Total Cerebral Small Vessel Disease Score Research Articles

Hippocampal fimbria atrophy and its mediating effect between cerebral small vessel disease and cognitive impairment

We aimed to investigate the relationship between the volume reduction in hippocampal (HP) subregions and cognitive impairment in patients with cerebral small vessel disease (CSVD). Clinical, cognitive, and magnetic resonance imaging data were obtained for 315 participants. The CSVD group included 146 participants with a total CSVD score of 1–4. 169 participants with a total CSVD score of zero were used as control group (CSVD-0). The volume differences of 19 HP subregions between CSVD and CSVD–0 groups were analyzed, and we investigated the hazard factors that might cause subregional volume reduction in HP. Mediation analysis was performed to detect the relationship among HP subregional volumes, CSVD burden, and cognitive function. In our results, significant differences can be found in the volumes of CA4 body, presubiculum–head, presubiculum–body, subiculum–body, GC–ML–DG–head, GC–ML–DG–body, fimbria, and HP tail between CSVD group and control group. Regression analysis showed that fimbria was the most impacted HP subregion by CSVD. And mediation analysis revealed fimbria volume was a mediator variable between total CSVD score and MoCA/SCWT score. These results suggest that the volumes of HP subregions, especially the fimbria, may be effective potential biomarkers for early detecting cognitive impairment in CSVD.

Associations of 10-year atherosclerotic cardiovascular disease risk scores with cerebral small vessel disease: the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study.

10-year atherosclerotic cardiovascular disease (ASCVD) risk scores were useful for predicting large vessel disease, but the relationships between them and cerebral small vessel disease (CSVD) were unclear. Our study aimed to evaluate associations of 10-year ASCVD risk scores with CSVD and its magnetic resonance imaging (MRI) markers. Community-dwelling residents from the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events study were included in this cross-sectional study. At baseline, we collected data related to the Framingham Risk Score (FRS), pooled cohort equation (PCE), prediction for ASCVD risk in China (China-PAR) and Systematic COronary Risk Evaluation model 2 (SCORE2), and classified participants into low, moderate and high groups. Participants underwent brain MRI scans. We evaluated white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces in basal ganglia (BG-EPVS) according to criteria of Wardlaw and Rothwell, and calculated total CSVD score and modified total CSVD score. A total of 3063 participants were included, and 53.5% of them were female. A higher FRS was associated with higher total CSVD score (moderate vs. low: cOR 1.89, 95% CI 1.53-2.34; high vs. low: cOR 3.23, 95%CI 2.62-3.97), and the PCE, China-PAR or SCORE2 score was positively related to total CSVD score (P < 0.05). Moreover, higher 10-year ASCVD scores were associated with higher odds of WMH (P < 0.05), lacunes (P < 0.05), CMBs (P < 0.05) and BG-EPVS (P < 0.05). The 10-year ASCVD scores were positively associated with CSVD and its MRI markers. These scores provided a method of risk stratification in the population with CSVD.

Association of Mean Upper Cervical Spinal Cord Cross-Sectional Area With Cerebral Small Vessel Disease: A Community-Based Cohort Study.

