YOUNG ONSET DEMENTIA: MECHANISMS OF SELECTIVE VULNERABILITY AND THEIR CONTRIBUTION TO DISEASE PRESENTATION (YOD-MOLECULAR)

The diagnosis of young-onset disorders causing dementia, such as young-onset Alzheimer’s disease (YOAD) and Frontotemporal dementia (FTD) is often delayed since these disorders often present with non-memory symptoms, such as problems with behaviour, social cognition, language, or perception. These symptoms have been associated with focal degeneration of specific cortical brain regions, but we still lack an understanding of why and how these specific regions are affected, while this information can be crucial for the development of treatment. Our multidisciplinary YOD-MOLECULAR project aims to i) improve the diagnosis of FTD and YOAD by creating a novel Young-Onset Dementia (YOD) test battery that captures affected non-memory domains; ii) develop data-driven models that define the most vulnerable and earliest affected brain regions in non-memory YOAD and FTD phenotypes; iii) identify from these vulnerable regions, the underlying disease mechanisms at the molecular and cellular level in YOAD and FTD, and iv) integrate clinical and biological data using Artificial Intelligence (AI) to generate comprehensive and meaningful clinical-biological YOD subtypes. YOD-MOLECULAR interconnects four work packages led by clinicians, language and AI experts, and basic scientists together with biotech companies, patient representatives, young entrepreneurs, ethic experts, and knowledge institutes. Throughout YOD-MOLECULAR, AI addresses specific challenges, relating to clinical, pathological, neuroimaging and molecular data modelling. Through earlier and accurate diagnosis and the identification of targets for biomarker and drug development we facilitate individualised disease management, reduction of healthcare costs, and improved quality of life.