Mixed-location cerebral microbleeds as a biomarker of neurodegeneration in a memory clinic population

Cerebral microbleeds (CMBs) in the lobar and deep locations are associated with two distinct pathologies: cerebral amyloid angiopathy and hypertensive arteriopathy. However, the role of mixed-location CMBs in neurodegeneration remains unexplored. We investigated the associations between strictly lobar, strictly deep and mixed-location CMBs with markers of neurodegeneration. This study recruited 477 patients from a memory clinic who underwent 3T MRI scans. CMBs were categorized into strictly lobar, strictly deep and mixed-location. Cortical thickness, white matter volume and subcortical structural volumes were quantified using Free-Surfer. Linear regression models were performed to assess the association between CMBs and cerebral atrophy, and the mean difference (β) and 95% confidence intervals (CIs) were reported. In the regression analyses, mixed-location CMBs were associated with smaller cortical thickness of limbic region [β=-0.01; 95% CI=-0.02,-0.00, p=0.007) as well as with smaller accumbens volume [β=-0.01; 95% CI=-0.02,-0.00, p=0.004) and presubiculum region of hippocampus [β=-0.01; 95% CI=-0.02,-0.00, p=0.002). Strictly lobar CMBs were associated with smaller total white matter volume [β=-0.03; 95% CI=-0.04,-0.01, p<0.001] and with region specific white mat

Neuropsychiatric Correlates of Small Vessel Disease Progression in Incident Cognitive Decline: Independent and Interactive Effects

BACKGROUND: Cerebral small vessel disease (SVD) and neuropsychiatric symptoms (NPS) independently increase the risk of cognitive decline. While their co-existence has been reported in the preclinical stage of dementia, longitudinal data establishing the prognosis of their associations, especially in an Asian context remains limited. OBJECTIVE: This study investigated the role of SVD and NPS progressions on cognitive outcomes over 2 years in a dementia-free elderly cohort. METHODS: 170 dementia-free elderly with baseline and 2-year neuropsychological assessments and MRI scans were included in this study. White matter hyperintensities (WMH), lacunes, and microbleeds (CMBs) were graded as markers of SVD. The Ne

CT-based volumetric measures obtained through deep learning: Association with biomarkers of neurodegeneration

INTRODUCTION: Cranial computed tomography (CT) is an affordable and widely available imaging modality that is used to assess structural abnormalities, but not to quantify neurodegeneration. Previously we developed a deep-learning–based model that produced accurate and robust cranial CT tissue classification. // MATERIALS AND METHODS: We analyzed 917 CT and 744 magnetic resonance (MR) scans from the Gothenburg H70 Birth Cohort, and 204 CT and 241 MR scans from participants of the Memory Clinic Cohort, Singapore. We tested associations between six CT-based volumetric measures (CTVMs) and existing clinical diagnoses, fluid and imaging biomarkers, and measures of cognition. // RESULTS: CTVMs differentiated cognitively healthy individuals from dementia and prodromal dementia patients with high accuracy levels comparable to MR-based measures. CTVMs were significantly associated with measures of cognition and biochemical markers of neurodegeneration. // DISCUSSION: These findings suggest the potential future use of CT-based volumetric measures as an informative first-line examination tool for neurodegenerative disease diagnostics after further validation

Sex Differences in Poststroke Cognitive Impairment: A Multicenter Study in 2343 Patients With Acute Ischemic Stroke

BACKGROUND: Poststroke cognitive impairment (PSCI) occurs in about half of stroke survivors. Cumulative evidence indicates that functional outcomes of stroke are worse in women than men. Yet it is unknown whether the occurrence and characteristics of PSCI differ between men and women. METHODS: Individual patient data from 9 cohorts of patients with ischemic stroke were harmonized and pooled through the Meta-VCI-Map consortium (n=2343, 38% women). We included patients with visible symptomatic infarcts on computed tomography/magnetic resonance imaging and cognitive assessment within 15 months after stroke. PSCI was defined as impairment in ≥1 cognitive domains on neuropsychological assessment. Logistic regression analyses were performed to compare men to women, adjusted for study cohort, to obtain odds ratios for PSCI and individual cognitive domains. We also explored sensitivity and specificity of cognitive screening tools for detecting PSCI, according to sex (Mini-Mental State Examination, 4 cohorts, n=1814; Montreal Cognitive Assessment, 3 cohorts, n=278). RESULTS: PSCI was found in 51% of both women and men. Men had a lower risk of impairment of attention and executive functioning (men: odds ratio, 0.76 [95% CI, 0.61-0.96]), and language (men: odds ratio, 0.67 [95% CI, 0.45-0.85]), but a higher risk of verbal memory impairment (men: odds ratio, 1.43 [95% CI, 1.17-1.75]). The sensitivity of Mini-Mental State Examination (<25) for PSCI was higher for women (0.53) than for men (0.27; P=0.02), with a lower specificity for women (0.80) than men (0.96; P=0.01). Sensitivity and specificity of Montreal Cognitive Assessment (<26.) for PSCI was comparable between women and men (0.91 versus 0.86; P=0.62 and 0.29 versus 0.28; P=0.86, respectively). CONCLUSIONS: Sex was not associated with PSCI occurrence but affected domains differed between men and women. The latter may explain why sensitivity of the Mini-Mental State Examination for detecting PSCI was higher in women with a lower specificity compared with men. These sex differences need to be considered when screening for and diagnosing PSCI in clinical practice

Sex Differences in Poststroke Cognitive Impairment : A Multicenter Study in 2343 Patients With Acute Ischemic Stroke

