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Scientific relevance. Being the main class of medicinal products for dyslipidaemia treatment, statins are widely used in clinical practice in various patient populations. However, statins can cause statin-associated muscle symptoms (SAMS), which are the most frequent and, in some cases, even life-threatening adverse reactions associated with these medicinal products.Aim. The study aimed to perform a systematic review of the epidemiology, classification, and physiological pathogenesis of SAMS, risk factors for this complication, and clinical guidelines for primary care physicians regarding the identification and treatment of patients with SAMS.Discussion. SAMS is an umbrella term that covers various forms of myopathies associated with satin therapy. According to the published literature, the prevalence of SAMS varies considerably and may depend on the study design, inclusion criteria, and the medicinal product used. SAMS has multiple putative pathogenic pathways that include genetically determined processes, abnormalities in mitochondrial function, defects in intracellular signalling and metabolic pathways, and immune-mediated reactions. The main known risk factors for developing SAMS include high-dose statins, drug–drug interactions, genetic polymorphisms, female sex, older age, Asian race, history of kidney, liver, and muscle disease, and strenuous physical activity. Given the lack of universally recognised algorithms for diagnosing SAMS, clinicians should consider the clinical presentation and the temporal relationship between statin therapy and symptoms. Other factors to consider include changes in muscle-specific enzyme levels and, in some cases, the results of blood tests for antibodies to 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase.Conclusions. To ensure the safety of statin therapy, it is essential to raise clinicians’ awareness of the risk factors for SAMS, indicative clinical and laboratory findings, and the need for dynamic patient monitoring, including the involvement of clinical pharmacologists.

Intracranial hemorrhage (ICH) is characterized by a high level of disability and mortality. One of the most important reasons that lead to an increased risk and an increase in the ICH prevalence are antithrombotic drugs: anticoagulant, antiplatelet and thrombolytic. The main risk factors for ICH are advanced age, arterial hypertension, and the use of antithrombotic drugs of different groups. Treatment of ICH while taking drugs affecting hemostasis, is an extremely difficult task and there is not enough sufficiently convincing recommendations and evidence. The decision to resume therapy with the drug, that led to the development of ICH, and the timing of this resumption, is also not a completely clear problem that requires a balance between ischemic and hemorrhagic complications. The most important aspect of prevention is strict adherence to current recommendations regarding combinations of antithrombotic drugs and protocols for thrombolytic therapy, which will minimize the risks of ICH.

Intracerebral hemorrhage (ICH), which is a form of hemorrhagic stroke, is an extremely serious disease. This pathology is characterized by very high levels of disability and mortality. Despite the improvement in the treatment of those diseases that can lead to ICH, its frequency is currently increasing, which is largely due to the use of drugs, in which case the term «drug-induced intracerebral hemorrhage» (DI ICH) is used. One of the main reasons for drug-induced ICH is an increase in the frequency of prescribing anticoagulant therapy for the prevention of ischemic stroke in atrial fibrillation, as well as dual antithrombotic therapy. In addition to anticoagulants, thrombolytic drugs can lead to the development of this pathology. According to the literature, an increase in the risk of developing ICH is also associated with therapy with antidepressants from the group of selective serotonin reuptake inhibitors, as well as high doses of statins. Risk factors for this adverse reaction are age, smoking, hypertension, and thrombocytopenia. Treatment of DI ICH is an extremely difficult task and includes the withdrawal of the culprit medication, antihypertensive therapy, correction of intracranial hypertension, and, in some cases, the administration of antidotes. The main method of prevention is the use of antiplatelet drugs and other drugs, the use of which is associated with an increased risk of developing DI ICH, in strict accordance with modern protocols and recommendations.

Atrial fibrillation (AF) is the main cause of cardioembolic ischemic stroke (IS), it occurs in 25–35% of patients with IS, and its presence increases the risk of recurrent stroke compared with patients with sinus rhythm. The main method of preventing recurrent IS in AF is the administration of oral anticoagulants (OACs); in non-valvular AF, direct OACs (DOACs) have an advantage. Meta-analysis of randomized clinical trials showed a 19% greater reduction of stroke and systemic embolism risk in the DOACs group compared to warfarin (p

Drug-induced tremor (DIT) is a term used to describe tremors that develop or increase in severity due to various medications administration. As multiple drugs are associated with DIT it is quite common in clinical practice and medication dose is frequently associated with tremor severity. DIT is associated with commonly prescribed drugs such as amiodarone, antidepressants, β-agonists, cyclosporine, lithium, tacrolimus and valproic acid. DIT mechanisms include dopamine receptors block, gamma-aminobutyric acid depletion, cholinergic deficiency. DIT risk factors include older age, female sex, longer administration of drugs associated with tremor or/and their administration in higher doses, history of tremor in the patient and/or relatives, excessive caffeine intake. It is necessary to establish a causal relationship between the use of a potential inducer drug and the development/intensification of tremor to diagnose DIT. If DIT is detected, the inducer drug should be discontinued or its dose reduced. To decrease DIT risk, it is recommended to avoid prescribing drugs which are most commonly associated with DIT.

Among drug-induced liver injuries (DILI), the cholestatic type is second in frequency (from 20 to 40%), the most common is the hepatocellular variant (up to 78%). For this reason, practitioners of various specialties, including neurologists and psychiatrists, do not monitor cholestasis parameters, and drug-induced liver injury with cholestasis (DILIС) remains unrecognized. The urgency of this problem is great, because the frequency of deaths in DILIС is only slightly lower than t in the hepatocellular type; in addition, it DILIС is much more likely to become persistent increasing the risk of chronic liver injury.Among the drugs used in neurology and psychiatry, the “leaders” in terms of the number of DILIС are antidepressants, both tricyclic (amitriptyline, imipramine) and selective serotonin reuptake inhibitors (SSRIs: paroxetine, sertraline, fluoxetine, citalopram, escitalopram), antidepressants), antipsychotics (chlorpromazine, fluphenazine), anticonvulsants (mainly carbamazepine).If the patient has a history of DILI caused by any of the forementioned medications, the agent should be switched to another drug from the same group with a minimal risk of DILI. If there is a history of DILI associated with antidepressants, it is recommended to choose SSRIs. It is necessary to monitor not only the activity of transaminases and bilirubin, but also the cholestasis parameters (alkaline phosphatase, γ-glutamyl transpeptidase) during treatment.

