Diagnostic and prognostic precision medicine for bvfrontotemporal dementia DIPPAFTD

The behavioural variant of frontotemporal dementia (bvFTD) is a common cause of early-onset dementia that presents with changes in behavior and personality. It is often misdiagnosed and mistaken for a psychiatric disorder, such as depression or bipolar disorder. Unlike with Alzheimer’s disease, we still lack reliable tests that enable a diagnosis of bvFTD. Recent research attention has been on hereditable forms of FTD; 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. 

Goal

The aim of the project is to contribute towards an early and accurate identification of bvFTD versus psychiatric disorders, which is crucial for appropriate management and treatment. Moreover, our results will increase the ability to predict rate of progression in non-familial bvFTD and other patients presenting with behavioral changes, that is essential for enrolment in drug trials and personalized treatments. 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 curcial for trial enrolment, whereass early PPD identification will lead to the appropriate psychatric treatments.  

Approach

In this project, we will combine existing data from cohorts from several countries including clinical, neuroimaging, and blood markers combined with novel markers that were developed by the participants of the project. We will also collect data from deceased bvFTD and psychiatric patients who had their diagnosis confirmed through pathological examination of their brains in a brain bank. We will define which of the available markers are the best predictors of the bvFTD diagnosis. We will apply the identified markers in new patient cohorts to be established and by using a statistic modeling approach, we aim to create a paradigm that enables both accurate diagnosis and prediction of the clinical course (prognosis).

Results

The project has yielded relevant findings, such as that the concentrations of NfL and GFAP measured in blood were higher in sporadic bvFTD patients than in patients with psychiatric disorders. In addition, the study showed that NfL was better at distinguishing between bvFTD and psychiatric disorders than GFAP. Another finding was that FDG-PET appears to provide an excellent distinction between bvFTD and PPD. Very special is the unexpected finding that there are more men with sporadic bvFTD than women. The discovery of this sex difference has now led to new studies into sex differences in sporadic bvFTD. In addition, the study has shown that it is important to investigate sporadic bvFTD separately from hereditary bvFTD, so that important clues are no longer missed.