Neurotrophins and Neurotrophic Therapy (Based on the Cerebrolysin Model) in the Treatment of Elderly Patients with Cognitive Disorders and Depression. Part 2

Background: сognitive impairment and late depression, along with dementia, are the most common mental disorders in elderly and senile patients. Currently, more and more attention is being paid to preventive therapeutic approaches in the treatment of these conditions and to the study of drugs with multimodal neuroprotective and neurotrophic properties that contribute to the strengthening of the so-called endogenous system of protection and recovery of the brain, which is a kind of barrier to the incipient neurodegeneration. Objective: to present a review of domestic and foreign modern studies devoted to the study of the multimodal effects of the drug cerebrolysin, which has neurotrophin-like properties, and the results of its use in the treatment of cognitive disorders that do not reach the degree of dementia, as well as late depression. Material and methods: using the keywords “late age, mild cognitive disorders, depression, MCI syndrome, therapy, cerebrolysin”, we searched for scientifi c articles in the MEDLINE and PubMed databases for the period 2000–2020. Conclusion: the data presented in the review showed that cerebrolysin, acting as a multi-target drug, affects multiple molecular mechanisms of the pathogenesis of pre-dementia cognitive disorders and late-age depression. The drug detects a neurotrophin-like effect, improves the processes of neuroplasticity and can help enhance the protection and restoration of the brain under various pathological infl uences. Neurobiological studies and the results of a pilot prospective study indicate the preventive potential of cerebrolysin in preventing the development or slowing the progression of the neurodegenerative process of Alzheimer’s type. In the studies presented in the review, the ability of cerebrolysin to increase the effectiveness of modern antidepressant therapy (with second-generation drugs) in the elderly has been shown, presumably by potentiating the therapeutic effect of antidepressants or by improving their tolerability, which makes it possible to safely use higher doses of antidepressants in the elderly and senile patients.

Neurotrophins and Neurotrophic Therapy (Based on the Cerebrolysin Model) in the Treatment of Elderly Patients with Cognitive Disorders and Depression. Part 1

Background: Alzheimer’s disease (AD) is the most common neurocognitive disorder and a global health problem. The prevalence of AD is increasing dramatically, and will double in two decades to reach 100 million cases worldwide. Therefore, the development of disease-modifying therapies that can delay or even prevent the onset and progression of AD has become a global priority.Objective: to present a review of domestic and foreign modern studies covering the pathogenesis of AD and disease-modifying therapy.Material and methods: the keywords “Alzheimer’s disease, late age, mild cognitive impairment, depression, therapy, cerebrolysin, effectiveness” were used to search for scientifi c articles in MEDLINE and PUBMED databases for the period 1980–2020.Results and conclusions: since the pathophysiology of AD is multifactorial, it is not surprising that all attempts to change the course of the disease with drugs aimed at a single therapeutic goal were unsuccessful. Thus, combined multimodal therapy using several drugs with a single mechanism of action or multi-purpose drugs seems to be the most promising strategy for both effective therapy of AD and its prevention. Cerebrolysin, acting as a multimodal peptidergic drug with a proven neurotrophic effect, has not only an immediate therapeutic effect on AD, which may refl ect its potential benefi t for modifying the course of the disease. Numerous clinical trials have shown that cerebrolysin is safe and effective in the treatment of AD, and can also enhance and prolong the effectiveness of cholinergic drugs, especially in patients with moderate AD. In this review, we summarize the achievements in the study of the therapeutic signifi cance of the drug and its effect on the pathogenesis of AD, paying special attention to the mechanisms of neurotrophic action. The review presents the results of both preclinical and clinical studies of cerebrolysin in the treatment of AD and pre-dementia cognitive disorders, as well as late depression.

IMMUNOLOGICAL MARKERS OF LONG-TERM EFFECTS OF TREATMENT IN PATIENTS WITH MILD COGNITIVE IMPAIRMENT

The goal of this research was to study the clinical efficacy of course-based neurotrophic therapy in mild cognitive impairment (MCI) and the effect of therapy on immune parameters in patients, and to assess the prognostic value of the dynamics of immune parameters during the year after treatment. 20 patients with MCI receiving intravenous Cerebrolysin (20 infusions of 30 ml with increasing dose during the first four days) were examined. Neuropsychological and immunological examination was carried out immediately before the study, after 3 months., 6 months and after 1 year after the end of treatment. It was found that after therapy, patients had a long-term decrease in the severity of systemic inflammatory response, and that marked signs of systemic inflammation at the beginning of follow-up combined with a persistent decrease in the level of immunoglobulin G in dynamics were prognostic markers of MCI progression. In conclusion, it wass shown that neurotrophic therapy has a good clinical effect and has a favorable immunomodulatory effect in aMCI, and the relationship between the dynamics of humoral immunity and systemic inflammation and the risk of progression of cognitive impairment in patients within 1 year after therapy was established.