[Drug-induced cognitive impairment and dementia]. / Lekarstvenno-indutsirovannye kognitivnye narusheniya i dementsiya.

One of the reasons for the development or worsening of cognitive impairment (CI) may be the use of a number of drugs: non-steroidal anti-inflammatory drugs, antiarrhythmics, antidepressants, glucocorticosteroids, antitumor drugs and a number of others. The negative effect of drugs on cognitive functions is realized due to many pathophysiological mechanisms: disruption of hormonal regulation, decreased neuronal excitability, increased activity of gamma-aminobutyric acid receptors, decreased cerebral circulation, atrophic changes in the brain; many mechanisms have not been fully established. Risk factors for the development of drug-induced CIs are: old age or childhood, brain damage, chronic diseases, genetic factors, the patient's initial CI, polypharmacy, dose and duration of drug use, acute infectious diseases, metabolic disorders, dehydration, acute urinary retention, etc. To diagnose and differentially diagnose drug-induced CI, it is necessary to establish a connection between the start of taking a suspected drug-inducer and a decrease in cognitive functions. The first step in the treatment of drug-induced CI is the abolition of an inducer drug or a reduction in its dose, in cases where it is impossible to discontinue the drug and there is no replacement, special slow-release dosage forms can be considered. The main measures to prevent drug-induced CI include the use of drugs with the lowest risk of their development, assessment of drug interactions, and the use of modern scales to assess the risk of developing this side-effect (anticholinergic burden scale, etc.).

[Mental disorders in blepharospasm]. / Psikhicheskie rasstroistva pri blefarospazme.

OBJECTIVE: To analyze mental disorders in blepharospasm (BS) before and after botulinum therapy (BT). MATERIAL AND METHODS: We examined 25 patients with BS (9 men and 16 women), aged 50 to 85 years (mean 64.1±18.5), with BS (main study group). The control group consisted of 20 healthy individuals (7 men and 13 women, mean age 63.5±8.5). Patients were examined before and after BT (after 3 weeks) using a diagnostic structured interview Mini International Neuropsychiatric Interview, GAD-7, PHQ-9, fear of negative assessment (short version) and The Liebowitz Social Anxiety Scale (LSAS). RESULTS: Fifty-six percent of patients with BS, as assessed by the GAD-7, showed a high level of anxiety, while depression, measured by the PHQ-9 and found in 52% of patients, was mainly manifested by mild disorders. In the group of patients with BS, the mean scores were higher on the GAD-7, PHQ-9, fear of negative assessment (p<0.001) and LSAS (p<0.05) than in the control group. After treatment with BT, the levels of anxiety and depression in patients with BS decreased slightly and remained higher compared with the control group. Psychiatric examination in the majority (64%) of patients revealed mental disorders that could not be explained by the occurrence of BS. The remaining 36% of patients had adaptation disorders (nosogenic reactions) caused by BS. Affective mental pathology (recurrent depressive disorder and dysthymia) and anxiety disorders (social phobia and adjustment disorders) were more often observed in the main study group compared with the control group (24% versus 5% and 68% versus 10%, respectively). CONCLUSION: A significant proportion of patients with BS have anxiety and depressive disorders, the severity of which does not depend only on the severity of motor symptoms and does not significantly decrease after successful BT, but is caused by mental disorders that preceded the manifestation of BS. Identification of mental disorders to varying degrees associated with BS, not only on the basis of psychometric scales, but also consultation with a psychiatrist, will allow, in addition to the correction of motor symptoms of BS, to differentiate the therapeutic approach through psychotherapy and psychopharmacotherapy.

[Management of patients with insomnia and polymorbidity: expert consensus]. / Vedenie patsientov s insomniei pri polimorbidnoi patologii: konsensus ekspertov.

Sleep disorders are becoming increasingly important due to the high comorbidity with other diseases and a significant impact on the patient's quality of life. Insomnia is the most common sleep disorder both in the general population and in patients with multimorbid pathology. Its prevalence in the general population is 6-15%, while in patients with somatic diseases it increases up to 20-40% and can reach 90% in patients with comorbid mental disorders. Another problem is the development of drug-induced insomnia. Insomnia has negative impact on the prognosis of comorbid diseases, including an increased risk of death, more severe disease, and a worse quality of life. The presence of sleep disorders makes it difficult to effectively treat the underlying disease, so it is extremely important to identify and correct these disorders in the early stages, therefore recommendations for the diagnosis of insomnia in polymorbid patients are proposed. Modern methods of treating acute and chronic insomnia and features of insomnia treatment in polymorbid patients are also discussed.

[Modern issues of improving the prognosis in patients with atrial fibrillation after ischemic stroke].

The anticoagulant therapy with a priority of direct oral anticoagulants is an approach to the prevention of recurrent stroke in patients with atrial fibrillation (AF) that has presently proved its efficacy and is stated in international clinical guidelines. An extensive evidence-based database demonstrates advantages of rivaroxaban over other drugs of this class in secondary prevention of stroke in AF. Furthermore, these advantages are combined with the optimal safety profile. The rivaroxaban treatment may provide the most favorable prognosis due to the prevention of recurrent stroke in AF, reducing the rate of kidney disease progression, and slowing vascular atherosclerosis. An important beneficial feature of rivaroxaban is once-a-day intake, which is important in the context of a high incidence of cognitive disorders in this patient category, and may improve their compliance and, thus, help achieving the expected profile of treatment efficacy. Thus, rivaroxaban can be regarded as a drug of choice for secondary prevention of stroke in AF.

