Intervention Review

Cholinesterase inhibitors for dementia with Lewy bodies

  1. Rebecca Wild1,*,
  2. Tor ACL Pettit2,
  3. Alistair Burns3

Editorial Group: Cochrane Dementia and Cognitive Improvement Group

Published Online: 21 JUL 2003

Assessed as up-to-date: 27 APR 2008

DOI: 10.1002/14651858.CD003672


How to Cite

Wild R, Pettit TACL, Burns A. Cholinesterase inhibitors for dementia with Lewy bodies. Cochrane Database of Systematic Reviews 2003, Issue 3. Art. No.: CD003672. DOI: 10.1002/14651858.CD003672.

Author Information

  1. 1

    Royal Bolton Infirmary, Belmont Day Hospital, Bolton, UK

  2. 2

    Cheadle Royal Hospital, Cheadle, Cheshire, UK

  3. 3

    University of Manchester, Psychiatric Research Group, Manchester, UK

*Rebecca Wild, Belmont Day Hospital, Royal Bolton Infirmary, Minnerva Road, Bolton, BL4 7AA, UK. Rebecca.Wild@rbh.nhs.uk.

Publication History

  1. Publication Status: Stable (no update expected for reasons given in 'What's new')
  2. Published Online: 21 JUL 2003

SEARCH

 

Abstract

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

Background

Dementia with Lewy bodies (DLB) was first described in 1983, and clinical diagnostic criteria were published in the early to mid 1990s. It has been suggested DLB may account for up to 15-25% of cases of dementia among people aged over 65, although autopsy suggests much lower rates. Characteristic symptoms are dementia, marked fluctuation of cognitive ability, early and persistent visual hallucinations and spontaneous motor features of Parkinsonism. Falls, syncope, transient disturbances of consciousness, neuroleptic sensitivity, and hallucinations in other modalities are also common. This combination of features can be difficult to manage as neuroleptics can make the Parkinsonian and cognitive symptoms worse. There is evidence to suggest that the cholinesterase inhibitors may be beneficial in this disorder; small case series indicate that cholinesterase inhibitors are safe, and will improve both cognitive deficits and neuropsychiatric symptoms in DLB.

Objectives

To assess the use of cholinesterase inhibitors in DLB.

Search methods

The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 25 February 2002 using the terms 'Lewy body', 'Lewy bodies' and 'Lewy'. This register contains records from all major health care databases and trial databases and is updated regularly.

Selection criteria

Randomized, double-blindtrials in which treatment with cholinesterase inhibitors was administered and compared with alternative interventions in patients with DLB are included.

Data collection and analysis

Two reviewers (TP, RW) independently assessed quality of trials according to criteria described in the Cochrane Collaboration Handbook. Each drug was to be examined separately, and together as a group. We also analysed data by time to outcome measurement; short-term (up to one month), medium term (one month up to six months) and long term (Six months and longer).

The primary outcome measures of interest are in the following areas:neuropsychiatric features. i.e. psychiatric symptoms and behavioural disturbances, cognitive function, activities of daily living, global assessments, quality of life, including maintaining role and social functioning, effect on carers, safety as measured by incidence of adverse events and side effects, acceptability of treatment as measured by withdrawal from trials, and by patient/carer assessment, institutionalization and death.

Main results

There was one included trial of rivastigmine compared with placebo on 120 patients.

Neuropsychiatric Inventory
The 10-item test found no significant difference between the two groups in change of scores from baseline using intention-to-treat (ITT) analysis at 20 weeks and last observation carried forward (LOCF) analysis. The treatment effect was statistically significant in favour of rivastigmine if only observed cases (OC) were analysed (WMD -6.94, 95% CI -11.59 to -2.29, P=0.003). There were similar results for the NPI-4, with only the OC analysis showing a significant superiority of rivastigmine to placebo at 20 weeks (WMD -3.75, 95%CI -6.62 to -0.88, P=0.01).

MMSE:
Analysis of these results showed no statistically significant difference between the two groups at 20 weeks.

CGC-plus:
Analysis of the proportion of patients who had no change or became worse found no statistically significant difference between the two groups at 20 weeks for the ITT, LOCK and OC analyses.

Adverse Events:
The placebo group experienced significantly fewer adverse events than the treatment group (54/59 vs 46/61,OR 3.52, 95%CI 1.19 to 10.43). However, using ITT analysis of 20-week data, there was no significant difference between the two groups when serious adverse events were considered.
There were no significant differences in death rates between the two groups at 20 weeks.

Drop-out Rates:
Analysis of these results showed no difference between the two groups at 20 weeks using ITT analysis.

Authors' conclusions

Patients with dementia with Lewy bodies who suffer from behavioural disturbance or psychiatric problems may benefit from rivastigmine if they tolerate it, but the evidence is weak. Further trials using rivastigmine are needed, as are trials of other cholinesterase inhibitors in dementia with Lewy bodies.

 

Plain language summary

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

No convincing evidence from one trial of the efficacy of cholinesterase inhibitors for dementia with Lewy bodies

The characteristic features of dementia with Lewy bodies are dementia, marked fluctuation of cognitive ability, early and persistent visual hallucinations and spontaneous motor features of Parkinsonism. Other symptoms are repeated falls, syncope, transient disturbances of consciousness, neuroleptic sensitivity, and hallucinations in other modalities. This combination of features can be particularly difficult to manage, as antipsychotic drugs used to treat hallucinations, delusions and agitation will worsen Parkinsonian symptoms. The one included trial (of rivastigmine compared with placebo on 120 patients) showed no statistically significant difference between the two groups at 20 weeks. A possible beneficial effect on neuropsychiatric features was found only in analysis of observed cases, and may therefore be due to bias.

