DIFFERENTIAL EFFECT OF CDP-CHOLINE ON BRAIN CYTOSOLIC CHOLINE LEVELS IN YOUNGER AND OLDER SUBJECTS AS MEASURED BY PROTON MAGNETIC-RESONANCESPECTROSCOPY

Phosphatidylcholine (PtdCho), which is essential for membrane integrit y and repair, is reduced in brain cell membranes with age. Evidence fr om both animal and in vitro studies indicates that cytidine 5' diphosp hate choline (CDP-choline) can increase the synthesis of PtdCho; howev er, the effect of CDP-choline on brain choline metabolism has not prev iously been studied in human subjects. In this study, in vivo proton m agnetic resonance spectroscopy (H-1-MRS) was used to measure brain lev els of cytosolic, choline-containing compounds before and after single oral doses of CDP-choline. Three hours after dosing, plasma choline i ncreased similarly in younger (mean age 25 years) and older subjects ( mean age 59 years). However, while the choline resonance in brain incr eased by 18% on average in younger subjects, it decreased by almost 6% in older subjects (P = 0.028), These results may be explained by a pr eviously observed decrease in brain choline uptake, but not cytidine u ptake, in older Subjects. Additional intracellular cytidine following the administration of CDP-choline should lead to the increased incorpo ration of choline already present in brain into membrane PtdCho, which is not MRS-visible, consequently lowering the brain choline resonance below that of pre-treatment values. These results suggest that the cy tidine moiety of CDP-choline stimulates phosphatidylcholine synthesis in human brain cell membranes in older subjects.