14 results on '"de Leeuw, Frank-Erik"'
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2. sj-docx-1-wso-10.1177_17474930231159267 – Supplemental material for Cognitive impairment after a stroke in young adults: A systematic review and meta-analysis
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Weterings, Rosemarije PC, Kessels, Roy PC, de Leeuw, Frank-Erik, and Piai, Vitória
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FOS: Clinical medicine ,Cardiology ,Medicine ,110904 Neurology and Neuromuscular Diseases - Abstract
Supplemental material, sj-docx-1-wso-10.1177_17474930231159267 for Cognitive impairment after a stroke in young adults: A systematic review and meta-analysis by Rosemarije PC Weterings, Roy PC Kessels, Frank-Erik de Leeuw and Vitória Piai in International Journal of Stroke
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- 2023
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3. sj-docx-1-wso-10.1177_17474930231159267 – Supplemental material for Cognitive impairment after a stroke in young adults: A systematic review and meta-analysis
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Weterings, Rosemarije PC, Kessels, Roy PC, de Leeuw, Frank-Erik, and Piai, Vitória
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FOS: Clinical medicine ,Cardiology ,Medicine ,110904 Neurology and Neuromuscular Diseases - Abstract
Supplemental material, sj-docx-1-wso-10.1177_17474930231159267 for Cognitive impairment after a stroke in young adults: A systematic review and meta-analysis by Rosemarije PC Weterings, Roy PC Kessels, Frank-Erik de Leeuw and Vitória Piai in International Journal of Stroke
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- 2023
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4. sj-docx-1-wso-10.1177_17474930231169132 – Supplemental material for How often does white matter hyperintensity volume regress in cerebral small vessel disease?
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Brown, Robin B, Tozer, Daniel J, Egle, Marco, Tuladhar, Anil M, de Leeuw, Frank-Erik, and Markus, Hugh S
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FOS: Clinical medicine ,Cardiology ,Medicine ,110904 Neurology and Neuromuscular Diseases - Abstract
Supplemental material, sj-docx-1-wso-10.1177_17474930231169132 for How often does white matter hyperintensity volume regress in cerebral small vessel disease? by Robin B Brown, Daniel J Tozer, Marco Egle, Anil M Tuladhar, Frank-Erik de Leeuw and Hugh S Markus in International Journal of Stroke
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- 2023
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5. Disentangling the effects of Alzheimer's and small vessel disease on white matter fibre tracts
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Dewenter, Anna, Jacob, Mina A, Dichgans, Martin, Franzmeier, Nicolai, Duering, Marco, Consortium, SVDs@target, Initiative, Alzheimer’s Disease Neuroimaging, Cai, Mengfei, Gesierich, Benno, Hager, Paul, Kopczak, Anna, Biel, Davina, Ewers, Michael, Tuladhar, Anil M, and de Leeuw, Frank Erik
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cerebral small vessel disease ,Amyloidogenic Proteins ,CADASIL ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,diagnostic imaging [White Matter] ,pathology [Alzheimer Disease] ,Cross-Sectional Studies ,All institutes and research themes of the Radboud University Medical Center ,pathology [Brain] ,pathology [White Matter] ,methods [Diffusion Magnetic Resonance Imaging] ,Humans ,pathology [Cerebral Small Vessel Diseases] ,Neurology (clinical) ,ddc:610 ,Vascular Diseases ,diagnostic imaging [Cerebral Small Vessel Diseases] ,diagnostic imaging [Alzheimer Disease] ,diagnostic imaging [Brain] ,Alzheimer’s disease ,fixel-based analysis ,diffusion magnetic resonance imaging - Abstract
Alzheimer’s disease and cerebral small vessel disease are the two leading causes of cognitive decline and dementia and coexist in most memory clinic patients. White matter damage as assessed by diffusion MRI is a key feature in both Alzheimer’s and cerebral small vessel disease. However, disease-specific biomarkers of white matter alterations are missing. Recent advances in diffusion MRI operating on the fixel level (fibre population within a voxel) promise to advance our understanding of disease-related white matter alterations. Fixel-based analysis allows derivation of measures of both white matter microstructure, measured by fibre density, and macrostructure, measured by fibre-bundle cross-section. Here, we evaluated the capacity of these state-of-the-art fixel metrics to disentangle the effects of cerebral small vessel disease and Alzheimer’s disease on white matter integrity. We included three independent samples (total n = 387) covering genetically defined cerebral small vessel disease and age-matched controls, the full spectrum of biomarker-confirmed Alzheimer’s disease including amyloid- and tau-PET negative controls and a validation sample with presumed mixed pathology. In this cross-sectional analysis, we performed group comparisons between patients and controls and assessed associations between fixel metrics within main white matter tracts and imaging hallmarks of cerebral small vessel disease (white matter hyperintensity volume, lacune and cerebral microbleed count) and Alzheimer’s disease (amyloid- and tau-PET), age and a measure of neurodegeneration (brain volume). Our results showed that (i) fibre density was reduced in genetically defined cerebral small vessel disease and strongly associated with cerebral small vessel disease imaging hallmarks; (ii) fibre-bundle cross-section was mainly associated with brain volume; and (iii) both fibre density and fibre-bundle cross-section were reduced in the presence of amyloid, but not further exacerbated by abnormal tau deposition. Fixel metrics were only weakly associated with amyloid- and tau-PET. Taken together, our results in three independent samples suggest that fibre density captures the effect of cerebral small vessel disease, while fibre-bundle cross-section is largely determined by neurodegeneration. The ability of fixel-based imaging markers to capture distinct effects on white matter integrity can propel future applications in the context of precision medicine.
