Subclinical stage of the disease precedes the clinical stage of moderate cognitive decline in Alzheimer's disease (AD). Subjective cognitive decline (SCD) — a condition in which the level of cognitive function habitual for the subject gradually begins to decrease. In 2021, researchers from the National Institute on Aging and the Alzheimer's Association (NIA-AA) clinical criteria for the diagnosis of SCD have been proposed, as well as features that increase the probability of preclinical stage AD in patients with moderate cognitive impairment have been identified. Patients should be offered a complex of examinations — questionnaires regarding the impact of memory impairment on current cognitive activity (forgetfulness, searching for things, difficulty finding words, etc.), testable self-report of cognitive dynamics, neuropsychological testing and diagnosis of pathopsychological changes such as depression and anxiety. It would appear that counselling in the form of interviews and/or testing of persons able to provide relevant information about the patient should be included in the examination of patients with complaints of memory disorders, regardless of their degree of severity. It may be necessary to conduct a survey on the patient’s daily activity, ability to self-service (score, orientation, planning, control and so on), as well as to obtain information about any memory-related changes that have become visible to others, because it is the data from the partner/relative that increase the predictive value of the diagnostic. The modern approach to the study of cognitive functions in elderly people without dementia in the long-term is certainly able to help identify people with a high risk of developing AD.

Hepatolenticular degeneration (HLD) or Wilson-Konovalov disease (OMIM277900) is a hereditary monogenic autosomal recessive degenerative disease related to metabolic diseases - a category of storage diseases. HLD has been studied for more than 130 years. During this time, more classifications of this disease were proposed. In this review, we systematized all the proposed classifications of HLD. And we noticed, they are based on the following criteria: 1) clinical signs of the disease; 2) the sequence of their appearance as the pathology progresses (with the primary appearance of signs of liver or brain damage); 3) severity of the disease. This review also systematizes data on the clinical picture of HLD.

Arnold-Chiari malformation or Chiari malformation (CM1) is the name of a group of deformities of the posterior fossa and hindbrain (cerebellum, pons and medulla oblongata). The pathogenetic basis of this disease is associated with herniation of the cerebellar tonsils through the foramen magnum. CM1 is classified as a rare disease. CM1 can present with a wide variety of symptoms, also non-specific, with consequent controversies on diagnosis and surgical decision-making, particularly in asymptomatic or minimally symptomatic. Syringomyelia (Syr), hydrocephalus, craniocervical instability, encephalocele, scoliosis, spina bifida and spinal dysraphism are the most common comorbidities that may present at the time of diagnosis or develop secondarily. Most attention has been paid to syringomyelia complicated by CM1 (CM1-related Syr). Formation of single or multiple fluid-filled cavities in the spinal cord and/or bulb as a result of pulse changes in intracranial pressure associated with disruption of normal cerebrospinal fluid circulation due to morphological abnormalities of the brain at the magnum level. This condition can be complicated by a rarer disease caused by the development of damage to the anterior horns of the spinal cord - amyotrophic sclerosis (ALS syndrome). In this brief literature review we are trying to demonstrate the mean pathogenic basis of amyotrophic lateral sclerosis in patients with chiari 1 malformation associated syringomyelia.

The effect of anticonvulsants on bone mineral density changes in epileptic patients is an important and relevant scientific question. This brief review focuses on assessing the existing knowledge on how antiepileptic drugs affect bone mineral density. The review examines the various mechanisms that may influence bone mineral density when anticonvulsants are taken. Based on a literature search and analysis, advances in the field are identified and their contribution to the current understanding of the issue is assessed. Overall, this review can serve as an informative resource for understanding the relationship between antiepileptic drugs and bone mineral density and as a direction for future research.

