cSVD Burden Research Articles

Differences in Alzheimer's Disease and Related Dementias Pathology Among African American and Hispanic Women: A Qualitative Literature Review of Biomarker Studies.

IntroductionThe population of older adults with Alzheimer’s disease and Related Dementias (ADRD) is growing larger and more diverse. Prevalence of ADRD is higher in African American (AA) and Hispanic populations relative to non-Hispanic whites (nHW), with larger differences for women compared to men of the same race. Given the public health importance of this issue, we sought to determine if AA and Hispanic women exhibit worse ADRD pathology compared to men of the same race and nHW women. We hypothesized that such differences may explain the discrepancy in ADRD prevalence.MethodsWe evaluated 932 articles that measured at least one of the following biomarkers of ADRD pathology in vivo and/or post-mortem: beta-amyloid (Aß), tau, neurodegeneration, and cerebral small vessel disease (cSVD). Criteria for inclusion were: (1) mean age of participants >65 years; (2) inclusion of nHW participants and either AA or Hispanics or both; (3) direct comparison of ADRD pathology between racial groups.ResultsWe included 26 articles (Aß = 9, tau = 6, neurodegeneration = 16, cSVD = 18), with seven including sex-by-race comparisons. Studies differed by sampling source (e.g., clinic or population), multivariable analytical approach (e.g., adjusted for risk factors for AD), and cognitive status of participants. Aß burden did not differ by race or sex. Tau differed by race (AA < nHW), and by sex (women > men). Both severity of neurodegeneration and cSVD differed by race (AA > nHW; Hispanics < nHW) and sex (women < men). Among the studies that tested sex-by-race interactions, results were not significant.ConclusionFew studies have examined the burden of ADRD pathology by both race and sex. The higher prevalence of ADRD in women compared to men of the same race may be due to both higher tau load and more vulnerability to cognitive decline in the presence of similar Aß and cSVD burden. AA women may also exhibit more neurodegeneration and cSVD relative to nHW populations. Studies suggest that between-group differences in ADRD pathology are complex, but they are too sparse to completely explain why minority women have the highest ADRD prevalence. Future work should recruit diverse cohorts, compare ADRD biomarkers by both race and sex, and collect relevant risk factor and cognitive data.

Renal Dysfunction Is Associated with Middle Cerebral Artery Pulsatility Index and Total Burden of Cerebral Small Vessel Disease

Background and Purpose: Renal dysfunction is known to affect vasculature and lead to systemic arterial stiffness. It also independently increases the risk of cerebral small vessel disease (cSVD) and stroke. We aimed to examine the effect of renal dysfunction on cerebral hemodynamics and the burden of cSVD. Methods: Of the 412 patients admitted to Seoul National University Hospital, between May 2015 and 2019, with lacunar infarction and no major intracranial arterial stenosis observed on magnetic resonance angiography, we included 283 patients who had undergone a transcranial Doppler (TCD) ultrasound after 72 h of stroke onset. The patients were divided into renal dysfunction (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m² at admission) and control (eGFR ≥60 mL/min/1.73 m²) groups. We investigated the correlations between renal function, the pulsatility index (PI), and the total MRI burden of cSVD. Furthermore, multivariate analysis was performed to assess the association between renal dysfunction and the PI of the middle cerebral artery (MCA) measured through TCD ultrasound. Results: Among the total patients, 74 (26.1%) had renal dysfunction (eGFR <60 mL/min/1.73 m² at admission). Patients with renal dysfunction were significantly older, showed higher pulse pressure, and had a higher prevalence of hypertension, diabetes mellitus, and coronary artery disease. Renal dysfunction was significantly associated with higher distal cerebrovascular flow resistance (median PI 1.12, interquartile range [IQR]: 0.85–1.57 vs. controls 0.84, IQR: 0.54–1.22; p < 0.001). Also, patients with renal dysfunction had a significantly higher total MRI burden of cSVD (median cSVD score 2, IQR: 1–3 vs. controls median score 1, IQR: 0–2; p < 0.001). There was an inverse proportional relationship between the PI and eGFR. Finally, multivariate analysis showed renal dysfunction (adjusted odds ratio: 4.516, 95% confidence interval: 1.051–20.292) and older age (adjusted odds ratio: 1.076, 95% confidence interval: 1.038–1.114) as independent predictors of a high PI. Conclusions: Renal dysfunction is independently associated with a high PI of MCA. Renal dysfunction leads to systemic arterial stiffness including stiffness in cerebral arteries, thus increasing the burden of cSVD. Therefore, noninvasive screening for high PI by TCD in kidney failure patients might be helpful.

