Álvarez XA, Laredo M, Corzo D, Fernández-Novoa L, Mouzo R, Perea JE, et al.
Citicoline improves memory performance in elderly subjects.
Meth Find Exp Clin Pharmacol 1997; 19:201-10.

   
Abstract
Citicoline is a choline donor involved in the biosynthesis of brain phospholipids and acetylcholine extensively used in the treatment of neurodegenerative diseases. In this study we investigated the effects of the oral administration of citicoline alone (C1000:1000 mg/day; C500:500 mg/day) or in combination with nimodipine (C +NI:300 + 90 mg/day) during 4 weeks on memory performance in elderly subjects with memory deficits and without dementia (N = 24; age = 66.12 +/- 10.78 years; MMS score = 31.69 +/- 2.76).

  
Results indicated that citicoline in comparison with placebo improves memory in free recall tasks, but not in recognition tests. A significant improvement in word recall (5.17 +/- 1.1 vs. 3.95 +/- 1.2 omissions; p < 0.005), immediate object recall (6.5 +/- 1.6 vs. 5.5 +/- 1.2 omission; p < 0.05) and delayed object recall (8.5 +/- 2.1 vs. 6.7 +/- 2.4 omissions; p < 0.005) was observed after citicoline treatment. Similar results were found in the three subgroups of treatment (8 subjects per group), suggesting that citicoline possesses memory-enhancing activity at doses of 300-1000 mg/day. A decrease in systolic blood pressure and minor changes in lymphocyte cell counting were also observed in old subjects after receiving citicoline. These effects are consistent with the vasoregulatory and neuroimmune actions of citicoline and suggest that this compound may improve memory by acting on mechanisms of brain neurotropism and cerebrovascular regulation. According to the present results, showing that citicoline improves memory performance in elderly subjects, we concluded that this molecule is suitable for the treatment of memory deficits in old people.
    

Psychopharmacology (2002) 161:248–254
DOI 10.1007/s00213-002-1045-y
 
S.M. Babb • L.L. Wald • B.M. Cohen
R.A. Villafuerte • S.A. Gruber • D.A. Yurgelun-Todd
P.F. Renshaw
 
Chronic citicoline increases phosphodiesters in the brains of healthy older subjects: an in vivo phosphorus magnetic resonance spectroscopy study
 
Abstract Rationale:
Phosphatidylcholine (PtdCho) in brain cell membranes decreases with age. Evidence from both animal and in vitro studies indicates that CDP-choline (citicoline) administration may increase phosphatidylcholine (PtdCho) synthesis and might reverse PtdCho loss. Objectives: We investigated whether oral citicoline can increase PtdCho synthesis in the brains of older subjects by measuring levels of phosphorus-containing metabolites using proton-decoupled phosphorus magnetic resonance spectroscopy (31P-MRS) before and after citicoline treatment. Methods: All subjects took 500 mg citicoline once orally each day for 6 weeks, then took either citicoline or placebo once orally per day for a second 6-week period. Subjects underwent a 31P-MRS scan at baseline and following 6 and 12 weeks of treatment.

  
Results:
Treatment with citicoline for 6 weeks was associated with a 7.3% increase from baseline levels in brain phosphodiesters (P=0.008), including an 11.6% increase in glycerophosphoethanolamine (P=0.002) and a 5.1% increase in glycerophosphocholine (P=0.137). Subjects who continued to take citicoline for the second 6-week period did not show significant additional increases in the levels of these metabolites. No changes were seen in other phosphorus-containing metabolites. There was a correlation between improvement on the California Verbal Learning Test and increase in phosphodiesters.

  
Conclusions:
The increases in phosphodiesters seen in this study indicate that phospholipid synthesis and turnover were stimulated by 6 weeks of oral citicoline. These results in humans support previous in vitro and animal studies and suggest that the administration of oral citicoline may be of use in reversing age-related changes in the brain.

 
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