Cerebral Small Vessel Disease Score Research Articles

The associations of increased cerebral small vessel disease with cognitive impairment in neurosyphilis presenting with ischemic stroke.

Background and PurposeIschemic stroke is a common clinical feature of neurosyphilis, but its accompanying cognitive decline is often overlooked. The mechanisms of cognitive impairment in neurosyphilis presenting with ischemic stroke are not fully understood. Cerebral small vessel disease (CSVD) was recently shown to predict post‐stroke cognitive decline. Therefore, this study aims to validate the correlation between CSVD and cognitive impairment in neurosyphilis presenting with ischemic stroke.MethodsWe enrolled 179 neurosyphilis patients diagnosed as acute ischemic stroke and performed a 12‐month cognitive assessment follow‐up. CSVD burden was evaluated by neuroimaging markers, including white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs), and perivascular spaces (PVS). We performed multivariate logistic regression analysis to determine the association between cognitive decline and total CSVD burden score in neurosyphilis patients.ResultsThe neurosyphilis participants had a significantly higher total CSVD score and lower cognitive function score compared with the syphilis‐uninfected patients. Acute cognitive impairment was associated with total CSVD score, extensive microbleeds, and Grade 3 WMHs. After 12‐month follow‐up, the poor prognosis of post‐stroke cognitive impairment was associated with a higher burden of CSVD and extensive microbleeds.ConclusionsCerebral small vessel disease loads in neurosyphilis patients presenting with ischemic stroke are independently associated with acute cognitive impairment and have a prospective value for post‐stroke cognitive outcomes.

Abstract P332: Cerebral Small Vessel Disease Score in CADASIL: Relationships to Cognitive Dysfunctions

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small vessel disease (cSVD) linked to NOTCH3 mutations and leading to the early onset of stroke and vascular cognitive impairment. Neuroimaging features of CADASIL include extensive white matter hyperintensity, lacunes, cerebral microbleeds and enlarged perivascular spaces. Researchers from the Rotterdam study recently proposed a MRI-based cSVD Score reflecting the overall burden of cerebrovascular injury (Yilmaz et al., 2018). Here, we explored the relevance of this cSVD Score in distinguishing CADASIL subjects from non-carriers and its relationships to cognition. We evaluated 26 NOTCH3 mutation carriers and 25 non-carriers from large Colombian families. Of the CADASIL subjects, 4 had previous strokes (symptomatic) and 22 had no history of strokes (asymptomatic). All subjects underwent a 3T MRI and a neuropsychological evaluation. Structural MRI markers of cSVD, as well as the cSVD Score, were quantified in each subject following established protocols. Demographic, cognitive and neuroimaging features across groups are presented in Table 1. The cSVD Score significantly differed between groups, after adjusting for age (Figure 1-A). In CADASIL subjects, the cSVD Score was negatively related to performance in Memory, Processing Speed, Executive Function, after accounting for age and education (Figure 1-B). These results suggest that the cSVD Score could be a useful marker of disease severity in CADASIL. Longitudinal studies are now needed to determine if this score allows predicting clinical outcomes in CADASIL, such as stroke or dementia.

Cerebral Small Vessel Disease Load Predicts Functional Outcome and Stroke Recurrence After Intracerebral Hemorrhage: A Median Follow-Up of 5 Years.

