scholarly journals Rivaroxaban for Prevention of Covert Brain Infarcts and Cognitive Decline

Stroke ◽  
2020 ◽  
Vol 51 (10) ◽  
pp. 2901-2909
Author(s):  
Mukul Sharma ◽  
Robert G. Hart ◽  
Eric E. Smith ◽  
Jacqueline Bosch ◽  
John W. Eikelboom ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Magnetic Resonance ◽  
Cognitive Decline ◽  
Odds Ratio ◽  
White Matter Hyperintensities ◽  
Cerebral Microbleeds ◽  
Cognitive Tests ◽  
Brain Infarcts ◽  
End Point

Background and Purpose: Covert brain infarcts are associated with cognitive decline. It is not known whether therapies that prevent symptomatic stroke prevent covert infarcts. COMPASS compared rivaroxaban with and without aspirin with aspirin for the prevention of stroke, myocardial infarction, and vascular death in participants with stable vascular disease and was terminated early because of benefits of rivaroxaban 2.5 mg twice daily plus aspirin over aspirin. We obtained serial magnetic resonance imagings and cognitive tests in a consenting subgroup of COMPASS patients to examine treatment effects on infarcts, cerebral microbleeds, and white matter hyperintensities. Methods: Baseline and follow-up magnetic resonance imagings were completed in 1445 participants with a mean (SD) interval of 2.0 (0.7) years. Whole-brain T1, T2 fluid-attenuated inversion recovery, T2* sequences were centrally interpreted by blinded, trained readers. Participants had serial measurements of cognition and function. The primary end point was the proportion of participants with incident covert infarcts. Secondary end points were the composite of clinical stroke and covert brain infarcts, cerebral microbleeds, and white matter hyperintensities. Results: At baseline, 493 (34.1%) participants had infarcts. Incident covert infarcts occurred in 55 (3.8%) participants. In the overall trial rivaroxaban plus aspirin reduced ischemic stroke by 49% (0.7% versus 1.4%; hazard ratio [95% CI], 0.51 [0.38–0.68]). In the magnetic resonance imaging substudy the effects of rivaroxaban+aspirin versus aspirin were: covert infarcts: 2.7% versus 3.5% (odds ratio [95% CI], 0.77 [0.37–1.60]); Covert infarcts or ischemic stroke: 2.9% versus 5.3% (odds ratio [95% CI], 0.53 [0.27–1.03]). Incident microbleeds occurred in 6.6% of participants and 65.7% of participants had an increase in white matter hyperintensities volume with no effect of treatment for either end point. There was no effect on cognitive tests. Conclusions: Covert infarcts were not significantly reduced by treatment with rivaroxaban and aspirin but estimates for the combination of ischemic stroke and covert infarcts were consistent with the effect on ischemic stroke in the overall trial. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01776424.

Subclinical Vascular Brain Lesions in Young Adults With Acute Ischemic Stroke

Stroke ◽  
2021 ◽  
Author(s):  
Valeria De Giuli ◽  
Mario Grassi ◽  
Michele Besana ◽  
Marialuisa Zedde ◽  
Andrea Zini ◽  
...  
Keyword(s):  
Young Adults ◽  
Ischemic Stroke ◽  
Magnetic Resonance ◽  
Odds Ratio ◽  
White Matter Hyperintensities ◽  
Hazard Ratio ◽  
Brain Lesions ◽  
End Point ◽  
Stroke In Young Adults ◽  
Stroke In Young