The association of markers of cerebral small vessel disease and brain atrophy with incidence and course of depressive symptoms - the maastricht study

BackgroundCerebral small vessel disease (CSVD) and neurodegeneration may be involved in the development and persistence of late-life depressive symptoms, but longitudinal evidence is scarce. We investigated the longitudinal associations of markers of CSVD and brain atrophy with incident depressive symptoms and the course of depressive symptoms, above and below 60 years of age. MethodsWhite matter hyperintensity volumes (WMH), presence of lacunar infarcts and cerebral microbleeds, and white matter, grey matter, and cerebral spinal fluid volumes were assessed at baseline by 3T MRI in The Maastricht Study (mean age 59.5±8.5 years, 49.6% women, n=4,347; 16,535 person-years of follow-up). Clinically relevant depressive symptoms (9-item Patient Health Questionnaire≥10) were assessed at baseline and annually over seven years. We used Cox regression and multinomial logistic regression analyses adjusted for demographic, cardiovascular, and lifestyle risk factors. ResultsAbove 60 years of age, larger WMH volumes were associated with an increased risk for incident depressive symptoms (HR[95%CI]:1.24[1.04;1.48] per SD) and a persistent course of depressive symptoms (OR:1.44[1.04;2.00] per SD). Total CSVD burden was associated with persistent depressive symptoms irrespective of age (adjusted OR:1.58[1.03;2.43]), while no associations were found for general markers of brain atrophy. LimitationssOur findings need replication in other large-scale population-based studies. ConclusionsOur findings may suggest a temporal association of larger WMH volume with the incidence and persistence of late-life depression in the general population and may provide a potential target for the prevention of chronic late-life depression.

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

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

DAY-TO-DAY HOME BLOOD PRESSURE VARIABILITY IS ASSOCIATED WITH CEREBRAL SMALL VESSEL DISEASE BURDEN IN A MEMORY CLINIC POPULATION

Objective: High visit-to-visit blood pressure variability (BPV) has been associated with cognitive decline and cerebral small vessel disease (cSVD), in particular with cerebrovascular lesions. It is likely that the causes and consequences of high BPV depend on which temporal resolution is investigated. Day-to-day BPV has been related to cognitive function, but has not been investigated in relation to cSVD. Therefore, we aimed to investigate the cross-sectional association between day-to-day BPV and total cSVD MRI burden, in older memory clinic patients. Design and method: We included outpatients referred to our memory clinic, who underwent cerebral MRI as part of their diagnostic assessment. Four markers of cSVD were visually rated, resulting in a score between 0 and 4: presence of microbleed(s), presence of lacune(s), severe white matter hyperintensities and enlarged perivascular spaces in the basal ganglia. Home blood pressure (BP) measurements were performed for one week according to international guidelines. After removal of day 1, BPV was defined as the coefficient of variation (CV). We used multivariable ordinal logistic regression analyses adjusted for age, sex, smoking, diabetes, history of cardiovascular disease and mean BP to assess the association between total cSVD score and BPV. Results: In 82 patients (aged 71.2 ± 7.9 years), mean home BP was 140/79 ± 15/9 mmHg. Dementia and mild cognitive impairment were present in 46% and 34%, respectively. 22% of the study population had a total cSVD score of 0. These frequencies 24%, 26%, 20% and 8% for scores of 1, 2, 3 and 4, respectively. Systolic CV was associated with total cSVD burden, with the adjusted odds ratio per point increase in CV = 1.30, 95% confidence interval = 1.05–1.61, p = 0.018. There were no differences in diastolic CV and mean BP between the cSVD groups. When we differentiated between morning and evening BP, only evening BPV remained significantly associated with total cSVD burden. Conclusions: Day-to-day systolic BPV is associated with cSVD burden in memory clinic patients. Future research should indicate whether lowering day-to-day systolic BPV should be included in BP management in older people with memory complaints.