Background: Uncertainty exists over the long-term prognostic significance of cerebral small vessel disease (CSVD) in primary intracerebral hemorrhage (ICH).Methods: We performed a longitudinal analysis of CSVD and clinical outcomes in consecutive patients with primary ICH who had MRI. Baseline CSVD load (including white matter hyperintensities [WMH], cerebral microbleeds [CMBs], lacunes, and enlarged perivascular spaces [EPVS]) was evaluated. The cumulative CSVD score was calculated by combining the presence of each CSVD marker (range 0–4). We followed participants for poor functional outcome [modified Rankin scale [mRS] ≥ 4], stroke recurrence, and time-varying survival during a median follow-up of 4.9 [interquartile range [IQR] 3.1–6.0] years. Parsimonious and fuller multivariable logistic regression analysis and Cox-regression analysis were performed to estimate the association of CSVD markers, individually and collectively, with each outcome.Results: A total of 153 patients were included in the analyses. CMBs ≥ 10 [adjusted OR [adOR] 3.252, 95% CI 1.181–8.956, p = 0.023] and periventricular WMH (PWMH) (adOR 2.053, 95% CI 1.220–3.456, p = 0.007) were significantly associated with poor functional outcome. PWMH (adOR 2.908, 95% CI 1.230–6.878, p = 0.015) and lobar CMB severity (adOR 1.811, 95% CI 1.039–3.157, p = 0.036) were associated with stroke recurrence. The cumulative CSVD score was associated with poor functional outcome (adOR 1.460, 95% CI 1.017–2.096) and stroke recurrence (adOR 2.258, 95% CI 1.080–4.723). Death occurred in 36.1% (13/36) of patients with CMBs ≥ 10 compared with 18.8% (22/117) in those with CMB < 10 (adjusted HR 2.669, 95% CI 1.248–5.707, p = 0.011). In addition, the cumulative CSVD score ≥ 2 was associated with a decreased survival rate (adjusted HR 3.140, 95% CI 1.066–9.250, p = 0.038).Conclusions: Severe PWMH, CMB, or cumulative CSVD burden exert important influences on the long-term outcome of ICH.

Modified cerebral small vessel disease score is associated with vascular cognitive impairment after lacunar stroke.

We conducted a cross-sectional study to characterize the relationship between total and modified small vessel disease (SVD) score with vascular cognitive impairment (VCI). Patients (n = 157) between the ages of 50 and 85 years old who had suffered their first lacunar infarction were analyzed prospectively. Brain magnetic resonance imaging was performed to identify SVD manifestations, which were used to calculate total or modified SVD scores. Neuropsychological assessments measured cognitive function. Spearman correlation analysis demonstrated that the total and modified SVD scores were associated with overall cognition as well as with function in the executive and visuospatial domains. The associations remained significant in linear regression after adjusting for age, sex, education and vascular risk factors. Binary logistic regression and chi-squared trend tests revealed that VCI risk increased significantly with SVD burden based on the modified SVD score. Subsequent chi-squared testing demonstrated that the VCI rate was significantly higher in patients with a modified SVD score of 5-6 than in patients without any SVD burden. Our results suggest that both the total and modified SVD scores show a negative association with cognitive function, but the modified SVD score may be better at identifying patients at high VCI risk.

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.

Optical coherence tomography angiography in cognitively impaired patients: Vascular and neurodegenerative perspectives

AbstractBackgroundVascular and neuronal changes in the retina may reflect cerebral small vessel disease (CSVD) and neurodegeneration in the brain. We aimed to compare radial peripapillary capillary (RPC) network density and RNFL thickness between diagnostic groups using optical coherence tomography angiography (OCTA) imaging. Then, we evaluated whether the RPC network density correlated with CSVD markers and whether RNFL correlated with Aβ or brain cortical thickness.MethodIn this prospective, cross‐sectional, observational study, subjects were recruited from February 2018 to March 2019. Retinal vascular [Capillary density (CD) of the radial peripapillary capillary (RPC) network] and neurodegeneration markers [retinal nerve fiber layer (RNFL) thickness at four quadrants] were measured using optical coherence tomography (OCT) and OCT angiography (OCTA) imaging. Brain vascular (CSVD score), and neurodegeneration markers [brain cortical thickness] were assessed using 3D brain magnetic resonance imaging. We compared CD and RNFL thickness between ADCI, SVCI, and CN group. Then, we evaluated correlation between retinal imaging markers (CD and RNFL) and brain imaging markers (CSVD score and cortical thickness)ResultThe mean (SD) age of total 60 participants was 70.3 (9.0) years and 21 (35%) of them were male. The SVCI group showed lower CD in the temporal quadrant of RPC network compared to the CN group (mean (sd), 42.34 (6.29) vs 48.45 (7.08); p = 0.002), and lower CD in the superior quadrant of RPC network (mean (sd), 60.14 (6.42) vs 64.15 (6.39); p = 0.021) compared with the ADCI group. The CD was negatively correlated with CSVD score in the superior (regression coefficient, ‐0.050; 95% CI, ‐0.083 to 0.017; p=0.004) and temporal (regression coefficient, ‐0.042; 95% CI, ‐0.070 to ‐0.014; p=0.004) quadrants of the RPC network. RNFL thickness did not differ among the groups nor did it correlate with cortical thickness.ConclusionThe importance of the CD of the RPC network rather than RNFL thicknesses should be highlighted in evaluating cerebral pathology. Moreover, noninvasive and rapid acquisition of OCTA images has the potential to be used as a peripheral imaging tool to screen for the degree of CSVD.

