Effect Of Small Vessel Disease Research Articles

Effect of Cerebral Small Vessel Disease Burden on Outcomes in Patients With Acute Ischemic Stroke Receiving Endovascular Treatment.

BackgroundCerebral small vessel disease (SVD) is common in the aging population. The study aimed to evaluate the effect of SVD on functional outcomes in patients with acute ischemic stroke (AIS) receiving endovascular treatment (EVT).MethodsFrom a prospective registry, we selected patients with AIS receiving EVT. SVD features, including white matter hyperintensities (WMH), lacunes and brain atrophy, were assessed on MRI and a validated SVD score was calculated to reflect the total SVD burden.ResultsAmong 137 patients included, 106 had none-mild SVD burden and 31 had moderate-severe SVD burden. The moderate-severe SVD burden group showed a significantly higher modified Rankin Scale score at 90 d (median, 4 versus 1 points, adjusted common odds ratio 0.32 [95% CI, 0.14–0.69], P < 0.01) and a significantly smaller improvement of NIHSS at 24 h (median, –3 versus –3 points, adjusted β coefficient 4.02 [95% CI, 0.57–7.48], P = 0.02) and 7 days (median, –4 versus –6 points, adjusted β coefficient 4.71 [95% CI, 1.06–8.36], P = 0.01) than the none-mild group. There was no significant difference in successful recanalization, death within 90 days, symptomatic intracranial hemorrhage within 24 h between two groups (all P > 0.05). Additionally, for each single SVD feature, brain atrophy and WMH, but not lacunes, were associated with the functional outcome.ConclusionModerate-severe SVD burden was associated with poor early and late functional outcomes in patients with AIS receiving EVT. Our results suggest that SVD score may act as a good predictor of outcomes in these patients.

Abstract P499: The Effect of Small Vessel Disease Burden on Core/Penumbra Mismatch and Outcomes in Extended Window Thrombectomy

Objective: Recent studies have shown the benefit of revascularization in select patients with extended window large vessel occlusion (EWLVO). We sought to assess the effect of cerebral small vessel disease (CSVD) burden on eligibility for intervention with mechanical thrombectomy (MT) and functional outcomes in patients with EWLVO. Methods: We conducted a retrospective single-center study of 135 patients with anterior circulation LVO who presented in the extended time window, 6 to 24 hours from LKW, between August 2018 and March 2020. All patients underwent perfusion imaging at initial presentation and those with target ischemic core to penumbra mismatch profiles, as defined by DAWN/DEFUSE3 criteria, were treated with MT. Included patients were evaluated for CSVD burden using T2-FLAIR MRI. The Fazekas scale (0-3) was used to quantify the amount of white matter T2 hyperintense lesions in both the periventricular (PVWM) and deep white matter (DWM). Patients’ functional outcomes were assessed at 90 days using the mRS. Multivariate ordinal logistic regression models were used and adjusted for age, gender, thrombus location and LKW to perfusion imaging time. Patient information was collected from the Houston Methodist Hospital Outcomes Based Prospective Endpoints in Stroke (HOPES) registry. Results: Of the 135 patients, 111 met imaging inclusion criteria for revascularization with MT for EWLVO. MT was deferred in 44 of these patients due to other clinical exclusions or patient refusal. Patients ineligible for MT were approximately 13 times more likely to have a higher PVWM Fazekas grade (OR =13.53, 95% CI. [2.94 - 62.39], p=0.001) and 17 times more likely to have a higher DWM Fazekas grade (OR =17.54, 95% CI. [4.20 - 73.17], p&lt;0.001), when compared to patients who were eligible for MT. Patients who did not meet criteria for MT were nearly 7 times more likely to have poor functional outcomes at 90 days (OR =6.85, 95% CI. [2.09 - 22.44], p=0.001). Conclusion: Based on our analytical cohort of EWLVO patients, those with severe CSVD burden were more likely to be excluded from MT and had worse functional outcomes. Poor cerebrovascular reserve and diminished collateral flow leading to rapid infarct progression in patients with greater CSVD burden may be a potential explanation.

Small vessel disease more than Alzheimer's disease determines diffusion MRI alterations in memory clinic patients.

