Double-blind placebo-controlled study with citicoline in APOE genotyped Alzheimer's disease patients. Effects on cognitive performance, brain bioelectrical activity and cerebral perfusion

Cytidine 5'-diphosphocholine (citicoline) is a an endogenous intermediate i n the biosynthesis of structural membrane phospholipids and brain acetylcho line. Citicoline has been extensively used for the treatment of neurodegene rative disorders associated with head trauma, stroke brain aging, cerebrova scular pathology and Alzheimer's disease. In this study we have investigate d the efficacy and safety of the treatment with citicoline versus placebo i n patients with Alzheimer disease. Thirty patients (age = 73.0 +/- 8.5 year s; range =: 57-87 years) with mild to moderate senile dementia (GDS: stages 3-6) of the Alzheimer type were included in a double-blind; randomized and placebo-controlled clinical trial. After a 2-week period of drug washout, patients were treated with i) placebo (n = 17; age = 73 +/- 5 years) or ii) 1,000 mg/day of citicoline (n = 13; age = 76 +/- 9 years)for 12 weeks (84 days). Examinations were done at baseline (T0) and after the 12 weeks of tr eatment (T12). As compared to placebo, citicoline improved cognitive perfor mance in Alzheimer's disease patients with APOE E4 (ADAS: difference betwee n groups = -3.2 +/- 1.8 scores p < 0.05; ADAS-cog: difference between group s = -2.3 +/- 1.5, ns); and this improvement on cognition was more pronounce d (ADAS, p < 0.01; ADAS-cog: difference between groups = -2.8 +/- 1.3, p < 0.06) in patients with mild dementia (GDS < 5). Citicoline also increased c erebral blood flow velocities iii comparison with placebo (p < 0.05) when t ranscranial Doppler recordings from both hemispheres were considered togeth er; as well as diastolic velocity in the left middle cerebral artery (p < 0 .05). Patients treated with citicoline showed an increase in the percentage of brain bioelectrical activity of alpha (occipital electrodes) and theta type (left side electrodes), accompanied by a decrease in relative delta ac tivity particularly marked in the left temporal lobe. Significant differenc es with respect to placebo (p < 0.05) were observed for theta activity in s everal fronto-parieto-temporal electrodes of the left hemisphere. Treatment with citicoline tended to reduce serum IL-1 beta levels mainly after 4 wee ks of administration, with no modified blood histamine content. In addition , neither adverse side effects nor alterations in biological and hematologi cal parameters were induced by citicoline. The present data indicate that c iticoline (1,000 mg/day) is well tolerated and improves cognitive performan ce, cerebral blood perfusion and the brain bioelectrical activity pattern i n AD patients. According to our results, it seems that citicoline might be a useful treatment in Alzheimer's disease, and that the efficacy of this co mpound is greater in patients with mild mental deterioration and/or bearing the epsilon 4 allele of the APOE. (C) 1999 Prous Science. All rights reser ved.