Total Small Vessel Disease Score Research Articles

Abstract MP42: Arterial Spin Labeling Imaging Assessment of Cerebrovascular Reactivity in Hypertensive Small Vessel Disease

Objective: Cerebrovascular reactivity (CVR) represents the phenomenon that cerebral vessels dilate or constrict in response to vasoactive stimuli, and CVR impairment may contribute to the brain injury caused by cerebral small vessel disease (SVD). We aim to determine the CVR in hypertensive intracerebral hemorrhage (ICH) and to identify its vascular dysfunction. Methods: 21 patients with spontaneous hypertensive ICH (strictly deep or mixed deep and lobar hemorrhages, mean age 62.5 ± 11.3 years) and 10 control subjects (mean age 66.1 ± 6.0) were enrolled for CVR measurement. Each participant received a brain MRI study, and CVR was calculated as cerebral blood flow (CBF) change using arterial spin labeling (ASL) sequence at baseline and 10 minutes after intravenous dipyridamole injection (0.57mg/Kg). Traditional MRI markers for SVD including cerebral microbleed, white matter hyperintensity, lacune and MRI-visible enlarged perivascular space were also evaluated to determine the total small vessel disease score. Results: Hypertensive ICH patients showed reduced CVR in the basal ganglia (CBF change 22.4 ± 22.7% vs. 41.7 ± 18.3, p=0.026), the frontal (15.1 ± 11.9 vs. 26.6 ± 9.9, p=0.013) and the temporal lobes (14.7 ± 11.1 vs. 26.2 ± 10.0, p=0.010) compared to control subjects (Figure). These differences remained significant in multivariable models after adjusting for age, sex, hypertension, diabetes, and hyperlipidemia. Within ICH groups, the CBF change in basal ganglia was significantly correlated with total small vessel disease score (R=-0.58, p=0.006), but not with individual MRI markers. Conclusion: Patients with advanced HTN-SVD demonstrated impaired vasoconstriction after dipyridamole challenge in basal ganglia, frontal and temporal lobes. Our findings provide safe approaches for whole brain CVR mapping in small vessel disease, and identify the potential physiological basis of vascular dysfunction in HTN-SVD.

Abstract P62: Older Adults With Cerebral Small Vessel Disease Show Increased Levels of Circulating Vascular Endothelial Growth Factor D

Introduction: Cerebral small vessel disease (SVD) resulting from pathological changes in cerebral microvessels is a common precursor of stroke and dementia. Progressive and insidious damage to the cerebral microvasculature may trigger angiogenic processes to promote vessel repair. However, few previous studies have explored the angiogenic response to SVD. In a cohort of older adults with early evidence of SVD, we aimed to examine circulating levels of vascular endothelial growth factor D (VEGF-D)—a secreted glycoprotein with high angiogenic and lymphangiogenic potential—which has previously been linked to heart failure, atrial fibrillation, and ischemic stroke. Methods: Sixty independently living older adults (mean age = 69.7 years; SD = 7.5; age range 55-90 years; 38.3% male) free of dementia or clinical stroke were recruited from the community and underwent venipuncture and brain MRI. Plasma was assayed for proangiogenic factors (VEGF-A, VEGF-C, VEGF-D, Tie-2, Flt-1). MRI changes thought to represent microvascular pathologies (white matter hyperintensities, microbleeds and lacunes) were evaluated and total SVD load was determined using a previously validated score. Multiple linear regression examined the relationship between circulating proangiogenic proteins levels and total SVD load. Results: Moderate/severe white matter hyperintensity burden was identified by Fazekas scale in 40.0% of participants, small lacunes were identified in 13.3% and microbleeds in 6.7%. Simple linear regression revealed a positive relationship between circulating VEGF-D and total SVD score (p = .019), which remained significant in multiple regression controlling for age, sex and Framingham stroke score (p = .017). VEGF-D was significantly positively correlated with VEGF-C (r = .37), Flt-1 (r = .31) and Tie-2 (r = .42). Conclusions: These findings suggest that elevated levels of circulating VEGF-D correspond with greater damage to the cerebral microvasculature in older adults with no history of clinical stroke or dementia. Additional studies are warranted to determine whether activation of systemic proangiogenic growth factors represents an early attempt to rescue the vascular endothelium and repair damage in cerebral SVD.

