The evaluation of the clustering of magnetic resonance imaging (MRI) signs into MRI types and their relationship with circulating markers of vascular wall damage were performed in 96 patients with cerebral small vessel disease (cSVD) (31 men and 65 women; mean age, 60.91 ± 6.57 years). The serum concentrations of the tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor-A (VEGF-A), and hypoxia-inducible factor 1-α (HIF-1α) were investigated in 70 patients with Fazekas stages 2 and 3 of white matter hyperintensities (WMH) and 21 age- and sex-matched volunteers with normal brain MRI using ELISA. The cluster analysis excluded two patients from the further analysis due to restrictions in their scanning protocol. MRI signs of 94 patients were distributed into two clusters. In the first group there were 18 patients with Fazekas 3 stage WMH. The second group consisted of 76 patients with WMH of different stages. The uneven distribution of patients between clusters limited the subsequent steps of statistical analysis; therefore, a cluster comparison was performed in patients with Fazekas stage 3 WMH, designated as MRI type 1 and type 2 of Fazekas 3 stage. There were no differences in age, sex, degree of hypertension, or other risk factors. MRI type 1 had significantly more widespread WMH, lacunes in many areas, microbleeds, atrophy, severe cognitive and gait impairments, and was associated with downregulation of VEGF-A compared with MRI type 2. MRI type 2 had more severe deep WMH, lacunes in the white matter, no microbleeds or atrophy, and less severe clinical manifestations and was associated with upregulation of TNF-α compared with MRI type 1. The established differences reflect the pathogenetic heterogeneity of cSVD and explain the variations in the clinical manifestations observed in Fazekas stage 3 of this disease.

Cerebral small vessel disease (SVD) is one of the leading causes of cognitive impairment and stroke. The importance of endothelial dysfunction and high blood–brain barrier (BBB) permeability in pathogenesis, together with ischemia, is under discussion. The aim of this study was to clarify the relationship between tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), and magnetic resonance imaging (MRI) signs of SVD. We examined 71 patients (23 men and 48 women; mean age: 60.5 ± 6.9 years) with clinical and MRI signs of SVD, and 21 healthy volunteers with normal MRIs. All subjects underwent 3T MRI and measurements of t-PA and PAI-1 levels. An increase in t-PA level is correlated with the volume of white matter hyperintensities (WMH) (R = 0.289, p = 0.034), severity on the Fazekas scale (p = 0.000), and with the size of subcortical (p = 0.002) and semiovale (p = 0.008) perivascular spaces. The PAI-1 level is not correlated with the t-PA level or MRI signs of SVD. The correlation between t-PA and the degree of WMH and perivascular spaces’ enlargement, without a correlation with PAI-1 and lacunes, is consistent with the importance of t-PA in BBB disruption and its role in causing brain damage in SVD.

Age-dependent cerebral small vessel disease (CSVD) is a common disease with a high social burden characterized by heterogeneity of forms and frequent comorbidity with Alzheimer’s disease (AD). Previously, we identified two MRI types of CSVD with specific clinical presentation and, probably, different mechanisms. The present study included 34 patients with CSVD and white matter hyperintensity (WMH) of stage Fazekas (F) 3 (mean age 61.7 ± 8.9) and 11 volunteers (mean age 57.3 ± 9.7). Total RNA was isolated from peripheral blood leukocytes. The expression of 58 protein-coding genes associated with CSVD and/or AD and 4 reference genes were assessed as part of the original panel for the NanoString nCounter analyzer. Testing results were validated by real-time PCR. There was a significant decrease in the expression levels of the ACOX1, CD33, CD2AP, TNFR1, and VEGFC genes in MRI type 2 relative to the control group as well as a decrease in the expression level of the CD33 gene in MRI type 2 compared to MRI type 1. Processes associated with inflammatory pathways with decreased expression of the identified genes are important in the development of MRI type 2 of CSVD. Given the direct connection of the established genes with AD, the importance of this form of CSVD in comorbidity with AD has been assumed.

