teaching Hospital of Jilin University, Changchun, Jilin, China. 7. Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China. 8. Department of Neurology, The Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou, China. 9. Department of Neurology, Beijing Hospital, Beijing, China. 10. Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei, China. 11. Department of Neurology, Qilu Hospital of Shandong University, Jinan, Shandong, China. 12. Department of Neurology, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China. 13. Department of Neurology, Northern Jiangsu People's Hospital of Yangzhou University, Yangzhou, Jiangsu, China. 14. Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China. 15. Department of Neurology, Anshan Changda Hospital, Anshan, Liaoning, China. 16. Department of Neurology, The First Affiliated Hospital of Liaoning Medical College, Jinzhou, Liaoning, China.
Abstract
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 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.
RCT Entities:
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 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.
Authors: Joseph Kwan; Melanie Hafdi; Lorraine L W Chiang; Phyo K Myint; Li Siang Wong; Terry J Quinn Journal: Cochrane Database Syst Rev Date: 2022-07-14
Authors: Teresa Liu-Ambrose; John R Best; Jennifer C Davis; Janice J Eng; Philip E Lee; Claudia Jacova; Lara A Boyd; Penelope M Brasher; Michelle Munkacsy; Winnie Cheung; Ging-Yuek R Hsiung Journal: Neurology Date: 2016-10-19 Impact factor: 9.910