Total Cerebral Small Vessel Disease Burden Research Articles

Cerebral small vessel disease modifies outcomes after minimally invasive surgery for intracerebral haemorrhage

BackgroundMinimally invasive surgery (MIS) for spontaneous supratentorial intracerebral haemorrhage (ICH) is controversial but may be beneficial if end-of-treatment (EOT) haematoma volume is reduced to ≤15 mL. We explored whether MRI...

Associations between semi-quantitative evaluation of intracranial arterial calcification and total cerebral small vessel disease burden score: a retrospective case-control study.

Arteriosclerotic cerebral small vessel disease (aCSVD) is a cause of cognitive impairment, dementia, and stroke. Developing a better understanding of the risk factor of aCSVD is key to reducing the incidence of these conditions. This study investigated the association between intracranial arterial calcification (IAC) and total cerebral small vessel disease (CSVD) burden score. This is a retrospective study, the subjects were transient ischemic attack (TIA) or acute ischemic stroke (AIS) patients. The data of 303 inpatients admitted to our study hospital between December 2018 and July 2020 were analyzed. Four imaging markers of CSVD (lacunes, white matter hyperintensities, cerebral microbleeds, and enlarged perivascular spaces) were evaluated by magnetic resonance imaging, and a total CSVD burden score was calculated. The experimental group was divided into four subgroups according to total CSVD burden score (1-4 points). Patients without CSVD (0 points) served as the control group. Head computerized tomography (CT) scans were used to assess ICA, using Babiarz's method. The correlations between IAC and single imaging markers of CSVD were determined using Spearman's rank correlation. Binary logic regression analysis and multivariate ordered logic regression analysis were used to determine the associations between IAC and aCSVD. IAC was positively correlated with total CSVD burden score (r = 0.681), deep white matter hyperintensities (r = 0.539), periventricular white matter hyperintensities (r = 0.570), cerebral microbleeds (r = 0.479), lacunes (r = 0.541), and enlarged perivascular spaces (r = 0.554) (all p < 0.001). After adjusting for the confounding factors of age, diabetes, and hypertension, aCSVD was independently associated with IAC grade 1-2 [odds ratio (OR) = 23.747, 95% confidence interval (CI) = 8.376-67.327] and IAC grade 3-4 (OR = 30.166, 95% CI = 8.295-109.701). aCSVD severity was independently associated with IAC grade 3-4 (OR = 4.697, 95% CI = 1.349-16.346). IAC is associated with the total CSVD burden score and single imaging signs.

Correlation analysis and predictive model construction of metabolic syndrome, complete blood count-derived inflammatory markers, and overall burden of cerebral small vessel disease

BackgroundThe high burden of cerebral small vessel disease (CSVD) on neuroimaging is a significant risk factor for stroke, cognitive dysfunction, and emotional disorders. Currently, there is a lack of studies investigating the correlation between metabolic syndrome (MetS), complete blood count-derived inflammatory markers, and total CSVD burden. This study aims to evaluate the total CSVD imaging load using machine learning (ML) algorithms and to explore further the relationship between MetS, complete blood count-derived inflammatory markers, and CSVD load. MethodsWe included CSVD patients from Xijing Hospital (2012–2022). Univariate and lasso regression analyses identified variables linked to CSVD neuroimaging burden. Six ML models predicted CSVD burden based on MetS and inflammatory markers. Model performance was evaluated using ROCauc, PRauc, DCA, and calibration curves. The SHAP method validated model interpretability. The best-performing model was selected to develop a web-based calculator using the Shiny package. ResultsThe Logistic regression model outperformed others in predicting CSVD burden. The model incorporated MetS, neutrophil-to-lymphocyte ratio (NLR), homocysteine (Hcy), age, smoking status, cystatin C (CysC), uric acid (UA), and prognostic nutritional index (PNI). ConclusionMetS, NLR, Hcy and CSVD high load were positively correlated, and the Logistic regression model could accurately predict the total CSVD load degree.