The article presents the chronology of the symposium «How to Deal with Pain in the 21st Century? Experts' opinions», which took place on November 8 during the XII interdisciplinary international congress «Manage Pain». The lectures discussed issues of non-steroidal anti-inflammatory drugs (NSAIDs), including etoricoxib (Atorika tabs), administration on the example of a clinical case, problems of terminology associated with the concepts of «lumbago» and «sciatica», rare clinical syndromes (for example, heavy-purse syndrome) that we need to differentiate nonspecific back pain with, strategies for choosing NSAIDs in patients with osteoarthritis, the importance of timely administration of NSAIDs in the prevention of chronic pain syndromes, the influence of emotional and cognitive factors on the back pain chronization. The benefits of etoricoxib (Atorika) in the treatment of chronic back pain were reviewed, as well as the evidence for its safety.

Drug-induced parkinsonism (DIP) is the most common drug-induced movement disorder and is most commonly associated with antipsychotic drugs, monoamine reuptake inhibitors, and calcium channel blockers. DIP manifests as a typical movement disorder, which makes it practically indistinguishable from idiopathic Parkinson's disease (PD) and requires differential diagnosis. DIP symptoms develop fairly quickly (hours to weeks) after the antipsychotic is started or after the dose is increased. Therefore, DIP is predominantly a clinical diagnosis that must be kept in mind when a patient develops typical symptoms during treatment onset or increasing the dose of drugs that most often lead to such an adverse reaction (ADR). DIP evaluation includes using the Naranjo algorithm, which helps assess a causal relationship between drug intake and the development of parkinsonism symptoms. The primary DIP treatment is the reduction of the dose of the inducer drug, or its cancellation, or replacement with another drug. In patients with schizophrenia and antipsychotic-induced DIP, dose reduction, replacement with another medication, or prescription of a drug with anticholinergic activity may be possible. The awareness of the doctor and the patient about the possibility of developing this ADR is crucial in the prevention of DIP. Therefore, choosing a drug with the lowest risk of developing DIP is necessary for pharmacotherapy.

Drug-induced parkinsonism (DIP) is one of the most frequent extrapyramidal disorders that develops against the background of prescribing a large number of medications. Initially, DIP was described as an adverse drug reactions (ADRs) against the background of the use of antipsychotic drugs, but later recognized as ADRs of a number of other drugs, including prokinetics, antidepressants, calcium channel blockers and antiepileptic drugs. The relative risk of developing LIP on the background of taking typical antipsychotics increased by 2.92 times compared to patients who do not take these drugs. The risk of developing DIP in patients receiving flunarizine is increased by 2.75-4.07 times. The risk of DIP with the use of antidepressants is increased by 2.14 times, among the drugs of this group with an increased risk of DIP, the use of selective serotonin reuptake inhibitors is most often associated with DIP (relative risk 1.24). Among other antidepressants, there is evidence of the development of DIP against the background of the use of duloxetine, mirtazapine, amitriptyll clomipramine, venlafaxine, trazodone. Among anticonvulsants, DIP can rarely develop against the background of the appointment of valproic acid, gabapentin, pregabalin, carbamazepine, oxcarbazepine. The risk of DIP in patients receiving metoclopramide is extremely low (0.06%), but it is 2.16 times higher compared to people who do not take this drug. Among drugs from other groups, DIP can occur against the background of the use of lithium carbonate, tacrolimus, cyclosporine, amiodarone, captopril, amphotericin B. If DIP develops, it is necessary, if possible, to reduce the dose or cancel the inducer drug, or replace it with another drug with minimal risk of DIP. Symptoms of DIP most often regress within a few weeks or months after dose reduction or withdrawal of the drug inducer. If the symptoms persist longer, it is necessary to exclude the presence of Parkinson’s disease or dementia with with Lewy bodies.

The disease caused by the SARS-CoV-2 virus is multi-organ and involves almost all organs and systems. Myalgias and arthralgias and, in particular, back pain are common symptoms of COVID-19 and can be observed both at the onset of the disease and in the postcovid period. The causes of muscle and joint damage include both systemic inflammation and direct viral injury. Traditionally, musculoskeletal pain is treated with non-steroidal anti-inflammatory drugs. However, using this drug class in patients with COVID-19 requires caution due to the presence of comorbid diseases and possible complications of viral infection. The review discusses clinical variants and pathophysiological mechanisms of joints and muscles damage in patients with COVID-19 and treatment tactics for patients with musculoskeletal pain.

The worldwide prevalence of prediabetes is steadily increasing, with up to a third of patients already showing signs of diabetic neuropathy (DN). Prediabetes includes impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or a combination of both.Recent diagnostic criteria of prediabetes according to Russian, European, and American clinical guidelines are presented. The review covers the most common forms of DN in patients with prediabetes (distal symmetric sensory polyneuropathy, painful DN, cardiovascular autonomic neuropathy) and their prevalence. Recommended methods of DN screening are discussed: diagnostic scales, sensory testing, nerve conduction study, autonomic testing, corneal confocal microscopy. The results of studies evaluating instrumental methods for diagnosing peripheral nervous system (PNS) dysfunction in prediabetes are discussed. Management tactics in patients with prediabetes and PNS dysfunction should include non-pharmacological and pharmacological interventions. Combining a low-calorie diet and regular physical activity can delay the development of diabetes mellitus and reduce the severity of neuropathic pain. In patients with painful DN, the first-line therapy includes pregabalin, gabapentin, and duloxetine. Since there is no current data on the effect of hypoglycemic therapy on the risks of development and/or progression of DN in patients with prediabetes, antioxidants are considered pathogenetic therapy. Alpha-lipoic acid (Berlition®) in the management of patients with prediabetes is discussed.