Microstructural alterations as assessed by diffusion tensor imaging (DTI) are key findings in both Alzheimer's disease (AD) and small vessel disease (SVD). We determined the contribution of each of these conditions to diffusion alterations. We studied six samples (N = 365 participants) covering the spectrum of AD and SVD, including genetically defined samples. We calculated diffusion measures from DTI and free water imaging. Simple linear, multivariable random forest, and voxel-based regressions were used to evaluate associations between AD biomarkers (amyloid beta, tau), SVD imaging markers, and diffusion measures. SVD markers were strongly associated with diffusion measures and showed a higher contribution than AD biomarkers in multivariable analysis across all memory clinic samples. Voxel-wise analyses between tau and diffusion measures were not significant. In memory clinic patients, the effect of SVD on diffusion alterations largely exceeds the effect of AD, supporting the value of diffusion measures as markers of SVD.

The effect of small vessel disease on motor and cognitive function in Parkinson’s disease

ObjectivesSmall vessel disease (SVD) has been associated with motor and cognitive impairments in neurodegenerative diseases. We investigated SVD markers using brain magnetic resonance imaging (MRI) and the global SVD score in Parkinson's disease (PD). Patients and methodsSeventy-one patients with PD were assessed for vascular risk factors, motor severity, and motor phenotype. Global cognition was evaluated using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Based on the MoCA score, we categorized cases into normal (>23) or cognitively impaired (≤23). We calculated the total SVD score (range, 0–4) based on white matter hyper intensities (WMHs), lacunae, cerebral microbleeds (MBs), and enlarged perivascular spaces (PVSs). In addition, we evaluated global brain atrophy. ResultsThere were no significant associations with total SVD score and vascular risk factors, PD severity, and motor phenotype. Increasing age and reduced MMSE and MoCA scores were associated with increased SVD burden. Logistic regression analyses demonstrated that periventricular WMH (PVH), PVS in the basal ganglia (BG-PVS), and atrophy were predictors of cognitive impairment in PD. ConclusionThe contribution of SVD may be important in elderly patients with PD. Impaired cognition due to SVD-related brain changes was associated with BG-PVS and PVH. These measures suggest that PD with PVS can provide novel insights into SVD.

Effect of small-vessel disease on cognitive trajectory after atrial fibrillation-related ischaemic stroke or \xa0TIA

Post-stroke dementia is common but has heterogenous mechanisms that are not fully understood, particularly in patients with atrial fibrillation (AF)-related ischaemic stroke or TIA. We investigated the relationship between MRI small-vessel disease markers (including a composite cerebral amyloid angiopathy, CAA, score) and cognitive trajectory over 12 months. We included patients from the CROMIS-2 AF study without pre-existing cognitive impairment and with Montreal Cognitive Assessment (MoCA) data. Cognitive impairment was defined as MoCA < 26. We defined “reverters” as patients with an “acute” MoCA (immediately after the index event) score < 26, who then improved by ≥ 2 points at 12 months. In our cohort (n = 114), 12-month MoCA improved overall relative to acute performance (mean difference 1.69 points, 95% CI 1.03–2.36, p < 0.00001). 12-month cognitive impairment was associated with increasing CAA score (per-point increase, adjusted OR 4.09, 95% CI 1.36–12.33, p = 0.012). Of those with abnormal acute MoCA score (n = 66), 59.1% (n = 39) were “reverters”. Non-reversion was associated with centrum semi-ovale perivascular spaces (per-grade increase, unadjusted OR 1.83, 95% CI 1.06–3.15, p = 0.03), cerebral microbleeds (unadjusted OR 10.86, 95% CI 1.22–96.34, p = 0.03), and (negatively) with multiple ischaemic lesions at baseline (unadjusted OR 0.11, 95% CI 0.02–0.90, p = 0.04), as well as composite small-vessel disease (per-point increase, unadjusted OR 2.91, 95% CI 1.23–6.88, p = 0.015) and CAA (per-point increase, unadjusted OR 6.71, 95% CI 2.10–21.50, p = 0.001) scores. In AF-related acute ischaemic stroke or TIA, cerebral small-vessel disease is associated both with cognitive performance at 12 months and failure to improve over this period.