 

摘要

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

背景

使用乙醯膽鹼酯酉每(Cholinesterase)抑制劑治療路易士體失智症

路易士體失智症(DLB)首次在1983年被提出,有關這種疾病的臨床診斷依據則是在1990年代早期至中期被公開,有人推測,65歲以上患有失智症的老人中有15至25%是罹患路易士體失智症,然而符合解剖學診斷的比例則較低,路易士體失智症的特徵症狀包括了失智、明顯的認知功能變化、早期或持續視覺幻覺(visual hallucinations)和自發性類似帕金森氏症的運動徵狀。此外,跌倒、暈厥,短暫意識障礙,對於抗精神病藥敏感和其他形式的幻覺也是常見的徵狀。這種混合性的病徵並不容易治療,因為抗精神病藥物可能會使得帕金森氏症或是認知相關的症狀更為惡化,目前有證據推測乙醯膽鹼酯酉每(Cholinesterase)抑制劑可能對這類的疾病有所幫助,有一些小型的試驗指出乙醯膽鹼酯酉每(Cholinesterase)抑制劑是安全的並且可能可以提升DLB疾病中的認知功能障礙和神經精神症狀。

目標

本研究的主要目的在於評估使用乙醯膽鹼酯酉每(Cholinesterase)抑制劑治療DLB的效果。

搜尋策略

2002年2月25日利用「‘Lewy body’、‘Lewy bodies’和‘Lewy’」等關鍵字針對Specialized Register of the Cochrane Dementia and Cognitive Improvement Group資料庫進行檢索,這個資料庫包含了所有主要健康照護資料庫和試驗資料庫中的資料,並且會進行定期性的更新。

選擇標準

比較使用乙醯膽鹼酯酉每(Cholinesterase)抑制劑和其他替代性介入治療法治療DLB效果的隨機性雙盲試驗都會被納入本研究中。

資料收集與分析

有2位審查者(TP、RW)分別依據Cochrane Collaboration Handbook中的規範進行試驗品質評估,每一種藥物都會被分別和集中為一組的測試,我們也會分析時間和治療成果、短期(至少一個月)、中期(1個月以上至個月)和長期(6個月以上)的成果,主要的治療成果包括了:神經精神症狀(也就是精神狀況和行為障礙)、認知功能、每日生活行為、整體評量、生活品質包括維持的角色和社會功能、對照護者的影響、藉由評估不良事件和副作用的發生率來進行安全性判斷、藉由試驗中移出的狀況和患者或照護者的評估來進行治療的接受度、入住安養機構或死亡的評估。

主要結論

有1個試驗係針對120名患者試驗使用rivastigmine藥物和安慰劑的治療效果進行比較,神經精神量表(Neuropsychiatric Inventory)結果:在第20週針對患者進行意圖治療(ITT)和進行觀察值前推法分析(last observation carried forward analysis,LOCF)可以發現,在兩個組別中患者對於量表上的10個項目評量結果並沒有出現顯著差異,治療效果顯示如果針對觀察個案(OC)進行分析時,使用rivastigmine的治療是有療效的(WMD值為 −6.94,95%的信心區間介於 −11.59至 −2.29之間,p = 0.003)。相似的結果也出現在神經精神分析結果NPI4的試驗成果上,只有OC分析結果顯示在20週時,使用rivastigmine的效果會優於使用安慰劑的效果(WMD值為 −375,95%的信心區間介於 −6.62至 −0.88之間,p = 0.01)。MMSE試驗結果:進行MMSE試驗時發現在第20週,兩組的治療成果並沒有顯著差異。CGCplus試驗結果:針對症狀沒有改變或是症狀更加惡化的患者所進行的分析發現,兩組在第20週時,在ITT、LOCK和OC分析結果上並沒有統計學上的顯著差異。不良事件:安慰劑組比治療組所出現的不良事件明顯較少(54/59和46/61,OR值為0.52,95%的信心區間介於1.19至10.43之間),但是針對第20週的數據進行ITT分析時發現,兩組在嚴重不良試驗的發生率上並沒有顯著差異,此外,這兩組在第20週時的死亡率也沒有顯著差異。移出率:針對這些結果進行分析顯示,兩個組別在第20週時進行ITT分析並沒有差異。

作者結論

DLB患者通常都會承受行為障礙或是精神上的疾病,這樣的狀況在患者可以忍受的前提下,可以經由使用rivastigmine獲得改善,但是目前實質的證據相當薄弱,因此需要進行更多使用rivastigmine或是其他乙醯膽鹼酯酉每抑制劑用來治療DLB得試驗來證明這樣的推論。

翻譯人

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

總結

由一個試驗所提出不是非常明確的證據說明使用乙醯膽鹼酯酉每抑制劑來治療DLB。DLB的主要特徵為患者出現失智症、明顯的認知功能波動、早期和持續視覺幻覺和自發性類似帕金森氏症的運動障礙。此外,跌倒,暈厥,短暫意識障礙,對於抗精神病藥敏感和其他形式的幻覺也是常見的徵狀,這種混合性的病徵並不容易治療,因為用來治療幻覺、錯覺和躁動的抗精神病藥物可能會使得帕金森氏症更為惡化,有一個被納入研究的試驗(針對120名患者比較使用rivastigmine和安慰劑的效果)顯示在兩個組別的治療中,第20週的治療成果並沒有顯著差異,只有進行OS分析時才會發現使用rivastigmine可能會對神經精神疾病有所幫助,但這可能是因為試驗的偏差所造成的結果。