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- 2022
6. sj-docx-1-wso-10.1177_17474930221137019 – Supplemental material for The global burden of cerebral small vessel disease in low- and middle-income countries: A systematic review and meta-analysis
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Lam, Bonnie Yin Ka, Cai, Yuan, Akinyemi, Rufus, Biessels, Geert Jan, van den Brink, Hilde, Chen, Christopher, Cheung, Chin Wai, Chow, King Ngai, Chung, Henry Kwun Hang, Duering, Marco, Fu, Siu Ting, Gustafson, Deborah, Hilal, Saima, Hui, Vincent Ming Ho, Kalaria, Rajesh, Kim, SangYun, Lam, Maggie Li Man, de Leeuw, Frank Erik, Li, Ami Sin Man, Markus, Hugh Stephen, Marseglia, Anna, Zheng, Huijing, O’Brien, John, Pantoni, Leonardo, Sachdev, Perminder Singh, Smith, Eric E, Wardlaw, Joanna, and Mok, Vincent Chung Tong
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FOS: Clinical medicine ,Cardiology ,Medicine ,110904 Neurology and Neuromuscular Diseases - Abstract
Supplemental material, sj-docx-1-wso-10.1177_17474930221137019 for The global burden of cerebral small vessel disease in low- and middle-income countries: A systematic review and meta-analysis by Bonnie Yin Ka Lam, Yuan Cai, Rufus Akinyemi, Geert Jan Biessels, Hilde van den Brink, Christopher Chen, Chin Wai Cheung, King Ngai Chow, Henry Kwun Hang Chung, Marco Duering, Siu Ting Fu, Deborah Gustafson, Saima Hilal, Vincent Ming Ho Hui, Rajesh Kalaria, SangYun Kim, Maggie Li Man Lam, Frank Erik de Leeuw, Ami Sin Man Li, Hugh Stephen Markus, Anna Marseglia, Huijing Zheng, John O’Brien, Leonardo Pantoni, Perminder Singh Sachdev, Eric E Smith, Joanna Wardlaw and Vincent Chung Tong Mok in International Journal of Stroke
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- 2022
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7. sj-docx-1-eso-10.1177_23969873221132032 – Supplemental material for Subacute cognitive impairment after first-ever transient ischemic attack or ischemic stroke in young adults: The ODYSSEY study
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Schellekens, Mijntje MI, Boot, Esther M, Verhoeven, Jamie I, Ekker, Merel S, van Alebeek, Mayte E, Brouwers, Paul JAM, Arntz, Renate M, van Dijk, Gert W, Gons, Rob AR, van Uden, Inge WM, den Heijer, Tom, de Kort, Paul LM, de Laat, Karlijn F, van Norden, Anouk, Vermeer, Sarah E, van Zagten, Marian SG, van Oostenbrugge, Robert J, Wermer, Marieke JH, Nederkoorn, Paul J, van Rooij, Frank G, van den Wijngaard, Ido R, de Leeuw, Frank-Erik, Kessels, Roy PC, and Tuladhar, Anil M
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FOS: Clinical medicine ,Cardiology ,Medicine ,110904 Neurology and Neuromuscular Diseases - Abstract
Supplemental material, sj-docx-1-eso-10.1177_23969873221132032 for Subacute cognitive impairment after first-ever transient ischemic attack or ischemic stroke in young adults: The ODYSSEY study by Mijntje MI Schellekens, Esther M Boot, Jamie I Verhoeven, Merel S Ekker, Mayte E van Alebeek, Paul JAM Brouwers, Renate M Arntz, Gert W van Dijk, Rob AR Gons, Inge WM van Uden, Tom den Heijer, Paul LM de Kort, Karlijn F de Laat, Anouk van Norden, Sarah E Vermeer, Marian SG van Zagten, Robert J van Oostenbrugge, Marieke JH Wermer, Paul J Nederkoorn, Frank G van Rooij, Ido R van den Wijngaard, Frank-Erik de Leeuw, Roy PC Kessels and Anil M Tuladhar in European Stroke Journal
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- 2022
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8. sj-docx-1-wso-10.1177_17474930221137019 – Supplemental material for The global burden of cerebral small vessel disease in low- and middle-income countries: A systematic review and meta-analysis
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Lam, Bonnie Yin Ka, Cai, Yuan, Akinyemi, Rufus, Biessels, Geert Jan, van den Brink, Hilde, Chen, Christopher, Cheung, Chin Wai, Chow, King Ngai, Chung, Henry Kwun Hang, Duering, Marco, Fu, Siu Ting, Gustafson, Deborah, Hilal, Saima, Hui, Vincent Ming Ho, Kalaria, Rajesh, Kim, SangYun, Lam, Maggie Li Man, de Leeuw, Frank Erik, Li, Ami Sin Man, Markus, Hugh Stephen, Marseglia, Anna, Zheng, Huijing, O’Brien, John, Pantoni, Leonardo, Sachdev, Perminder Singh, Smith, Eric E, Wardlaw, Joanna, and Mok, Vincent Chung Tong
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FOS: Clinical medicine ,Cardiology ,Medicine ,110904 Neurology and Neuromuscular Diseases - Abstract
Supplemental material, sj-docx-1-wso-10.1177_17474930221137019 for The global burden of cerebral small vessel disease in low- and middle-income countries: A systematic review and meta-analysis by Bonnie Yin Ka Lam, Yuan Cai, Rufus Akinyemi, Geert Jan Biessels, Hilde van den Brink, Christopher Chen, Chin Wai Cheung, King Ngai Chow, Henry Kwun Hang Chung, Marco Duering, Siu Ting Fu, Deborah Gustafson, Saima Hilal, Vincent Ming Ho Hui, Rajesh Kalaria, SangYun Kim, Maggie Li Man Lam, Frank Erik de Leeuw, Ami Sin Man Li, Hugh Stephen Markus, Anna Marseglia, Huijing Zheng, John O’Brien, Leonardo Pantoni, Perminder Singh Sachdev, Eric E Smith, Joanna Wardlaw and Vincent Chung Tong Mok in International Journal of Stroke
