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  • 1
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    Online Resource
    Sex-specific lesion pattern of functional outcomes after stroke
    Oxford University Press (OUP) ; 2022
    In:  Brain Communications Vol. 4, No. 2 ( 2022-03-01)
    Details
    In: Brain Communications, Oxford University Press (OUP), Vol. 4, No. 2 ( 2022-03-01)
    Abstract: Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent study, we reported sex divergences in lesion topographies: specific to women, acute stroke severity was linked to lesions in the left-hemispheric posterior circulation. We here determined whether these sex-specific brain manifestations also affect long-term outcomes. We relied on 822 acute ischaemic patients [age: 64.7 (15.0) years, 39% women] originating from the multi-centre MRI-GENIE study to model unfavourable outcomes (modified Rankin Scale & gt;2) based on acute neuroimaging data in a Bayesian hierarchical framework. Lesions encompassing bilateral subcortical nuclei and left-lateralized regions in proximity to the insula explained outcomes across men and women (area under the curve = 0.81). A pattern of left-hemispheric posterior circulation brain regions, combining left hippocampus, precuneus, fusiform and lingual gyrus, occipital pole and latero-occipital cortex, showed a substantially higher relevance in explaining functional outcomes in women compared to men [mean difference of Bayesian posterior distributions (men – women) = −0.295 (90% highest posterior density interval = −0.556 to −0.068)]. Once validated in prospective studies, our findings may motivate a sex-specific approach to clinical stroke management and hold the promise of enhancing outcomes on a population level.
    Type of Medium: Online Resource
    ISSN: 2632-1297
    URL: Article
    DOI: 10.1093/braincomms/fcac020
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 3020013-1
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  • 2
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    Abstract 3319: Prediction Of Lesion Expansion In Stroke Patients Using Acute MRI
    Ovid Technologies (Wolters Kluwer Health) ; 2012
    In:  Stroke Vol. 43, No. suppl_1 ( 2012-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 43, No. suppl_1 ( 2012-02)
    Abstract: Background: We investigated whether MRI-based algorithms combining acute DWI & PWI can be used to identify patients likely to experience lesion expansion. Methods: We analyzed MRI from 181 unilateral stroke patients who underwent DWI & PWI ≤ 12h from last seen well and had follow-up imaging (F/u) ≥4 days with lesions ≥ 1 cm 3 . Apparent diffusion coefficient, T2, DWI, CBF, CBV, MTT and Tmax (time of peak of deconvolved residue function) maps were co-registered, normalized and used as covariates in a model that produced infarction risk maps. Coefficients were calculated from 111 non-lysed patients and applied to 70 patients who received mechanical or drug lysis. Area under generated receiver operating characteristic curves (AUC) were calculated. Regional analyses were performed comparing mean risk values in Core (acute DWI), Growth (F/u - Core), Reverse (Core - F/u) and Normal (ipsilesional hemisphere - F/u) regions. Predicted lesion volumes (PLV) using a 50% risk threshold and post-hoc artifact removal for classifying infarcted tissue were correlated with the measured lesion volumes (MLV) on F/u. Values are median [IQR] or mean±SD. Results: The thrombolysis-treated group differed significantly from the non-lysis group in admission NIH Stroke Scale scores (12 [9-16] vs 6 [3-13] ; P 〈 0.001), time-to-MRI (4.8±1.9 h vs 5.9±2.8 h; P=0.005), acute DWI lesion volumes (21 [7-56] vs 11 [3-36] cm 3 ; P=0.02) and F/u lesion volumes (39 [12-72] vs 17 [6-56] cm 3 ; P=0.02). No significant difference was found between age (67±15 vs 65±17 years old), male sex (59% vs 67%) and time to F/u (15 [6-47] vs 10 [6-46] days). Significant differences in predicted risk between the 4 regions were found for both lysed (Core: 0.72±0.15; Growth: 0.41±0.13; Reverse: 0.64±0.16; Normal: 0.25±0.06; P 〈 0.0001) and non-lysed groups (Core: 0.72±0. 