Background and Purpose: Subclinical vascular brain lesions are highly prevalent in elderly patients with stroke. Little is known about predisposing factors and their impact on long-term outcome of patients with stroke at a young age. Methods: We quantified magnetic resonance-defined subclinical vascular brain lesions, including lacunes and white matter hyperintensities, perivascular spaces and cerebral microbleeds, and assessed total small-vessel disease (SVD) score in patients with first-ever acute ischemic stroke aged 18 to 45 years, and followed them up, as part of the multicentre Italian Project on Stroke in Young Adults. The primary end point was a composite of ischemic stroke, transient ischemic attack, myocardial infarction, or other arterial events. We assessed the predictive accuracy of magnetic resonance features and whether the addition of these markers improves outcome prediction over a validated clinical tool, such as the Italian Project on Stroke in Young Adults score. Results: Among 591 patients (males, 53.8%; mean age, 37.5±6.4 years), 117 (19.8%) had subclinical vascular brain lesions. Family history of stroke was associated with lacunes (odds ratio, 2.24 [95% CI, 1.30–3.84]) and total SVD score (odds ratio, 2.06 [95% CI, 1.20–3.53] for score≥1), hypertension with white matter hyperintensities (odds ratio, 2.29 [95% CI, 1.22–4.32]). After a median follow-up of 36.0 months (25th–75th percentile, 38.0), lacunes and total SVD score were associated with primary end point (hazard ratio, 2.13 [95% CI, 1.17–3.90] for lacunes; hazard ratio, 2.17 [95% CI, 1.20–3.90] for total SVD score ≥1), and the secondary end point brain ischemia (hazard ratio, 2.55 [95% CI, 1.36–4.75] for lacunes; hazard ratio, 2.61 [95% CI, 1.42–4.80] for total SVD score ≥1). The predictive performances of the models, including magnetic resonance features were comparable to those of the random model. Adding individual magnetic resonance features to the Italian Project on Stroke in Young Adults score did not improve model prediction. Conclusions: Subclinical vascular brain lesions affect ≈2 in 10 young adults with ischemic stroke. Although lacunes and total SVD score are associated with thrombotic recurrence, they do not improve accuracy of outcome prediction over validated clinical predictors.

scholarly journals Prevalence of Cerebral Microbleeds in Thai Patients with Ischemic Stroke

2017 ◽  
Vol 08 (02) ◽  
pp. 216-220 ◽  
Author(s):  
Artit Potigumjon ◽  
Arvemas Watcharakorn ◽  
Pornpatr A. Dharmasaroja
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Magnetic Resonance ◽  
White Matter Lesions ◽  
Cerebral Microbleeds ◽  
National Institutes Of Health ◽  
Asian Origin ◽  
Chinese Study ◽  
Japanese Studies ◽  
Magnetic Resonance Imaging Mri

ABSTRACT Background: With the widespread use of magnetic resonance imaging (MRI), cerebral microbleeds (CMBs) are commonly detected. Ethnicity seems to play a role in the prevalence of CMB, with higher prevalence in participants from Asian origin. The purpose of the study is to look for the prevalence of CMBs and associated factors in Thai patients with ischemic stroke. Methods: Patients with acute ischemic stroke who had MRI and magnetic resonance angiography during January–August 2014 were included in the study. T2*-weighted gradient-recalled echo was used to define CMBs. Baseline characteristics, stroke subtypes, and severity of white matter lesions were compared between patients with and without CMBs. Results: Two hundred patients were included in the study. Mean age of the patients was 61-year-old. Mean National Institutes of Health Stroke Scale was 8. The prevalence of CMBs was 20% (39/200 patients). Hypertension (odds ratio [OR] 3.05, 95% confidence interval [CI] 1.07–8.68, P = 0.037), and moderate-to-severe white matter lesions (Fazekas 2–3, OR 7.61, 95% CI 3.06–18.95, P < 0.001) were related to the presence of CMBs. Conclusions: CMBs were found in 20% of patients with ischemic stroke, which was lower than those reported from Japanese studies but comparable to a Chinese study. CMBs were associated with hypertension and severity of the white matter lesions.