The purpose of this study was to investigate the association between the mean upper cervical spinal cord cross-sectional area (MUCCA) and the risk and severity of cerebral small vessel disease (CSVD). Community-dwelling residents in Lishui City, China, from the cross-sectional survey in the PRECISE cohort study (Polyvascular Evaluation for Cognitive Impairment and Vascular Events) conducted from 2017 to 2019. We included 1644 of 3067 community-dwelling adults in the PRECISE study after excluding those with incorrect, incomplete, insufficient, or missing clinical or imaging data. Total and modified total CSVD scores, as well as magnetic resonance imaging features, including white matter hyperintensity, lacunes, cerebral microbleeds, enlarged perivascular spaces, and brain atrophy, were assessed at the baseline. The Spinal Cord Toolbox was used to measure the upper cervical spinal cord cross-sectional area of the C1 to C3 segments of the spinal cord and its average value was taken as MUCCA. Participants were divided into 4 groups according to quartiles of MUCCA. Associations were analyzed using linear regression models adjusted for age, sex, current smoking and drinking, medical history, intracranial volume, and total cortical volume. The means±SD age of the participants was 61.4±6.5 years, and 635 of 1644 participants (38.6%) were men. The MUCCA was smaller in patients with CSVD than those without CSVD. Using the total CSVD score as a criterion, the MUCCA was 61.78±6.12 cm2 in 504 of 1644 participants with CSVD and 62.74±5.94 cm2 in 1140 of 1644 participants without CSVD. Using the modified total CSVD score, the MUCCA was 61.81±6.04 cm2 in 699 of 1644 participants with CSVD and 62.91±5.94 cm2 in 945 of 1644 without CSVD. There were statistical differences between the 2 groups after adjusting for covariates in 3 models. The MUCCA was negatively associated with the total and modified total CSVD scores (adjusted β value, -0.009 [95% CI, -0.01 to -0.003] and -0.007 [95% CI, -0.01 to -0.0006]) after adjustment for covariates. Furthermore, the MUCCA was negatively associated with the white matter hyperintensity burden (adjusted β value, -0.01 [95% CI, -0.02 to -0.003]), enlarged perivascular spaces in the basal ganglia (adjusted β value, -0.005 [95% CI, -0.009 to -0.001]), lacunes (adjusted β value, -0.004 [95% CI, -0.007 to -0.0007]), and brain atrophy (adjusted β value, -0.009 [95% CI, -0.01 to -0.004]). The MUCCA and CSVD were correlated. Spinal cord atrophy may serve as an imaging marker for CSVD; thus, small vessel disease may involve the spinal cord in addition to being intracranial.

Association between Life’s Essential 8 and Cerebral Small Vessel Disease

BackgroundGiven that associations of Life’s Essential 8 (LE8) and cerebral small vessel disease (CSVD) or its imaging markers were unclear, we examined relationship between them.MethodsThe cross-sectional study included community residents...

Prevalence and Risk Factors of Cerebral Small Vessel Disease from a Population-Based Cohort in China

Introduction: Cerebral small vessel disease (CSVD) is a significant burden of morbidity and mortality among elderly people around the world. Epidemiological data with complete CSVD evaluations and a large sample size in the general population are still limited. Methods: Community-dwelling residents in Lishui city in China from the cross-sectional survey of the Polyvascular Evaluation for Cognitive Impairment and Vascular Events (PRECISE) study were included in this study from 2017 to 2019. All participants underwent 3 Tesla brain magnetic resonance images to assess CSVD imaging markers. Demographic and risk factor data were collected. The general and age-specific prevalence of lacune, confluent white matter hyperintensity (WMH), moderate-severe enlarged perivascular spaces (EPVS), cerebral microbleed (CMB), and total CSVD score (an ordinal scale from 0 to 4, counting the presence of four imaging markers of CSVD) was evaluated. Associations between vascular risk factors and these markers were analyzed by multivariable logistic regression. Results: A total of 3,063 participants were enrolled. The mean age was 61.2 years and 46.5% were men. The most prevalent CSVD marker was confluent WMH (16.7%), followed by CMB (10.2%), moderate-severe EPVS in the basal ganglia (BG-EPVS) (9.8%), and lacune (5.6%). 30.5% of the participants have at least one of the four markers (total CSVD score ≥1 points). The prevalence of CSVD markers increases as age increases. Age and hypertension were independent risk factors for four CSVD markers and the total CSVD score. Conclusions: In this Chinese cohort with community-based adults aged 50–75 years, our findings showed a prevalence of 30.5% for CSVD. The most prevalent CSVD marker was confluent WMH, followed by CMB, moderate-severe BG-EPVS, and lacune. The risk factors for CSVD must be strictly screened and controlled in adults living in the community.