Stroke is an acute disturbance of the blood supply to the brain, characterized by the sudden onset of focal neurological symptoms, which persists for more than 24 hours or leads to the death of the patient in a shorter period of time due to cerebrovascular pathology. In the world and in Russia, stroke remains one of the leading causes of death and disability. At the same time, ischemic stroke (IS) is more common – about 80% of cases. Many classes of drugs, such as oral contraceptives, nonsteroidal anti-inflammatory drugs, and various psychoactive substances, can contribute to the development of drug-induced IS (DI IS). Data upon the frequency of DI IS is limited. In part, this reflects the problem of identifying and confirming the causal relationship between drug prescription and the development of IS. DI IS risk factors include: abuse of caffeine and alcohol, older age, smoking, drug addiction, high doses of drugs containing provoking agents, the simultaneous use of several drugs, the presence of comorbid diseases. Adverse drug reactions develop due to the following pathophysiological mechanisms: cerebral embolism, vasoconstriction of cerebral arteries, vasculitis of the central nervous system, orthostatic hypotension. The management of a patient with a DI IS does not differ significantly from the management of a patient with IS of a different etiology and includes thrombolysis or mechanical thromboextraction (in the absence of contraindications), as well as rational methods of secondary prevention. It is necessary to completely cancel or reduce the dose of the drug, the use of which led to the development of a stroke. DI IS prevention measures include the choice of drugs with the lowest risk of its occurrence and the use of modern scales for assessing the risk of this phenomenon.

Administration of a rational and safe drug therapy is one of the most challenging issues for healthcare professionals. The frequency of hospitalizations due to the adverse drug reactions in the years 2000 — 2015 was estimated at 6.3 (3.3—11.0 %) for developed countries and 5.5 % (1.1—16.9 %) for developing countries. It is known that alcohol intake is a risk factor for many socially significant diseases, including arterial hypertension, coronary heart disease, chronic heart failure, etc., however, many doctors pay insufficient attention to the fact that many drugs, for example, beta-blockers, antidepressants, bezodisepines, calcium antagonists, can interact with alcohol when consumed simultaneously and, thus, increase the risks of adverse drug reactions. There are 2 main types of interactions between alcohol and drugs: pharmacokinetic (at the stage of absorption, distribution, metabolism and elimination) and pharmacodynamic (at the stage of effects and receptors). For example: the simultaneous intake of alcohol and paracetamol leads to the formation of toxic metabolites due to the induction of cytochrome P450 isoenzymes by alcohol. Another example is decrease in presystemic elimination and stimulation of the metabolism of tricyclic antidepressants; an increase in the elimination of imipramine and desipramine in patients with chronic alcoholism after detoxification therapy, and so on. In this article, the authors analyzed and systematized data from open literature sources in order to inform health care professionals about the possible risks associated with the interaction of alcohol and drugs and various pharmacological groups.

Recently, maximum attention has been drawn to the earliest forms of cognitive deficit - pre-mild cognitive decline (PMCD), which includes subjective (SjCD) and subtle cognitive decline (SCD), being the most promising in cognitive decline prevention.Objective: to assess the influence of genetic and comorbid emotional-affective factors on PMCD in middle-aged patients.Patients and methods. The study included 50 middle-aged people (60.76±9.5 years) with cognitive complaints. All patients underwent a cardiovascular assessment, including: biochemistry blood test (lipid profile, urea, glucose, vitamin В12, folic acid, homocysteine, thyroid hormones), duplex scan of the extracranial arteries, blood assay for АРОЕ4 determination, neuropsychological assessment with quantitative neuropsychological methods, emotional-affective background evaluation. In addition, magnetic resonance imaging (MRI) with morphometry of the hippocampus was performed in 20 patients.Results and discussion. Arterial hypertension, diabetes mellitus, and changes in laboratory parameters are significantly were more frequent in patients with SCD than patients with SjCD. The neuropsychological assessment showed maximum differences between SjCD and SCD groups in tests that evaluated reaction time (verbal fluency test, trail making test, part A, digit symbol substitution test, and Munsterberg test). Analysis of neuroimaging parameters revealed a smaller volume of the right hippocampus in APOE4 carriers. patients without depression performed significantly better on memory tasks, when depression was included in the analysis. In addition, patients with depression showed a significantly more pronounced degree of cortical atrophy on MRI.Conclusion. Patients with SCD have lower scores in neuropsychological tests than patients with SjCD. In addition, we observed a high significance of cardiovascular and emotional-affective risk factors in the PMCD development, emphasizing the importance of their evaluation and treatment in the management of patients with PMCD.