Intracerebral Hemorrhage in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy: Prevalence, Clinical and Neuroimaging Features and Risk Factors.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic cerebral small vessel disease. The role of intracerebral hemorrhage (ICH) in CADASIL remains elusive. The present study aims to investigate the prevalence, characteristics, and risk factors for ICH in CADASIL. This retrospective cross-sectional study investigated ICH and cerebral microbleeds (CMBs) in brain susceptibility-weighted imaging or T2*-weighted gradient-recalled echo images of 127 Taiwanese patients with genetically confirmed CADASIL. We analyzed CMBs, lacunes, white matter hyperintensity, and perivascular space. The total small vessel disease score (range, 0-4) was calculated to estimate the overall magnetic resonance imaging burden of small vessel disease. Multivariate regression analysis was performed to identify factors related to ICH lesions in CADASIL. Thirty-seven ICH lesions, including 15 symptomatic and 22 asymptomatic lesions, were found in 27 (21.3% [95% CI, 14.0%-30.9%]) of the 127 patients with CADASIL. The thalamus and lobar regions were the most common ICH locations, and 72.7% of the lobar hemorrhages occurred silently. Patients with CADASIL with ICH lesions more often had hypertension and a higher total small vessel disease score than those without ICH (odds ratio [95% CI]: 3.22 [1.25-8.30] and 3.79 [1.51-9.51]). The presence of CMBs in the brain stem and a total CMB count >10 were independently associated with ICH lesions in patients with CADASIL, with odds ratio (95% CI) of 5.82 (1.80-18.80) and 3.83 (1.08-13.67), respectively. ICH is an underestimated but important manifestation of CADASIL. The location and number of CMBs are associated with the presence of ICH lesions in patients with CADASIL.

Association of Bone Mineral Density to Cerebral Small Vessel Disease Burden.

To test the hypothesis that bone mineral loss is mechanistically related to cerebral small vessel disease (SVD), we investigated the relationship between bone mineral density and the prevalence and intensity of SVD among patients with stroke. We analyzed data of 1,190 consecutive patients with stroke who were >50 years of age and underwent both brain MRI and dual-energy x-ray absorptiometry from the stroke registry of Chung-Ang University Hospital in Seoul, Korea. The patients were categorized into 3 groups according to their bone mineral density (normal, osteopenia, and osteoporosis). White matter hyperintensities, silent lacunes, cerebral microbleeds, and extensive perivascular space were assessed from brain MRI. Multinomial logistic regression model was used to examine the association between osteoporosis and total SVD score. We also recruited 70 patients with stroke to study serum bone turnover markers and microRNAs related to both cerebral atherosclerosis and bone metabolism to understand bone and brain interaction. Osteoporosis was determined among 284 patients (23.9%), and 450 patients (37.8%) had osteopenia. As bone mineral density decreased, total SVD score and the incidence of every SVD phenotype increased except strictly lobar cerebral microbleeds. Multinomial logistic regression analysis showed that osteoporosis was independently associated with severe SVD burden. The levels of microRNA-378f were significantly increased among the patients with osteoporosis and maximal total SVD score and positively correlated with parathyroid hormone and osteocalcin. These findings suggest a pathophysiologic link between bone mineral loss and hypertensive cerebral arteriolar degeneration, possibly mediated by circulating microRNA.

Association between large artery stenosis, cerebral small vessel disease and risk of ischemic stroke.

We aimed to assess the associations of large artery stenosis (LAS) and cerebral small vessel disease (CSVD) with the risk of ischemic stroke and to investigate their respective and combined contributions. In the prospective population-based Shunyi Study, 1,082 stroke-free participants aged 55.9±9.1 years were included. Participants were followed for incident stroke throughout the study period (2013-2019). Total small vessel disease score was used to measure CSVD burden. Cervico-cerebral large artery stenosis was evaluated via brain magnetic resonance angiography and carotid ultrasound. We estimated the risk of ischemic stroke in relation to LAS and CSVD with Cox regression models. During a mean follow-up of 4.2 years, 34 participants (3.1%) experienced at least one ischemic stroke. Severe LAS (≥50% stenosis versus no stenosis: HR=3.27 (95% CI: 1.31-8.18)) and high CSVD burden (total small vessel disease score 2-4 versus 0 point: HR=12.73 (4.83-33.53)) were associated with increased stroke risk independently. In multivariate models, CSVD burden (7.72%) explained a larger portion of the variation in stroke risk than severity of LAS (3.49%). Our findings identified that both LAS and CSVD were associated with future ischemic stroke in asymptomatic subjects, while those with high CSVD burden deserve more attention in primary prevention of stroke.

