2,404 results on '"Greenberg, Steven M."'
Search Results
2. Is CAA a perivascular brain clearance disease? A discussion of the evidence to date and outlook for future studies
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van Veluw, Susanne J., Benveniste, Helene, Bakker, Erik N. T. P., Carare, Roxana O., Greenberg, Steven M., Iliff, Jeffrey J., Lorthois, Sylvie, Van Nostrand, William E., Petzold, Gabor C., Shih, Andy Y., and van Osch, Matthias J. P.
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- 2024
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3. Left ventricular hypertrophy and left atrial size are associated with ischemic strokes among non-vitamin K antagonist oral anticoagulant users
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Das, Alvin S., Gökçal, Elif, Fouks, Avia Abramovitz, Horn, Mitchell J., Regenhardt, Robert W., Viswanathan, Anand, Singhal, Aneesh B., Schwamm, Lee H., Greenberg, Steven M., and Gurol, M. Edip
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- 2023
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4. Cross-Vendor Test-Retest Validation of Diffusion Tensor Image Analysis along the Perivascular Space (DTI-ALPS) for Evaluating Glymphatic System Function
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Liu, Xiaodan, Barisano, Giuseppe, Shao, Xingfeng, Jann, Kay, Ringman, John M, Lu, Hanzhang, Arfanakis, Konstantinos, Caprihan, Arvind, DeCarli, Charles, Gold, Brian T, Maillard, Pauline, Satizabal, Claudia L, Fadaee, Elyas, Habes, Mohamad, Stables, Lara, Singh, Herpreet, Fischl, Bruce, van der Kouwe, Andre, Schwab, Kristin, Helmer, Karl G, Greenberg, Steven M, Wang, Danny JJ, and Consortium, for the MarkVCID
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Biomedical and Clinical Sciences ,Clinical Sciences ,Humans ,Glymphatic System ,Diffusion Tensor Imaging ,Female ,Male ,Reproducibility of Results ,Adult ,Middle Aged ,Software ,Image Processing ,Computer-Assisted ,Diffusion tensor image analysis along the perivascular space ,Neurofluids ,Brain ,glymphatic system ,MarkVCID consortium ,MarkVCID Consortium ,Clinical sciences - Abstract
The diffusion tensor image analysis along the perivascular space (DTI-ALPS) method was proposed to evaluate glymphatic system (GS) function. However, few studies have validated its reliability and reproducibility. Fifty participants' DTI data from the MarkVCID consortium were included in this study. Two pipelines by using DSI studio and FSL software were developed for data processing and ALPS index calculation. The ALPS index was obtained by the average of bilateral ALPS index and was used for testing the cross-vendor, inter-rater and test-retest reliability by using R studio software. The ALPS index demonstrated favorable inter-scanner reproducibility (ICC=0.77 to 0.95, P< 0.001), inter-rater reliability (ICC=0.96 to 1, P< 0.001) and test-retest repeatability (ICC=0.89 to 0.95, P< 0.001), offering a potential biomarker for in vivo evaluation of GS function.
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- 2023
5. Multi-Site Cross-Site Inter-Rater and Test-Retest Reliability and Construct Validity of the MarkVCID White Matter Hyperintensity Growth and Regression Protocol.
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Bahrani, Ahmed A, Abner, Erin L, DeCarli, Charles S, Barber, Justin M, Sutton, Abigail C, Maillard, Pauline, Sandoval, Francisco, Arfanakis, Konstantinos, Yang, Yung-Chuan, Evia, Arnold M, Schneider, Julie A, Habes, Mohamad, Franklin, Crystal G, Seshadri, Sudha, Satizabal, Claudia L, Caprihan, Arvind, Thompson, Jeffrey F, Rosenberg, Gary A, Wang, Danny JJ, Jann, Kay, Zhao, Chenyang, Lu, Hanzhang, Rosenberg, Paul B, Albert, Marilyn S, Ali, Doaa G, Singh, Herpreet, Schwab, Kristin, Greenberg, Steven M, Helmer, Karl G, Powel, David K, Gold, Brian T, Goldstein, Larry B, Wilcock, Donna M, and Jicha, Gregory A
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Biomedical and Clinical Sciences ,Biological Psychology ,Clinical Sciences ,Neurosciences ,Psychology ,Aging ,Alzheimer's Disease ,Acquired Cognitive Impairment ,Brain Disorders ,Dementia ,Clinical Trials and Supportive Activities ,Neurodegenerative ,Clinical Research ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Neurological ,Humans ,White Matter ,Reproducibility of Results ,Magnetic Resonance Imaging ,Alzheimer Disease ,Cognitive Dysfunction ,Dementia ,Vascular ,Biomarkers ,Alzheimer's disease ,cerebrovascular disease ,dementia ,longitudinal ,Mark VCID ,small vessel ischemic disease ,white matter hyperintensity ,Alzheimer’s disease ,MarkVCID ,Cognitive Sciences ,Neurology & Neurosurgery ,Clinical sciences ,Biological psychology - Abstract
BackgroundWhite matter hyperintensities (WMH) that occur in the setting of vascular cognitive impairment and dementia (VCID) may be dynamic increasing or decreasing volumes or stable over time. Quantifying such changes may prove useful as a biomarker for clinical trials designed to address vascular cognitive-impairment and dementia and Alzheimer's Disease.ObjectiveConducting multi-site cross-site inter-rater and test-retest reliability of the MarkVCID white matter hyperintensity growth and regression protocol.MethodsThe NINDS-supported MarkVCID Consortium evaluated a neuroimaging biomarker developed to track WMH change. Test-retest and cross-site inter-rater reliability of the protocol were assessed. Cognitive test scores were analyzed in relation to WMH changes to explore its construct validity.ResultsICC values for test-retest reliability of WMH growth and regression were 0.969 and 0.937 respectively, while for cross-site inter-rater ICC values for WMH growth and regression were 0.995 and 0.990 respectively. Word list long-delay free-recall was negatively associated with WMH growth (p < 0.028) but was not associated with WMH regression.ConclusionsThe present data demonstrate robust ICC validity of a WMH growth/regression protocol over a one-year period as measured by cross-site inter-rater and test-retest reliability. These data suggest that this approach may serve an important role in clinical trials of disease-modifying agents for VCID that may preferentially affect WMH growth, stability, or regression.
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- 2023
6. Cerebral Amyloid Angiopathy
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Greenberg, Steven M. and van Veluw, Susanne J.
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- 2024
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7. Temporal Ordering of Biomarkers in Dutch-Type Hereditary Cerebral Amyloid Angiopathy
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Koemans, Emma A., Rasing, Ingeborg, Voigt, Sabine, van Harten, Thijs W., van der Zwet, Reinier G.J., Kaushik, Kanishk, Schipper, Manon R., van der Weerd, Nelleke, van Zwet, Erik W., van Etten, Ellis S., van Osch, Matthias J.P., Kuiperij, Bea, Verbeek, Marcel M., Terwindt, Gisela M., Greenberg, Steven M., van Walderveen, Marianne A.A., and Wermer, Marieke J.H.
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- 2024
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8. Cortical superficial siderosis is associated with reactive astrogliosis in cerebral amyloid angiopathy
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Auger, Corinne A., Perosa, Valentina, Greenberg, Steven M., van Veluw, Susanne J., and Kozberg, Mariel G.
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- 2023
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9. Decreased ratios of matrix metalloproteinases to tissue-type inhibitors in cerebrospinal fluid in sporadic and hereditary cerebral amyloid angiopathy
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Vervuurt, Marc, de Kort, Anna M., Jäkel, Lieke, Kersten, Iris, Abdo, Wilson F., Schreuder, Floris H. B. M., Rasing, Ingeborg, Terwindt, Gisela M., Wermer, Marieke J. H., Greenberg, Steven M., Klijn, Catharina J. M., Kuiperij, H. Bea, and Verbeek, Marcel M.
