Neuroimaging and Clinical Biomarkers in the Familial and Sporadic FTD Spectrum – from the Presymptomatic to the Symptomatic Disease Stage

Frontotemporal dementia (FTD) is the second most common type of early-onset dementia, in which symptoms commonly become apparent before the age of 65. The clinical spectrum is heterogeneous, ranging from a predominant behavioural manifestation (behavioural variant FTD; bvFTD) to progressive language deterioration (primary progressive aphasia; PPA) and parkinsonism. 10-30% of FTD cases have an autosomal dominant pattern of inheritance. Mutations in the progranulin (GRN) and microtubule-associated protein tau (MAPT) genes, and a repeat expansion in chromosome 9 open reading frame 72 (C9orf72) are the three most common causes. Familial FTD allows the identification of pathogenic mutation carriers in their presymptomatic phase – a critical time-window for treatment as the pathological damage is at its minimum and potentially still reversible. However, with promising avenues opening for disease-modifying therapies in clinical trials, we currently lack robust biomarkers for (familial) FTD. These biomarkers will be essential for improving diagnostic accuracy, staging and prognosis, onset prediction, and monitoring disease progression and treatment response. In this thesis, we have therefore investigated potential neuroimaging and neuropsychological biomarkers in the familial and sporadic FTD spectrum.

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