Gender is an important factor affecting the risk of drug-induced adverse reactions in patients. According to scientific literature, the risk of drug-induced symptoms, syndromes, and diseases is 1.5–1.7 times higher in women than in men. The aim of the study was to analyse and systematise data on the factors responsible for increased risk of drug-induced diseases in women. It was demonstrated that the increased risk of complications in women following the use of certain pharmacological classes of drugs is associated with a combination of factors that affect pharmacokinetics and pharmacodynamics. These factors include anatomical and physiological characteristics, specificity of enzyme and transport protein activity/expression. Women, compared to men, have higher percentage of adipose tissue and lower percentage of water in the body, which affects the volume of distribution of lipophilic agents, such as opioids and benzodiazepines, resulting in their accumulation in the body. Women have a lower rate of renal excretion and elimination, as compared to men, which may lead to adverse reactions following the use of medicines with predominantly urinary excretion. Changes in the endocrine profile in women taking sex steroids as replacement therapy or a contraceptive measure, as well as fluctuations in endogenous sex steroids during the menstrual cycle, pregnancy, perimenopause, influence the volume of distribution, the activity of cytochrome P450 enzymes, and the glomerular filtration rate, and, thus, may affect the pharmacokinetics and pharmacodynamics of other medicinal products, which, in turn, affect the safety of pharmacotherapy. In order to increase the safety of pharmacotherapy in women, it is necessary to consider the revealed specific pharmacokinetic and pharmacodynamic parameters of the medicine in a given group of patients when selecting the treatment regimen, including the dosage regimen and routes of administration.

Daytime somnolence may be a symptom of different somatic, neurological and psychiatric diseases and develop due to abuse and/or discontinuation of various medications. Drug- induced hypersomnia (DIH) is defined as hypersomnolence caused by the intake of multiple drugs. DIH is one of the most frequently reported effects and/or side effects of drugs. DIH prevalence varies widely and can be as high as 75% in patients receiving specific medications. DIH risk factors include elderly and senile age, impaired drug metabolism, serum drug concentration, method and frequency of drug administration, single and daily doses of drugs, etc., as in many other drug- induced diseases and syndromes. DIH can occur both due to sedative agents administration and withdrawal of psychostimulants and other activating psychotropic medications. Most often, the development of DIH is associated with the use of levodopa-carbidopa, antipsychotics, antidepressants. The pathogenesis of DIH is complex and multifactorial and is associated with the mechanism of action of individual drugs and the presence of concomitant diseases. The article discusses the risk assessment of DIH development due to various medications, diagnosis and management tactics of patients with DIH.

One of the depression causes is the use of certain drugs, and in this case, the term drug-induced depression (DID), medication-induced or iatrogenic depression is used. Symptoms of DID are similar to those observed in patients with other types of depression. DID is also associated with morbidity and mortality. Its development leads to a decrease in treatment adherence, and in some cases, to discontinuation of drugs that have predictive value. The main point in the management of patients with DID is the rapid detection and correction of symptoms and the application of prompt measures to prevent their development when prescribing certain drugs. The features of the course of DID, pathogenetic mechanisms and risk factors for its development, possible approaches to the treatment and prevention are discussed.

Some patients are more likely to have drug-induced diseases due to a number of risk factors, such as older age. The aim of the study was to analyse the effect of older age on pharmacokinetics and pharmacodynamics of medicines and the risk of developing drug-induced diseases. The analysis of scientific literature demonstrated that changes in the functions of body organs and systems caused by natural aging processes may potentially affect pharmacokinetics and pharmacodynamics of medicines and increase the risk of adverse drug reactions. For instance, older people have a decreased cardiac output both at rest and during exercise, weight loss, loss of elasticity of elastic vessels, a reduced number of functioning nephrons, poorer renal filtration capacity, decreased liver volume, a reduced number of functioning hepatocytes, decreased hepatic blood flow. These changes directly affect absorption, metabolism, distribution, and excretion of medicines, which in turn can affect their safety profiles. Consideration of age-related changes in the functions of body organs and systems, regular monitoring of the efficacy and safety of the prescribed medicine, changing the dosage regimen, and revision of the treatment sheet by healthcare professionals will help optimize pharmacotherapy and reduce the risk of adverse reactions and drug-induced diseases in older patients.

The neurological manifestations of the novel coronavirus COVID-19 infection caused by SARS-CoV-2 are extremely diverse. At the same time, there is currently very little data on the neurological complications of COVID-19. There are more and more publications on the presence of a complication, such as cognitive impairment (CI). The latter is analyzed in patients with COVID-19 during their hospital stay and later on. The paper discusses possible mechanisms, including a hyperinflammatory state (cytokine storm), coagulopathy, and the neurotropic effect of the virus, which may play a role in the development of CI in patients with COVID-19. It considers management tactics for patients with CI in the presence of coronavirus infection and the possibility of their correction with citicoline (Noocil®).

Drug-induced dystonia (DID) is a rarely diagnosed adverse reaction to a sufficiently large number of drugs. Acute DID (ADID) occurs soon after starting to take a drug or raising its dose, and switching from one antipsychotic medication to another, especially to its injectable dosage form. Tardive DID (TDID) develops a few months or years after starting drug intake or 3 months after stopping therapy. The diagnosis of TDID is based on the persistence of dystonic hyperkinesis for more than 1 month, the use of a dopamine receptor blocking agent, and the absence of other causes of its development. The risk factors for DID are male sex; young age (less than 30 years of age); a history of dystonic reactions; hypocalcemia, alcohol use while taking the drug. DID is most commonly related to therapy with antipsychotics, metoclopramide, antidepressants, and antiepileptic drugs. The short-term use of anticholinergic drugs (benzotropin, diphenhydramine) is effective in treating ADID. Anticholinergic drugs and atypical antipsychotics (clozapine, quetiapine), benzodiazepines, muscle relaxants (baclofen), and dopamine reuptake inhibitors (tetrabenazine) are used to treat TDID. To prevent DID, it is very important that a physician should be aware of that this unwanted adverse reaction may occur and that a drug with the lowest risk for DID should be chosen.

