Functional MRI as a biomarker in the presymptomatic and early stage of FTD

Frontotemporal dementia (FTD) is a syndrome with behavioural and/or language problems caused by neurodegeneration of the frontal and temporal cortices. Severe impairment in social cognition is associated with atrophy of the anterior cingulate cortex (ACC) and frontal insula (FI). This atrophy pattern correlates with reduced functional connectivity in the so-called ?Salience Network? (SN) on resting-state fMRI in FTD. An autosomal dominant form caused by MAPT or Progranulin gene mutations exists in 20-30 percent, with the first clinical symptoms presenting between the ages of 40?60 years. The actual onset of the disease probably precedes symptoms by years, but the exact onset remains unknown. The ACC plays a role in conflict monitoring and subsequent conforming behavioural adjustments, as demonstrated in task-related fMRI. Our research aim is to investigate changes in resting-state and task-related fMRI in early FTD and in the presymptomatic stage. Resting-state fMRI and social cognition tasks will be performed longitudinally over a 4 year-period in presymptomatic mutation carriers from GRN and MAPT families, and controls. In addition, task-related fMRI with a Stroop task and a social conformity task will be carried out in patients with early FTD, presymptomatic carriers and controls. If these techniques prove to be reliable tools to detect earliest changes in the disease process, they can be used as functional biomarkers in clinical practice and pharmacological trials. The package of our protocol and datasets of resting-state and task-related fMRI changes can be applied as products to other universities all over the world.