15; Growth:0.42±0.12; Reverse: 0.64±0.15; Normal: 0.22±0.05; P 〈 0.0001). AUCs of the prediction for the non-lysed group were higher than for the lysed group (0.86±0.09 vs 0.81±0.11; P 〈 0.001). Correlations between PLV and MLV were significant for both lysed (R=0.57, P 〈 0.001) and non-lysed groups (R=0.85, P 〈 0.001). Mismatch between PLV and Core volumes (i.e. predicted lesion growth) was significantly correlated with actual lesion growth for the non-lysed group (R=0.49, P 〈 0.001) but not for the lysed group (R=0.04, P=0.72). Conclusion: Mismatch in PLV and core can be used to identify patients most likely to experience lesion expansion if not given reperfusion therapy. The performance of the models was reduced in thrombolysed patients, which we propose is due to salvage of tissue that would have otherwise infarcted. MRI-based algorithms may identify patients who are not candidates for thrombolysis, yet have tissue to salvage. This may be useful as imaging selection criteria for future investigational trials of reperfusion therapy in extended time windows or for patients with unclear onsets.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.43.suppl_1.A3319
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
    detail.hit.zdb_id: 1467823-8
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  • 3
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    The relevance of rich club regions for functional outcome post‐stroke is enhanced in women
    Wiley ; 2023
    In:  Human Brain Mapping Vol. 44, No. 4 ( 2023-03), p. 1579-1592
    Details
    In: Human Brain Mapping, Wiley, Vol. 44, No. 4 ( 2023-03), p. 1579-1592
    Abstract: This study aimed to investigate the influence of stroke lesions in predefined highly interconnected (rich‐club) brain regions on functional outcome post‐stroke, determine their spatial specificity and explore the effects of biological sex on their relevance. We analyzed MRI data recorded at index stroke and ~3‐months modified Rankin Scale (mRS) data from patients with acute ischemic stroke enrolled in the multisite MRI‐GENIE study. Spatially normalized structural stroke lesions were parcellated into 108 atlas‐defined bilateral (sub)cortical brain regions. Unfavorable outcome (mRS  〉  2) was modeled in a Bayesian logistic regression framework. Effects of individual brain regions were captured as two compound effects for (i) six bilateral rich club and (ii) all further non‐rich club regions. In spatial specificity analyses, we randomized the split into “rich club” and “non‐rich club” regions and compared the effect of the actual rich club regions to the distribution of effects from 1000 combinations of six random regions. In sex‐specific analyses, we introduced an additional hierarchical level in our model structure to compare male and female‐specific rich club effects. A total of 822 patients (age: 64.7[15.0], 39% women) were analyzed. Rich club regions had substantial relevance in explaining unfavorable functional outcome (mean of posterior distribution: 0.08, area under the curve: 0.8). In particular, the rich club‐combination had a higher relevance than 98.4% of random constellations. Rich club regions were substantially more important in explaining long‐term outcome in women than in men. All in all, lesions in rich club regions were associated with increased odds of unfavorable outcome. These effects were spatially specific and more pronounced in women.
    Type of Medium: Online Resource
    ISSN: 1065-9471 , 1097-0193
    URL: Issue
    URL: Article
    DOI: 10.1002/hbm.v44.4
    DOI: 10.1002/hbm.26159
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 1492703-2
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  • 4
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    Does medial temporal lobe thickness mediate the association between risk factor burden and memory performance in middle-aged or older adults with metabolic syndrome?
