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Cytidinediphosphocholine (CDP-choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly

  • Review
  • Intervention

Authors

  • Mario Fioravanti,

    Corresponding author
    1. University of Rome "La Sapienza", Department of Psychiatric Science and Psychological Medicine, Rome, Italy
    • Mario Fioravanti, Department of Psychiatric Science and Psychological Medicine, University of Rome "La Sapienza", P.le A. Moro, 5, Rome, 00185, Italy. mario.fioravanti@uniroma1.it.

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  • Motokazu Yanagi

    1. Tezukayama University, Dept of Food and Nutrition, Faculty of Contemporary Human Life Science, Nara 631-8585, Japan
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Abstract

Background

CDP-choline (cytidine 5'-diphosphocholine) is a precursor essential for the synthesis of phosphatidylcholine, one of the cell membrane components that is degraded during cerebral ischaemia to free fatty acids and free radicals. Animal studies suggest that CDP-choline may protect cell membranes by accelerating resynthesis of phospholipids. CDP-choline may also attenuate the progression of ischaemic cell damage by suppressing the release of free fatty acids. CDP-choline is the endogenous compound normally produced by the organism. When the same substance is introduced as a drug it can be called citicoline.

CDP-choline is mainly used in the treatment of disorders of a cerebrovascular nature. The many years of its presence in the clinical field have caused an evolution in dosage, method of administration, and selection criteria of patients to whom the treatments were given. Modalities of the clinical studies, including length of observation, severity of disturbance, and methodology of evaluation of the results were also heterogeneous. In spite of uncertainties about its efficacy due to these complexities, CDP-choline is a frequently prescribed drug for cognitive impairment in several European countries, especially when the clinical picture is predominantly one of cerebrovascular disease, hence the need for this review.

Due to its effects on the adrenergic and dopaminergic activity of the CNS, CDP-choline has also been used as an adjuvant in the treatment of Parkinson's disease.

Objectives

To assess the efficacy of CDP-choline (cytidinediphosphocholine) in the treatment of cognitive, emotional, and behavioural deficits associated with chronic cerebral disorders in the elderly.

Search methods

The trials were identified from a last updated search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 22 April 2004 using the terms CDP-choline, CDP, citicoline, cytidine diphosphate choline or diphosphocholine. The Register contains records from all major health-care databases and many ongoing trials databases and is updated regularly.

Selection criteria

All relevant unconfounded, double-blind, placebo-controlled, randomized trials of CDP-choline for cognitive impairment due to chronic cerebral disorders were considered for inclusion in the review.

Data collection and analysis

Two reviewers independently reviewed the included studies, extracted the data, and pooled it when appropriate and possible. The pooled odd ratios (95% Confidence Interval (CI)) or the average differences (95% CI) were estimated. No intention-to-treat data were available from the studies included.

Main results

Fourteen studies were included in this review. Some of the included studies did not present numerical data suitable for analysis. Description of participants varied over the years and by type of disorders and severity, and ranged from aged individuals with subjective memory disorders to patients with Vascular Cognitive Impairment (mild to moderate), Vascular Dementia or Senile Dementia (mild to moderate). Seven of the included studies observed the subjects for a period between 20 to 30 days, one study was of 6 weeks duration, four studies used periods extending over 2 and 3 months, one study observed continuous administration over 3 months and one study was prolonged, with 12 months of observation. The studies were heterogeneous in dose, modalities of administration, inclusion criteria for subjects, and outcome measures. Results were reported for the domains of attention, memory testing, behavioural rating scales, global clinical impression and tolerability. There was no evidence of a beneficial effect of CDP-choline on attention. There was evidence of benefit of CDP-choline on memory function and behaviour. The drug was well tolerated.

Authors' conclusions

There was some evidence that CDP-choline has a positive effect on memory and behaviour in at least the short to medium term. The evidence of benefit from global impression was stronger, but is still limited by the duration of the studies. Further research with CDP-choline should focus on longer term studies in subjects who have been diagnosed with currently accepted standardised criteria, especially Vascular Mild Cognitive Impairment (VaMCI) or vascular dementia.

