Carotid artery stenosis is related to cerebral small vessel disease magnetic resonance imaging burden.

Background: Cerebral small vessel disease (CSVD) encompasses conditions that affect small blood vessels of the brain, the most common being atherosclerosis. Magnetic resonance imaging (MRI) CSVD markers include lacunar strokes (LS), white matter hyperintensities (WMH), microbleeds, enlarged perivascular spaces (EPVS), and brain atrophy. Large and small cerebral arteries share an anatomical and functional connection, but the role of large vessel atherosclerosis in atherosclerotic CSVD hasn't been established. The aim of this study was to evaluate the involvement of large vessel pathology in atherosclerotic CSVD. Methods: This cross-sectional study included 98 patients treated at the Neurology Clinic of the University Clinical Center of Serbia in Belgrade, from February 2018 to December 2023, who had atherosclerotic CSVD confirmed by neuroimaging and underwent extracranial color duplex sonography. Data on patients' gender, age, cerebrovascular risk factors (dyslipidemia, hypertension, diabetes mellitus, smoking status), ultrasonography findings (intima-media thickness - IMT, carotid and vertebral artery stenosis, and hemodynamics), and CSVD imaging markers were collected, and the CSVD MRI burden score was calculated. Results: Age correlated with LS and WMH (p < 0.05 for both). Hypertension correlated with WMH (p = 0.016), and smoking with LS (p = 0.043). Brain atrophy was more common in women (p = 0.016). The majority of patients had low-grade (<50 %) carotid stenosis. There was a strong correlation between all morphological parameters of internal carotid artery stenosis and the CSVD burden score (p < 0.05 for all). The hemodynamic parameters of internal carotid artery stenosis and morphological and hemodynamic parameters of vertebral artery stenosis didn't correlate with the CSVD burden score. Conclusions: This study shows a strong correlation between cerebral large and small vessel pathology. We recommend the use of extracranial color duplex sonography in the evaluation of patients with CSVD as a supplementary method for follow-up, as this would allow the identification of patients whose condition might progress.

Aberrant brain structural-functional connectivity coupling associated with cognitive dysfunction in different cerebral small vessel disease burdens.

AIMS: Emerging evidence suggests that cerebral small vessel disease (CSVD) pathology changes brain structural connectivity (SC) and functional connectivity (FC) networks. Although network-level SC and FC are closely coupled in the healthy population, how SC-FC coupling correlates with neurocognitive outcomes in patients with different CSVD burdens remains largely unknown. METHODS: Using multimodal MRI, we reconstructed whole-brain SC and FC networks for 54 patients with severe CSVD burden (CSVD-s), 106 patients with mild CSVD burden (CSVD-m), and 79 healthy controls. We then investigated the aberrant SC-FC coupling and functional network topology in CSVD and their correlations with cognitive dysfunction. RESULTS: Compared with controls, the CSVD-m patients showed no significant change in any SC-FC coupling, but the CSVD-s patients exhibited significantly decreased whole-brain (p = 0.014), auditory/motor (p = 0.033), and limbic modular (p = 0.011) SC-FC coupling. For functional network topology, despite no change in global efficiency, CSVD-s patients exhibited significantly reduced nodal efficiency of the bilateral amygdala (p = 0.024 and 0.035) and heschl gyrus (p = 0.001 and 0.005). Notably, for the CSVD-s patients, whole-brain SC-FC coupling showed a significantly positive correlation with MoCA (r = 0.327, p = 0.020) and SDMT (r = 0.373, p = 0.008) scores, limbic/subcortical modular SC-FC coupling showed a negative correlation (r = -0.316, p = 0.025) with SCWT score, and global/local efficiency (r = 0.367, p = 0.009 and r = 0.353, p = 0.012) showed a positive correlation with AVLT score. For the CSVD-m group, whole-brain and auditory/motor modular SC-FC couplings showed significantly positive correlations with SCWT (r = 0.217, p = 0.028 and r = 0.219, p = 0.027) and TMT (r = 0.324, p = 0.001 and r = 0.245, p = 0.013) scores, and global/local efficiency showed positive correlations with AVLT (r = 0.230, p = 0.020 and r = 0.248, p = 0.012) and SDMT (r = 0.263, p = 0.008 and r = 0.263, p = 0.007) scores. CONCLUSION: Our findings demonstrated that decreased whole-brain and module-dependent SC-FC coupling associated with reduced functional efficiency might underlie more severe burden and worse cognitive decline in CSVD. SC-FC coupling might serve as a more sensitive neuroimaging biomarker of CSVD burden and provided new insights into the pathophysiologic mechanisms of clinical development of CSVD.

