OBJECTIVE: To study the efficacy and safety of the use of annual course therapy of choline alfoscerate (CA) as a drug potentially capable of slowing or preventing the transition of amnesic type mild cognitive impairment (aMCI) into clinically pronounced dementia in a three-year open comparative study, as well as to explore the possibility of predicting the preventive effect of such therapy based on a number of clinical and biological parameters. MATERIAL AND METHODS: The study included 100 patients with aMCI, randomly divided into 2 groups: the therapeutic group consisted of 50 patients who received CA course therapy once a year for 3 years (20 intravenous infusions of 1000 mg (4 ml) in 100 ml of saline solution for 4 weeks) and a comparison group of 50 patients who underwent an annual examination at the center and did not receive therapy. Clinical and psychopathological, psychometric, immunological, follow-up, and statistical methods were used. RESULTS: A comparative three-year prospective study conducted in a group of aMCI patients treated with annual course therapy of CA for 3 years and aMCI patients who did not receive therapy with similar initial demographic, diagnostic, psychometric and immunological characteristics showed a lower progression of cognitive deficits (12.2% and 39.1%, respectively) and a lower conversion rate (8.2% and 26.1%, respectively) to dementia in the therapeutic group compared with the comparison group. The differences between the initial and final (after 1, 2 and 3 years of follow-up) cognitive functioning indicators in the therapeutic group and the comparison group were significant (p<0.05) on all scales and tests in favor of the therapeutic group throughout the entire follow-up period. CONCLUSION: The results allow us to consider CA as a possible model of preventive dementia therapy aimed at preventing the progression of cognitive deficits and the development of dementia in people at high risk of developing AD - patients with aMCI.
Cognitive Dysfunction , Dementia , Glycerylphosphorylcholine , Humans , Cognitive Dysfunction/prevention & control , Cognitive Dysfunction/drug therapy , Female , Male , Aged , Dementia/prevention & control , Prospective Studies , Glycerylphosphorylcholine/therapeutic use , Glycerylphosphorylcholine/administration & dosage , Treatment Outcome , Middle Aged , Disease Progression , Aged, 80 and over
OBJECTIVE: Evaluation of the efficacy and safety of the drug Acatinol Memantine, 20 mg (once daily) in comparison with the drug Acatinol Memantine, 10 mg (twice daily) in patients with moderate to moderate severe vascular dementia. MATERIAL AND METHODS: The study included 130 patients aged 50-85 years of both sexes with instrumentally and clinically confirmed vascular dementia. The patients were randomized into 2 groups. Group I consisted of 65 patients receiving Akatinol Memantine, 20 mg once daily, group II - 65 patients receiving Akatinol Memantine, 10 mg twice daily for 24 weeks. Clinical, parametric and statistical research methods were used. The Alzheimer's disease assessment scale, the cognitive subscale (ADAS-cog), the short mental Status Assessment Scale (MMSE) and the general clinical impression scale for patients condition and illness severity (CGI-C and CGI-S) and the Hamilton Depression Rating scale (HAM-D) were used. Adverse events were collected and analyzed. RESULTS: At week 24, both groups showed statistically significant positive change in ADAS-cog total score: in group I the total score was 27.2±8.76 points (absolute difference from baseline 3.5 points; p<0.01), and in group II - 26.1±7.86 points (absolute difference from baseline 2.5 points; p<0.01) with no statistically significant differences between groups. Evaluation of secondary efficacy criteria (change in ADAS-cog total score at week 12 and MMSE at weeks 4, 12, and 24) also revealed statistically significant benefit in both groups compared to baseline with no significant differences between groups. Statistically significant improvement was noticed on CGI-S and CGI-C scales in both groups. Akatinol Memantine was safe and well tolerated in both groups. CONCLUSION: The study showed no lesser efficacy and safety of Akatinol Memantine, 20 mg (once daily) compared to Akatinol Memantine, 10 mg (twice daily) in patients with moderate and moderately severe vascular dementia.