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- 2023
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10. MRI free water as a biomarker for cognitive performance: Validation in the MarkVCID consortium
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Maillard, Pauline, Hillmer, Laura J, Lu, Hanzhang, Arfanakis, Konstantinos, Gold, Brian T, Bauer, Christopher E, Kramer, Joel H, Staffaroni, Adam M, Stables, Lara, Wang, Danny JJ, Seshadri, Sudha, Satizabal, Claudia L, Beiser, Alexa, Habes, Mohamad, Fornage, Myriam, Mosley, Thomas H, Rosenberg, Gary A, Singh, Baljeet, Singh, Herpreet, Schwab, Kristin, Helmer, Karl G, Greenberg, Steven M, DeCarli, Charles, and Caprihan, Arvind
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Biomedical and Clinical Sciences ,Clinical Sciences ,Acquired Cognitive Impairment ,Clinical Research ,Brain Disorders ,Dementia ,biomarker ,diffusion tensor imaging ,free water ,small vessel disease ,vascular contributions to cognitive impairment and dementia ,VCID ,white matter injury ,Genetics ,Neurosciences ,Biological psychology - Abstract
IntroductionTo evaluate the clinical validity of free water (FW), a diffusion tensor imaging-based biomarker kit proposed by the MarkVCID consortium, by investigating the association between mean FW (mFW) and executive function.MethodsBaseline mFW was related to a baseline composite measure of executive function (EFC), adjusting for relevant covariates, in three MarkVCID sub-cohorts, and replicated in five, large, independent legacy cohorts. In addition, we tested whether baseline mFW predicted accelerated EFC score decline (mean follow-up time: 1.29 years).ResultsHigher mFW was found to be associated with lower EFC scores in MarkVCID legacy and sub-cohorts (p-values
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- 2022
11. Instrumental validation of free water, peak‐width of skeletonized mean diffusivity, and white matter hyperintensities: MarkVCID neuroimaging kits
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Maillard, Pauline, Lu, Hanzhang, Arfanakis, Konstantinos, Gold, Brian T, Bauer, Christopher E, Zachariou, Valentinos, Stables, Lara, Wang, Danny JJ, Jann, Kay, Seshadri, Sudha, Duering, Marco, Hillmer, Laura J, Rosenberg, Gary A, Snoussi, Haykel, Sepehrband, Farshid, Habes, Mohamad, Singh, Baljeet, Kramer, Joel H, Corriveau, Roderick A, Singh, Herpreet, Schwab, Kristin, Helmer, Karl G, Greenberg, Steven M, Caprihan, Arvind, DeCarli, Charles, Satizabal, Claudia L, and Consortium, for the MarkVCID
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Biomedical and Clinical Sciences ,Clinical Sciences ,Prevention ,Biomedical Imaging ,Clinical Trials and Supportive Activities ,Neurosciences ,Clinical Research ,4.1 Discovery and preclinical testing of markers and technologies ,Detection ,screening and diagnosis ,biomarker ,diffusion tensor imaging ,free water ,magnetic resonance imaging ,peak-width skeletonized mean diffusivity ,small vessel disease ,vascular contributions to cognitive impairment and dementia ,VCID ,white matter hyperintensity ,white matter injury ,MarkVCID Consortium ,peak‐width skeletonized mean diffusivity ,Genetics ,Biological psychology - Abstract
IntroductionTo describe the protocol and findings of the instrumental validation of three imaging-based biomarker kits selected by the MarkVCID consortium: free water (FW) and peak width of skeletonized mean diffusivity (PSMD), both derived from diffusion tensor imaging (DTI), and white matter hyperintensity (WMH) volume derived from fluid attenuation inversion recovery and T1-weighted imaging.MethodsThe instrumental validation of imaging-based biomarker kits included inter-rater reliability among participating sites, test-retest repeatability, and inter-scanner reproducibility across three types of magnetic resonance imaging (MRI) scanners using intra-class correlation coefficients (ICC).ResultsThe three biomarkers demonstrated excellent inter-rater reliability (ICC >0.94, P-values 0.98, P-values 0.98, P-values
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- 2022
12. Histopathology of Cerebral Microinfarcts and Microbleeds in Spontaneous Intracerebral Hemorrhage
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Jolink, Wilmar M. T., van Veluw, Susanne J., Zwanenburg, Jaco J. M., Rozemuller, Annemieke J. M., van Hecke, Wim, Frosch, Matthew P., Bacskai, Brian J., Rinkel, Gabriël J. E., Greenberg, Steven M., and Klijn, Catharina J. M.
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- 2023
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13. MarkVCID cerebral small vessel consortium: II. Neuroimaging protocols
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Lu, Hanzhang, Kashani, Amir H, Arfanakis, Konstantinos, Caprihan, Arvind, DeCarli, Charles, Gold, Brian T, Li, Yang, Maillard, Pauline, Satizabal, Claudia L, Stables, Lara, Wang, Danny JJ, Corriveau, Roderick A, Singh, Herpreet, Smith, Eric E, Fischl, Bruce, Kouwe, Andre, Schwab, Kristin, Helmer, Karl G, Greenberg, Steven M, and Consortium, for the MarkVCID
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Biomedical and Clinical Sciences ,Neurosciences ,Clinical Sciences ,Clinical Research ,Brain Disorders ,Aging ,Biomedical Imaging ,Detection ,screening and diagnosis ,4.2 Evaluation of markers and technologies ,Neurological ,Aged ,Angiography ,Biomarkers ,Brain ,Cerebral Small Vessel Diseases ,Cognitive Dysfunction ,Female ,Humans ,Magnetic Resonance Imaging ,Male ,Neuroimaging ,Tomography ,Optical Coherence ,acquisition protocol ,biomarker ,magnetic resonance imaging ,optical computed tomography angiography ,quality assurance ,small vessel disease ,vascular contributions to cognitive impairment and dementia ,MarkVCID Consortium ,Geriatrics ,Clinical sciences ,Biological psychology - Abstract
The MarkVCID consortium was formed under cooperative agreements with the National Institute of Neurologic Diseases and Stroke (NINDS) and National Institute on Aging (NIA) in 2016 with the goals of developing and validating biomarkers for the cerebral small vessel diseases associated with the vascular contributions to cognitive impairment and dementia (VCID). Rigorously validated biomarkers have consistently been identified as crucial for multicenter studies to identify effective strategies to prevent and treat VCID, specifically to detect increased VCID risk, diagnose the presence of small vessel disease and its subtypes, assess prognosis for disease progression or response to treatment, demonstrate target engagement or mechanism of action for candidate interventions, and monitor disease progression during treatment. The seven project sites and central coordinating center comprising MarkVCID, working with NINDS and NIA, identified a panel of 11 candidate fluid- and neuroimaging-based biomarker kits and established harmonized multicenter study protocols (see companion paper "MarkVCID cerebral small vessel consortium: I. Enrollment, clinical, fluid protocols" for full details). Here we describe the MarkVCID neuroimaging protocols with specific focus on validating their application to future multicenter trials. MarkVCID procedures for participant enrollment; clinical and cognitive evaluation; and collection, handling, and instrumental validation of fluid samples are described in detail in a companion paper. Magnetic resonance imaging (MRI) has long served as the neuroimaging modality of choice for cerebral small vessel disease and VCID because of its sensitivity to a wide range of brain properties, including small structural lesions, connectivity, and cerebrovascular physiology. Despite MRI's widespread use in the VCID field, there have been relatively scant data validating the repeatability and reproducibility of MRI-based biomarkers across raters, scanner types, and time intervals (collectively defined as instrumental validity). The MRI protocols described here address the core MRI sequences for assessing cerebral small vessel disease in future research studies, specific sequence parameters for use across various research scanner types, and rigorous procedures for determining instrumental validity. Another candidate neuroimaging modality considered by MarkVCID is optical coherence tomography angiography (OCTA), a non-invasive technique for directly visualizing retinal capillaries as a marker of the cerebral capillaries. OCTA has theoretical promise as a unique opportunity to visualize small vessels derived from the cerebral circulation, but at a considerably earlier stage of development than MRI. The additional OCTA protocols described here address procedures for determining OCTA instrumental validity, evaluating sources of variability such as pupil dilation, and handling data to maintain participant privacy. MRI protocol and instrumental validation The core sequences selected for the MarkVCID MRI protocol are three-dimensional T1-weighted multi-echo magnetization-prepared rapid-acquisition-of-gradient-echo (ME-MPRAGE), three-dimensional T2-weighted fast spin echo fluid-attenuated-inversion-recovery (FLAIR), two-dimensional diffusion-weighted spin-echo echo-planar imaging (DWI), three-dimensional T2*-weighted multi-echo gradient echo (3D-GRE), three-dimensional T2 -weighted fast spin-echo imaging (T2w), and two-dimensional T2*-weighted gradient echo echo-planar blood-oxygenation-level-dependent imaging with brief periods of CO2 inhalation (BOLD-CVR). Harmonized parameters for each of these core sequences were developed for four 3 Tesla MRI scanner models in widespread use at academic medical centers. MarkVCID project sites are trained and certified for their instantiation of the consortium MRI protocols. Sites are required to perform image quality checks every 2 months using the Alzheimer's Disease Neuroimaging Initiative phantom. Instrumental validation for MarkVCID MRI-based biomarkers is operationally defined as inter-rater reliability, test-retest repeatability, and inter-scanner reproducibility. Assessments of these instrumental properties are performed on individuals representing a range of cerebral small vessel disease from mild to severe. Inter-rater reliability is determined by distribution of an independent dataset of MRI scans to each analysis site. Test-retest repeatability is determined by repeat MRI scans performed on individual participants on a single MRI scanner after a short (1- to 14-day) interval. Inter-scanner reproducibility is determined by repeat MRI scans performed on individuals performed across four MRI scanner models. OCTA protocol and instrumental validation The MarkVCID OCTA protocol uses a commercially available, Food and Drug Administration-approved OCTA apparatus. Imaging is performed on one dilated and one undilated eye to assess the need for dilation. Scans are performed in quadruplicate. MarkVCID project sites participating in OCTA validation are trained and certified by this biomarker's lead investigator. Inter-rater reliability for OCTA is assessed by distribution of OCTA datasets to each analysis site. Test-retest repeatability is assessed by repeat OCTA imaging on individuals on the same day as their baseline OCTA and a different-day repeat session after a short (1- to 14-day) interval. Methods were developed to allow the OCTA data to be de-identified by the sites before transmission to the central data management system. The MarkVCID neuroimaging protocols, like the other MarkVCID procedures, are designed to allow translation to multicenter trials and as a template for outside groups to generate directly comparable neuroimaging data. The MarkVCID neuroimaging protocols are available to the biomedical community and intended to be shared. In addition to the instrumental validation procedures described here, each of the neuroimaging MarkVCID kits will undergo biological validation to determine its ability to measure important aspects of VCID such as cognitive function. The analytic methods for the neuroimaging-based kits and the results of these validation studies will be published separately. The results will ultimately determine the neuroimaging kits' potential usefulness for multicenter interventional trials in small vessel disease-related VCID.