The Association between Cerebral Small Vessel Disease and the Gut Microbiome: A Cross-Sectional Analysis

BackgroundRecent studies have demonstrated an association between the gut microbiome and cognitive function. However, the associations between the gut microbiome and brain parenchyma damage, and their underlying mechanisms, remain unclear. Materials and MethodsWe performed a cross-sectional sub-analysis using data from our prospective cohort study to determine the association between the gut microbiome and cerebral small vessel disease (SVD). We assessed patient demographics, risk factors, cognitive function, brain imaging, voxel-based specific regional analysis system for Alzheimer's Disease (VSRAD, indicating brain atrophy), and the gut microbiome as indicated by enterotypes and faecal microbiome metabolites. We then analysed the associations between total SVD scores, cognitive function, and the gut microbiome. ResultsWe analysed data from 87 patients without dementia or a history of stroke, 64 of whom exhibited mild cognitive impairment. Higher total SVD scores were associated with cognitive decline and behavioural and psychological symptoms. Compared with all other patients, patients with enterotype I (Bacteroides >30%) were more likely to have cognitive decline (median scores: Mini-Mental State Examination, 25 vs. 27, P = 0.047; Clinical Dementia Rating-Sum of Boxes, 1.5 vs. 0.5, P = 0.002) and present with cerebral SVD and high VSRAD scores (1.01 vs. 0.57, P = 0.012). Furthermore, faecal metabolites were significantly higher in patients with higher total SVD scores compared with those with lower scores. Multivariable logistic regression analyses indicated that certain gut microbiomes may double the risk of white matter hyperintensity. ConclusionsThe gut microbiome is associated with cerebral SVD.

Correlation between total cerebral small vessel disease score and retinal vessel diameters in patients with mild stroke

Objective: To explore the relationship between the total cerebral small vessel disease (CSVD) score and retinal vessel diameters in patients with mild stroke. Methods: The patients with mild stroke who were hospitalized in the Second People's Hospital of Changzhou, Nanjing Medical University from March to December 2019 were continuously collected (National Institutes of Health Stroke Scale score≤3 points). All patients completed the head magnetic resonance imaging and retinal fundus photography examination, and then the retinal arteriovenous diameter was measured semi-automatically based on the pictures. According to the total CSVD score (0-4 points), the patients were divided into 5 groups. The baseline characteristics of the patients were compared. Moreover, the correlation of total CSVD with retinal blood vessel diameters were analyzed by spearman and linear regression. Results: A total of 206 patients were enrolled. There were 69, 51, 41, 30, and 15 patients with 0, 1, 2, 3, and 4 points, respectively. In CSVD subgroups, there were significant differences in age, duration of hypertension and diabetes (all P<0.05). The central retinal artery equivalent (CRAE), (CSVD scores 0-4 were (126±12) μm, (118±11) μm, (108±11) μm, (99±8) μm, (90±7) μm, P<0.001) and arteriole-to-venule ratio (AVR) (CSVD scores 0-4 were 0.65±0.05, 0.60±0.04, 0.56±0.04, 0.49±0.03, 0.44±0.02, P<0.001) were different in CSVD subgroups. With the increase of CSVD score, the diameter of artery and AVR became smaller. The total CSVD was significantly correlated with AVR by Spearman correlation analysis (r= 0.818, P<0.001). By constructing a linear regression equation model, the coefficient of determination of the total CSVD score (R2=0.694) was higher than that of lacunes, white matter hyperintensities, cerebral microbleeds and enlarged perivascular space. After adjusting for age, course of hypertension and diabetes, and different types of CSVD, further multiple linear regression analysis revealed that the total CSVD score was still an independent related factor of AVR (β=-0.039, P<0.001, 95%CI=-0.051--0.028). Conclusions: Total CSVD score is negatively correlated with retinal artery diameters and AVR. Additionally, the total CSVD score can better reflect the degree of cerebral microvascular lesions than single type CSVD.

Addition of Aβ42 to Total Cerebral Small Vessel Disease Score Improves the Prediction for Cognitive Impairment in Cerebral Small Vessel Disease Patients.