The clinical characteristics of cerebral small vessel disease patients with motoric cognitive risk syndrome during single- and dual-task walking

ObjectiveWe aimed to (1) identify neuroimaging biomarkers of distinguishing motoric cognitive risk syndrome (MCRS) risk among older Chinese adults with cerebral small vessel disease (CSVD) and (2) detect differences in gait parameters and neuroimaging biomarkers between CSVD individual with and without MCRS, especially during dual-task walking (DTW). MethodsWe enrolled 126 inpatients with CSVD who were divided into two groups according to MCRS status. Data on basic parameters, variability, asymmetry, and coordination were collected during single-task walking (STW) and DTW. Neuroimaging features (white matter hyperintensities, lacunes, and microbleeds) and total disease burden were calculated. Analysis of variance and logistic regression analyses were applied to assess the role of STW, DTW, and neuroimaging biomarkers in MCRS. ResultsIn total, 126 consecutive inpatients with CSVD were included (84 and 42 patients were classified as MCRS-negative and MCRS-positive, respectively). The MCRS-positive group showed poorer performance for nearly all gait parameters compared with the MCRS-negative group during cognitive DTW. Meanwhile, all gait parameters except asymmetry were assessed in participants with MCRS for significant deterioration during cognitive DTW compared with that during STW. However, only basic parameters differed between STW and cognitive DTW in participants without MCRS. A significant independent association between total CSVD scores and MCRS was also detected. ConclusionsFor CSVD patients, with higher total CSVD burden rather than any single neuroimaging marker, was linked to a greater risk of MCRS. In addition, CSVD individuals with MCRS had higher variability and phase coordination index (PCI), especially in cognitive DTW. Thus, they should concentrate more on their gait variability or coordination and reduce secondary task loads while walking in daily life, especially in cognitive secondary tasks.

A Nomogram Including Total Cerebral Small Vessel Disease Burden Score for Predicting Mild Vascular Cognitive Impairment in Patients with Type 2 Diabetes Mellitus.

Total cerebral small vessel disease (CSVD) burden score is an important predictor of vascular cognitive impairment (VCI). However, few predictive models of VCI in type 2 diabetes mellitus (T2DM) patients have included the total CSVD burden score, especially in the early stage of VCI. To develop and validate a nomogram that includes the total CSVD burden score to predict mild VCI in patients with T2DM. A total of 322 eligible participants with T2DM who were divided into mild and normal cognitive groups were enrolled in this retrospective study. Demographic data, laboratory data and imaging markers of CSVD were collected. The total CSVD burden score was calculated by combining the different CSVD markers. Step-backward multivariable logistic regression analysis with the Akaike information criterion was applied to select significant predictors and develop a best-fit predictive nomogram. The performance of the nomogram was assessed in terms of discriminative ability, calibrated ability, and clinical usefulness. The nomogram model consisted of five variables: age, education, hemoglobin A1c level, serum homocysteine level, and total CSVD burden score. A nomogram with these variables showed good discriminative ability (area under the receiver operating characteristic curve was 0.801 in internal verification). In addition, the Hosmer-Lemeshow test (χ2 =9.226, P=0.417) and bootstrap-corrected calibration plot indicated that the nomogram had good calibration. The Brier score of the predictive model was 0.178. Decision curve analysis demonstrated that when the threshold probability ranged between 16% and 98%, the use of the nomogram to predict mild VCI in patients with T2DM provide a greater net benefit. The nomogram, composed of age, education, stroke, HbA1c level, Hcy level, and total CSVD burden score, had good predictive accuracy and may provide clinicians with a practical tool for predicting the risk of mild VCI in T2DM patients.

Development and validation of a diagnostic model for cerebral small vessel disease among rural older adults in China.

Cerebral small vessel disease (CSVD) visible on MRI can be asymptomatic. We sought to develop and validate a model for detecting CSVD in rural older adults. This study included 1,192 participants in the MRI sub-study within the Multidomain Interventions to Delay Dementia and Disability in Rural China. Total sample was randomly divided into training set and validation set. MRI markers of CSVD were assessed following the international criteria, and total CSVD burden was assessed on a scale from 0 to 4. Logistic regression analyses were used to screen risk factors and develop the diagnostic model. A nomogram was used to visualize the model. Model performance was assessed using the area under the receiver-operating characteristic curve (AUC), calibration plot, and decision curve analysis. The model included age, high blood pressure, white blood cell count, neutrophil-to-lymphocyte ratio (NLR), and history of cerebral infarction. The AUC was 0.71 (95% CI, 0.67-0.76) in the training set and 0.69 (95% CI, 0.63-0.76) in the validation set. The model showed high coherence between predicted and observed probabilities in both the training and validation sets. The model had higher net benefits than the strategy assuming all participants either at high risk or low risk of CSVD for probability thresholds ranging 50-90% in the training set, and 65-98% in the validation set. A model that integrates routine clinical factors could detect CSVD in older adults, with good discrimination and calibration. The model has implication for clinical decision-making.