Do Gendered Psychosocial Factors Explain Sex Differences in White Matter Hyperintensities?

Women have a greater burden than men of white matter hyperintensities (WMH), a marker of cerebral small vessel disease (cSVD). Psychosocial factors including education, household income, neighborhood socioeconomic status (nSES), happiness, and depression may differ by gender and could explain women’s higher burden of WMH. In a cohort of older adults (N=250, median age=82, 58% women, 39% Black), we found that women had lower education, household income, nSES and were less happy and more depressed. Race stratified Spearman correlations showed women had greater whole brain WMH volume in white participants only (white: rho=0.23, p=0.004; Black: rho=-0.05, p=0.64). In partial Spearman correlations, education, happiness, and depression attenuated but did not fully explain the relationship when added individually or all together to the model for whites (fully adjusted rho=0.19, p=0.03). Gendered psychosocial factors may partially explain sex differences in WMH; interventions targeting these factors may reduce cSVD burden, particularly in white women.

New Insights in Addressing Cerebral Small Vessel Disease: Association With the Deep Medullary Veins.

ObjectiveTo assess the suitability of deep medullary vein visibility in susceptibility weighted imaging—magnetic resonance imaging studies as a method for the diagnosis and evaluation of cerebral small vessel disease progression.MethodsA total of 92 patients with CSVD were enrolled and baseline clinical and imaging data were reviewed retrospectively. Neuroimaging biomarkers of CSVD including high-grade white matter hyperintensity (HWMH), cerebral microbleed (CMB), enlarged perivascular space (PVS), and lacunar infarct (LI) were identified and CSVD burden was calculated. Cases were grouped accordingly as mild, moderate, or severe. The DMV was divided into six segments according to the regional anatomy. The total DMV score (0–18) was calculated as the sum of the six individual segmental scores, which ranged from 0 to 3, for a semi-quantitative assessment of the DMV based on segmental continuity and visibility.ResultsThe DMV score was independently associated with the presence of HWMH, PVS, and LI (P < 0.05), but not with presence and absence of CMB (P > 0.05). Correlation between the DMV score and the CSVD burden was significant (P < 0.05) [OR 95% C.I., 1.227 (1.096–1.388)].ConclusionThe DMV score was associated with the presence and severity of CSVD.

Twenty-Four-Hour Ambulatory Blood Pressure Variability Associated With Cerebral Small Vessel Disease MRI Burden and Its Progression in Inpatients With Cerebrovascular Disease.

Background: Lacunar infarcts, white matter lesions, cerebral microbleed, enlarged perivascular space and brain atrophy are regarded as magnetic resonance imaging (MRI) manifestations of cerebral small vessel disease (cSVD). 24-hour blood pressure variability (BPV) has been reported to relate with cerebral small vessel disease, but the impact of 24-h BPV on the total MRI cSVD burden and its progression in inpatients with cerebrovascular disease has not been investigated yet.Methods: We enrolled inpatients with cerebrovascular disease, who underwent the 24-h ambulatory blood pressure monitoring (ABPM) and the brain MRI scan at baseline and had the follow-up brain MRI images stored in the clinical information system of our hospital. BPV was quantified by the calculation of standard deviation (SD), coefficient of variation (CV), weighted standard deviation (wSD) of blood pressure record. We evaluated the total cSVD score on baseline MRI and the MRI followed-up to obtain the total burden of cSVD. The cSVD burden progression was estimated through the comparison of the total cSVD score on the two MRIs.Results: A total of 140 patients with an average age of 65.6 years were finally enrolled, 82.9% (116/140) of whom had one or more cSVD markers. After a median of 4.4 years follow-up, cSVD score progression were found in 50.7% (71/140) of the patients. Both SD and CV of SBP and DBP during 24-h and daytime as well as the SBP wSD differed significantly among different total cSVD score groups. The SBP SD and CV during 24-h and daytime, the SBP SD in nighttime, the DBP SD and CV during the daytime were significantly higher in the cSVD progression group than those in the cSVD no-progression group. The SBP wSD and the DBP wSD were significantly higher in the cSVD progression group than those in the cSVD no-progression group. Logistic regression analyses revealed that daytime SBP SD and SBP wSD were independent risk factors for total cSVD burden [daytime SBP SD: OR = 1.628, 95% CI = 1.105–2.398 (per 5 mmHg increase in SD), P = 0.014; SBP wSD: OR = 2.248, 95% CI = 1.564–3.230 (per 5 mmHg increase in wSD), P < 0.001)] and SBP wSD was a significant predictor for cSVD progression [OR = 2.990, 95% CI = 1.053–8.496 (per 5 mmHg increase in wSD), P = 0.040].Conclusion: Higher BPV were significantly related with total cSVD burden in inpatients with cerebrovascular disease. SBP SD during daytime and SBP wSD were independent risk factor for total cSVD burden and SBP wSD was an predictive factor for cSVD progression.

