Cytidine 5'-diphosphocholine (citicoline) is an endogenous intermediate in the biosynthesis of structural membrane phospholipids and brain acetylcholine. Citicoline is widely used in the treatment of neurodegenerative disorders associated with head injury, stroke, brain aging, cerebrovascular pathology, and Alzheimer's disease. In this study, we investigated the efficacy and safety of treatment with citicoline and placebo in patients with Alzheimer's disease. Thirty patients (age = 73.0 +/- 8.5 years; range = 57-87 years) with mild to moderate senile dementia of the Alzheimer's type (GDS: stages 3-6) were enrolled in a double-blind, randomized, placebo-controlled clinical trial. After a 2-week washout period, patients were treated with either i) placebo (n = 17; age = 73 +/- 5 years) or ii) 1000 mg/day citicoline (n = 13; age = 76 +/- 9 years) for 12 weeks (84 days). The studies were performed at baseline (T0) and after 12 weeks of treatment (T12). Compared with placebo, citicoline improved cognitive performance in patients with Alzheimer's disease and APOE E4 (ADAS: between-group difference = -3.2 +/- 1.8 points, p < 0.05; ADAS-cog: between-group difference = -2.3 +/- 1.5, ns); and this cognitive improvement was more pronounced (ADAS, p < 0.01; ADAS-cog: between-group difference = -2.8 +/- 1.3, p < 0.06) in patients with mild dementia (GDS < 5). Citicoline also increased cerebral blood flow velocity compared to placebo (p < 0.05) when transcranial Doppler recordings from both hemispheres were considered together, as well as diastolic velocity of the left middle cerebral artery (p < 0.05). Patients treated with citicoline showed a percentage increase in brain bioelectrical activity of alpha (occipital electrodes) and theta type (left electrodes), accompanied by a decrease in relative delta activity, especially in the left temporal lobe. Significant differences in theta activity were observed in several fronto-parieto-temporal electrodes of the left hemisphere compared to placebo (p < 0.05). Citicoline treatment generally reduced serum IL-1 beta levels, especially after 4 weeks of administration, while blood histamine levels were unchanged. Furthermore, citicoline did not induce any adverse side effects or changes in biological and hematological parameters. The current data show that citicoline (1000 mg/day) is well tolerated and improves cognitive performance, cerebral blood perfusion, and brain bioelectrical activity patterns in AD patients. Our results suggest that citicoline may be a useful treatment in Alzheimer's disease, and that the efficacy of this compound is greater in patients with mild mental decline and/or carrying the APOE epsilon 4 allele.
Source: https://pubmed.ncbi.nlm.nih.gov/10669911/