摘要

背景

使用胞二磷膽鹼(Cytidinediphosphocholine,CDPcholine)對於老年人慢性腦部疾病有關的認知和行為障礙的影響

CDPcholine(cytidine 5'diphosphocholine)是一種合成磷脂醯膽鹼 (phosphatidylcholine)所需的前驅物,而磷脂醯膽鹼又是一種細胞膜組成物,在大腦局部缺血受到自由脂肪酸和自由基攻擊時便會使細胞膜受到破壞,動物試驗的結果推測CDPcholine可能可以藉由快速的重新合成磷脂質來達到保護細胞膜的功能,CDPcholine也可能可以減少因為釋放出來的游離脂肪酸對缺血細胞的傷害,CDPcholine是一種由有機體產生的內生型化合物,當同樣的物質被製備成藥物時便稱為胞磷膽鹼(citicoline),CDPcholine主要被應用在治療腦血管疾病,當多年前以胞磷膽鹼的形式出現時,便開始研究劑量的多寡、藥物的給予方式和適合治療的病患。有關於胞磷膽鹼的研究包括觀察期長短、病症的嚴重程度和評估試驗的方法學都存在有異質性,儘管因為其本身的複雜特性而對於其功效不甚確定,CDPcholine在歐洲國家仍是一種常被用來治療腦血管疾病的處方藥物,也因此需要進行本研究的檢視,因為其會影響CNS的腎上腺素和多巴胺的活性,CDPcholine也被用來作為治療帕金森氏症的輔助藥物。

目標

本研究的主要目的在於評估CDPcholine對於老年人慢性腦部疾病中有關治療認知、情緒和行為能力的功效。

搜尋策略

2004年4月22日針對最新更新的Specialized Register of the Cochrane Dementia and Cognitive Improvement Group資料庫進行檢索,檢索時的關鍵字包括有「CDPcholine、CDP、 citicoline、 cytidine diphosphate choline 或 diphosphocholine」,這個資料庫包括有主要健康照護資料庫和許多正在進行中的試驗資料庫內的資料,該資料庫也會進行定期的更新。

選擇標準

所有相關的無干擾、雙盲、安慰劑對照的隨機試驗,只要針對CDPcholine對於慢性腦部疾病的認知障礙進行治療進行功效比較的試驗都可能被納入本研究中。

資料收集與分析

有2個審閱者分別審閱被納入的試驗,進行資料萃取和在可能且適當的狀況下集中資料進行分析,整體OR值(95%信心區間)和平均差異(95%信心區間)都會被進行評估。試驗中並沒有取得可用的意圖治療試驗進行分析。

主要結論

有14個試驗被納入本研究中,有些被納入的試驗並沒有呈現數字化的數據以進行分析。有關被納入試驗的患者存有許多變異,這包括觀察的時間,疾病的種類和嚴重程度,病患可以從老年人合併輕微記憶抱怨到血管性認知功能障礙(輕度至中度)到血管性失智症或是老年性失智症(輕度至中度)。有7個被納入的試驗針對患者的觀察長達20至30年,有一個試驗僅進行6星期,有4個試驗的觀察時間為2和3個月,有個試驗持續觀察治療狀況3個月以上,而另一個試驗則延長觀察時間至12個月,這些試驗在劑量、發病處理、納入試驗標準和治療成果評估上都存在有異質性,治療成果是以注意力、記憶力測試、行為評分量表、整體臨床評量和耐受性進行評估,並沒有證據顯示使用CDPcholine對於注意力有所幫助,但是有證據可以說明CDPcholine對於記憶和行為能力有所幫助。患者對藥物具有良好的耐受性。

作者結論

有一些有關CDPcholine的試驗證據顯示CDPcholine對於短期至長期的記憶力和行為能力有所幫助。由整體評量所得到正面證據較為強烈,但是這個結果仍因為試驗時間的長短而有所限制。未來有關CDPcholine的試驗應該著眼於比較長期的評估,並收入符合現代可接受、標準的診斷準則,特別是輕度血管型認知障礙(VaMCI)和血管型失智症。

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

有些與CDPcholine有關的證據支持使用CDPcholine治療老年人合併認知功能障礙以及患有慢性大腦疾病患者,在記憶力及行為能力方面最少在短期及中期上是有所助益。患有慢性腦血管疾病的患者其認知能力下降可能不會與阿茲海默失智症一樣對於抗失智症藥物的治療產生作用。有一些證據顯示CDPcholine可以對這些患者的記憶力和行為產生適度且持續性的改善,然而這些發現受限於只有短期臨床對照觀察,因為除了一個試驗外其他的試驗時間都沒有超過3個月。醫師對於這些患者進行主觀的評估皆出現正面且一致的結果,並且在不同試驗之間都沒有注意到相關的副作用。

Plain language summary

Some evidence that CDP-choline has a positive effect on memory and behaviour in at least the short/medium term in elderly people with cognitive deficits associated with chronic cerebral disorders of the brain

Patients with cognitive deficits associated with chronic cerebrovascular disorders may not respond to anti-dementia treatments in the same manner as can be observed in cases of Alzheimer's dementia. There is some evidence that CDP-choline provides modest but consistent improvement of memory and behaviour in these patients. These findings, however, are limited by the relatively short-term of clinical controlled observations which in all studies but one lasted for no more than three months. Subjective evaluations of these patients as given by their doctors were consistently positive and no noticeable side effects were evidenced in the various studies over the years.