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.

Exploration of the etiology of single small subcortical infarctions using high-resolution vessel wall MRI.

We aimed to explore imaging indicators for diagnosing the etiology of single small subcortical infarctions (SSI) using high-resolution vessel wall imaging (HR-VWI). Patients with acute isolated subcortical cerebral infarction were prospectively enrolled and classified as having large artery atherosclerosis (LAA), stroke of undetermined etiology (SUD), or small artery disease (SAD). The infarct information, the cerebral small vessel disease (CSVD) score, morphological characteristics of the lenticulostriate arteries (LSAs), and plaque characteristics were compared between the three groups. Seventy seven patients were enrolled (30 LAA, 28 SUD, and 19 SAD). The total CSVD score of the LAA (P = 0.001) and SUD groups (P = 0.017) was significantly lower than that of the SAD group. The number and total length of LSA branches in the LAA and SUD groups were shorter than in the SAD group. Moreover, the total length laterality index (LI) of the LSAs in the LAA and SUD groups was greater than in the SAD group. The total CSVD score and LI of total length were independent predictors for the SUD and LAA groups. The remodeling index of the SUD group was significantly higher than that of the LAA group (P = 0.002); positive remodeling was dominant in the SUD group (60.7%), whereas remodeling in the LAA group was primarily non-positive (83.3%). SSI with and without plaques on the carrier artery may have different modes of pathogenesis. Patients with plaques may also have a coexisting mechanism of atherosclerosis.

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.

Culprit Plaques of Large Parent Arteries, Rather than Cerebral Small Vessel Disease, Contribute to Early Neurological Deterioration in Stroke Patients with Intracranial Branch Atheromatous Disease

Introduction: Intracranial branch atheromatous disease (BAD) has been applied to occlusions that occur at the origin of large caliber penetrating arteries due to the microatheromas or large parent artery plaques. This study aimed to explore the association between culprit plaques of large parent arteries, neuroimaging markers of cerebral small vessel disease (CSVD), and the risk of early neurological deterioration (END) in stroke patients with BAD. Methods: A total of 97 stroke patients with BAD in the vascular territories of the lenticulostriate arteries or paramedian pontine arteries, diagnosed using high-resolution magnetic resonance imaging, were prospectively recruited in this observational study. A culprit plaque in the middle cerebral artery was defined as the only arterial plaque on the ipsilateral side of an infarction visible on diffusion-weighted imaging. A culprit plaque in the basilar artery (BA) was identified when it was observed within the same axial slices of an infarction or on the adjacent upper or lower slice, whereas a plaque within the BA located in the ventral region was considered non-culprit. If more than one plaque was present in the same vascular territory, the most stenotic plaque was chosen for the analysis. Four CSVD neuroimaging markers, including white matter hyperintensity, lacunes, microbleeds, and enlarged perivascular spaces, were evaluated in accordance with the total CSVD score. The associations between neuroimaging features of lesions within large parent arteries, neuroimaging markers of CSVD, and the risk of END in stroke patients with BAD were investigated using logistic regression analysis. Results: END occurred in 41 stroke patients (42.27%) with BAD. The degree of large parent artery stenosis (p < 0.001), culprit plaques of large parent arteries (p < 0.001), and plaque burden (p < 0.001) were significantly different between the END and non-END groups in stroke patients with BAD. In logistic regression analysis, culprit plaques of large parent arteries (odds ratio, 32.258; 95% confidence interval, 4.140–251.346) were independently associated with the risk of END in stroke patients with BAD. Conclusions: Culprit plaques of large parent arteries could predict the risk of END in stroke patients with BAD. These results suggest that lesions in the large parent arteries, rather than damage to the cerebral small vessels, contribute to END in stroke patients with BAD.

Overall cerebral small vessel disease burden is associated with outcome of acute ischemic stroke after mechanical thrombectomy.

