Galantamine for vascular cognitive impairment

 

Abstract

Background

Vascular dementia is the second most common form of dementia. Cholinesterase inhibitors modestly improve a broad range of symptoms in some patients with Alzheimer's disease through enhancement of cholinergic neurotransmission. These drugs may also be beneficial in vascular dementia as reductions in acetylcholine and acetyltransferase activity have been reported.

Objectives

To assess the efficacy of galantamine in the treatment of people with vascular cognitive impairment or vascular dementia or "mixed" dementia.

Search methods

Trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 19 April 2005 using the terms: galantamine. galanthamine, reminyl. All major health care databases and many ongoing trial databases within the scope of the group are searched regularly to keep this Register up to date.

Selection criteria

All unconfounded randomised double-blind trials comparing galantamine with placebo were eligible for inclusion.

Data collection and analysis

Two RCTs fulfilling the inclusion criteria were included in this review. Two reviewers independently extracted the data from these two inclusion studies.

Main results

Two trials employing randomized, double-blind, parallel-group methodology were included. GAL-INT-6 reported sub-group data for a pure population of vascular dementia patients showing no significant differences in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog/11) and Clinician's Interview-based Impression of Change (CIBIC-plus) when galantamine was compared against placebo. When data combining patients with vascular dementia diagnosed according to recognised criteria with a population of patients with Alzheimer's disease and coincidental radiographic findings of cerebrovascular disease was analysed, statistically significant improvements in cognition (ADAS-cog), global functioning (CIBIC-plus), activities of daily living (DAD) and behaviour (NPI) were noted. In the galantamine treated group, significantly higher numbers of patients dropped out and withdrew due to an adverse event.

Limited data was available at the time of publication for a second larger trial (GAL-INT-26) involving patients with vascular dementia diagnosed using standard criteria. Statistically significant benefits favouring galantamine over placebo in assessments of cognition (ADAS-cog/11; p < 0.001) and executive function (Executive Interview, EXIT-25, p = 0.041) were recorded. No differences in outcome in measures of behaviour (Neuropsychiatric Inventory, NPI), daily living (Alzheimer's Disease Cooperative Study-Activities of Daily Living inventory, ADCS-ADL) and global functioning (CIBIC-plus) in this trial were seen.

Authors' conclusions

Limited data were available when considering the impact of galantamine on vascular dementia or vascular cognitive impairment. The data available at the time of review suggest some advantage over placebo in the areas of cognition and executive functioning in one trial but this was not seen in a second trial which included smaller numbers of relevant patients. In both considered trials galantamine produced higher rates of gastrointestinal side-effects. More studies are needed before firm conclusions can be drawn.

 

Plain language summary

No consistent evidence of efficacy of galantamine in vascular cognitive impairment

The efficacy of galantamine has been tested in two RCTs for the treatment of vascular dementia and for a mixed population of Alzheimer's disease patients with evidence of cerebrovascular disease. The rationale behind its use is to correct the cholinergic deficit seen in vascular dementia. This review found evidence of benefit in measures of cognition including executive functioning in one study but no clear advantage over placebo in another study when patients with pure vascular dementia were considered. Both studies indicated higher rates of nausea and vomiting in actively treated participants.

 

摘要

背景

Galantamineg使用於血管型認知功能障礙

血管性失智是第二常見失智症的類型。膽鹼酯脢抑制劑經由增加膽鹼性的神經傳導物質而可以適度的改善阿茲海默氏症的症狀。有報告指出這些藥物也可經由減少乙醯膽鹼和乙醯轉移酵素活性進而對血管性失智症產生幫助。

目標

評估使用galantamin在治療血管性認知障礙或血管性失智症或混合性失智症的療效。�

搜尋策略

2005年4月19號搜尋Specialized Register of the Cochrane Dementia and Cognitive Improvement Group資料庫，針對「 galantamine. galanthamine, reminyl」等關鍵字進行檢索，也定期搜尋主要健康保健資料庫跟很多進行中的試驗資料庫中的資料，以保持資料的更新。

選擇標準

所有比較galantamine與安慰劑的unconfounded randomised doubleblind試驗均納入本研究中。

資料收集與分析

有個RCT試驗符合本研究的納入規範，兩個閱審者各自從這兩個納入試驗提取數據。

主要結論

有2個使用隨機，雙盲，平行組方法的試驗被納入本研究中。GALINT6顯示使用galantamine和安慰劑在治療純粹血管型失智症患上，對於Alzheimer's Disease Assessment Scalecognitive subscale (ADAScog/11) 和 Clinician's Interviewbased Impression of Change (CIBICplus)的評量結果並沒有顯著的差異。若是合併血管型失智症患者與阿茲海默氏症併有腦血管疾病的患者一起分析，則可以發現在認知功能(ADAScog)、整體功能(CIBICplus)、日常生活功能(DAD)和行為(NPI)上有顯著統計上的差異。在galantamine治療組，明顯有較高比例的病患因為不良事件退出或中止試驗。在第二大型試驗(GALINT26)公開時，只有獲得有限的資料，而此試驗收錄標準診斷準則的血管性失智患者。統計上顯示使用Galantamine比起安慰劑有較好的認知功能(ADAScog/11; p < 0.001)和執行能(Executive Interview, EXIT25, p = 0.041)。在這個試驗顯示Galantamine對於行為(Neuropsychiatric Inventory, NPI) ，日常生活(Alzheimer's Disease Cooperative StudyActivities of Daily Living inventory, ADCSADL) 和整體功能(CIBICplus)在並無療效。

作者結論

只有有限的資料探討有關galantamine對於血管性失智症或血管性認知功能障礙的影響。在進行這篇回顧文章時，獲得的資料顯示一個試驗發現galantamine與安慰劑相比，對於認知功能以及執行能力有一些療效，但這些療效並沒有在另一個較小型、收錄相關病患的試驗中被發現。這二個試驗均顯示galantamine會產生較高比例的胃腸副作用。需要更多的試驗才能做出明確的結論。

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

沒有一致的證據顯示Galantamine在血管性認知功能障礙上是有療效的。兩個RCTs試驗檢驗galantamine使用在治療血管性失智症和混合阿茲海默氏症與腦血管疾病的病患。使用此藥物的理由是為了矯正血管性失智症上膽鹼的缺乏。此回顧性的文章可以發現，其中一試驗顯示galantamine對於認知功能包括執行能力是有療效的，但另一個只收錄純萃血管性失智症病患的試驗則無顯示療效。兩個試驗均顯示使用galantamine的病患有較高比例的噁心和嘔吐現象。