N. D. Selezneva

Prognosis of Progressive Cognitive Deficit in Elderly Patients with Mild Cognitive Impairment Receiving Long-Term Treatment (3-year observations)

The aim of the present work was to assess individual prognoses for Cerebrolysin treatment efficacy in mild cognitive impairment syndrome (MCIS) and to identify the most informative tests for prognosticating the development of dementia. A total of 53 patients with the amnestic type of MCIS were treated with Cerebrolysin for three years with regular neuropsychological and psychiatric clinical testing, with analysis of the results by nonparametric statistics, cluster analysis, and linear discriminant analysis. This combination of mathematical methods allowed decreases in cognitive functions to the level of dementia to be predicted. A “risk group” with a rapid decrease in cognitive functions and the threat of dementia was identified,i.e., a group with low therapeutic efficacy. Tests were ranked in terms of their prognostic value.

Potential of Preventive Treatment of Alzheimer’s Disease: Results of a Three-Year Prospective Open Comparative Trial of the Efficacy and Safety of Courses of Treatment with Cerebrolysin and Cavinton in Elderly Patients with Mild Cognitive Impairment Syndrome

Studies were performed in three Russian centers (Moscow, St. Petersburg, Nizhnii Novgorod). The cohort consisted of 110 patients whose mental state corresponded to the concept of “mild cognitive impairment” (MCI). Patient status was assessed using widely accepted scales (MMSE, GDS, CDR, etc.) and a battery of neuropsychological tests. ApoE genotypes were also identified. Patients were divided into two comparable groups depending on treatment: 55 patients received cerebrolysin and 55 received Cavinton. The data provided evidence that treatment with cerebrolysin was more effective than treatment with Cavinton in terms of slowing the progression of cognitive deficit and delaying the time at which the patients qualified for the diagnosis of Alzheimer’s disease. Cerebrolysin was more effective in patients with MCI and the ApoE4+ genotype, i.e., patients in the high risk group for Alzheimer’s disease. Adverse events were rare in both groups.

Clinical efficacy and safety of choline alfoscerate in the treatment of late-onset cognitive impairment

AIM To study the efficacy and safety of cereton (choline alfoscerate) in the treatment of elderly patients with amnestic type of mild cognitive impairment (aMCI), which often represents a pre-dementia (symptomatic) stage of Alzheimers disease (AD). MATERIAL AND METHODS Fifty patients (40 women and 10 men; mean age 68,8 years) received three-month therapy with cereton in a dose of 1200 mg/day in 3 divided doses. Fifteen patients received the same treatment again within 1 year. Immediate and delayed (7-9 months after treatment) effects of therapy, including those dependent on the ApoE genotype were assessed with a neuropsychological test battery. RESULTS Psychometric measures showed a significant improvement after treatment with cereton. ApoE4 allele noncarriers performed better on tests of immediate and delayed reproduction of 10 words. Although, most indicators achieved in the end of therapy course decreased 7-9 months after treatment, the level of patients cognitive functioning remained at a higher level than before treatment. A repeated course of cereton treatment prevents cognitive deficit increasing during the follow-up period (10-12 months). CONCLUSION The drug is well-tolerated and safe and can be recommended for preventive treatment of dementia in patients with high AD risk, in particular in elderly patients with aMCI syndrome.

Противовоспалительные эффекты нейротрофической терапии (применение церебролизина при мягком когнитивном снижении)

AIM To study clinical effects of cerebrolysin and its impact on systemic inflammation markers and immunity in mild cognitive impairment (MCI). MATERIAL AND METHODS Twenty patients with MCI were treated with cerebrolysin administered intravenously during 4 weeks. Serum levels of immunoglobulins, inflammatory markers, neurotrophic factors were measured in dynamics in patients and controls using ELISA. RESULTS An effect of cerebrolysin was found in MCI patients including the older group (mean age 78±1.1 years). An improvement was seen 6 and/or 22 weeks after treatment. Four types of response to neurotrophic treatment (fast long-term, fast short-term, delayed long-term), without effect were determined, the longer duration of positive effect of cerebrolysin was shown. There were differences in the indices of humoral immunity, clinical blood test results, cortisol and neurotrophin levels assessed before and after treatment between the patients with- and without positive effect of cerebrolysin. CONCLUSION The high clinical effect of neurotrophic therapy with cerebrolysin in MCI shows its anti-inflammatory and immunotropic action that suggests the impact of cerebrolysin on the pathogenesis of MCI.