Relationship between burden of cerebral small vessel disease on imaging and cognitive impairment of COPD patients.

OBJECTIVE: This study aims to explore the relationship between the burden of cerebral small vessel disease (CSVD) on imaging and cognitive impairment (CI) in patients with chronic obstructive pulmonary disease (COPD). METHODS: The study included 118 COPD patients admitted to Changxing People's Hospital between July 2020 and July 2023. All patients received a 1.5 T MRI of the brain and pulmonary function tests. A cognitive function assessment was conducted via the Montreal Cognitive Assessment (MoCA) scale, and patients were divided into two groups. The relationship between the MoCA and CSVD burden score was analyzed by Pearson correlation, and to identify risk factors, multiple logistic regression analysis was performed. RESULTS: The study showed a negative correlation between the MoCA and CSVD burden score in COPD patients (r=-0.479, P<0.001). Multiple logistic regression analysis found that age (OR=2.264, 95 % CI: 1.426-3.596, P<0.001), COPD grade (OR=3.139, 95 % CI: 2.012-4.898, P<0.001), as well as CSVD burden score (OR=5.336, 95 % CI: 1.191-23.900, P<0.001) were the independent risk factors for CI in COPD patients (P<0.05). CONCLUSION: When screening for cognitive impairment in COPD patients, the CSVD burden score can be used in conjunction with cognitive assessment scales to make judgments.

Decreased Local Specialization of Brain Structural Networks Associated with Cognitive Dysfuntion Revealed by Probabilistic Diffusion Tractography for Different Cerebral Small Vessel Disease Burdens.

To reveal the network-level structural disruptions associated with cognitive dysfunctions in different cerebral small vessel disease (CSVD) burdens, we used probabilistic diffusion tractography and graph theory to investigate the brain network topology in 67 patients with a severe CSVD burden (CSVD-s), 133 patients with a mild CSVD burden (CSVD-m) and 89 healthy controls. We used one-way analysis of covariance to assess the altered topological measures between groups, and then evaluated their Pearson correlation with cognitive parameters. Both the CSVD and control groups showed efficient small-world organization in white matter (WM) networks. However, compared with CSVD-m patients and controls, CSVD-s patients exhibited significantly decreased local efficiency, with partially reorganized hub distributions. For regional topology, CSVD-s patients showed significantly decreased nodal efficiency in the bilateral anterior cingulate gyrus, caudate nucleus, right opercular inferior frontal gyrus (IFGoperc), supplementary motor area (SMA), insula and left orbital superior frontal gyrus and angular gyrus. Intriguingly, global/local efficiency and nodal efficiency of the bilateral caudate nucleus, right IFGoperc, SMA and left angular gyrus showed significant correlations with cognitive parameters in the CSVD-s group, while only the left pallidum showed significant correlations with cognitive metrics in the CSVD-m group. In conclusion, the decreased local specialization of brain structural networks in patients with different CSVD burdens provides novel insights into understanding the brain structural alterations in relation to CSVD severity. Cognitive correlations with brain structural network efficiency suggest their potential use as neuroimaging biomarkers to assess the severity 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.

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

Purpose: 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). Methods: 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. Results: 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 [ß (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 [ß (95% CI): 0.27 (0.06 to 0.47); P = 0.012], BMI [ß (95% CI): 0.61 (0.00-1.22)] and systolic BP [ß (95% CI): 0.16 (0.09-0.23); P < 0.001]. Conclusions: 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.

A new nomogram including total cerebral small vessel disease burden for individualized prediction of early-onset depression in patients with acute ischemic stroke.