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- 2022
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9. Additional file 1 of Impact of the lockdown on acute stroke treatments during the first surge of the COVID-19 outbreak in the Netherlands
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Benali, Faysal, Stolze, Lotte J., Rozeman, Anouk D., Dinkelaar, Wouter, Coutinho, Jonathan M., Emmer, Bart J., Gons, Rob A. R., Yo, Lonneke F. S., van Tuijl, Julia H., Boukrab, Issam, van Dam-Nolen, Dianne H. K., van den Wijngaard, Ido R., Lycklama �� Nijeholt, Geert J., de Laat, Karlijn F., van Dijk, Lukas C., den Hertog, Heleen M., Flach, H. Zwenneke, Wermer, Marieke J. H., van Walderveen, Marianne A. A., Brouwers, Paul J. A. M., Bulut, Tomas, Vermeer, Sarah E., Bernsen, Marie Louise E., Uyttenboogaart, Maarten, Bokkers, Reinoud P. H., Boogaarts, Jeroen D., de Leeuw, Frank-Erik, van der Worp, H. Bart, van der Schaaf, Irene C., Schonewille, Wouter J., Vos, Jan A., Remmers, Michel J. M., Imani, Farshad, Dippel, Diederik W. J., van Zwam, Wim H., Nederkoorn, Paul J., and van Oostenbrugge, Robert J.
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Additional file 1: Supplemental table 1. Subdivision in regions. *Total number of new COVID-19 hospital admissions in all hospital in a region from March 15th, 2020 until May 11th, 2020, based on data from the Dutch public health service (GGD)16 and Statistics Netherlands (CBS)17. This illustrates the severity of crowding due to COVID-19 in a region. Supplemental figure 1. Map of the different regions with corresponding EVT-centers. *Total number of new COVID-19 hospital admissions in all hospital in a region from March 15th, 2020 until May 11th, 2020, based on data from the Dutch public health service (GGD) [16] and Statistics Netherlands (CBS) [17]. This illustrates the severity of crowding due to COVID-19 in a region. Supplemental table 2. All treated AIS-patients from March 15th until May 11th, 2020 (lockdown) and 2019 (reference), subdivided in regions. * All times are displayed in minutes.
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- 2022
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10. Disruption of rich club organisation in cerebral small vessel disease
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Tuladhar, Anil M., Lawrence, Andrew, Norris, David G., Barrick, Thomas R., Markus, Hugh S., de Leeuw, Frank-Erik, and Magnetic Detection and Imaging
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Neuroinformatics ,Diffusion tensor imaging ,Diffusion Tensor Imaging ,Rich club organization ,Structural networks ,Medizin ,Cerebral small vessel disease ,structural networks ,graph-theory ,Graph-theory ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,150 000 MR Techniques in Brain Function ,rich club organisation - Abstract
Contains fulltext : 170472.pdf (Publisher’s version ) (Open Access) Cerebral small vessel disease (SVD) is an important cause of vascular cognitive impairment. Recent studies have demonstrated that structural connectivity of brain networks in SVD is disrupted. However, little is known about the extent and location of the reduced connectivity in SVD. Here they investigate the rich club organisation-a set of highly connected and interconnected regions-and investigate whether there is preferential rich club disruption in SVD. Diffusion tensor imaging (DTI) and cognitive assessment were performed in a discovery sample of SVD patients (n = 115) and healthy control subjects (n = 50). Results were replicated in an independent dataset (49 SVD with confluent WMH cases and 108 SVD controls) with SVD patients having a similar SVD phenotype to that of the discovery cases. Rich club organisation was examined in structural networks derived from DTI followed by deterministic tractography. Structural networks in SVD patients were less dense with lower network strength and efficiency. Reduced connectivity was found in SVD, which was preferentially located in the connectivity between the rich club nodes rather than in the feeder and peripheral connections, a finding confirmed in both datasets. In discovery dataset, lower rich club connectivity was associated with lower scores on psychomotor speed (beta = 0.29, P < 0.001) and executive functions (beta = 0.20, P = 0.009). These results suggest that SVD is characterized by abnormal connectivity between rich club hubs in SVD and provide evidence that abnormal rich club organisation might contribute to the development of cognitive impairment in SVD. Hum Brain Mapp 38:1751-1766, 2017. (c) 2017 Wiley Periodicals, Inc.