Rationale, design, and baseline participant characteristics in the MRI and cognitive substudy of the cardiovascular outcomes for people using anticoagulation strategies trial

2018 ◽  
Vol 14 (3) ◽  
pp. 270-281 ◽  
Author(s):  
Mukul Sharma ◽  
Robert G Hart ◽  
Eric E Smith ◽  
Jackie Bosch ◽  
Fei Yuan ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
White Matter ◽  
Cognitive Decline ◽  
Acetylsalicylic Acid ◽  
Peripheral Artery Disease ◽  
White Matter Hyperintensities ◽  
Peripheral Artery ◽  
Brain Infarcts ◽  
Artery Disease

Background Covert vascular disease of the brain manifests as infarcts, white matter hyperintensities, and microbleeds on MRI. Their cumulative effect is often a decline in cognition, motor impairment, and psychiatric disorders. Preventive therapies for covert brain ischemia have not been established but represent a huge unmet clinical need. Aims The MRI substudy examines the effects of the antithrombotic regimens in COMPASS on incident covert brain infarcts (the primary outcome), white matter hyperintensities, and cognitive and functional status in a sample of consenting COMPASS participants without contraindications to MRI. Methods COMPASS is a randomized superiority trial testing rivaroxaban 2.5 mg bid plus acetylsalicylic acid 100 mg and rivaroxaban 5 mg bid against acetylsalicylic acid 100 mg per day for the combined endpoint of MI, stroke, and cardiovascular death in individuals with stable coronary artery disease or peripheral artery disease. T1-weighted, T2-weighted, T2*-weighted, and FLAIR images were obtained close to randomization and near the termination of assigned antithrombotic therapy; biomarker and genetic samples at randomization and one month, and cognitive and functional assessment at randomization, after two years and at the end of study. Results Between March 2013 and May 2016, 1905 participants were recruited from 86 centers in 16 countries. Of these participants, 1760 underwent baseline MRI scans that were deemed technically adequate for interpretation. The mean age at entry of participants with interpretable MRI was 71 years and 23.5% were women. Coronary artery disease was present in 90.4% and 28.1% had peripheral artery disease. Brain infarcts were present in 34.8%, 29.3% had cerebral microbleeds, and 93.0% had white matter hyperintensities. The median Montreal Cognitive Assessment score was 26 (interquartile range 23–28). Conclusions The COMPASS MRI substudy will examine the effect of the antithrombotic interventions on MRI-determined covert brain infarcts and cognition. Demonstration of a therapeutic effect of the antithrombotic regimens on brain infarcts would have implications for prevention of cognitive decline and provide insight into the pathogenesis of vascular cognitive decline.

scholarly journals Cerebral Microbleeds and White Matter Hyperintensities in Cognitively Healthy Elderly: A Cross-Sectional Cohort Study Evaluating the Effect of Arterial Stiffness

2015 ◽  
Vol 5 (2) ◽  
pp. 41-51 ◽  
Author(s):  
Anna-Märta Gustavsson ◽  
Erik Stomrud ◽  
Kasim Abul-Kasim ◽  
Lennart Minthon ◽  
Peter M. Nilsson ◽  
...  
Keyword(s):  
Cognitive Function ◽  
White Matter ◽  
Arterial Stiffness ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Cerebral Microbleeds ◽  
Small Vessel ◽  
Cognitive Tests ◽  
Vessel Disease ◽  
Healthy Elderly