PurposeTo investigate the associations between concentrations of Aβ40 and Aβ42 and vascular cognitive impairment (VCI) in cerebral small vessel disease (CSVD) patients and evaluate the value of combination of levels of Aβ40 or Aβ42 and the total CSVD score in predicting VCI.Patients and MethodsA total of 199 CSVD patients were divided into VCI group and non-VCI group according to the criteria of VCI. Demographic data, MRI markers of CSVD, blood pressure, vascular risk factors, laboratory markers, and serum Aβ40 and Aβ42 concentration were collected. Univariate analysis was performed with the Student’s t-test, Mann–Whitney U-test or Chi-square test. Variables with P<0.10 in univariate analysis were then included in multivariate analysis that used a backward stepwise logistic regression model. The predictive values were assessed with receiver operating characteristic (ROC) curve.ResultsVCI was determined in 112 CSVD patients (56.3%). Hyperlipidemia (OR: 1.618, 95% CI: 1.265–3.049), the total CSVD score (OR: 1.414, 95% CI: 1.213–2.278) and serum Aβ42 concentration (OR: 1.401, 95% CI: 1.212–1.946) were independent risk factors for VCI in CSVD patients with adjustment for age, education years, diabetes and fasting blood-glucose (FBG). The area under curves (AUCs) were 0.640 (SE: 0.040, 95% CI: 0.563–0.718), 0.733 (SE: 0.035, 95% CI: 0.664–0.802) and 0.827 (SE: 0.030, 95% CI: 0.768–0.887), respectively, for the total CSVD score, serum Aβ42 concentration and their combination applied in predicting VCI in CSVD patients. Z test demonstrated that the AUC of combination prediction was significantly higher than individual prediction (0.827 vs 0.640, Z=3.740, P<0.001; 0.827 vs 0.733, Z=2.039, P=0.021).ConclusionCombination of Aβ42 and total CSVD score could significantly elevate the predictive value of cognitive impairment in CSVD patients.

Total small vessel disease burden and functional outcome in patients with ischemic stroke.

Cerebral small vessel disease (SVD) is comprised of lacunes, cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), and enlarged perivascular space (EPVS). We investigated the cumulative effect of SVD on 3-month functional outcome following ischemic stroke using the total SVD score. The total SVD score of 477 acute ischemic stroke patients with adequate brain MRI was analyzed. We used multivariable ordinal logistic regression analysis to investigate the independent impact of total SVD score on ordinal modified Rankin Scale (mRS) score at 3-month after ischemic stroke. Mean age was 66±14 years, and 61% were men. The distribution of the total SVD score from 0 to 4 was 27%, 24%, 26%, 16%, and 7%, respectively. The proportion of mRS scores 2 or greater was 16% and 47% in total SVD score 0 and 4, respectively. Multivariable ordinal logistic regression analysis results showed that compared with the total SVD score of 0, total SVD scores of 2, 3, and 4 were independently associated with higher mRS scores with adjusted odds ratios (95% confidence intervals) of 1.68 (1.02-2.76), 2.24 (1.25-4.00), and 2.00 (1.02-4.29). Lacunes, CMBs, WMHs but not EPVS were associated with mRS scores at 3 months. However, the impact of each SVD marker on stroke outcome was smaller than that of the total SVD score. We found an independent association between total SVD scores and functional outcome at 3 months following ischemic stroke. The total SVD score may be useful for stratification of patients who are at a high-risk of unfavorable outcomes.

Cerebral Small Vessel Disease MRI Features Do Not Improve the Prediction of Stroke Outcome.

To determine whether the total small vessel disease (SVD) score adds information to the prediction of stroke outcome compared to validated predictors, we tested different predictive models of outcome in patients with stroke. White matter hyperintensity, lacunes, perivascular spaces, microbleeds, and atrophy were quantified in 2 prospective datasets of 428 and 197 patients with first-ever stroke, using MRI collected 24 to 72 hours after stroke onset. Functional, cognitive, and psychological status were assessed at the 3- to 6-month follow-up. The predictive accuracy (in terms of calibration and discrimination) of age, baseline NIH Stroke Scale score (NIHSS), and infarct volume was quantified (model 1) on dataset 1, the total SVD score was added (model 2), and the improvement in predictive accuracy was evaluated. These 2 models were also developed in dataset 2 for replication. Finally, in model 3, the MRI features of cerebral SVD were included rather than the total SVD score. Model 1 showed excellent performance for discriminating poor vs good functional outcomes (area under the curve [AUC] 0.915), and fair performance for identifying cognitively impaired and depressed patients (AUCs 0.750 and 0.688, respectively). A higher SVD score was associated with a poorer outcome (odds ratio 1.30 [1.07-1.58], p = 0.0090 at best for functional outcome). However, adding the total SVD score (model 2) or individual MRI features (model 3) did not improve the prediction over model 1. Results for dataset 2 were similar. Cerebral SVD was independently associated with functional, cognitive, and psychological outcomes, but had no clinically relevant added value to predict the individual outcomes of patients when compared to the usual predictors, such as age and baseline NIHSS.

