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Olga N Tkacheva,1 Nadezda K Runikhina,1 Valentina S Ostapenko,1 Natalia V Sharashkina,1 Elen A Mkhitaryan,1,2 Julia S Onuchina,1 Sergei N Lysenkov,1,3 Nikolai N Yakhno,2 Yan Press4–6 1Pirogov Russian National Medical University, The Russian Clinical Research Center for Gerontology, Moscow, Russia; 2Neurology Department, Sechenov First Moscow State Medical University, Moscow, Russia; 3Department of Evolution, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia; 4Department of Family Medicine, Siaal Research Center for Family Medicine and Primary Care, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; 5Yasski Clinic, Comprehensive Geriatric Assessment Unit, Clalit Health Services, Beer-Sheva, Israel; 6Unit for Community Geriatrics, Division of Health in the Community, Ben-Gurion University of the Negev, Beer-Sheva, Israel Background: Geriatric syndromes (GSs) are common in older adults and have a significant effect on their quality of life, disability, and use of health care resources. Few studies have assessed the prevalence of GSs in Russia. The aim of this study is to assess the prevalence of GSs among older adults living in the community in Moscow. Methods: A cross-sectional study was conducted in four community clinics in Moscow. A total of 1,220 patients completed a screening questionnaire, and 356 of them also underwent a comprehensive geriatric assessment (CGA). Results: The mean age of the 1,220 participants was 74.9±6.1 years; 75.5% were women. Based on the questionnaire, 58.3% reported visual or hearing impairment, 58.2% cognitive impairment, 46% mood disorder, 42% difficulty walking, 28.3% urinary incontinence, 21.3% traumatic falls (over the previous year), and 12.2% weight loss. The mean number of GSs per patient was 2.9±1.5. Based on CGA, a decline in Instrumental Activity of Daily Living score was identified in 34.8% of the patients, a risk of malnutrition (Mini-Nutritional Assessment score, 17–23.5) in 25.8%, probable cognitive impairment (Mini-Mental State Examination score 5) in 36.2%. On the whole, patients demonstrated good mobility (average walking speed, 1±0.2 m/s) and hand grip strength (23.9±6.4 kg in women and 39.1±8.3 kg in men), but poor balance (only 39.4% were able to maintain their balance on one leg for 10 s or more). Conclusion: The results of this study demonstrate a high prevalence of GSs among community-dwelling people aged 65 years and older in Moscow. The results provide a better understanding of the needs of older adults in Russia and can facilitate planning for medical and social assistance for this population. Keywords: geriatric syndromes, comprehensive geriatric assessment, questionnaire, community-dwelling, Russia

Dementia is one of the main challenges to modern society. According to estimated data, as of 2019, there were 1.949.811 people living In Russia with dementia of various etiology. At the same time, there have been no large epidemiological studies of dementia in the Russian Federation. The article provides an overview of the available data on the epidemiology of cognitive impairment (CI) In Russia given from various sources. Not only estimated, but also available clinical data were analyzed. In general, the obtained prevalence values for CI are comparable to global values. Thus, in an epidemiological study of people over 60 years of age in a separate district of Moscow, the prevalence of dementia was 10.4%, Alzheimer's disease 4.5%. A study of outpatients aged 60 years and older showed a high prevalence of both dementia and non-dementia CI at general medical appointments (incidence of dementia 7.8%, MCI 49.6%). It has been shown that the problem of non-dementia CI is already relevant in people of pre-retirement age (the prevalence of non-dementia CI in patients 55-64 years old is 36.8-44.8%). Unique data obtained in a population of institutionalized centenarians (prevalence of dementia 69%), as well as data on the relationship of CI with both somatic and demographic factors are presented.

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.

Cognitive impairment is one of the most common causes of reduced quality of life in older people. The aim of the study to evaluate impact of functional status, physical health and cognitive functions in women aged 55-64 years old. The study included 250 women aged 55-64 years (mean age 59,3±2,9 years). Socio-demographic and economic factors, functional and cognitive status were analyzed, the presence and prevalence of geriatric syndromes and their association with social, demographic and economic characteristics, risk factors for the development of chronic non-communicable diseases were studied. The prevalence of cognitive impairments was independently associated with education level, low income of patients, diabetes mellitus, glomerular filtration rate, and vertebral artery diameter. In this case, the level of education was a protective factor.