Alzheimer Disease , Dementia, Vascular , Female , Humans , Male , Activities of Daily Living , Alzheimer Disease/drug therapy , Alzheimer Disease/psychology , Cognition , Dementia, Vascular/drug therapy , Double-Blind Method , Memantine/adverse effects , Treatment Outcome , Middle Aged , Aged , Aged, 80 and over
OBJECTIVE: To evaluate the efficacy, safety, and compliance to therapy with Mioreol, first used as part of routine clinical practice in patients with moderate-to-severe dementia due to AD. MATERIAL AND METHODS: The study was conducted as a non-interventional observational program. The work was performed on a group of 48 patients with moderate-to-severe AD aged from 60 to 90 years (median age 74 [69; 77]). The therapeutic dose of Mioreol was 10 mg donepezil + 20 mg memantine, the drug was taken orally, once a day at the same time, regardless of meals. The duration of the course of therapy was 24 weeks. The effects of the drug were assessed using the MMSE, ADAS-Cog, NPI, and CGI scales before the start of therapy and by the end of 12 and 24 weeks of treatment. RESULTS: The use of Mioreol in six-month therapy of AD patients with moderate-to-severe dementia improved not only cognitive but also a wide range of non-cognitive mental disorders. There was an improvement in the CGI-C scale in more than 50% of included patients, positive dynamics on the ADAS-cog scale (6.5 points reduction in total score) and reduction of non-cognitive mental disorders on the NPI scale (4 points reduction in total score). CONCLUSION: Fixed-dose combination therapy with Mioreol is an effective and well-tolerated treatment option for patients with moderate-to-severe AD. A combination of fixed-dose therapeutic doses of donepezil and memantine is potentially more appropriate than the simultaneous use of two recommended drugs for the treatment of AD, which will improve treatment adherence in patients with moderate to severe AD.
Alzheimer Disease , Donepezil , Memantine , Aged , Humans , Alzheimer Disease/drug therapy , Combined Modality Therapy , Donepezil/therapeutic use , Memantine/therapeutic use , Russia , Middle Aged , Aged, 80 and over
The aging of the population and the associated increase in the share of cognitive impairments in the structure of a wide range of diseases are a serious challenge for modern healthcare. Difficulties in the treatment of cognitive disorders are determined by many factors, including the age of patients, comorbidity, forced polypragmasia and the adequacy of the dosage of drugs that restore cognitive activity. The experts discussed information about the therapeutic potential of the drug Cerebrolysin in the treatment of cognitive disorders of various origins, stated significant experience of its effective and safe use in many clinical studies in mild and moderate forms of dementia. At the same time, there was a lack of consistent and systematic data on the dosage regimen, frequency, and duration of use of the drug in different forms of cognitive impairment and the degree of their severity. The aim of the international council of experts was to determine the optimal dosage regimens of the drug Cerebrolysin in patients with various etiologies and severity of cognitive impairment. The result of the work was the approval of a unified scheme for the use of the drug Cerebrolysin, considering the severity of the disease and its duration.
Alzheimer Disease , Cognition Disorders , Cognitive Dysfunction , Nootropic Agents , Humans , Nootropic Agents/therapeutic use , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/chemically induced , Cognition Disorders/drug therapy , Amino Acids/therapeutic use , Alzheimer Disease/drug therapy
OBJECTIVE: To evaluate the long-term effects of annual course therapy with Cerebrolysin on cognitive functioning and the risk of transition to dementia in relatives of patients with Alzheimer's disease (AD) with amnestic-type mild cognitive decline syndrome (aMCI) in comparison with the same group untreated relatives. MATERIAL AND METHODS: The cohort included 88 first-degree relatives of BA patients with aMCI syndrome aged 50 to 82 years (mean age 65.0±9.9 years) of which 46 people received course therapy with Cerebrolysin and 42 people were not treated. Clinical, neuropsychological, statistical methods were used. Conducted annual course therapy with Cerebrolysin (a total of 3 courses of infusion therapy: for a course of 20 intravenous infusions of 20 ml of Cerebrolysin in 100 ml of isotonic saline) followed by a follow-up study after 3 months after the end of the therapeutic period. The dynamics of cognitive functioning in the therapeutic group was compared with the corresponding dynamics in the comparison group over the same period. The assessment was carried out on day 0, by the end of 1, 14, 27 and 30 months research. RESULTS: In the therapeutic group, according to the CGI-I scale, by the end of the 3rd course of therapy, in 95.7% of cases, a pronounced or moderate improvement was achieved after each of the courses on all scales and tests. In this group, by the end of the therapeutic period, a significant improvement in the initial mean group scores was established. According to the all scales and tests, a significant improvement of the initial average group scores was found after each course of therapy (p<0.05). In the comparison group there was a significant deterioration (p<0.05) of the average group scores of most of the cognitive scales and test by the end of the observation. The annual conversion from aMCI to dementia due to probable AD was 9.5% only in the comparison group. The average group indicators of all scales and tests significantly worsened starting from the 14th month of observation in the comparison group. CONCLUSION: The absence of cases of aMCI conversion to dementia in the treated patients for 2.5 years of observation can serve as confirmation of a disease-modifying effect in Cerebrolysin. These results indicate the need for more extensive clinical studies of the preventive effects of Cerebrolysin and to explore the possibility of including such therapy in drug prevention programs for AD in people at high risk for this disease.