    Elsevier BV ; 2017
    In:  Neuroscience Letters Vol. 636 ( 2017-01), p. 225-232
    Details
    In: Neuroscience Letters, Elsevier BV, Vol. 636 ( 2017-01), p. 225-232
    Type of Medium: Online Resource
    ISSN: 0304-3940
    URL: Article
    DOI: 10.1016/j.neulet.2016.10.010
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 1498535-4
    SSG: 12
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  • 5
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    White matter hyperintensity burden in acute stroke patients differs by ischemic stroke subtype
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Neurology Vol. 95, No. 1 ( 2020-07-07), p. e79-e88
    Details
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 95, No. 1 ( 2020-07-07), p. e79-e88
    Abstract: To examine etiologic stroke subtypes and vascular risk factor profiles and their association with white matter hyperintensity (WMH) burden in patients hospitalized for acute ischemic stroke (AIS). Methods For the MRI Genetics Interface Exploration (MRI-GENIE) study, we systematically assembled brain imaging and phenotypic data for 3,301 patients with AIS. All cases underwent standardized web tool–based stroke subtyping with the Causative Classification of Ischemic Stroke (CCS). WMH volume (WMHv) was measured on T2 brain MRI scans of 2,529 patients with a fully automated deep-learning trained algorithm. Univariable and multivariable linear mixed-effects modeling was carried out to investigate the relationship of vascular risk factors with WMHv and CCS subtypes. Results Patients with AIS with large artery atherosclerosis, major cardioembolic stroke, small artery occlusion (SAO), other, and undetermined causes of AIS differed significantly in their vascular risk factor profile (all p 〈 0.001). Median WMHv in all patients with AIS was 5.86 cm 3 (interquartile range 2.18–14.61 cm 3 ) and differed significantly across CCS subtypes ( p 〈 0.0001). In multivariable analysis, age, hypertension, prior stroke, smoking (all p 〈 0.001), and diabetes mellitus ( p = 0.041) were independent predictors of WMHv. When adjusted for confounders, patients with SAO had significantly higher WMHv compared to those with all other stroke subtypes ( p 〈 0.001). Conclusion In this international multicenter, hospital-based cohort of patients with AIS, we demonstrate that vascular risk factor profiles and extent of WMH burden differ by CCS subtype, with the highest lesion burden detected in patients with SAO. These findings further support the small vessel hypothesis of WMH lesions detected on brain MRI of patients with ischemic stroke.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    URL: Article
    DOI: 10.1212/WNL.0000000000009728
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 6
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    Endothelial progenitor cells are depleted in older adults with cognitive impairment and white matter volume loss : Molecular and cell biology/vascular factors
    Wiley ; 2020
    In:  Alzheimer's & Dementia Vol. 16, No. S3 ( 2020-12)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 16, No. S3 ( 2020-12)
    Abstract: Depletion of endothelial progenitor cells (EPCs) has been linked to vascular disease and both mild cognitive impairment (MCI) and Alzheimer’s disease (AD) dementia. EPCs have been shown to support oligodendrocyte precursor cell proliferation in the oligovascular niche, suggesting a potential role in protecting white matter (WM) integrity. We studied the relationship between in vitro EPC proliferation and both WM volume and cognitive function. Method Sixty‐three community dwelling older adults (M age = 70.94; SD age = 7.39), free of dementia or clinical stroke, underwent venipuncture, neuropsychological testing, and brain MRI. Blood leukocyte fractions were cultured over one week in colony forming unit (CFU)‐Hill media to produce EPCs. On the 5th day, colonies were counted. Cognitive function was measured by a comprehensive neuropsychological battery and the Clinical Dementia Rating (CDR) Scale. WM volumes were measured by Region‐of‐interest (ROI) analysis on T1‐MPRAGE scans using FreeSurfer 5.3. Univariate Analysis of Covariance (ANCOVA) compared CFU‐Hill counts and CDR scores, and multiple linear regression analyses determined the relationship between CFU‐Hill counts, neuropsychological tests and WM ROIs, after controlling for age, sex and education. Result CFU‐Hill counts were depleted in participants with CDR = 0.5 [ F (1, 51) = 5.84, p = 0.02]. Lower CFU‐Hill counts were associated with worse performances on tests of executive functioning [(1) Animals: F (4, 60) = 4.10, p = 0.005; ΔR 2 = 0.16; β= 0.41; ΔF = 12.51, p = 0.001; (2) Fruits and Vegetables: F (4, 60) = 4.00, p = 0.006; β=0.36; ΔR 2 = 0.12; ΔF = 7.54, p = 0.009; (3) Trails B: F (4, 44)=9.43; p 〈 0.001; β= 0.24; ΔR 2 = 0.057; ΔF = 4.69, p = 0.036]. Posterior corpus callosum volume positively predicted CFU‐Hill counts [ F (5, 42)=2.62; p =0.038; β= 0.41; ΔR 2 = 0.14; ΔF = 7.69, p = 0.008]. Conclusion Findings suggest EPCs may be linked to impaired cognition and WM volume loss in older adults, potentially implicating EPCs in protecting against vascular‐related WM injury and resulting executive dysfunction. Further studies of EPCs, WM integrity, and executive dysfunction are warranted to evaluate a potential protective role for EPCs in cerebrovascular disease with implications for dementia risk assessment and prevention.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v16.S3
