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

  • Review
  • Intervention


  • 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.

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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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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.


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.




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。




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。










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



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.