Periodic Reporting for period 1 - MES-CoBraD (Multidisciplinary Expert System for the Assessment & Management of Complex Brain Disorders) Reporting period: 2021-04-01 to 2022-09-30 Summary of the context and overall objectives of the project Millions of Europeans of all ages live with brain disorders that threaten their quality of life and impact the sustainability of health systems. Contributing to this field, the EU-funded MES-CoBraD project aims to improve the diagnostic accuracy and therapeutic outcomes of complex brain disorders, such as epilepsy, dementia, and sleep disorders. To do this, it will combine real-world data from diverse populations from varying backgrounds through thorough, cost-efficient and fast protocols. The project will draw on expertise in medicine, engineering, computer science, amongst others, to ultimately help improve the quality of lives of those living with such disorders, as well as caregivers and society.The Multidisciplinary Expert System for the Assessment & Management of Complex Brain Disorders (MES-CoBraD) is an interdisciplinary project combining Real-World Data (RWD) from multiple clinical and consumer sources through comprehensive, cost-efficient, and fast protocols towards improving diagnostic accuracy and therapeutic outcomes in people with Complex Brain Disorders (CoBraD), as reflected in Neurocognitive (Dementia), Sleep, and Seizure (Epilepsy) disorders and their interdependence. It brings together internationally recognized experts in medicine, engineering, computer science, social health science, law, and marketing and communication from across Europe, and combines clinical information and scientific research in CoBraD with technical innovation in secure data-sharing platforms, artificial intelligence algorithms, expert systems of precision and personalized care, and advanced data analytics, with a primary focus on improving the quality of life of patients, their caregivers, and the society at large. It leverages RWD from diverse CoBraD populations across cultural, socioeconomic, educational, and health system backgrounds, with special attention on including vulnerable populations and minorities in an equitable manner and engaging key stakeholders to maximize project impact. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far During the first reporting period M1-M18 (1/4/2021 – 30/9/2022), the MES-CoBraD project set a solid basis for the implementation of its ambitious use-cases. Having a multi-layered and parallel approaches to performing research and developing innovations, ranging from the most practical results all the way to the most ambitious, the consortium has been working towards defining and implementing its research protocols, collecting data from multiple sources, integrating, and harmonising them based on scientifically and ethically sound commonly agreed upon rules, and designing research hypotheses. At the same time, to implement the requirements meticulously collected and prioritised, and to be able to test these hypotheses, the MES-CoBraD platform was designed, including its various components and modules, to support the development of a technology that will be sustainable and expandable, aiming at a robust, secure, and integrated platform with a single UI and an innovative approach to incorporating research and clinical protocols with business processes, analytics and Artificial Intelligence. The development of the platform is fully underway at this stage and able to present very promising tangible results. While the medical and technical work is done, ethics and legal work was performed to ensure there is no misuse of resources on several levels, while dissemination and stakeholder engagement activities have put all of the interested parties in the loop, regarding the project’s progress. Planning for the future, the project’s exploitation and innovation strategies are following and documenting the project’s results to make them available to the various stakeholder communities as soon as they become formalised. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) During the first 18 months of the study we have established a novel time-effective, and probably cost-effective diagnostic protocol for assessing CoBraD across domains of cognitive, sleep, and seizure disorders, ranging from daily RWD applied in clinic or at home. This already indicates a faster and earlier process of diagnosing people with CoBraD and allowing for deep phenotyping their presentation in a comprehensive manner. Published results from group members funded through the MES-CoBraD project have already revealed a number of findings in CoBraD. Specifically, (a) different episodic memory measures are associated with cortical atrophy in specific brain regions in adults with Down syndrome and Alzheimer’s disease, (b) MRI cortical mean diffusivity is a promising and sensitive biomarker for assessing neurodegeneration-related microstructural changes in primary progressive aphasia, (c) there are 577 genes whose expression is associated with the spatial spreading of tau in neurodegenerative disorders (topological vulnerability), including APOE and glutamatergic synaptic genes, such as SLC1A2, supporting specific drug development strategies targeting the gradient expression of this set of genes. With regards to prognostic objectives, (a) members of the MES-CoBraD Consortium have identified that pGFAP and pNfL levels differ in Frontotemporal Dementia and Alzheimer’s Disease, and their combination is useful for distinguishing between the two. Importantly, also, pGFAP is helpful to track disease severity and predict greater cognitive decline during follow-up in patients with FTD, a marker we have been lacking until now. Additionally, (b) our members identified that MRI-based cortical microstructure is a noninvasive biomarker that independently predicts subsequent cognitive decline, neurodegeneration, and clinical progression, a feature that can be useful in real world trials. Finally, (c) analyzing cognitive data from people with Down syndrome, scientific analyses support the need for population health plans to screen for AD-related cognitive decline from the fourth decade of life and provide longitudinal data to inform clinical trials in adults with DS to prevent AD.With regards to protocols that assess therapeutic intervention efficacy and safety in CoBraD, we have identified that (a) Cognitive Behavioral Therapy for Insomnia is helpful in improving insomnia in people with Mild Cognitive Impairment, while at the same time allowing for tapering of central nervous system sedatives. We are actively pursuing in follow up assessments whether it also helps in delaying cognitive decline over time.Scientific Objective 4: Implement an effective clinical management Expert System algorithm for CoBraD that is well-tolerated and accepted by patients and their caregivers During the first 18 months of the project, we have provided technical partners with the scientific operations that an Expert System is required to perform for guiding the Assessment and Management of CoBraD. This is a representation of methodological operations identified in our hypothesis testing protocols (D4.2 D4.3) and whose high-level outputs are assessed through a defined validation framework and end-user feedback, including test-case executions, to examine if Platform modules are assessed as-intended. We anticipate, as planned from the start of the project, to start assessing this key objective from M24 onwards. MES-CoBraD Poster - LIBER Conference 2022.jpg