Atrial fibrillation (AF) and cognitive impairment (CI) are among the most important problems of the modern health care system, which are characterized by an extremely high prevalence with the increasing trend of the latter; they lead to lower quality of life, shorter duration, and a larger number of disabled people. The specific feature of AF and CI is the presence of common risk factors. To date, the data of an increasing number of studies allow cerebral microbleeds (CMBs) to be considered as a new risk factor for CI, inter alia in patients with AF. In recent years, special attention has been paid to the role of oral anticoagulants (OACs) in the prevention of CI in AF, which is reflected in a number of studies and meta-analyses. In terms of the effect of OACs on the risk of CMBs, there is reason to believe that the latter increases with the use of warfarin, the effects of direct OACs (DOAC) in this regard require further investigation. At the same time, among the DOACs, apixaban is the only drug that has been proven to have no negative effect on the risk of CMBs in a randomized controlled clinical trial. In general, the available data indicate the positive effect of OACs in reducing the risk of CI and dementia in AF; moreover, DOACs have an advantage in this respect. Among the DOACs, apixaban is promising due to its optimal efficacy and safety profile.

Arterial hypertension is one of the main modifiable risk factor for cognitive impairement (CI). Most frequently executive dysfunction is seen independent of age. Pathophysiological mechanisms linking hypertension and CI include the impact of increased blood pressure on large and small cerebral arteries. Large arteries dysfunction leads to occlusion, remodeling and arterial stiffness. Hypertension also causes small arteries dysfunction: lipohyalinosis and fibrinoid necrosis and due to insufficient amount of anastomosis and collaterals can lead to white matter damage. Treatment approach for patients with hypertension and CI should be multimodal and include treatment of the main cause of CI (antihypertensive therapy, statins and antithrombotics if necessary), symptomatic therapy (e.g. anti-dementia medications) and pathogenic treatment drugs that influence microcirculation, neuromethabolic therapy. Antihypertensive therapy is known to decrease dementia incidence, but the interclass differences remain unclear. Nicergoline (the ergot alkaloid derivative) is used in 30 countries to treat CI. Nicergoline improves CI due to its multidoi modal action, which includes increasing glucose metabolism in the brain, stimulation of cholinergic neurotransmission, increasing cerebral blood flow, influencing microcirculation due to decreasing arterial stiffness, blocking α1-adrenergic receptors. Nicergoline is effective in treating hypertensive patients with CI according to the data of a number of studies and meta-analysis. Evidencebased data also shows good tolerance profile of nicergoline.

Atrial fibrillation (AF) is a common rhythm disorder, especially in the elderly and senile people, and its incidence is expected to be only increasing. Another urgent problem of modern health care is cognitive impairment (CI) and dementia, which are also highly prevalent. Studies show that AF and CI are closely interrelated: patients with this heart rhythm disturbance are at increased risk for both CI in general and dementia in particular, their cognitive decline progresses faster regardless of whether AF is paroxysmal or permanent. The association between CI and AF is largely due to the commonality of risk factors, the main of which are considered to be elevated blood pressure, atherosclerotic vascular damage, diabetes mellitus, and age. To date, the specific pathogenetic mechanisms of CI development in AF have been described, indicating that both vascular and neurodegenerative changes are implicated in cognitive decline in the presence of cardiac arrhythmias in question. These changes include a history of stroke, the well-known risk factor for the cardioembolic type of which is AF; microembolism and microhemorrhage; predisposition to prothrombotic states; cerebral hypoperfusion and a proinflammatory shift associated with this arrhythmia. In addition, a potential adverse effect on CI can be produced by the use of antagonists of vitamin K, since the latter is an important trophic factor necessary for normal cognitive functioning.

Many classes of medications, such as antipsychotics, anticonvulsants, anticholinergics, and other commonly prescribed drugs, can cause cognitive impairment (CI). The negative effect of drugs on cognitive functions is due to the following pathophysiological mechanisms: a reduction in neuronal excitability, an increase in gamma-aminobutyric acid activity, and decreases in enzyme activity, the number of receptors, cerebral perfusion, as well as brain atrophy; moreover, a number of mechanisms have not been fully studied. An important role in the development of drug-induced CI is played by predisposing (senility or childhood, brain damage, chronic diseases, functional disorders, genetic causes, initial cognitive decline, polypragmasia), and precipitating (acute diseases, infections, metabolic disorders, dehydration, acute urinary retention, malnutrition, environmental influences, etc.) factors. The dose of a drug, the duration of its use is of absolute value. There is a need for the differential diagnosis of CI induced by drugs and CI directly related to the diseases, for which these drugs are prescribed. Drug-induced CI should be suspected if an association is established between a decline of cognitive functions and the start of drug intake. The treatment of this CI involves primarily dose withdrawal or reduction and the use of sustained-release dosage forms, if available. In some cases, cognitive training and/or special drug therapy may be required to correct the CI that has occurred. The measures to prevent drug-induced KI include the choice of the lowest-risk drugs, the use of current side-effect rating scales, in particular an anticholinergic burden scale.

Management of patients with cognitive impairment is one of the most relevant and important problems of neurology. It is especially important to identify cognitive impairment at the early (pre-dementia) stages, when appropriate medical measures are implemented, the progression of cognitive decline can be slowed down or stopped. Near-moderate cognitive decline (NMCD) at elderly and senile ages may be a predictor for the development of clinically significant cognitive impairment up to dementia. In most Western works, NMCD is associated with subjective cognitive decline, but it would be more legitimate to distinguish a form (a stage) of mild cognitive decline among NMCDs. It is assumed that NMCD is not necessarily a precursor to more severe cognitive impairment – the former can be a manifestation of age-related changes, emotional-affective disorders, and neurological and somatic diseases, although their presence substantially increases the risk of moderate and severe cognitive impairment. The review provides current ideas about the initial forms of cognitive decline, as well as neuroimaging data in these patients. It considers the influence of emotional-affective and cardiovascular factors on the development of cognitive deficit.

