[Neuroimaging of cerebral small vessel disease in mild cognitive impairment in older adults.]

Cerebral small vessel disease (CSVD) - is a clinical and radiological phenomenon characteristic of older adults. Currently, the extent of white matter lesions (WML) in patients with moderate cognitive disorders remains uncertain. Also, the relationship of cognitive impairment with the volume of WML has not been sufficiently studied. The aim of the study was to analyze the WML volumes in patients with subcortical vascular mild cognitive impairment (svMCI) and in the control group according to magnetic resonance imaging (MRI). The study included 50 people: 25 patients with svMCI (average age 75,88±4,04 years) and 25 conditionally healthy volunteers (average age 69,96±3,07 years). Significant differences in the volume of WML between the study groups were obtained. The fraction of hypointense WML was 0,74±0,41 in patients with svMCI and 0,15±0,07 in the control group. In the correlation analysis in the svMCI group, only the function of mental control showed a negative relationship with the fraction of WML. The data obtained suggest that the assessment of the volume of WML is important in patients with svMCI, but does not fully explain the decline in cognitive functions.

Impaired Sphingolipid Hydrolase Activities in Dementia with Lewy Bodies and Multiple System Atrophy.

The synucleinopathies are a group of neurodegenerative diseases characterized by the oligomerization of alpha-synuclein protein in neurons or glial cells. Recent studies provide data that ceramide metabolism impairment may play a role in the pathogenesis of synucleinopathies due to its influence on alpha-synuclein accumulation. The aim of the current study was to assess changes in activities of enzymes involved in ceramide metabolism in patients with different synucleinopathies (Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA)). The study enrolled 163 PD, 44 DLB, and 30 MSA patients as well as 159 controls. Glucocerebrosidase, alpha-galactosidase, acid sphingomyelinase enzyme activities, and concentrations of the corresponding substrates (hexosylsphingosine, globotriaosylsphingosine, lysosphingomyelin) were measured by liquid chromatography tandem-mass spectrometry in blood. Expression levels of GBA, GLA, and SMPD1 genes encoding glucoceresobridase, alpha-galactosidase, and acid sphingomyelinase enzymes, correspondently, were analyzed by real-time PCR with TaqMan assay in CD45 + blood cells. Increased hexosylsphingosine concentration was observed in DLB and MSA patients in comparison to PD and controls (p < 0.001) and it was associated with earlier age at onset (AAO) of DLB (p = 0.0008). SMPD1 expression was decreased in MSA compared to controls (p = 0.015). Acid sphingomyelinase activity was decreased in DLB, MSA patients compared to PD patients (p < 0.0001, p < 0.0001, respectively), and in MSA compared to controls (p < 0.0001). Lower acid sphingomyelinase activity was associated with earlier AAO of PD (p = 0.012). Our data support the role of lysosomal dysfunction in the pathogenesis of synucleinopathies, namely, the pronounced alterations of lysosomal activities involved in ceramide metabolism in patients with MSA and DLB.

[Comparative analysis of unsaturated indicators fatty acids in elderly patients in initial stages of Alzheimer's disease and vascular dementia.]

A decrease in cognitive functions up to the development of dementia in the elderly is associated with a decrease in the blood level of polyunsaturated fatty acids, especially Omega-3, which occurs against the background of oxidative stress. The paper presents a comparative analysis of the spectrum of polyunsaturated fatty acids and the activity of individual components of the enzymatic antioxidant system in the blood of elderly people with impaired cognitive performance to the level of «mild cognitive decline¼ (MCI AD, prodromal Alzheimer's disease) or vascular etiology (MCI VaD, prodromal vascular dementia) compared with older people without signs of cognitive impairment. A decrease in the concentration of Omega-3 polyunsaturated fatty acids in the blood of both groups of the examined patients was revealed compared with the control group. In patients with AD MCI, a sharp decrease in the concentration of arachidonic acid (Omega-6) was detected compared with patients with MCI VaD and the control group. The decrease in the activity of the antioxidant enzymatic system and the decrease in polyunsaturated fatty acids due to their peroxidation revealed in this study indicate an intensification of the OS processes in patients with impaired cognitive functions. The question of the pathogenetic role of arachidonic acid in patients predisposed in the future to the development of AD is discussed.

Plasma cytokine profile in synucleinophaties with dementia.