Relevance of cerebral small vessel disease load scores in first-ever lacunar infarction

AimTo reveal the correlation between total cerebrovascular disease load and primary lacunar infarction. BackgroundCerebral small vessel disease (CSVD) is the lack of specific clinical manifestations, whose clinical diagnoses are highly dependent on neuroimaging results. Total CSVD load scores may be more suitable for the assessment of overall brain function damage caused by CSVD. Little is known about whether the association between imaging markers of CSVD and CSVD total load scores at the time of first-ever lacunar infarction (LI). Methodsclinical data of 396 patients hospitalised from September 2016 to May 2018 due to a first-ever LI (case group), along with patients diagnosed with CSVD based on imaging alone and those with no abnormalities (control group) based on magnetic resonance imaging (MRI). Binary logistic regression and multiple ordered logistic regression were used to analyse the characteristics of imaging markers of CSVD in patients with first-ever LI, including different total score burden and distribution, and the relationship between different markers. ResultsIn 396 patients, smoking, cholesterol level and total small vessel disease (SVD) score were all significantly associated with the first-ever LI. There were more LI, cerebral microbleeds (CMB), white matter hyperintensities (WMH), and moderate to severe enlarged perivascular spaces (EPVS) in the first-ever LI group, relative to controls (p < 0.01). The Fazekas scores for periventricular WMH, deep WMH, and total Fazekas score were all significantly higher in patients with first-ever LI relative to those with no cerebral abnormalities (p < 0.01). An analysis of various imaging markers of CSVD revealed a significant correlation between the presence and degree of any marker and the severity of other markers, even after adjusting for the presence of other markers (p < 0.05). ConclusionsThe first-ever LI group exhibited higher total CSVD score loads, a greater number of lacunae, CMB, severe WMH and moderate to severe EPVS. Smoking is an independent risk factor in patients with first-ever LI.

Hypertensive Arteriopathy and Cerebral Amyloid Angiopathy in Patients with Cognitive Decline and Mixed Cerebral Microbleeds.

Hypertensive arteriopathy (HA) and cerebral amyloid angiopathy (CAA) may contribute to the development of mixed cerebral microbleeds (CMBs). Recently, the total small vessel disease (SVD) scores for HA and CAA were proposed, which are determined by a combination of MRI markers to reflect overall severity of these microangiopathies. We investigated whether or not total HA-SVD and CAA-SVD scores could be used to predict overlap of HA and CAA in patients with mixed CMBs. Fifty-three subjects with mixed CMBs were retrospectively analyzed. MRI markers (CMBs, lacunes, perivascular space, white matter hyperintensity [WMH] and cortical superficial siderosis [cSS]) were assessed. The HA-SVD score and CAA-SVD score were obtained for each subject. Anterior or posterior WMH was also assessed using the age-related white matter changes scale. The two scores were positively correlated (ρ= 0.449, p < 0.001). The prevalence of lobar dominant CMB distribution (p < 0.001) and lacunes in the centrum semiovale (p < 0.001) and the severity of WMH in the parieto-occipital lobes (p = 0.004) were significantly higher in the high CAA-SVD score group. cSS was found in four patients with high CAA-SVD score who showed lobar-dominant CMB distribution and severe posterior WMH. Mixed CMBs are mainly due to HA. Assessing both two scores may predict the overlap of HA and CAA in individuals with mixed CMBs. Patients with a high CAA-SVD score may have some degree of advanced CAA, especially when lobar predominant CMBs, severe posterior WMH, lobar lacunes, or cSS are observed.