Pain has a significant impact on the quality of life of patients with multiple sclerosis (MS). However, the neurophysiological mechanisms of central neuropathic pain in a MS course are not known. We hypothesized that changes in power spectral density (PSD) that take place in the electroencephalography (EEG) of MS patients with and without the central neuropathic pain (CNP) would differ. The study aimed to assess the features of quantitative EEG using the PSD indicator along with peak frequencies in the standard frequency bands in MS patients with and without CNP. We have analyzed the quantitative spectral content of the EEG at a resting state in 12 MS patients with CNP, 12 MS patients without CNP, and 12 gender- and age-matched healthy controls using fast Fourier transformation. Based on the ANOVA, at the group level, the theta band absolute and relative PSD showed an increase, whereas alpha band relative PSD showed a decrease in MS patients both with and without CNP. However, only in MS with CNP group, the absolute and relative PSD in the beta1 and beta2 bands increased and exceeded that in patients without pain. Only MS patients with CNP demonstrated the significantly increased absolute PSD for the theta, beta1, and beta2 frequency bands in most regions of interest. In the theta band, MS patients with CNP displayed the increase in absolute spectral power for the mid-temporal derivation of the right hemisphere and the increase in relative spectral power for the prefrontal derivation of this hemisphere. In the beta1 band, the increase in absolute spectral power was observed for the three temporal derivations of the right hemisphere, whereas in the beta2 band, for the occipital, parietal, and temporal lobes of both hemispheres. In the alpha band, only a relative spectral power decrease was revealed for the occipital lobes of both hemispheres and parietal lobe of the right hemisphere. In MS patients with CNP, the frequencies of the dominant spectral power (peak frequencies) in the high-frequency beta band were higher than in the healthy control in posterior areas of the left hemisphere. Data could represent central nervous system alterations related to central neuropathic pain in MS patients that lead to the disturbances in cortical communication., (Copyright © 2020 Krupina, Churyukanov, Kukushkin and Yakhno.)

Objective: To evaluate the frequency of C9orf72 -associated frontotemporal dementia (FTD) in the Russian population and to study clinical features of GGGGCC-repeat expansion carriers., Material and Methods: Twenty-eight patients with FTD are included in the study: 15 with a behavioral variant of FTD (bvFTD) and 13 with a agrammatic/non-fluent variant of primary progressive aphasia (avPPA). The mean age was 62 years (34-80), the mean disease duration was 4 years (1-10). The positive family history was noted in 46% of cases. DNA diagnosis was performed using repeat-primed polymerase chain reaction., Results: The frequency of the C9orf72 repeat expansion in patients with FTD was 14%, in patients with bvFTD 20%, in patients with avPPA 8%. The mean age of disease onset in the expansion carriers was 63 (55-75) years. The frequency of the C9orf72 repeats expansion in familial FTD cases was 31%, in sporadic cases 7%. bvFTD with parkinsonian syndrome was noted in two out of four cases, bvFTD with amyotrophic lateral sclerosis (ALS) was shown in one case, avPPA with ALS was shown in one case. One female patient with bvFTD with parkinsonian syndrome presented with cognitive fluctuations that required a differential diagnosis with Lewy body disease., Conclusion: This is the first study of the genetic structure of FTD in the Russian population. The prevalence and clinical characteristics of C9orf72 -associated FTD were defined, in particular, the spectrum of motor symptoms was shown along with behavioral and aphasic disturbances. DNA diagnosis plays an important role in confirming the diagnosis and selection of patients for potential disease-modifying treatment.

An important approach to an early diagnosis of Parkinson's disease (PD) is screening for peripheral biomarkers in patients at the early clinical stage. In this study, we evaluated catecholamine concentration changes in the tear fluid of untreated PD patients as biomarkers. Norepinephrine and dopamine concentrations in the tear fluid of patients were found to increase compared to those in age controls, which was especially pronounced on the side where motor symptoms appeared. On the contrary, the epinephrine concentration in the tear fluid of patients was reduced bilaterally. Since there was no reason to consider the markers found in the clinical stage of PD as markers of the preclinical stage, we additionally studied the tear fluid composition in mouse neurotoxic models of PD preclinical and clinical stages. The norepinephrine concentration in the tear fluid of mice from the clinical stage model was found to be higher than that in controls; in the preclinical stage model, the norepinephrine concentration had a tendency to increase. Therefore, both PD patients and mice from PD preclinical and clinical stage models manifest unidirectional changes in their tear fluid compositions, which may be considered as promising biomarkers for the development of early diagnosis., (Copyright ® 2019 National Research University Higher School of Economics.)