    DOI: 10.1002/alz.046352
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2201940-6
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  • 7
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    Importance of Treatment Status in Links Between Type 2 Diabetes and Alzheimer’s Disease
    American Diabetes Association ; 2019
    In:  Diabetes Care Vol. 42, No. 5 ( 2019-05-01), p. 972-979
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 42, No. 5 ( 2019-05-01), p. 972-979
    Abstract: To investigate relationships among type 2 diabetes treatment, Alzheimer’s disease(AD) biomarkers, and risk for dementia. RESEARCH DESIGN AND METHODS Participants were from the Alzheimer's Disease Neuroimaging Initiative (N = 1,289) and were dementia-free at baseline and underwent health assessment, cognitive testing, and MRI. A subset (n = 900) obtained a lumbar puncture to determine cerebrospinal fluid (CSF) phosphorylated tau (p-tau), total tau (t-tau), and β-amyloid 1-42 (Aβ1-42). Participants were grouped by fasting blood glucose and medication history: euglycemia (EU), prediabetes (PD), untreated diabetes (UD), and treated diabetes (TD). Relationships were investigated between treatment status and CSF biomarkers and risk for dementia. RESULTS The UD group displayed greater p-tau, t-tau, and p-tau/Aβ1-42 levels than the EU, PD, and TD groups (P values & lt;0.05) and higher t-tau/Aβ1-42 than the EU and PD groups (P values & lt;0.05). The UD group progressed to dementia at higher rates than the EU group (hazard ratio 1.602 [95% CI 1.057–2.429]; P = 0.026). CONCLUSIONS Treatment status may alter the relationship between type 2 diabetes and both AD biomarker profile and risk for dementia. UD is associated with elevated tau pathology and risk for dementia, whereas TD is not. Although this study is observational and therefore causality cannot be inferred, findings support the potential importance of treatment status in AD risk associated with type 2 diabetes.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc18-1399
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
    detail.hit.zdb_id: 1490520-6
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  • 8
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    Data_Sheet_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Neuroscience Vol. 16 ( 2022-8-25)
    Details
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 16 ( 2022-8-25)
    Abstract: A substantial number of patients with acute ischemic stroke (AIS) experience multiple acute lesions (MAL). We here aimed to scrutinize MAL in a large radiologically deep-phenotyped cohort. Materials and methods Analyses relied upon imaging and clinical data from the international MRI-GENIE study. Imaging data comprised both Fluid-attenuated inversion recovery (FLAIR) for white matter hyperintensity (WMH) burden estimation and diffusion-weighted imaging (DWI) sequences for the assessment of acute stroke lesions. The initial step featured the systematic evaluation of occurrences of MAL within one and several vascular supply territories. Associations between MAL and important imaging and clinical characteristics were subsequently determined. The interaction effect between single and multiple lesion status and lesion volume was estimated by means of Bayesian hierarchical regression modeling for both stroke severity and functional outcome. Results We analyzed 2,466 patients (age = 63.4 ± 14.8, 39% women), 49.7% of which presented with a single lesion. Another 37.4% experienced MAL in a single vascular territory, while 12.9% featured lesions in multiple vascular territories. Within most territories, MAL occurred as frequently as single lesions (ratio ∼1:1). Only the brainstem region comprised fewer patients with MAL (ratio 1:4). Patients with MAL presented with a significantly higher lesion volume and acute NIHSS (7.7 vs. 1.7 ml and 4 vs. 3, p FDR & lt; 0.001). In contrast, patients with a single lesion were characterized by a significantly higher WMH burden (6.1 vs. 5.3 ml, p FDR = 0.048). Functional outcome did not differ significantly between patients with single versus multiple lesions. Bayesian analyses suggested that the association between lesion volume and stroke severity between single and multiple lesions was the same in case of anterior circulation stroke. In case of posterior circulation stroke, lesion volume was linked to a higher NIHSS only among those with MAL. Conclusion Multiple lesions, especially those within one vascular territory, occurred more frequently than previously reported. Overall, multiple lesions were distinctly linked to a higher acute stroke severity, a higher total DWI lesion volume and a lower WMH lesion volume. In posterior circulation stroke, lesion volume was linked to a higher stroke severity in multiple lesions only.