Association of Cerebral Small Vessel Disease and Cognitive Decline After Intracerebral Hemorrhage.

To determine whether MRI-based cerebral small vessel disease (CSVD) burden assessment, in addition to clinical and CT data, improved prediction of cognitive impairment after spontaneous intracerebral hemorrhage (ICH). We analyzed data from ICH survivors enrolled in a single-center prospective study. We employed 3 validated CSVD burden scores: global, cerebral amyloid angiopathy (CAA)-specific, and hypertensive arteriopathy (HTNA)-specific. We quantified cognitive performance by administering the modified Telephone Interview for Cognitive Status test. We utilized linear mixed models to model cognitive decline rates, and survival models for new-onset dementia. We calculated CSVD scores' cutoffs to maximize predictive performance for dementia diagnosis. We enrolled 612 ICH survivors, and followed them for a median of 46.3 months (interquartile range 35.5-58.7). A total of 214/612 (35%) participants developed dementia. Higher global CSVD scores at baseline were associated with faster cognitive decline (coefficient -0.25, standard error [SE] 0.02) and dementia risk (sub-hazard ratio 1.35, 95% confidence interval 1.10-1.65). The global score outperformed the CAA and HTNA scores in predicting post-ICH dementia (all p < 0.05). Compared to a model including readily available clinical and CT data, inclusion of the global CSVD score resulted in improved prediction of post-ICH dementia (area under the curve [AUC] 0.89, SE 0.02 vs AUC 0.81, SE 0.03, p = 0.008 for comparison). Global CSVD scores ≥2 had highest sensitivity (83%) and specificity (91%) for dementia diagnosis. A validated MRI-based CSVD score is associated with cognitive performance after ICH and improved diagnostic accuracy for predicting new onset of dementia.

Caliber of Intracranial Arteries as a Marker for Cerebral Small Vessel Disease.

Background: The dilation of intracranial large arteries caliber, may transfer more hemodynamic burden to the downstream brain capillaries, which, in the long run, results in cerebral small vessel disease (CSVD). This study aimed to investigate the relationship between intracranial artery calibers and small vessel disease.Methods: Patients with first-ever ischemic stroke of lacunar infarction subtype were enrolled via Nanjing Stroke Registry Program. An intracranial arterial Z-score, named the brain arterial remodeling (BAR) score, was calculated by averaging the calibers of the seven main intracranial arteries. Among the enrolled patients, those with a BAR score < −1 SD were deemed to have small intracranial artery calibers; those with a BAR score >1 SD were deemed to have large intracranial artery calibers and those with a between BAR score were deemed to have normal intracranial artery calibers. Imaging markers of CSVD, including lacuna, white matter hyperintensity (WMH), enlarged perivascular spaces (EPVS) and cerebral microbleeds (CMBs) were rated and then summed to obtain a total CSVD score.Results: A total of 312 patients were involved in this study, patients with BAR score >1 SD were older (P = 0.039), and more prone to having a history of myocardial infarction (P = 0.033). The Spearman's rank correlation coefficient between the BAR score and total CSVD score is 0.320 (P < 0.001). Binary logistic regression found that BAR score >1 SD was correlated with lacuna (OR = 1.987; 95% CI, 1.037–3.807; P = 0.039); severe WMH (OR = 1.994; 95% CI, 1.003–3.964; P = 0.049); severe EPVS (OR = 2.544; 95% CI, 1.299–4.983; P = 0.006) and CSVD (OR = 2.997; 95% CI 1.182–7.599; P = 0.021). Ordinal logistic regression analysis found that age (OR = 1.028; 95% CI, 1.007–1.049; P = 0.009), hypertension (OR = 3.514; 95% CI, 2.114–5.769; P < 0.001) and BAR score >1 SD (OR = 2.418; 95% CI, 1.350–4.330; P = 0.003) were correlated with the total CSVD score.Conclusions: Patients with large intracranial arterial calibers may have heavier CSVD burden. The mechanisms of this association warrant further study.