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.

Distinct association between cerebral arterial pulsatility and subtypes of cerebral small vessel disease.

BackgroundIncreased arterial resistance is a potential pathological mechanism of cerebral small vessel disease (cSVD).AimIn this study, we aimed to investigate the association between pulsatility index (PI) representing cerebral arterial resistance and subtypes of cSVD in patients with lacunar stroke.MethodsWe included consecutive lacunar stroke patients between 2010 and 2013. White matter hyperintensity (WMH) volume was rated using semi-automated quantitative methods. Additionally, the presence of old lacunar infarct (OLI), cerebral microbleed (CMB), or enlarged perivascular space (EPVS) was also evaluated. The relationship between PI, measured in each middle cerebral artery, and the subtype/burden of cSVD was analyzed in the relevant hemisphere.ResultsA total of 206 lacunar patients were included and 412 hemispheres were analyzed (mean age: 64 years, male: 68.4%). In multivariable analysis, PI was positively associated with the WMH volume [beta = 1.372, 95% confidence interval (CI) = 0.624 to 2.120, P < 0.001] after adjusting for confounders. PI was also related to the presence of OLI (adjusted odds ratio = 11.37, 95% CI = 2.55–48.56, P = 0.001); however, this relationship was not significant in CMB or EPVS. Regarding the cSVD burden, PI increased according to the WMH tertiles (P for trend < 0.001), the burden of OLI (P for trend < 0.001), and EPVS tertiles (P for trend < 0.001), showing a quantitative relationship.ConclusionsIpsilateral PI is closely associated with cSVD in patients with lacunar stroke. Furthermore, this association is different between subtypes of cSVD, which is suggestive of underlying pathophysiological differences.

Alterations of the Whole Cerebral Blood Flow in Patients With Different Total Cerebral Small Vessel Disease Burden.

BackgroundCerebral small vessel disease (CSVD) is a common age-related vascular disease of the brain associated with slowly accumulating tissue damage. At present, total CSVD burden score is a commonly used method to evaluate the severity of the disease.PurposeTo observe whether global and regional cerebral perfusion is related to total CSVD score and to explore global and regional cerebral blood flow (CBF) changes in patients with different degrees of CSVD.MethodsWe collected 130 subjects with different total burden score of CSVD (0 point: 33 subjects, 1 point: 39 subjects, 2 points: 24 subjects, 3 points: 24 subjects, 4 points: 10 subjects). Total CSVD burden score was evaluated by clinically routine sequences (T2WI, T2-FLAIR, T1WI, DWI, and SWAN sequence). Global and regional CBF were calculated and correlation analysis was used to investigate the relationship between total CSVD score and CBF of the whole brain and several brain regions.ResultsThe analysis results showed that there was a negative correlation between total CSVD burden score and global CBF (r = −0.33, p = 0.001). Total CSVD burden score also had moderately negative correlations with CBF of almost all the brain regions.ConclusionCSVD is a disease that affects the whole brain. With the increase of total CSVD burden score, the global and regional CBF decreased. The CSVD total burden score could be used to evaluate the overall condition of brain perfusion.