Objectives: The present study was designed to evaluate the effects of total cerebral small vessel disease (CSVD) on early-onset depression after acute ischemic stroke (AIS), and to develop a new nomogram including total CSVD burden to predict early-onset post-stroke depression (PSD). Methods: We continuously enrolled patients with AIS who were hospitalized at the First Affiliated Hospital of Soochow University between October 2017 and June 2019. All patients were assessed for depressive symptoms using the 17-item Hamilton Depression Scale (HAMD-17) at 14 ± 2 days after the onset of AIS. The diagnosis for depression was made according to the American Diagnostic and Statistical Manual of Mental Disorders Version 5 (DSM-5). The demographic and clinical data were collected including total CSVD burden. On the basis of a multivariate logistic model, the independent factors of early-onset PSD were identified and the predictive nomogram was generated. The performance of the nomogram was evaluated by Harrell's concordance index (C-index) and calibration plot. Results: A total of 346 patients were enrolled. When contrasted to a 0 score of total CSVD burden, the score ≥2 (moderate to severe total CSVD burden) was an independent risk factor for early-onset PSD. Besides, gender, cognitive impairments, baseline Barthel Index (BI), and plasma fibrinogen were independently associated with early-onset PSD. The nomogram based on all these five independent risk factors was developed and validated with an Area Under Curve (AUC) of 0.780. In addition, the calibration plot revealed an adequate fit of the nomogram in predicting the risk of early-onset depression in patients with AIS. Conclusions: Our study found the total CSVD burden score of 2-4 points was an independent risk factor of early-onset PSD. The proposed nomogram based on total CSVD burden, gender, cognitive impairments, baseline BI, and plasma fibrinogen concentration gave rise to a more accurate and more comprehensive prediction for early-onset PSD.

Total Burden of Cerebral Small Vessel Disease on MRI May Predict Cognitive Impairment in Parkinson's Disease.

(1) Objective: to investigate the association between the total burden of cerebral small vessel disease (CSVD) and cognitive function in Parkinson's disease (PD). (2) Methods: this retrospective study compared clinical and neuroimaging characteristics of 122 PD patients to determine the association between cognitive decline and total burden of CSVD in PD. All patients underwent brain MRI examinations, and their total CSVD burden scores were evaluated by silent lacunar infarction (SLI), cerebral microbleeds (CMB), white matter hyperintensities (WMH), and enlarged perivascular spaces (EPVS). The cognitive function was assessed by administering Mini-Mental State Examination (MMSE). Receiver-operating characteristic (ROC) curve and the area under the ROC curve (AUC) were performed to quantify the accuracy of the total burden of CSVD and PVH in discriminating PD patients with or without cognitive impairment. (3) Results: the PD patients with cognitive impairment had a significantly higher SLI, CMB, periventricular hyperintensities (PVH), deep white matter hyperintensities (DWMH), enlarged perivascular spaces of basal ganglia (BG-EPVS), and the total CSVD score compared with no cognitive impairment. Total CSVD score and MMSE had a significant negative correlation (r = -0. 483). Furthermore, total burden of CSVD and PVH were the independent risk factors of cognitive impairment in PD, and their good accuracy in discriminating PD patients with cognitive impairment from those with no cognitive impairment was confirmed by the results of ROC curves. (4) Conclusions: total burden of CSVD tightly linked to cognitive impairment in PD patients. The total burden of CSVD or PVH may predict the cognitive impairment in PD.

Periventricular white matter hyperintensities are associated with gait and balance in patients with minor stroke.

Objective: Cerebral small vessel disease (CSVD) is associated with gait and balance deficits in older adults. However, the effect of CSVD-related brain injury on post-stroke mobility is unknown. This study aimed to investigate the association of CSVD with gait and balance impairment after a minor stroke. Methods: A total of 273 patients with a minor stroke (NIHSS ≤ 5 points) who were hospitalized at the Affiliated Hospital of Qingdao University were enrolled. The manifestations of white matter hyperintensities (WMH), lacunes, enlarged perivascular spaces (EPVS), and cerebral microbleeds (CMB) were statistically analyzed according to magnetic resonance imaging results, and the total burden score of CSVD was calculated. Gait function was assessed by a 6-m walking speed test, and balance function was assessed by the timed-up-and-go (TUG) test. Linear regression analysis was applied to determine the association after adjusting for key variables. Results: The correlation results showed that in patients with minor stroke, age, sex, smoking history, and the infarct site were associated with gait speed, and age and the infarct site were associated with the TUG test. In the univariate linear regression model, periventricular white matter hyperintensities (PVWMH), deep white matter hyperintensities (DWMH), and the total burden of CSVD were correlated with gait speed, while only PVWMH correlated with the TUG test. After adjusting for confounders, only PVWMH were independent predictors of gait speed (ß = -0.089, p < 0.05) and the TUG test (ß = 0.517, p < 0.05). Conclusions: Our study confirmed that CSVD is associated with gait and balance disorders after a minor stroke. PVWMH are independent predictors of gait and balance disorders in patients with minor stroke. These findings should be confirmed in larger prospective studies.