Vascular disease and multiple sclerosis: a post-mortem study exploring their relationships.

Vascular comorbidities have a deleterious impact on multiple sclerosis clinical outcomes but it is unclear whether this is mediated by an excess of extracranial vascular disease (i.e. atherosclerosis) and/or of cerebral small vessel disease or worse multiple sclerosis pathology. To address these questions, a study using a unique post-mortem cohort wherein whole body autopsy reports and brain tissue were available for interrogation was established. Whole body autopsy reports were used to develop a global score of systemic vascular disease that included aorta and coronary artery atheroma, cardiac hypertensive disease, myocardial infarction and ischaemic stroke. The score was applied to 85 multiple sclerosis cases (46 females, age range 39 to 84 years, median 62.0 years) and 68 control cases. Post-mortem brain material from a subset of the multiple sclerosis (n = 42; age range 39-84 years, median 61.5 years) and control (n = 39) cases was selected for detailed neuropathological study. For each case, formalin-fixed paraffin-embedded tissue from the frontal and occipital white matter, basal ganglia and pons was used to obtain a global cerebral small vessel disease score that captured the presence and/or severity of arteriolosclerosis, periarteriolar space dilatation, haemosiderin leakage, microinfarcts, and microbleeds. The extent of multiple sclerosis-related pathology (focal demyelination and inflammation) was characterized in the multiple sclerosis cases. Regression models were used to investigate the influence of disease status on systemic vascular disease and cerebral small vessel disease scores and, in the multiple sclerosis group, the relationship between multiple sclerosis-related pathology and both vascular scores. We show that: (i) systemic cardiovascular burden, and specifically atherosclerosis, is lower and cerebral small vessel disease is higher in multiple sclerosis cases that die at younger ages compared with control subjects; (ii) the association between systemic vascular disease and cerebral small vessel disease is stronger in patients with multiple sclerosis compared with control subjects; and (iii) periarteriolar changes, including periarteriolar space dilatation, haemosiderin deposition and inflammation, are key features of multiple sclerosis pathology outside the classic demyelinating lesion. Our data argue against a common primary trigger for atherosclerosis and multiple sclerosis but suggest that an excess burden of cerebral small vessel disease in multiple sclerosis may explain the link between vascular comorbidity and accelerated irreversibility disability.

Brachial-Ankle Pulse Wave Velocity is Related to the Total Cerebral Small-Vessel Disease Score in an Apparently Healthy Asymptomatic Population

