You will be provided with the titles and abstracts of a collection of medical RCT reports studying a clinical question -- for instance, the efficacy of an intervention on some medical outcome. Please write a few sentences synthesizing the findings of these reports, which could serve as a conclusion section for a systematic review article. Your response should not include any other text. The RCT reports are below.



Title 1:
Double-blind placebo-controlled study with citicoline in APOE genotyped Alzheimer's disease patients. Effects on cognitive performance, brain bioelectrical activity and cerebral perfusion.
Abstract 1:
Cytidine 5'-diphosphocholine (citicoline) is a an endogenous intermediate in the biosynthesis of structural membrane phospholipids and brain acetylcholine. Citicoline has been extensively used for the treatment of neurodegenerative disorders associated with head trauma, stroke, brain aging, cerebrovascular pathology and Alzheimer's disease. In this study we have investigated the efficacy and safety of the treatment with citicoline versus placebo in patients with Alzheimer disease. Thirty patients (age = 73.0 +/- 8.5 years; 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 treatment (T12). As compared to placebo, citicoline improved cognitive performance in Alzheimer's disease patients with APOE E4 (ADAS: difference between groups = -3.2 +/- 1.8 scores, p < 0.05; ADAS-cog: difference between groups = -2.3 +/- 1.5, ns); and this improvement on cognition was more pronounced (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 cerebral blood flow velocities in comparison with placebo (p < 0.05) when transcranial Doppler recordings from both hemispheres were considered together, 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 activity particularly marked in the left temporal lobe. Significant differences with respect to placebo (p < 0.05) were observed for theta activity in several fronto-parieto-temporal electrodes of the left hemisphere. Treatment with citicoline tended to reduce serum IL-1 beta levels, mainly after 4 weeks of administration, with no modified blood histamine content. In addition, neither adverse side effects nor alterations in biological and hematological parameters were induced by citicoline. The present data indicate that citicoline (1,000 mg/day) is well tolerated and improves cognitive performance, cerebral blood perfusion and the brain bioelectrical activity pattern in 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 compound is greater in patients with mild mental deterioration and/or bearing the epsilon 4 allele of the APOE.


Title 2:
[Double-blind study on the effect of citicholine on the senile brain].
Abstract 2:
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Title 3:
CDP-choline in the treatment of chronic cerebrovasculopathies.
Abstract 3:
Ninety-two patients affected by chronic cerebrovasculopathy were treated with cytidine diphosphate choline (CDP-choline) 1000 mg/day i.m. or with placebo, in a double-blind study. Two cycles of therapy of 4 weeks each were performed, with an interval of 1 week. There were 46 patients in each group with chronic cerebrovascular diseases, and the two groups were comparable as far as mental deterioration was concerned. The following psychometric tests were administered: Toulouse-Piéron (attention to non-verbal stimuli), Randt Memory test (memory), Sandoz Clinical Assessment of Geriatrics (SCAG, measurement of the behavioral and emotional control). The comparison between the two groups revealed significant improvements in the CDP-choline group compared with the placebo group in some of the attention capabilities (decrease in the number of wrong answers at the Toulouse-Piéron test), of the mnemonic capabilities ('General Information' subtest of Randt Memory test) and behavioral capabilities (SCAG 'affective disturbances' score). No side-effects were detected in the CDP-choline group.


Title 4:
Citicoline improves verbal memory in aging.
Abstract 4:
To test the verbal memory of older volunteers given citicoline.
                A randomized, double-blind, placebo-controlled, parallel group design was employed in the initial study. After data analysis, a subgroup was identified whose members had relatively inefficient memories. These subjects were recruited for a second study that used a crossover design. The subjects took either placebo or citicoline, 1000 mg/d, for 3 months in the initial study. In the crossover study, subjects took both placebo and citicoline, 2000 mg/d, each for 2 months.
                The subjects were 47 female and 48 male volunteers 50 to 85 years old. They were screened for dementia, memory disorders, and other neurological problems. Of the subjects with relatively inefficient memories, 32 participated in the crossover study.
                Verbal memory was tested at each study visit using a logical memory passage. Plasma choline concentrations were measured at baseline; at days 30, 60, and 90 in the initial study; and at day 60 of each treatment condition in the crossover study. Plasma choline concentrations and memory scores were analyzed using repeated-measures analysis of variance and covariance, followed by planned comparisons when appropriate.
                In the initial study, citicoline therapy improved delayed recall on logical memory only for the subjects with relatively inefficient memories. In the crossover study, the higher dosage of citicoline was clearly associated with improved immediate and delayed logical memory.
                Citicoline therapy improved verbal memory functioning in older individuals with relatively inefficient memories. Citicoline may prove effective in treating age-related cognitive decline that may be the precursor of dementia.


Title 5:
Long-term citicoline (cytidine diphosphate choline) use in patients with vascular dementia: neuroimaging and neuropsychological outcomes.
Abstract 5:
Cytidine diphosphate choline (citicoline) has been previously shown to have efficacy in reducing the functional impairments associated with acute stroke. Citicoline is thought to have neuroprotective benefits and has been used for the treatment of chronic cerebrovascular disorders, though its effectiveness has not been fully tested. This randomized, double-blind clinical trial was conducted to determine whether daily citicoline treatment improves neurocognitive and neuroimaging outcome over 12 months among patients diagnosed with vascular dementia (VaD).
                30 patients diagnosed with VaD, based upon NINDS-AIREN and DSM-IV criteria, were randomized and treated with either 500 mg of citicoline or placebo twice per day. Patients were assessed at baseline, and at 6, and 12 months on a battery of neurocognitive tests. Neuroimaging measures of total brain volume and subcortical/periventricular hyperintensity (SH) volume on magnetic resonance imaging (MRI) were collected at baseline and the 12-month follow-up.
                The citicoline and placebo treatment groups did not differ in their neuropsychological performance at baseline and the 12-month follow-up. Significant declines in neuropsychological performance were noted, as well as significantly increased SH and reduced total brain volumes on MRI for both groups at the 12-month follow-up.
                The efficacy of long-term citicoline treatment for cognitive impairment and neuropathological decline in those patients already meeting criteria for VaD does not appear to be substantiated by the current study.
                Copyright 2003 S. Karger AG, Basel


Title 6:
[Evaluation of the effects of citicoline in chronic cerebrovascular diseases].
Abstract 6:
A double-blind random block trial was carried out on 58 patients suffering from chronic cerebrovascular diseases as defined by the "Ad Hoc Committee, Paris 1980". The trial was carried out to assess the effects of citicoline on chronic cerebrovascular disease. Particular attention was paid to the selection of the assessment tools (neuropsychological and psychological tests). Citicoline treatment brought about an improvement in awareness and perceptive-motor faculties. This effect can be attributed to an overall drug action on neural energy metabolism.
There was some evidence that CDP-choline has a positive effect on memory and behaviour in at least the short to medium term. The evidence of benefit from global impression was stronger, but is still limited by the duration of the studies. Further research with CDP-choline should focus on longer term studies in subjects who have been diagnosed with currently accepted standardised criteria, especially Vascular Mild Cognitive Impairment (VaMCI) or vascular dementia.