Degenerative and vascular cognitive discorders

Presentation

This team, made up of clinical and pre-clinical researchers, is multidisciplinary. It is located at the interface between neurology, pharmacology and imaging. The research project is focused on the translational, transnosographic and multimodal study of cognitive disorders associated with degenerative processes or neurovascular lesions, starting from the observation that the mechanisms are entangled.

NEWS

PRESS

Covid-19
A smartphone test with almost immediate results, designed in Lille and Marseille

VIDEO

  • STAFF
  • RESEARCH INTEREST
  • PROJECT TEAM
  • PUBLICATIONS

Associate Professors/Professors – University-Associated

Pr Régis Bordet
MD, Ph.D., Hospital Practitioner.
University of Lille, Faculty of Medicine.

Pr. Etienne Allard, PH
Dr. Michèle Bastide,  MCF
Dr. Karim Belarbi,  MCF
Pr. Vincent Berezowski,  PR
Dr. Maxime Bertoux,  CR Inserm
Dr. Nacim Betrouni,  CR Inserm
Dr. Muriel Boucart,  DR CNRS
Pr. Yaohua Chen,  PH
Pr. Charlotte Cordonnier,  PU-PH
Pr. Luc Defebvre,  PU-PH
Dr. Julie Deguil,  MCF
Dr.Xavier Delbeucke, MD.
Neuropsychologue
Pr. Christine Delmaire,  PH
Pr. Arnaud Delval,  PU-PH
Pr. Dominique Deplanque,  PU-PH
Pr. Philippe Derambure,  MD, PU-PH
Dr. Jean-Christophe Devedjian, MCF

Pr. David Devos, PU-PH

Pr. Kathy Dujardin, PR
Pr. Patrick Duriez,  PR
Dr. Sophie Gautier,  MCU-PH
Pr. Ilde Hénon,  PH
Dr. Grégory Kuchcinski  MCU-PH
Pr. Xavier Leclerc,  PU-PH

Dr. Quentin Lenoble,  MCF


Pr. Didier Leys,   PU-PH
Pr. Marie-Anne Mackowiak,   PH
Pr. Thomas Modine,  PH
Pr. Christelle Monaca,  PU-PH
Dr. Caroline Moreau,  PU-PH
Dr. Thavarak Ouk,   MCU-PH
Pr. Olivier Outteryck,  PH
Pr. Florence Pasquier,  PU-PH
Dr. Olivier Petrault,  MCF
Pr. Jean-Pierre Pruvo,  PU-PH
Pr. Jean-François Rouland,  PU-PH
Pr. Franck Semah,  PU-PH
Pr. Céline Tard,  PH
Pr. Thi Ha Chau Tran,  PH


Research support staff

Anne-Marie Bordet,  ARC, CHU Lille
Laetitia Breuilh,  ARC, CHU Lille
Marion Buchet,  Admin, CHU Lille
Thibaut Dondaine, IH, CHU Lille
Flore Gouel, IH, CHU Lille
Aurélie Jonneaux, ITA, CHU Lille
Charlotte Laloux,  IR, ULille
Renaud Lopes, IH, CHU Lille
Maud Pétrault, AI, ULille
Elodie Ringot, Admin, CHU Lille
Valerie Santraine, ARC, CHU Lille
Christian Sueur, AJT, ULille
Kelly Timmerman,  AI, CDD
Romain Viard, IH, CDD
Aude Warniez, IR, ULille


Post-Doctorants

Dr. Romain Barus, PharmD. PhD
Dr. Sandrine Bergeron, PharmD. PhD
Dr. Cécile Bordier, PhD

Dr. François Quesque, PhD

Dr. Anne-Sophie Rolland, PhD


Doctoral students

Valentin Bachet

Marie-Amandine Bonte

Hind Bouchaoui

Martin Bretzner

Guillaume Carey

Louise Carton

Jean-Baptiste Davion

Véronique De Conto

Delila Liling

Quentin Devignes

Chirine El Katrib

Clémentine Garric

 

Morgan Gautherot

 

