Chronic Citicoline Increases Phosphodiesters in the Brains of Healthy Older Subjects: An In Vivo Phosphorus Magnetic Resonance Spectroscopy Study

Author: Babb SM. Wald LL. Cohen BM. Villafuerte RA. Gruber SA. Yurgelun-Todd DA. Renshaw PF.
Institution: Consolidated Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA.
Source: Psychopharmacology. 161(3):248-54, 2002 May.


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 ((31)P-MRS) before and after citicoline treatment.

METHODS: All subjects took 500 mg citicoline once orally each day for 6 weeks, and then took either citicoline or placebo once orally per day for a second 6-week period. Subjects underwent a (31)P-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.