[Assessment of the significance of dilated perivascular spaces and nocture arterial hypertension in the development of Alzheimer's disease]. / Otsenka znacheniya rasshirennykh perivaskulyarnykh prostranstv i nochnoi arterial'noi gipertenzii v razvitii bolezni Al'tsgeimera.

OBJECTIVE: To study the severity and localization of dilated perivascular spaces (DPVS), the levels of protein markers of amyloidosis and neurodegeneration in the cerebrospinal fluid (CSF) at different daily blood pressure (BP) profiles in patients with Alzheimer's disease (AD) and other types of cognitive impairment. MATERIAL AND METHODS: A total of 119 people, aged 53 to 92 years, including 55 patients with AD, 27 patients with vascular cognitive disorders (VCD), 19 patients with frontotemporal degeneration (FTD). All patients underwent BP monitoring for 24 hours using a standard oscillometric measurement method, lumbar puncture to assess Aß-42 and Aß-40 amyloid protein, total and phosphorylated tau protein in the CSF, magnetic resonance imaging tomography of the brain with subsequent assessment of the severity of expansion and localization of DPVS according to the G.M. Potter scale. RESULTS: In 58.3% of patients with AD, there is no adequate reduction in BP at night in comparison with patients with VCD (p<0.05). A significant degree of expansion of the DPVS turned out to be most typical for patients with AD: grade 3 was detected in 45.7% of patients, and the maximum, grade 4, was detected in 13.4%. At the same time, DPVSs were significantly more often detected in the group of subjects with insufficient reduction in diastolic BP (DBP) at night. A strong inverse correlation was established between the level of Aß-42 in the CSF and the variability of DBP at night (r= -0.92; p<0.05). The decrease in the level of Aß-42 in AD, especially at the prodromal stage, is directly related to the low variability of DBP at night, which is more characteristic of an insufficient decrease or increase in BP during night sleep. CONCLUSION: Patients with AD were characterized by an insufficient decrease in BP at night, which is associated with the severity and degree of maximum expansion of the DPVS. A decrease in the level of Aß-42 amyloid protein in the CSF strongly correlates with the variability of DBP at night.

[Multi-center open comparative randomized study of efficacy and safety of Akatinol Memantine 20 mg (single-doses) vs Akatinol Memantine 10 mg (double-doses) in patients with vascular dementia]. / Mnogotsentrovoe otkrytoe sravnitel'noe randomizirovannoe issledovanie effektivnosti i bezopasnosti primeneniya preparata Akatinol Memantin, 20 mg (odnokratnyi priem) v sravnenii s preparatom Akatinol Memantin, 10 mg (dvukratnyi priem) u patsientov s sosudistoi dementsiei.

OBJECTIVE: Evaluation of the efficacy and safety of the drug Acatinol Memantine, 20 mg (once daily) in comparison with the drug Acatinol Memantine, 10 mg (twice daily) in patients with moderate to moderate severe vascular dementia. MATERIAL AND METHODS: The study included 130 patients aged 50-85 years of both sexes with instrumentally and clinically confirmed vascular dementia. The patients were randomized into 2 groups. Group I consisted of 65 patients receiving Akatinol Memantine, 20 mg once daily, group II - 65 patients receiving Akatinol Memantine, 10 mg twice daily for 24 weeks. Clinical, parametric and statistical research methods were used. The Alzheimer's disease assessment scale, the cognitive subscale (ADAS-cog), the short mental Status Assessment Scale (MMSE) and the general clinical impression scale for patients condition and illness severity (CGI-C and CGI-S) and the Hamilton Depression Rating scale (HAM-D) were used. Adverse events were collected and analyzed. RESULTS: At week 24, both groups showed statistically significant positive change in ADAS-cog total score: in group I the total score was 27.2±8.76 points (absolute difference from baseline 3.5 points; p<0.01), and in group II - 26.1±7.86 points (absolute difference from baseline 2.5 points; p<0.01) with no statistically significant differences between groups. Evaluation of secondary efficacy criteria (change in ADAS-cog total score at week 12 and MMSE at weeks 4, 12, and 24) also revealed statistically significant benefit in both groups compared to baseline with no significant differences between groups. Statistically significant improvement was noticed on CGI-S and CGI-C scales in both groups. Akatinol Memantine was safe and well tolerated in both groups. CONCLUSION: The study showed no lesser efficacy and safety of Akatinol Memantine, 20 mg (once daily) compared to Akatinol Memantine, 10 mg (twice daily) in patients with moderate and moderately severe vascular dementia.