Over the past three decades, the definition and diagnostic boundaries of Alzheimer's disease (AD) have been repeatedly revised due to significant progress in understanding of the pathogenesis of neurodegeneration associated with Alzheimer's disease and development of high-tech diagnostic methods. The current approach to diagnosing AD is based on the discovery of biomarkers that reflect the two main neuropathological processes involved in the development of primary neurodegeneration underlying AD-abnormal amyloidogenesis and neuronal degeneration. The currently available diagnostic tools are limited to the detection of cerebrospinal biomarkers and/or assessment of the abnormal amyloid and tau protein burden in the brain via amyloid and tau positron emission tomography ligands. Practical implementation (mostly in the research field) of the biological model of AD diagnosis has led to a significant expansion of its diagnostic boundaries with the inclusion of predementia AD stages: asymptomatic and symptomatic, the latter is clinically corresponding to amnestic mild cognitive impairment (aMCI-amnestic mild cognitive impairment). On the one hand, this approach significantly expands the possibilities to study and use preventive technologies aiming to avert or delay the progression of predementia cognitive impairment to dementia but, on the other, it is associated with a number of negative implications from both the clinical and ethical points of view. A significant limitation of purely biological diagnosis of AD based on biomarker levels is due to the low prognostic value of biomarkers, which can cause diagnostic confusion in certain circumstances. Moreover, since the future evolution of the asymptomatic stage is not yet clear and there are still no reliable ways to prevent the cognitive and behavioral symptoms associated with AD, disclosure of stressful information about this "terrifying" diagnosis to patients can cause irreversible damage by triggering depressive disorder, which is a risk factor of AD itself. The current knowledge about AD prognosis in amyloid-positive cognitively unimpaired patients is insufficient. The most adequate approach to early AD diagnostics appears to be the clinical and biological model, as recommended by the International Working Group (IWG2021), which requires a combination of the clinical AD phenotype and the detection of biomarkers specific to this disease. The article discusses the potential directions for the development of biological diagnostic methods, including those based on the so-called peripheral (plasma) biomarker technologies and promising directions for the development of biological methods of secondary AD prevention.
Alzheimer Disease , Cognitive Dysfunction , Humans , Alzheimer Disease/diagnosis , Alzheimer Disease/prevention & control , Amyloid beta-Peptides , Cognitive Dysfunction/diagnosis , Biomarkers , Early Diagnosis , Amyloidogenic Proteins
OBJECTIVE: To evaluate the change of a number of clinical and immunological parameters of patients with amnestic type Mild Cognitive Impairment (aMCI) in the course of therapy with Choline alfoscerate (α-GPC) in order to develop a monitoring and predicting system of its effectiveness in people at risk for Alzheimer's disease. MATERIAL AND METHODS: Thirty patients with aMCI, aged 56 to 82 years (mean age 68.8±9.4 years), received course therapy with α-GPC in capsules of 400 mg 3 times a day (1200 mg per day) for 3 months. Therapeutic efficacy evaluation according to psychometric tests and scales was carried out three times (0, 45 and 90 days), immunological parameters of leukocyte elastase (LE) and α1-protease inhibitor (α1-PI) were evaluated twice on days 0 and 90 of therapy. RESULTS: A good therapeutic effect over the course treatment with α-GPC, both in terms of cognitive functioning and a number of immunological parameters in patients with aMCI was shown. Significant clinical and immunological correlations included both an improvement in cognitive functions (according to MMSE and the Boston Naming Test) and an increase in LE activity level after the completion of a course of α-GPC therapy, which suggest that an increase in LE functional activity can be considered as a potential marker of a positive therapeutic response to α-GPC treatment in aMCI patients. CONCLUSION: This study shows high significance of further research in assessing the role of immune mechanisms of α-GPC therapeutic efficacy in aMCI patients and the possibility of using immunological parameters as prognostic markers of its therapeutic effect.