IntroductionCerebral small-vessel disease (CSVD) is an extensive cerebrovascular disease associated with many poor outcomes. Previous studies have shown that brachial-ankle pulse wave velocity (baPWV) is related to various neuroimaging signatures, but its association with the total CSVD burden remains unknown. We aimed to explore whether baPWV is related to the total CSVD score and to establish a cutoff for detecting the presence and severity of CSVD, which may guide clinical preventive measures. MethodsWe retrospectively selected 684 neurologically healthy participants to explore correlations between baPWV and the total CSVD score and each of its components (lacunes, white matter hyperintensity (WMH), perivascular space (PVS), and cerebral microbleeds (CMBs)). Subsequently, we established two receiver operating characteristic (ROC) curves to study the effectiveness of baPWV in predicting CSVD (scores 1-4) and severe CSVD (scores 3–4). ResultsThe median baPWV was 13.16 m/s, which increased significantly with increasing scores (0–4). BaPWV was significantly higher among persons with each component of the total CSVD score than among those without any components. Multivariable ordinal logistic regression analyses showed that a one-unit (m/s) change in baPWV significantly increased the total CSVD score by 0.012. The optimal baPWV cutoffs for detecting CSVD and severe CSVD were 13.12 m/s and 15.63 m/s, respectively. ConclusionsBaPWV was positively correlated with the total CSVD score, suggesting that baPWV measurement is a useful method for early diagnosis of CSVD, which may contribute to preventing and controlling CSVD progression in the general population of China.

Associations of Blood Pressure and Carotid Flow Velocity with Brain Volume and Cerebral Small Vessel Disease in a Community-Based Population.

Cerebral small vessel disease (CSVD) is a common finding on brain magnetic resonance imaging (MRI). We previously demonstrated that high blood pressure (BP) and low carotid flow velocity were associated with cerebrovascular disease. However, their associations with brain volume and CSVD remain to be determined. A total of 721 adults (≥ 50years) from the community-based I-Lan Longitudinal Aging Study were included. Flow velocities at the common (CCA) and internal carotid artery (ICA), including peak systolic velocity (PSV) and end-diastolic velocity (EDV), were measured with Doppler ultrasound. We further detected the presence of CSVD including lacune, microbleed, and white matter hyperintensity (WMH) on brain MRI, which were used to construct a combined CSVD score. General linear regression and logistic regression analysis were exploited to evaluate the association between carotid flow velocity, BP, brain volume, and CSVD. The mean of white matter, gray matter, and WMH volume were 422.2cm3, 546.9cm3, and 2.61cm3, respectively. The proportion of lacune and microbleed were 11.1% and 14.2%, respectively. The CSVD score were negatively associated with gray (r = - 0.121, p < .01) and white matter volume (r = 0.058, p = 0.12), but positively associated with systolic BP (beta = 1.02, p = 0.0017). EDV at common carotid artery associated positively with white matter volume (beta = 1.013, p = 0.0064) and negatively predicted the presence CSVD (odds ratio [OR] = 0.93, p = 0.0023). In the ordinal logistic regression analysis adjusting for age, sex, total intracranial volume education, low-density lipoprotein cholesterol, and fasting glucose, compared with hypertensive subjects with low EDV, normotensive subjects with low, middle, and high EDV had an odds ratio of 0.656 (0.327-1.318), 0.429 (0.261-0.705), and 0.272 (0.147-0.502) for CSVD score, respectively. High SBP and low carotid flow velocities were independently associated with brain volume and CSVD. These associations may be involved in the pathophysiology of cognitive function decline.

Cerebral small vessel disease or intracranial large vessel atherosclerosis may carry different risk for future strokes

BackgroundThe effect of cerebral small vessel disease (CSVD) and intracranial arterial stenosis (ICAS) on stroke outcomes remains unclear.MethodsData of 1045 patients with minor stroke or transient ischaemic attack (TIA) were...

Lower Blood Pressure, Small-Vessel Disease, and Apathy in Older Persons With Mild Cognitive Deficits.