Sabine Krohn

Laura Mahoney Sanchez

 

Sandra Mouchref

Marco Pasi

Laurent Puy

Quentin Vannod

Laurent Zikos

Scientific and medical context

The general scientific objective of the team is to contribute to the societal challenge of cognitive disorders, linked to neurological and mental illnesses. Indeed, the number of people with cognitive decline will double in the next 25 years, due to the increase in life expectancy. This significant increase in the prevalence of cognitive disorders is certainly linked to Alzheimer's disease (AD) but also to neurovascular pathologies and other neurodegenerative pathologies. Vascular and metabolic risk factors themselves contribute to the emergence of cognitive disorders, either directly or through their role in the constitution of silent brain lesions or their interaction with the pathophysiology of neurodegenerative or neurovascular diseases. The societal, family and medico-economic consequences will be significant, leading some to speak of a "tsunami of health care".

 

An original positioning at the clinical-imaging-pharmacology interface

This field is complex due to the intricacies and requires a multidisciplinary approach, which the team brings given its composition and the results it has already generated on the interactions between degenerative lesions and vascular lesions, on those between cognitive and psychobehavioral signs (especially motor and emotional), on the pathophysiological role of ferroptosis or dysconnectivity, and on the advances in pharmacological development, both symptomatic and 'disease-modifying. The aim is to propose, by an original approach combining clinical-imaging-pharmacology :

 

  1. a new model for the organization of the management of cognitive disorders, free from the current nosographic frameworks by identifying common physiopathological processes;
  2. a use of biomarkers and algorithms for a better diagnostic typology and an optimization of pharmacological development;
  3. inclusion in the field of human and social sciences by reflecting on what these cognitive disorders represent at the individual and social levels.

A multimodal and multidisciplinary approach :

 To meet the general scientific objective and its medical or social purposes, the project will be broken down into three axes, with for each axis specific questions developed by project-teams and a multimodal methodological approach:

 

  1. pre-clinical and clinical modeling of degenerative and vascular cognitive disorders;
  2. the study of the pathophysiological bases of degenerative and vascular cognitive   disorders;
  3. the development of innovative pharmacological strategies.


Leader Nacim Betrouni

NeuroRadioMics: Markers of Neurodegeneration and big data modelling


Leader Karim Belarbi
Neurodegeneration, neuroinflammation and cognition

Leader Caroline Moreau

Axial symptoms : biomakers for neurodegenerative diseases


Leader Kathy Dujardin

Cognitive and behavioral disorders associated with Parkinson’s disease


Leader Michèle Bastide
Metabolic disorders and cognition

Leader Muriel Boucart
Visual cognition

Leader Renaud Lopes

Multimodal imaging and network analysis of neurological disorders


Leader David Devos
New therapeutic concepts of cerebral addressing ("Brain infusion")

Leader Jean-Christophe Devedjian
Ferroptosis and neuronal death: Molecular and pharmacological mechanisms, evaluation of therapeutic strategies

Leader Régis Bordet
Cognitive disorders post ischemic stroke: prediction, evaluation, pharmacological approach

Leader Maxime Bertoux
Social & affective cognition in neurodegenerative diseases: study of cognitive architecture, harmonization of concepts, improvement of clinical evaluation, identification of anatomical markers of dysfunction, cultural differences and consideration of social, economic and educational variability.

Publications

2020

Hong S, Prokopenko D, Dobricic V, Kilpert F, Bos I, Vos SJB, Tijms BM, Andreasson U, Blennow K, Vandenberghe R, Cleynen I, Gabel S, Schaeverbeke J, Scheltens P, Teunissen CE, Niemantsverdriet E, Engelborghs S, Frisoni G, Blin O, Richardson JC, Bordet R, Molinuevo JL, Rami L, Alzheimer’s Disease Neuroimaging Initiative (ADNI), Kettunen P, Wallin A, Lleó A, Sala I, Popp J, Peyratout G, Martinez-Lage P, Tainta M, Dobson RJB, Legido-Quigley C, Sleegers K, Van Broeckhoven C, Ten Kate M, Barkhof F, Zetterberg H, Lovestone S, Streffer J, Wittig M, Franke A, Tanzi RE, Visser PJ, Bertram L . Genome-wide association study of Alzheimer's disease CSF biomarkers in the EMIF-AD Multimodal Biomarker. Discovery dataset. Transl Psychiatry. 2020 Nov 22;10(1):403. doi: 10.1038/s41398-020-01074-z. PMID: 33223526.