To investigate the association between the overall cerebral small vessel disease (CSVD) burden and the therapeutic outcome of mechanical thrombectomy (MT) in patients with acute anterior circulation large-vessel occlusion stroke. Data of patients who achieved successful revascularization after MT for acute anterior circulation large-vessel occlusion stroke in the Ningbo Medical Center Lihuili Hospital between April 2017 and January 2022 were retrospectively analyzed. The overall CSVD burden was evaluated by total CSVD score based on MRI images. According to the 90-day modified Rankin Scale (mRS) score, the participants were divided into the Good outcome group (mRS score 0-2) and Poor outcome group (mRS score 3-6). Multivariate Logistic regression was applied to assess the relationship between the overal CSVD burdern and 90-day outcome. In total, 145 eligible patients were included and classified into the Good outcome group (n = 77, 62.3% males, mean age: 64.92 ± 13.67 years) and Poor outcome group (n = 68, 50% males, mean age: 69.76 ± 10.88 years). Symptomatic intracranial hemorrhage (OR = 2.788, 95%CI: 1.143-8.745, P = 0.048), poor preoperative collateral status (OR = 3.619, 95%CI: 1.670-7.844, P = 0.001), and high total CSVD score (score 2: OR = 3.800, 95%CI: 1.173 = 12.311, P = 0.026; score 3: OR = 7.529, 95%CI: 1.555-36.460, P = 0.012) were independently prognostic for poor 90-day outcome in patients receiving MT. This study identified that the overall CSVD burden was independently associated with the prognosis of patients receiving MT for acute anterior circulation large-vessel occlusion stroke.

The relationship between severe extracranial artery stenosis or occlusion and cerebral small vessel disease in patients with large artery atherosclerotic cerebral infarction.

Extracranial artery stenosis (ECAS) is associated with the presence of individual markers of cerebral small vessel disease (CSVD). Here, we investigated the relationship between severe extracranial artery stenosis or occlusion and CSVD in patients with large artery atherosclerotic (LAA) cerebral infarction. A total of 128 patients with LAA cerebral infarction who met our specific inclusion criteria were selected, including 92 males and 36 females. These patients were divided into three groups based on whether they had severe symptomatic extracranial arterial stenosis or occlusion, severe asymptomatic extracranial artery stenosis or occlusion, or severe extracranial artery stenosis or occlusion (both symptomatic and asymptomatic). Intra-group comparisons were then performed to examine whether there were any differences in the total CSVD scores and Fazekas scores. Patients with severe extracranial arterial stenosis or occlusion and those with severe asymptomatic extracranial arterial stenosis or occlusion had a significantly higher total CSVD score (P < 0.05), but there were no significant differences between the groups in terms of Fazekas scores. Furthermore, there were no significant difference in the total CSVD scores and Fazekas scores when compared between patients with or without severe symptomatic extracranial arterial stenosis or occlusion. Severe stenosis or occlusion of the contralateral extracranial artery may increase the incidence of CSVD in patients with LAA cerebral infarction. Active and effective clinical intervention following comprehensive evaluation should be undertaken for unilateral cerebral infarction patients with severe stenosis or occlusion of the contralateral extracranial arterial.

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.

Associations of sleep apnea risk and oxygen desaturation indices with cerebral small vessel disease burden in patients with stroke.