(1) Introduction: Despite modern therapies, approximately 20-30% of patients with schizophrenia remain resistant to psychopharmacotherapy. Clozapine is the only antipsychotic with proven efficacy for treatment resistance in schizophrenia (TRS). The most common adverse drug reaction (ADR) during clozapine administration are metabolic disturbances, particularly metabolic syndrome (MS). Because MS leads to a twofold increase in mortality from cardiovascular disease and a 1.5-fold increase in mortality from all causes, and clozapine is often the only treatment option for TRS, it is critical to monitor and management metabolic abnormalities. The high interindividual differences in the development of clozapine-induced MS suggest that genetic factors may play an important role. (2) Purpose: The aim of this study was to identify relevant single nucleotide polymorphisms (SNPs) of candidate genes for clozapine-induced MS, because based on these data, a genetic risk panel can be constructed to assess the likelihood of developing clozapine-induced MS in patients with schizophrenia. (3) Materials and Methods: We searched for full-text publications in PubMed, Web of Science, Springer, Google Scholar, and electronic libraries in English and Russian, available from inception to 30 October 2023. Keywords were the following: metabolic disturbances, clozapine, metabolic syndrome, schizophrenia, genes, adverse drug reactions, antipsychotics, pharmacogenetics, genetic biomarker, single nucleotide variant, polymorphism, association, variation, and metabolic syndrome genes. (4) Results: we included 6 naturalistic cross-sectional open-label trials, included patients with schizophrenia, schizoaffective, schizophreniform disorder or psychotic disorder, who were treated with first and second generations antipsychotics, among which there was also clozapine and 1 meta-analysis which reviewed association between HTR2C gene polymorphisms and anti-psychotic-induced MS in schizophrenia patients. According to the results of our scoping review the carriage of SNPs in the studied candidate genes associated with clozapine-induced MS are the following: 1) CYP1A2 gene: genotype AA of rs762551 (NG_008431.2:g.32035C>A); 2) CYP2C19 gene: CYP2C19*2 polymorphism; 3) HTR2C gene: genotype CC of rs518147 (NM_000868.2:c.-697G>C), minor allele C of rs1414334 (NG_012082.3:g.324497C>G), genotype CC of rs518147 (NM_000868.2:c.-697G>C), genotype GG of rs12836771 (NG_012082.3:g.71829A>G); 4) LEP gene: genotypes AG and GG of rs7799039 (NG_044977.1:g.475G>A); 5) LEPR gene: genotypes AG and GG of rs1137101 (NG_015831.2:g.177266A>G). (4) Conclusions: Uncovering the genetic biomarkers of clozapine-induced MS may provide a key to developing a strategy for the personalized prevention and treatment of this ADRs of clozapine in patients with schizophrenia spectrum disorders in real clinical practice.

Epilepsy often accompanies congenital cerebral palsy (CP). Canalopathies can be the cause of congenital epilepsy. The aim of the study is to determine the influence of various determinants on the course of epilepsy. Materials and methods: The results of clinical and genetic analysis of 136 cases of cerebral palsy (CP) with epilepsy are presented. The patients were divided into groups according to the syndromes according to the classification of CP (Panteliadis and R. Korinthenberg, 2005). Epileptic syndromes were divided into three groups: focal childhood epilepsy with structural brain changes and benign epileptiform discharges (BEDC) in EEG - 41 children (30.1%), structural focal epilepsy - 37 children (27.2%), epileptic encephalopathies 58 children (42.7%). Pathogenic variants in genes were confirmed by next generation sequencing (NGS) Sanger methods of venous blood. Results. Remission was more difficult to achieve in patients with determinants of regulation of general aspects of cellular metabolism, mitochondrial function, cytoskeleton formation and function, and transport across the outer membrane. The need for polypharmacy was in the groups that regulate the function of mitochondria, the formation and functioning of the cytoskeleton, and the regulation of membrane excitability. Conclusion. Determinant analysis provides a better understanding of the mechanisms of patient responsiveness to anticonvulsant therapy. The determinant of mitochondrial function most significantly affects its effectiveness. Probably, the violation of energy metabolism in the cell neutralizes the stabilization of the neuronal membrane under the influence of anticonvulsants. The determinant of the formation and functioning of the cytoskeleton, according to our preliminary data, is associated with the formation of malformations of the brain. In this case, the refractoriness of epilepsy can be secondary and determined by the severity of structural changes in the brain.

Objective: The aim of the study was to study the clinical features of essential tremor (ET) in residents of the Republic of Sakha (Yakutia) in various ethnic groups.
Material and methods. The study involved 53 patients with an established diagnosis of essential tremor. All patients underwent a detailed neurological examination with a quantitative assessment of the severity and severity of tremor, as well as the degree of maladjustment and activity in everyday life using unified scales.
Results and Discussions. It was revealed that the clinical variant of essential tremor-plus, associated with a more severe course and disability of patients. In the representatives of the Russian ethnic group, with the classic version of essential tremor, a combination of head tremor and hand tremor is observed, as well as a more rapid progression of disease symptoms. Representatives of the Yakut ethnic group in the clinical picture of essential tremor-plus are statistically significantly more likely to have a dystonic head position.
Conclusion. Clinical variability of essential tremor with differences in the ethnic aspect in the rate of progression and in the frequency of the combination of action tremor with dystonic head position was demonstrated.