Aim: Parasomnia, a syndrome of rapid eye movement sleep behavior disorder (RBD), is a common non-motor impairment in patients with Parkinson's disease (PD). The relationship between RBD with other symptoms of PD affecting night sleep, in particular, nocturia, is understudied. An aim of the study was to determine the symptoms related to night sleep disturbances in PD patients with RBD and assess the dynamics of these disturbances with the disease progression taking into account RBD onset., Material and Methods: One hundred and forty patients (72 male and 68 female) with PD without dementia (mean age 61.98±0.79 years, PD stage - 2.35±0.05, duration 5.82±90.65 years) were examined. Motor disorders were assessed with the unified Parkinson's disease rating scale (UPDRS), sleep disturbances and frequent night urinations were evaluated with the Parkinson's Disease Sleep Scale (PDSS). The diagnosis of probable RBD was based on reports of patients or their relatives on the dream-related motor activity and vocalization. Quality-of-life was evaluated with the Parkinson's Disease Questionnaire (PDQ-39). Patients were followed up after 2.5 years., Results: Probable RBD was diagnosed in 46.43% of patients, including 30.77%, who developed the syndrome before the manifestation of motor symptoms, 16.92% patients with simultaneous development of RBD and motor symptoms and 52.31% with RBD development >2 years after motor disorders. Patients with RBD differed from those without parasomnia by the higher severity of nocturia. After 2.5 years of follow-up, the severity of disease was greater in patients with RBD assessed by UPDRS, quality-of-life indices, severity of nocturia and episodes of nocturia. The highest frequency of episodes of nocturia was noted in patients with early onset of RBD before the manifestation of motor symptoms., Conclusion: RBD in patients with PD is associated with the rapid progress of nocturia, higher degree of worsening of daily activities and deterioration of quality of life. The relationship between RBD and progression of nighttime urination suggests common pathophysiological mechanisms of their development, which include the structural changes in the brain stem nuclei. The diagnosis of RBD is one of the markers of spreading of neurodegenerative pathology into the brain stem that resulted in the unfavorable disease course.

The paper presents original study results of cognitive changes associated with aging in the absence of neurodegenerative, vascular and other significant for cognition disorders in period from 50 to 85 years. It was shown that aging is associated with moderate memory decrease predominantly because of retrieval deficit but not acquisition insufficiency. It was also shown that aging is associated with non-severe executive dysfunction (lack of planning and control). According usual neuropsychological approaches pattern of cognitive changes described above reflects anterior cortical dysfunction or/and impaired interaction between frontal lobes and subcortical basal ganglia. Shows what physiological changes occur with age in the field of memory and executive functions, which is of great clinical importance for the differential diagnosis of normal aging and early stages of common in the elderly cerebral diseases.

Aim: To determine the prevalence and severity of non-cognitive nervous and psychiatric disorders (NNPD) in a behavioral variant of frontotemporal dementia., Material and Methods: Twenty-nine patients with BVFTD, aged from 41 to 73 years (mean 60.7±8.1 years), were studied. All patients underwent neurological and neuropsychological examinations. NNPD were assessed using the Neuropsychiatric Inventory (J. Cummings et al). Twenty-seven patients underwent brain MRI with T1, T2 and FLAIR sequences., Results: The most clinically significant symptoms of NNPD were apathy, behavioral disinhibition, eating disorders, abnormal motor activity and euphoria. Irritability, sleep disorders and excitement were less frequent. Anxiety and depression were identified in 13.8 and 20.7% of the patients, respectively. The severity of NNPD can increase and their spectrum can be qualitatively changed with the disease progression that indicates the spread of the neurodegenerative process., Conclusion: Patients with BVFTD had all NNPD with the exception of delusion and hallucinations. The character and degree of severity of some emotional, affective and behavioral disorders are associated with the predominant localization of the pathological process in frontal and temporal brain regions.