Ribaldi F, Altomare D, Jovicich J, Ferrari C, Picco A, Pizzini FB, Soricelli A, Mega A, Ferretti A, Drevelegas A, Bosch B, Müller BW, Marra C, Cavaliere C, Bartrés-Faz D, Nobili F, Alessandrini F, Barkhof F, Gros-Dagnac H, Ranjeva JP, Wiltfang J, Kuijer J, Sein J, Hoffmann KT, Roccatagliata L, Parnetti L, Tsolaki M, Constantinidis M, Aiello M, Salvatore M, Montalti M, Caulo M, Didic M, Bargallo N, Blin O, Rossini P, Schonknecht P, Floridi P, Payoux P, Visser PJ,Bordet R, Lopes R, Tarducci R, Bombois S, Hensch T, Fiedler U, Richardson JC, Frisoni GB, Marizzoni M. Accuracy and reproducibility of automated white matter hyperintensities segmentation with lesion segmentation tool: A European multi-site 3T study. Magn Reson Imaging. 2020 Nov 18:S0730-725X(20)30643-3. doi: 10.1016/j.mri.2020.11.008. Epub ahead of print. PMID: 33220450.

Shi L, Winchester LM, Liu BY, Killick R, Ribe EM, Westwood S, Baird AL, Buckley NJ, Hong S, Dobricic V, Kilpert F, Franke A, Kiddle S, Sattlecker M, Dobson R, Cuadrado A, Hye A, Ashton NJ, Morgan AR, Bos I, Vos SJB, Ten Kate M, Scheltens P, Vandenberghe R, Gabel S, Meersmans K, Engelborghs S, De Roeck EE, Sleegers K, Frisoni GB, Blin O, Richardson JC, Bordet R, Molinuevo JL, Rami L, Wallin A, Kettunen P, Tsolaki M, Verhey F, Lleó A, Alcolea D, Popp J, Peyratout G, Martinez-Lage P, Tainta M, Johannsen P, Teunissen CE, Freund-Levi Y, Frölich L, Legido-Quigley C, Barkhof F, Blennow K, Rasmussen KL, Nordestgaard BG, Frikke-Schmidt R, Nielsen SF, Soininen H, Vellas B, Kloszewska I, Mecocci P, Zetterberg H, Morgan BP, Streffer J, Visser PJ, Bertram L, Nevado-Holgado AJ,Lovestone S. Dickkopf-1 Overexpression in vitro Nominates Candidate Blood Biomarkers Relating to Alzheimer's Disease Pathology. J Alzheimers Dis. 2020;77(3):1353-1368. doi: 10.3233/JAD-200208. PMID: 32831200.

Ba K, Casolla B, Caparros F, Bricout N, Della Schiava L, Pasi M, Dequatre-Ponchelle N, Bodenant M, Bordet R, Cordonnier C, Hénon H, Leys D. Early epileptic seizures in ischaemic stroke treated by mechanical thrombectomy:influence of rt-PA. J Neurol. 2020 Aug 14. doi: 10.1007/s00415-020-10155-4. Epub ahead of print. PMID: 32797298.

Lombardo D, Cassé-Perrot C, Ranjeva JP, Le Troter A, Guye M, Wirsich J, Payoux P, Bartrés-Faz D, Bordet R, Richardson JC, Felician O, Jirsa V, Blin O, Didic M, Battaglia D. Modular slowing of resting-state dynamic functional connectivity as a marker of cognitive dysfunction induced by sleep deprivation. Neuroimage. 2020 Jul 29;222:117155. doi: 10.1016/j.neuroimage.2020.117155. Epub ahead of print. PMID: 32736002.