    Type of Medium: Online Resource
    ISSN: 1662-453X
    URL: Article
    URL: Article
    DOI: 10.3389/fnins.2022.994458
    DOI: 10.3389/fnins.2022.994458.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2411902-7
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  • 9
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    HIV, Vascular Risk Factors, and Cognition in the Combination Antiretroviral Therapy Era: A Systematic Review and Meta-Analysis
    Cambridge University Press (CUP) ; 2021
    In:  Journal of the International Neuropsychological Society Vol. 27, No. 4 ( 2021-04), p. 365-381
    Details
    In: Journal of the International Neuropsychological Society, Cambridge University Press (CUP), Vol. 27, No. 4 ( 2021-04), p. 365-381
    Abstract: Mounting evidence indicates that vascular risk factors (VRFs) are elevated in HIV and play a significant role in the development and persistence of HIV-associated neurocognitive disorder. Given the increased longevity of people living with HIV (PLWH), there is a great need to better elucidate vascular contributions to neurocognitive impairment in HIV. This systematic review and meta-analysis examine relationships between traditional VRFs, cardiovascular disease (CVD), and cognition in PLWH in the combination antiretroviral therapy era. Methods: For the systematic review, 44 studies met inclusion criteria and included data from 14,376 PLWH and 6,043 HIV-seronegative controls. To better quantify the contribution of VRFs to cognitive impairment in HIV, a robust variance estimation meta-analysis ( N = 11 studies) was performed and included data from 2139 PLWH. Results: In the systematic review, cross-sectional and longitudinal studies supported relationships between VRFs, cognitive dysfunction, and decline, particularly in the domains of attention/processing speed, executive functioning, and fine motor skills. The meta-analysis demonstrated VRFs were associated with increased odds of global neurocognitive impairment (odds ratio [OR ]= 2.059, p = .010), which remained significant after adjustment for clinical HIV variables ( p = .017). Analyses of individual VRFs demonstrated type 2 diabetes ( p = .004), hyperlipidemia ( p = .043), current smoking ( p = .037), and previous CVD ( p = .0005) were significantly associated with global neurocognitive impairment. Conclusions: VRFs and CVD are associated with worse cognitive performance and decline, and neurocognitive impairment in PLWH. Future studies are needed to examine these relationships in older adults with HIV, and investigate how race/ethnicity, gender, medical comorbidities, and psychosocial factors contribute to VRF-associated cognitive dysfunction in HIV.
    Type of Medium: Online Resource
    ISSN: 1355-6177 , 1469-7661
    URL: Article
    DOI: 10.1017/S1355617720001022
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2000018-2
    SSG: 5,2
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  • 10
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    Big Data Approaches to Phenotyping Acute Ischemic Stroke Using Automated Lesion Segmentation of Multi-Center Magnetic Resonance Imaging Data
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Stroke Vol. 50, No. 7 ( 2019-07), p. 1734-1741
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 50, No. 7 ( 2019-07), p. 1734-1741
    Abstract: We evaluated deep learning algorithms’ segmentation of acute ischemic lesions on heterogeneous multi-center clinical diffusion-weighted magnetic resonance imaging (MRI) data sets and explored the potential role of this tool for phenotyping acute ischemic stroke. Methods— Ischemic stroke data sets from the MRI-GENIE (MRI-Genetics Interface Exploration) repository consisting of 12 international genetic research centers were retrospectively analyzed using an automated deep learning segmentation algorithm consisting of an ensemble of 3-dimensional convolutional neural networks. Three ensembles were trained using data from the following: (1) 267 patients from an independent single-center cohort, (2) 267 patients from MRI-GENIE, and (3) mixture of (1) and (2). The algorithms’ performances were compared against manual outlines from a separate 383 patient subset from MRI-GENIE. Univariable and multivariable logistic regression with respect to demographics, stroke subtypes, and vascular risk factors were performed to identify phenotypes associated with large acute diffusion-weighted MRI volumes and greater stroke severity in 2770 MRI-GENIE patients. Stroke topography was investigated. Results— The ensemble consisting of a mixture of MRI-GENIE and single-center convolutional neural networks performed best. Subset analysis comparing automated and manual lesion volumes in 383 patients found excellent correlation (ρ=0.92; P 〈 0.0001). Median (interquartile range) diffusion-weighted MRI lesion volumes from 2770 patients were 3.7 cm 3 (0.9–16.6 cm 3 ). Patients with small artery occlusion stroke subtype had smaller lesion volumes ( P 〈 0.0001) and different topography compared with other stroke subtypes. Conclusions— Automated accurate clinical diffusion-weighted MRI lesion segmentation using deep learning algorithms trained with multi-center and diverse data is feasible. Both lesion volume and topography can provide insight into stroke subtypes with sufficient sample size from big heterogeneous multi-center clinical imaging phenotype data sets.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.119.025373
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 1467823-8
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