Leukoaraiosis and lacunes are associated with poor clinical outcomes in ischemic stroke patients treated with intravenous thrombolysis.

The effect of preexisting small vessel disease on outcomes of patients with ischemic stroke treated with i.v. thrombolysis is not fully understood. We aim to investigate the effect of combined leukoaraiosis and lacunes as detected on unenhanced brain computer tomography at baseline on clinical outcomes after i.v. thrombolysis. We analyzed data from the Canadian Alteplase for Stroke Effectiveness Study. Small vessel disease was assessed on baseline computer tomography rating for leukoaraiosis and lacunes. We dichotomized the burden of small vessel disease to "absent or moderate" and "severe." Clinical outcomes at 90 days included excellent outcome (mRS = 0-1), good outcome (mRS = 0-2), and the occurrence of symptomatic intracerebral hemorrhage. Sensitivity analysis was performed on two age groups (≤80 versus >80). We ran logistic regression adjusting for confounders to evaluate independent effect of small vessel disease on outcomes. There were 820 patients with available brain computer tomography with mean age (±SD) of 71.3 (±13.2), 455 (55.5%) were male. Of these, 123 (15%) patients had severe small vessel disease at baseline. Age group analysis revealed significant associations of small vessel disease only in patients aged ≤80. After adjustment for confounders, presence of severe small vessel disease reduced the chances of both excellent (OR = 0.42, 95% CI = 0.24-0.74) and good outcome (OR = 0.35, 95% CI = 0.21-0.58) and with an increased risk of symptomatic intracerebral hemorrhage (OR = 5.91; 95% CI = 2.40-14.57). When considered together as radiological expressions of small vessel disease, presence and severity of severe leukoaraiosis and lacunes on baseline computer tomography scan are associated with poor clinical outcomes in patients treated with i.v. thrombolysis.

Small vessel disease/white matter disease of the brain and its association with osteoporosis.

BackgroundEvidence now suggests the role of neural effect on bone mass control. The effect of small vessel disease of the brain on osteoporosis has not been studied. The aim of this study was to investigate the association of white matter disease (WMD) of the brain with osteoporosis in the elderly.MethodsIn this retrospective cross-sectional study, 780 consecutive patient charts between 2010 and 2011 were reviewed in the Senior’s Outpatient Clinic at the University of Alberta Hospital. Subjects with brain computerized tomography (CT) were included in the study. Subjects with incomplete information, intracranial hemorrhage, acute stroke, cerebral edema, and/or normal pressure hydrocephalus on the CT were excluded. WMD was quantified on CT using Wahlund’s scoring protocol. Osteoporosis information was obtained from the chart, which has been diagnosed based on bone mineral density (BMD) information. Logistic regression analysis was done to determine the association of WMD severity with osteoporosis after controlling for confounding vascular risk factors.ResultsOf the 505 subjects who were included in the study, 188 (37%) had osteoporosis and 171 (91%) of these osteoporotic subjects were females. The mean age was 79.8 ± 7.04 years. The prevalence of WMD in osteoporosis subjects was 73%. In the unadjusted logistic regression analysis, there was a significant association between WMD severity and osteoporosis (odds ratio (OR): 1.10; 95% confidence interval (CI): 1.05 - 1.14; P < 0.001) and the significance remained in the adjusted model, after correcting for age, sex and all vascular risk factors (OR: 1.11; 95% CI: 1.05 - 1.18; P < 0.001).ConclusionWMD severity of the brain was associated with osteoporosis in the elderly.

Hippocampal and Amygdala Size in Patients with Ischemic Stroke: Does Small Vessel Disease Play a Role?

