Effects of acute CDP-choline treatment on resting state brain oscillations in healthy volunteers.

CDP-choline (cytidine-5'-diphosphocholine) is a phospholipid used to treat cognitive disorders, presumably repairing and maintaining brain cell membranes. Additional mechanisms may include enhanced cholinergic neurotransmission as the α7 nicotinic receptor actions of choline and increased acetylcholine synthesis accompanying CDP-choline administration may modulate brain oscillations underlying cognitive processes. This study utilizes electroencephalographic (EEG) recordings in healthy volunteers to evaluate CDP-choline induction of an oscillatory response profile associated with nicotinic stimulation. Resting state EEG was acquired in 24 male volunteers administered low (500mg) and moderate (1000mg) doses of CDP-choline in a randomized placebo-controlled, crossover trial. Consistent with nicotinic agonist treatment, spectral analysis showed dose-dependent reductions in delta and increases in alpha oscillations, which were also accompanied by decreases in beta and gamma oscillatory activity. These findings support the posit that CDP-choline cognitive enhancement involves multiple mechanisms including facilitated nicotinic cholinergic action.

Neurocognitive effects of acute choline supplementation in low, medium and high performer healthy volunteers.

Novel pharmacological treatments targeting alpha 7 nicotinic acetylcholine receptor (α7 nAChR) hypofunction in schizophrenia have shown mixed success in ameliorating cognitive impairments associated with this disorder. Choline, a selective agonist at α7 receptors is increased with oral administration of cytidine 5'-diphosphocholine (CDP-choline), the cognitive effects of which were assessed in healthy volunteers. Using the CogState test battery, behavioral performance in schizophrenia-relevant cognitive domains was assessed in 24 male participants following a single low (500mg) and moderate (1000mg) dose of CDP-choline. Relative to placebo, CDP-choline improved processing speed, working memory, verbal learning, verbal memory, and executive function in low baseline performers, while exerting no effects in medium baseline performers, and diminishing cognition in high baseline performers. Dose effects varied with cognitive domain but were evident with both the 500mg and 1000mg doses. These preliminary findings of cognitive enhancement in relatively impaired performers are consistent with the α7 receptor mechanism and support further trials with CDP-choline as a potential pro-cognitive strategy for cognitive impairment in schizophrenia.

CDP-choline: effects of the procholine supplement on sensory gating and executive function in healthy volunteers stratified for low, medium and high P50 suppression.

Diminished auditory sensory gating and associated neurocognitive deficits in schizophrenia have been linked to altered expression and function of the alpha-7 nicotinic acetycholinergic receptor (α7 nAChR), the targeting of which may have treatment potential. Choline is a selective α7 nAChR agonist and the aim of this study was to determine whether cytidine 5'-diphosphocholine (CDP-choline), or citicoline, a dietary source of choline, increases sensory gating and cognition in healthy volunteers stratified for gating level. In a randomized, placebo-controlled, double-blind design involving acute administration of low, moderate doses (500 mg, 1000 mg) of CDP-choline, 24 healthy volunteers were assessed for auditory gating as indexed by suppression of the P50 event-related potential (ERP) in a paired-stimulus (S1, S2) paradigm, and for executive function as measured by the Groton Maze Learning Task (GMLT) of the CogState Schizophrenia Battery. CDP-choline improved gating (1000 mg) and suppression of the S2 P50 response (500 mg, 1000 mg), with the effects being selective for individuals with low gating (suppression) levels. Tentative support was also shown for increased GMLT performance (500 mg) in low suppressors. These preliminary findings with CDP-choline in a healthy, schizophrenia-like surrogate sample are consistent with a α7 nAChR mechanism and support further trials with choline as a pro-cognitive strategy.