Spatiotemporal gait characteristics during single- and dual-task walking are associated with the burden of cerebral small vessel disease.

Gait impairment is a common symptom among individuals with cerebral small vessel disease (CSVD). However, performance differences between single-task walking (STW) and dual-task walking (DTW) among individuals with CSVD remain unclear. Therefore, we aimed to examine differences in gait characteristics during STW and DTW as well as the association between gait performance and neuroimaging markers. We enrolled 126 older individuals with CSVD. The speed, cadence, stride length, stride time, and their dual-task cost (DTC) or variability were measured under the STW, motor-cognitive DTW (cognitive DTW), and motor-motor DTW (motor DTW) conditions. We examined neuroimaging features such as white matter hyperintensities (WMHs), lacunes, microbleeds, and total burden. Further, we analysed the association of neuroimaging markers with gait performance, including gait variability and DTC. Almost all spatiotemporal characteristics, as well as their DTCs or variabilities, showed significant among-group differences according to disease severity in the cognitive DTW condition; however, relatively lesser differences were observed in the STW and motor DTW conditions. The total CSVD burden score was moderately correlated with all the spatial parameters, as well as their DTCs or variabilities, in the cognitive DTW condition. Moreover, WMHs showed a correlation with speed, stride time, and cadence, as well as their DTCs, in the cognitive DTW condition. Furthermore, lacunes showed a moderate correlation with speed, stride length, and the DTC of speed, whilst microbleeds were only related to the DTC of stride length in the cognitive DTW condition. Neuroimaging biomarkers were not correlated with spatiotemporal parameters in STW and motor DTW conditions after Bonferroni correction. Moreover, the correlation coefficient between the total CSVD burden score and gait parameters was greater than those of other biomarkers. Parameters in the cognitive DTW condition are more appropriate than those in the motor DTW condition for the evaluation of gait abnormalities in patients with CSVD. Moreover, the total CSVD burden score might have better predictive utility than any single neuroimaging marker. Patients with CSVD, especially those with moderate-to-severe disease, should concentrate more on their gait patterns and reduce the load of secondary cognitive tasks whilst walking in daily life.

Relationship between Serum Irisin Levels and MRI-Measured Cerebral Small Vessel Disease in Japanese Men.

Irisin, an exercise-induced myokine, is a potential neurotrophic factor; however, its relationship with cerebral small vessel disease (CSVD) remains unknown. Therefore, we investigated whether serum irisin levels are associated with CSVD in healthy Japanese men. We analyzed data from 720 men free of stroke and participated in this observational study. Serum irisin levels were measured by enzyme-linked immunosorbent assay. CSVD was assessed on deep and subcortical white matter hyperintensities (DSWMHs), periventricular hyperintensities (PVHs), lacunar infarcts (LIs), and cerebral microbleeds (CMBs) on brain magnetic resonance imaging. We calculated the total CSVD score (ranges 0-4) to express the total CSVD burden. We computed the adjusted odds ratios (ORs), with 95% confidence intervals (CIs), of the total CSVD score and individual CSVD features using logistic regression models according to the quartiles of irisin (reference: Q1). Serum irisin levels were associated with lower ORs of higher (vs. zero or lower score) total CSVD score, with the lowest risk (OR, 0.63; 95% CI, 0.41-0.97) being observed in Q3 compared to Q1 after adjustment of potential covariates. Similar results were obtained for younger adults (＜65 years). Among individual CSVD features, irisin was associated with a reduced risk of LIs in the total sample and PVHs, LIs, and CMBs in younger adults. No relationship was observed in older adults (≥ 65 years). Serum irisin levels were associated with less burden of total CSVD in healthy Japanese men. Serum irisin levels were also related with a reduced risk of PVHs, LIs, and CMBs, but not DSWMHs.

