Introduction. Contributing to high disability and mortality, cerebral small vessel disease (cSVD) is a common condition in senior and elderly individuals. Objective: to assess the 5-year survival as well as cognitive and MRI changes in patients with cSVD and cognitive impairment (CI). Materials and methods. A prospective 5-year study included 54 patients (of them 37 women; mean age: 60.51 6.76 years) with cSVD, CIs, and white matter hyperintensities (WMHs; Fazekas 23). Twenty-two subjects were followed up to assess cognitive functions and a type of CI, cSVD MRI features, WMH, white and grey matter, and cerebrospinal fluid (CSF) volume as well as microstructural brain changes and correlate cognitive and MRI parameters at 5 years timepoint after the baseline. Results. Dementia developed in 14% of the subjects and 14% of the subjects died over a 5-year period. The subjects assessed twice had controlled hypertension (HTN). CIs worsened in the domain of executive functions and memory with mixed-type CI worsening. The follow-up showed that the WMH and CSF volume increased while the white matter volume decreased and axial diffusivity increased in the corpus callosum. The CSF volume correlated with the Stroop Test results and delayed memory (r = 0.803 and r = 0.701, respectively) and with white matter atrophy (r = 0.256) while the latter correlated with the axial diffusivity increased in the corpus callosum (r = 0.560). Conclusion. cSVD with advanced WMHs is associated with high mortality and dementia progression. General cognition assessment and MRI scan are not enough sensitive to assess disorder progression over a 5-year period. Stroop Test and Delayed 10-Word Recall Test results and transition to mixed-type CI indicate CI worsening and, therefore, can be used for the follow-up assessment. Cognitive decline in extensive cSVD is mediated by the brain matter atrophy and altered CSF circulation.

Introduction. Cerebral small vessel disease (CSVD), associated with age and vascular risk factors, as well as the main cause of vascular and degenerative mixed cognitive impairment (CI). Previously established microstructural predictors of CI (axial diffusion in normal-appearing periventricular white matter of the posterior left frontal lobe, the right midcingulate cortex, and the middle posterior part of the corpus callosum) can be used to calculate an integrative factor, exceeding the threshold value for which indicates the presence of CI. The use of this factor in the diagnosis of CI in CSVD is supported by the fact that leading mechanisms of CSVD are involved in the damage to areas of the brain that are strategic for CI. The aim of this study was to clarify the link between the known microstructural predictors of CI in CSVD and MRI findings that correspond to the main mechanisms of CSVD. Materials and methods. Patients (n = 74; including 48 women; average age 60.6 6.9 years) with CSVD and CI of varying severity underwent phase-contrast MRI and voxel-based morphometry (3T) to assess arterial, venous and CSF flow, as well as atrophy. Results. The established microstructural predictors of CI correlated with measures of arterial and venous blood flow, as well as atrophy. Linear regression models allow us to estimate cognitive impairment (CI) predictors in cerebral small vessel disease (CSVD), based on increased arterial velocity pulse index, CSF flow at the level of the cerebral aqueduct, cerebral aqueduct area and lateral ventricles volume, when there is reduced blood flow in the superior sagittal sinus and the overall arterial blood flow. Conclusion. The ability to calculate microstructural predictors of CI due to CSVD, based on MRI findings, indicates the validity of using an integrative measure of microstructural predictors of CI as a diagnostic tool of CI in CSVD.

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 prevalent age-related disorder that leads to progressive white matter damage, resulting in cognitive decline and depression. This study explored the neural network mechanisms of emotional dysregulation in CSVD, focusing on both depression and alexithymia and considering the broader context of studies on emotional cardiovascular risk factors. Study participants (n = 196, age 37-75) were assessed for CSVD, arterial hypertension, depressive symptoms, and alexithymia. Emotional dysregulation, defined by depression and alexithymia, was estimated using a structural equation model accounting for the potential of bidirectional links with CSVD. To investigate the connectivity of networks involved in emotional processing, 167 participants underwent resting-state functional MRI. The study showed that emotional dysregulation was associated with reduced functional connectivity between the salience and language networks and within the language network. Age was associated with reduced functional connectivity within the salience and language networks, suggesting a possibility of synergistic deleterious effects. The revealed alterations in brain connectivity might reflect the dysfunction of the system of allostasis, explaining the observed symptoms of depression and alexithymia, as well as the previous findings on emotional cardiovascular risk factors.