BackgroundObstructive sleep apnea (OSA) is associated with cerebral small vessel disease (CSVD). Nonetheless, whether OSA-risk determined by a simple screening questionnaire or indices quantifying nocturnal hypoxemia other than the conventional apnea–hypopnea index (AHI) by the home sleep apnea test (HSAT) associated with CSVD burden remains uncertain.MethodsFrom 2018 to 2021, we recruited patients with transient ischemic attack (TIA)/minor stroke from the Queen Mary Hospital Acute Stroke Unit and TIA/Stroke Outpatient Clinics. Logistic regression models were applied to determine the association of baseline OSA-risk (on STOP-BANG questionnaire) or HSAT-derived indices quantifying nocturnal hypoxemia with global burden/individual markers of CSVD on MRI. Indices included oxygen desaturation (≥3%) index (ODI), minimum oxygen saturation (SpO2), percentage of total sleep time with an oxygen saturation <90% (CT90%), and desaturation duration (≥3%, DesDur).ResultsIn 283 patients with TIA/minor stroke (mean age 65 years, 64% men), OSA-risk was significantly associated with total CSVD score (multivariate-adjusted odds ratio: 1.23, 95% confidence interval 1.01–1.51), presence of lacunes [1.39 (1.09–1.79)] and burden of basal ganglia PVSs [1.32 (1.06–1.67)]. In 85/283 patients who completed HSAT, neither AHI, minimum SpO2 nor CT90% was associated with CSVD burden. Nonetheless, ODI and DesDur remained significantly associated with total CSVD score after covariate adjustment: ODI [1.04 (1.01–1.07)] and DesDur [1.04 (1.01–1.08)].ConclusionIn patients with TIA/minor stroke, high OSA-risk was associated with a greater CSVD burden. Oxygen desaturation indices (ODI and DesDur) rather than AHI were independently associated with global CSVD burden, indicating that longer and more severe desaturations may contribute to the pathogenesis of CSVD.

Daily blood pressure profile and blood–brain barrier permeability in patients with cerebral small vessel disease

Cerebral small vessel disease (CSVD) plays an important role in cognitive impairment, stroke, disability, and death. Hypertension is the main risk factor for CSVD. The use of antihypertensive therapy has not resulted in the expected decrease in CSVD complications, which may be related to the underestimation of significance of daily blood pressure profile for blood–brain barrier (BBB) permeability. 53 patients with CSVD of varying severity (mean age 60.08 ± 6.8 years, 69.8% women, subjects with treated long-standing hypertension vs. normotensive subjects − 84.8% vs. 15.2%) and 17 healthy volunteers underwent ambulatory blood pressure monitoring (ABPM) and MRI, including T1-weighted dynamic contrast-enhanced magnetic resonance imaging for assessing BBB permeability. Most of ABPM parameters in CSVD patients did not differ from controls, but were associated with the severity of white matter hyperintensity (WMH) and the total CSVD score. BBB permeability in normal-appearing white matter (NAWM) and grey matter (GM) was significantly higher in CSVD patients, and the severity of BBB permeability remained similar in patients with different stages of WMH. Among BBB permeability parameters, the area under the curve, corresponding to an increase in the contrast transit time in NAWM, had the greatest number of correlations with deviations of ABPM parameters. BBB permeability in CSVD is a universal mechanism of NAWM and GM damage associated with a slight increase in ABPM parameters. It is obvious that the treatment of hypertension in patients with not severe WMH should be more aggressive and carried out under the control of ABPM.

White Matter Free Water Outperforms Cerebral Small Vessel Disease Total Score in Predicting Cognitive Decline in Persons with Mild Cognitive Impairment.

Vascular pathology is an important partner of Alzheimer's disease (AD). Both total cerebral small vessel disease (CSVD) score and white matter free water (FW) are useful markers that could reflect cerebral vascular injury. We aim to investigate the efficacy of these two metrics in predicting cognitive declines in patients with mild cognitive impairment (MCI). We enrolled 126 MCI subjects with 3D T1-weighted images, fluid-attenuated inversion recovery images, T2* images, diffusion tensor imaging images, cerebrospinal fluid biomarkers and neuropsychological tests from the Alzheimer's Disease Neuroimaging Initiative database. The total CSVD score and FW values were calculated. Simple and multiple linear regression analyses were applied to explore the association between vascular and cognitive impairments. Linear mixed effect models were constructed to investigate the efficacy of total CSVD score and FW on predicting cognitive decline. FW was associated with baseline cognition and could predict the decline of executive and language functions in MCI subjects, while no association was found between total CSVD score and cognitive declines. FW is a promising imaging marker for investigating the effect of CSVD on AD progression.