Correlation of blood pressure levels at different time periods throughout the day with total CSVD burden and MRI imaging markers.

Hypertension is an important risk factor for atherosclerotic cerebral small vessel disease (CSVD). Higher blood pressure is associated with a higher CSVD burden and the presence of relevant magnetic resonance imaging (MRI) markers. However, the effect of blood pressure level on CSVD burden and imaging markers including white matter hyperintensity (WHM), lacune, enlarged perivascular spaces (EPVS), and cerebral microbleed (CMB) remains unknown. The purpose of this study was to investigate the correlation between blood pressure level and CSVD burden at different time periods throughout the day. In total, 144 in-patients with CSVD (66.4 ± 9.8 years, 50% male) were enrolled and underwent brain MRI, and 24-h ambulatory blood pressure was assessed. Patients were categorized into five groups according to their MRI-evaluated total CSVD burden scores (0-4). Spearman's correlation analysis was performed to examine the correlation between blood pressure levels at different time periods and the total CSVD score or the markers of periventricular WMH, deep WMH, lacune, EPVS, and CMB. Of the 144 patients, 83.3% (120/144) harbored one or more CSVD markers of interest. The systolic blood pressure (SBP) of 24-h, daytime, nighttime, and morning differed significantly among the five groups. The SBP levels increased significantly with the total CSVD scores during 24 h (P = 0.018), daytime (P = 0.018), and nighttime (P = 0.035). Spearman's correlation analysis demonstrated that the SBP of 24 h, daytime, nighttime, and morning and the diastolic blood pressure (DBP) of 24 h and morning positively and significantly correlated with the total CSVD score (P < 0.05). A logistic regression analysis indicated that both morning SBP and DBP were independent risk factors for total CSVD burden (OR = 1.13, 95% CI: 1.02-1.23, P = 0.015; OR = 1.19, 95% CI: 1.06-1.33, P = 0.005). Spearman's correlation analysis indicated a significant positive correlation between morning SBP and higher deep WMH Fazekas score (r = 0.296, P < 0.001), EPVS grade in the basal ganglia (r = 0.247, P = 0.003), and the presence of lacune (r = 0.173, P = 0.038) and CMB (r = 0.326, P < 0.001). Morning DBP only correlated positively with the presence of CMB (r = 0.292, P < 0.001). Higher SBP signficantly correlated with total CSVD burden in patients with atherosclerotic CSVD. Early morning blood pressure level is an important indicator to reflect the severity of CSVD patients.

Arteriolosclerosis CSVD: a common cause of dementia and stroke and its association with cognitive function and total MRI burden.

Arteriolosclerosis cerebral small vessel disease (CSVD) is a common type of CSVD. This study aimed to explore the factors associated with cognitive function and total MRI burden related to the disease. The demographic characteristics, clinical manifestations, cognitive function score, Barthel Index (BI), blood test index, and follow-up results of arteriolosclerosis CSVD patients treated for the first time in our hospital from January 2014 to August 2022 were collected. White matter hyperintensity (WMH) Fazekas score, total MRI burden, and cerebral atrophy grade were evaluated according to brain MRI findings. Factors associated with CSVD cognitive function were analyzed by binary logistic regression. The correlative factors related to the total MRI burden of CSVD were analyzed by ordered multiple logistic regression. A total of 146 patients were included in this study, of which 132 cases (90.4%) had hypertension. There were 108 patients (74.0%) with cognitive dysfunction, 97 patients (66.4%) with balance and gait disorders, and 83 patients (56.8%) with moderate-to-severe dependence in daily life (BI ≤ 60 points). Of 146 patients, 79 (54.1%) completed clinical and imaging follow-ups for a median of 3 years. The number of patients with cognitive impairment and BI ≤ 60 points after follow-up significantly increased compared with the first admission (P < 0.001). There were also significant differences in total MRI burden (P = 0.001), WMH Fazekas score, and cerebral atrophy grade (P < 0.001). Mean age (P = 0.012), median deep WMH Fazekas score (P = 0.028), and median deep (P < 0.001) and superficial (P =0.002) cerebral atrophy grade of patients with cognitive impairment at first admission were all higher than those with non-cognitive impairment. Multivariate analysis showed that deep cerebral atrophy was independently and significantly associated with cognitive impairment of CSVD (P = 0.024), and hypertension was significantly and independently associated with total MRI burden (P = 0.001). The disease course of arteriolosclerosis CSVD may be related to cognitive function and total MRI burden. Deep cerebral atrophy was an independent risk factor for cognitive dysfunction in arteriolosclerosis CSVD, and hypertension was an independent risk factor for total MRI burden.

