Donepezil for vascular cognitive impairment
Editorial Group: Cochrane Dementia and Cognitive Improvement Group
Published Online: 26 JAN 2004
Assessed as up-to-date: 6 JUN 2005
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
How to Cite
Malouf R, Birks J. Donepezil for vascular cognitive impairment. Cochrane Database of Systematic Reviews 2004, Issue 1. Art. No.: CD004395. DOI: 10.1002/14651858.CD004395.pub2.
- Publication Status: Edited (no change to conclusions)
- Published Online: 26 JAN 2004
Vascular disease is the second commonest cause of dementia after Alzheimer's disease. There are difficulties in classifying patients with this type of cognitive impairment owing to varied clinical presentation and different types of arterial disease. There is some degree of overlap in the neuropathology of Alzheimer's and vascular dementia. Deficient cholinergic neurotransmission, a characteristic of Alzheimer's disease, has been postulated to contribute to the cognitive impairment of vascular disease of the brain. Cholinesterase inhibitors, such as donepezil, may therefore be a rational treatment.
To assess the clinical efficacy and tolerability of donepezil on cognitive function, clinical global impression, activities of daily living and social functioning of people with vascular cognitive impairment.
Relevant randomized controlled trials were identified from a search of the Cochrane Dementia and Cognitive Improvement Group Specialized Register on 7 June 2005 using the terms donepezil, E2020 and Aricept. This Register consists of records from all major healthcare databases and many ongoing trials databases. Unpublished trials were requested from the drug company Eisai Inc and they provided us with the required data.
All unconfounded randomized double-blind trials comparing donepezil with placebo were eligible for inclusion. Trials using combinations of donepezil with other pharmacological interventions were excluded.
Data collection and analysis
Both reviewers assessed studies against the criteria for inclusion and extracted data. Data were pooled where appropriate, and weighted mean differences or Peto odds ratios with 95% confidence intervals calculated. Intention-to-treat analysis was undertaken when possible.
Two large-scale, randomized, double-blind, parallel-group controlled trials were identified for inclusion. A total of 1219 people with mild to moderate cognitive decline due to probable or possible vascular dementia (according to the NINCDS/AIREN criteria and the Hachinski Ischemia Scale) were recruited. Donepezil, at doses of 5 or 10 mg a day was compared with placebo for 24 weeks. For each outcome measure, mean change from baseline at weeks 12 and 24, using a last observation carried forward analysis, was calculated.
The donepezil groups showed statistically significantly better performance than the placebo groups on the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) at 12 and 24 weeks.
The donepezil groups produced statistically significantly better scores than the placebo groups on the Mini-Mental State Examination (MMSE) at 12 and 24 weeks.
The sum of the boxes of the Clinical Dementia Rating (CDR-SB) showed at 24 weeks a statistically significant benefit of 10 mg donepezil daily over both placebo and a 5 mg daily dosage.
The Clinician's Interview-Based Impression of Change-plus version (CIBIC-plus) showed improved global function of participants taking 5 mg of donepezil daily compared with the placebo group but this was not seen in the higher dose group.
Activities of daily living and social behaviour:
On the Instrumental Activity of Daily Living (IADL) scale, there was no statistically significant difference between the groups taking donepezil 5 mg per day donepezil and placebo, but the group taking 10 mg of donepezil a day showed benefit compared with placebo
There were statistically significant benefit for donepezil at either dosage compared with placebo on the Alzheimer's Disease Functional Assessment and Change Scale (ADFACS).
Tolerability and adverse effects:
Broad range of adverse events were reported in the studies and data confirmed that donepezil was well tolerated, and most of the side effects were transient and were resolved by stopping the medication. Some of these events, especially nausea, diarrhoea, anorexia and cramp appeared more frequently on the 10 mg dose where there was a statistically significant difference compared with placebo.
The drop-out rate was similar between the groups, 84.2% (330) patients completed the studies. The withdrawal rate was low and due mainly to side effects.
Evidence from the available studies support the benefit of donepezil in improving cognition function, clinical global impression and activities of daily living in patients with probable or possible mild to moderate vascular cognitive impairment after 6 months treatment. Extending studies for longer periods would be desirable to establish the efficacy of donepezil in patients with advanced stages of cognitive impairment. Moreover, there is an urgent need for establishing specific clinical diagnostic criteria and rating scales for vascular cognitive impairment.
Plain language summary
Evidence of efficacy of donepezil for people with mild or moderate vascular cognitive impairment
Acetylcholine is a neurotransmitter involved in memory function. Acetylcholinesterase inhibitors, such as donepezil, inhibit the breakdown of acetylcholine and have been shown to be of benefit for people with mild to moderate Alzheimer's disease. Deficits in acetylcholine mediated neurotransmission have been postulated in cognitive impairment due to vascular disease of the brain. Two large-scales randomized trials provide evidence of beneficial effects from donepezil at doses of 5 or 10 mg per day over 24 weeks. The drug was well tolerated and drop-out rate was low.
相關的隨機對照試驗是利用下列關鍵字「donepezil, E2020 和 Aricept」，在2005年6月7號搜尋Cochrane Dementia and Cognitive Improvement Group Specialized Register資料庫收錄的。這個資料庫包含所有主要健康照料資料庫和許多進行中的試驗資料庫。藥廠Eisai Inc也提供我們需要的未公開試驗。
所有比較donepezil和安慰劑治療效果的unconfounded randomized doubleblind 試驗都被納入研究中。試驗若使用donepezil合併其他藥物進行治療則被排除。
2個大規模隨機式雙盲平行組對照試驗被納入研究中，其中共包含1219位輕度至中度的血管失智症患者 (根據NINCDS/AIREN規範和Hachinski 局部缺血量表)。每日使用Donepezil劑量5或10 mg與安慰劑比較24週，從每個測量結果為初期到12和24週的平均變化，使用最後觀察伴隨前面的分析來進行計算。 認知功能： 使用donepezil的組別在12及24週使用ADASCog評量表進行評分時，比安慰劑組具有明顯的進步。 使用donepezil的組別比安慰劑組在第12和24週利用MMSE評量表進行評分時也可以獲得明顯較佳的得分結果。 整體功能： 第24週進行CDRSB評估的結果顯示，使用10毫克donepezil的治療效果明顯優於安慰劑組或是使用5毫克donepezil的組別。 CIBICplus的評分結果顯示每天使用5毫克donepezil的患者比安慰劑組的患者在CIBICplus的評分上較為理想，但是這樣的結果並沒有出現在使用高劑量的組別。 每日生活功能和社交行為： 利用IADL表進行評分的結果顯示，在每天使用5毫克donepezil和安慰劑組間並沒有顯著差異，但是每天使用10毫克則顯示比安慰劑有較好的結果。 不管使用多少劑量的donepezil，都會比使用安慰劑的組別在ADFACS結果上出現明顯的好處。 耐受性及不良事件： 在研究中有提出各種不同不良事件，並且資料顯示患者對於donepezil具有良好的耐受性。大部分的副作用是暫時性的，或是停藥後便會改善。與安慰劑組相比，10毫克donepezil較常出現一些不良事件，特別是噁心、腹瀉、缺乏食慾和腹部痙攣。 Dropout： 不同組別的dropout大致相似，84.2％(330名患者)病患完成試驗。退出率是很低的，且大部分都是因為副作用的緣故。
此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。