BACKGROUNDIn older persons, both high and low blood pressure (BP) levels are associated with symptoms of apathy. Population characteristics, such as burden of cerebral small‐vessel disease (CSVD), may underlie these apparently contradictory findings. We aimed to explore, in older persons, whether the burden of CSVD affects the association between BP and apathy.DESIGNCross‐sectional study.SETTINGPrimary care setting, the Netherlands.PARTICIPANTSCommunity‐dwelling older persons (mean age = 80.7 years; SD = 4.1 years) with mild cognitive deficits and using antihypertensive treatment, participating in the baseline measurement of the magnetic resonance imaging substudy (n = 210) of the Discontinuation of Antihypertensive Treatment in the Elderly Study Leiden.MEASUREMENTSDuring home visits, BP was measured in a standardized way and apathy was assessed with the Apathy Scale (range = 0‐42). Stratified linear regression analyses were performed according to the burden of CSVD. A higher burden of CSVD was defined as 2 or more points on a compound CSVD score (range = 0‐3 points), defined as presence of white matter hyperintensities (greater than median), any lacunar infarct, and/or two or more microbleeds.RESULTSIn the entire population, those with a lower systolic and those with a lower diastolic BP had more symptoms of apathy (β = −.35 [P = .01] and β = −.66 [P = .02], respectively). In older persons with a higher burden of CSVD (n = 50 [24%]), both lower systolic BP (β = −.64, P = .02) and lower diastolic BP (β = −1.6, P = .01) were associated with more symptoms of apathy, whereas no significant association was found between BP and symptoms of apathy in older persons with a lower burden of CSVD (n = 160).CONCLUSIONSParticularly in older persons with a higher burden of CSVD, lower BP was associated with more symptoms of apathy. Adequate BP levels for optimal psychological functioning may vary across older populations with a different burden of CSVD. J Am Geriatr Soc 68:1811‐1817, 2020.

Cerebral small vessel disease score and atherosclerosis burden – A population study in community-dwelling older adults

ObjectiveCerebral small vessel disease (cSVD) and large artery atherosclerosis (LAA) are related to different pathogenetic mechanisms. However, relationships between single biomarkers of cSVD and LAA affecting isolated vascular beds have been reported. Using the Atahualpa Project cohort, we aimed to assess the association between cSVD score categories and LAA burden in community-dwelling older adults. Patients and methodsAtahualpa individuals aged ≥60 years undergoing assessment of the cSVD score and LAA in the peripheral, carotid extracranial, and intracranial vascular beds (n = 333) were included. Multivariate models were fitted to assess independent associations between the cSVD score and LAA burden. ResultsThe cSVD score was 0 points in 62 % individuals, 1 point in 19 %, 2 points in 13 %, and 3–4 points in 7 %. LAA involved the extracranial carotid bed in 43 % individuals, the intracranial bed in 36 %, and the peripheral bed in 20 %. One vascular bed was involved in 111 (33 %) individuals, two beds in 75 (23 %), and three beds in 23 (7 %). The remaining 124 (37 %) had no atherosclerosis. Ordinal logistic regression models showed progressively greater associations between higher categories of cSVD score and the odds of having more beds involved with LAA. Multinomial logistic regression models showed associations between categories of cSVD score and LAA burden, but only when two or three vascular beds were involved. ConclusionThis study demonstrates robust associations between the cSVD score and LAA, which become evident at the upper end of the spectrum of cSVD score (3–4 points) and LAA burden (2–3 vascular beds involved).

Associations of Arterial Stiffness and Carotid Atherosclerosis with Cerebral Small Vessel Disease in a Rural Community-Based Population.

Aims: We aimed to examine the associations of four extracranial artery indicators with cerebral small vessel disease (CSVD) and its total burden.Methods: A total of 904 individuals aged 55–65 years old were included from the Taizhou Imaging Study. CSVD markers, including lacunes (LAC), white matter hyperintensities (WMH), cerebral microbleeds (CMB), and perivascular spaces (PVS), were rated based on brain magnetic resonance imaging. We also measured extracranial artery indices, including the brachial-ankle pulse wave velocity (baPWV), the ankle-brachial index, the carotid intima-media thickness (IMT), and carotid plaque. Linear and binary logistic regressions were adopted to test the associations among these four artery indicators and each CSVD marker when appropriate. Additionally, ordinal and multinomial logistic regressions were performed to assess the relationships between artery indicators and total CSVD score (range from 0–4 points).Results: A total of 443 (49.0%) participants were found to have at least one of the CSVD markers, including 172 (19.0%) with WMH, 184 (20.4%) with LAC, 147 (16.3%) with CMB, and 226 (25.0%) with PVS. Increased baPWV was significantly associated with each CSVD marker, increasing carotid IMT was associated with LAC and PVS, and the presence of carotid plaque was associated with WMH volume and PVS. Moreover, per SD increment of baPWV (odds ratio [OR]: 1.29, 95% confidence interval [CI]: 1.11–1.50) and the presence of carotid plaque (OR: 1.42, 95% CI: 1.05–1.92) were significantly associated with greater total CSVD scores.Conclusion: Increased baPWV and the presence of carotid plaque appear to be associated with total CSVD burden in rural regions in China.