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- 2021
14. A Roadmap for Developing Plasma Diagnostic and Prognostic Biomarkers of Cerebral Cavernous Angioma With Symptomatic Hemorrhage (CASH)
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Girard, Romuald, Li, Yan, Stadnik, Agnieszka, Shenkar, Robert, Hobson, Nicholas, Romanos, Sharbel, Srinath, Abhinav, Moore, Thomas, Lightle, Rhonda, Shkoukani, Abdallah, Akers, Amy, Carroll, Timothy, Christoforidis, Gregory A, Koenig, James I, Lee, Cornelia, Piedad, Kristina, Greenberg, Steven M, Kim, Helen, Flemming, Kelly D, Ji, Yuan, and Awad, Issam A
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Reproductive Medicine ,Biomedical and Clinical Sciences ,Rare Diseases ,Neurosciences ,Prevention ,Brain Disorders ,Detection ,screening and diagnosis ,4.1 Discovery and preclinical testing of markers and technologies ,4.2 Evaluation of markers and technologies ,Cardiovascular ,Good Health and Well Being ,Biomarkers ,Brain Neoplasms ,Capillary Permeability ,Cerebral Hemorrhage ,Female ,Hemangioma ,Cavernous ,Hemangioma ,Cavernous ,Central Nervous System ,Humans ,Inflammation Mediators ,Longitudinal Studies ,Machine Learning ,Magnetic Resonance Imaging ,Male ,Prognosis ,Transcriptome ,Cavernous angioma with symptomatic hemorrhage ,Cavernous angioma ,Cerebral cavernous malformation ,Symptomatic hemorrhage ,Machine learning ,Plasma ,QSM ,Clinical Sciences ,Neurology & Neurosurgery ,Clinical sciences ,Biological psychology - Abstract
BackgroundCerebral cavernous angioma (CA) is a capillary microangiopathy predisposing more than a million Americans to premature risk of brain hemorrhage. CA with recent symptomatic hemorrhage (SH), most likely to re-bleed with serious clinical sequelae, is the primary focus of therapeutic development. Signaling aberrations in CA include proliferative dysangiogenesis, blood-brain barrier hyperpermeability, inflammatory/immune processes, and anticoagulant vascular domain. Plasma levels of molecules reflecting these mechanisms and measures of vascular permeability and iron deposition on magnetic resonance imaging are biomarkers that have been correlated with CA hemorrhage.ObjectiveTo optimize these biomarkers to accurately diagnose cavernous angioma with symptomatic hemorrhage (CASH), prognosticate the risk of future SH, and monitor cases after a bleed and in response to therapy.MethodsAdditional candidate biomarkers, emerging from ongoing mechanistic and differential transcriptome studies, would further enhance the sensitivity and specificity of diagnosis and prediction of CASH. Integrative combinations of levels of plasma proteins and characteristic micro-ribonucleic acids may further strengthen biomarker associations. We will deploy advanced statistical and machine learning approaches for the integration of novel candidate biomarkers, rejecting noncorrelated candidates, and determining the best clustering and weighing of combined biomarker contributions.Expected outcomesWith the expertise of leading CA researchers, this project anticipates the development of future blood tests for the diagnosis and prediction of CASH to clinically advance towards precision medicine.DiscussionThe project tests a novel integrational approach of biomarker development in a mechanistically defined cerebrovascular disease with a relevant context of use, with an approach applicable to other neurological diseases with similar pathobiologic features.
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- 2021
15. Antiplatelet Agent Use After Stroke due to Intracerebral Hemorrhage
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Al-Shahi Salman, Rustam and Greenberg, Steven M.
