Call for Projects 2017-1
The selected projects for the first “VasCog” Call for project in 2017 are:
Project led by Dr Nacim Betrouni (UMR1171)
DATAMICS : a bigdata approach for early detection of post-stroke cognitive disorders
For neurodegenerative diseases and considering the lack of efficient therapeutical strategy, early diagnosis of disorders is a crucial key point during the care pathway to propose preventive care. Imaging biomarkers, extracted from patients’ cohorts data studies, consist on promissing research domain.
In this study, with the hypothesis that the disease evolution can be characterized by imaging attributes extracted from image grey levels or “RadioMics”, we will explore the combination of such attributes with datamining methods to build efficient, non invasive and easily usable predictive models in clinical practice.
The method will be established on data extracted from the Lille STROKDEM patients cohorts and will focuse first on MRI data obtained 72 hours after stroke to detect patients most at risk of development of cognitive disorders. In a second time and with the use of Big Data analysis approach, the predictive model will be further completed with biological data or neurocognitive test results
On a longer term, this approach will be spread to data obtained from other cohorts with similar protocols such as PITCH and TABASCO cohorts.
Project led by Pr David DEVOS (UMR1171)
Potentiation of cognitive functions in healthy elderly by association of methylphenidate and cognitive training: Proof of concept study in order to develop a synergic symptomatic treatment for the vascular cognitive disorders
Currently, there is no available drug to treat the symptoms of vascular cognitive disorders that affect millions of people worldwide. There are several key treatments to control the vascular risks associated with the neurovascular and neurodegenerative pathological processes. Thus, an urgent need for efficacious symptomatic therapies is required to be associated with these etiopathogenic treatments, notably at the early stage of cognitive disorders preceding dementia. Methylphenidate is indicated at high dose (1 mg/kg/day) in children having attention deficit and hyperkinetic disorder (ADHD). At lower dose, it is considered as the best cognitive enhancer drug.
Numerous studies proved the acute efficacy in healthy young and aged population. However, there is no proof of efficacy with chronic administration, outside ADHD, and concerns remain about longterm cardiac and vascular risks in elderly and particularly in people with vascular risk factors. The demonstration of long-term efficacy of cognitive training is also lacking in neurological diseases. Moreover, the effect appears to be very limited at the very advanced stage of dementia, for which the neuronal plasticity is too reduced to expect a benefit of training.
Our hypothesis is that the association of cognitive training and low dose of methylphenidate, which both increase the neuronal plasticity, will be synergic to induce a significant improvement of cognitive function. We believe that the improvement will be powerful enough i) to have an impact on the daily living (such as driving) and to persist at long-term. Finally, short-term treatment would reduce the safety concerns.
We aim to proof the concept that low dose of methylphenidate associated with active cognitive training during 6 weeks can improve the cognitive function in healthy aged volunteers with a persistent effect at 3 months, in a monocentric randomised double blind placebo controlled clinical trial in 120 persons in 4 groups (i.e. cognitive training with and without methylphenidate vs placebo) in Lille.
The clinical demonstration of an improvement of cognitive functions through an enhanced neuronal plasticity in elderly (having higher capacity than patients with neurological diseases) will promote the development of this new paradigm of short-term symptomatic treatment with persistent effects for chronic vascular cognitive disorders.
We are in the position with all partners of the University/CHU of Lille to perform the clinical trial from the preparation of the drug and placebo to the safety monitoring. The healthy volunteers will be recruited at the Clinical Investigation Center of the CHU of Lille.
Project led by Elsa HEYMAN (EA 7369)
Exercise and cocoa flavanols in Type 1 diabetes: New therapeutic strategies to improve cognitive
functions – Implications of vascular function and cortical plasticity
Justification – In type 1 diabetes (T1D), chronic hyperglycemia leads to a number of health
complications, including negative impact on brain structure and function. Possible mechanisms through which hyperglycaemia causes damage to the brain are by increasing oxidative stress and reducing cerebral vasoreactivity to acute stimuli. Regular physical activity results in improvement of long-term glycemic control in T1D patients and has well known positive effects on cognitive functions in non-diabetic humans, possibly through the improvement of antioxidant defenses, vascular function, and the promotion of neuroplasticity through neurotrophins, like Brain Derived Neurotrophic Factor. Alongside physical activity, evidence is growing that nutritional interventions can also play a role in delaying the onset and progression of neurodegenerative diseases. For example, cocoa flavanols (from the group of polyphenols), which are powerful antioxidants able to boost nitric-oxide dependent vasodilatation, have been proved to stimulate neurogenesis and improve cognitive function in non-diabetic subjects. While patients with long-standing T1D are prone to the so-called Diabetes Associated Cognitive Decline, the specific protective effects of such non-pharmacological therapeutics (i.e. exercise training and flavanol-enriched diet) remain unstudied.
Scientific objectives – We aim at investigating the effects of novel and promising non
pharmacological therapeutics, i.e. 4-month intake of dark chocolate enriched in cocoa flavanols or 4- month aerobic exercise training, compared with 4-month placebo dark chocolate intake and no training, on performances in tasks involving memory & executive functions, in patients with uncomplicated T1D.
Perimeter and Research Teams involved – The current project will provide a proof-of-concept for the use of novel non-pharmacological therapeutics for improving cognitive performances in patients who are not yet suffering from overt cognitive impairments, but who are at high risk for long term mild cognitive decline. Pharmacological interventions may indeed have non-negligible side effects, which appear unacceptable when dealing with prevention. The challenge will also be to gain more insight into the possible mechanisms behind the putative positive brain adaptations by using functional (cortical vasoreactivity, non-invasive cortical Brain Stimulation induced plasticity, neural activity) and molecular (blood markers of NO bioavailibility, oxidative stress and neuroplasticity)
approaches. The close collaboration of scientists from various disciplines, i.e. exercise physiology (‘Physical activity, Muscle Health team’ from EA 7369, E. Heyman), endocrinology and nutrition (Department of Endocrinology, Pr. P. Fontaine), and clinical neurophysiology (EA 1046 Pr. P. Derambure, Pr. R. Bordet, Lille University Hospital) will be the key to the success of this integrative project. The flavanol-enriched and the placebo dark chocolates will be conceived and manufactured with our two industrial partners, Naturex and the Chocolate factory of Beussent-Lachelle (regional), which allows us to control all the steps of chocolate processing. In turn, the project results will help them to develop new products beneficial for health.