Intervention Review

Donepezil for dementia in people with Down syndrome

  1. Monica Mohan1,*,
  2. Peter K Carpenter2,
  3. Cathy Bennett3

Editorial Group: Cochrane Developmental, Psychosocial and Learning Problems Group

Published Online: 21 JAN 2009

Assessed as up-to-date: 29 OCT 2008

DOI: 10.1002/14651858.CD007178.pub2


How to Cite

Mohan M, Carpenter PK, Bennett C. Donepezil for dementia in people with Down syndrome. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD007178. DOI: 10.1002/14651858.CD007178.pub2.

Author Information

  1. 1

    The Burden Centre, Department of Neuropsychiatry, Neuropsychology and Epileptology, Bristol, Avon, UK

  2. 2

    Bath and North Somerset PCT, Department of Learning Disability, Bristol, UK

  3. 3

    University of Leeds, Cochrane UGPD Group, Leeds, West Yorkshire, UK

*Monica Mohan, Department of Neuropsychiatry, Neuropsychology and Epileptology, The Burden Centre, The North Bristol Trust, Frenchay Hospital, Bristol, Avon, BS16 1JB, UK. drmonicamohan@yahoo.co.uk .

Publication History

  1. Publication Status: New
  2. Published Online: 21 JAN 2009

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Alzheimer's dementia (AD) is the most common form of dementia in people with Down Syndrome [DS]. Acetylcholine is a chemical found in the brain that has an important role in memory, attention, reason and language. Donepezil a reversible inhibitor of acetylcholinesterase, which is thought to maintain levels of acetylcholine, and is reported to have some benefits for people with AD in the general population. It is important to note that people with DS tend to present with AD at a much younger age than the normal population as well as having subtle differences in physiology (e.g. metabolism and heart rate) and may therefore have different requirements from the general population.

Objectives

To determine the effectiveness and safety of donepezil for people with DS who develop AD.

Search methods

CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, BIOSIS, SCI, SSCI and the NRR were searched up to October 2008. We contacted the manufacturers of donepezil as well as experts in the field, to ask about reports of unpublished or ongoing trials.

Selection criteria

Randomised controlled trials of participants with DS and AD in which treatment with donepezil was administered compared with a placebo group.

Data collection and analysis

Data were extracted from the published reports of the one relevant study identified.

Main results

The one study included in this review is a small (n=30) randomised controlled trial lasting 24 weeks. It was followed-up by an open label study with a crossover design.

No significant differences were found on any four validated outcomes including global functioning and three measures of cognitive abilities and behavioural problems. 6 out of 16 carers (37%) of participants on donepezil and 2 out of 15 (13%) on placebo reported improvement. No data were available for day to day skills, institutionalisation, reduction in carers' stress or economic outcomes. Half the intervention group and 20% of the placebo group reported adverse events; two participants left because of adverse events.

Authors' conclusions

To date there is only one small randomised controlled study on the effect of donepezil. This shows, at best, a modest, non statistically significant trend in favour of people with Down syndrome and Alzheimer's dementia who are able to tolerate donepezil (this drug is currently only dispensed in relatively large doses and is contraindicated for those with cardiac and respiratory problems).This study does not provide good evidence on which to base practice. Findings in an open-label follow up to this study suggest possible benefit in some individuals. Further, larger randomised controlled studies with longer-term follow up are required.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Donepezil for dementia in people with Down Syndrome

Donepezil is a drug which is thought to discourage the breakdown of acetylcholine, which is a neurotransmitter in the brain that is important to how memory functions. Acetylcholine is lacking in people with Alzheimer's disease (AD). The drug donepezil has been reported to have benefits for people with mild to moderate Alzheimer's disease who do not have Down syndrome. However, people with DS tend to present with AD at a much younger age than the general population as well as being physically different in terms of size, metabolism and heart rate, and may therefore have different requirements.

