S. I. Gavrilova

[The activity of blood serum cholinesterases and neprilysin as potential biomarkers of mild-cognitive impairment and Alzheimer's disease].

OBJECTIVE To analyze the activity of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and neprilysin (NEP) in the blood serum in elderly people with different types of cognitive impairment and evaluate the effect of ceraxon on the biochemical parameters. MATERIAL AND METHODS Three groups of patients: without cognitive disorders (controls--CG), with amnestic mild cognitive impairment (а-MCI) and with Alzheimers disease (AD were studied). RESULTS AND CONCLUSION The activity of AChE, BChE and NEP was reduced in the blood serum of patients with a-MCI and, to the greater extent, in patients with AD compared to CG and correlated with the level of cognitive dysfunction evaluated by MMSE, ADAS-cog, and other tests. For the first time, it has been shown that treatment of a-MCI patients with ceraxon (citicolin) results in an increase of the activity of blood serum AChE, BChE and NEP to the values observed in the CG. Thus, the activities of blood serum AChE, BChE and NEP reflect the level of cognitive dysfunction and can be used as prognostic biomarkers of the level of dementia progression in patients with impaired memory.

Prognosis of mild cognitive impairment syndrome: Data from a two-year clinical follow-up study

The psychopathological structure and prognostic significance of mild cognitive impairment syndrome (MCI) were studied in a two-year prospective study of randomized cohorts of elderly subjects whose mental state corresponded to the criteria for MCI. A total of 40 patients aged from 50 to 80 years were studied. Patients underwent clinical history-taking, neuropsychological, psychometric, and genetic investigations (genotyping for ApoE), as well as brain imaging studies. The psychopathological structure and psychometric characteristics of MCI syndrome are presented. Clinical and genetic factors with prognostic significance are identified.

Experience of the antidepressive therapy with valdoxan (agomelatine) in a psychogeriatric unit of the psychiatric hospital

OBJECTIVE To assess therapeutic efficacy, tolerability and safety of valdoxan (agomelatine) in the treatment of depression in elderly inpatients of the psychiatric hospital. MATERIAL AND METHODS The study included 20 patients, aged 60 years and older, with depression of varying severity. Patients received valdoxan in standard doses 25-50 mg/day during 42 days. RESULTS Valdoxan showed a good balanced profile (in terms of indicators of depression, anxiety and anhedonia) of therapeutic response and tolerability in inpatients with mild to moderate depression. The use of valdoxan led to a significant reduction of depressive disorders and anxiety already in the early period of treatment. The severity of anhedonia decreased to the 14th day of treatment. A significant improvement in cognitive functioning of patients was noted to the end of treatment. CONCLUSION Valdoxan can be recommended for treatment of mild and moderate depression in inpatients of psychiatric hospitals.

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.

Cholinergic Treatment of Alzheimer’s Disease and Its Influence on Health and the Quality of Life of Carers

The efficacy and safety of four-month courses of rivastigmine and changes in measures of carer burden were studied in a non-randomized group of 25 patients with Alzheimer’s disease (AD). All patients received p.o. rivastigmine and 22 patients received antipsychotic therapy along with rivastigmine on admission. Treatment was continued for 16 weeks (12 weeks in hospital and four weeks in out-patient conditions). These studies showed that the use of rivastigmine in AD patients with behavioral and psychotic disorders at the stage of moderately severe dementia not only improved the patients’ cognitive functions, but also had positive effects in terms of decreasing psychotic and behavioral disorders. Inclusion of rivastigmine in the complex treatment of AD patients led to significant decreases in the need for psychotherapeutic agents, and in some patients to complete withdrawal of all antipsychotics. It is extremely important to emphasize that the use of rivastigmine in patients with moderately severe AD and behavioral disorders led to significant (up to 30%) decreases in the time spent on the care and supervision of the patients, along with decreases in the level of stress and improvements in the health of carers, indicating increases in the quality of life of both patients and their families.

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.

Comparative Dynamics of EEG Parameters in Elderly Patients with Depression during Monotherapy and Combined Treatment

Objective. To perform a comparative analysis of changes in the functional status of the brain by quantitative electroencephalography (EEG) during combined antidepressant treatment (venlafaxine and Cerebrolysin) and monotherapy (venlafaxine) of elderly patients with depression. Materials and methods. A total of 40 patients aged 60–79 (mean 67.1 ± 5.7) years took part in the study and were randomized to two groups. Patients of group 1 received venlafaxine at a dose of 75–150 mg/day for four weeks. Patients of group 2 received venlafaxine for four weeks along with Cerebrolysin (20 i.v. drip infusions of 20.0 ml in 100 ml of isotonic NaCl solution). Results and discussion. Both groups of patients noted signifi cant improvements in status by the end of treatment courses in terms of clinical assessment and the HAMD-17, CGI-S, CGI-I, and MMSE scales. Quantitative EEG studies showed that combined therapy with venlafaxine and Cerebrolysin in patients of group 2 led to more marked improvements in the functional state of the brain (increases in spectral power and normalization of the frequency of the parietal-occipital α rhythm) than seen in patients of group 1, who received monotherapy with venlafaxine.