Tardive dyskinesia (TD) is a type caused by the use of different medications. The pathogenesis of TD is associated with dopamine receptor blockade, gamma-aminobutyric acid depletion, cholinergic deficiency, oxidative stress, impaired synaptic plasticity, and neurotoxicity. TD most often occurs after taking metoclopramide, antipsychotics, antidepressants, calcium channel blockers, and other drugs.The review considers an adequate assessment of the potential risk of TD when the patient uses prescribed drugs, as well as the monitoring and correction of risk factors for TD, discontinuation or replacement of drugs that potentially cause TD, as well as its treatment.

Atrial fibrillation (AF) is one of the most common cardiac arrhythmias in clinical practice and important additional risk factor for the development of cognitive impairment (CI) and dementia as it has been shown in recent studies. According to the Diagnostic and statistical manual of mental disorders latest revision CI refers to a decrease of one or more higher cortical functions that provide the processes of perception, storage, transformation and transmission of information compared to the premorbid level. The main hypothesis that explains the relationship between AF and dementia is the assumption that in the presence of this arrhythmia a brain substance is damaged due to microembolism and cerebral microbleeding. The high clinical significance of AF as well as CI served as a background for the development by European experts several consensus documents concerning the problem of the relationships between these conditions. In addition, they emphasize the role of anticoagulant therapy as a preventing tool for the development of stroke, which can be a factor in the CI progression in patients with AF, with particular priority to direct oral anticoagulants (DOACs). In randomized clinical trials, meta-analyses and systematic reviews have been shown that the use of DOACs, as compared to vitamin K antagonists, is a more rational strategy for preventing stroke associated with AF. Among the DOAC class, rivaroxaban is worth noticing as a drug that has a favorable efficacy profile for primary and secondary stroke prevention. Rivaroxaban distinguishing characteristics are a once daily administration as well as a calendar package which is practically important for patients with CI.

Headache is considered to be one of the main symptoms of arterial hypertension (HT). Complaints of headache are presented by many patients with HT: from 44% to 87%. It is obvious that the majority of complaints of headache in patients with HT is not due to headaches due to increased blood pressure (BP), but multimorbidity (polymorbidity) – the presence of coexisting primary headaches, most often, as in the population as a whole, chronic tension headache (57-85%) and migraine (15-30%). On the other hand, the frequency of HT in patients with migraine ranges from 32% to 44%. The relationship between migraine and HT may be due to common exogenous (external) and endogenous (genetic) factors, as well as common pathophysiological mechanisms. External risk factors, which can be associated with both migraine and HT, include the nature of the diet (excessive consumption of table salt with food), low physical activity, chronic stress; both diseases are also associated with the presence of a connection with the metabolic syndrome. The role of hyperactivation of the renin-angiotensin-aldosterone and adrenergic system and endothelial dysfunction are actively discussed. Angiotensin-converting enzyme takes an active part in the BP control and vascular tone; it is known that some angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) have demonstrated efficacy in preventing migraine attacks. The presence of HT can contribute to the chronic course of primary headache, and effective treatment of HT with antihypertensive drugs, on the contrary, can have a positive effect on the course of primary headaches. Antihypertensive drugs reduce the frequency of headaches compared to placebo, but heterogeneity between different classes was revealed. There was a statistically significant decrease in the frequency of headaches compared to placebo during treatment with beta-blockers, ACEI, ARB, diuretics, while calcium antagonists did not reduce the frequency of headaches. According to a number of studies, the frequency of headaches during the treatment with ARB (candesartan) is comparable to that in the placebo group. Some antihypertensive drugs are used to prevent migraine attacks.

The paper reviews the data available in the literature on and the results of the authors' own investigations of the signs of brain damage in hypertension in its early stages. The signs of early brain damage in hypertension can be considered as deteriorated control functions, white matter hyperintensities (WMH), as evidenced by the standard modes of magnetic resonance imaging (MRI), decreased fractional anisotropy in the frontal lobes, as shown by diffusion tensor MRI, and reduced cerebral perfusion. The latter two signs are detected even in hypertensive patients without WMH. Cognitive function testing and brain MRI using special regimens make it possible to identify a group of hypertensive patients at higher risk for cerebrovascular complications just in the early stages of the disease.

Arterial hypertension (HT) is one of the main recognized risk factors for the development of cognitive impairment and dementia. The results of most studies indicate that the presence of HT in elderly and senile people is associated with a decrease in cognitive functions and an increased risk of dementia in people of this age group, although some studies have identified the so-called "U-shaped curve”. The state of cognitive functions in middle-aged patients with HT has been studied to a much lesser extent, but it has been established that the presence of HT in middle age is associated with deterioration of cognitive functions and an increased risk of dementia in the elderly. In middle-aged hypertensive patients, cognitive impairment affected all cognitive domens, but to a greater extent - neurodynamic indicators of cognitive functions (speech activity, ability to concentrate, speed of cognitive processes). There are few data that levels of systolic blood pressure (BP) during the day, during wakefulness and sleep periods, insufficient night BP decrease, increased daily BP variability, and increased magnitude of the morning BP rise are interrelated with deterioration of the control functions/speed of cognitive processes. Pathogenetic aspects of the relationship of cognitive impairment and HT are diverse and include the hyperactivation of neuro-humoral systems (renin-angiotensin-aldosterone and sympathoadrenal, hypothalamic-pituitary-adrenal system dysfunction, reduction of cerebral perfusion, endothelial dysfunction. Anxiety-depressive disorders are of great importance in the occurrence of cognitive impairment in patients with HT, their interrelation is complex, dualistic, possibly due to a decrease in brain perfusion.