[Efficacy and safety of mexidol across age groups in the acute and early recovery stages of hemispheric ischemic stroke (results of additional sub-analysis of a randomized double blind multicenter placebo-controlled study, in parallel groups trial EPICA)]. / Effektivnost' i bezopasnost' Meksidola u patsientov raznykh vozrastnykh grupp v ostrom i rannem vosstanovitel'nom periodakh polusharnogo ishemicheskogo insul'ta (rezul'taty subanaliza randomizirovannogo dvoinogo slepogo mul'titsentrovogo platsebo-kontroliruemogo v parallel'nykh gruppakh issledovaniya EPIKA).

AIM: To evaluate the efficacy and safety of prolonged sequential therapy with mexidol in the acute and early recovery stages of hemispheric ischemic stroke (IS) across age groups according to the World Health Organization classification. MATERIAL AND METHODS: The study is an additional analysis across age groups among patients participated in the randomized double blind multicenter placebo-controlled, in parallel groups trial EPICA. All subjects (62 men and 88 women) were subdivided into age groups: younger than 60 years, 60-65 years, 76-90 years. Additionally, all participants were divided into 2 populations: ITT (Intent to treat population, patients who received at least one treatment/placebo dose) and PP (Per protocol population, patients who received treatment per study protocol). Results of Modified Rankin scale (mRs) at the end of treatment period, Barthel index, Beck depression inventory, European Quality of Life Questionnaire were assessed. RESULTS: The efficacy of mexidol assessed with all the scales did not differ depending on the age group. By the end of treatment, the mean mRS score was lower in the 76-90 years subgroup (in both populations), compared to placebo (p<0.001). The decrease in mean mRS score (Visit 1-5) was more prominent in patients aged 60-65 years (p=0.025), including patients with diabetes mellitus (DM). Patients aged 76-90 years and patients with DM, compared to placebo, had a decrease of the severity of cognitive-affective depression symptoms (p=0.049 and p=0.02) and an increase in patients without problems with everyday activities (p=0.007 and p=0.02). Patients with DM, compared to placebo, also had the higher levels of everyday activity (p=0.023) and quality of life (p=0.045). There were no statistically significant differences in the frequency of side-effects in patients of all groups. CONCLUSION: It is recommended to include mexidol in therapy of patients with IS in the acute and early rehabilitation stages in all age groups, including patients with DM.

[Drug-induced restless legs syndrome]. / Lekarstvenno-indutsirovannyi sindrom bespokoinykh nog.

Restless legs syndrome (RLS) is a sensorimotor disorder characterized by complaints of a strong desire to move legs during periods of rest or inactivity, which is relieved by movement (most pronounced in the evening or at night). Multiple studies have reported drug-induced RLS caused by antipsychotics, antidepressants and antiepileptic medications. Risk factors for drug-induced RLS include older age, gastrointestinal diseases, high medication dose, simultaneous use of ≥2 drugs. The mechanism of drug-induced RLS is most often associated with the effect of medications on various receptors and neurotransmitter systems, in particular, the dopamine system. Drug-induced RLS treatment includes identification and withdrawal of a drug that caused RLS or a decrease in its dosage. Prevention of drug-induced RLS is based on compliance with the principles of rational pharmacotherapy.

[Hypertension and insomnia].

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.

[Drug-induced seizures: prevalence, risk factors, treatment and prevention]. / Lekarstvenno-indutsirovannye épilepticheskie pristupy: rasprostranennost', faktory riska, lechenie i profilaktika.

There is a growing interest to the problem of drug-induced epileptic seizures (ES) due to their relatively high prevalence, poor prognosis, a large number of different drugs associated with the development of drug-induced ES, and low awareness among general practitioners. Drug-induced ES are most often associated with the use of antidepressants, antipsychotics, antiepileptic drugs (overdose or as a result of discontinuation), antibiotics, immunosuppressants and immunomodulators, antitumor agents, analgesics, central nervous system stimulators, anesthetics etc. The prevalence of drug-induced ES varies with different drugs. It is estimated that about 6.1% of the first occurring ES are drug-induced. Risk factors for drug-induced ES include a history of epilepsy or ES, cancer, blood-brain barrier dysfunction, several concomitant neurological diseases, mental disorders, childhood, old and very old age, fever, impaired liver metabolism in patients with liver diseases, impaired drug excretion in patients with kidney diseases, polypharmacy, pharmacokinetic properties of the drugs themselves, allowing them to penetrate the blood-brain barrier in the central nervous system (lipophilicity, transport and communication with blood plasma proteins), drug concentration in blood serum, method and frequency of drug administration, single and daily doses of drugs. No clinical guidelines for the management of patients with drug-induced ES are available. It is recommended to identify patients at risk: elderly patients, patients with impaired liver and kidney function and patients receiving drugs that can cause ES and/or lower the seizure threshold. Benzodiazepines are the first-line treatment in drug-induced status epilepticus, barbiturates and propofol are the second-line treatment. The general principles for the prevention of drug-induced ES include careful selection of the optimal dose of drugs that can cause ES, especially in patients with impaired liver and/or kidney function, monitoring of several parameters in blood serum (for example, liver enzymes, electrolytes, glucose etc.), monitoring of the blood plasma concentration of certain drugs, avoiding the simultaneous administration of several drugs that stimulate the central nervous system, and a rapid discontinuation of such drugs.