[Traumatic brain injury as risk factor of Alzheimer's disease and possibilities of pathogenetic therapy]. / Cherepno-mozgovaya travma kak faktor riska bolezni Al'tsgeimera i vozmozhnosti patogeneticheskoi terapii.

The article examines the potential role of brain mechanical damage as a trigger for the development of neurodegenerative changes. Attention is paid to dysfunction of the neurovascular unit, and disruption of the functional and compensatory capabilities of blood flow. The importance of microhemorrhages that occur in the acute period of injury and the formation of first focal and then diffuse neuroinflammation is emphasized. The importance of mitochondrial dysfunction was separately determined as a significant factor in increasing the risk of developing Alzheimer's disease (AD) in patients after traumatic brain injury (TBI). In TBI, there is a decrease in the expression of tight junction (TC) proteins of endothelial cells, such as occludin, claudin, JP, which leads to increased permeability of the blood-brain barrier. TBI, provoking endothelial dysfunction, contributes to the development of metabolic disorders of ß-amyloid and tau protein, which in turn leads to worsening vascular damage, resulting in a vicious circle that can ultimately lead to the development of AD and dementia. Age-related changes in cerebral arteries, which impair perivascular transport of interstitial fluid, are currently considered as an important part of the «amyloid cascade¼, especially against the background of genetically mediated disorders of glial membranes associated with defective aquaporin-4 (encoded by the APOE4). Studies in animal models of TBI have revealed an increase in tau protein immunoreactivity and its phosphorylation, which correlates with the severity of injury. A comprehensive analysis of research results shows that the cascade of reactions triggered by TBI includes all the main elements of the pathogenesis of AD: disorders of energy metabolism, microcirculation and clearance of cerebral metabolic products. This leads to a disruption in the metabolism of amyloid protein and its accumulation in brain tissue with the subsequent development of tauopathy. Cerebrolysin, by modulating the permeability of the blood-brain barrier, blocks the development of neuroinflammation, reduces the accumulation of pathological forms of proteins and may be slow down the progression of neurodegeneration.

[General mechanisms of the pathogenesis of neurodenerative and cerebrovascular diseases and the possibilities of their correction]. / Obshchie mekhanizmy patogeneza neirodenerativnykh i tserebrovaskulyarnykh zabolevanii i vozmozhnosti ikh korrektsii.

The recent research has revealed several common pathogenetic mechanisms underlying both vascular and neurodegenerative processes. This refers to chronic cerebral hypoperfusion, pathology of neurovascular units and the blood-brain barrier. The process of brain recovery in various lesions is realized due to the mechanisms of neuroplasticity. Using the example of Cerebrolysin, which has a multimodal effect, which includes an effect on the blood-brain barrier, a neurotrophic effect, an improvement in the drainage function of the brain, an anti-inflammatory effect, a direct effect on neurovascular units, the advantage of simultaneous action on various links of pathogenesis can be shown.

[Complex diagnostic of cognitive impairment]. / Kompleksnaia differentsial'naia diagnostika kognitivnykh narushenii.