Impaired glymphatic system as evidenced by low diffusivity along perivascular spaces is associated with cerebral small vessel disease: a population-based study

ObjectiveThis study aims to investigate the associations of glymphatic system with the presence, severity and neuroimaging phenotypes of cerebral small vessel disease (CSVD) in a community-based population.MethodThis report included 2219...

Associations of deep medullary veins with vascular risk factors, laboratory indicators, and cerebral small vessel disease: A population-based study.

Deep medullary veins (DMVs) were not considered a typical marker of cerebral small vessel disease (CSVD) due to limited understanding of their involvement in pathology of CSVD. This study aimsto investigate potential vascular risk factors for DMVs and their associations with CSVD. In total, 1909 community-dwelling participants were included in this analysis. Demographic, clinical, laboratory, and imaging data were collected. DMV scores (0-18) werecalculated as the sum of bilateral frontal, parietal, and occipital regional scores using a semiquantitative visual scale (0-3). The presence, total burden, and imaging markers of CSVD were assessed. Linear regression analyses were conducted to explore potential vascular factors for DMV scores. Binary and ordinal logistic regression analyses were performed to investigate the associations of DMV scores with CSVD and its markers. Mean age was 61.8(SD 6.5)years, and 1027 (53.8%) of participants were men. The median DMV scores were14 (IQR 12-16). DMV scores wererelated to age, male sex, body mass index, diastolic blood pressure, hypercholesterolaemia, atrial fibrillation, current drinking, total cholesterol, triglycerides, low-density lipoprotein, hemoglobin A1c, leukocytes, lymphocytes, hemoglobin, and platelets (p<.05). DMV scores wereassociated with the presence and total burden of CSVD (Rothwell's scale), modified white matter hyperintensity burden, and enlarged perivascular spaces in centrum semiovale (p<.05). However, these associations between DMV scoresand CSVD disappeared after adjusting for potential confounders. Several conventional vascular factors were associated with DMVs. The relationship between DMVs and CSVD was vulnerable, suggesting decreased visible and discontinuous DMVs may differ mechanistically from traditional markers of CSVD.

Effect of dynamic cerebral autoregulation on the association between deep medullary vein changes and cerebral small vessel disease.

Changes in the deep medullary vein (DMV) are reported to be associated with cerebral small vessel disease (CSVD). While the mechanisms of this association are unclear, dynamic cerebral autoregulation (dCA) has been speculated to participate in this association. Thus, we aimed to verify the association between DMV changes and total CSVD burden and further investigate the effect of dCA function on this correlation. In this prospective study, 95 Asian patients aged ≥18 years were included in the final assessment. DMV scores and total CSVD burden were determined using magnetic resonance imaging sequences. Transfer function analysis was performed to analyze dCA function. Generalized linear regressions were used to assess the relationship between DMV changes and total CSVD burden as well as between DMV changes and dCA function. An interaction model was utilized to assess the effect of dCA function on the association between DMV changes and total CSVD burden. Generalized linear models showed a significant positive association between DMV changes and total CSVD burden (p = 0.039) and a significant negative association between DMV changes and dCA function (p = 0.018). The interaction model demonstrated a significant positive interaction of dCA impairment on the association between DMV changes and the total CSVD burden (p = 0.02). Thus, we came to the conclusion that changes in DMV were correlated independently with both CSVD and dCA impairment and furthermore, impaired dCA function play an interaction effect on the association between DMV changes and the total CSVD burden. Our results can help improve the understanding of the complex pathogenesis and progression of CSVD, thereby facilitating early intervention and treatment development.