Immune response may play a pivotal role in the pathogenesis of the common synucleinopathy as Parkinson's disease (PD) and could be mediated with the accumulation of neurotoxic alpha-synuclein. There is limited evidence for immune response in another synucleinopathy as dementia with Lewy bodies (DLB). Recent data suggest that immune response may contribute to cognitive impairment. We aimed to estimate plasma cytokine profile in patients with synucleinopathies with dementia (PD dementia (PDD), DLB). Plasma cytokine levels (interferon-gamma (IFN-gamma), interleukin (IL)-4 (IL-4), IL-6, IL-10, tumor necrosis factor alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1)). were estimated in 16 patients with DLB, 19 patients with PDD, 28 patients with PD without dementia (PD) and 19 individuals without neurological disorders (controls) using Luminex array system. Cognitive status was assessed with the Mini-Mental State Examination (MMSE). TNF-alpha and IL-6 plasma levels were elevated in patients with synucleinopathies with dementia (DLB, PDD) compared to controls and IL-10 plasma level was increased in PDD compared to controls (p < 0.05). IFN-gamma levels were decreased in PD and PDD patients compared to controls (p < 0.001, p = 0.026, respectively) and in PD patients than in DLB patients (p = 0.032). Patients with PD, PDD, and DLB were characterized by increased plasma levels of MCP-1 compared to controls (p < 0.001). At the same time, no differences in TNF-alpha, IL-10, IL-6 plasma levels in PD patients compared to controls were found. Our study demonstrated more pronounced immune response in synucleinopathies associated with dementia compared to PD without demetia.

[What is normal cognitive aging?]

Using the Addenbrooke's Cognitive Examination (ACE-III), the Stroop Test (ST), the Wechsler Memory Scale (WMS), and the Frontal Assessment Battery (FAB), we examined 44 respondents of an almost healthy «age norm¼ from 52 to 95 years old. Depending on age, the sample was divided into 2 groups, the first group included people under the age of 65 years (64 years old inclusive), the second group consisted of subjects over 65 years old. Statistically significant differences in the results of the survey of respondents of the two groups by the ACE-III were found in Memory and Total score indicators, while the level of cognitive functioning measured by the ACE-III decreased with age. The results of comparing the survey data using the Stroop Test indicate a decrease in the pace of work under load conditions and a weakening in the flexibility of organization of mental activity and concentration of attention, as well as increased interference in individuals of a more age group examined by us. Correlation analysis of the Stroop test data and the age of the examined showed cognitive control over information processing decreases, interfering influences increase, accuracy and pace of activity decrease, and the activity itself becomes more rigidas age increases. The results of the correlation analysis of the indicators of the WMS and age demonstrated a decrease in the level of mental control over activity, a deterioration of memory in the visual modality, and a progressive working memory reduction as age increases. With the growth of age, a decrease in frontal (executive) functions of healthy subjects, evaluated by the FAB, was found.

[A study of the duration of the disease as a risk factor for the development of hospitalization in elderly psychiatric patients.]

Phenomenon of hospitalism in elderly patients with mental disorders is an extremely important clinical, social and economic problem. 155 patients of the gerontopsychiatric hospital were examined, 75 of them showed signs of hospitalism, and 80 made up a control group. A subgroup of patients with signs and short duration of the disease was isolated, the duration of treatment in the hospital of these patients was 133,5±42,24 days (in the corresponding control subgroup 72,11±37,11 days, p<0,05). This subgroup was characterized by greater impulsiveness as a personality trait and less adaptive coping strategies. A subgroup of patients with signs of hospitalism and a longer duration of the disease also had a longer stay in the hospital compared to patients with a similar experience of illness without hospitalism (249,67±63,56 and 79,58±39,52 days, respectively, p<0,05). For this subgroup of patients, the factors associated with the development of hospitalism were higher anxiety and depression in the current psychoemotional state, a smaller representation of adaptive cognitive coping and less sensitivity to the disease, all differences are significant at p<0,05.

[Oxidative stress and its effect on cells functional activity of alzheimer's disease].

The paper summarizes literature data on the importance of oxidative stress as one of the pathogenetic mechanisms in Alzheimer's disease. The paper describes the main specific and nonspecific ways of reactive oxygen species generation in the course of the disease development. The effect of reactive oxygen species generated by the functional activity of cells, i.e. apoptosis and mitotic cycle, is shown. The role of the regulatory system of nodal cells is performed by phosphorylation/dephosphorylation process which is associated with intense phosphorylation of tau protein and mitosis-specific proteins. In Alzheimer's disease, the regulating function of peptidyl-prolyl isomerases in particular of Pin1 associated with maintaining a balanced state of phosphorylation/dephosphorylation processes is disturbed. Taking into consideration the multifactorial impairment of the cell cycle control, this process should be considered from the standpoint of the general state of metabolic processes, and oxidative stress has one of the key positions in aging.

[The recovery model of schizophrenia: could it be currently used?]. / Vosstanovitel'naya model' terapii shizofrenii: vypolnima li ona v sovremennykh usloviyakh?

UNLABELLED: The long-term antipsychotic treatment remains one of the main methods of treatment of schizophrenia. Drug choice is determined by a plethora of factors though two groups of antipsychotics (traditional neuroleptics and atypical antipsychotics) are currently the basic ones. The development of a new generation of atypical antipsychotics has given the possibility to improve significantly treatment RESULTS: The article presents the data on pharmacodynamics and pharmacokinetic properties of ziprasidone, its efficacy and safety in schizophrenia, including its treatment-refractory forms.