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- 2023
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16. Clinical and neuroimaging risk factors associated with the development of intracerebral hemorrhage while taking direct oral anticoagulants
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Das, Alvin S., Gökçal, Elif, Regenhardt, Robert W., Warren, Andrew D., Biffi, Alessandro, Goldstein, Joshua N., Kimberly, W. Taylor, Viswanathan, Anand, Schwamm, Lee H., Rosand, Jonathan, Greenberg, Steven M., and Gurol, M. Edip
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- 2022
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17. Progression of cerebral amyloid angiopathy: a pathophysiological framework
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Koemans, Emma A, Chhatwal, Jasmeer P, van Veluw, Susanne J, van Etten, Ellis S, van Osch, Matthias J P, van Walderveen, Marianne A A, Sohrabi, Hamid R, Kozberg, Mariel G, Shirzadi, Zahra, Terwindt, Gisela M, van Buchem, Mark A, Smith, Eric E, Werring, David J, Martins, Ralph N, Wermer, Marieke J H, and Greenberg, Steven M
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- 2023
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18. Seven-Year Experience From the National Institute of Neurological Disorders and Stroke–Supported Network for Excellence in Neuroscience Clinical Trials
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Cudkowicz, Merit, Chase, Marianne K, Coffey, Christopher S, Ecklund, Dixie J, Thornell, Brenda J, Lungu, Codrin, Mahoney, Katy, Gutmann, Laurie, Shefner, Jeremy M, Staley, Kevin J, Bosch, Michael, Foster, Eric, Long, Jeffrey D, Bayman, Emine O, Torner, James, Yankey, Jon, Peters, Richard, Huff, Trevis, Conwit, Robin A, Shinnar, Shlomo, Patch, Donna, Darras, Basil T, Ellis, Audrey, Packer, Roger J, Marder, Karen S, Chiriboga, Claudia A, Henchcliffe, Claire, Moran, Joyce Ann, Nikolov, Blagovest, Factor, Stewart A, Seeley, Carole, Greenberg, Steven M, Amato, Anthony A, DeGregorio, Sara, Simuni, Tanya, Ward, Tina, Kissel, John T, Kolb, Stephen J, Bartlett, Amy, Quinn, Joseph F, Keith, Kellie, Levine, Steven R, Gilles, Nadege, Coyle, Patricia K, Lamb, Jessica, Wolfe, Gil I, Crumlish, Annemarie, Mejico, Luis, Iqbal, Muhammad Maaz, Bowen, James D, Tongco, Caryl, Nabors, Louis B, Bashir, Khurram, Benge, Melanie, McDonald, Craig M, Henricson, Erik K, Oskarsson, Björn, Dobkin, Bruce H, Canamar, Catherine, Glauser, Tracy A, Woo, Daniel, Molloy, Angela, Clark, Peggy, Vollmer, Timothy L, Stein, Alexander J, Barohn, Richard J, Dimachkie, Mazen M, Le Pichon, Jean-Baptiste, Benatar, Michael G, Steele, Julie, Wechsler, Lawrence, Clemens, Paula R, Amity, Christine, Holloway, Robert G, Annis, Christine, Goldberg, Mark P, Andersen, Mariam, Iannaccone, Susan T, Smith, A Gordon, Singleton, J Robinson, Doudova, Mariana, Haley, E Clarke, Quigg, Mark S, Lowenhaupt, Stephanie, Malow, Beth A, Adkins, Karen, Clifford, David B, Teshome, Mengesha A, and Connolly, Noreen
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Neurosciences ,Clinical Trials and Supportive Activities ,Stroke ,Clinical Research ,Brain Disorders ,Clinical Trials as Topic ,Humans ,National Institute of Neurological Disorders and Stroke (U.S.) ,Nervous System Diseases ,Neurology ,United States ,NeuroNEXT Clinical Study Sites ,Clinical Sciences ,Cognitive Sciences ,Neurology & Neurosurgery - Abstract
ImportanceOne major advantage of developing large, federally funded networks for clinical research in neurology is the ability to have a trial-ready network that can efficiently conduct scientifically rigorous projects to improve the health of people with neurologic disorders.ObservationsNational Institute of Neurological Disorders and Stroke Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) was established in 2011 and renewed in 2018 with the goal of being an efficient network to test between 5 and 7 promising new agents in phase II clinical trials. A clinical coordinating center, data coordinating center, and 25 sites were competitively chosen. Common infrastructure was developed to accelerate timelines for clinical trials, including central institutional review board (a first for the National Institute of Neurological Disorders and Stroke), master clinical trial agreements, the use of common data elements, and experienced research sites and coordination centers. During the first 7 years, the network exceeded the goal of conducting 5 to 7 studies, with 9 funded. High interest was evident by receipt of 148 initial applications for potential studies in various neurologic disorders. Across the first 8 studies (the ninth study was funded at end of initial funding period), the central institutional review board approved the initial protocol in a mean (SD) of 59 (21) days, and additional sites were added a mean (SD) of 22 (18) days after submission. The median time from central institutional review board approval to first site activation was 47.5 days (mean, 102.1; range, 1-282) and from first site activation to first participant consent was 27 days (mean, 37.5; range, 0-96). The median time for database readiness was 3.5 months (mean, 4.0; range, 0-8) from funding receipt. In the 4 completed studies, enrollment met or exceeded expectations with 96% overall data accuracy across all sites. Nine peer-reviewed manuscripts were published, and 22 oral presentations or posters and 9 invited presentations were given at regional, national, and international meetings.Conclusions and relevanceNeuroNEXT initiated 8 studies, successfully enrolled participants at or ahead of schedule, collected high-quality data, published primary results in high-impact journals, and provided mentorship, expert statistical, and trial management support to several new investigators. Partnerships were successfully created between government, academia, industry, foundations, and patient advocacy groups. Clinical trial consortia can efficiently and successfully address a range of important neurologic research and therapeutic questions.
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- 2020
19. Harmonizing brain magnetic resonance imaging methods for vascular contributions to neurodegeneration
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Smith, Eric E, Biessels, Geert Jan, De Guio, François, de Leeuw, Frank Erik, Duchesne, Simon, Düring, Marco, Frayne, Richard, Ikram, M Arfan, Jouvent, Eric, MacIntosh, Bradley J, Thrippleton, Michael J, Vernooij, Meike W, Adams, Hieab, Backes, Walter H, Ballerini, Lucia, Black, Sandra E, Chen, Christopher, Corriveau, Rod, DeCarli, Charles, Greenberg, Steven M, Gurol, M Edip, Ingrisch, Michael, Job, Dominic, Lam, Bonnie YK, Launer, Lenore J, Linn, Jennifer, McCreary, Cheryl R, Mok, Vincent CT, Pantoni, Leonardo, Pike, G Bruce, Ramirez, Joel, Reijmer, Yael D, Romero, Jose Rafael, Ropele, Stefan, Rost, Natalia S, Sachdev, Perminder S, Scott, Christopher JM, Seshadri, Sudha, Sharma, Mukul, Sourbron, Steven, Steketee, Rebecca ME, Swartz, Richard H, van Oostenbrugge, Robert, van Osch, Matthias, van Rooden, Sanneke, Viswanathan, Anand, Werring, David, Dichgans, Martin, and Wardlaw, Joanna M
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Biomedical and Clinical Sciences ,Clinical Sciences ,Neurodegenerative ,Biomedical Imaging ,Brain Disorders ,Neurosciences ,Neurological ,Cerebrovascular disease ,Stroke ,Dementia ,Magnetic resonance imaging ,Radiology ,Genetics ,Biological psychology - Abstract
IntroductionMany consequences of cerebrovascular disease are identifiable by magnetic resonance imaging (MRI), but variation in methods limits multicenter studies and pooling of data. The European Union Joint Program on Neurodegenerative Diseases (EU JPND) funded the HARmoNizing Brain Imaging MEthodS for VaScular Contributions to Neurodegeneration (HARNESS) initiative, with a focus on cerebral small vessel disease.MethodsSurveys, teleconferences, and an in-person workshop were used to identify gaps in knowledge and to develop tools for harmonizing imaging and analysis.ResultsA framework for neuroimaging biomarker development was developed based on validating repeatability and reproducibility, biological principles, and feasibility of implementation. The status of current MRI biomarkers was reviewed. A website was created at www.harness-neuroimaging.org with acquisition protocols, a software database, rating scales and case report forms, and a deidentified MRI repository.ConclusionsThe HARNESS initiative provides resources to reduce variability in measurement in MRI studies of cerebral small vessel disease.