In this article, the authors discussed the various aspects of pre-dementia stages of cognitive impairment, predominantly of neurodegenerative etiology. The modern conception of the pathophysiology of initial stages of cognitive impairment, the potential for lifetime pathological markers of amyloidosis and neurodegeneration are discussed. The authors proposed to use the concept of 'early signs of cognitive impairment'. The algorithm of the complex early diagnosis of cognitive impairment as well as the opportunities and prospects of clinical, neuropsychological, neuroimaging and laboratory examination methods are presented. The data on main diseases characterized by cognitive impairment and prospects for the use of new highly informative methods for early and differential diagnosis of Alzheimer's disease and vascular cognitive impairment are discussed.

[Primary headache - risk factor or comorbid pathology in cognitive impairment]. / Pervichnaia golovnaia bol' - faktor riska ili komorbidnaia patologiia pri kognitivnykh narusheniiakh.

Currently, the relationship between headache and dementia is considered more widely than just a comorbidity. The severity of migraine and tension-type headache and the severity of cognitive impairment are strongly correlated. Common pathophysiological mechanisms underlie the relationship between primary headache and cognitive impairment. Antinociceptive changes in primary headaches and in glutamate excitotoxicity in dementia developed due to hyper excitability of NMDA receptors are strongly interdependent. It is important in the aspect of possible correction of this pathology by NMDA-antagonists. Memantine not only slows the progression of cognitive symptoms in dementia, but also significantly influences the frequency and severity of primary headache.

[Pathomorphological changes in dementia: a priority of domestic researchers]. / Patomorfologicheskie izmeneniya pri dementsii: prioritet otechestvennykh issledovatelei.

The authors analyze the clinical and pathomorphological description of dementia presented in the dissertation of S.A. Belyakov written under the supervision of professor I.P. Merzheevsky. This description was made 19 years before the A. Alzheimer discovery. The classification of dementia suggested by S.A. Belyakov is presented.

[Comprehensive early diagnosis of cognitive impairment].

OBJECTIVE: To study cognitive function, CSF biochemical markers of amyloidosis and neurodegeneration, cerebral metabolism using PET, cerebral volumetric changes and metabolic content of the cingular gyrus using magnetic resonance spectroscopy (MRS) in patients with amnesic and neurodynamic variants of mild cognitive impairment (MCI). MATERIAL AND METHODS: Authors examined 369 patients with cognitive impairment of different severity. All patients underwent neuropsychological examination. To deter-mine the levels of ß-amyloid and tau-protein,a lumbar puncture was performed in 125 patients and 20 controls. 18-Fluorine deoxyglucose positron emission tomography (FCSRT) was performed in 77 patients. Assessment of metabolite levels by MRS and volumetric parameters by magnetic resonance morphometry was done in 92 patients. RESULTS AND CONCLUSION: The «free and cued selective reminding test¼ and «trail making test¼ showed the best diagnostic value in the early differential diagnosis of amnesic and neurodynamic variants of MCI. A decrease in beta-amyloid-42 protein and an increase in tau-protein in CSF are early markers of neurodegenerative dementia as well as of the additional involvement of the neurodegeneration in cerebrovascular disease. Specific areas of glucose hypometabolism on preclinical stages of dementia were identified using FCSRT. Spectroscopy and morphometry based on magnetic resonance can predict neurodegeneration in the cingular cortex, frontal and temporal brain.

[Possibilities of pharmacological modulation of brain glutamatergic system in the treatment of vascular cognitive impairment].

An aim of the study was to investigate the efficacy and safety of noojerone (memantine) in patients with cognitive impairment comorbid to brain ischemia, stages II-III. The main group (30 patients, aged 64-86 years) was treated with noojerone in addition to standard therapy according to dosage scheme during 6 months. The control group (15 patients, aged 61-78 years) received standard therapy only. Patients underwent somatic and neurological examinations, along with neuropsychological testing (MMSE, FAB and other tests). The use of noojerone in complex treatment decreased cognitive impairment in the main group compared to the control one. The most distinct changes were noted on MMSE. Statistically significant changes appeared during the 12th week. The maximal effect was observed when the drug was applied during 6 months. Noojerone was well-tolerated by the patients.