Long-Term Use of Metformin Is Associated With Reduced Risk of Cognitive Impairment With Alleviation of Cerebral Small Vessel Disease Burden in Patients With Type 2 Diabetes.

Objective: Type 2 diabetes (T2D) is a risk factor for cognitive impairment and cerebral small vessel disease (CSVD). The relation of metformin use and cognitive impairment or CSVD is not clear. The objective of this study was to investigate the cross-sectional effects of long-term use of metformin on total CSVD burden and cognitive function in patients with T2D.Methods: A total of 234 participants with T2D from the memory clinic in Hebei General Hospital were enrolled in this retrospective study. Duration of metformin use and dosage were recorded. Along with cerebral magnetic resonance imaging (MRI) examination, Mini-Mental State Examination (MMSE) was also performed to assess their cognitive status. We determined the validated total CSVD score (ranging from 0–4) by combining four markers of CSVD that were visually rated. We used binary logistic regression analysis, ordinal logistic regression analysis and mediation analysis to assess the relation of long-term use of metformin with CSVD burden and cognitive function.Results: Binary logistic regression analysis showed long-term use of metformin was associated with reducing the risk of cognitive impairment (OR: 0.446; 95% Confidence Interval (CI): 0.249 to 0.800; P = 0.007), after adjustment of potential confounders, such as total CSVD burden score, age, HbA1c, hypertension, history of stroke, homocysteine, body mass index, TG and HDL-C. Ordinal logistic regression analysis suggested that long-term use of metformin was associated with alleviation of total CSVD burden score (OR: 0.583; 95% CI: 0.359 to 0.943; P = 0.027), after adjusting for age, HbA1c, hypertension, history of stroke, homocysteine, body mass index, TG and HDL-C. Mediation analysis showed significant mediation by the presence of severe CSVD burden score for long-term use of metformin in relation to cognitive impairment.Conclusion: Long-term use of metformin was associated with lower rates of cognitive impairment and lower total CSVD burden score in patients with T2D. A proportion of the relation between long-term use of metformin and cognitive impairment may be attributable to alleviation of CSVD burden.

A Novel Imaging Biomarker for Cerebral Small Vessel Disease Associated With Cognitive Impairment: The Deep-Medullary-Veins Score

Objective: To explore the biomarkers of cerebral small vessel disease (CSVD) associated with cognitive impairment.Methods: A total of 69 patients with CSVD were enrolled in the study, and baseline clinical and imaging data were reviewed retrospectively. The following neuroimaging biomarkers of CSVD were identified: high-grade white matter hyperintensity (HWMH), cerebral microbleeds (CMB), enlarged perivascular space (PVS), and lacunar infarct (LI). A total score for CSVD was calculated. The deep medullary veins (DMVs) were divided into six segments according to the regional anatomy. The total DMV score (0–18) was derived from the sum of the scores of the six individual segments, the scores of which ranged from 0 to 3, for a semiquantitative assessment of the DMV that was based on segmental continuity and visibility.Results: The DMV score, patient age, and total CSVD score were independently associated with the presence or absence of cognitive impairment in patients with CSVD (P < 0.05). By integrating patient age and the total CSVD and DMV scores, the area under the curve of the receiver operating characteristic curve (AUROC) for predicting CSVD associated with cognitive impairment was 0.885, and the sensitivity and specificity were 64.71 and 94.23%, respectively.Conclusions: The DMV score may be a novel imaging biomarker for CSVD associated with cognitive impairment. The integration of the DMV score with age and total CSVD score should increase the predictive value of the DMV score for CSVD associated with cognitive impairment.

Cerebral Small Vessel Disease Burden Related to Carotid Intraplaque Hemorrhage Serves as an Imaging Marker for Clinical Symptoms in Carotid Stenosis.

