CDP-Choline Preserves Memory
in Aging Brains
Or, How to Extract the Truth From a Fruitcake
In an ideal world, the scientists working on a particular problem would design and execute studies that were not only internally flawless but beautifully coordinated with each other so as to create a seamless fabric of perfectly complementary results. The data from any one experiment could then be easily compared with those from any other experiment, the two sets of data combining synergistically and yielding a pellucid picture greater than the sum of its parts.
Wake up! It was just a dream! Such a dream might well have visited the authors of a recently published meta-analysis: a comprehensive, critical, comparative analysis of previously published studies selected according to rigorous standards of scientific quality. The topic of their investigation was the efficacy of CDP-choline, a natural biochemical compound that has been in widespread use in Europe to treat cognitive, emotional, and behavioral deficits associated with chronic cerebral disorders in the elderly. In other words, the reviewers were asking: What is the weight of the best scientific evidence for CDP-choline in this regard?
HOW GOOD IS CDP-CHOLINE?
Let us cut to the chase, and then fill in the background. The meta-analysis revealed the following:1
- There was no significant evidence of a beneficial effect of CDP-choline on attention.
- There were modest but significant beneficial effects of CDP-choline on memory function and behavior, at least in the short-term duration of the studies in question.
- In terms of clinical global impression, or how the patients felt, overall, there was a significant improvement in those who received CDP-choline vs. those who received placebo.
- The CDP-choline was well tolerated, with few adverse side effects and no problems of any significance.
The reviewers concluded that, "There is some evidence that CDP-choline has a positive effect on memory and behavior in at least the short term. The evidence of benefit from global impression is stronger, but is still limited by the duration of the studies. There is evidence that the effect of treatment is more homogeneous for patients with cognitive impairment secondary to cerebrovascular disorder. Other studies with a more appropriate length of treatment are recommended owing to the chronic and irreversible nature of the disorders for which this treatment is indicated."
To date there have been nearly 1000 papers published on CDP-choline, and the studies seem to be trending toward age-related cognitive decline (from which we all suffer) rather than more clearly defined degenerative diseases such as Alzheimer's. Two of the significant categories for CDP-choline use are neuroprotection and stabilization of cell membranes,2 which are good ideas for those of us wanting to be around for some time. As well, CDP-choline has been successfully used to improve retinal and cortical responses in glaucoma.3
In a study published after the period of the meta-analysis, CDP-choline was given in amounts of 500-1000 mg/day for a period of 4 weeks to 24 elderly (mean age of 66 years) subjects with memory deficits and without dementia.4 In comparison with placebo, CDP-choline improved memory in free recall tasks but not in recognition tests. A significant improvement in word recall, immediate object recall, and delayed object recall was observed after the treatment.
The results suggest that CDP-choline possesses memory-enhancing activity at doses of 500-1000 mg/day. Also noted were decreases in systolic blood pressure and minor changes in lymphocyte counts. Thus CDP-choline appears to be a vasoregulator and neuroimmune enhancer. Its memory-improving mechanisms probably involve brain neurotropism and cerebrovascular regulation.
WHAT CDP-CHOLINE IS AND DOES
CDP-choline is shorthand for cytidine-5'-diphosphocholine (also known as citicoline), a chemical intermediate in the formation of a class of compounds called phosphatidylcholines. These are also known as lecithins, and they are found in the cell membranes of all organs, but especially brain and nerve tissue. Under conditions of cerebral ischemia (insufficient blood supply to the brain), lecithins are degraded to free fatty acids and unstable entities called free radicals, which are highly toxic. It is believed from animal studies that CDP-choline may protect cell membranes by accelerating the resynthesis of lecithins. It may also slow the course of ischemic cell damage by suppressing the degradation of lecithins.
Despite some uncertainties about its efficacy, CDP-choline has long been popular in several European countries for the treatment of cognitive impairment, especially in conjunction with chronic cerebrovascular disease. It has also been used with l-dopa in the treatment of Parkinson's disease.
Now let us look at how the meta-analysis was done.
OF INCONSIDERATE AUTHORS AND OTHER THINGS
In order to get as comprehensive and fair a picture as possible of the clinical efficacy of CDP-choline, the reviewers compiled every known study from the last three decades on the use of this compound in elderly patients with chronic cerebral conditions associated with cognitive impairment. They examined the studies according to exacting standards of scientific integrity and excluded those that did not make the grade. Among the criteria for inclusion in the meta-analysis were that the studies had to have been randomized, placebo-controlled, and double-blind, and they had to have been focused exclusively on the kind of cerebral disorders described above.
When the smoke cleared, 11 of the 73 candidate studies were accepted, and the other 62 were rejected. The successful 11 came primarily from continental Europe and dated from 1978 to 1996. The average age of the patients involved was over 60 years in all the studies, and many of them included patients who were over 70. Most of the studies were performed with a CDP-choline dose of 1000 mg per day, administered parenterally (i.e., other than through the gastrointestinal tract), for periods ranging from three weeks to three months.
Do not let that neat little summary deceive you into thinking that evaluating the results of these 11 studies was a piece of cake - a meta-analysis never is. The problem is that the authors of all those studies were inconsiderate enough not to inhabit the ideal world we started out with. No two studies did things the same way - they never do. There were variations in many aspects of the experimental protocols that made the job of the reviewers frustratingly difficult.
If you're comparing apples and oranges and pears and plums, and the occasional banana (a piece of fruitcake is what it is), it takes great skill, and sophisticated statistical methods, to reduce all the data to forms that are meaningfully comparable. It's a dirty, rotten job, but fortunately for science and for all of us, there are some who are willing and able to do it.
Ultimately, the findings of the meta-analysis make it clear that CDP-choline is good for aging brains. Thank you, gentlemen.
- Fioravanti M, Yanagi M. Cytidinediphosphocholine (CDP choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly (Cochrane Review). In The Cochrane Library, Issue 2, 2000. Oxford: Update Software.
- Davalos A. Neuroprotective agents. Neurologia 1999;14 Suppl 4:49-53.
- Parisi V, Manni G, Colacino G, Bucci MG. Cytidine-5'-diphosphocholine (citicoline) improves retinal and cortical responses in patients with glaucoma. Ophthalmology 1999 Jun;106(6):1126-34.
- Alvarez XA, Laredo M, Corzo D, Fernandez-Novoa L, Mouzo R, Perea JE, Daniele D, Cacabelos R. Citicoline improves memory performance in elderly subjects. Methods Find Exp Clin Pharmacol 1997 Apr;19(3):201-10.