Differential effect of CDP-choline on brain cytosolic choline levels in younger and older subjects as measured by proton magnetic resonance spectroscopy

Phosphatidylcholine (PtdCho), which is essential for membrane integrity and repair, is reduced in brain cell membranes with age. Evidence from both animal and in vitro studies indicates that cytidine 5′ diphosphate choline (CDP-choline) can increase the synthesis of PtdCho; however, the effect of CDP-choline on brain choline metabolism has not previously been studied in human subjects. In this study, in vivo proton magnetic resonance spectroscopy (¹H-MRS) was used to measure brain levels of cytosolic, cholinecontaining compounds before and after single oral doses of CDP-choline. Three hours after dosing, plasma choline increased similarly in younger (mean age 25 years) and older subjects (mean age 59 years). However, while the choline resonance in brain increased 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 previously observed decrease in brain choline uptake, but not cytidine uptake, in older subjects. Additional intracellular cytidine following the administration of CDP-choline should lead to the increased incorporation 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 cytidine moiety of CDP-choline stimulates phosphatidylcholine synthesis in human brain cell membranes in older subjects.