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- 2017
11. Predicting the presence of macrovascular causes in non-traumatic intracerebral haemorrhage: the DIAGRAM prediction score
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Hilkens, Nina A., van Asch, Charlotte J. J., Werring, David J., Wilson, Duncan, Rinkel, Gabriël J. E., Algra, Ale, Velthuis, Birgitta K., de Kort, G. rard A. P., Witkamp, Theo D., van Nieuwenhuizen, Koen M., de Leeuw, Frank-Erik, Schonewille, Wouter J., de Kort, Paul L. M., Dippel, Diederik W. J., Raaymakers, Theodora W. M., Hofmeijer, Jeannette, Wermer, Marieke J. H., Kerkhoff, Henk, Jellema, Korné, Bronner, Irene M., Remmers, Michel J. M., Bienfait, Henri Paul, Witjes, Ron J. G. M., Jäger, H. Rolf, Greving, Jacoba P., Klijn, Catharina J. M., Boogaarts, H. B., van Dijk, E. J., Schonewille, W. J., Pellikaan, W. M. J., Puppels-de Waard, C., de Kort, P. L. M., Peluso, J. P., van Tuijl, J. H., Hofmeijer, J., Joosten, F. B. M., Dippel, D. W., Khajeh, L., Raaijmakers, T. W. M., Wermer, M. J., van Walderveen, M. A., Kerkhoff, H., Zock, E., Jellema, K., Lycklama, G. J., Bronner, I. M., Remmers, M. J. M., Witjes, R. J. G. M., Bienfait, H. P., Droogh-Greve, K. E., Donders, R. C. J. M., Kwa, V. I. H., Schreuder, T. H., Franke, C. L., Straver, J. S., Jansen, C., Bakker, S. L. M., Pleiter, C. C., Visser, M. C., van Asch, C. J. J., Velthuis, B. K., Rinkel, G. J. E., van Nieuwenhuizen, K. M., Klijn, C. J. M., Neurology, and Amsterdam Neuroscience - Neurovascular Disorders
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Computed Tomography Angiography ,Clinical Neurology ,Logistic regression ,Magnetic resonance angiography ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,All institutes and research themes of the Radboud University Medical Center ,Predictive Value of Tests ,Risk Factors ,Internal medicine ,Non traumatic ,medicine ,Humans ,030212 general & internal medicine ,cardiovascular diseases ,Prospective Studies ,Aged ,Cerebral Hemorrhage ,Netherlands ,Central Nervous System Vascular Malformations ,Prediction score ,medicine.diagnostic_test ,business.industry ,Arteriovenous malformation ,Digital subtraction angiography ,Middle Aged ,medicine.disease ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,nervous system diseases ,Cerebral Angiography ,Psychiatry and Mental health ,Logistic Models ,Cohort ,Angiography ,Cardiology ,Surgery ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Magnetic Resonance Angiography - Abstract
ObjectiveA substantial part of non-traumatic intracerebral haemorrhages (ICH) arises from a macrovascular cause, but there is little guidance on selection of patients for additional diagnostic work-up. We aimed to develop and externally validate a model for predicting the probability of a macrovascular cause in patients with non-traumatic ICH.MethodsThe DIagnostic AngioGRAphy to find vascular Malformations (DIAGRAM) study (n=298; 69 macrovascular cause; 23%) is a prospective, multicentre study assessing yield and accuracy of CT angiography (CTA), MRI/ magnetic resonance angiography (MRA) and intra-arterial catheter angiography in diagnosing macrovascular causes in patients with non-traumatic ICH. We considered prespecified patient and ICH characteristics in multivariable logistic regression analyses as predictors for a macrovascular cause. We combined independent predictors in a model, which we validated in an external cohort of 173 patients with ICH (78 macrovascular cause, 45%).ResultsIndependent predictors were younger age, lobar or posterior fossa (vs deep) location of ICH, and absence of small vessel disease (SVD). A model that combined these predictors showed good performance in the development data (c-statistic 0.83; 95% CI 0.78 to 0.88) and moderate performance in external validation (c-statistic 0.66; 95% CI 0.58 to 0.74). When CTA results were added, the c-statistic was excellent (0.91; 95% CI 0.88 to 0.94) and good after external validation (0.88; 95% CI 0.83 to 0.94). Predicted probabilities varied from 1% in patients aged 51–70 years with deep ICH and SVD, to more than 50% in patients aged 18–50 years with lobar or posterior fossa ICH without SVD.ConclusionThe DIAGRAM scores help to predict the probability of a macrovascular cause in patients with non-traumatic ICH based on age, ICH location, SVD and CTA.