Association of Cerebral Small Vessel Disease Burden with Neuropsychiatric Symptoms in Non-Demented Elderly: A Longitudinal Study.

BACKGROUND: The links between cerebral small vessel disease (CSVD) burden and neuropsychiatric symptoms (NPS) have not been fully studied. OBJECTIVE: We aimed to explore the associations of the CSVD burden with Neuropsychiatric Inventory (NPI) total scores and its subsyndromes in the elderly without dementia. METHODS: We investigated 630 non-demented participants from the Alzheimer's Disease Neuroimaging Initiative. All of them had NPI assessments and 3 Tesla MRI scans at baseline and 616 had longitudinal NPI assessments during the follow-up. Linear mixed-effects models were used to investigate the cross-sectional and longitudinal associations of CSVD burden with NPI total scores and its subsyndromes. RESULTS: Higher CSVD burden longitudinally predicted more serious neuropsychiatric symptoms, including NPS (p &lt; 0.0001), hyperactivity (p = 0.0006), affective symptoms (p = 0.0091), and apathy (p &lt; 0.0001) in the total participants. Lacunar infarcts (LIs), white matter hyperactivities (WMHs), and cerebral microbleeds (CMBs) might play important roles in the occurrence of NPS, since they were longitudinally associated with specific neuropsychiatric subsyndromes. LIs contributed to hyperactivity (p = 0.0092), psychosis (p = 0.0402), affective symptoms (p = 0.0156), and apathy (p &lt; 0.0001). WMHs were associated with hyperactivity (p = 0.0377) and apathy (p = 0.0343). However, CMBs were only related to apathy (p = 0.0141). CONCLUSION: CSVD burden was associated with multiple neuropsychiatric symptoms, suggesting the importance of monitoring and controlling vascular risk factors. Different markers of CSVD were associated with specific subsyndromes of NPS, suggesting that different markers tended to occur in different encephalic regions.

The Relationship Between ADAMTS13 Activity and Overall Cerebral Small Vessel Disease Burden: A Cross-Sectional Study Based on CSVD.

Objectives: This study aimed to investigate the association between plasma von Willebrand factor (VWF) level, ADAMTS13 activity, and neuroimaging features of cerebral small vessel disease (CSVD), including the CSVD neuroimaging markers and the overall CSVD burden. Methods: CSVD patients admitted to our hospital from 2016 to 2020 were recruited. Plasma VWF level and ADAMTS13 activity were measured. The overall effect of CSVD on the brain was described as a validated CSVD score. We evaluated the association between VWF levels, ADAMTS13 activity, and the increasing severity of CSVD score by the logistic regression model. Results: We enrolled 296 patients into this study. The mean age of the sample was 69.0 years (SD 7.0). The mean VWF level was 1.31 IU/mL, and the ADAMTS13 activity was 88.01 (SD 10.57). In multivariate regression analysis, lower ADAMTS13 activity and higher VWF level was related to white matter hyperintensity (WMH) [ß = -7.31; 95% confidence interval (CI) (-9.40, -4.93); p<0.01; ß = 0.17; 95% confidence interval (0.11, 0.23); p<0.01], subcortical infarction (SI) [(ß = -9.22; 95% CI (-11.37, -7.06); p<0.01); ß = 0.21; 95% confidence interval (0.15, 0.27); p<0.01] independently, but not cerebral microbleed (CMB) [(ß = -2.3; 95% CI (-4.95, 0.05); p = 0.22); ß = 0.02; 95% confidence interval (-0.05, 0.08); p = 0.63]. Furthermore, ADAMTS13 activity was independently negatively correlated with the overall CSVD burden (odd ratio = 21.33; 95% CI (17.46, 54.60); p < 0.01) after adjustment for age, history of hypertension, and current smoking. Conclusions: Reducing ADAMTS13 activity change is related to white matter hyperintensity, subcortical infarction, but not with cerebral microhemorrhage. In addition, ADAMTS13 may have played an essential role in the progression of CSVD.

Gait Impairment and Upper Extremity Disturbance Are Associated With Total Magnetic Resonance Imaging Cerebral Small Vessel Disease Burden.