Total small vessel disease score and functional outcomes following acute intracerebral hemorrhage

BackgroundIndividual cerebral small vessel disease (SVD) markers are independent predictors for poor prognosis following intracerebral hemorrhage (ICH), however, the impact of the cumulative SVD burden on outcomes remains unclear. We aimed to investigate the association between the global SVD burden and functional outcomes following ICH. MethodsWe retrospectively evaluated a consecutive cohort of patients with ICH who underwent brain magnetic resonance imaging and magnetic resonance angiography, from a prospective registry. We identified the presence and severity of the SVD markers (cerebral microbleeds, lacunar infarctions, periventricular hyperintensities, and deep white matter hyperintensities) and summed them to obtain the modified total SVD score (0-4). Poor functional outcomes were defined as a modified Rankin Scale score at discharge ≥ 3. A multivariate logistic regression model was used to assess the association between patient outcomes and the SVD score. ResultsA total of 144 patients were included (65.0 ± 12.2 years, 67.4% male). The modified total SVD score was potentially associated with poor functional outcomes (odds ratio [OR] 1.72, 95% confidence interval [CI] 0.97-3.03) after adjustment for age, sex, history of stroke, chronic kidney disease, prior use of antithrombotic agents, the National Institutes of Health Stroke Scale score on admission, the non-lobar location of ICH, and hematoma volume on admission. Moreover, among older patients (≥ 65 years), the SVD score was associated with poor outcomes (OR 3.11, 95% CI 1.01-9.55). Among those with supratentorial ICH, the score remained significant (OR 2.06, 95% CI 1.11-3.83). ConclusionsThe modified total SVD score may have predictive value for poor functional outcomes following ICH.

Examining the Relationship between Semiquantitative Methods Analysing Concentration-Time and Enhancement-Time Curves from Dynamic-Contrast Enhanced Magnetic Resonance Imaging and Cerebrovascular Dysfunction in Small Vessel Disease.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be used to examine the distribution of an intravenous contrast agent within the brain. Computational methods have been devised to analyse the contrast uptake/washout over time as reflections of cerebrovascular dysfunction. However, there have been few direct comparisons of their relative strengths and weaknesses. In this paper, we compare five semiquantitative methods comprising the slope and area under the enhancement-time curve, the slope and area under the concentration-time curve ( and ), and changes in the power spectrum over time. We studied them in cerebrospinal fluid, normal tissues, stroke lesions, and white matter hyperintensities (WMH) using DCE-MRI scans from a cohort of patients with small vessel disease (SVD) who presented mild stroke. The total SVD score was associated with in WMH (), but not with the other four methods. In WMH, we found higher was associated with younger age () and fewer WMH (), whereas increased with younger age () and WMH burden (). Our results show the potential of different measures extracted from concentration-time curves extracted from the same DCE examination to demonstrate cerebrovascular dysfunction better than those extracted from enhancement-time curves.

Total small vessel disease score and cerebro-cardiovascular events in healthy adults: The Kashima scan study.

We explored the association between the total small vessel disease score obtained from baseline magnetic resonance imaging and subsequent cerebro-cardiovascular events in neurologically healthy Japanese adults. The presence of small vessel disease features, including lacunae, cerebral microbleeds, white matter changes, and basal ganglia perivascular spaces on magnetic resonance imaging, was summed to obtain a "total small vessel disease score" (range, 0-4). After excluding participants with previous stroke or ischemic heart disease, intracranial artery stenosis (≥50%), or cerebral aneurysm (≥4 mm), a total of 1349 participants (mean age, 57.7 years; range, 22.8-85.0 years; 46.9% male) were classified into three groups by total small vessel disease score: 0 (n = 984), 1 (n = 269), and ≥2 (n = 96). Cerebro-cardiovascular events (i.e., any stroke, transient ischemic attack, ischemic heart disease, acute heart failure, and aortic dissection) were defined as the primary end point. The hazard ratio (HR) of events during follow-up was calculated using Cox proportional hazards modeling with adjustments for age, sex, hypertension, diabetes mellitus, and smoking. Cumulative event-free rates were estimated using the Kaplan-Meier method. During follow-up (mean, 6.7 years), 35 cerebro-cardiovascular (16 cerebrovascular) events were identified. Higher small vessel disease score was associated with increased risk of cerebro-cardiovascular events (HR per unit increase, 2.17; 95% confidence interval, 1.36-3.46; P = 0.001). Events were more frequent among participants with higher score (P < 0.001, log-rank test). This study offered additional evidence for the clinical relevance of total small vessel disease score, suggesting the score as a promising tool to predict the risk of subsequent vascular events even in healthy populations.

