Huperzine A for Alzheimer's disease

 

Abstract

Background

Alzheimer's disease (AD) has become a major public health problem around the world due to its increasing prevalence, long duration, caregiver burden, and high financial cost of care. The degeneration of acetylcholine-containing neurons in the basal forebrain has been implicated in the symptoms of AD. Cholinesterase inhibitors may block the degradation of acetylcholine, thus increasing the efficacy of the remaining cholinergic neurons. Huperzine A is a linearly competitive, reversible inhibitor of acetyl cholinesterase that is said to have both central and peripheral activity with the ability to protect cells against hydrogen peroxide, beta-amyloid protein (or peptide), glutamate, ischemia and staurosporine-induced cytotoxicity and apoptosis. These properties might qualify Huperzine A as a promising agent for treating dementia (including AD).

Objectives

To assess the efficacy and safety of Huperzine A for the treatment of patients with AD.

Search methods

The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group was searched on 1 February 2006 using the search term: huperzin*. The CDCIG Specialized register contains records from all major health care databases (MEDLINE, EMBASE, PsycINFO, CINAHL, SIGLE, ISTP, INSIDE, LILACS) as well as from many trials databases and grey literature sources. In addition, the CBM and AMED databases and relevant websites were searched and some journals were hand-searched. Specialists in the field were approached for unpublished material and any publications found were searched for additional references.

Selection criteria

All relevant randomized controlled trials (RCTs) studying the efficacy and safety of Huperzine A for AD.

Data collection and analysis

Data were extracted independently by two reviewers using a self-developed data extraction form and entered into RevMan 4.2.10 software. Meta-analyses were performed when more than one trial provided data on a comparable outcome on sufficiently similar patients. Random effects analyses were performed whenever heterogeneity between results appeared to be present. Standardized differences in mean outcome measures were used due to the use of different scales and periods of treatment.

Main results

Six trials including a total of 454 patients met our inclusion criteria. The methodological quality of most included trials was not high. It was shown that compared to placebo, Huperzine A had beneficial effects on the improvement of general cognitive function measured by MMSE (WMD 2.81; 95% CI 1.87 to 3.76; P < 0.00001) and ADAS-Cog at six weeks (WMD 1.91; 95% CI 1.27 to 2.55) and at 12 weeks (WMD 2.51; 95% CI 1.74 to 3.28), global clinical assessment measured by CDR (WMD -0.80; 95% CI -0.95 to -0.65) and CIBIC-plus (OR 4.32, 95% CI 2.37 to 7.90), behavioral disturbance measured by ADAS-non-Cog at six weeks (WMD -1.33, 95%CI -2.12 to -0.54) and at 12 weeks (WMD -1.52, 95% CI-2.39 to -0.65), and functional performance measured by ADL (WMD = -7.17; 95% CI -9.13 to -5.22; P < 0.00001). However, Huperzine A was not superior to placebo in the improvement of general cognitive function measured by Hasegawa Dementia Scale (HDS) (WMD: 2.78; 95% CI -0.17 to 5.73, P = 0.06) and specific cognitive function measured by Weshler Memory Scale (WMS) (WMD = 6.64; 95% CI -3.22 to 16.50; P = 0.19). No data were available on quality of life and caregiver burden. The adverse events of Huperzine A were mild and there were no significant differences of adverse events between Huperzine A groups and control groups.

Authors' conclusions

From the available evidence, Huperzine A seems to have some beneficial effects on improvement of general cognitive function, global clinical status, behavioral disturbance and functional performance, with no obvious serious adverse events for patients with AD. However, only one study was of adequate quality and size. There is therefore inadequate evidence to make any recommendation about its use. Rigorous design, randomized, multi-centre, large-sample trials of Huperzine A for AD are needed to further assess the effects.

 

Plain language summary

There is currently insufficient evidence of the effects of Huperzine A for Alzheimer's disease (AD).

Huperzine A is derived from Chinese club moss Huperzia serrata, and is described as having several properties which may be beneficial for AD. This review looked for randomized trials comparing Huperzine A with control in patients with AD. Six trials were identified but most trials were of low methodological quality. Although Huperzine A seemed to have some beneficial effects on improvement of general cognitive function, global clinical status, behavioral disturbance and functional performance for patients with AD, the small trials with limited numbers of patients and the low methodological quality resulted in cautious assessment of the results. More large, high-quality randomized trials are needed.