Bordet R, Deplanque D. Brain-liver axis: a new pathway for cognitive disorders related to hepatic fibrosis. Eur J Neurol. 2020 Jul 28. doi: 10.1111/ene.14454. Epub ahead of print. PMID: 32725648.

Tang EYH, Price CI, Robinson L, Exley C, Desmond DW, Köhler S, Staals J, Yin Ka Lam B, Wong A, Mok V, Bordet R, Bordet AM, Dondaine T, Lo JW, Sachdev PS, Stephan BCM; STROKOG Collaboration. Assessing the Predictive Validity of Simple Dementia Risk Models in Harmonized Stroke Cohorts. Stroke. 2020 Jul;51(7):2095-2102. doi: 10.1161/STROKEAHA.120.027473. Epub 2020 Jun 17. PMID:32568644; PMCID: PMC7306263.

Bordet R. Is the drug a scientific, social or political object? Therapie. 2020 Jul-Aug;75(4):389-391. doi: 10.1016/j.therap.2020.05.012. Epub 2020 May 23. PMID: 32482295; PMCID: PMC7244431.

Barus R, Bergeron S, Auger F, Laloux C, Skrobala E, Bongiovanni A, Potey C, Bordet R, Chen Y, Gautier S. Sex Differences in Cognitive Impairment Induced by Cerebral Microhemorrhage. Transl Stroke Res. 2020 May 21. doi:10.1007/s12975-020-00820-1. Epub ahead of print. PMID: 32440818.

Quattrini G, Pievani M, Jovicich J, Aiello M, Bargalló N, Barkhof F, Bartres-Faz D, Beltramello A, Pizzini FB, Blin O, Bordet R, Caulo M, Constantinides M, Didic M, Drevelegas A, Ferretti A, Fiedler U, Floridi P, Gros-Dagnac H, Hensch T, Hoffmann KT, Kuijer JP, Lopes R, Marra C, Müller BW, NobiliF, Parnetti L, Payoux P, Picco A, Ranjeva JP, Roccatagliata L, Rossini PM, Salvatore M, Schonknecht P, Schott BH, Sein J, Soricelli A, Tarducci R, TsolakiM, Visser PJ, Wiltfang J, Richardson JC, Frisoni GB, Marizzoni M; PharmaCog Consortium. Amygdalar nuclei and hippocampal subfields on MRI: Test-retest reliability of automated volumetry across different MRI sites and vendors. Neuroimage. 2020 Sep;218:116932. doi: 10.1016/j.neuroimage.2020.116932. Epub 2020 May 13. PMID: 32416226.

Lo JW, Crawford JD, Samaras K, Desmond DW, Köhler S, Staals J, Verhey FRJ, Bae HJ, Lee KJ, Kim BJ, Bordet R, Cordonnier C, Dondaine T, Mendyk AM, Lee BC, Yu KH, Lim JS, Kandiah N, Chander RJ, Yatawara C, Lipnicki DM, Sachdev PS; STROKOG Collaboration*. Association of Prediabetes and Type 2 Diabetes With Cognitive Function After Stroke: A STROKOG Collaboration Study. Stroke. 2020 Jun;51(6):1640-1646. doi: 10.1161/STROKEAHA.119.028428. Epub 2020 May 14. PMID:32404039.

Larrouquere L, Gabin M, Poingt E, Mouffak A, Hlavaty A, Lepelley M, Khouri C, Bellier A, Alexandre J, Bedouch P, Bertoletti L, Bordet R, Bouhanick B, Jonville-Bera AP, Laporte S, Le Jeunne C, Letinier L, Micallef J, Naudet F, Roustit M, Molimard M, Richard V, Cracowski JL. Genesis of an emergency public drug information website by the French Society of Pharmacology and Therapeutics during the COVID-19 pandemic. Fundam Clin Pharmacol. 2020 Jun;34(3):389-396. doi: 10.1111/fcp.12564. PMID: 32394481; PMCID: PMC7273039.

