Health care organisation
The healthcare objective of the VasCog FHU teams was to foster a multidisciplinary and translational research environment which would benefit to clinical routine healthcare pathways, and allows setting of large cohorts of patients, major academic and industrial trials.
Stroke-associated cognitive disorders (CDs)
- To improve prediction of Post-stroke CDs, a novel MRI tool so-called radiomics (with patent submission; VasCog Funded project) was developed and several biological markers were identified with Firalis SA. Combination of both should allow CI prediction with a predictive index of 0.95 (Prospective validation study planned).
- Other symptomatic indicators such as fatigue and anxiety were also identified in the context of stroke-associated CI. These symptoms are now well taken into account in a global management of stroke patient to decrease the symptomatic burden (Ponchel et al, 2016 and 2017).
- As secondary prevention was found to decrease post-stroke CI, the CEOPS multicentre clinical trial is currently conducted to assess the impact to involve a referent nurse and a patient’s caregiver from social circle in a nurse-led multimodal and long-term management of the risk factors after stroke, with 15 French centres, 290 (of 410 planned) patients included (Mendyk et al, 2017).
- To further limit brain injury contributing to post-stroke CI, optimisation of recanalization through pharmacological thrombolysis and more recently through thrombectomy was developed since recanalization is the most critical step during the acute phase of stroke.
- In the context of the ClinMine project (supported by the French ARS) and in partnership with Inria and Alicante company, a bioinformatic tool was developed to improve patient stratification from hospital database (demographic data, clinical symptoms and evolution, biological or genomic information, physiological and imaging parameters). This will allow better clustering of patients and more personalized treatments (Dhaenens et al, 2017)
Populations at high risk of cognitive deficit: diabetic patients
- To test the relevance of a specific clinical care pathway between the department of diabetology and the memory clinic at the Lille University Hospital, the frequency of cognitive impairment in diabetes patients and the profiles of these patients at risk for CDs were determined. From November 2015 to March 2016, a prospective study (Pr Vambergue and Dr Bombois) was conducted to evaluate the global cognitive functions of 191 diabetes patients, using the Montreal Cognitive Assessment (MOCA) test. Results showed that 35% of the tested patients had CI with a MOCA score < 26 points. Those patients were significantly older and had strong co-morbidities including history of stroke (paper under submission). These results had immediate repercussions in the care management of these diabetes patients since the systematic testing of patient cognition helped clinicians to early detect CDs and to correctly adapt the anti-diabetic therapies in this population at high risk of poor diabetes control.
This study has allowed close collaboration between diabetologists and specialists of the memory clinic, and a general reorganization of the diabetes patient’s care pathway at the Lille University Hospital is under progress. Moreover, a second cohort of diabetic patients (DiaboloCog study) is under investigation to characterize the pathophysiological pathway of CDs in this population, using a multimodal approach based on cognitive evaluation, biological sampling, imaging, high resolution EEG and biomarkers for neurodegenerative diseases (VasCog funded project, Pr Vambergue).
Despite detection of CI, more than 1/3 of the diabetic patients didn’t come to the referred memory consultation. The possible reasons were the severity of the CI, the old age, the over-numerous medical visits and severe co-morbidities of the patients as well as the lack of information on the objectives of the memory consultation. We therefore consider the set-up of an advanced memory consultation within the department of diabetology and the development of dedicated information leaflet, therapeutic education programs and communication actions toward the general audience…
In a same way, the number of diabetes patients referred to the memory clinic decreased after the study. This fact highlights the urgent need to better advertise cognitive disorders as common diabetes complications and the need of systematic cognitive assessments in diabetes patients. Diabetologists and general practitioner must be better informed on this complication and the tools to detect it. This major educational outcome has been integrated in the VasCog AUEC training course starting in 2018-2019 in Lille.
- To better screen diabetes patients with CI, we propose to detect such patients before the medical visit, using an abridged version of the MOCA (MOCA 5-min) administrable by phone. The use of this MOCA 5-min in French language requires adaptation and validation. This study directed by Pr K. Dujardin and Pr D. Deplanque has received approval by the local ethic committee in late 2017, and inclusions are currently on-going (VasCog Funded project).
- We have also focused on 2 rare populations of diabetes patient at risk of CDs to improve their healthcare pathway: type 1 diabetes patients before and after Langerhans islets transplantation (30 patients referred by Pr Vanthyghem since Oct2015) and myotonic dystrophy type 1 patients with high risk of diabetes (Dr Tard, VasCog funded project, 18 patients assessed so far)
- A proof of concept study has also been funded to test a new non-pharmacological therapy (cocoa flavanol and exercise) in type 1 diabetes patient at risk for long term CI (Dr Heyman, VasCog Funded project)
Populations at high risk of cognitive deficit: patients with cerebral small vessels disease
- A coordinated care pathway for patients with cerebral vascular injuries has been organized between the stroke unit and the memory clinic in Lille for more than 30 years. This allows, in close collaborations with diabetologists and cardiologists of the Lille University Hospital, a strong national and international visibility and leads to participation to numerous clinical trials and cohorts of patients in the field of vascular cognitive disorders (see appendix 2): PHRC COVARAD, PHRC LEOPOLD, CEOPS, A3ICH, RESTART study… Specifically, a cohort of patients with cerebral amyloid angiopathy associated with lobar vascular bleedings and cognitive disorders is on-going, which has already allowed a high-level publication (Moulin et al., 2016), the participation in a phase 2 randomized, double blind placebo vs ponezumab clinical trial (EudraCT Number: 2013-001557-27), and to the organization in Lille of the International Conference on Cerebral Amyloid Angiopathy (ICAA) in September 2018.
- As currently no symptomatic treatment of chronic vascular CDs exists, a study (PACTE-1 trial) was proposed to prove the effect of a novel therapeutic strategy based on low dose of methylphenidate associated with cognitive training during 6 weeks on cognitive functions of healthy elderly and validate it persistent effect at 3 months (Pr Devos, VasCog Funded project)
- Before we started our project on this topic, a systematic review conducted by one of us (Pr Cordonnier) together with the Edinburgh team (UK) showed that brain microbleeds may be present in normal controls, but are more frequent in patients with stroke, especially small-vessel diseases and in patients with Alzheimer’s disease. They are mainly subcortical in small-vessel diseases and cortical in Alzheimer’s disease (Cordonnier et al, 2007).