Background: Arterial stiffness reflects the ageing processes in the vascular system, and studies have shown an association between reduced cognitive function and cerebral small vessel disease. Small vessel disease can be visualized as white matter hyperintensities (WMH) and lacunar infarcts but also as cerebral microbleeds on brain magnetic resonance imaging (MRI). We aimed to investigate if arterial stiffness influences the presence of microbleeds, WMH and cognitive function in a population of cognitively healthy elderly. Methods: The study population is part of the Swedish BioFinder study and consisted of 208 individuals without any symptoms of cognitive impairment, who scored >27 points on the Mini-Mental State Examination. The participants (mean age, 72 years; 59% women) underwent MRI of the brain with visual rating of microbleeds and WMH. Arterial stiffness was measured with carotid-femoral pulse wave velocity (cfPWV). Eight cognitive tests covering different cognitive domains were performed. Results: Microbleeds were detected in 12% and WMH in 31% of the participants. Mean (±standard deviation, SD) cfPWV was 10.0 (±2.0) m/s. There was no association between the presence of microbleeds and arterial stiffness. There was a positive association between arterial stiffness and WMH independent of age or sex (odds ratio, 1.58; 95% confidence interval, 1.04-2.40, p < 0.05), but the effect was attenuated when further adjustments for several cardiovascular risk factors were performed (p > 0.05). Cognitive performance was not associated with microbleeds, but individuals with WMH performed slightly worse than those without WMH on the Symbol Digit Modalities Test (mean ± SD, 35 ± 7.8 vs. 39 ± 8.1, p < 0.05). Linear regression revealed no direct associations between arterial stiffness and the results of the cognitive tests. Conclusions: Arterial stiffness was not associated with the presence of cerebral microbleeds or cognitive function in cognitively healthy elderly. However, arterial stiffness was related to the presence of WMH, but the association was attenuated when multiple adjustments were made. There was a weak negative association between WMH and performance in one specific test of attention. Longitudinal follow-up studies are needed to further assess the associations.

scholarly journals Association between homocysteine and white matter hyperintensities in asymptomatic intracranial arterial stenosis: results from a population-based study

2019 ◽  
Author(s):  
Hao Yin ◽  
Xiang Wang ◽  
Yuan-yuan Zhao ◽  
Xiao-kang Ji ◽  
Shao-wei Sang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
White Matter ◽  
Magnetic Resonance ◽  
White Matter Hyperintensities ◽  
Population Based ◽  
Arterial Stenosis ◽  
Chinese People ◽  
Intracranial Arterial Stenosis ◽  
Population Based Study

Abstract Background: Although homocysteine (Hcy) and white matter hyperintensities (WMH) have been proven to be correlated with increased risks of ischemic stroke, there have been few studies addressing the association between serum Hcy and WMH in a population with asymptomatic intracranial arterial stenosis (aICAS). Thus, the aim of the present study is to describe the association between Hcy and WMH in rural-dwelling Chinese people with aICAS. Methods: In this study, 150 participants diagnosed as aICAS by magnetic resonance angiography were recruited from the Kongcun Town Study, which was a population-based study aimed to investigate the prevalence of aICAS in general population aged 40 to 90 years old, free of ischemic stroke history, and living in the Kongcun town, Pingyin county, Shandong, China. Data on demographics, risk factors, and serum Hcy levels were collected via interview, clinical examination, and laboratory tests. The WMH volumes were calculated through the lesion segmentation tool system for the Statistical Parametric Mapping package based on magnetic resonance imaging. The association between Hcy and WMH volume was analyzed using both linear and logistic regression analysis. Results: After adjusting for all confounders, high Hcy (HHcy) (serum Hcy ≥15umol/L) was significantly associated with severe WMH (the highest quartile in WMH volume) (OR: 2.972, 95%CI: 1.017-7.979, P <0.05). However, with changing of WMH volumes, only trends towards association with HHcy were observed in all 3 models (P values only slightly exceeded 0.05). After being stratified by age, sex, or ever smoking, the association between HHcy and WMH became more significant in participants who were ≥60 years old, male, or ever smoker. Conclusions: HHcy is associated with severe WMH in rural-dwelling Chinese people with aICAS, especially in participants ≥60 years old, male participants, or ever smokers, indicating these may be risk factors that contribute to the association between HHcy and severe WMH.