[Cognitive Disorders and Dementia in Old Patients With Arterial Hypertension].

The article describes the definition of dementia, its diagnostic criteria, classification. Differences in the pathogenesis and clinical manifestations of different types of dementia are considered. The issues of interrelation of arterial hypertension and the risk of development of cognitive disorders and dementia in old and very old people are discussed in detail. Data on the effect of antihypertensive drugs of different groups on the risk of dementia and the state of cognitive functions are presented. The evidence base of dihydropyridine calcium antagonist amlodipine and thiazide-like diuretic indapamide-retard is discussed with respect to the prevention of dementia and cognitive decline and their beneficial effect on cognitive function in patients with arterial hypertension.

[Cognitive functions, emotional status, MRI measurements in treatment-naïve middle-aged patients with uncomplicated essential arterial hypertension]. / Kognitivnye funktsii, émotsional'nyi status i pokazateli magnitno-rezonansnoi tomografii u nelechenykh patsientov srednego vozrasta s neoslozhnennoi arterial'noi gipertenziei.

AIM: To study cognitive functions, anxiety and depression levels, 24-hour blood pressure (BP) profile, cerebral blood flow (CBF) perfusion in treatment-naive middle-aged patients with uncomplicated essential arterial hypertension (EAH) depending on the white matter hyperintensities (WMH) burden. MATERIAL AND METHODS: Forty-one hypertensive patients (mean age 46.2±4.6 years) and 41 healthy volunteers (mean age 50.3±6.7 years) were enrolled to the study. All subjects underwent brain MRI (MAGNETOM Skyra 3.0T, T1, T2 FSE, T2 FLAIR, T1 MPRAGE, ASL), Montreal cognitive assessment (MoCa), 10-word learning task, verbal fluency test, trail making test, Stroop color and word test, anxiety and depression assessment with Hamilton rating scales, 24-hour blood pressure monitoring (ABPM). RESULTS: WMH were found in 22 (53.7%) hypertensive patients and in 3 (7.3%) healthy volunteers (p=0.0002). Hypertensive patients had the significantly lower CBF compared to controls (p<0.001). CONCLUSION: WMH were identified in treatment-naive middle-aged patients with uncomplicated mild to moderate EAH. There was an association between WMH and lower CBF in the cortical plate of frontal lobes, SBP variability and worse cognition. Cerebral hypoperfusion can cause cognitive impairment even in the earliest stages of EAH, which increases due to emotional disorders.

[Brain Perfusion, Cognitive Functions, and Vascular Age in Middle Aged Patients With Essential Arterial Hypertension].

OBJECTIVE: This study aimed to assess the cognitive functions and cerebral blood flow measured with arterial spin labeling (ASL) and their possible correlations with vascular age in untreated middle-aged patients with grade 1-2 essential arterial hypertension (EAH). METHODS: We examined 73 subjects aged 40-59 years (33 with EAH and 40 healthy volunteers [controls]). Neuropsychological assessment included Montreal Cognitive Assessment (MoCA), Trail Making test (part A and part B), Stroop Color and Word Test, verbal fluency test (phonemic verbal fluency and semantic verbal fluency), 10­item word list learning task. All subjects underwent brain MRI. MRI protocol included ASL. Vascular age was calculated by two techniques - using Framingham Heart Study risk tables and SCORE project scales. RESULTS: Patients with EAH had lower performance on phonemic verbal fluency test and lower mean MoCA score (29.2±1.4 vs. 28.1±1.7 points) compared to controls (13.4±3.2, р=0.002; 29.2±1.4, p=0.001, respectively). White matter hyperintensities (WMH) were present in 7.5 % controls and in 51.5 % EAH patients (р=0.0002). Cerebral blood flow (CBF) in EAH patients was lower in both right (39.1±5.6 vs. 45.8±3.2 ml / 100 g / min) and left frontal lobes of the brain (39.2±6.2 и 45.2±3.6 ml / 100 g / min, respectively) compared to controls (р.

[24­Hour Arterial Pressure Variability: Prognostic Significance, Methods of Evaluation, Effect of Antihypertensive Therapy].

We discuss in this article problems of prognostic significance of 24­hour arterial pressure variability (24hAPV), as well as the role of 24hAPV in development and progression of various target organs damage by arterial hypertension. We also present literature data on impact of various regimens of antihypertensive therapy on 24hAPV, and on ability of fixed-dose perindopril/amlodipine to lower 24­hAPV.