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- 2017
12. A Novel Imaging Marker for Small Vessel Disease Based on Skeletonization of White Matter Tracts and Diffusion Histograms
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Baykara, Ebru, Gesierich, Benno, Ertl-Wagner, Birgit, Ewers, Michael, Schmidt, Reinhold, de Leeuw, Frank-Erik, Biessels, Geert Jan, Dichgans, Martin, Duering, Marco, Adam, Ruth, Tuladhar, Anil Man, Biesbroek, J Matthijs, Koek, Huiberdina L, Ropele, Stefan, Jouvent, Eric, Initiative, Alzheimer's Disease Neuroimaging, and Chabriat, Hugues
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Adult ,Male ,physiopathology [Cognitive Dysfunction] ,diagnostic imaging [Cognitive Dysfunction] ,methods [Diffusion Tensor Imaging] ,diagnostic imaging [White Matter] ,etiology [Cognitive Dysfunction] ,Young Adult ,Alzheimer Disease ,Humans ,Cognitive Dysfunction ,ddc:610 ,Aged ,Aged, 80 and over ,Reproducibility of Results ,Middle Aged ,White Matter ,Diffusion Tensor Imaging ,complications [Cerebral Small Vessel Diseases] ,Cerebral Small Vessel Diseases ,Female ,diagnostic imaging [Cerebral Small Vessel Diseases] ,standards [Diffusion Tensor Imaging] ,diagnostic imaging [Alzheimer Disease] ,Biomarkers - Abstract
To establish a fully automated, robust imaging marker for cerebral small vessel disease (SVD) and related cognitive impairment that is easy to implement, reflects disease burden, and is strongly associated with processing speed, the predominantly affected cognitive domain in SVD.We developed a novel magnetic resonance imaging marker based on diffusion tensor imaging, skeletonization of white matter tracts, and histogram analysis. The marker (peak width of skeletonized mean diffusivity [PSMD]) was assessed along with conventional SVD imaging markers. We first evaluated associations with processing speed in patients with genetically defined SVD (n = 113). Next, we validated our findings in independent samples of inherited SVD (n = 57), sporadic SVD (n = 444), and memory clinic patients with SVD (n = 105). The new marker was further applied to healthy controls (n = 241) and to patients with Alzheimer's disease (n = 153). We further conducted a longitudinal analysis and interscanner reproducibility study.PSMD was associated with processing speed in all study samples with SVD (p-values between 2.8 × 10(-3) and 1.8 × 10(-10) ). PSMD explained most of the variance in processing speed (R(2) ranging from 8.8% to 46%) and consistently outperformed conventional imaging markers (white matter hyperintensity volume, lacune volume, and brain volume) in multiple regression analyses. Increases in PSMD were linked to vascular but not to neurodegenerative disease. In longitudinal analysis, PSMD captured SVD progression better than other imaging markers.PSMD is a new, fully automated, and robust imaging marker for SVD. PSMD can easily be applied to large samples and may be of great utility for both research studies and clinical use. Ann Neurol 2016;80:581-592.
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- 2016
13. Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection
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Debette, Stéphanie, Kamatani, Yoichiro, Wolf, Christiane, Agabiti Rosei, Enrico, Lanfranconi, Silvia, Ferrarese, Carlo, Susani, Emanuela, Bicocca, Milano, Giacalone, Giacomo, Paolucci, Stefano, Palmirotta, Raffaele, Paciaroni, Maurizio, Ballabio, Elena, Dittrich, Ralf, Parati, Eugenio A, Ciusani, Emilio, Fluri, Felix, Hatz, Florian, Gisler, Dominique, Amort, Margareth, Bevan, Steve, James, Tom, Olsson, Sandra, Holmegaard, Lukas, Touzé, Emmanuel, Altintas, Ayse, Martin, Juan José, Kittner, Steven, MItchell, Braxton, Stine, Colin, O'Connell, Jeff, Dueker, Nicole, Koudstaal, Peter J, de Lau, Lonneke M L, Hofman, Albert, Southerland, Andrew M, Verhaaren, Benjamin F, Uitterlinden, Andre G, Montaner, Joan, Mendioroz, Maite, Yadav, Sunaina, Khan, Muhammad Saleem, Wilder, Michael, van Dijk, Ewoud, Maaijwee, Noortje, Rutten-Jacobs, Loes, Samson, Yves, Kramer, Jamie, Malik, Shaneela, Brott, Thomas G, Brown, Robert D, Singleton, Andrew, Hardy, John, Rich, Stephen S, Tanislav, Christian, Jungehülsing, Jan, Abboud, Shérine, Béjot, Yannick, Caso, Valeria, Bersano, Anna, Gschwendtner, Andreas, Metso, Tiina M, Sessa, Maria, Cole, John, Lamy, Chantal, Medeiros, Elisabeth, Beretta, Simone, Bonati, Leo H, Grau, Armin J, Michel, Patrik, Majersik, Jennifer J, Sharma, Pankaj, Kloss, Manja, Kalashnikova, Ludmila, Nazarova, Maria, Dobrynina, Larisa, Bartels, Eva, Guillon, Benoit, van den Herik, Evita G, Fernandez-Cadenas, Israel, Jood, Katarina, Nalls, Michael A, De Leeuw, Frank-Erik, Chauhan, Ganesh, Jern, Christina, Cheng, Yu-Ching, Werner, Inge, Metso, Antti J, Lichy, Christoph, Lyrer, Philippe A, Brandt, Tobias, Boncoraglio, Giorgio B, Wichmann, Heinz-Erich, Gieger, Christian, Engelter, Stefan T, Johnson, Andrew