Different antihypertensive drugs differently affect cognitive function, and data on the effect of single-pill combination (SPC) of antihypertensive drugs on cognitive function are presented only in single studies.Aim. To investigate the impact of amlodipine/valsartan SPC (A/V SPC) on blood pressure (BP) level and cognitive functions in the middle-aged antihypertensive treatment-naive patients with stage II grade 1-2 essential arterial hypertension.Methods. A group of patients with stage II grade 1-2 essential arterial hypertension who had not previously received regular antihypertensive treatment (n=38, age 49.7±7.0 years) was retrospectively formed. All the patients were treated with A/V SPC and all of them achieved target office BP (less than 140/90 mm Hg). And after 12-week follow-up (since the time of reaching the target BP) the antihypertensive treatment efficacy assessment using ambulatory BP monitoring (ABPM) were performed in all included hypertensive patients. Age-matched healthy people with normal BP (n=20, mean age 45.4±5.1years) represented a control group. In all participants cognitive functions were evaluated by 5 different tests at baseline and at the end of follow-up: Montreal Cognitive Assessment (MoCA); Trail Making test (part A and part B), Stroop Color and Word Test; verbal fluency test; 10-item word list learning task. Baseline Hamilton depression and anxiety rating scale data were also available in all individuals.Results. According to the ABPM data 24-hour, day-time and night-time systolic, diastolic and pulse BP significantly decreased after the treatment with A/V SPC (p

One of the most frequent complaints of patients with hypertension (HT) is dizziness. Dizziness is understood as a variety of subjective sensations that patients define as “dizziness” – a sense of instability when walking, the illusion of rotation of surrounding objects, the feeling of approaching fainting, the inability to concentrate, and “fog” in the head. Experts share the systemic dizziness (vertigo) and non-systemic. The causes of vertigo in most cases are diseases of the inner ear (Meniere's disease, benign paroxysmal positional vertigo [BPPV], vestibular neuronitis. The most common form of dizziness is psychogenic dizziness. In the vast majority of cases, HT is not the cause of dizziness. The most common cause of vestibular (systemic) dizziness in patients with HT, as in the general population, is BPPV, and the most common cause of non-systemic dizziness is psychogenic dizziness. Among other causes of dizziness in patients with HT should be kept in mind too fast and/or intensive lowering of blood pressure, rhythm and conduction disorders, orthostatic hypotension (especially in elderly and senile patients in the presence of concomitant diabetes).

Elevated pulse pressure (PP) is the one of simplest and most accessible markers of vascular damage and increased arterial stiffness in hypertension (HTN). To date, an extensive body of evidence has been accumulated in terms of the PP effect on central nervous system (CNS), leading to neuronal damage and death, which contribute to the development and progression of cognitive impairment (CI). Elevated PP violate the blood-brain barrier, can intensify the production of reactive oxygen species in the CNS, lead to endothelial dysfunction, microbleeds and directly stimulate the amyloid beta creation, which is a substrate of Alzheimer’s disease. Due to the important role of increased PP in CI, an important aspect of antihypertensives’ effects is their impact on PP and the ability to reduce it. Among antihypertensives, a single-pill combination of amlodipine/indapamide sustained release deserves special attention, since it has a body of evidence for reducing PP and thereby improving cognitive functioning in patients with HTN, which in turn will improve their quality of life.

The disease caused by COVID-19 is multi-organ and involves almost all organs and systems. Myalgias and arthralgias and back pain are common symptoms of COVID-19 and can be observed both at the onset of the disease and in the postcoid period. The cause of muscle and joint damage is both systemic inflammation and direct damage by the virus. Musculoskeletal pain can be observed both at the onset of the disease and in the post-COVID period. Traditionally, musculoskeletal pain is treated with NSAIDs, however, the use of this group of drugs in patients with COVID-19 requires caution as to comorbidity and possible complications of viral infection. The article discusses clinical variants and pathogenetic mechanisms of damage of joints and muscles against the background of COVID-19 infection as well as treatment tactics for patients with skeletal muscle syndrome.

Objective: to investigate the effect of indapamide/perindopril fixed-dose combination (FC) on 24-hour blood pressure (BP) and cognitive functions in antihypertensive treatment-naive middle-aged patients with uncomplicated grade 1–2 essential arterial hypertension (EAH) . Patients and methods. The open prospective study enrolled 25 patients (9 men and 16 women) aged 40–59 years with a diastolic BP of 90–109 mm Hg and/or a systolic BP of 140–179 mm Hg, as evidenced by routine measurements. As starting antihypertensive therapy, the patients received indapamide 1.25/perindopril 5 mg FC once daily in the morning; if necessary, after 2 weeks (if the routine blood pressure was ≥140/90 mm Hg) they took indapamide 2.5/perindopril 10 mg once daily in the morning. The follow-up period was 14–16 weeks. Before and at the end of the follow-up, the patients underwent 24-hour ambulatory BP monitoring (ABPM) and evaluation of cognitive functions using the Montreal Cognitive Assessment (MoCA), ten-words test (immediate and delayed word recall), verbal association test (literal and categorical associations), number connecting test (Trail making test (TMT), part A and numbers and letters connecting test (TMT) part B), and Stroop test. Results. At the end of the follow-up period, treatment with indapamide/perindopril fixed-dose combination showed a statistically significant reduction in BPs, as evidenced by routine measurements and ABPM (during 24-hour, and awake and sleep periods); a statistically significant cognitive improvement: an increase in the number of the so-called words in the ten-words test during both immediate (from 5.5±1.6 6.5±1.5 words; p=0.02 vs baseline) and delayed (from 6.2±1.7 to 7.4±1.4 words; p=vs baseline) recalls, a decrease in the performance time of TMTB (from 112.6±42.5 to 90.4±28.4 sec; p=0.02) and Stroop test Part 3 (from 135.5±50.1 to 112.6±19.6 sec; p=0.02), and a larger number of called words in the categorical associations test (from 6.5±2.4 to 8.1±2.9 words; p=0.02). Conclusion. The results obtained indicate that in treatment-naive middle-aged patients with EAH, indapamide/perindopril fixed-dose combination assures an effective reduction in BPs, as evidenced by routine measurements and ABPM, also improves cognitive functions, particularly attention, information processing speed, semantic memory, cognitive flexibility, and short-term and long-term memory.