ASSOCIATION BETWEEN CEREBRAL SMALL VESSEL DISEASE AND MILD MOTOR PARKINSONIAN SIGNS IN PATIENTS WITH LACUNAR STROKES AND TRANSIENT ISCHEMIC ATTACKS

Background: Both cerebral small vessel disease (SVD) and Mild Parkinsonian signs (MPS) are serious conditions affecting elderly patient, but, the association between them remain unclear. Objective: Examine the association between SVD, Total SVD burden and MPS in patients with Transient Ischemic Attacks (TIA) and Lacunar Strokes. Patients and Methods: We performed a cross-sectional study among 36 patients admitted with either TIA or Lacunar Stroke, but not known to have Parkinson’s disease or Parkinsonism. Patients were recruited from Al-Azhar University Hospitals during the period from June, 2016 to May 2018. Mean age was 73.38 ± 8.3 years, 58.3% males. MPS was evaluated via Unified Parkinson's Disease Rating Scale Part III. Brain MRI was used to determine SVD (lacunar infarctions [LIs], white matter hyperintensities [WMH], cerebral microbleeds [CMBs], and Enlarged Perivascular spaces [EPVSs]). Total SVD score was calculated based upon presence/absence of these four SVD markers. Results: In a multivariate analysis, we found that the presence of LIs, WMHs, CMBs, and total SVD score were significantly associated with MPS, whereas EPVSs were not. We found a strong correlation between SVD score & MPS score. We also found a significant association between total SVD score and Rigidity & Bradykinesia. GFR was found to significantly correlate with SVD score & MPS score. Conclusion: Our results provided additional evidence that SVD and especially total SVD burden, might be a surrogate marker for MPS and support the support the hypothesis of a vascular contribution to MPS in older adults.

ASSOCIATION BETWEEN CEREBRAL SMALL VESSEL DISEASE AND MILD MOTOR PARKINSONIAN SIGNS IN PATIENTS WITH LACUNAR STROKES AND TRANSIENT ISCHEMIC ATTACKS

Background: Both cerebral small vessel disease (SVD) and Mild Parkinsonian signs (MPS) are serious conditions affecting elderly patient, but, the association between them remain unclear. Objective: Examine the association between SVD, Total SVD burden and MPS in patients with Transient Ischemic Attacks (TIA) and Lacunar Strokes. Patients and Methods: We performed a cross-sectional study among 36 patients admitted with either TIA or Lacunar Stroke, but not known to have Parkinson’s disease or Parkinsonism. Patients were recruited from Al-Azhar University Hospitals during the period from June, 2016 to May 2018. Mean age was 73.38 ± 8.3 years, 58.3% males. MPS was evaluated via Unified Parkinson's Disease Rating Scale Part III. Brain MRI was used to determine SVD (lacunar infarctions [LIs], white matter hyperintensities [WMH], cerebral microbleeds [CMBs], and Enlarged Perivascular spaces [EPVSs]). Total SVD score was calculated based upon presence/absence of these four SVD markers. Results: In a multivariate analysis, we found that the presence of LIs, WMHs, CMBs, and total SVD score were significantly associated with MPS, whereas EPVSs were not. We found a strong correlation between SVD score & MPS score. We also found a significant association between total SVD score and Rigidity & Bradykinesia. GFR was found to significantly correlate with SVD score & MPS score. Conclusion: Our results provided additional evidence that SVD and especially total SVD burden, might be a surrogate marker for MPS and support the support the hypothesis of a vascular contribution to MPS in older adults.

Predictors for Late Post-Intracerebral Hemorrhage Dementia in Patients with Probable Cerebral Amyloid Angiopathy.

Cerebral amyloid angiopathy (CAA) accounts for the majority of lobar intracerebral hemorrhage (ICH); however, the risk factors for dementia conversion after ICH occurrence in CAA patients are unknown, especially in the long-term period after ICH. Therefore, we aimed to unravel the predictors for late post-ICH dementia (6 months after ICH event) in probable CAA patients. From a large consecutive MRI prospective cohort of spontaneous ICH (2006-2017), we identified probable CAA patients (modified Boston criteria) without dementia 6 months post-ICH. Cognitive outcome during follow-up was determined based on the information from standardized clinical visit notes. We used Cox regression analysis to investigate the association between baseline demographic characteristics, past medical history, MRI biomarkers, and late post-ICH dementia conversion (dementia occurred after 6 months). Among 97 non-demented lobar ICH patients with probable CAA, 25 patients (25.8%) developed dementia during a median follow-up time of 2.5 years (IQR 1.5-3.8 years). Pre-existing mild cognitive impairment, increased white matter hyperintensities (WMH) burden, the presence of disseminated cortical superficial siderosis (cSS), and higher total small vessel disease score for CAA were all independent predictors for late dementia conversion. In probable CAA patients presenting with lobar ICH, high WMH burden and presence of disseminated cSS are useful neuroimaging biomarkers for dementia risk stratification. These findings have implications for clinical practice and future trial design.