Alzheimer Disease , Cognitive Dysfunction , Humans , Middle Aged , Aged , Glycerylphosphorylcholine/therapeutic use , Neuropsychological Tests , Cognitive Dysfunction/psychology , Alzheimer Disease/drug therapy , Alzheimer Disease/psychology , Cognition
The care of a patient with Alzheimer's disease (AD) is considered from the perspective of an ecosystem, that is, a systemic approach describing effective partnership, collaboration and research aimed at creating value, involving all participants in the AD patient journey. The effectiveness of this ecosystem is only possible with the involvement of all stakeholders in its development, including patients, healthcare professionals at all levels, government agencies, private companies, and patient organizations. The unmet health care and information needs of patients with AD are a consequence of barriers in the AD ecosystem. Key barriers for the patient include low awareness and stigmatization of the disease in society, lack of quality epidemiological data, difficulties in timely diagnosis, lack of prevention programs, unpreparedness of most physicians to conduct AD patient rehabilitation, and other factors. Based on the analysis of the ecosystem of AD and the patient pathway, 10 main directions (strategies) necessary for the formation of the ecosystem were identified: conducting research in the diagnosis and epidemiology of AD, creating and implementing a cognitive health program, forming a legal framework, raising public awareness, optimizing patient routing for timely diagnosis, organizing a network of memory clinics/laboratories, creating a register of patients with dementia, developing digital solutions and supporting social projects.
Alzheimer Disease , Alzheimer Disease/diagnosis , Alzheimer Disease/epidemiology , Alzheimer Disease/therapy , Delivery of Health Care , Ecosystem , Humans , Russia/epidemiology
OBJECTIVE: To determine the long-term (three-year) prognosis of the cognitive deficits progression in elderly people with amnestic mild cognitive impairment (aMCI) based on the analysis of the initial clinical and immunological parameters. MATERIAL AND METHODS: This study is based on a clinical and follow-up study of 252 outpatients with aMCI, who were observed in the Federal State Budgetary Scientific Institution «Mental Health Research Center¼ from 2018 to 2020. The psychometric assessment complex included the following scales and tests: MMSE, MoCA, The 10 words test, BNT, David Wechsler's Scale, subtest 6, CDT, Memory test of 5 geometric shapes, BVRT Test, DRS - Mattis Dementia Rating Scale: Verbal fluency, DRS - Mattis Dementia Rating Scale, The Munsterberg Test. As part of the study, the level of cytokines (TNF-a, IL-1, IL-6, IL-8, IL-10) in the blood serum was determined in all patients by enzyme immunoassay (ELISA), using diagnostic kits manufactured by Cytokine LLC. RESULTS: In patients with a progression of aMCI syndrome, an increase in proinflammatory cytokines IL-1, IL-6, IL-8, TNF-α is initially detected, which may reflect the level of systemic inflammation or functional insufficiency of anti-inflammatory mechanisms. In turn, the group with a subsequent improvement in cognitive functioning, on the contrary, is distinguished by an initially increased level of the anti-inflammatory interleukin system (IL-10). CONCLUSION: We provide new data on the presence of systemic inflammation and immune disturbances and their association with clinical course of disease in the majority of elderly patients with aMCI. CONCLUSION: Signs of a chronic low-level systemic inflammatory response in patients with aMCI is the unfavorable prognosis criterion: in such patients, cognitive deficit significantly progresses or dementia due to Alzheimer disease develops within three years.