The article is devoted to the role of antihypertensive drugs in cerebroprotection, importance of such drugs in reducing the risk of stroke and cognitive disorders in patients with arterial hypertension (AH). The article provides the definition, classification and pathogenetic mechanisms of cognitive impairment in elevated blood pressure (BP). It also presents epidemiological characteristics of the incidence of stroke and cognitive disorders in hypertension. The influence of elevated blood pressure as a factor increasing the risk of cerebrovascular complications is considered. Particular attention is paid to the issue of a sharp rise in BP in the early morning hours, which is typical for patients with AH. The clinical significance of excessive early morning hypertension is discussed. The authors emphasize the difficulties and importance of correcting the morning rises in blood pressure as one of the objectives of antihypertensive therapy. The article presents data on the distinctive features of the pharmacokinetics and pharmacodynamics of candesartan, an angiotensin II receptor blocker with an extremely long-term action. The clinical efficacy of candesartan in the treatment of AH and the risk of cerebrovascular complications, especially stroke and cognitive impairment, has been demonstrated from the point of view of evidence-based medicine.

Diffusion tensor magnetic resonance imaging (DT-MRI) is the only noninvasive technique that makes it possible to study white matter microstructure in vivo and to quantify the images obtained. Objective: to study white matter in middle-aged treatment-naХve patients with uncomplicated grade 1–2 essential hypertension (EH), by using DT-MRI. Patients and methods. The investigation enrolled 82 people aged 40–59 years (41 patients with EH and 41 healthy individuals (a control group)). Twenty-four blood pressure monitoring and brain MRI were performed in different modes (T1 MPRAGE, T2 TSE, T2 FLAIR, and DTI). Results. White matter hyperintensities (WMHs) were found in 7.3% of the healthy individuals and in 53.7% of the hypertensive patients (p=0.0002). The latter had significantly lower fractional anisotropy (FA) values in the white matter of the left inferior frontal gyrus than the healthy individuals (0.39±0.06 and 0.45±0.09, respectively; p

Arterial spin labeling (ASL) is a promising non-invasive method to assess cerebral perfusion, which identifies a decrease in cerebral blood flow (CBF).Objective: to assess cerebral perfusion in middle-aged untreated patients with uncomplicated grade 1–2 hypertension compared to same-age healthy controls.Patients and methods. 33 patients with essential hypertension and 40 healthy individuals (a control group) at the age of 40–59 years were examined. 24-hour blood pressure (BP) monitoring and brain magnetic resonance imaging were performed in different modes (T1 MPRAGE, T2 TSE, T2 FLAIR, DTI, and ASL).Results. White matter hyperintensive changes were found in 7.5% of the healthy individuals and in 51.5% of the hypertensive patients (p = 0.0002). In hypertensive patients, CBF in the cortical plate of anterior frontal regions was significantly (p < 0.001) lower than that in the controls: right CBF, 39.1±5.6 and 45.8±3.2 ml/100 g/min, respectively; left CBF, 39.2±6.2 and 45.2±3.6 ml/100 g/min, respectively. In hypertensive patients with white matter hyperintensive changes, CBF was significantly lower than that in the controls: right CBF, 38.5±5.9 ml/100 g/min (p = 0.0001); left CBF, 39.2±6.7 ml/100 g/min (p = 0.002), and in those without these changes, right CBF was 39.5±5.1 ml/100 g/min (p = 0.0002); left CBF was 38.9±4.3 ml/100 g/min (p = 0.00002). Correlation analysis revealed significant inverse correlations of CBF with BP and systolic BP variability.Conclusion. Lower cerebral perfusion occurs in middle-aged untreated patients with uncomplicated grade 1–2 hypertension even in the absence of white matter hyperintensity foci.

Hypertension is one of the main modifiable risk factors for cognitive impairment (CI) and dementia in middle-aged and elderly patients. CI occurs in patients with hypertension even with its short duration and is manifested by controlling dysfunctiona and cognitive speed decline. The paper presents the results of a neuropsychological examination in 50 patients of middle age (47.54±5.2 years) with short-term (2.6±5.5 years) and uncomplicated hypertension. Stable blood pressure normalization during antihypertensive therapy improves cognitive function and prevents the progression of CI and the development of dementia. The use of nicergoline in patients with hypertension and CI is discussed.

Insomnia is frequently detected in patients with arterial hypertension (AH): from 19% to 47.9% of all cases according to epidemiological studies. On the other hand, the frequency of hypertension in patients with insomnia ranges from 21.4% to 50.2%, whereas in patients without insomnia, from 11.0% to 41.8%. In single studies in which patients with insomnia underwent ambulatory blood pressure monitoring (ABPM), these patients showed higher nocturnal blood pressure levels. Recent data suggests that insomnia is also a risk factor for hypertension. Among the pathogenetic mechanisms explaining the relationship between hypertension and insomnia, an increase in the activity of the main neuroendocrine stress systems, sympatho - adrenal and hypothalamic - pituitary - adrenal, and the frequent presence of concomitant anxiety disorders are discussed. To determine the sleep quality in patients with insomnia, the Pittsburgh Sleep Quality Index (PSQI) is most often used, patients with hypertension in a number of studies had higher total PSQI score compared to individuals with normal blood pressure. PSQI score correlates with systolic and diastolic blood pressure level, as well as with the presence of non - dipper blood pressure profile. Both hypertension and insomnia are associated with impaired cognitive functions. However, the relationship between cognitive impairment and insomnia is rather contradictory, which is most associated with the methodology for assessing cognitive functions and differences in the initial clinical and demographic characteristics of the examined patient population.