Cerebral small vessel disease (CSVD) is a significant cause of cognitive impairment (CI), disability, and mortality. The insufficient effectiveness of antihypertensive therapy in curbing the disease justifies the search for potential targets for modifying therapy and indicators supporting its use. Using a laser-assisted optical rotational cell analyzer (LORRCA, Mechatronics, The Netherlands), the rheological properties and deformability of erythrocytes before and after incubation with 10 μmol/L of L-arginine, the nitric oxide (NO) donor, blood–brain barrier (BBB) permeability assessed by dynamic contrast-enhanced MRI, clinical, and MRI signs were studied in 73 patients with CSVD (48 women, mean age 60.1 ± 6.5 years). The control group consisted of 19 volunteers (14 women (73.7%), mean age 56.9 ± 6.4 years). The erythrocyte disaggregation rate (y-dis) after incubation with L-arginine showed better performance than other rheological characteristics in differentiating patients with reduced NO bioavailability/NO deficiency by its threshold values. Patients with y-dis > 113 s⁻¹ had more severe CI, arterial hypertension, white matter lesions, and increased BBB permeability in grey matter and normal-appearing white matter (NAWM). A test to assess changes in the erythrocyte disaggregation rate after incubation with L-arginine can be used to identify patients with impaired NO bioavailability. L-arginine may be part of a therapeutic strategy for CSVD with CI.

Introduction. Cerebral small vessel disease (CSVD) is one of the leading causes of vascular and mixed cognitive impairment (CI). Treatment options for CSVD-associated CI are limited. Repetitive transcranial magnetic stimulation (rTMS) is a promising non-drug treatment option. The aim of the study was to evaluate the effects of 10 rTMS sessions of the left dorsolateral prefrontal cortex (DLPFC) on cognitive functions in CSVD patients. Materials and methods. The study included 30 patients with CSVD and moderate CI randomized to the active (DLPFC stimulation; n = 20) and control (vertex stimulation; n = 10) groups. Both groups received 10 sessions of high-frequency rTMS. The DLPFC target was selected based on the individual paradigm fMRI data with a focus on executive functions. Cognitive function was assessed using the Montreal Cognitive Assessment Scale (MoCA), the Trail Making Test (TMT), the Tower of London Test, and the Rey–Osterrieth Complex Figure Test before, immediately after, and 3 months after the stimulation. Adverse events were assessed using standardized questionnaires. Results. The active group showed a significantly better effect compared to the control group according to MoCA, TMT A and B, The Tower of London Test, delayed recall on the Rey–Osterrieth Complex Figure Test immediately after the stimulation and MoCA, TMT A and B and The Tower of London 3 months after the stimulation. Adverse events in the study were mild and did not affect treatment adherence. Conclusion. rTMS is a promising, safe, and well-tolerated treatment option for mild cognitive impairment in CSVD. However, additional research is needed to make recommendations for its clinical use.

ЦЕЛЬ ИССЛЕДОВАНИЯ Разработать тест индивидуальной доступности оксида азота (NO) на основе изменения реологических свойств эритроцитов после инкубации с донатором NO и оценить роль данных нарушений в поражении мозга и развитии когнитивных расстройств при церебральной микроангиопатии (ЦМА). МАТЕРИАЛ И МЕТОДЫ У 73 пациентов с ЦМА (48 (65,8%) женщин, средний возраст 60,1±6,5 года) оценены реологические свойства эритроцитов до и после инкубации с 10 мкмоль/л L-аргинина — донатора NO с помощью лазерного оптического ротационного клеточного анализатора, проницаемость гематоэнцефалического барьера (ГЭБ) методом МРТ-Т1-динамического контрастирования. РЕЗУЛЬТАТЫ Среди исследуемых показателей реологических свойств эритроцитов лучшие характеристики по ROC-анализу имела скорость дезагрегации эритроцитов после инкубации с L-аргинином (площадь под кривой 0,733 (0,609—0,856), чувствительность 67%, специфичность 79%). Пациенты с превышением порогового значения скорости дезагрегации эритроцитов >113 с^–1 имели более тяжелые когнитивные расстройства, артериальную гипертензию, поражение белого вещества и повышенную проницаемость ГЭБ в сером и неизмененном белом веществе. ЗАКЛЮЧЕНИЕ Удлиненная скорость дезагрегации эритроцитов у пациентов с ЦМА после инкубации с L-аргинином указывает на риск прогрессирования заболевания, обусловленный снижением биодоступности NO/нарушением функциональной системы L-аргинин-eNOS-NO. Данный тест может использоваться для оценки индивидуальной биодоступности NO и потенциально — для показаний к модифицирующей терапии донаторами NO, например L-аргинином. Необходимы клинические исследования по стандартизации и оценке эффективности терапии донаторами NO у пациентов с ЦМА и когнитивными расстройствами.