Cerebral Microbleeds and White Matter Hyperintensities are Associated with Cognitive Decline in an Asian Memory Clinic Study

2021 ◽  
Vol 18 ◽  
Author(s):  
Bibek Gyanwali ◽  
Benedict Lui ◽  
Chuen Seng Tang ◽  
Eddie Jun Yi Chong ◽  
Henri Vrooman ◽  
...  
Keyword(s):  
Executive Function ◽  
White Matter ◽  
Cognitive Decline ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Cerebral Microbleeds ◽  
Future Research ◽  
Amyloid Angiopathy ◽  
Linear Regression Models ◽  
Interaction Factor

Background: Cerebral small vessel disease (SVD); lacunes, cerebral microbleeds (CMBs), and white matter hyperintensities (WMH) have a vital role in cognitive impairment and dementia. SVD in lobar location is related to cerebral amyloid angiopathy, whereas SVD in a deep location with hyper- tensive arteriopathy. It remains unclear how different locations of SVD affect long-term cognitive de- cline. The present study aimed to analyse the association between different locations and severity of SVD with global and domain-specific cognitive decline over the follow-up interval of 3 years. Methods: We studied 428 participants who had performed MRI scans at baseline and at least 3 neuro- psychological assessments. Locations of lacunes and CMBs were categorized into strictly lobar, strictly deep and mixed-location, WMH volume into anterior and posterior. The National Institute of Neurological Disorders and Stroke-Canadian Stroke Network Harmonization Neuropsychological Battery was used to assess cognitive function. To analyse the association between baseline location and severity of SVD with cognitive decline, linear regression models with generalized estimated equations were constructed to calculate the mean difference, 95% confidence interval and two-way interaction factor between time and SVD. Results: Increased numbers of baseline CMBs were associated with a decline in global cognition as well as a decline in executive function and memory domains. Location-specific analysis showed simi- lar results with strictly lobar CMBs. There was no association with strictly deep and mixed-location CMBs with cognitive decline. Baseline WMH volume was associated with a decline in global cogni- tion, executive function and memory. Similar results were obtained with anterior and posterior WMH volumes. Lacunes and their locations were not associated with cognitive decline. Conclusion: Strictly lobar CMBs, as well as WMH volume in anterior and posterior regions, were associated with cognitive decline. Future research focuses are warranted to evaluate interventions that may prevent cognitive decline related to SVD.

scholarly journals Magnetic Resonance Imaging White Matter Hyperintensities and Mechanism of Ischemic Stroke

Stroke ◽  
1999 ◽  
Vol 30 (10) ◽  
pp. 2053-2058 ◽  
Author(s):  
Riitta Mäntylä ◽  
Hannu J. Aronen ◽  
Oili Salonen ◽  
Tarja Pohjasvaara ◽  
Mauno Korpelainen ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Ischemic Stroke ◽  
White Matter ◽  
Magnetic Resonance ◽  
White Matter Hyperintensities ◽  
Resonance Imaging

scholarly journals Sustained Opening of the Blood-Brain Barrier with Progressive Accumulation of White Matter Hyperintensities Following Ischemic Stroke

2019 ◽  
Vol 9 (1) ◽  
pp. 16 ◽  
Author(s):  
Imama Naqvi ◽  
Emi Hitomi ◽  
Richard Leigh
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Acute Stroke ◽  
Blood Brain Barrier ◽  
White Matter Hyperintensities ◽  
Brain Barrier ◽  
Common Finding ◽  
Blood Brain ◽  
History Of ◽  
Iv Tpa

