2017 Call for Projects-2

2017 Call for Projects-2

CONNECTOME-BASED ANALYSIS OF BRAIN ORGANIZATION IN LONG TERM COGNITIVE DISORDERS AFTER STROKE – COBALTS

Project led by Dr Renaud Lopes (UMR s 1171, Inserm, Lille University, Lille University Hospital)

Scientific objectives

COBALTS concerns the study of mechanisms induced by acute infarct and small vessel disease (SVD) lesions on the long-term cognitive decline on a cohort of patients free of dementia when admitted for a first stroke and with their followed-up over a 3-year period. Network-based features from DTI will be developed to assess the contribution of SVD lesions on the prediction of long-term cognitive decline after stroke.

Justification

Cognitive impairment occurs frequently in post-stroke patients, with a prevalence ranges from 20% to 80% depending on the diagnostic criteria of post-stroke cognitive impairment (PSCI). Ischemic stroke and pre-existing brain vulnerability such as SVD contribute to the pathogenesis of PSCI, but the underlying mechanisms related to PSCI are not known. The measures commonly used to assess the impact of lesions on the cognitive decline, such as ischemic volume and Fazekas score, do not correlate well with global cognitive decline due to the strict brain spatial network organization. In this project, we assume that specific disconnections of distant regions, secondary to white matter tracts lesions, may alter brain networks responsible for long-term global cognitive decline.

Perimeter

The efficiency of network-based features from DTI in the prediction of long-term cognitive decline will be evaluated in relation to clinical and neuropsychological data of stroke patients. Thus, several medical departments will be involved in this multidisciplinary project.

The funding of 6-month trainee will allow:

  • DTI post-processing
  • Structural connectivity analysis
  • Evaluation of network disruption according to the importance of SVD biomarkers.

Cognitive and histology consequences of disseminated brain microbleeds

Project led by Pr Vincent Berezowsky (UMR-1171)

This sexperimental research project has the objective to clarify the status of silent disseminated brain microbleeds.

It aim to test the capacity of microbleeds to induce on healthy mice, a long term cognitive decline (12 months timeline, behavior impairments) and/or induce a neurvascular fragility (cell suffering biomarkers or microvessels hemostatic regulation). To know how microlesions and impaired vessels evolute could allow a better understanding of the link with cognitive decline but also the test of the effects of some drugs such as oral direct anticoagulants, which the use is currently under discussion in patients with brain stroke risks or presenting brain microbleeds.

This project is handle exclusively by the drug research departement of the UMR1171 which has set up a unique method to induce brain microbleeds in mice.

This project is justified by the biological and exploratory aspect of this non-investigated topic which requires numerous ressources (immunohistochemistery) and the access to a live animal imaging platform, available in Lille. to answer this crucial neurological question will open new insights of disease modifier therapeutica targets or novel diagnosis biomarkers.

Role of insuline resistance in the cognitive disorders of patients with myotonic dystrophy type 1

Project led by Dr Céline Tard (CHU Lille, UMRS1171)

Objectives :

The principal objective of the project is to demonstrate that in patients with myotonic dystrophy type 1, resistance to insuline is associated or not with a rapid progression of cognitive disorders. Secondary objectives are (i) to better characterize the cognitive disorders and their profile function of the onset of diabetes (ii) to evaluate if the cognitive disorders mechanisms is linked or not with the development of a tauopathy.

Justification :

Cognitive impairments in adult forms of myotonic dystrophy are very heterogeneous. Impairements of executive functions , visuo-spacial functions or the theory of mind are usually described and can progress into dementia. However, patients are affected at different degree. In myotonic dystrophy type 1 (the most frequent form), patients exhibits expansions of the CTG triplicate which impair the alternative mRNA splicing of various proteins, including the receptor to insuline and the Tau protein. Therefore, patients have a risk to develop resistance to insuline and diabetes. Regarding brain histology, some Tau protein deposition and neurofibrillary degenerations have been described.  They are therefore a model of genetic susceptibility to develop a Tauopathy, with potential amplification by resistance to insuline.  The project hypothesis is that cognitive disorders are more accute (earlier and more severe) in patient with resistance to insuline inside the myotonic dystrophy group of patients. By investigating the disorders progression in this specific population, we could set up a study model of interactions between resistance to insuline/diabetes and tauopathy onset.

Perimeter :

Parameter of interest will combine data on cognitive evaluation, conventionnal and non conventionnal MRI, Tau specific PET scan and lumbar punction for cerebrospinal fluid biomarkers.