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Séminaire impromptu - Stéphanie DebetteGenetic and environmental risk factors for cerebrovascular disease and brain aging

Abstract :

Stroke and dementia are leading causes of death and disability. Improving our understanding of the risk factors and pathophysiological mechanisms underlying these disorders is essential for preventative strategies aiming at reducing the burden of these diseases at the individual and population level. I will be discussing various epidemiological approaches, using extensive clinical information, high throughput genotyping and quantitative imaging markers, to explore the risk factors for cerebrovascular disease and cognitive decline, both in a hospital-based and population-based setting. Findings related to MRI-markers of structural and vascular brain aging, to cerebral small vessel disease, an important but understudied cause of stroke and dementia, and to cervical artery dissection, a major cause of ischemic stroke in young adults, will be presented in greater detail. 

Selected publications

  1. Abdominal obesity is associated with lower gray matter volume: A Mendelian randomization study. Debette S, Wolf C, Lambert JC, Crivello F, Soumaré A, Zhu YC, Schilling S, Dufouil C, Mazoyer B, Amouyel P, Tzourio C, Elbaz A. Neurobiol Aging 2013, in press
     
  2. Common variants at 12q14 and 12q24 are associated with hippocampal volume. Bis JC, DeCarli C, Smith AV, van der Lijn F, Crivello F, Fornage M, Debette S, Shulman JM, Schmidt H, Srikanth V, Schuur M,  Yu L, Choi SH, Sigurdsson S, Verhaaren B, DeStefano AL, Lambert JC, Jack CR, Struchalin M, Stankovich J, Ibrahim-Verbaas CA, Fleischman D, Zijdenbos A, den Heijer T, Mazoyer B, Coker LH, Enzinger C, Danoy P, Amin N, Arfanakis K, van Buchem M, de Bruijn RFAG, Beiser A, Dufouil C, Huang J, Cavalieri M, Thomson R, Niessen WJ, Chibnik LB, Gislason GK, Hofman A, Pikula A, Amouyel P, Freeman KB, Phan TG, Oostra BA, Stein JL, Medland SE, Vasquez AA, Hibar DP, Wright MJ, Franke B, Martin NG,  Thompson PM, for the ENIGMA Consortium, Nalls M, Uitterlinden AG, Au R, Elbaz A, Beare RJ, van Swieten JC, Lopez O, Harris TB, Chouraki V, Breteler MMB, De Jager PL, Becker JT,, Vernooij MW, Knopman D, Fazekas F, Wolf PA, van der Lugt A, Gudnason V, Longstreth WTJr., Brown MA,  Bennett DA, van Duijn CM,  Mosley TH, Schmidt R, Tzourio C, Launer LJ, Ikram MA, Seshadri S.  Nat Genet. 2012; 44:545-51.
     
  3. Midlife vascular risk factor exposure accelerates structural brain aging and cognitive decline. Debette S, Seshadri S, Beiser A, Au R, Himali JJ, Palumbo C, Wolf PA, DeCarli C. Neurology. 2011; 77: 461-468
     
  4. ApoE and MRI-markers of cerebrovascular disease: A systematic review and meta-analysis. Schilling S, Seshadri S, Sachdev PS, DeStefano A, Mather K, Beiser A, Wen W, Hogh P, Raz N, DeCarli C, Zhu YC, Romero R, Lunetta KL, Farrer L, Dufouil C, Kuller LH, Mazoyer B, Tzourio C, Debette S. Neurology 2013; 81:292-300
     
  5. Large Vessel Correlates of Cerebral Small Vessel Disease. Brisset M, Boutouyrie P, Pico F, Zhu YC, Zureik M, Dufouil C, Mazoyer B, Laurent S, Tzourio C, Debette S. Neurology 2013; 80:662-669.
     
  6. Genome-Wide Association Studies of Cerebral White Matter Lesion Burden: the CHARGE Consortium. Fornage M, Debette S, Bis JC, Schmidt H, Ikram MA, Dufouil C, Sigurdsson S, Lumley T, Fazekas F, Vrooman H, Shibata D, DeStefano AL, Maillard P, Zijdenbos A, Smith A, De Boer R, Cushman M, Mazoyer B, Heiss G, Vernooij MW, Enzinger C, Glazer NL, Beiser A, Knopman D, Cavalieri M, Niessen W, Harris TB, Petrovik K, Lopez OL, Au R, Lambert JC, Hofman A, Gottesman R, Garcia M, Heckbert SR, Atwood L, Catellier D, Uitterlinden AG, Yang Q, Smith NL, Aspelund T, Romero JR, Rice K, Taylor KD, Nalls M, Rotter JI, Sharret R, van Duijn CM, Amouyel P, Wolf PA, Gudnason V, van der Lugt A, Boerwinkle E, Psaty BM, Seshadri S, Tzourio C, Breteler MMB, Mosley TH, Schmidt R, Longstreth WT, DeCarli C, Launer L. Ann Neurol, 2011; 69: 928-939.
     
  7. The Clinical Importance of White Matter Hyperintensities on Brain Magnetic Resonance Imaging: Systematic Review and Meta-analysis. Debette S & Markus HS. BMJ 2010; 341:c3666
  8. Association of Vascular Risk Factors With Cervical Artery Dissection and Ischemic Stroke in Young Adults. All starred first authors and last authors contributed equally to this manuscript. Debette S, Metso T, Pezzini A, Abboud S, Metso A, Leys D, Bersano A, Louillet F, Caso V, Lamy C, Medeiros E, Samson Y, Grond-Ginsbach C, Engelter ST, Thijs V, Beretta S, Béjot Y, Sessa M, Muiesan ML, Amouyel P, Castellano M, Arveiler D, Tatlisumak T, Dallongeville J, for the CADISP Group. Circulation, 2011; 123: 1537-1544.
     
  9. Differential features of carotid and vertebral artery dissection. Debette S, Grond-Ginsbach C, Bodenant M, Kloss M, Engelter S, Metso T, Pezzini A, Brandt T, Caso V, Touzé E, Metso A, Canaple S, Abboud S, Giacalone G, Lyrer P, del Zotto E, Giroud M, Samson Y, Dallongeville J, Tatlisumak T, Leys D, Martin JJ, for the CADISP group. Neurology. 2011; 77: 1174-1181
     
  10. CADISP-genetics: an International project searching for genetic risk factors of cervical artery dissections. Debette S, Metso TM, Pezzini A, Engelter ST, Leys D, Lyrer P, Metso AJ, Brandt T, Kloss M, Lichy C,  Hausser I, Touzé E, Markus HS, Abboud S, Caso V, Bersano A, Grau A, Altintas A, Amouyel P, Tatlisumak T, Dallongeville J, Grond-Ginsbach C, on behalf of the CADISP-group. Int J Stroke. 2009; 4:224–230.
     
  11. Cervical Artery Dissections: Predisposing Factors, Diagnosis and Outcome. Debette S, Leys D. Lancet Neurol. 2009; 8:668-678. 

Focus


Stéphanie Debette

MCU-PH, Epidémiologie et Neurologie, Hôpital Lariboisière et Inserm U740, Université Paris 7, DHU Neurovasc Sorbonne Paris-Cité, Paris, France

Chaire d’Excellence ANR Université de Versailles St Quentin en Yvelines - Inserm U708

Adjunct Associate Professor, Department of Neurology, Boston University School of Medicine, the Framingham Heart Study, Boston, USA