BACKGROUND: Analysis of structural magnetic resonance images is essential to assessing the main substrate of cognitive impairment in sporadic age-related cerebral small vessel disease, accounting for up to 45% of all dementia cases. Variations in the results of magnetic resonance morphometry applied in cerebral small vessel disease require extensive studies and clinical correlation. AIM: To assess cerebral atrophy features in cognitive impairment in patients with cerebral small vessel disease by surface-based morphometry. MATERIALS AND METHODS: A prospective study was conducted to assess patients with cerebral small vessel disease and cognitive impairments of varying severity levels (subjective, moderate, and dementia) and sex- and age-matched groups of volunteers. The assessment included the analysis of signs of cerebral small vessel disease based on the results of magnetic resonance imaging with the computation of general cerebral small vessel disease index and processing T1 multiplanar reconstruction images by surface-based morphometry to quantify general and regional brain parameters, including the thickness of the cerebral cortex. RESULTS: The main group consisted of 173 patients with cerebral small vessel disease, whereas the control group included 47 healthy volunteers. As the severity of brain structural changes and cognitive impairments increased, a significant (p 0.05) decrease in the cortical thickness of certain regions following a similar pattern was reported, particularly in the cingulate gyri, mainly their posterior sections; medial and middle sections of the frontal lobes, various areas of the insular cortex, and temporoparietal areas, particularly the supramarginal gyri. The brain volumes (overall, gray matter, and white matter volumes) in cerebral small vessel disease were significantly different only in controls but not between patients with cognitive impairment of different severity levels. The hyperintense white matter volume was significantly different between patients with dementia and moderate cognitive impairment, dementia, and subjective cognitive impairment (p 0.0001). CONCLUSIONS: The results confirm secondary/mixed atrophy in cerebral small vessel disease. The clarification of the severity level of cognitive impairment in cerebral small vessel disease based on atrophy data is limited by the wide variety of regions with significant cortical thinning. Thus, the quantification of the cortex can only be a supplementary method in predicting cerebral small vessel disease progression.

Introduction. Cerebral small vessel disease (CSVD) as well as the Alzheimer's disease (AD) and their comorbidities are the most common causes of cognitive impairments (CIs). Objective: to evaluate the predictive power of the biochemical neurodegeneration markers in patients with CSVD and AD. Materials and methods. We assessed the following neurodegeneration markers in 68 patients with CSVD (61.0 8.6 years; 60.3% males), 17 patients with AD (65.2 8.3 years; 35.3% males), and 26 healthy volunteers (59.9 6.7 years; 38.5% males): neuron-specific enolase (NSE), glial fibrillary acid protein (GFAP), neurofilament light polypeptide (NEFL) in blood (for all patients) and in cerebrospinal fluid (CSF; in patients with CSVD and AD). We assessed the predictive power of those markers with ROC analysis. Results. As compared to the control group, serum GFAP in patients with CSVD showed its predictive power at 0.155 ng/ml (sensitivity 74%; specificity 70%). Serum NEFL 0.0185 ng/ml (sensitivity 82%; specificity 96%) and NSE 4.95 g/ml (sensitivity 77%; specificity 71%) showed their predictive power in patients with AD. CSF GFAP 1.03 ng/ml (sensitivity 84%; specificity 88%), CSF NSE 19.10 g/ml (sensitivity 88%; specificity 91%), serum NEFL 0.021 ng/ml (sensitivity 71%; specificity 76%), serum NSE /CSF NSE ratio 0.273 ng/ml (sensitivity 87%; specificity 88%) help differentiate CSVD from AD. Conclusions. We found that serum GFAP can be a useful diagnostic marker in patients with CSVD, while serum NEFL and serum NSE can help identify the AD. In addition, CSF GFAP and CSF NSE as well as serum NEFL and serum NSE/CSF NSE can help differentiate CSVD from AD. We can use those markers in clinical and research practice to identify the vascular and neurodegenerative causes of CIs and their comorbidities, which is of a great importance in developing specific treatment and predicting the course of the disease.