Alzheimer Disease , Cognitive Dysfunction , Aged , Cognitive Dysfunction/diagnosis , Follow-Up Studies , Humans , Neuropsychological Tests , Prognosis
OBJECTIVE: To study the effects of a three-month course of therapy with citicoline, aimed at preventing the progression of cognitive deficit in 1st-degree relatives of patients with Alzheimer's disease (AD), depending on the carriage of the ApoE4(+) genotype. MATERIAL AND METHODS: Study participants: 82 blood relatives of AD patients, 66 of them with signs of minimal cognitive dysfunction (group 1) objectively confirmed by clinical neuropsychological examination and 16 people with mild cognitive decline syndrome (group 2). Open comparative multidisciplinary study of the dynamics of cognitive status in relatives of AD patients who received a three-month course of citicoline therapy. The baseline indicators of the cognitive functioning of the relatives of the two groups were compared with the indicators at the end of the three-month course of therapy with citicoline in a daily dose of 1000 mg, depending on whether the treated persons had genotypes ApoE4(+) or ApoE4(-). Clinical-psychopathological, neuropsychological, psychometric, molecular-genetic, statistical. RESULTS: An association of the ApoE4(-) genotype with a significantly more pronounced positive effect of the course therapy with citicoline was established according to the general clinical impression (CGI-I scale), indicators of cognitive functioning (MMSE and MoCA scales), as well as according to most psychometric tests (with the exception of the number repetition test in reverse order), as well as for almost all indicators of the neuropsychological «express method¼ (excluding the parameter of the volume of visual memory). CONCLUSION: The results of course therapy with citicoline showed a negative effect of the carriage of the ε4 allele of the ApoE gene on the efficiency of treatment of blood relatives of AD patients who had signs of cognitive decline before the start of therapy, which did not reach the level of dementia. The obtained data can serve as the basis for the development of preventive therapeutic measures aimed at preventing the progression of cognitive deficit and the development of dementia in the group at high risk of developing dementia - in 1st degree relatives of AD patients, especially in carriers of the ApoE4(+) genotype.
Alzheimer Disease , Cognitive Dysfunction , Alzheimer Disease/drug therapy , Alzheimer Disease/genetics , Apolipoproteins E/genetics , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/genetics , Cytidine Diphosphate Choline/therapeutic use , Genotype , Humans , Neuropsychological Tests
INTRODUCTION: Alzheimer's disease (AD) is a multifactorial disease that leads to a progressive memory loss, visualspatial impairments, emotional and personality changes. As its earliest pre-dementia clinical stage, amnestic mild cognitive impairment syndrome (aMCI) is currently considered. Neuroinflammation plays a role in the development and progression of aMCI and the initial stage of AD, which can be supported by immunological disorders of a systemic character. Study of factors, including infections, influencing immune disorders and systemic inflammatory response in patients with aMCI, is of great importance.The aim of this study was to obtain new data on the possible role of herpesvirus infections in the development and progression of aMCI. MATERIAL AND METHODS: 100 patients with aMCI diagnosis, 45 patients with AD, 40 people from the control group were enrolled into the study. The frequency of DNA detection of herpesviruses (Epstein-Barr virus (EBV), human herpesviruses (HHV) type 6 and 7, cytomegalovirus (CMV)), the levels of viral load and the serological markers of herpesvirus infections (IgG to HHV-1, IgG to CMV) were determined. Immunological studies included an assessment of the level of the main pro-inflammatory and anti-inflammatory cytokines, and indicators of humoral and cellular immunity. RESULTS: The study found an increased detection rate of EBV in saliva and a higher level of EBV DNA in saliva in aMCI and AD than in the control group. A relationship between the presence of active EBV infection and changes in immunological parameters in patients with aMCI were found. It was also discovered that the level of IgG antibodies to CMV is associated with the stage of AD. DISCUSSION: The results indicate a possible role of EBV- and CMV-induced infections in the development of immunological changes which are typical for mild cognitive impairment and in the progression of AD. CONCLUSION: The obtained data can be important for prognostic methods addressing AD development, including its pre-dementia stage, and for new approaches to individualized treatment and prevention.
Alzheimer Disease , Epstein-Barr Virus Infections , Herpesviridae Infections , Cytomegalovirus , Cytomegalovirus Infections , Epstein-Barr Virus Infections/complications , Herpesvirus 4, Human/immunology , Herpesvirus 6, Human/genetics , Humans , Immunoglobulin G , Neuroinflammatory Diseases
OBJECTIVE: To study the effectiveness of interfering visual stimuli inhibition using the flanker task in a group of healthy young and healthy old participants, and in a group of participants with mild cognitive impairment (MCI). MATERIAL AND METHODS: Reaction times and accuracy, as well as the diffusion model of reaction times with parameters reflecting perceptual and motor processes, stimulus processing speed, and conservativeness of response selection were analyzed. RESULTS: We found reduced speed and accuracy in older age, especially in MCI patients. The reduction was especially pronounced in patients with the incongruent distracters. For diffusion model parameters, perceptual and motor processes took longer with older age, reduced processing speed was found only in pathological aging, and specific effectiveness reduction for incongruent probes in patients was driven by increased conservativeness of responses. CONCLUSIONS: The results indicate the joint influence of normal and pathological aging processes on patients with MCI. The deceleration of the perceptual-motor components of the reaction time reflects the processes of normal cognitive aging, while the deceleration of the processing speed (in the presence of any distractors, including congruent ones) characterizes pathological cognitive aging. Differential diagnosis of normal and pathological cognitive changes is possible using data based on the analysis of reaction time components. It is important to take into account the conservativeness of responses as a factor slowing down the reaction time in pathological and normal cognitive aging.