Objective: The effect of Small Vessel Disease (SVD) on the size of the hippocampus and amygdala remains uncertain. We carried out an MRI volumetry study to investigate the association between the volume of White Matter Lesions (WMLs) and the size of the hippocampus and amygdala. Methods: One hundred patients with ischemic stroke were recruited in this study, with their MRIs analyzed using automatic volumetry. The volumes of the hippocampus, amygdala, Cortical Gray Matter (CGM), and WMLs were measured and standardized with intracranial volume. The subjects were divided into two groups stratified by smaller and larger hippocampus, amygdala, and CGM volumes (with the median as the cut-off), respectively. The demographic, clinical, and imaging variables of the two groups were compared in term of smaller and larger volumes in these three regions. Results: Multivariate logistic regression showed that WML volume (odds ratio [OR] = 1.869, p=0.004) and sex (male, OR=5.714, p=0.004) were significant predictors of a smaller hippocampus. Age (OR=1.062, p=0.033) was the only significant predictor of a smaller amygdala. Age and sex were predictive of a smaller CGM volume. Conclusions: The hippocampus may be vulnerable to SVD in patients with ischemic stroke, suggesting that hippocampal atrophy may result from a mixture of ischemic and degenerative pathologies. Whether SVD plays a role in atrophy of the amygdala remains uncertain.

The effects of small vessel disease and amyloid burden on neuropsychiatric symptoms: a study among patients with subcortical vascular cognitive impairments

Neuropsychiatric symptoms (NPS) affect the quality of life of patients with dementia and increase the burden on caregivers. We aimed to evaluate how small vessel disease (SVD) such as lacunae or white matter hyperintensities (WMH), and amyloid burden affect NPS. We recruited 127 patients with subcortical vascular cognitive impairment who were assessed with brain magnetic resonance imaging, Pittsburgh compound-B (PiB) positron emission tomography and the neuropsychiatric inventory (NPI). To explore the association between lacunae, WMH, or PiB retention ratio and NPS, we performed multivariate regression analysis after controlling for possible confounders. Each additional lacuna, especially in the frontal region, was associated with higher odds of depression, apathy, aberrant motor behavior, nighttime behavior, appetite changes, and higher score of total NPI; larger WMH volume, especially in the frontal region, was associated with higher odds of apathy and higher score of total NPI. Furthermore, for the effects of lacunae or WMH on total NPI score we set Clinical Dementia Rating Sum of Boxes as the mediator. Greater PiB retention ratio was associated with higher odds of delusions and irritability. The SVD and amyloid pathologies did not show interactive effects on NPS. Our findings suggested that SVD and amyloid burden independently affected specific NPS.

Loss of white matter integrity is associated with gait disorders in cerebral small vessel disease

Gait disturbances are common in the elderly. Cerebral small vessel disease, including white matter lesions and lacunars infarcts, is thought to disrupt white matter tracts that connect important motor regions, hence resulting in gait disturbances. Pathological studies have demonstrated abnormalities in white matter that may appear normal on brain imaging. The loss of integrity in such normal-appearing white matter may partly be due to small vessel disease and may play a role in causing gait disturbances. The white matter regions involved in these gait disturbances, both in white matter lesions and normal-appearing white matter, remain unclear. We, therefore, aimed to investigate the relation between the location of white matter lesions and gait using voxel-based morphometry analysis, as well as between white matter integrity and gait by applying tract-based spatial statistics to diffusion tensor imaging parameters. Magnetic resonance imaging was carried out on 429 individuals in the age range of 50 and 85 years, with cerebral small vessel disease without dementia or parkinsonism. Gait was assessed quantitatively. White matter lesions, especially in the centrum semiovale and periventricular frontal lobe, were related to a lower gait velocity, shorter stride length and broader stride width. Loss of white matter integrity, as indicated by a lower fractional anisotropy and higher mean diffusivity, in numerous regions was related to a lower gait performance. Most of these regions were located in the normal-appearing white matter. The strongest significant association was found in the corpus callosum, particularly the genu. Most of the associations in the normal-appearing white matter disappeared after controlling for white matter lesions and lacunar infarcts, except for some in the corpus callosum. In conclusion, our study showed that using a combination of voxel-based morphometry analysis of the white matter lesions and diffusion tensor imaging is of added value in investigating the pathophysiology of gait disturbances in subjects with small vessel disease. Our data demonstrate that, in elderly subjects with small vessel disease, widespread disruption of white matter integrity, predominantly in the normal-appearing white matter, is involved in gait disturbances. In particular, loss of fibres interconnecting bilateral cortical regions, especially the prefrontal cortex that is involved in cognitive control on motor performance, may be important. The most important mechanisms underlying affected normal-appearing white matter are probably a direct effect of small vessel disease or, indirectly, remote effects of white matter lesions and lacunar infarcts.