Associations between computed tomography markers of cerebral small vessel disease and hemorrhagic transformation after intravenous thrombolysis in acute ischemic stroke patients.

Hemorrhagic transformation (HT) is common among acute ischemic stroke patients after treatment with intravenous thrombolysis (IVT). We analyzed potential relationships between markers of cerebral small vessel disease (CSVD) and HT in patients after IVT. This study retrospectively analyzed computed tomography (CT) data for acute ischemic stroke patients before and after treatment with recombinant tissue plasminogen activator at a large Chinese hospital between July 2014 and June 2021. Total CSVD score were summed by individual CSVD markers including leukoaraiosis, brain atrophy and lacune. Binary regression analysis was used to explore whether CSVD markers were related to HT as the primary outcome or to symptomatic intracranial hemorrhage (sICH) as a secondary outcome. A total of 397 AIS patients treated with IVT were screened for inclusion in this study. Patients with missing laboratory data (n = 37) and patients treated with endovascular therapy (n = 42) were excluded. Of the 318 patients included, 54 (17.0%) developed HT within 24-36 h of IVT, and 14 (4.3%) developed sICH. HT risk was independently associated with severe brain atrophy (OR 3.14, 95%CI 1.43-6.92, P = 0.004) and severe leukoaraiosis (OR 2.41, 95%CI 1.05-5.50, P = 0.036), but not to severe lacune level (OR 0.58, 95%CI 0.23-1.45, P = 0.250). Patients with a total CSVD burden ≥1 were at higher risk of HT (OR 2.87, 95%CI 1.38-5.94, P = 0.005). However, occurrence of sICH was not predicted by CSVD markers or total CSVD burden. In patients with acute ischemic stroke, severe leukoaraiosis, brain atrophy and total CSVD burden may be risk factors for HT after IVT. These findings may help improve efforts to mitigate or even prevent HT in vulnerable patients.

Critical closing pressure as a new hemodynamic marker of cerebral small vessel diseases burden.

To investigate cerebrovascular hemodynamics, including critical closing pressure (CrCP) and pulsatility index (PI), and their independent relationship with cerebral small vessel disease (CSVD) burden in patients with small-vessel occlusion (SVO). We recruited consecutive patients with SVO of acute cerebral infarction who underwent brain magnetic resonance imaging (MRI), transcranial Doppler (TCD) and CrCP during admission. Cerebrovascular hemodynamics were assessed using TCD. We used the CSVD score to rate the total MRI burden of CSVD. Multiple regression analysis was used to determine parameters related to CSVD burden or CrCP. Ninety-seven of 120 patients (mean age, 64.51 ± 9.99 years; 76% male) completed the full evaluations in this study. We observed that CrCP was an independent determinant of CSVD burden in four models [odds ratio, 1.41; 95% confidence interval (CI), 1.17-1.71; P < 0.001] and correlated with CSVD burden [β (95% CI): 0.05 (0.04-0.06); P < 0.001]. In ROC analysis, CrCP was considered as a predictor of CSVD burden, and AUC was 86.2% (95% CI, 78.6-93.9%; P < 0.001). Multiple linear regression analysis showed that CrCP was significantly correlated with age [β (95% CI): 0.27 (0.06 to 0.47); P = 0.012], BMI [β (95% CI): 0.61 (0.00-1.22)] and systolic BP [β (95% CI): 0.16 (0.09-0.23); P < 0.001]. CrCP representing cerebrovascular tension is an independent determinant and predictor of CSVD burden. It was significantly correlated with age, BMI and systolic blood pressure. These results provide new insights in the mechanism of CSVD development.

Implication of heart rate variability on cerebral small vessel disease: A potential therapeutic target.