Objective: To report a patient in whom an acute ischemic stroke precipitated chronic blood-brain barrier (BBB) disruption and expansion of vascular white matter hyperintensities (WMH) into regions of normal appearing white matter (NAWM) during the following year. Background: WMH are a common finding in patients with vascular risk factors such as a history of stroke. The pathophysiology of WMH is not fully understood; however, there is growing evidence to suggest that the development of WMH may be preceded by the BBB disruption in the NAWM. Methods: We studied a patient enrolled in the National Institutes of Health Natural History of Stroke Study who was scanned with magnetic resonance imaging (MRI) after presenting to the emergency room with an acute stroke. After a treatment with IV tPA, she underwent further MRI scanning at 2 h, 24 h, 5 days, 30 days, 90 days, 6 months, and 1-year post stroke. BBB permeability images were generated from the perfusion weighted imaging (PWI) source images. MRIs from each time point were co-registered to track changes in BBB disruption and WMH over time. Results: An 84-year-old woman presented after acute onset right hemiparesis, right-sided numbness and aphasia with an initial NIHSS of 13. MRI showed diffusion restriction in the left frontal lobe and decreased blood flow on perfusion imaging. Fluid attenuated inversion recovery (FLAIR) imaging showed bilateral confluent WMH involving the deep white matter and periventricular regions. She was treated with IV tPA without complication and her NIHSS improved initially to 3 and ultimately to 0. Permeability maps identified multiple regions of chronic BBB disruption remote from the acute stroke, predominantly spanning the junction of WMH and NAWM. The severity of BBB disruption was greatest at 24 h after the stroke but persisted on subsequent MRI scans. Progression of WMH into NAWM over the year of observation was detected bilaterally but was most dramatic in the regions adjacent to the initial stroke. Conclusions: WMH-associated BBB disruption may be exacerbated by an acute stroke, even in the contralateral hemisphere, and can persist for months after the initial event. Transformation of NAWM to WMH may be evident in areas of BBB disruption within a year after the stroke. Further studies are needed to investigate the relationship between chronic BBB disruption and progressive WMH in patients with a history of cerebrovascular disease and the potential for acute stroke to trigger or exacerbate the process leading to the development of WMH.

scholarly journals ASPREE-NEURO study protocol: A randomized controlled trial to determine the effect of low-dose aspirin on cerebral microbleeds, white matter hyperintensities, cognition, and stroke in the healthy elderly

2016 ◽  
Vol 12 (1) ◽  
pp. 108-113 ◽  
Author(s):  
Stephanie A Ward ◽  
Parnesh Raniga ◽  
Nicholas J Ferris ◽  
Robyn L Woods ◽  
Elsdon Storey ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
White Matter ◽  
Primary Prevention ◽  
Magnetic Resonance ◽  
Controlled Trial ◽  
Brain Magnetic Resonance Imaging ◽  
Cerebral Microbleeds ◽  
Resonance Imaging ◽  
Healthy Elderly ◽  
Cerebral Microbleed

Rationale Cerebral microbleeds seen on brain magnetic resonance imaging are markers of small vessel disease, linked to cognitive dysfunction and increased ischemic and hemorrhagic stroke risk. Observational studies suggest that aspirin use may induce cerebral microbleeds, and associated overt intracranial hemorrhage, but this has not been definitively resolved. Aims ASPREE-NEURO will determine the effect of aspirin on cerebral microbleed development over three years in healthy adults aged 70 years and over, participating in the larger ‘ASPirin in Reducing Events in the Elderly (ASPREE)’ primary prevention study of aspirin. Sample size Five hundred and fifty-nine participants provide 75% power (two-sided p value of 0.05) to determine an average difference of 0.5 cerebral microbleed per person after three years. Methods and design A multi-center, randomized placebo-controlled trial of 100 mg daily aspirin in participants who have brain magnetic resonance imaging at study entry, one and three years after randomization and who undergo cognitive testing at the same time points. Study outcomes The primary outcome is the number of new cerebral microbleeds on magnetic resonance imaging after three years. Secondary outcomes are the number of new cerebral microbleeds after one year, change in volume of white matter hyperintensity, cognitive function, and stroke. Discussion ASPREE-NEURO will resolve whether aspirin affects the presence and number of cerebral microbleeds, their relationship with cognitive performance, and indicate whether consideration of cerebral microbleeds alters the risk-benefit profile of aspirin in primary prevention for older people. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12613001313729.

Predictors for cognitive decline in patients with confluent white matter hyperintensities

2012 ◽  
Vol 8 ◽  
pp. S96-S103 ◽  
Author(s):  
Vincent Mok ◽  
Yunyun Xiong ◽  
Kelvin K. Wong ◽  
Adrian Wong ◽  
Reinhold Schmidt ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Decline ◽  
White Matter Hyperintensities
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