Терапевтический мониторинг и прогноз эффективности нейротрофической терапии у пациентов с синдромом мягкого когнитивного снижения амнестического типа

AIM To perform therapeutic monitoring and prediction of the neurotrophic therapy efficacy in patients with amnestic type of mild cognitive impairment (aMCI) in a model of course cerebrolysin therapy. MATERIAL AND METHODS The study involved a group of 19 elderly patients who met the diagnostic criteria of aMCI. All patients received a course of neurotrophic therapy consisting of 20 intravenous infusions of cerebrolysin (30 ml of cerebrolysin in 100 ml of isotonic sodium chloride solution). To assess the therapy efficacy, psychometric scales (CGI, MMSE, MoCA-test, МDRS, FAB, Clock Drawing Test, BNT, Word Recall test, delayed reproduction of 10 words, naming digits in a direct and reverse order) were used at 0, 4, 10 and 26 weeks of the study. Antibodies to p75 neurotrophin receptor (NTR) were measured by ELISA in blood serum of 19 patients before cerebrolysin therapy and after 10 and 26 weeks of treatment. RESULTS AND CONCLUSION The study showed that аMCI patients had an increased level of antibodies against P75NTR that was significantly decreased after 5.5 month of cerebrolysin treatment. Therefore, it can be a potential biomarker of long-term therapeutic effect of cerebrolysin treatment in aMCI patients. The modified fragment 155-164 of P75 NTR determined in the serum of patients can be an effective indicator for monitoring and predicting the efficacy of long-term neurotrophic therapy.

Levels of Proinflammatory Cytokines and Growth Factor VEGF in Patients with Alzheimer’s Disease and Mild Cognitive Impairment

Objective. To assess the levels of cytokines (IFN-α, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-15, TNF-α) and IL-1 receptor antagonist (IL-1RA), as well as the levels of vascular endothelial growth factor (VEGF) and its antagonist – soluble receptor (sVEGFR1) – in the serum of patients with Alzheimer’s disease (AD) with early (EOAD) and late (LOAD) onset and mild cognitive impairment (MCI). Materials and methods. Levels of cytokines, soluble IL-1β antagonist IL-1RA, VEGF, and sVEGFR1 were studied by ELISA in the blood of 20 patients with AD and 11 with MCI. The values obtained were related to the severity of cognitive impairments identified by neuropsychological investigations. Results and conclusions. Differences were found in the levels of the key inflammatory cytokines (IL-8, TNF-α, IL-12), VEGF, and sVEGFR1, as well as anti-inflammatory proteins in EOAD, LOAD, and MCI. These features are felt to provide evidence of the pheno- and genotypic variation in this disease, which requires further study.

A Clinical Trial of the Use of Agomelatine for the Treatment of Depression in Elderly Patients in Out-Patient Conditions

Study aim. The therapeutic efficacy and tolerance of agomelatine (Valdoxan) in mild and moderate depressive states were studied in out-patient conditions in a contingent of elderly patients. Materials and methods. Patients aged 60–75 years with mild and moderate depression (ICD-10) were treated with agomelatine. Agomelatine was given at doses of 25–50 mg/day as a single evening dose for six weeks. Results. The therapeutic effect of agomelatine was clearly apparent within two weeks of starting treatment. Agomelatine had a balanced spectrum of action in relation to symptoms of anxiety and depression, significantly improving patients’ quality of life measures. It had no negative influences on cognitive functions and there were no serious adverse events. Conclusions. The results obtained here allow agomelatine to be recommended for use in out-patient practice for the treatment of elderly patients with mild and moderate depressive disorders.