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Vascular and degenerative risk factors for cognitive impairment

The main topic of this team is the study of pathophysiology and pharmacology of vascular and degenerative cognitive disorders and dementia with an emphasis on mixed dementia that is the pathological model allowing to understand the vascular mechanisms of neurodegeneration and to assess the interest of their pharmacological modulation. We have a long-term expertise of cohort-based studies showing the involvement of brain vascular lesions (stroke, white matter lesion, microbleeds) in vascular or degenerative cognitive disorders as well as pharmacology of neuroprotection and cerebral plasticity in vascular or degenerative brain disorders and their consequences. The project is divided into three scientific programs:
  • Modelisation and pathophysiology of vascular cognitive disorders: the occurrence of stroke is associated with development of cognitive disorders or dementia with mixed vascular and degenerative mechanisms. These cognitive consequences can occur de novo or on pre-existing cognitive disorders or dementia. To better understand interactions between vascular and degenerative mechanisms, we study in both preclinically (in vivo models) and clinically (cohort studies) the long term consequences of stroke with different methodological approaches: behavior assessment, electrophysiology, imaging, neuropathology and histology, cellular and molecular biology.
  • Vascular risk factors, brain hypoxia and neurodegeneration : Vascular and metabolic risk factors are associated with a faster cognitive decline during Alzheimer disease and other dementia. This effect could result from several interactions with evolution of neurodegeneration and its consequences: (i) induction of additional lesions; (ii) interaction with specific pathophysiological patways (such amyloid cascade) ; loss of cognitive compensatory mechanism. Moreover drugs or lifestyle changes (physical activity, nutrition) treating these metabolic and vascular risk factors could have a disease-modifier effect supporting the deleterious effect of these risk factors. We explore this hypothesis with an emphasis on the role of the brain hypoxia resulting from endothelial dysfunction associated to risk factors.
  • New pharmacological targets for degenerative and vascular cognitive disorders: The aim of this part of the project is to identify new pharmacological targets or better understand the effect of already marketed drugs to improve both symptomatic (cognitive and behavioral impairment) and disease-modifier treatment (neuroprotection, brain plasticity). We explore several targets such as sigma-1 receptor, nuclear receptors (in particular PPAR) or metal chelation.

The team 'Alzheimer's disease and vascular pathologies' involves neurologist, pharmacologists, scientific, imaging specialists to develop this project with dual preclinical and clinical approaches. In a methodological point of view, the team has expertise in:

  • Animal model
  • Cohort-based or interventional clinical studies
  • Preclinical and clinical MRI and Pet-scan
  • Behavioral and cognitive assessment
  • Preclinical and clinical pharmacology
  • Electrophysiology (patch-clamp, EEG)
  • Histology and neuropathology
  • Cellular and molecular tools (immunohistochemistry, western-blot, Q-PCR)

 

Laboratory's name
Vascular and degenerative risk factors for cognitive impairment
Head of the lab
Régis Bordet
Contact DN2M
Régis Bordet
Email
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Telephone
+33 3 20 44 54 59
Address
Departement de Pharmacologie Médicale – Faculté de médecine
Pôle Recherche – CHRU Lille  – 1, Place Verdun – 59045 Lille Cedex