This study aimed to investigate the relationships of heart rate variability (HRV) with the presence, severity, and individual neuroimaging markers of cerebral small vessel disease (CSVD). A total of 4676 participants from the Third China National Stroke Registry (CNSR-III) study were included in this cross-sectional analysis. CSVD and its markers, including white matter hyperintensity (WMH), lacunes, enlarged perivascular spaces (EPVS), cerebral microbleeds (CMBs), and brain atrophy (BA), were evaluated. Two common HRV parameters, including the square root of the mean of the sum of the squares of differences between adjacent N-N intervals (RMSSD) and the standard deviation of all N-N intervals (SDNN), were used to evaluate the function of the autonomic nervous system (ANS). Binary or ordinal logistic regression analyses were performed to investigate the association between HRV and CSVD. In addition, two-sample mendelian randomization (MR) analyses were performed to investigate the causality of HRV with CSVD. RMSSD was significantly associated with total burden of CSVD (Wardlaw's scale, common odds ratio [cOR] 0.80, 95% confidence interval [CI] 0.67-0.96, p=0.02; Rothwell's scale, cOR 0.75, 95% CI 0.60-0.93, p=0.008) and the presence of CSVD (Rothwell, OR 0.75, 95% CI 0.60-0.93, p=0.008). However, no significant associations between SDNN and the presence or total burden of CSVD were observed. Moreover, RMSSD was related to WMH burden (OR 0.80, 95% CI 0.66-0.96, p=0.02), modified WMH burden (cOR 0.82, 95% CI 0.69-0.97, p=0.02), and Deep-WMH (OR 0.75, 95% CI 0.62-0.91, p=0.003), while SDNN was related to Deep-WMH (OR 0.80, 95% CI 0.66-0.96, p=0.02) and BA (cOR 0.80, 95% CI 0.68-0.95, p=0.009). Furthermore, adding HRV to the conventional model based on vascualr risk factorsenhanced the predictive performance for CSVD, as validated by the integrated discrimination index (p < 0.05). In addition, no causality between HRV and CSVD was observed in two-sample MR analyses. Decreased HRV may be a potential risk factor of CSVD, implying the possible role of the ANS in the pathogenesis of CSVD.

Systemic Immune-Inflammation Index is Associated with Cerebral Small Vessel Disease Burden and Cognitive Impairment.

This study sought to explore the associations of the systemic immune-inflammation index (SII) with total cerebral small vessel disease (CSVD) burden and cognitive impairment. We enrolled 201 patients in the retrospective study with complete clinical and laboratory data. The SII was calculated as platelet count × neutrophil count/lymphocyte count. Cognitive function was evaluated by the Mini-Mental State Examination (MMSE). Total CSVD burden was assessed based on magnetic resonance imaging. We performed logistic regression models, Spearman correlation, and mediation analysis to evaluate the associations of SII with CSVD burden and cognitive impairment. After adjustment for confounding factors in the multivariate binary logistic regression model, elevated SII (odds ratio [OR], 3.263; 95% confidence interval [CI], 1.577-6.752; P = 0.001) or severe CSVD burden (OR, 2.794; 95% CI, 1.342-5.817; P = 0.006) was significantly associated with the risk of cognitive impairment. Correlation analyses revealed that SII levels were negatively associated with MMSE scores (rs = -0.391, P < 0.001), and positively associated with the total CSVD burden score (rs = 0.361, P < 0.001). Moreover, SII was significantly related to the severity of the CSVD burden (OR, 2.674; 95% CI, 1.359-5.263; P = 0.004). The multivariable-adjusted odds ratios (95% CI) in highest tertile versus lowest tertile of SII were 8.947 (3.315-24.145) for cognitive impairment and 4.945 (2.063-11.854) for severe CSVD burden, respectively. The effect of higher SII on cognitive impairment development was partly mediated by severe CSVD burden. Elevated SII is associated with severe CSVD burden and cognitive impairment. The mediating role of severe CSVD burden suggests that higher SII may contribute to cognitive impairment through aggravating CSVD burden.

Subclinical Hypothyroidism is Associated with Cognitive Impairment in Patients with Cerebral Small Vessel Disease.