Chan Kwong A, Cassé-Perrot C, Costes-Salon MC, Jouve E, Lanteaume L, Audebert C, Rouby F, Lefebvre MN, Ranjeva JP, Beck A, Deplanque D, Ponchel A, Vervueren C, Truillet R, Babilon C, Auffret A, Richardson JC, Payoux P, Bartrés-Faz D, Blin O, Bordet R, Micallef J; Pharmacog Consortium. An Alzheimer Disease Challenge Model: 24-Hour Sleep Deprivation in Healthy Volunteers, Impact on Working Memory, and Reversal Effect of Pharmacological Intervention: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study. J Clin Psychopharmacol. 2020 May/Jun;40(3):222-230. doi: 10.1097/JCP.0000000000001199. PMID: 32332458.

Moreau C, Rolland AS, Pioli E, Li Q, Odou P, Barthelemy C, Lannoy D, Demailly A, Carta N, Deramecourt V, Auger F, Kuchcinski G, Laloux C, Defebvre L, Bordet R, Duce J, Devedjian JC, Bezard E, Fisichella M, Devos D. Intraventricular dopamine infusion alleviates motor symptoms in a primate model of Parkinson's disease. Neurobiol Dis. 2020 Jun;139:104846. doi:10.1016/j.nbd.2020.104846. Epub 2020 Mar 20. PMID: 32205254.

Maestrini I, Tagzirt M, Gautier S, Dupont A, Mendyk AM, Susen S, Tailleux A, Vallez E, Staels B, Cordonnier C, Leys D, Bordet R. Analysis of the association of MPO and MMP-9 with stroke severity and outcome: Cohort study. Neurology. 2020 Jul 7;95(1):e97-e108. doi: 10.1212/WNL.0000000000009179. Epub 2020 Feb 28. PMID:32111692.

French Association of Addictovigilance Centres, Micallef J, Mallaret M, Lapeyre-Mestre M, Daveluy A, Victorri-Vigneau C, Peyrière H, Debruyne D, DeheulS, Bordet R, Chevallier C, Perault-Pochat MC, Le Boisselier R, Libert F, Chaouachi L, Gillet P. Warning on increased serious health complications related to non-medical use of nitrous oxide. Therapie. 2020 Jan 17:S0040-5957(20)30005-6. French. doi: 10.1016/j.therap.2020.01.002. Epub ahead of print. PMID: 32063400.

Marizzoni M, Ferrari C, Babiloni C, Albani D, Barkhof F, Cavaliere L, Didic M, Forloni G, Fusco F, Galluzzi S, Hensch T, Jovicich J, Marra C, Molinuevo JL, Nobili F, Parnetti L, Payoux P, Ranjeva JP, Ribaldi F, Rolandi E, Rossini PM, Salvatore M, Soricelli A, Tsolaki M, Visser PJ, Wiltfang J, Richardson JC, Bordet R, Blin O, Frisoni GB. CSF cutoffs for MCI due to AD depend on APOEε4 carrier status. Neurobiol Aging. 2020 May;89:55-62. doi: 10.1016/j.neurobiolaging.2019.12.019. Epub 2019 Dec 30. PMID: 32029236.

Westwood S, Baird AL, Anand SN, Nevado-Holgado AJ, Kormilitzin A, Shi L, Hye A, Ashton NJ, Morgan AR, Bos I, Vos SJB, Baker S, Buckley NJ, Ten Kate M, Scheltens P, Teunissen CE, Vandenberghe R, Gabel S, Meersmans K, Engelborghs S, De Roeck EE, Sleegers K, Frisoni GB, Blin O, Richardson JC, Bordet R, Molinuevo JL, Rami L, Wallin A, Kettunen P, Tsolaki M, Verhey F, Lléo A, Sala I, Popp J, Peyratout G, Martinez-Lage P, Tainta M, Johannsen P, Freund-Levi Y, Frölich L, Dobricic V, Legido-Quigley C, Bertram L, Barkhof F, Zetterberg H, Morgan BP, Streffer J, Visser PJ, Lovestone S. Validation of Plasma Proteomic Biomarkers Relating to Brain Amyloid Burden in the EMIF-Alzheimer's Disease Multimodal Biomarker Discovery Cohort. J Alzheimers Dis. 2020;74(1):213-225. doi: 10.3233/JAD-190434. PMID: 31985466; PMCID: PMC7175945.