Abstract 7: Cerebral Small Vessel Disease Burden and Association With Post-Surgical Rebleeding and Long-Term Outcome in Intracerebral Hemorrhage Patients From the Mistie III Trial

Objectives: To examine the effect of cerebral small vessel disease (CSVD) markers and CSVD burden on hematoma expansion and long-term functional outcomes in large spontaneous intracerebral hemorrhage (ICH) &gt;30 mL. Method: Retrospective analysis of 288 patients from the MISTIE III trial with qualified MRI sequences. MISTIE III evaluated minimally invasive surgery plus alteplase (vs medical management). We identified 6 CSVD markers including lacunes, cerebral microbleeds (CMB), enlarged perivascular space (EPVS), white matter hyperintensities (WMH), cortical superficial siderosis (cSS), and acute DWI positive lesions. First 5 components were reviewed on day 1 MRI and DWI lesions on day 7. The primary outcome was death or major disability at one year (modified Rankin score 4-6). Secondary outcome was post-surgical rebleeding, defined as symptomatic or asymptomatic hemorrhage expansion within 72 hours post last dose of alteplase. Result: Unfavorable outcome occurred in 65.9% at one year. Post-surgical ICH expansion occurred in 34 (22.9%) of 148 surgical patients. Mean time from symptom onset to first MRI was 0.94 (IQR 0.2-6.3) days. Most individual CSVD markers were more common in patients with unfavorable vs. favorable outcome: CMB≧5 (26.1% vs 15.0%, p=0.03), DWI lesions (65.8%vs 49.6%, p=0.006), cSS (16.8% vs 7.1%, p=0.02) severe WMH (67.7% vs 29.9%, p&lt;0.001) severe EPVS in basal ganglia (19.3% vs 10.2%, p=0.047), and lacunes (11.2% vs 6.3%, p=0.21), In the multivariable adjusted model, cumulative CSVD score (one point for each component: CMB≥5, severe EPVS in basal ganglia, lacunes, severe WMH and cSS) was independently associated with unfavorable outcome (OR 0.56, 95%CI 0.41-0.76, p&lt;0.001; AUC 0.855). We did not find a relationship between either independent CSVD markers or CSVD score with post-surgical ICH expansion. Cumulative CSVD score in multivariable analysis adjusted for predictors of hematoma expansion had OR 0.77 (95% CI 0.50-1.19, p=0.77; AUC 0.659). Conclusion: In large volume ICH patients with long-term follow-up, heavy burden of CSVD at ICH onset remains an independent predictor of unfavorable outcome, and particularly severe white matter hyperintensities. CSVD markers did not show association with post-surgical ICH expansion.

Cerebral Small Vessel Disease Burden and All-Cause Mortality: Mayo Clinic Florida Familial Cerebrovascular Diseases Registry

