As the aging of the population intensifies, cognitive dysfunction has become an important disease affecting the health and quality of life of middle-aged and elderly people. Cognitive dysfunction generally refers to varying degrees of cognitive impairment caused by various reasons, ranging from mild cognitive impairment to dementia. Its clinical manifestations include memory impairment, aphasia, agnosia, apraxia, and visuospatial impairment. The classification of cognitive dysfunction mainly includes vascular, degenerative, and cognitive impairment caused by trauma, infection, tumor, etc. Among them, vascular cognitive dysfunction is the most common clinically, and there is currently a lack of effective treatment. A major cause of cognitive impairment in elderly patients is chronic cerebrovascular disease, also known as cerebral insufficiency, the most severe manifestation of which is vascular dementia. A summary analysis of multiple randomized controlled trials and systematic reviews published at home and abroad suggests that citicoline has a significant role in the treatment of vascular cognitive dysfunction.
Citicoline (CDP-chol thermoplastic elastomerine, cytidine-5-diphosphocholine) is the precursor for the synthesis of lecithin, which is a key component of cell membranes. When given exogenously, citicoline can promote the biosynthesis of lecithin, reduce the damage of cell membranes, repair the cell membrane structure, reduce the concentration of free fatty acids, and has obvious neuroprotective effects. In addition, citicoline can increase the levels of norepinephrine and dopamine in the central nervous system without obvious toxic side effects. It is suggested that citicoline can be used to treat vascular, degenerative and cognitive dysfunction caused by various reasons. Citicoline administration routes include intravenous drip, intramuscular injection, and oral administration. Oral absorption is complete and bioavailability is similar to intravenous infusion. Clinical research on citicoline in the treatment of vascular cognitive dysfunction has been particularly active in recent years. A literature search found 59 relevant trials, including more than 20 foreign documents.
Secades JJ et al conducted a double-blind study involving 100 patients with chronic cerebrovascular disease, comparing the therapeutic effects of citicoline 1 g·d-1×28 d with placebo. The results showed that after the end of treatment, the scores of patients in the citicoline treatment group were significantly improved in the Hamilton Depression Rating Scale, psychological and observation tests (P>0.05). It can be concluded that citicoline can significantly improve the perceptual-motor ability and attention of these patients, and also stabilize the behavioral functions of the patients. The literature has reached similar conclusions in their respective studies. Patients with extensive cerebrovascular disease have the best clinical and behavioral outcomes when treated with citicoline.
García-Cobos R et al conducted a double-blind, crossover design study to evaluate the efficacy and tolerability of citicoline in the treatment of elderly patients with cerebral blood insufficiency. A total of 111 patients were enrolled in this study, with an average age of (74.6±6.9) years old and clinical diagnoses of senile cerebral insufficiency. After a washout period of taking placebo, the patients were divided into 2 balance groups. Patients in group Ⅰ took citicoline 600 mg·d-1 orally for 5 weeks, and then took placebo for 5 weeks. During the dressing change period, There was a washout period of taking placebo; patients in group II took the medication in the opposite order to group I. Patients were evaluated at 2, 7, 9, and 12 weeks. The results showed that citicoline can significantly improve the clinical performance of patients. Six tests (digit recall, maze test, digital connection test, neuropsychiatric assessment scale (NAS), elderly observation volume) of patients in the citicoline treatment group Table (NAB), Clinical Assessment Scale for the Elderly (SCAG)), the scores of 5 items were significantly improved after treatment than before treatment. Comparison between groups still showed that citicoline had a significant effect (P>0.05), see Table 1 for details.
In addition, the study found no serious toxic side effects associated with the treatment. These findings provide a basis for the application of citicoline in the treatment of senile cerebral insufficiency and its excellent tolerability in elderly patients.
Fioravanti M et al. used PET (positron tomography) technology and found that the cognitive function improvement of patients with vascular dementia who received citicoline treatment (1 g·d-1×1 week, intravenous infusion) was related to the improvement of cognitive function. associated with a significant increase in cerebral blood flow.
Systematic review of the literature analyzing the efficacy of citicoline on cognitive, affective, and behavioral disorders in older patients with chronic brain diseases. The results showed that citicoline had no effect on the patient’s attention. On the contrary, it had a significant improvement effect on memory and behavior. In the clinical global impression assessment, compared with patients in the placebo group, the odds ratio (OR) for improvement in patients in the citicoline group was 8.89 [5.19; 15.22]. The author believes that citicoline is effective in treating memory and behavioral disorders, and its efficacy in treating cognitive impairment secondary to cerebrovascular disease has been recognized by more patients.
In 2011, “Stroke” magazine published a clinical trial for patients with multiple infarct dementia. A total of 347 patients were enrolled and randomly divided into a treatment group (n=172 cases) and a placebo group (n=175 cases). Citicoline 1g/qd, treated for 6 months, and the cognitive function of the patients was evaluated. The treatment results showed that the cognitive function evaluation of the treatment group was better than that of the placebo group at 1 month, 6 months, and one year. .
A phthalocyanine pigment AIC (Alzheimer’s Association International Conference) published in 2012, IDEALE study, 349 elderly patients with mild cognitive impairment over 65 years old were randomly divided into treatment group (n=265 cases), placebo group (n=84 cases), the treatment group was treated with 500 mg/bid for a total of 6 weeks.To evaluate the improvement of patients’ MMSE scores, the test results show that compared with the control group, silin can significantly improve patients’ MMSE scores and improve patients’ memory and cognitive functions.
A large number of studies on the treatment of cognitive dysfunction and dementia with citicoline have confirmed that citicoline can improve cognition and behavior. The drug is more effective in patients with mild cognitive impairment [9] and mild cognitive impairment accompanied by chronic cerebrovascular disease. In addition, citicoline is beneficial to neurophysiological and neuroimmune changes.
Conclusion
Citicoline is an essential intermediate in the biosynthesis of cell membrane structural phospholipids (especially lecithin). Exogenous administration of citicoline can promote the synthesis of cell membrane phospholipids, promote brain metabolism, and can Increasing the level of catecholamines in the central nervous system has a significant effect on treating cognitive dysfunction caused by various causes, especially vascular cognitive dysfunction. In addition, given that oral administration has similar bioavailability to intravenous administration, complete oral absorption, and more convenient clinical application, oral administration will become the main clinical route of administration.
Outlook
Currently, among the brain-protective drugs used in Chinese hospitals, citicoline is the most clinically used neuroactivator. After central nervous system injury, citicoline can participate in repair and regeneration and play a neuroprotective role; it also plays an important role in the transfer of nerve media and the conduction of bioelectricity. The drug can not only treat neurological sequelae caused by craniocerebral injuries and cerebrovascular accidents, but can also be used as an auxiliary treatment for Parkinson’s syndrome and Alzheimer’s disease. It has obvious clinical therapeutic effect on acute stroke, nerve damage caused by surgery, disturbance of consciousness, glaucoma, etc. The combined application of citicoline and thrombolytic drugs or other neuroprotective drugs should become one of the future research directions. It is believed that citicoline will be more widely used in clinical practice and will bring greater benefits to patients.