Optical coherence tomography angiography as a potential screening tool for cerebral small vessel diseases

BackgroundThe retina and the brain share anatomic, embryologic, and physiologic characteristics. Therefore, retinal imaging in patients with brain disorders has been of significant interest. Using optical coherence tomography angiography (OCTA), a novel quantitative method of measuring retinal vasculature, we aimed to evaluate radial peripapillary capillary (RPC) network density and retinal nerve fiber layer (RNFL) thickness in cognitively impaired patients and determine their association with brain imaging markers.MethodsIn this prospective cross-sectional study, a total of 69 patients (138 eyes) including 29 patients with amyloid-positive Alzheimer’s disease-related cognitive impairment (ADCI), 25 patients with subcortical vascular cognitive impairment (SVCI), and 15 amyloid-negative cognitively normal (CN) subjects were enrolled. After excluding eyes with an ophthalmologic disease or poor image quality, 117 eyes of 60 subjects were included in the final analyses. 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 OCTA and OCT imaging. Brain vascular (CSVD score) and neurodegeneration markers (cortical thickness) were assessed using 3D brain magnetic resonance imaging. The CD and RNFL thickness and their correlation with brain imaging markers were investigated.ResultsThe SVCI group showed lower CD in the temporal quadrant of the RPC network compared to the CN group (mean (SD), 42.34 (6.29) vs 48.45 (7.08); p = 0.001). When compared to the ADCI group, the SVCI showed lower CD in the superior quadrant (mean (SD), 60.14 (6.42) vs 64.15 (6.39); p = 0. 033) as well as in the temporal quadrant (ADCI 45.76, SVCI 42.34; p = 0.048) of the RPC network. The CD was negatively correlated with CSVD score in the superior (B (95%CI), − 0.059 (− 0.097 to − 0.021); p = 0.003) and temporal (B (95%CI), − 0.048 (− 0.080 to − 0.017); p = 0.003) quadrants of the RPC network. RNFL thickness did not differ among the groups nor did it correlate with cortical thickness.Conclusions and relevanceThe microvasculature of the RPC network was related to the CSVD burden. However, the RNFL thickness did not reflect cerebral neurodegeneration. Noninvasive and rapid acquisition of the OCTA image might have the potential to be used as a screening tool to detect CSVD.

High triglyceride-glucose index is associated with subclinical cerebral small vessel disease in a healthy population: a cross-sectional study

BackgroundThe triglyceride-glucose (TyG) index is a marker of insulin resistance (IR) and has been associated with various metabolic syndromes, cardiovascular diseases, and cerebrovascular diseases. However, limited information is available regarding its association with subclinical cerebral small vessel disease (cSVD). In this study, we evaluated the relationship between the TyG index and cSVD, including silent brain infarcts (SBIs) and white matter hyperintensity (WMH).MethodsWe assessed health check-up participants aged 40–79 years from 2006 to 2013. The TyG index was calculated using the log scale of fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2. The Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was also calculated. This was compared with two insulin surrogates and cSVD as another IR indicator and compared the association between two insulin surrogates and cSVD. SBI was measured for both prevalence and burden. The WMH volume was quantitatively rated using a computer-assisted semi-automated technique.ResultsA total of 2615 participants were evaluated (median age: 56 years, male sex: 53%). In the multivariable logistic regression analysis, the TyG index was seen to be associated with SBI prevalence (adjusted odds ratio: 1.39; 95% confidence interval [CI] = 1.06–1.81). Further quantitative analyses showed a positive dose–response relationship between the TyG index and SBI burden (P for trend = 0.006). In multivariable linear regression analysis, the TyG index was also found to be related to the volume of WMH (β = 0.084; 95% CI = 0.013 to 0.154). Additionally, the TyG index showed a similar or slightly stronger association with the prevalence of SBI and the volume of WMH than did HOMA-IR.ConclusionsA high TyG index was associated with a higher prevalence and burden of cSVD in a neurologically healthy population. This marker of IR could be a convenient and useful predictor of cSVD.