To investigate the association between subclinical hypothyroidism (SCH) and cognitive function in patients with cerebral small vessel disease (CSVD). We evaluated 528 patients with CSVD in this retrospective study. SCH was defined as elevated levels of thyroid stimulating hormone with normal concentrations of free thyroxine. Magnetic resonance imaging was performed to assess the total CSVD burden score and the Montreal Cognitive Assessment was used to measure the cognitive function. Participants were grouped based on cognitive function or total CSVD burden score. Multivariate logistic regression and mediation analysis models were used to estimate the association of SCH with cognitive function and CSVD burden. SCH was an independent risk factor for cognitive impairment in patients with CSVD after adjustment for potential confounding factors (OR: 1.939; 95% CI: 1.170 to 3.213; P=0.010). Additionally, SCH was independently associated with severe CSVD burden after adjustment for potential confounding factors (OR: 1.668; 95% CI: 1.085 to 2.564; P=0.020). Mediation analysis found a significant moderating effect (P=0.021) of the severe CSVD burden on the relation between SCH and cognitive impairment after adjustment for potential confounding factors. A 30.1% of the total effect between this relation was attributable to the presence of severe CSVD burden. SCH was associated with an increased risk of cognitive impairment in patients with CSVD. The mediating role of severe CSVD burden suggests that SCH may lead to cognitive impairment through the presence of severe CSVD burden. These findings may suggest strategies for screening for SCH in the context of cognitive impairment in patients with severe CSVD.

Exosomal miR-320e as a Novel Potential Biomarker for Cerebral Small Vessel Disease.

Cerebral small vessel disease (CSVD) with an insidious onset can cause overall neurological dysfunction and dementia, bringing a massive burden to society. However, thepathogenesisof CSVD iscomplex and reliable non-invasive biomarkers for diagnosis are still not available at present. Our study aimed to investigate abnormal exosomal miRNA patterns via microarray analysis and identify candidate biomarkers for CSVD. We isolated exosomes from the plasma of all subjects and identified exosomes via currently universally accepted methods. The miRNAs were profiled through microarrays, and then the expression of selected differentially expressed miRNAs was validated through RT-PCR. GO and KEGG analysis predicted possible functions of differentially expressed miRNAs. Receiver operating characteristic (ROC) curve was employed to observe the diagnostic value of selective miRNAs. Finally, the relationship between the expression of miR-320e and the CSVD burden was analyzed. A total of 14 miRNAs displayed differential enrichment levels with |fold change|≥1.5 and p<0.05 through miRNA microarray analysis. The RT-PCR analysis validated that exosomal miR-320e was significantly downregulated in CSVD patients (p<0.0001). ROC curve analysis of exosomal miR-320e showed the area under the curve of 0.752. According to the multivariable analysis, miR-320e was an independent predictor of white matter hyperintensity ([aOR]= 0.452, 95% confidence interval [CI]= 0.258-0.792, p=0.006) and exhibited a negative correlation with the load of periventricular white matter hyperintensities (p=0.0021) and deep white matter hyperintensities (p=0.0018), respectively. In addition, it exhibited a negative correlation with total CSVD burden score(r=-0.276, p=0.001). In our study, plasma exosomal miR-320e has a certain diagnostic value for CSVD, and a significant correlation with imaging burden of CSVD. Overall, exosomal miR-320e has the potential to be a novel biomarker for CSVD, but further research with a large sample size is necessary to assess its clinical utility.

Association of deep medullary veins with the neuroimaging burden of cerebral small vessel disease

This study aimed to explore the association between deep medullary veins (DMVs) and the neuroimaging burden of cerebral small vessel disease (CSVD). In this cross-sectional study based on a retrospective analysis, a total of 248 patients (183 males and 65 females; mean age ± standard deviation, 69.5±14.8 years) diagnosed with CSVD with complete imaging and clinical data were enrolled. Neuroimaging markers of CSVD, including white matter hyperintensities, lacunes, prominent perivascular spaces (PVSs), and cerebral microbleeds (CMBs), were identified, and the total burden of CSVD was scored. Both DMV number and DMV score were used for assessment using susceptibility-weighted imaging (SWI). With the exception of perivascular spaces, more severe neuroimaging markers were observed in patients with a higher DMV score. After adjustments were made for age and body mass index (BMI), a higher DMV score (β=1.39; P<0.001) and smaller DMV number (β=-2.55; P=0.001) were associated with an increased CSVD burden. The degree of CMBs was independently correlated with both DMV score (β=1.60; P<0.001) and DMV number (β=-2.27; P=0.009). The association between lacunes and DMV score was also significant (β=0.97; P=0.026). Both DMV score and DMV number are potential imaging indicators of CSVD.