Funding Information: Dr Exalto is supported by Alzheimer Nederland WE.03-2019-15 and Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation (CVON 2018-28 & 2012-06). The Meta-VCI Map consortium is supported by Vici Grant 918.16.616 from The Netherlands Organisation for Health Research and Development (ZonMw) to Dr Biessels. Harmonization analyses were supported by a Rudolf Magnus Young Talent Fellowship from the University Medical Center Utrecht Brain Center to Dr Biesbroek. The CASPER cohort was supported by Maastricht University, Health Foundation Limburg, and Stichting Adriana van Rinsum-Ponsen. The CROMIS-2 cohort was funded by the UK Stroke Association and the British Heart Foundation (grant number TSA BHF 2009/01). The CU-STRIDE cohort was supported by the Health and Health Services Research Fund of the Food and Health Bureau of the Government of Hong Kong (grant number 0708041), the Lui Che Woo Institute of Innovative Medicine, and Therese Pei Fong Chow Research Center for Prevention of Dementia. The GRECogVASC cohort was funded by Amiens University Hospital and by a grant from the French Ministry of Health (grant number DGOS R1/2013/144). The MSS-2 cohort is funded by the Wellcome Trust (grant number WT088134/Z/09/A to Dr Wardlaw) and the Row Fogo Charitable Trust. The PROCRAS cohort was funded via ZonMW as part of the TopZorg project in 2015 (grant number 842003011). The CODECS cohort (ongoing) is supported by a grant from Stichting Coolsingel (grant number 514). The Bundang VCI and Hallym VCI cohort groups do not wish to report any relevant funding sources. At the time of contribution, Dr Hamilton was funded by the College of Medicine and Veterinary Medicine at the University of Edinburgh and was supported by the Wellcome Trust through the Translational Neuroscience PhD program at the University of Edinburgh. Publisher Copyright: © 2023 Lippincott Williams and Wilkins. All rights reserved.Peer reviewedPublisher PD

Network impact score is an independent predictor of post-stroke cognitive impairment: A multicenter cohort study in 2341 patients with acute ischemic stroke

BACKGROUND: Post-stroke cognitive impairment (PSCI) is a common consequence of stroke. Accurate prediction of PSCI risk is challenging. The recently developed network impact score, which integrates information on infarct location and size with brain network topology, may improve PSCI risk prediction. AIMS: To determine if the network impact score is an independent predictor of PSCI, and of cognitive recovery or decline. METHODS: We pooled data from patients with acute ischemic stroke from 12 cohorts through the Meta VCI Map consortium. PSCI was defined as impairment in ≥ 1 cognitive domain on neuropsychological examination, or abnormal Montreal Cognitive Assessment. Cognitive recovery was defined as conversion from PSCI 24 months) and cognitive recovery or decline using logistic regression. Models were adjusted for age, sex, education, prior stroke, infarct volume, and study site. RESULTS: We included 2341 patients with 4657 cognitive assessments. PSCI was present in 398/844 patients (47%) 24 months. Cognitive recovery occurred in 64/181 (35%) patients and cognitive decline in 26/287 (9%). The network impact score predicted PSCI in the univariable (OR 1.50, 95%CI 1.34-1.68) and multivariable (OR 1.27, 95%CI 1.10-1.46) GEE model, with similar ORs in the logistic regression models for specified post-stroke intervals. The network impact score was not associated with cognitive recovery or decline. CONCLUSIONS: The network impact score is an independent predictor of PSCI. As such, the network impact score may contribute to a more precise and individualized cognitive prognostication in patients with ischemic stroke. Future studies should address if multimodal prediction models, combining the network impact score with demographics, clinical characteristics and other advanced brain imaging biomarkers, will provide accurate individualized prediction of PSCI. A tool for calculating the network impact score is freely available at https://metavcimap.org/features/software-tools/lsm-viewer/

Impact of Cerebral Microbleeds in Stroke Patients with Atrial Fibrillation

OBJECTIVES: Cerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with Vitamin K antagonists, direct oral anticoagulants, antiplatelets, and combination therapy (i.e. concurrent oral anticoagulant and antiplatelet) METHODS: We included patients with documented atrial fibrillation from the pooled individual patient data analysis by the Microbleeds International Collaborative Network. Risks of subsequent intracranial hemorrhage and ischemic stroke were compared between patients with and without microbleeds, stratified by antithrombotic use. RESULTS: A total of 7,839 patients were included. The presence of microbleeds was associated with an increased relative risk of intracranial hemorrhage (aHR 2.74, 95% confidence interval 1.76 - 4.26) and ischemic stroke (aHR 1.29, 95% confidence interval 1.04 - 1.59). For the entire cohort, the absolute incidence of ischemic stroke was higher than intracranial hemorrhage regardless of microbleeds burden. However, for the subgroup of patients taking combination of anticoagulant and antiplatelet therapy, the absolute risk of intracranial hemorrhage exceeded that of ischemic stroke in those with 2-4 microbleeds (25 vs 12 per 1,000 patient-years) and ≥11 microbleeds (94 vs 48 per 1,000 patient-years). INTERPRETATION: Patients with atrial fibrillation and high burden of microbleeds receiving combination therapy have a tendency of higher rate of intracranial hemorrhage than ischemic stroke, with potential for net harm. Further studies are needed to help optimize stroke preventive strategies in this high-risk group. This article is protected by copyright. All rights reserved

INFLUENCE OF CEREBRAL SMALL VESSEL DISEASE ON COGNITIVE DECLINE AND DEMENTIA IN AN ASIAN POPULATION

Ph.DDOCTOR OF PHILOSOPHY (SOM