Cerebral Small Vessel Disease Burden Is Associated With Accelerated Poststroke Cognitive Decline: A 1-Year Follow-Up Study.

This study investigated the association between small vessel disease (SVD) burden, a combination of multiple SVD markers and cognitive dysfunction after stroke. The study sample comprised 451 patients with first-ever acute ischemic stroke. Cognitive functions were assessed with the Mini-Mental State Examination (MMSE) at 3, 9, and 15 months after the index stroke. Cognitive impairment was defined as an MMSE score of ≤26. A total SVD score, indicating SVD burden, was constructed by summing the scores of the 4 SVD markers (white matter hyperintensities [WMHs], lacunes, cerebral microbleeds, and perivascular spaces) ascertained by magnetic resonance imaging (range: 0-4). The association between SVD burden and cognitive dysfunction was assessed with linear mixed models or generalized estimating equation models, as appropriate. The majority of patients had mild-to-moderate stroke and at least one identifiable SVD marker. Cognitive impairment was found in about one-third of patients. After adjusting for confounding factors, the SVD burden was associated with MMSE scores (β = -0.37, P = .003) and cognitive impairment (odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.02-1.42). SVD burden was specifically associated with the performance of MMSE subscores including orientation to place and time, calculation, and word recall. Of the SVD markers, WMHs was the most robust predictor of decrease in MMSE scores (β = -0.25, P = .01) and cognitive impairment (OR = 1.14, 95% CI = 1.01-1.29). Cerebral SVD burden is associated with decreased MMSE scores, suggesting cognitive dysfunction during the first year after mild-to-moderate acute ischemic stroke.

Plasma Klotho concentration is associated with the presence, burden and progression of cerebral small vessel disease in patients with acute ischaemic stroke.

Klotho is a soluble or membrane-bound anti-aging protein, whose protective actions are important for a prudential function of many organs. Because Klotho and cerebral small vessel disease (SVD) are associated with ageing process and endothelial dysfunction, it is possible that Klotho has an association with cerebral SVD. We aimed to investigate the association of plasma Klotho concentration with the presence, burden and progression of cerebral SVD. We prospectively enrolled 262 patients with first-ever acute cerebral infarction, performed brain MRI and collected their blood samples within 24 hours of admission. An enzyme-linked immunosorbent assay was used for evaluating plasma Klotho concentration. We estimated the total SVD score of each patient after determining the presence and burden of high-grade white matter hyperintensities (HWMHs), cerebral microbleeds (CMBs), high-grade perivascular spaces (HPVSs) and asymptomatic lacunar infarctions (ALIs). Univariate and multivariate analyses were conducted to investigate association of Klotho with cerebral SVD and the total SVD score. Of the 262 patients, 152 (58.0%) were men. The mean age of these patients was 64.7 years. The mean ± standard deviation of plasma Klotho concentration was 329.8 ± 194.1 pg/mL. In multivariate analysis, plasma Klotho concentration was negatively associated with the presence of HWMHs [Odds ratio (OR): 0.13, p = 0.047], HPVSs (OR: 0.22, p = 0.024) and ALIs (OR: 0.53, p = 0.021) but not associated with the presence of CMBs (OR: 0.39, p = 0.404). Plasma Klotho concentration was also negatively related to the total SVD score (unstandardized coefficients beta: −0.895, standard error = 0.317, p = 0.005, R2 = 0.239). Furthermore, plasma Klotho concentration was negatively related to the presence (OR: 0.75, 95% CI: 0.59–0.96, p = 0.025) and severity of cerebral SVD progression (OR: 0.72, 95% CI: 0.56–0.92, p = 0.009). In conclusion, plasma Klotho concentration was negatively associated with the presence, burden and progression of cerebral SVD.