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- 2019
20. Spontaneous vasomotion propagates along pial arterioles in the awake mouse brain like stimulus-evoked vascular reactivity
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Munting, Leon P, Bonnar, Orla, Kozberg, Mariel G, Auger, Corinne A, Hirschler, Lydiane, Hou, Steven S, Greenberg, Steven M, Bacskai, Brian J, and van Veluw, Susanne J
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- 2023
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21. Enlarged perivascular spaces in the basal ganglia are associated with arteries not veins
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Oltmer, Jan, primary, Mattern, Hendrik, additional, Beck, Julia, additional, Yakupov, Renat, additional, Greenberg, Steven M, additional, Zwanenburg, Jaco JM, additional, Arts, Tine, additional, Düzel, Emrah, additional, van Veluw, Susanne J, additional, Schreiber, Stefanie, additional, and Perosa, Valentina, additional
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- 2024
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22. Left atrial appendage closure in patients with atrial fibrillation and acute ischaemic stroke despite anticoagulation
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Abramovitz Fouks, Avia, primary, Yaghi, Shadi, additional, Selim, Magdy H, additional, Gökçal, Elif, additional, Das, Alvin S, additional, Rotschild, Ofer, additional, Silverman, Scott B, additional, Singhal, Aneesh B, additional, Kapur, Sunil, additional, Greenberg, Steven M, additional, and Gurol, Mahmut Edip, additional
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- 2024
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23. Cerebral Amyloid Angiopathy and Nontraumatic Subdural Hemorrhage
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Bax, Francesco, primary and Greenberg, Steven M., additional
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- 2024
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24. Deferoxamine mesylate in patients with intracerebral haemorrhage (i-DEF): a multicentre, randomised, placebo-controlled, double-blind phase 2 trial
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Selim, Magdy, Foster, Lydia D, Moy, Claudia S, Xi, Guohua, Hill, Michael D, Morgenstern, Lewis B, Greenberg, Steven M, James, Michael L, Singh, Vineeta, Clark, Wayne M, Norton, Casey, Palesch, Yuko Y, Yeatts, Sharon D, Investigators, i-DEF, Dolan, Monica, Yeh, Erlinda, Sheth, Kevin, Kunze, Kimberly, Muehlschlegel, Susanne, Nieto, Iryna, Claassen, Jan, Falo, Cristina, Huang, David, Beckwith, Anne, Messe, Steven, Yates, Melissa, O'Phelan, Kristine, Escobar, Andrea, Becker, Kyra, Tanzi, Patricia, Gonzales, Nicole, Tremont, Chad, Venkatasubramanian, Chitra, Thiessen, Rosita, Save, Supriya, Verrault, Steven, Collard, Karin, DeGeorgia, Michael, Cwiklinski, Valerie, Thompson, Bradford, Wasilewski, Lesley, Andrews, Charles, Burfeind, Robert, Torbey, Michel, Hamed, Mohammad, Butcher, Kenneth, Sivakumar, Leka, Varelas, Nicolaou, Mays-Wilson, Kathleen, Leira, Enrique, Olalde, Heena, Silliman, Scott, Calhoun, Rhonda, Dangayach, Neha, Renvill, Ricardo, Malhotra, Rishi, Kordesch, Kristina, Lord, Aaron, Calahan, Thomas, Geocadin, Romergryko, Parish, Michelle, Frey, James, Harrigan, Mary, Leifer, Dana, Mathias, Ryna, Schneck, Michael, Bernier, Tara, Gonzales-Arias, Sergio, Elysee, Josette, Lopez, George, Volgi, Josephine, Brown, Robert, Jasak, Sara, Phillips, Stephen, Jarrett, Judith, Gomes, Joao, McBride, Moneen, Aldrich, Francois, Aldrich, Charlene, Kornbluth, Joshua, Bettle, Michelle, Goldstein, Joshua, Tirrell, Gregory, Shaw, Qaisar, and Jonczak, Karin
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Neurosciences ,Clinical Research ,Clinical Trials and Supportive Activities ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Aged ,Cerebral Hemorrhage ,Deferoxamine ,Double-Blind Method ,Female ,Humans ,Infusions ,Intravenous ,Iron Chelating Agents ,Male ,Medical Futility ,Middle Aged ,Negative Results ,Prospective Studies ,Risk Assessment ,Treatment Outcome ,i-DEF Investigators ,Clinical Sciences ,Neurology & Neurosurgery - Abstract
BackgroundIron from haemolysed blood is implicated in secondary injury after intracerebral haemorrhage. We aimed to assess the safety of the iron chelator deferoxamine mesylate in patients with intracerebral haemorrhage and to establish whether the drug merits investigation in a phase 3 trial.MethodsWe did a multicentre, futility-design, randomised, placebo-controlled, double-blind, phase 2 trial at 40 hospitals in Canada and the USA. Adults aged 18-80 years with primary, spontaneous, supratentorial intracerebral haemorrhage were randomly assigned (1:1) to receive deferoxamine mesylate (32 mg/kg per day) or placebo (saline) infusions for 3 consecutive days within 24 h of haemorrhage onset. Randomisation was done via a web-based trial-management system centrally in real time, and treatment allocation was concealed from both participants and investigators. The primary outcome was good clinical outcome, which was defined as a modified Rankin Scale score of 0-2 at day 90. We did a futility analysis: if the 90% upper confidence bound of the absolute risk difference between the two groups in the proportion of participants with a good clinical outcome was less than 12% in favour of deferoxamine mesylate, then to move to a phase 3 efficacy trial would be futile. Primary outcome and safety data were analysed in the modified intention-to-treat population, comprising only participants in whom the study infusions were initiated. This trial is registered with ClinicalTrials.gov, number NCT02175225, and is completed.FindingsWe recruited 294 participants between Nov 23, 2014, and Nov 10, 2017. The modified intention-to-treat population consisted of 144 patients assigned to the deferoxamine mesylate group and 147 assigned to the placebo group. At day 90, among patients with available data for the primary outcome, 48 (34%) of 140 participants in the deferoxamine mesylate group, and 47 (33%) of 143 patients in the placebo group, had modified Rankin Scale scores of 0-2 (adjusted absolute risk difference 0·6% [90% upper confidence bound 6·8%]). By day 90, 70 serious adverse events were reported in 39 (27%) of 144 patients in the deferoxamine mesylate group, and 78 serious adverse events were reported in 49 (33%) of 147 patients in the placebo group. Ten (7%) participants in the deferoxamine mesylate and 11 (7%) in the placebo group died. None of the deaths were judged to be treatment related.InterpretationDeferoxamine mesylate was safe. However, the primary result showed that further study of the efficacy of deferoxamine mesylate with anticipation that the drug would significantly improve the chance of good clinical outcome (ie, mRS score of 0-2) at day 90 would be futile.FundingUS National Institutes of Health and US National Institute of Neurological Disorders and Stroke.
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- 2019
25. The Boston criteria version 2.0 for cerebral amyloid angiopathy: a multicentre, retrospective, MRI–neuropathology diagnostic accuracy study
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Charidimou, Andreas, Boulouis, Gregoire, Frosch, Matthew P, Baron, Jean-Claude, Pasi, Marco, Albucher, Jean Francois, Banerjee, Gargi, Barbato, Carmen, Bonneville, Fabrice, Brandner, Sebastian, Calviere, Lionel, Caparros, François, Casolla, Barbara, Cordonnier, Charlotte, Delisle, Marie-Bernadette, Deramecourt, Vincent, Dichgans, Martin, Gokcal, Elif, Herms, Jochen, Hernandez-Guillamon, Mar, Jäger, Hans Rolf, Jaunmuktane, Zane, Linn, Jennifer, Martinez-Ramirez, Sergi, Martínez-Sáez, Elena, Mawrin, Christian, Montaner, Joan, Moulin, Solene, Olivot, Jean-Marc, Piazza, Fabrizio, Puy, Laurent, Raposo, Nicolas, Rodrigues, Mark A, Roeber, Sigrun, Romero, Jose Rafael, Samarasekera, Neshika, Schneider, Julie A, Schreiber, Stefanie, Schreiber, Frank, Schwall, Corentin, Smith, Colin, Szalardy, Levente, Varlet, Pascale, Viguier, Alain, Wardlaw, Joanna M, Warren, Andrew, Wollenweber, Frank A, Zedde, Marialuisa, van Buchem, Mark A, Gurol, M Edip, Viswanathan, Anand, Al-Shahi Salman, Rustam, Smith, Eric E, Werring, David J, and Greenberg, Steven M
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- 2022
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26. Seed to Bleed: Iatrogenic Cerebral Amyloid Angiopathy
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Greenberg, Steven M. and Charidimou, Andreas
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- 2023
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27. Perivascular space dilation is associated with vascular amyloid-β accumulation in the overlying cortex
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Perosa, Valentina, Oltmer, Jan, Munting, Leon P., Freeze, Whitney M., Auger, Corinne A., Scherlek, Ashley A., van der Kouwe, Andre J., Iglesias, Juan Eugenio, Atzeni, Alessia, Bacskai, Brian J., Viswanathan, Anand, Frosch, Matthew P., Greenberg, Steven M., and van Veluw, Susanne J.
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- 2022
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28. Intensive Blood Pressure Lowering and DWI Lesions in Intracerebral Hemorrhage: Exploratory Analysis of the ATACH-2 Randomized Trial
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Shoamanesh, Ashkan, Cassarly, Christy, Morotti, Andrea, Romero, Javier M., Oliveira-Filho, Jamary, Schlunk, Frieder, Jessel, Michael, Butcher, Kenneth, Gioia, Laura, Ayres, Alison, Vashkevich, Anastasia, Schwab, Kristin, Afzal, Mohammad Rauf, Martin, Renee H., Qureshi, Adnan I., Greenberg, Steven M., Rosand, Jonathan, and Goldstein, Joshua N.
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- 2022
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29. External ventricular drain placement is associated with lower mortality after intracerebral hemorrhage with intraventricular hemorrhage
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Warren, Andrew D., Li, Qi, Schwab, Kristin, McKaig, Brenna, Goldstein, Alexa N., Greenberg, Steven M., Viswanathan, Anand, Anderson, Christopher, Gurol, M. Edip, Patel, Aman, and Goldstein, Joshua N.
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- 2022
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30. Sex differences in histopathological markers of cerebral amyloid angiopathy and related hemorrhage.