 

摘要

背景

Huperzine A 治療阿茲海默症

由於阿茲海默症(AD)日趨增多、患者患病期間長，造成照護者負荷，並且耗費高額照顧成本，因此阿茲海默症已經變成全球重大的公共健康問題。 阿茲海默症與基底前腦(basal forebrain)中含有乙醯膽鹼的神經元退化有關。膽鹼酯抑制劑可阻斷乙醯膽鹼裂解，因此可以增加剩下的膽鹼生產神經元的功效。Huperzine A 是一種乙醯膽鹼酯脢線性競爭、可逆轉的抑制劑，據信它對於中樞以及末梢有作用，可以保護細胞抵抗過氧化氫、乙型－澱粉樣蛋白(或胜月太)、谷氨酸、缺血及星形孢菌素誘導?胞毒性以及細胞死亡。Huperzine A的特性可能可以有希望作為治療失智症藥劑(包含阿茲海默症)。

目標

評估使用Huperzine A治療AD病患的療效及安全性。

搜尋策略

2006年2月1日使用huperzin*搜尋Cochrane Dementia and Cognitive Improvement Group Specialized Register。該資料庫不但含有所有主要健康照護資料庫(MEDLINE、EMBASE、PsycINFO、CINAHL、SIGLE、ISTP、INSIDE、LILACS)的記錄，也有進行中臨床試驗資料庫的資料以及灰色文獻來源的資料。 此外，也搜尋CBM及AMED資料庫以及相關的網址，而以人工方式搜尋一些期刊則。回顧作者也與本領域專家接觸，以獲得未公布的材料；並且搜尋所有找到的刊物，以獲得額外的參考文獻。

選擇標準

所有有關的隨機對照試驗(randomized controlled trials (RCTs))用於研究Huperzine A對於AD的功效及安全性。

資料收集與分析

2位回顧作者採用自行研發的表格摘錄數據並且輸入到RevMan 4.2.10軟體。 若超過一個試驗提供足夠人數且病人相似的可進行比較的結果，則進行統合分析。 若結果之間有異質性，則進行隨機效果分析。由於各個試驗所採用的評估方式以及治療期間不一，因此採用平均結果標準差方式進行分析。

主要結論

6項共含有454位病患的試驗符合納入回顧標準。大多數納入的試驗其方法上的品質並不高。 與安慰劑相比Huperzine A在改善一般認知功能時具有效益，以量表測量時，MMSE (WMD 2.81; 95% CI 1.87 to 3.76; P < 0.00001) and ADASCog at six weeks (WMD 1.91; 95% CI 1.27 to 2.55)以及在12周時(WMD 2.51; 95% CI 1.74 to 3.28)。在整體臨床評估上，以CDR (WMD −0.80; 95% CI −0.95 to −0.65)及CIBICplus (OR 4.32, 95% CI 2.37 to 7.90)量表測量，行為紊亂上，以ADL (WMD = −7.17; 95% CI −9.13 to −5.22; P < 0.00001)測量。 然而，由Hasegawa Dementia Scale (HDS) (WMD: 2.78; 95% CI −0.17 to 5.73, P = 0.06)及由Weshler Memory Scale (WMS) (WMD = 6.64; 95% CI −3.22 to 16.50; P = 0.19)所測量的特定認知功能(specific cognitive function)。沒有資料可用評估照護者的負荷及生活的品質。Huperzine A的不良事件輕微且在Huperzine A群組及控制群組間無顯著的不良事件的差異。

作者結論

由可利用的證據，Huperzine A看來對於改善一般認知功能、整體臨床狀態、行為紊亂及功能表現具有效益，同時對於AD病患無明顯的嚴重不良事件。 然而，僅有一項研究具有適當的品質及規模。因此沒有適當的證據來做出使用該藥物的建議。有必要進一步進行嚴格的設計、隨機的、多中心的(multicentre)、大樣本(largesample)的試驗，評估Huperzine A的效果。

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

目前沒有關於Huperzia A對於阿茲海默症(AD)功效的充足證據。Huperzine A是由中國石松子衍生而得，據描述具有數種可有益於AD疾病的特性。 雖然Huperzine A看似對於改善AD病患一般認知功能、整體臨床狀態、行為紊亂及功能的表現有益，但試驗規模小而病患數目有限且方法學上的品質低導致對其結果的評估要十分謹慎。 需要更多大型、高品質隨機試驗。