Therapeutic effects of CDP-choline in Alzheimer's disease. Cognition, brain mapping, cerebrovascular hemodynamics, and immune factors.

Cacabelos R, Caamano J, Gomez MJ, 
Fernandez-Novoa L, Franco-Maside A, Alvarez XA.

Institute for CNS Disorders, 
Basic and Clinical Neurosciences Research Center, 
La Coruna, Spain.
Ann N Y Acad Sci 1996 Jan 17;777:399-403


CDP-choline was given to patients with Alzheimer's disease (AD) at a daily dose of 1000 mg/day p.o. for one month. This compound slightly improved mental performance, tended to reduce theta activity in fronto-temporal regions, increasing alpha power in occipital areas, and enhanced cerebrovascular perfusion by increasing blood flow velocity and reducing pulsatility and resistance indexes.  In addition, CDP-choline diminished histamine and interleukin-1 levels in blood and serum, respectively, and increased plasma TNF.

Methods Find Exp Clin Pharmacol 1994 Oct;16(8):597-607
Brain mapping activity and mental performance after chronic treatment with CDP-choline in Alzheimer's disease.

Franco-Maside A, Caamano J, Gomez MJ, Cacabelos R. 
Department of Digital Diagnosis, 
Basic and Clinical Neurosciences Research Center,
La Coruna, Spain.

CDP-choline participates in brain phospholipid metabolism and acts as an endogenous intermediate in a biosynthetic pathway incorporating free choline into phosphatidylcholine and choline plasmalogens in several tissues, including the central nervous system (CNS). In patients with chronic cerebrovascular disorders, CDP-choline reduces the slow delta frequencies and increases alpha activity in spectral electroencephalogram analysis. We have studied the effect of CDP-choline (cytidine-S-diphosphate-choline; 1000 mg/day x 30 days, p.o.) on brain electrical activity mapping and mental performance in 19 Alzheimer's disease (AD) patients (10 males/9 females; age: 66.21 +/- 1.48 years; Mini-Mental State Examination (MMSE): 26.55 +/- 1.22, Spanish version max. score 35). EEG was registered from 19 electrodes placed according to the 10-20 system and digitalized online. Artefact-free 2-s periods were visually selected, submitted to a frequency analysis and averaged across periods.  CDP-choline significantly decreased spectral amplitude in the theta band in F4, F8, and T4 electrodes, and did not modify relative power parameters in any of the frequency bands (delta, theta, alpha, beta) as compared to basal recordings.  In patients with late-onset AD (LOAD; N = 6; age: 73.5 +/- 1.34 years; MMSE: 28.75 +/- 2.33), CDP-choline tended to increase relative alpha power in O1 and O2 electrodes. No changes were found in early-onset AD patients (EOAD; N = 13; age: 62.85 +/- 1.21 years; MMSE: 25.54 +/- 1.4).  We detected a significant improvement in mental performance after 1 month of treatment with CDP-choline in patients with early-onset AD in whom brain electrical activity data correlated with cognitive parameters.  It is likely that the bioelectrical changes induced by CDP-choline in AD are the result of its immunogenic and/or neurotrophic activity in the vicinity of the vascular microenvironment.

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