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Koemans, Emma A, Perosa, Valentina, Freeze, Whitney M, Lee, Hang, Kozberg, Mariel G, Coughlan, Gillian T, Buckley, Rachel F, Wermer, Marieke JH, Greenberg, Steven M, and van Veluw, Susanne J
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ALZHEIMER'S disease ,CEREBRAL amyloid angiopathy ,MAGNETIC resonance imaging ,CEREBRAL hemorrhage ,DATABASES - Abstract
Background: Men with cerebral amyloid angiopathy (CAA) may have an earlier onset of intracerebral hemorrhage and a more hemorrhagic disease course compared to women. In this cohort study, we investigated sex differences in histopathological markers associated with amyloid-β burden and hemorrhage in cognitively impaired individuals and patients with CAA, using neuropathological data from two autopsy databases. Methods: First, we investigated presence of parenchymal (Thal score) and vascular amyloid-β (CAA severity score) in cognitively impaired individuals from the National Alzheimer's Coordinating Center (NACC) neuropathology database. Next, we examined sex differences in hemorrhagic ex vivo magnetic resonance imaging (MRI) markers and local cortical iron burden and the interaction of sex on factors associated with cortical iron burden (CAA percentage area and vessel remodeling) in patients with pathologically confirmed clinical CAA from the Massachusetts General Hospital (MGH) CAA neuropathology database. Results: In 6120 individuals from the NACC database (45% women, mean age 80 years), the presence of parenchymal amyloid-β (odds ratio (OR) (95% confidence interval (CI)) =0.68 (0.53–0.88)) but not vascular amyloid-β was less in men compared to women. In 19 patients with definite CAA from the MGH CAA database (35% women, mean age 75 years), a lower microbleed count (p < 0.001) but a higher proportion of cortical superficial siderosis and a higher local cortical iron burden was found in men (p < 0.001) compared to women. CAA percentage area was comparable in men and women (p = 0.732). Exploratory analyses demonstrated a possible stronger negative relation between cortical CAA percentage area and cortical iron density in men compared to women (p = 0.03). Conclusion: Previously observed sex differences in hemorrhage onset and progression in CAA patients are likely not due to differences in global CAA severity between men and women. Other factors, such as vascular remodeling, may contribute, but future studies are necessary to replicate our findings in larger data sets and to further investigate the underlying mechanisms behind these complex sex differences. [ABSTRACT FROM AUTHOR]
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- 2024
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31. Cerebrovascular reactivity MRI as a biomarker for cerebral small vessel disease–related cognitive decline: Multi‐site validation in the MarkVCID Consortium.
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Liu, Peiying, Lin, Zixuan, Hazel, Kaisha, Pottanat, George, Xu, Cuimei, Jiang, Dengrong, Pillai, Jay J., Lucke, Emma, Bauer, Christopher E., Gold, Brian T., Greenberg, Steven M., Helmer, Karl G., Jann, Kay, Jicha, Gregory, Kramer, Joel, Maillard, Pauline, Mulavelil, Rachel M., Rodriguez, Pavel, Satizabal, Claudia L., and Schwab, Kristin
- Abstract
INTRODUCTION: Vascular contributions to cognitive impairment and dementia (VCID) represent a major factor in cognitive decline in older adults. The present study examined the relationship between cerebrovascular reactivity (CVR) measured by magnetic resonance imaging (MRI) and cognitive function in a multi‐site study, using a predefined hypothesis. METHODS: We conducted the study in a total of three analysis sites and 263 subjects. Each site performed an identical CVR MRI procedure using 5% carbon dioxide inhalation. A global cognitive measure of Montreal Cognitive Assessment (MoCA) and an executive function measure of item response theory (IRT) score were used as outcomes. RESULTS: CVR and MoCA were positively associated, and this relationship was reproduced at all analysis sites. CVR was found to be positively associated with executive function. DISCUSSION: The predefined hypothesis on the association between CVR and a global cognitive score was validated in three independent analysis sites, providing support for CVR as a biomarker in VCID. Highlights: This study measured a novel functional index of small arteries referred to as cerebrovascular reactivity (CVR).CVR was positively associated with global cognition in older adults.This finding was observed in three independent cohorts at three sites.Our statistical analysis plan was predefined before beginning data collection. [ABSTRACT FROM AUTHOR]
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- 2024
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32. Blood pressure from mid‐ to late life and risk of incident dementia
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McGrath, Emer R, Beiser, Alexa S, DeCarli, Charles, Plourde, Kendra L, Vasan, Ramachandran S, Greenberg, Steven M, and Seshadri, Sudha
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Prevention ,Brain Disorders ,Hypertension ,Cardiovascular ,Aging ,Dementia ,Acquired Cognitive Impairment ,Clinical Research ,Kidney Disease ,Neurological ,Adult ,Aged ,Blood Pressure ,Cohort Studies ,Female ,Humans ,Incidence ,Male ,Middle Aged ,Multivariate Analysis ,Prehypertension ,Proportional Hazards Models ,United States ,Clinical Sciences ,Neurosciences ,Cognitive Sciences ,Neurology & Neurosurgery - Abstract
ObjectiveTo determine the association between blood pressure during midlife (40-64 years) to late life (≥65 years) and risk of incident dementia.MethodsThis study included 1,440 (758 women, mean age 69 ± 6 years) Framingham Offspring participants who were free of dementia and attended 5 consecutive examinations at 4-year intervals starting at midlife (1983-1987, mean age 55 years) until late life (1998-2001, mean 69 years) and subsequently were followed up for incident dementia (mean 8 years). We determined the effect of midlife hypertension (≥140/90 mm Hg), late life hypertension, lower late life blood pressure (2-fold increase in dementia risk (HR 2.40, 95% CI 1.39-4.15).ConclusionsElevated blood pressure during midlife, persistence of elevated blood pressure into late life, and, among nonhypertensives, a steep decline in blood pressure during mid- to late life were associated with an increased dementia risk in a community-based cohort. Our data highlight the potential sustained cognitive benefits of lower blood pressures in midlife but also suggest that declining blood pressure in older adults with prehypertension or normotension, but not in those with hypertension, may be a risk marker for dementia.
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- 2017
33. Alzheimer's Disease–Related Dementias Summit 2016
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Corriveau, Roderick A, Koroshetz, Walter J, Gladman, Jordan T, Jeon, Sophia, Babcock, Debra, Bennett, David A, Carmichael, S Thomas, Dickinson, Susan L-J, Dickson, Dennis W, Emr, Marian, Fillit, Howard, Greenberg, Steven M, Hutton, Michael L, Knopman, David S, Manly, Jennifer J, Marder, Karen S, Moy, Claudia S, Phelps, Creighton H, Scott, Paul A, Seeley, William W, Sieber, Beth-Anne, Silverberg, Nina B, Sutherland, Margaret L, Taylor, Angela, Torborg, Christine L, Waddy, Salina P, Gubitz, Amelie K, and Holtzman, David M
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Acquired Cognitive Impairment ,Vascular Cognitive Impairment/Dementia ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Dementia ,Brain Disorders ,Neurosciences ,Alzheimer's Disease Related Dementias (ADRD) ,Aging ,Alzheimer's Disease ,Neurodegenerative ,2.1 Biological and endogenous factors ,Aetiology ,Neurological ,Alzheimer Disease ,Goals ,Humans ,Research ,United States ,Clinical Sciences ,Cognitive Sciences ,Neurology & Neurosurgery - Abstract
Goal 1 of the National Plan to Address Alzheimer's Disease is to prevent and effectively treat Alzheimer disease and Alzheimer disease-related dementias by 2025. To help inform the research agenda toward achieving this goal, the NIH hosts periodic summits that set and refine relevant research priorities for the subsequent 5 to 10 years. This proceedings article summarizes the 2016 Alzheimer's Disease-Related Dementias Summit, including discussion of scientific progress, challenges, and opportunities in major areas of dementia research, including mixed-etiology dementias, Lewy body dementia, frontotemporal degeneration, vascular contributions to cognitive impairment and dementia, dementia disparities, and dementia nomenclature.