The determinants of neurological phenotypes during acute hypertensive crises – a preliminary study

ABSTRACT Background and Purpose: Acute blood pressure elevations lead to wide spectrum of neurologic manifestations, ranging from no overt neurologic symptoms to catastrophic events like ICH. Little is known regarding the determinants of this clinical variability. We determined clinical and imaging features of hypertensive crisis patients with normal neurological examination, ICH and posterior reversible encephalopathy syndrome (PRES). Methods: Cranial MRI was performed in patients with hypertensive urgency or emergency but normal neurological examination. Their clinical characteristics, and imaging features regarding cerebral small vessel disease were compared to ICH and PRES patients. Results: Hypertensive ICH patients (n = 58) were older, less likely to have hyperlipidemia, less commonly used calcium channel blockers, and had higher burden of chronic cSVD features in comparison to hypertensive crisis patients with normal neurological findings (n = 51). Multivariate analyses revealed cSVD burden score (p = 0.003) to be related with ICH, while higher admission blood pressure levels (p < 0.001), hyperlipidemia (p = 0.006) and calcium channel blocker usage (p = 0.005) were more common in patients with normal neurological examination. The PRES (n = 9) group was comprised of younger patients with recent history of hypertension and low burden of cSVD. Conclusions: Hypertensive surge is associated with ICH when cSVD burden is high, probably caused by microvascular dysfunction secondary to long-standing hypertension, while the episode causes no structural damage if this burden is less. Although our observations are exploratory, short term but severe hypertension manifests with PRES possibly due to the absence of adaptive changes.

Prediction for the Total MRI Burden of Cerebral Small Vessel Disease With Retinal Microvascular Abnormalities in Ischemic Stroke/TIA Patients

Background and Purpose: The association of retinal microvascular abnormalities with the total cerebral small vessel disease (cSVD) burden found on brain MRI has not been determined. In the present study, we examined whether the retinopathy score could predict the total cSVD burden in ischemic stroke/transient ischemic attack (TIA) patients. A simple practical diagnostic tool may help identify candidates for MRI screening.Methods: We consecutively collected clinical data including retinal photography and cerebral MRI of ischemic stroke/TIA patients from August 2016 to August 2017 at our stroke center. The retinopathy score was assessed by the Keith-Wagener-Barker grading system for analyzing retinal microvascular abnormalities. To evaluate the total cSVD burden, the total cSVD score was assessed by awarding one point for the presence of each marker of cSVD on MRI. The clinical characteristics and retinopathy score were analyzed across patients for each total cSVD score. The association between the retinopathy score and the total cSVD score was analyzed.Results: Among the 263 enrolled patients, the frequency of hypertension in patients with a total cSVD score of 2, 3, or 4 was higher than that in patients with a score of 0 (69.5, 71.7, and 89.2% vs. 45.2% respectively, all P < 0.05). The retinopathy score was related to the total cSVD score (r = 0.687, P < 0.001). Adjusted multivariate ordinal regression showed that the retinopathy score was independently correlated with the total cSVD score (odds ratio [OR], 4.18; 95% confidence interval [CI], 3.07–5.70) after adjustment for age, history of hypertension, previous stroke/TIA and current smoking. The c statistics were 0.30 (95% CI, 0.24–0.37; P < 0.05), 0.46 (95% CI, 0.39–0.53; P = 0.303), 0.79 (95% CI, 0.72–0.86; P < 0.001), and 0.81 (95% CI, 0.74–0.88; P < 0.001) for predicting the total cSVD score of 1, 2, 3, and 4 respectively.Conclusions: These results suggest that retinal microvascular abnormalities have predictive value for severe total cSVD burden in ischemic stroke/TIA patients.

Pooled cohort risk equation and subclinical cerebrovascular diseases.