Cognitive Dysfunction , Aged , Aging , Cognition , Cognitive Dysfunction/diagnosis , Humans , Inhibition, Psychological , Reaction Time
BACKGROUND: Amnestic mild cognitive impairment (aMCI) is considered as a possible earliest pre-dementia clinical stage of Alzheimer's disease (AD). Taking into account the prominent role of neuroinflammation in the pathogenesis of AD, it is quite important to study possible immunological markers of the risk of aMCI progression and the changes in immune parameters in patients. OBJECTIVE: To study the immunological variants of aMCI and AD based on the parameters of humoral and cell immunity, levels of key cytokines and presence of systemic inflammation, and to explore the link between changes in the immune parameters and clinical prognosis. MATERIAL AND METHODS: One hundred patients with a diagnosis of aMCI, 45 patients with AD at the stage of mild to moderate dementia and 40 people without cognitive impairment (the control group) were enrolled into the study. Immunological assessment included determination of the concentration of key cytokines, C-reactive protein, circulating immune complexes and immunoglobulins (Ig A, M, G) in blood serum by ELISA, determination of the main subpopulations of lymphocytes by flow cytometry. RESULTS AND CONCLUSION: Four main immunological variants of aMCI syndrome associated with clinical prognosis were identified. The detected changes in immune parameters are important for further studies to assess an effect of viral and bacterial infections, intestinal microflora disorders on a clinical prognosis in patients with different immunological variants of aMCI syndrome.
Alzheimer Disease , Cognitive Dysfunction , Gastrointestinal Microbiome , Alzheimer Disease/diagnosis , Cognitive Dysfunction/diagnosis , Disease Progression , Humans , Neuropsychological Tests
OBJECTIVE: To assess the delayed effect of course therapy with cerebrolysin on the cognitive functioning of the first degree relatives of patients with Alzheimer's disease (AD), including, depending on the ApoE4 genotype. MATERIAL AND METHODS: A cohort of 72 blood relatives of patients with AD, including 46 with objectively confirmed clinical and neuropsychological examination signs of mild cognitive dysfunction (group 1) and 26 (group 2) with cognitive impairment that meets the diagnostic criteria of mild cognitive impairment (ICD-10 F06.7), was studied. The dynamics of the initial (0 day) indicators of cognitive functioning was compared immediately after a four-week course of treatment with cerebrolysin infusions, as well as 1 and 2 months after its completion, depending on the presence of ApoE4(+) or ApoE4(-) genotype. Clinical, psychopathological, psychometric, follow-up, molecular-genetic and statistical methods were used. RESULTS: A positive prolonged effect of course therapy with cerebrolysin on cognitive functioning of the first degree relatives of patients with AD was established in both groups. A significant negative effect of the ApoE4(+) genotype on the immediate and delayed effects of cerebrolysin treatment has been proven. CONCLUSION: The results can form the basis for the development of therapeutic measures aimed at preventing the progression of cognitive impairment and the development of dementia in the first degree relatives of patients with AD as those with the highest risk of dementia.