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- 2017
34. Multi-vendor and multisite evaluation of cerebrovascular reactivity mapping using hypercapnia challenge
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Liu, Peiying, Jiang, Dengrong, Albert, Marilyn, Bauer, Christopher E., Caprihan, Arvind, Gold, Brian T., Greenberg, Steven M., Helmer, Karl G., Jann, Kay, Jicha, Gregory, Rodriguez, Pavel, Satizabal, Claudia L., Seshadri, Sudha, Singh, Herpreet, Thompson, Jeffrey F., Wang, Danny J.J., and Lu, Hanzhang
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- 2021
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35. Loss of spontaneous vasomotion precedes impaired cerebrovascular reactivity and microbleeds in a mouse model of cerebral amyloid angiopathy
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Kozberg, Mariel G, primary, Munting, Leon P, additional, Maresco, Lee H, additional, Auger, Corinne A., additional, van den Berg, Maarten L, additional, Denis de Senneville, Baudouin, additional, Hirschler, Lydiane, additional, Warnking, Jan M, additional, Barbier, Emmanuel L, additional, Farrar, Christian T, additional, Greenberg, Steven M., additional, Bacskai, Brian, additional, and van Veluw, Susanne J., additional
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- 2024
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36. Association of Long-Term Blood Pressure Variability with Cerebral Amyloid Angiopathy-related Brain Injury and Cognitive Decline
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Sveikata, Lukas, primary, Zanon Zotin, Maria Clara, additional, Schoemaker, Dorothee, additional, Ma, Yuan, additional, Perosa, Valentina, additional, Chokesuwattanaskul, Anthipa, additional, Charidimou, Andreas, additional, During, Marco, additional, Gurol, Edip M., additional, Assal, Frederic, additional, Greenberg, Steven M., additional, and Viswanathan, Anand, additional
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- 2024
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37. Editorial: Cerebral amyloid angiopathy: from bench to bedside
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Sohrabi, Hamid R., primary, Greenberg, Steven M., additional, and Whiley, Luke, additional
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- 2024
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38. Abstract 150: Regional Molecular Alterations in Cerebral Amyloid Angiopathy-Related Hemorrhagic Lesions
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Gokcal, Elif, primary, Becker, Alex J, additional, Horn, Mitchell J, additional, Das, Alvin S, additional, Rosand, Jonathan, additional, Viswanathan, Anand, additional, Polimeni, Jonathan R, additional, Johnson, Keith A, additional, Greenberg, Steven M, additional, and Gurol, Edip M, additional
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- 2024
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39. Phantom-based standardization of CT angiography images for spot sign detection
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Morotti, Andrea, Romero, Javier M, Jessel, Michael J, Hernandez, Andrew M, Vashkevich, Anastasia, Schwab, Kristin, Burns, Joseph D, Shah, Qaisar A, Bergman, Thomas A, Suri, M Fareed K, Ezzeddine, Mustapha, Kirmani, Jawad F, Agarwal, Sachin, Shapshak, Angela Hays, Messe, Steven R, Venkatasubramanian, Chitra, Palmieri, Katherine, Lewandowski, Christopher, Chang, Tiffany R, Chang, Ira, Rose, David Z, Smith, Wade, Hsu, Chung Y, Liu, Chun-Lin, Lien, Li-Ming, Hsiao, Chen-Yu, Iwama, Toru, Afzal, Mohammad Rauf, Cassarly, Christy, Greenberg, Steven M, Martin, Renee’ Hebert, Qureshi, Adnan I, Rosand, Jonathan, Boone, John M, Goldstein, Joshua N, and On Behalf of ATACH-II and NETT Investigators
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Biomedical and Clinical Sciences ,Clinical Sciences ,Stroke ,Biomedical Imaging ,Bioengineering ,Clinical Trials and Supportive Activities ,Clinical Research ,Calibration ,Cerebral Hemorrhage ,Computed Tomography Angiography ,Hematoma ,Humans ,Iodine ,Phantoms ,Imaging ,Sensitivity and Specificity ,Software ,Intracerebral hemorrhage ,Spot sign ,CT angiography ,Phantom standardization ,ATACH-II and NETT Investigators ,Neurosciences ,Nuclear Medicine & Medical Imaging ,Clinical sciences - Abstract
PurposeThe CT angiography (CTA) spot sign is a strong predictor of hematoma expansion in intracerebral hemorrhage (ICH). However, CTA parameters vary widely across centers and may negatively impact spot sign accuracy in predicting ICH expansion. We developed a CT iodine calibration phantom that was scanned at different institutions in a large multicenter ICH clinical trial to determine the effect of image standardization on spot sign detection and performance.MethodsA custom phantom containing known concentrations of iodine was designed and scanned using the stroke CT protocol at each institution. Custom software was developed to read the CT volume datasets and calculate the Hounsfield unit as a function of iodine concentration for each phantom scan. CTA images obtained within 8 h from symptom onset were analyzed by two trained readers comparing the calibrated vs. uncalibrated density cutoffs for spot sign identification. ICH expansion was defined as hematoma volume growth >33%.ResultsA total of 90 subjects qualified for the study, of whom 17/83 (20.5%) experienced ICH expansion. The number of spot sign positive scans was higher in the calibrated analysis (67.8 vs 38.9% p
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- 2017
40. Cerebral Small Vessel Diseases and Sleep Related Strokes
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Lauer, Arne, Ay, Hakan, Bianchi, Matt, Charidimou, Andreas, Boulouis, Gregoire, Ayres, Alison, Vashkevich, Anastasia, Schwab, Kristin M., Singhal, Aneesh B., Viswanathan, Anand, Rost, Natalia S., Goldstein, Joshua N., Rosand, Jonathan, Schwamm, Lee H., Greenberg, Steven M., and Gurol, Mahmut Edip
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- 2020
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41. Longitudinal Progression of Magnetic Resonance Imaging Markers and Cognition in Dutch-Type Hereditary Cerebral Amyloid Angiopathy
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van Dijk, Suzanne E., van der Grond, Jeroen, Lak, Jessie, van den Berg-Huysmans, Annette, Labadie, Gerda, Terwindt, Gisela M., Wermer, Marieke J.H., Gurol, M. Edip, van Buchem, Mark A., Greenberg, Steven M., and van Rooden, Sanneke
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- 2022
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42. Fluid biomarkers in cerebral amyloid angiopathy
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Savar, Seyed Mehrdad, primary, Ma, Bin, additional, Hone, Eugene, additional, Jahan, Farzana, additional, Markovic, Shaun, additional, Pedrini, Steve, additional, Shemehsavar, Soudabeh, additional, Easwaran, Vandhana, additional, Taddei, Kevin, additional, Gardener, Samantha, additional, Chhatwal, Jasmeer P., additional, van Etten, Ellis S., additional, van Osch, Matthias J. P., additional, Clarke, Daniel, additional, Gnjec, Anastazija, additional, van Buchem, Mark A., additional, Wermer, Marieke J. H., additional, Hankey, Graeme J., additional, Greenberg, Steven M., additional, Martins, Ralph N., additional, and Sohrabi, Hamid R., additional
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- 2024
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43. Sensitivity and Specificity of the Boston Criteria Version 2.0 for the Diagnosis of Cerebral Amyloid Angiopathy in a Community-Based Sample
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Zanon Zotin, Maria Clara, primary, Makkinejad, Nazanin, additional, Schneider, Julie A., additional, Arfanakis, Konstantinos, additional, Charidimou, Andreas, additional, Greenberg, Steven M., additional, and van Veluw, Susanne J., additional
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- 2024
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44. Predicting Intracerebral Hemorrhage Growth With the Spot Sign
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Dowlatshahi, Dar, Brouwers, H Bart, Demchuk, Andrew M, Hill, Michael D, Aviv, Richard I, Ufholz, Lee-Anne, Reaume, Michael, Wintermark, Max, Hemphill, J Claude, Murai, Yasuo, Wang, Yongjun, Zhao, Xingquan, Wang, Yilong, Li, Na, Sorimachi, Takatoshi, Matsumae, Mitsunori, Steiner, Thorsten, Rizos, Timolaos, Greenberg, Steven M, Romero, Javier M, Rosand, Jonathan, Goldstein, Joshua N, and Sharma, Mukul