In 2013, the American College of Cardiology/American Heart Association (ACC/AHA) introduced a novel pooled cohort risk (PCR) model for atherosclerotic cardiovascular disease. In this study, we evaluated the relationship between the PCR score and cerebral large- and small-vessel diseases (cLVD and cSVD) in a healthy population, METHODS: We assessed consecutive health check-up volunteers from 2006 to 2013. We calculated the estimated 10-year atherosclerotic cardiovascular disease risk as the PCR score based on the 2013 ACC/AHA guidelines. We evaluated both cSVD/cLVD, including the prevalence of cLVD, lacunes and cerebral microbleed (CMB), and the volume of white matter hyperintensity (WMH). In addition to PCR score, the risk factors that were associated with outcome variables at P<0.10 in univariate analysis were included for further multivariable linear or regression analyses. A total of 2720 participants were evaluated (mean age, 57years, male sex, 54%). In multivariable analysis, PCR score was associated with WMH volume [β=0.361; 95% confidence interval (CI), 0.320-0.402, P<0.001], cLVD [adjusted odds ratio (aOR), 1.66; 95% CI, 1.29-2.16, P<0.001], lacunes (aOR, 1.80; 95% CI, 1.52-2.14, P<0.001) and CMBs (aOR, 1.75; 95% CI, 1.40-2.19, P<0.001). Furthermore, PCR score also showed dose-response tendencies according to the burden of cLVD, WMH, lacunes and CMB. A higher PCR score based on the ACC/AHA guidelines is closely associated with a higher prevalence and burden of cLVD and cSVD.

Abstract WP267: Association Between Arterial Resistance and Subtypes of Cerebral Small Vessel Disease

Introduction: Increased arterial resistance is a potential pathophysiological mechanism in the pathogenesis of cerebral small vessel disease (cSVD). In this study, we aimed to investigate the association between puslatility index (PI) representing cerebral arterial resistance and subtypes of cSVD in patients with stroke due to small vessel occlusion (SVO). Hypothesis: Pattern of increased arterial resistance may be different between individual subtypes of cSVD. Methods: We included consecutive patients with SVO between 2010 and 2013. White matter hyperintensity (WMH) volume was rated using semi-automated quantitative methods. And the presence of old lacunar infarct (OLI), cerebral microbleed (CMB), or enlarged perivascular space (EPVS) was also evaluated. The relationship between PI, measured with transcranial Doppler sonography in each middle cerebral artery, and subtypes/burden of cSVD was analyzed in the relevant hemisphere. Results: A total of 206 patients with 412 hemispheres were included (mean age: 64 years, male: 68%). In multivariable analysis, PI was positively associated with the WMH volume [beta = 1.372, 95% confidence interval (CI) = 0.624 to 2.120, P &lt; 0.001] after adjusting confounders. PI was also related to the presence of OLI (adjusted odds ratio = 11.37, 95% CI = 2.55-48.56, P = 0.001), however this relationship was not significant in CMB or EPVS. Regarding to the cSVD burden, PI increased according to the WMH tertiles ( P for trend &lt; 0.001), and burden of OLI ( P for trend = 0.004) in a dose-response manner. Conclusion: Association of cerebral arterial resistance is different between subtypes of cSVD, which is suggestive of underlying pathophysiological difference. Simple measure of PI seems to be useful to estimate the arterial resistance and the burden of cSVD.

Decreased visible deep medullary veins is a novel imaging marker for cerebral small vessel disease.

Visibility of deep medullary veins (DMVs) seen at SWI is predictive of poor prognosis in ischemic stroke. Few attentions have been paid to DMVs in atherosclerotic cerebral small vessel disease (aCSVD) which is attributed to long-term imbalanced microhemodynamics. We conducted this retrospective study to explore the association between DMVs profiles and aCSVD risk factors, neuroimaging markers. Two hundred and two patients identified as aCSVD from January 2017 to March 2019 were included in the study. Their demographic, clinical, laboratory, and neuroimaging data were reviewed. The quantity and morphology of DMVs were assessed with a 5-grade (range 0~4) visual rating scale. Total CSVD burden was calculated with an ordinal "SVD score" (range 0~4). Spearman rank correlation and multivariable logistic regression analysis were performed to determine the association between DMV scale and CSVD markers. DMV scale showed strong positive correlation with CSVD burden (rs = 0.629, P< 0.001). Age (OR 1.078, 95% CI 1.015-1.145, P = 0.015) and hypertension (OR 2.629, 95% CI 1.024-6.749, P = 0.045) were two demographic risk factors for high DMV scale. Among CSVD neuroimaging markers, periventricular WMH (OR 2.925, 95% CI 1.464-5.845, P = 0.002), deep WMH (OR 2.872, 95% CI 1.174-7.022, P = 0.021), lacunae (OR 1.961, 95% CI 1.181-3.254, P = 0.009), and cerebral atrophy (OR 2.046, 95% CI 1.079-3.880, P = 0.028) were associated with high DMV scale after adjusting for clinical and metabolic confounders. Multifactorial association between DMV scale and epidemiological, radiological contributors of aCSVD suggests DMV's involved pathomechanism may participate in aCSVD development. Attach importance to DMV radiological profile in aCSVD will provide more neuroimaging information for diagnosis and prognosis.