Alzheimer Disease , Cognitive Dysfunction , Alzheimer Disease/drug therapy , Alzheimer Disease/genetics , Alzheimer Disease/prevention & control , Amino Acids , Apolipoproteins E/genetics , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/genetics , Cognitive Dysfunction/prevention & control , Disease Progression , Genotype , Humans , Neuropsychological Tests
OBJECTIVE: Comparative evaluation of the effectiveness and safety of antidepressant monotherapy and combined antidepressant therapy with the inclusion of neuroprotectors in the treatment of depression in old and very old patients in a psychiatric hospital. MATERIALS AND METHODS: The study included 2 groups of patients from the cohort of patients hospitalized in the gerontopsychiatric unit with mild and moderate depression (according to the ICD-10 classification) aged 60 years and older. The groups are comparable in their main demographic and clinical characteristics. Both groups received antidepressant monotherapy with venlafaxine (21 people) or combined therapy with the same antidepressant, but in combination with cerebrolysin or carnicetine (40 people) for 8 weeks. The efficacy of antidepressant therapy was evaluated with HAMD-17 and HARS; the effect of treatment on the level of cognitive activity of patients with MMSE and the 10-word memory test. RESULTS: In the group of patients receiving combined antidepressant therapy, a significantly faster and more pronounced therapeutic response was observed compared to the group of patients treated with antidepressant monotherapy. In the group of combined therapy, an earlier (by 4 weeks) and significant (p<0.001) reduction of depressive and anxiety symptoms was established by the end of treatment, this group had a significantly higher number of respondents, as well as a better quality of therapeutic remission and a significant improvement in the cognitive functioning of patients compared to the monotherapy group. When comparing the effectiveness of different neuroprotectors (cerebrolysin or carnicetine), significant differences in the reduction of depressive and anxiety disorders in favor of carnicetine were established only at the end of the therapeutic course. CONCLUSION: Combined antidepressant therapy with a combination of treatment with an antidepressant and a drug with neuroprotective properties can increase the effectiveness of antidepressant therapy in old and very old patients. Both cerebrolysin and carnicetine can be recommended for use in a psychiatric hospital to improve the quality of the therapeutic response and reduce the time of hospitalization.
Depression , Depressive Disorder , Aged , Antidepressive Agents/therapeutic use , Anxiety , Depression/drug therapy , Depressive Disorder/drug therapy , Humans , Middle Aged , Treatment Outcome , Venlafaxine Hydrochloride/therapeutic use
The individual differences in the efficiency of DNA DSB repair were estimated by the level of residual γH2AX foci after γ-irradiation at a dose of 2 Gy, in lymphocytes of patients with amnestic mild cognitive impairment (AMCI) and Alzheimer's disease (AD) and of healthy volunteers. Lymphocytes were isolated from the peripheral blood of the examined patients and were frozen in a medium for freezing cells. Before the study, the lymphocytes were thawed, suspended in RPMI 1640 culture medium supplemented with 10% inactivated fetal bovine serum, and half of the cells were γ-irradiated at 4°C from a 60Co source on a GUT-200M facility at a dose of 2 Gy (a dose rate of 0.75 Gy/min). Control and irradiated lymphocytes were cultured for 24 h, collected, fixed, and stored until the study of the number of spontaneous and residual foci of γH2AX using fluorescent microscopy after staining with fluorescent labeled antibodies. In lymphocytes of patients with AMCI and AD a higher number of residual γH2AX foci in lymphocytes and the higher number of lymphocytes with foci were found compared with healthy volunteers. This indicates a decrease in the ability to repair DNA DSB in these patients. Indicators of cellular immunity and the concentration of TNF-α in the blood serum in the group of examined patients were normal. In the group of patients with the cognitive impairments (AMCI+AD), a correlation was found between the number of residual foci of γH2AX and the number of CD3+CD4+ lymphocytes and the concentration of proinflammatory cytokine TNF-α in the blood serum. This suggests the development of stronger neuroinflammation in patients with reduced ability to repair DNA DSB in this pathology.
Cognitive Dysfunction , DNA Breaks, Double-Stranded , DNA Repair , Histones , Lymphocytes , DNA , Healthy Volunteers , Humans
Conflict adaptation effect in interference control tasks (like Stroop task or flanker task) consists in better interference suppression in incongruent trials following an incongruent trial. In a flanker task is shown that in normal cognitive aging there is a null conflict adaptation effect and that in mild cognitive impairment there is a reversed (negative) conflict adaptation effect. Using the drift diffusion model of reaction time, it is shown that the change in conflict adaptation effect in mild cognitive impairment is associated with the absence of adaptive increase in processing speed in the presence of distractors. This can be interpreted as the rigidity of perceptual control mechanisms, which are responsible for strategic distribution of attention in older age and in pathological aging, in particular. The conclusion is drawn that reversed conflict adaptation effect may be an early marker of pathological cognitive aging.