Background and Purpose: Cerebral small vessel disease (cSVD)-including white matter hyperintensities (WMHs), cerebral microbleeds (CMBs), lacunes, and enlarged perivascular spaces (EPVS)-is related to gait impairment. However, the association between the total magnetic resonance imaging (MRI) cSVD burden and gait and upper extremity function remains insufficiently investigated. This study aimed to assess the correlation between the total MRI cSVD burden score and gait impairment as well as upper extremity impairment. Method: A total of 224 participants underwent MRI scans, and the presence of lacunes, WMHs, CMBs, and EPVS was evaluated and recorded as a total MRI cSVD burden score (range 0-4). Gait was assessed by 4-m walkway, Tinetti, Timed Up and Go (TUG), and Short Physical Performance Battery (SPPB) tests. Upper extremity function was assessed by 10-repeat hand pronation-supination time, 10-repeat finger-tapping time, and 10-repeat hand opening and closing time. Result: The mean age of the 224 participants was 60.6 ± 10.5 years, and 64.3% were men. Independent of age, sex, height, and vascular risk factors, multivariable linear regression analyses showed that a higher total MRI cSVD burden score was related to a shorter stride length, wider step width, higher cadence, and poorer performance on the Tinetti, TUG, and SPPB tests and upper extremity tests (all P < 0.05). Conclusion: Total MRI cSVD burden was associated with gait impairment and upper extremity disturbances, suggesting that total MRI cSVD burden might contribute to motor function decline. Longitudinal studies are required to determine whether there is a causal relationship between total MRI cSVD burden and motor function decline.

Macular Microvasculature Is Associated With Total Cerebral Small Vessel Disease Burden in Recent Single Subcortical Infarction.

PURPOSE: To assess the retinal microvasculature, choriocapillaris, and choroidal thickness in recent single subcortical infarction (RSSI) patients compared with healthy controls. We also assessed the correlation between the macular microvascular changes and choroidal changes with their clinical implications in RSSI patients. METHODS: Forty-six RSSI patients and 39 healthy controls (HC) were enrolled in our study. Magnetic resonance imaging (MRI) was done for all RSSI patients, and a total cerebral small vessel disease (CSVD) score was assessed for all patients. Swept-source optical coherence tomography (SS-OCT) was used to image and assess the choroidal thickness and SS-OCT angiography (SS-OCTA) was used to image and assess the macular microvasculature and choriocapillaris in all participants. Clinical information was collected for all participants. RESULTS: RSSI patients showed significantly sparser inner retinal microvasculature (P = 0.003) when compared with healthy controls. RSSI patients showed significantly thinner choroidal thickness (P < 0.001) when compared with HC. No significant difference (P = 0.247) was seen when the choriocapillaris was compared between the two groups. CSVD burden (P = 0.014) and NIHSS score (P = 0.010) showed significant correlation with the inner retinal microvasculature of RSSI patients. The inner retinal microvasculature (P = 0.016) and choroidal thickness (P = 0.018) showed a significant correlation with the MoCA scores in RSSI patients. CONCLUSIONS: Our report suggests that retinal and choroidal imaging may serve as useful indicators to expand our understanding of RSSI and its clinical validity.

The relation between total cerebral small vessel disease burden and gait impairment in patients with minor stroke.

Background and aims Individual MRI markers of cerebral small vessel disease are associated with gait impairment. The impact of total cerebral small vessel disease-related brain damage, expressed by a cerebral small vessel disease MRI burden score, on mobility after stroke, has not been considered, although this score gives a better representation of the overall effect of cerebral small vessel disease on the brain. We determined if the total cerebral small vessel disease burden is associated with gait impairment three years after minor stroke. Methods In total, 200 patients with minor lacunar or non-lacunar stroke (NIHSS ≤ 7) underwent a brain MRI at presentation. Presence of lacunes, white matter hyperintensities, cerebral microbleeds, and perivascular spaces were summed in a total cerebral small vessel disease MRI burden score (range 0-4). Gait disturbances, measured by timed-up-and-go test and self-reported stroke impact scale mobility domain were assessed three years after stroke. We tested associations adjusted for key variables by linear regression analysis. Results Total cerebral small vessel disease burden was not associated with gait impairment after minor stroke in all patients, nor in lacunar stroke patients ( n = 87). In non-lacunar stroke patients ( n = 113), total cerebral small vessel disease burden was associated with lower stroke impact scale mobility domain scores, independent of age, vascular risk factors, and stroke severity (unstandardized B -4.61; 95% CI -8.42; -0.79, p < 0.05). Conclusion Patients with non-lacunar stroke and a higher total cerebral small vessel disease burden have more subjective mobility impairment three years after stroke. The total cerebral small vessel disease MRI burden score is a possible marker to identify patients at risk for subjective gait impairment. These findings should be confirmed in larger studies.