D, Böttcher, Thomas, Castellano, Maurizio, Arveiler, Dominique, Ikram, M Arfan, Breteler, Monique M B, Padovani, Alessandro, Meschia, James F, Kuhlenbäumer, Gregor, Rolfs, Arndt, Pezzini, Alessandro, Worrall, Bradford B, Consortium, International Stroke Genetics, Ringelstein, Erich-Bernd, Zelenika, Diana, Tatlisumak, Turgut, Lathrop, Mark, Leys, Didier, Amouyel, Philippe, Dallongeville, Jean, Group, CADISP, Thijs, Vincent, Lemmens, Robin, Pandolfo, Massimo, Bodenant, Marie, Louillet, Fabien, Mas, Jean-Louis, Deltour, Sandrine, Leder, Sara, Léger, Anne, Canaple, Sandrine, Godefroy, Olivier, Markus, Hugh S, Giroud, Maurice, Jacquin, Agnès, Moulin, Thierry, Vullier, Fabrice, Tzourio, Christophe, Dos Santos, Michael, Malik, Rainer, Hausser, Ingrid, Thomas-Feles, Constanze, Weber, Ralf, Dichgans, Martin, Grond-Ginsbach, Caspar, Hacke, Werner, Giossi, Alessia, Volonghi, Irene, Costa, Paolo, del Zotto, Elisabetta, Morotti, Andrea, Poli, Loris, Lorenza Muiesan, Maria, Salvetti, Massimo, Epidémiologie des maladies chroniques: impact des intéractions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Epidemiologie-Biostatistique [Bordeaux], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux Ségalen [Bordeaux 2], Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Helsinki University Central Hospital [Finland] (HUCH), Heidelberg University Hospital [Heidelberg], University Hospital Basel [Basel], Università degli Studi di Brescia = University of Brescia (UniBs), University Hospitals Leuven [Leuven], Leuven Center for Cancer Biology (VIB-KU-CCB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), University of Cambridge [UK] (CAM), Institute for Stroke and Dementia Research (ISD), Klinikum der Universität [München]-Ludwig Maximilian University [Munich] (LMU), Ludwig-Maximilians-Universität München (LMU), University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Neurologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), University of Virginia, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Neurochirurgie Expérimentale [Brussels] (ULB 257), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Università degli Studi di Perugia = University of Perugia (UNIPG), Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), Ospedale San Raffaele, University of Maryland School of Medicine, University of Maryland System, Service de neurologie [Amiens], CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Klinikum Ludwigshafen [Germany], Service of Neurology [CHUV, Lausanne, Switzerland], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), University of Utah School of Medicine [Salt Lake City], Institute of Cardiovascular Research (ICR2UL), Royal Holloway [University of London] (RHUL), Ashford and St Peter's hospitals NHS foundation trust, Russian Academy of Sciences [Moscow] (RAS), Centre for Cognition and Decision Making [HSE, Moscow], Institut of Cognitive Neuroscience [HSE, Moscow] (ICN), Vysšaja škola èkonomiki = National Research University Higher School of Economics [Moscow] (HSE)-Vysšaja škola èkonomiki = National Research University Higher School of Economics [Moscow] (HSE), Zentrum für neurologische Gefäßdiagnostik - Center for Neurological Vascular Diagnostics [Munich, Germany], Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Department of Neurology [Erasmus MC, Rotterdam], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hospital Universitario Mutua de Terrassa, Vall d'Hebron University Hospital [Barcelona], Insitute of Neuroscience and Physiology, University of Gothenburg (GU), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], Schmieder Klinik [Heidelberg, Germany], Helmholtz Zentrum München = German Research Center for Environmental Health, Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), University Hospital Rostock, Progression tumorale et microenvironnement. Approches translationnelles et épidémiologie, Université de Strasbourg (UNISTRA)-CHU Strasbourg-Les Hôpitaux Universitaires de Strasbourg (HUS)-Institut Régional du Cancer-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), University of Brescia, Mayo Clinic [Jacksonville], Institute of Experimental Medicine - Institut für Experimentelle Medizin [Kiel, Germany] (IEM), Christian-Albrechts-Universität zu Kiel (CAU), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Centre d'Etude du Polymorphisme Humain (CEPH), Université Paris Diderot - Paris 7 (UPD7)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Fondation Jean Dausset, McGill University and Genome Quebec Innovation Centre, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, Pharmacologie de la mort neuronale et de la plasticité cérébrale, IFR114-Université de Lille, Droit et Santé, Réseau International des Instituts Pasteur (RIIP), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, The CADISP study has been supported by INSERM, Lille 2 University, Institut Pasteur de Lille and Lille University Hospital and received funding from the European