Imaging markers associated with the development of post-stroke depression and apathy: Results of the Cognition and Affect after Stroke - a Prospective Evaluation of Risks study.

IntroductionIt has been suggested that the development of post-stroke apathy (PSA) and depression (PSD) may be more strongly associated with generalised brain pathology, rather than the stroke lesion itself. The present study aimed to investigate associations between imaging markers of lesion-related and generalised brain pathology and the development of PSA and PSD during a one-year follow-up.Patients and methodsIn a prospective cohort study, 188 stroke patients received 3-Tesla MRI at baseline (three months post-stroke) for evaluation of lesion-related, vascular, and degenerative brain pathology. Presence of lacunes, microbleeds, white matter hyperintensities, and enlarged perivascular spaces was summed to provide a measure of total cerebral small vessel disease (cSVD) burden (range 0–4). The Mini International Neuropsychiatric Interview and Apathy Evaluation Scale were administered at baseline and repeated at 6- and 12-month follow-up to define presence of PSD and PSA, respectively.ResultsPopulation-averaged logistic regression models showed that global brain atrophy and severe cSVD burden (score 3–4) were significantly associated with the odds of having PSA (ORGEE 5.33, 95% CI 1.99–14.25 and 3.04, 95% CI 1.20–7.69, respectively), independent of stroke lesion volume and co-morbid PSD. Medium cSVD burden (score 2) was significantly associated with the odds of having PSD (ORGEE 2.92, 95% CI 1.09–7.78), independent of stroke lesion volume, co-morbid PSA, and pre-stroke depression. No associations were found with lesion-related markers.ConclusionsThe results suggest that generalised degenerative and vascular brain pathology, rather than lesion-related pathology, is an important predictor for the development of PSA, and less strongly for PSD.

Small vessel disease in patients with subarachnoid hemorrhage: Prevalence and associations with vasospasm occurrence, severity and clinical outcomes

Investigating the associations between cerebral small vessel disease (cSVD) burden and cerebral vasospasm (CVS), delayed cerebral ischemia (DCI) and clinical outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). Consecutive aSAH patients with initial (<7 days after onset) and 3-month follow-up brain magnetic resonance imaging (MRI) and clinical evaluation at 6 months were included. The cSVD burden score was built using MRI criteria. CVS was defined according to transcranial Doppler examination and computed tomography (CT) or digital subtraction angiography. DCI was defined by the appearance of hyperintense fluid-attenuated inversion recovery lesions, with territorial or cortico-subcortical distribution, between initial MRI and 3-month MRI. The modified Rankin scale of ≤2 at 6 months was considered a favorable outcome. Using univariate and multivariable analyses, we investigated the associations between cSVD and CVS, DCI and clinical outcome. A total of 113 patients were included in the study sample (median age 49.1 years (IQR 42.1-60.8), 70/113 females). The burden of cSVD was mild with a median of 0 (IQR 0-1). When comparing patients with no/mild versus those with moderate/severe cSVD burden, we did not find a univariable difference regarding vasospasm occurrence (60% versus 46.1%, p = 0.54), DCI (20.2% versus 23%, p = 0.66) or favorable outcome at 3 months (94% versus 83.3%, p = 0.20). There was a univariable trend towards more frequent favorable outcome in patients with no/milde white matter hyperintensities versus those with moderate/severe white matter hyperintensities (92% versus 85%, p = 0.09). In multivariable models, cSVD markers were not associated with CVS occurrence and severity, DCI or clinical outcome. In patients with mild aSAH, the burden of cSVD as assessed by MRI is minimal and is not associated with CVS, DCI or clinical outcome.