Background: The four-dimensional symptom questionnaire (4DSQ) is an originally Dutch self-report questionnaire that has been developed in primary care to distinguish non-specific general distress from depression, anxiety and somatization. In order to produce the appropriate translated Russian version the process of linguistic validation has been initiated. This process has been done according to the "Linguistic Validation Manual for Health Outcome Assessments" developed by MAPI institute., Objective: To produce the appropriate Russian version of the 4DSQ that is conceptually and linguistically equivalent to the original questionnaire., Methods: The original Dutch version of the 4DSQ was translated by one translator into Russian. The validated English version of the 4DSQ was translated by another translator into Russian without mutual consultation. The consensus version was created based on two translated versions. After that the back translation was performed to Dutch, some changes were implemented to the consensus Russian version and the second target version was developed based on these results. The second target version was sent to an appropriate group of reviewers. Based on their comments, the second target version was updated. After wards this version was tested in patients during cognitive interview. The study protocol was approved by the Independent Interdisciplinary Ethics Committee on Ethical Review for Clinical Studies, and in compliance with the Helsinki Declaration and ICH-GCP guidelines and local regulations. Enrolled patients provided written informed consent., Results: After the process of forward and backward translation, consultant and developer's comments, clinicians and cognitive review the final version of Russian 4DSQ was developed for assessment of distress, depression, anxiety and somatization., Conclusion: The Russian 4DSQ as a result of translation procedures and cognitive interviews linguistically corresponds to the original Dutch 4DSQ and could be assessed in psychometric validation for the further using in general practice.

Aim: To develop a new instrument able to identify pathological states and assess their changes during medication treatment. We aimed to study the typical practice of using alimemazine (teraligen) in patients with the diagnosis of autonomic nervous system disorder and to test the Russian version of @The Four-Dimensional Symptom Questionnaire@ (4DSQ) for measuring distress, depression, anxiety and somatization., Material and Methods: We examined 3053 patients (mean age 42.09 ± 11.71 years) who received teraligen in doses gradually increasing from 5 to 15 mg per day. The observational program was carried out in over 600 outpatient clinics of the Russian Federation. The 4DSQ was administered before treatment and 4 weeks after treatment. The Clinical Global Impression (CGI) scale was used before, during (after 2 weeks) and after (4 weeks) treatment with teraligen., Results and Conclusion: There was a significant improvement of patient's state assessed both by physicians (CGI scale) and by patients (96 and 98%, respectively). The 4DSQ was sensitive to the parameters of response to treatment with teraligen: parameters obtained at baseline and 4 weeks after the beginning of treatment differed significantly demonstrating a significant decrease in distress, anxiety and somatization.

Objective: Autonomic nervous system disorders are a frequent reason that makes patients to seek medical advice from general physicians and neurologists in outpatient clinics. The Dutch Four-Dimensional Symptoms Questionnaire (4DSQ) used for measuring distress, depression, anxiety and somatization is an adequate tool for identifying psychogenic factors for the development of autonomic disorders. An aim of the study was to localize the questionnaire to the Russian population., Material and Methods: The questionnaire was translated and the Russian version was subsequently psychometrically validated. The statistical analysis conducted for the verification of compatibility of the Russian version with the Dutch version was based on the survey of 243 patients., Results: All elements of the Russian version measured the same parameters of the Dutch 4DSQ. Some differences were identified., Conclusion: The analysis has confirmed the possibility of using the questionnaire in the Russian-speaking population using higher threshold values: +2 points for distress and anxiety, +4 points for somatization.

It has been postulated that Alzheimer disease (AD) is a systemic process, which involves multiple pathophysiological factors. A combination of pharmacotherapy and nonpharmacological interventions has been proposed to treat AD and other dementia. The nonpharmacological interventions include but are not limited to increasing sensory input through physical and mental activities, in order to modify cerebral blood flow and implementing nutritional interventions such as diet modification and vitamins and nutraceuticals therapy to vitalize brain functioning. This article highlights the recent research findings regarding novel treatment strategies aimed at modifying natural course of the disease and delaying cognitive decline through simultaneous implementation of pharmacological and nonpharmacological modulators as standardized treatment protocols.