Regional Development Fund (FEDER funds) and Région Nord-Pas-de-Calais in the framework of Contrat de Projets Etat-Region 2007–2013 Région Nord-Pas-de-Calais (grant 09120030), Centre National de Génotypage, the Emil Aaltonen Foundation, the Paavo Ilmari Ahvenainen Foundation, the Helsinki University Central Hospital Research Fund, the Helsinki University Medical Foundation, the Päivikki and Sakari Sohlberg Foundation, the Aarne Koskelo Foundation, the Maire Taponen Foundation, the Aarne and Aili Turunen Foundation, the Lilly Foundation, the Alfred Kordelin Foundation, the Finnish Medical Foundation, the Orion Farmos Research Foundation, the Maud Kuistila Foundation, the Finnish Brain Foundation, the Biomedicum Helsinki Foundation, Projet Hospitalier de Recherche Clinique Régional, Fondation de France, Génopôle de Lille, Adrinord, the Basel Stroke Funds, the Käthe-Zingg-Schwichtenberg-Fonds of the Swiss Academy of Medical Sciences and the Swiss Heart Foundation.L.H.B., S.T.E. and P.A.L. were supported, in part, by a grant from the Swiss National Science Foundation (33CM30-124119). S.D. is supported by a Chair of Excellence from the French National Research Agency (ANR). S.D. and M.D. are supported by a grant from the Leducq Foundation. M.D. is supported by the Vascular Dementia Research Foundation. I.F.-C. is supported by the Miguel Servet programme (CP12/03298) from the Spanish Ministry of Health (Instituto de Salud Carlos III). G.K. is a member of the Deutsche Forschungsgemeinschaft Cluster of Excellence 'Inflammation at Interfaces'. P.S. is supported by a Department of Health (UK) senior fellowship. A.M.S. is supported by the American Heart Association/American Stroke Association National Clinical Research Program (AHA 3CRP14140001). V.T. is supported by Fonds Wetenschappelijk Onderzoek Flanders., CADISP Group, RIKEN Center for Integrative Medical Science, Università degli Studi di Brescia [Brescia], University of Virginia [Charlottesville], Service des Urgences Cérébro-Vasculaires [CHU Pitié-Salpêtrière]], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Laboratoire de Neurologie Expérimentale [ULB, Brussels, Belgium] (ULB 257), Université Libre de Bruxelles [Bruxelles] (ULB)-Hôpital Erasme (Bruxelles), Università degli Studi di Perugia (UNIPG), Technische Universität München [München] (TUM)-Ludwig-Maximilians-Universität München (LMU), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), National Research University Higher School of Economics [Moscow] (HSE)-National Research University Higher School of Economics [Moscow] (HSE), Radboud university [Nijmegen], Helmholtz-Zentrum München (HZM), Westfälische Wilhelms-Universität Münster (WWU), The authors thank the staff and participants of all CADISP centers for their important contributions., Service des Urgences Cérébro-Vasculaires [CHU Pitié-Salpétriêre], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fondation Jean Dausset-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Erasmus MC other, Epidemiology, Debette, S, Kamatani, Y, Metso, T, Kloss, M, Chauhan, G, Engelter, S, Pezzini, A, Thijs, V, Markus, H, Dichgans, M, Wolf, C, Dittrich, R, Touzé, E, Southerland, A, Samson, Y, Abboud, S, Béjot, Y, Caso, V, Bersano, A, Gschwendtner, A, Sessa, M, Cole, J, Lamy, C, Medeiros, E, Beretta, S, Bonati, L, Grau, A, Michel, P, Majersik, J, Sharma, P, Kalashnikova, L, Nazarova, M, Dobrynina, L, Bartels, E, Guillon, B, Van Den Herik, E, Fernandez Cadenas, I, Jood, K, Nalls, M, De Leeuw, F, Jern, C, Cheng, Y, Werner, I, Metso, A, Lichy, C, Lyrer, P, Brandt, T, Boncoraglio, G, Wichmann, H, Gieger, C, Johnson, A, Böttcher, T, Castellano, M, Arveiler, D, Ikram, M, Breteler, M, Padovani, A, Meschia, J, Kuhlenbäumer, G, Rolfs, A, Worrall, B, Ringelstein, E, Zelenika, D, Tatlisumak, T, Lathrop, M, Leys, D, Amouyel, P, Dallongeville, J, Lemmens R, P, and Ferrarese, C
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Male ,[SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Myocardial Infarction ,Genome-wide association study ,Carotid Artery, Internal, Dissection ,Gastroenterology ,epidemiology [Carotid Artery, Internal, Dissection] ,Brain Ischemia ,0302 clinical medicine ,Migraine Disorder ,Odds Ratio ,Finland ,Vertebral Artery Dissection ,0303 health sciences ,education.field_of_study ,epidemiology [Hypercholesterolemia] ,MESH: Middle Aged ,MESH: Polymorphism, Single Nucleotide ,Phactr-1 protein, human ,MESH: Brain Ischemia ,MESH: Follow-Up Studies ,3. Good health ,MESH: Myocardial Infarction ,Human ,medicine.medical_specialty ,Migraine Disorders ,Hypercholesterolemia ,MESH: Vertebral Artery Dissection ,Lower risk ,genetics [Brain Ischemia] ,Article ,Follow-Up Studie ,MESH: Carotid Artery, Internal, Dissection ,03 medical and health sciences ,Genetic ,SDG 3 - Good Health and Well-being ,genetics [Carotid Artery, Internal, Dissection] ,Genetics ,Genetic predisposition ,epidemiology [Brain Ischemia] ,Humans ,epidemiology [Vertebral Artery Dissection] ,Polymorphism ,education ,Alleles ,MESH: Humans ,genetics [Vertebral Artery Dissection] ,MESH: Adult ,Odds ratio ,Microfilament Protein ,medicine.disease ,Adult ,Female ,Follow-Up Studies ,Genetic Pleiotropy ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Hypertension ,Microfilament Proteins ,Middle Aged ,Obesity ,Risk Factors ,Polymorphism, Single Nucleotide ,MESH: Genome-Wide Association Study ,Carotid Artery ,MESH: Female ,030217 neurology & neurosurgery ,epidemiology [Finland] ,Cervical Artery ,Vertebral artery dissection ,epidemiology [Hypertension] ,MESH: Hypertension ,MESH: Risk Factors ,MESH: Obesity ,Stroke ,Allele ,Dissection ,MESH: Finland ,MESH: Genetic Predisposition to Disease ,MESH: Hypercholesterolemia ,Single Nucleotide ,MESH: Migraine Disorders ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,epidemiology [Myocardial Infarction] ,[INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV] ,[SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing ,Population ,MESH: Genetic Pleiotropy ,physiology [Microfilament Proteins] ,Biology ,MESH: Microfilament Proteins ,Internal medicine ,ddc:570 ,medicine ,[INFO.INFO-IM]Computer Science [cs]/Medical Imaging ,030304 developmental biology ,epidemiology [Obesity] ,Risk Factor ,MESH: Alleles ,[INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV] ,Internal ,MESH: Odds Ratio ,MESH: Male ,epidemiology [Migraine Disorders] ,genetics [Microfilament Proteins] - Abstract
Item does not contain fulltext Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year). Minor cervical traumas, infection, migraine and hypertension are putative risk factors, and inverse associations with obesity and hypercholesterolemia are described. No confirmed genetic susceptibility factors have been identified using candidate gene approaches. We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69-0.82; P = 4.46 x 10(-10)), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 x 10(-3); combined P = 1.00 x 10(-11)). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.
- Published
- 2015
14. Metabolomic profiling in small vessel disease identifies multiple associations with disease severity
- Author
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Harshfield, Eric L, Sands, Caroline J, Tuladhar, Anil M, De Leeuw, Frank Erik, Lewis, Matthew R, and Markus, Hugh S
- Subjects
cognition ,small vessel disease ,Cerebral Small Vessel Diseases ,Leukoaraiosis ,Humans ,Dementia ,Prospective Studies ,metabolomics ,stroke ,Magnetic Resonance Imaging ,Severity of Illness Index ,3. Good health - Abstract
Cerebral small vessel disease is a major cause of vascular cognitive impairment and dementia. There are few treatments, largely reflecting limited understanding of the underlying pathophysiology. Metabolomics can be used to identify novel risk factors to better understand pathogenesis and to predict disease progression and severity. We analysed data from 624 patients with symptomatic cerebral small vessel disease from two prospective cohort studies. Serum samples were collected at baseline and patients underwent MRI scans and cognitive testing at regular intervals with up to 14 years of follow-up. Using ultra-performance liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy, we obtained metabolic and lipidomic profiles from 369 annotated metabolites and 54 764 unannotated features and examined their association with respect to disease severity, assessed using MRI small vessel disease markers, cognition and future risk of all-cause dementia. Our analysis identified 28 metabolites that were significantly associated with small vessel disease imaging markers and cognition. Decreased levels of multiple glycerophospholipids and sphingolipids were associated with increased small vessel disease load as evidenced by higher white matter hyperintensity volume, lower mean diffusivity normalized peak height, greater brain atrophy and impaired cognition. Higher levels of creatine, FA(18:2(OH)) and SM(d18:2/24:1) were associated with increased lacune count, higher white matter hyperintensity volume and impaired cognition. Lower baseline levels of carnitines and creatinine were associated with higher annualized change in peak width of skeletonized mean diffusivity, and 25 metabolites, including lipoprotein subclasses, amino acids and xenobiotics, were associated with future dementia incidence. Our results show multiple distinct metabolic signatures that are associated with imaging markers of small vessel disease, cognition and conversion to dementia. Further research should assess causality and the use of metabolomic screening to improve the ability to predict future disease severity and dementia risk in small vessel disease. The metabolomic profiles may also provide novel insights into disease pathogenesis and help identify novel treatment approaches.
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