Goal: Cerebral small vessel disease (CSVD) leads to cognitive decline, gait disturbances, mood changes, and an increased risk of stroke. The goal of this study is to describe the relationship between a composite radiographic CSVD score and all-cause mortality. Materials and Methods: Data were collected from a prospective registry of patients with and without cerebrovascular disease from November 2010 through April 2018. The radiographic Total CSVD Score (tSVD) ranges from 0 (minimal disease) to 4 (severe disease), based on detection of lacunar infarcts, cerebral microbleeds, perivascular spaces, and subcortical or periventricular white matter hyperintensities. All-cause mortality served as the primary endpoint. The independent relationship between CSVD burden and all-cause mortality was assessed using Cox regression models with significance being P < .05. Findings: Four hundred and forty-nine patients were included (mean age, 63 years; 50.1% [225 of 449] women). The hazard ratio for mortality significantly increased with advancing score (1.92, P = .014 score 1; 2.92, P < .001 score 2; 4.23, P < .001 combined scores 3 and 4). Significance remained despite adjustment for coexistent cerebrovascular risk factors aside from age. Conclusions: The clinically practical tSVD score may serve as a predictor for all-cause mortality in populations with high disease prevalence. Continued investigations are needed to better understand the effects of risk factor modification on mortality and pathogenesis with the goal of developing disease modifying therapies.

Insulin Resistance Is a Risk Factor for Overall Cerebral Small Vessel Disease Burden in Old Nondiabetic Healthy Adult Population.

Background and Purpose: This study aimed to investigate the association between insulin resistance (IR) and the overall cerebral small vessel disease (CSVD) burden.Methods: We recruited elderly, nondiabetic, healthy subjects prospectively. The overall effect of CSVD on the brain was described by a validated CSVD score. The homeostasis model assessment–estimated insulin resistance index (HOMA-IR) was used for IR estimation, and HOMA-IR ≥2.80 was defined as IR. We evaluated the association between IR and the increasing severity of CSVD score by ordinal regression models adjusting for demographics and cardiovascular risk factors.Results: A total of 156 healthy participants were recruited. The mean age was older in the IR group than in the non-IR group (70.03 vs. 67.45, p = 0.04), and the prevalence of hypertension was significantly higher in the IR group than in the non-IR group (82.35% vs. 53.28%, p < 0.01). In ordinal regression analysis, IR was positively associated with increasing severity of the total CSVD score (adjusted odds ratio, 3.74; 95% confidence interval, 1.63–5.08; p < 0.01) after adjusting traditional risk factors. Furthermore, HOMA-IR levels showed a positive dose-dependent correlation with the total CSVD score (p < 0.01, p for trend <0.01).Conclusions: IR is independently associated with increasing severity of the overall CSVD burden, independent of other clinical risk factors in an elderly, nondiabetic, healthy population. Furthermore, HOMA-IR level is correlated with the CSVD burden in a dose-dependent manner.

Total Cerebral Small Vessel Disease Burden Is Related to Worse Performance on the Mini-Mental State Examination and Incident Dementia: A Prospective 5-Year Follow-Up.

Individual cerebral small vessel disease (CSVD) may cause cognitive decline. However, the association between total burden of CSVD and cognitive deterioration in the general population remains unclear. We aimed to determine whether total CSVD score is associated with cognitive performance change and incident dementia in the general population. In the longitudinal population-based Taizhou Imaging Study, 556 participants free of neurological disorders underwent brain MRI and neuropsychological testing at baseline. A total of 456 participants were followed up for cognitive performance for a mean (standard deviation) of 4.6 (0.6) years. Total CSVD score (range 0-4) was calculated by assigning 1 point for the presence of each of the following markers: lacune, white matter hyperintensity, cerebral microbleed, and perivascular space. Beta regression was used to evaluate the association between total CSVD burden and MMSE score change. The association of prevalent CSVD with incident dementia was studied using Fisher's exact test. CSVDs were present in 262 individuals (47.1%). The total CSVD score was significantly associated with MMSE score decline (p = 0.001). Compared to those with no CSVD, participants with 4 CSVD markers had a steeper decline in MMSE score (β: -0.53, 95% CI: -0.86 to -0.21; p = 0.001). A total of 15 participants developed dementia during follow-up. The presence of more than three CSVD markers at baseline was associated with a significantly higher risk of dementia (p = 0.020). Total CSVD burden appears to be associated with MMSE score decline and incident dementia in a general population in China.