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Biomedical Imaging ,Stroke ,Detection ,screening and diagnosis ,4.2 Evaluation of markers and technologies ,Cerebral Angiography ,Cerebral Hemorrhage ,Disease Progression ,Hematoma ,Humans ,Predictive Value of Tests ,Time Factors ,Tomography ,X-Ray Computed ,cerebral hemorrhage ,hematoma expansion ,CT angiography ,spot sign ,intracerebral hemorrhage ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences ,Neurosciences ,Neurology & Neurosurgery - Abstract
Background and purposeHematoma expansion after acute intracerebral hemorrhage is common and is associated with early deterioration and poor clinical outcome. The computed tomographic angiography (CTA) spot sign is a promising predictor of expansion; however, frequency and predictive values are variable across studies, possibly because of differences in onset-to-CTA time. We performed a patient-level meta-analysis to define the relationship between onset-to-CTA time and frequency and predictive ability of the spot sign.MethodsWe completed a systematic review for studies of CTA spot sign and hematoma expansion. We subsequently pooled patient-level data on the frequency and predictive values for significant hematoma expansion according to 5 predefined categorized onset-to-CTA times. We calculated spot-sign frequency both as raw and frequency-adjusted rates.ResultsAmong 2051 studies identified, 12 met our inclusion criteria. Baseline hematoma volume, spot-sign status, and time-to-CTA were available for 1176 patients, and 1039 patients had follow-up computed tomographies for hematoma expansion analysis. The overall spot sign frequency was 26%, decreasing from 39% within 2 hours of onset to 13% beyond 8 hours (P
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- 2016
45. PSMD, a novel biomarker of small vessel disease, and its association with cognitive function — A comprehensive clinical validation study
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Luckey, Alison M., primary, Ghosh, Saptaparni, additional, Bernal, Rebecca, additional, Snoussi, Haykel, additional, Velarde, Angel G., additional, Trevino, Hector, additional, Goss, Monica, additional, Himali, Jayandra Jung, additional, Hillmer, Laura J., additional, Lu, Hanzhang, additional, Arfanakis, Konstantinos, additional, Gold, Brian T., additional, Bauer, Christopher E., additional, Kramer, Joel H., additional, Staffaroni, Adam M., additional, Stables, Lara, additional, Wang, Danny J.J., additional, Beiser, Alexa S., additional, Fornage, Myriam, additional, Mosley, Thomas H., additional, Rosenberg, Gary A., additional, Singh, Baljeet, additional, Singh, Herpreet, additional, Schwab, Kristin, additional, Helmer, Karl G., additional, Greenberg, Steven M., additional, Habes, Mohamad, additional, Arvind, Caprihan, additional, Seshadri, Sudha, additional, Decarli, Charles, additional, Maillard, Pauline, additional, and Satizabal, Claudia L., additional
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- 2023
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46. Neurofilament Light and mean Free Water as prognostic enrichment biomarkers for cognitive worsening and small vessel disease progression
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Maillard, Pauline, primary, Beiser, Alexa S., additional, Habes, Mohamad, additional, Tracy, Russell P., additional, Kautz, Tiffany F, additional, Saklad, Amy R., additional, Kivisäkk, Pia, additional, Lu, Hanzhang, additional, Arfanakis, Konstantinos, additional, Gold, Brian T., additional, Kramer, Joel H., additional, Wang, Danny J.J., additional, Rosenberg, Gary A., additional, Singh, Herpreet, additional, Schwab, Kristin, additional, Helmer, Karl G., additional, Greenberg, Steven M., additional, Arvind, Caprihan, additional, Seshadri, Sudha, additional, Decarli, Charles, additional, and Satizabal, Claudia L., additional
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- 2023
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47. Cross vendor test‐retest validation of diffusion tensor analysis along the perivascular space (DTI‐ALPS) method for evaluating glymphatic system function in vascular cognitive impairment and dementia (VCID)
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Liu, Xiaodan, primary, Barisano, Giuseppe, additional, Shao, Xingfeng, additional, Jann, Kay, additional, Ringman, John M, additional, Lu, Hanzhang, additional, Arfanakis, Konstantinos, additional, Arvind, Caprihan, additional, Decarli, Charles, additional, Gold, Brian T., additional, Maillard, Pauline, additional, Satizabal, Clandia L., additional, Fadaee, Elyas, additional, Habes, Mohamad, additional, Stables, Lara, additional, Singh, Herpreet, additional, Fischl, Bruce, additional, van der Kouwe, Andre J., additional, Schwab, Kristin, additional, Helmer, Karl G., additional, Greenberg, Steven M., additional, and Wang, Danny J.J., additional
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- 2023
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48. The Neuropathological Correlates of White Matter Hyperintensities in Cerebral Amyloid Angiopathy
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Makkinejad, Nazanin, primary, Zotin, Maria Clara Zanon, additional, Brink, Hilde, additional, Auger, Corinne A., additional, Iglesias, Juan Eugenio, additional, Greenberg, Steven M., additional, Perosa, Valentina, additional, and Veluw, Susanne J, additional
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- 2023
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49. Profiling amyloid‐β peptides as diagnostic biomarkers for cerebral amyloid angiopathy
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van den Berg, Emma, primary, de Kort, Anna M., additional, Kersten, Iris, additional, Brinkmalm, Gunnar, additional, Johansson, Kjell, additional, Marques, Tainá M., additional, Jäkel, Lieke, additional, Gobom, Johan, additional, Stoops, Erik, additional, Portelius, Erik, additional, Gkanatsiou, Eleni, additional, Abdo, Wilson F., additional, Rasing, Ingeborg, additional, Voigt, Sabine, additional, Koemans, Emma A., additional, Kaushik, Kanishk, additional, Warren, Andrew D., additional, Greenberg, Steven M., additional, Terwindt, Gisela M., additional, Wermer, Marieke J.H., additional, Klijn, Catharina J.M., additional, Schreuder, Floris H.B.M., additional, Zetterberg, Henrik, additional, Blennow, Kaj, additional, Kuiperij, H. Bea, additional, and Verbeek, Marcel M., additional
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- 2023
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50. Diagnostic value of lobar microbleeds in individuals without intracerebral hemorrhage
- Author
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Martinez‐Ramirez, Sergi, Romero, Jose‐Rafael, Shoamanesh, Ashkan, McKee, Ann C, Van Etten, Ellis, Pontes‐Neto, Octavio, Macklin, Eric A, Ayres, Alison, Auriel, Eitan, Himali, Jayandra J, Beiser, Alexa S, DeCarli, Charles, Stein, Thor D, Alvarez, Victor E, Frosch, Matthew P, Rosand, Jonathan, Greenberg, Steven M, Gurol, M Edip, Seshadri, Sudha, and Viswanathan, Anand
- Subjects
Neurosciences ,Clinical Research ,Brain Disorders ,Biomedical Imaging ,Rare Diseases ,4.2 Evaluation of markers and technologies ,Detection ,screening and diagnosis ,Aged ,Aged ,80 and over ,Brain ,Cerebral Amyloid Angiopathy ,Cerebral Hemorrhage ,Female ,Humans ,Magnetic Resonance Imaging ,Male ,Predictive Value of Tests ,Cerebral amyloid angiopathy ,Microbleed ,Intracerebral hemorrhage ,Boston criteria ,Sensitivity ,Specificity ,Predictive value ,Likelihood ratio ,Clinical Sciences ,Geriatrics - Abstract
IntroductionThe Boston criteria are the basis for a noninvasive diagnosis of cerebral amyloid angiopathy (CAA) in the setting of lobar intracerebral hemorrhage (ICH). We assessed the accuracy of these criteria in individuals with lobar microbleeds (MBs) without ICH.MethodsWe identified individuals aged >55 years having brain magnetic resonance imaging (MRI) and pathological assessment of CAA in a single academic hospital and a community-based population (Framingham Heart Study [FHS]). We determined the positive predictive value (PPV) of the Boston criteria for CAA in both cohorts, using lobar MBs as the only hemorrhagic lesion to fulfill the criteria.ResultsWe included 102 individuals: 55 from the hospital-based cohort and 47 from FHS (mean age at MRI 74.7 ± 8.5 and 83.4 ± 10.9 years; CAA prevalence 60% and 46.8%; cases with any lobar MB 49% and 21.3%; and cases with ≥2 strictly lobar MBs 29.1% and 8.5%, respectively). PPV of "probable CAA" (≥2 strictly lobar MBs) was 87.5% (95% confidence interval [CI], 60.4-97.8) and 25% (95% CI, 13.2-78) in hospital and general populations, respectively.DiscussionStrictly lobar MBs strongly predict CAA in non-ICH individuals when found in a hospital context. However, their diagnostic accuracy in the general population appears limited.
- Published
- 2015
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