Stamate D, Kim M, Proitsi P, Westwood S, Baird A, Nevado-Holgado A, Hye A, Bos I, Vos SJB, Vandenberghe R, Teunissen CE, Kate MT, Scheltens P, Gabel S, Meersmans K, Blin O, Richardson J, De Roeck E, Engelborghs S, Sleegers K, Bordet R, Ramit L, Kettunen P, Tsolaki M, Verhey F, Alcolea D, Lléo A, Peyratout G, Tainta M, Johannsen P, Freund-Levi Y, Frölich L, Dobricic V, Frisoni GB, Molinuevo JL, Wallin A, Popp J, Martinez-Lage P, Bertram L, Blennow K, Zetterberg H, Streffer J, Visser PJ, Lovestone S, Legido-Quigley C. A metabolite-based machine learning approach to diagnose Alzheimer-type dementia in blood: Results from the European Medical Information Framework for Alzheimer disease biomarker discovery cohort. Alzheimers Dement (N Y). 2019 Dec 18;5:933-938. doi: 10.1016/j.trci.2019.11.001. PMID: 31890857; PMCID:PMC6928349.

Drelon A, Kuchcinski G, Caparros F, Dequatre-Ponchelle N, Moulin S, Cordonnier C, Bordet R, Pruvo JP, Leys D. Remote brain hemorrhage after IV thrombolysis: Role of preexisting lesions. Neurology. 2020 Mar 3;94(9):e961-e967. doi: 10.1212/WNL.0000000000008874. Epub 2019 Dec 27. PMID:31882531.

Lebouvier T, Chen Y, Duriez P, Pasquier F, Bordet R. Antihypertensive agents in Alzheimer's disease: beyond vascular protection. Expert Rev Neurother. 2020 Feb;20(2):175-187. doi: 10.1080/14737175.2020.1708195. Epub 2019 Dec 27. PMID:31869274.

Bordet R, Camu W, De Seze J, Laplaud DA, Ouallet JC, Thouvenot E. Mechanism of action of s1p receptor modulators in multiple sclerosis: The double requirement. Rev Neurol (Paris). 2020 Jan-Feb;176(1-2):100-112. doi:10.1016/j.neurol.2019.02.007. Epub 2019 Nov 19. PMID: 31757428.

Lo JW, Crawford JD, Desmond DW, Godefroy O, Jokinen H, Mahinrad S, Bae HJ, Lim JS, Köhler S, Douven E, Staals J, Chen C, Xu X, Chong EJ, Akinyemi RO, Kalaria RN, Ogunniyi A, Barbay M, Roussel M, Lee BC, Srikanth VK, Moran C, Kandiah N, Chander RJ, Sabayan B, Jukema JW, Melkas S, Erkinjuntti T, Brodaty H, Bordet R, Bombois S, Hénon H, Lipnicki DM, Kochan NA, Sachdev PS; Stroke and Cognition (STROKOG) Collaboration. Profile of and risk factors for poststroke cognitive impairment in diverse ethnoregional groups. Neurology. 2019 Dec 10;93(24):e2257-e2271. doi: 10.1212/WNL.0000000000008612. Epub 2019 Nov 11. PMID: 31712368; PMCID: PMC6937495.

Betrouni N, Yasmina M, Bombois S, Pétrault M, Dondaine T, Lachaud C, Laloux C, Mendyk AM, Henon H, Bordet R. Texture Features of Magnetic Resonance Images: an Early Marker of Post-stroke Cognitive Impairment. Transl Stroke Res. 2020 Aug;11(4):643-652. doi: 10.1007/s12975-019-00746-3. Epub 2019 Nov 1. PMID:31677092.