Objectives: In patients with carotid stenosis, to investigate the relationship between carotid intraplaque hemorrhage (IPH) and total burden of cerebral small vessel disease (CSVD) and preliminarily explore whether the total CSVD burden as an imaging marker can distinguish the severity of clinical symptoms.Methods: A total of 108 patients (the mean age was 66 ± 7 years, and 85.2% were male) with unilateral carotid stenosis ≥50% underwent brain MRI and high-resolution MRI for carotid plaque characterization. The total burden of CSVD was calculated by accumulating one point according to the presence or severity of each of the four MRI markers: white matter hyperintensities, lacunes, perivascular spaces, and cerebral microbleeds. Recent clinical symptoms including transient ischemic attack, amaurosis fugax, and ischemic stroke were recorded. The association between intraplaque hemorrhage (IPH) and total CSVD burden was examined adjusted for other risk factors. The symmetry of CSVD burdens between the ipsilateral and contralateral hemispheres of IPH was tested. Imaging features (CSVD score, IPH, degree of stenosis, and completeness of the circle of Willis) were correlated with clinical symptoms by Kruskal–Wallis H test, Chi-square test, and Fisher's exact test.Results: Multivariable logistic regression analysis showed that IPH (OR = 2.98, 95% CI [1.39, 6.40], p = 0.005) was independently associated with a higher CSVD score. The presence of unilateral IPH was associated with the inter-hemispheric CSVD score difference (p = 0.004). Patients with stroke had a higher ipsilateral CSVD score than asymptomatic patients (p = 0.004) and those with transient ischemic attack/amaurosis fugax (p = 0.008). The statistical difference was marginally significant between symptoms and IPH (p = 0.057). No statistical difference was found between the symptoms and degree of stenosis and the completeness of the circle of Willis (p > 0.05).Conclusions: Carotid IPH is associated with an elevated total burden of CSVD in patients with carotid stenosis. Compared with the degree of stenosis, primary collaterals, and IPH, the total CSVD score might be a more effective imaging marker linked with clinical symptoms.

Higher cerebral small vessel disease burden is associated with smaller hematoma volume in mixed-location intracerebral hemorrhage.

To study the relationship between cerebral small vessel disease (CSVD) and hematoma volume in mixed-location intracerebral hemorrhage (ICH), and non-mixed ICH (hypertensive arteriopathy/cerebral amyloid angiopathy-related ICH). We consecutively collected patients with primary ICH with MRI. Mixed-location ICH was defined as having ICH or cerebral microbleeds (CMBs) in both lobar and deep regions. CSVD markers including lacunes, white matter hyperintensities (WMH), CMBs, and enlarged perivascular spaces (EPVS) were assessed on brain MRI during hospitalization. Multivariable binary logistic regression (≥30ml vs. <30ml) and linear regression analyses (log-transformed hematoma volume as dependent variable) were implemented to explore the association between CSVD and hematoma volume. Of the 167 included patients, 69 (41.3%) had mixed-location ICH, with higher prevalence of lacune, more CMB count, higher WMH score and total CSVD score than those with non-mixed ICH (all p<.001). Higher WMH score was associated with lower risk of hematoma volume ≥30ml (adjusted OR 0.521, 95% CI 0.299-0.908, p=.021) in patients with mixed-location ICH. Also, multivariable linear regression showed the association of smaller hematoma volume with higher CSVD burden, especially in mixed-location ICH (β=-0.349, p=.019 for CMB≥5; β=-0.183, p<.001 for WMH score; β=-0.456, p=.002 for EPVS>20 in basal ganglia and/or centrum semiovale; β=-0.256, p=.002 for CSVD score), while these relationships were not observed in non-mixed ICH. Higher CSVD burden is associated with smaller hematoma volume in mixed-location ICH, but not in non-mixed ICH, which is novel and needs further studies with larger sample size to confirm our results and explore the underlying mechanisms.