Project: Diagnostic and Prognostic Precision medicine Algorithm for behavioural variant FrontoTemporal Dementia

Acronym DIPPA-FTD (Reference Number: JPND2019-466-261)
Project Topic The behavioural variant of frontotemporal dementia (bvFTD) is a common cause of early-onset dementia with heterogeneity in underlying pathology, genetics, and natural course, demanding a customized approach to predict individual prognosis and develop personalized treatments. BvFTD is often mistaken for a primary psychiatric disorder (PPD), causing substantial diagnostic delay of up to 6 years on average. Unlike with Alzheimer’s disease, reliable in vivo biomarkers for FTD are not available yet. Recent research attention has been on genetic FTD (now known to differ pathologically and often clinically); however, the critical challenge is how to diagnose non-familial forms of bvFTD (which accounts for 80% of all cases) early in the disease course and therefore distinguish it from late-onset psychiatric disorders that may mimic bvFTD, in order to deliver relevant interventions and treatments. The creation of a diagnostic and prognostic model of sporadic bvFTD is highly needed and crucial to enable performing precision medicine. All members of our multidisciplinary consortium have a strong track record in bvFTD research. We selected the most promising results of our ongoing research, including neuropsychological and social cognitive markers; neuroimaging- based classifiers; serum neurofilaments, plasma neuronal derived exosome signatures, and cell free DNA. In this project, we will combine cohorts from several countries into a comprehensive retrospective discovery cohort to examine the above-mentioned markers focusing on sporadic cases and PPD, in addition to a large number of pathologically confirmed bvFTD and PPD cases. We will further collect a deeply phenotyped prospective multi-national cohort to validate these markers, in addition to collecting postmortem cases of clinically less well-defined bvFTD / PPD cases. We will use statistical modeling to create the best diagnostic and prognostic model for non-familial forms of bvFTD and PPD. As a subgoal we aim to determine underlying FTD pathology within the sporadic bvFTD group, to enable eventual patient stratification. Our project will contribute towards an early and accurate bvFTD identification, that is crucial for trial enrolment, whereas early PPD identification will lead to the appropriate psychiatric treatments. Our results will increase the ability to predict rate of progression in sporadic bvFTD and other patients presenting with behavioral changes, that is pivotal for patient stratification, trial design and personalized treatments.

Project partner

Number Name Role Country
1 Amsterdam University Medical Center Coordinator Netherlands
2 Department of Psychiatry and Psychotherapy of Technical University of Munich Partner Germany
3 McGill University Partner Canada
4 University of Milan Partner Italy
5 University of Sydney Partner Australia