Cognitive Dysfunction , Conflict, Psychological , Adaptation, Psychological , Aged , Attention , Cognition , Cognitive Dysfunction/diagnosis , Humans , Reaction Time
AIM: To develop a personalized approach to the appointment of a complex antidepressant therapy in combination with drugs of neuroprotective and neurotrophic action in depressed elderly patients based on the selection of predictors of low therapeutic response (LTR). MATERIAL AND METHODS: The study included 152 hospitalized patients, aged 60 years and older, with moderate and mild depression (ICD-10) who received monotherapy (44 people) with antidepressants of the new generation and complex therapy (108 people) with the same antidepressants in combination with neuroprotective drugs. In the monotherapy group, correlations between treatment efficacy (change in average total HAMD-17 scores) and a set of parameters, including socio-demographic data, results of psychopathological, somatic, standardized assessment and neuroimaging (CT) of the brain were analyzed. The validity of the established correlations as predictors of LTR was estimated based on a comparison of their frequency among the responders (≥50% reduction) and non-responders (<50% reduction). Comparison of the efficacy of therapy in groups of patients with mono - and complex therapy was carried out depending on the presence or absence of predictors of LTR. RESULTS: LTR predictors are living alone, complaints about memory loss and signs of pronounced diffuse lesions of the subcortical white matter of the brain, which are significantly more frequently observed in non-responders (p<0.05). The increase in the number of predictors (2 and more) correlates with a significant decrease in therapeutic efficacy (p<0.001). Patients with complex in structure and protracted depressions tend to decrease in efficiency, and in most of them (more than 87% of cases) LTR predictors are detected. In patients with LTR predictors, the complex therapy is significantly more effective than monotherapy, allowing in all cases to achieve 50% reduction of depressive symptoms by the 4th week of treatment. CONCLUSION: Personalized indications for the appointment of complex antidepressant therapy in combination with neuroprotective drugs in depressed elderly patients are formulated.
Antidepressive Agents , Depression , Psychotherapy , Aged , Depression/diagnosis , Humans , Treatment Outcome
AIM: Comparative evaluation of the efficacy and safety of antidepressant monotherapy and complex antidepressant therapy in combination with carnicetine in the treatment of depression in elderly patients in a psychiatric hospital. MATERIAL AND METHODS: Two groups of hospitalized patients, aged from 60 to 79 years, with mild or moderate depression (according to ICD-10), comparable in basic demographic and clinical characteristics, received mono- or complex (in combination with carnicetine) antidepressant therapy for 8 weeks. Treatment efficacy was assessed with HAM-D, HARS, CGI-S and CGI-I; the level of cognitive activity was assessed with MMSE, the 10-word memory test and clock drawing test. RESULTS: It has been established that the use of complex antidepressants therapy with the inclusion of carnicetine allows to achieve a more rapid and pronounced therapeutic response compared to antidepressant monotherapy. This is confirmed by the earlier (by the 4th week) and significant reduction of depressive and anxiety symptoms (p<0.01), a greater number of responders and better quality of depressive outcomes to the end of treatment and a more rapid improvement in cognitive functioning. CONCLUSION: The results allow us to recommend the inclusion of carnicetine for the augmentation of antidepressant therapy in elderly patients of the psychiatric hospital to achieve a more rapid and complete therapeutic response and reduce the duration of hospitalization.
Antidepressive Agents , Depressive Disorder , Aged , Antidepressive Agents/therapeutic use , Anxiety , Depressive Disorder/drug therapy , Humans , Middle Aged , Treatment Outcome
AIM: To evaluate the efficacy of course neurotrophic therapy with cerebrolysin in a group of first-degree relatives of Alzheimer's disease (AD) patients who had minimal cognitive dysfunction. MATERIAL AND METHODS: Sixty-seven relatives (mean age 57.6±14.2 y.o.) received cerebrolysin in the dose of 20 ml/day in intravenous drips in 100 ml isotonic saline. The duration of treatment was 1 month. RESULTS: The positive effect of course treatment on the CGI was established in 77.6% of the relatives. The scores on the MMSE and MoCA scales were significantly improved in the group with cognitive difficulties objectively confirmed by the clinical/neuropsychological examination (n=27) and in the group without cognitive difficulties (n=40). CONCLUSION: The positive effect of cerebrolysin on the cognitive status of the first-degree relatives of AD patients, regardless of their cognitive deficiency, was demonstrated.
Alzheimer Disease , Cognitive Dysfunction , Adult , Aged , Alzheimer Disease/complications , Cognitive Dysfunction/etiology , Disease Progression , Humans , Middle Aged , Neuropsychological Tests