This review identified one randomised controlled trial of donepezil in people with Down syndrome. This shows, at best, a modest, non statistically significant trend in favour of people with Down syndrome and Alzheimer's dementia who are able to tolerate donepezil. The trial was of good quality, but small. It is important to note that people with Down syndrome may often have other conditions which mean that the drug is not suitable for all. Further research is needed.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

Donepezil對於唐氏症患者之失智的治療

唐氏症候群 (DS) 最常發生的失智症為阿茲海默氏型之失智症 (AD) 。乙醯膽鹼是一種於腦中發現的化學物質,對於記憶力、注意力、邏輯及語言有著重要的角色。Donepezil是乙醯膽鹼的可逆抑制劑,被視為可以用來維持乙醯膽鹼的量,而被報告對於一般大眾的阿茲海默氏失智症患者有一些幫助。很重要的一點是唐氏症患者比起一般人來說容易在年紀較輕時即表現AD,也容易在生理方面也稍有不同 (例如代謝方面及心跳) ,因此或許比起一般大眾有著不同的需要。

目標

評估Donepezil對於有AD的DS患者的有效性及安全性

搜尋策略

我們搜尋在了2008年10月之前的CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, BIOSIS, SCI, SSCI及NRR等資料庫。我們聯絡了Donepezil的廠商以及這個領域的專家,詢問於尚未發表的報告或是正在進行中的試驗。

選擇標準

採用的是隨機控制試驗,比較在DS有AD的研究參與者身上Donepezil與安慰劑的使用。

資料收集與分析

資料是從已被報告的一個相關研究當中所篩選出來的。

主要結論

在這個回顧文獻當中包含了一個研究,是一項持續24週的小型 (n = 30) 隨機控制試驗。這個研究之後還有一個開放的研究,有著交叉比對的設計。在四項已驗證的成果,包括全面性的功能以及三項評估認知能力及行為問題的指標中,並未發現到有意義的差異。服用Donepezil的16位參與者之照顧者當中有6位 (37%) ,以及15位服用安慰劑當中的2位照顧者 (13%) 表示有進步的情形。在日常技能、機構化問題、照顧者壓力的減輕或經濟結果這幾個方面的資料是缺少的。在服藥組的一半及服用安慰劑組的20% 並報告了有副作用的事件。有兩位受試者因為副作用而未完成研究。

作者結論

目前只有一個小型隨機控制試驗是針對donepezil的效果。這充其量只表示在可耐受donepezil之唐氏症有阿茲海默氏失智症的患者身上使用此藥物,具作用不大、無統計上差異的有利傾向。 (這個藥目前只有相對大劑量的劑型,並且對於那些有心臟及呼吸系統問題的人是不可使用的) 。這個研究並無法提供臨床的良好証據。在接下來開放的研究追蹤當中的發現,認為在某些受試者身上可能是有益處的。需要的是更長期追蹤的更大型隨機控制的研究。

翻譯人

本摘要由成功大學附設醫院謝佩君翻譯。

此翻譯計畫由臺灣國家衛生研究院 (National Health Research Institutes, Taiwan) 統籌。

總結

在唐氏症併有失智症的患者身上使用Donepezil:Donepezil是一種阻止乙醯膽鹼分解的藥物,乙醯膽鹼是腦中的一種神經傳導物質,對記憶的作用相當重要。在阿茲海默氏失智症的病人身上,乙醯膽鹼是缺乏的。Donepezil這個藥物對於輕度至中度的阿茲海默氏失智症 (無唐氏症) 是有益處的。而唐氏症患者與一般大眾相比,較容易在較年輕時即表現出阿茲海默氏失智症,同時在生理方面,如體型、代謝、心跳速率各方面也和一般大眾不同,因此需求也可能會不同。這個回顧研究提出了使用Donepezil於唐氏症患者身上的一個隨機控制試驗。這充其量只表示在可耐受donepezil之唐氏症有阿茲海默氏失智症的患者身上使用此藥物,具作用不大、無統計上差異的有利傾向。這個研究有著良好的品質,但是是個小型研究。很重要要值得注意的是,有著唐氏症的患者通常會有一些其他的身體狀況,這意味著藥物並不是適用於所有的患者。需要更進一步的研究再來探討這個問題。