When performing maximum loads, an important criterion for assessing prospects is the achievement of the best result with the least metabolic changes in the body of athletes, which indicates the possibility of further increasing physical performance. The study of the mechanisms of energy supply and the reaction of body systems when testing performance under special conditions is one of the important conditions for the development of additional biochemical criteria for assessing the prospects of athletes. Purpose: To study genetic and physiological predictors of bioenergetic adaptation of skeletal muscles in athletes of cyclic sports. Methods: 76 athletes of cyclic sports (speed skating, running disciplines in track-and-field) of European origin who lived in the Southern Urals region took part in the study. The average age of the study participants was 22.1 ± 2.5 y.o. Experience in sports was at least 5 years. We used the Step One Real-Time PCR System (Applied Biosystems, USA) device for real-time polymerase chain reaction. The study of bio-energetic indicators of athletes' physical performance was carried out using the bicycle ergometry method (test with maximum load). Biochemical studies were carried out using a Lactate Scout Plus lactometer. Results: Significant differences were found in the ΔLa (%) indicator: in athletes with a dominant homozygous genotype R/R, lactate clearance during a 10-minute rest after performing a bicycle ergometer load is statistically significantly higher than in athletes with a recessive homozygous genotype X/X (20.14±12.74%, versus 11.11±3.12%; p<0.05). The major allele C (R) was associated with moderate and high lactate clearance (OR = 2.25 [95% CI: 0.99 – 5.11] and OR = 2.24 [95% CI: 0.91 – 5.51], respectively). At the same time, a statistically significant association was identified between the minor allele T(X) and the homozygous genotype TT (XX) with low lactate clearance (OR = 12.14 [95% CI: 1.30 – 13.55]). High values of lactate clearance indicate the utilization of lactate from peripheral blood and more efficient recovery processes in carriers of the major allele C (R). Conclusions: lactate clearance during a 10-minute rest period after a bicycle ergometer test with maximum load and DNA profiling of the ACTN3 gene rs1815739 can be recommended as significant physiological and genetic predictors of bioenergetic adaptation of skeletal muscles in cyclical sports athletes of Caucasian origin in the Southern Urals.

Antidepressants (ADs) include drugs of various pharmacological groups, which are mainly used for the treatment of mental disorders (major depressive disorder, obsessive-compulsive disorder, social phobia, panic disorder, generalized anxiety disorder, post-traumatic stress disorder), chronic pain and addiction diseases. Chronic use of ADs can lead to the development of cardiotoxic adverse drug reactions (ADRs). The most important cardiotoxic AD-induced ADRs are prolongation of the QT interval, ventricular tachycardia of the "pirouette" type (Torsades de Pointes - TdP). This narrative review analyzes and summarizes the results of studies on pharmacokinecis and pharmacogenetics of ADs on QT interval prolongation and updates physicians' knowledge of the risk of developing AD-induced TdP in patients with psychiatric disorders.

Introduction: The widespread misuse of opioids and cannabis is a notable global public health concern. The substantial public health concern due to the misuse of opioids and cannabis, individually and concurrently, is associated with vast societal implications. Identification of risk factors for developing misuse of these substances is of utmost importance. This study aims at developing a machine learning-based model to classify groups of opioid or cannabis dependents using family, microsocial, and medical history variables, and to identify the most significant variables associated with each group.
Methods: This naturalistic observational non-interventional study enrolled adult patients diagnosed with opioid use disorder, cannabis use disorder, or a combination of both. Machine learning models, including Stacking, Logistic Regression, Gradient Boosting, k-Nearest Neighbors (kNN), Naive Bayes, Support Vector Machines (SVM), Random Forest, and Decision Tree, were used to classify patients and predict their risk factors based on various personal history variables.
Results: The patient groups showed significant differences in their working fields, marital status before and after the formation of drug addiction, substance misuse in relatives, family type, parent-child relationships, and birth order. They also differed significantly in fleeing from home and personality types. Machine learning models provided high classification accuracy across all substance dependence groups, particularly for the cannabis group (>90% accuracy). Significant differences were found among the complex misuse group, where individuals faced severe psychosocial issues originating from the familial environment, such as a history of fleeing home, coming from a single-parent family, and dominant parent-child relationships.
Discussion: The methods used in this study provided robust and reliable assessments of the models' predictive performances. The results pointed to significant differences in familial and developmental factors between the three dependence groups. The complex dependence group showed more severe psychosocial issues originating from the family environment. This group also revealed a specific sequence of life events and conditions predictive of complex dependence. These findings highlight the importance of interventions that address risk factors across various life stages and domains. Conclusion: Early identification of high-risk individuals and understanding the risk factors can inform the development of effective interventions at both individual and societal levels, ultimately aiming at mitigating dependence risks and improving overall well-being. Further research with longitudinal designs and diverse populations are needed to increase our understanding of trajectory of addiction formation in order to deliver effective interventions for individuals at risk.