A total of 88 patients with progression of Parkinson's disease (PD) were studied. Cognitive impairments (CI) in PD were in most cases progressive in nature, predominantly because of increases in the severity of dysregulatory and neurodynamic disorders, impairments to visuospatial functions, and, in some cases, deficits in nominative speech function. A high frequency of transformation of moderate cognitive impairments to dementia was demonstrated over periods of 2-5 years. Predictors of the progression of CI in PD were identified: elderly age, later onset of disease, and the severity of PD. The greatest rate of progression of CI was seen in patients with initially more severe impairments of regulatory and visuospatial functions.

Neuropsychological studies of 50 patients with Lewy body dementia (LBD) and 50 patients with Alzheimer's disease (AD) were performed to assess the characteristics of the cognitive impairments in these diseases. In patients with dementias of similar severities, patients with LBD showed greater impairment of executive and visuospatial functions and had more marked neurodynamic dysfunction. Patients with AD showed more profound memory disorders.

Objectives: To determine demographic or disease-related factors that may influence the severity of autonomic dysfunction in idiopathic Parkinson's disease (IPD)., Methods: 532 patients with IPD aged between 55 and 75 years were included. Severity of autonomic dysfunction was assessed using a 9-item autonomic dysfunction score (ADS). In addition, several demographic factors (e. g. age, gender, comorbidities) and disease- related (e. g. motor stage, disease duration, antiparkinsonian therapy) factors were recorded. A group of 67 age-matched healthy volunteers served as a control group. Demographic and clinical data of this cross-sectional survey were analyzed by a logistic stepwise regression model to determine independent predictors of autonomic dysfunction., Results: IPD patients showed significantly higher ADS values than controls, even in the youngest age groups and in mild disease stages. Hoehn & Yahr (H&Y) stage, disease duration, age at onset and various therapy combinations all showed significant correlations with ADS. However, stepwise logistic regression revealed that age (OR 10.71; CI 7.17-16.0) and arterial hypertension (OR 3.05; CI 1.66-5.58) were the only independent risk factors associated with autonomic dysfunction. Linear regression indicated that ADS increases with age in controls as well as in patients, but with a significantly steeper slope in the latter., Conclusions: Autonomic dysfunction as an inherent feature of IPD is present already in early disease stages. According to a logistic regression model, the severity of autonomic dysfunction in IPD is primarily related to demographic but not to disease-related factors. This and the differences in predictors for motor versus autonomic decline may indicate at least partly independent neurodegenerative processes.

Idiopathic Parkinson's disease (PD) can be subdivided by its patterns of motor symptoms into tremor-dominant (TDT), akinetic-rigid (ART), and mixed type (MT). Our objective was to determine whether age at onset and family history are different in these three types. In total, 366 patients with PD were assigned in a standardized approach to one of the three subtypes. Age at onset and family history were obtained in all patients and all presumably affected family members were examined. Mean ages at disease onset were similar in all three groups, but distribution of age at onset was markedly different: monophasic in TDT with a peak around 60 years, biphasic in ART with two peaks, one in the middle of the sixth decade (earlier onset, ART-EO), another during the first half of the seventh decade (later onset, ART-LO), and increasing with age only in MT patients A positive family history was significantly associated only with TDT (odds ratio = 5.7) and ART-EO (odds ratio = 7.8), but not with MT or ART-LO patients. Segregation analysis suggested an autosomal recessive mode of transmission in ART-EO and an autosomal dominant mode of transmission in TDT.

A total of 52 patients with Parkinson's disease (PD), 11 with presumptive Alzheimer's disease (AD), and 20 healthy subjects were studied; subjects were aged 55-74 years. Neurological symptoms were assessed quantitatively, and the state of higher mental processes were evaluated using the Luriya method. A number of memory tests were also used. These studies showed that PD was almost always accompanied by memory impairment exceeding the age norm. The major mechanism for memory impairment in PD without dementia was inadequate independent organization of memory-related activity at the memorizing and retrieval stages. In PD with dementia, there was also a primary impairment. Differences in memory impairments were found in PD with dementia (deeper derangements of involuntary memory and of information processing during memorizing). Impairments of consolidation of traces were more dependent on the age at onset of PD, while inadequacy of independent organization of memory-related activity was more dependent on disease duration. Most memory parameters in PD correlated with the severity of disturbances in gait and postural reflexes. It is suggested that memory impairment in PD is a manifestation of the major pathological process, which shows a number of differences from other neurogeriatric diseases.