Defining the presymptomatic phase of frontotemporal dementia

Frontotemporal dementia (FTD) is a clinically, pathologically and genetically heterogeneous disorder. Whilst disease modifying therapy trials are mostly focused on the symptomatic phase, future studies will move earlier in the disease aiming to prevent symptom onset. This review summarizes the recent work to better understand this presymptomatic period.

The presymptomatic phase can be split into preclinical and prodromal stages. The onset of the preclinical phase is defined by the first presence of pathological inclusions of tau, TDP-43 or fused in sarcoma in the brain. Definitive biomarkers of these pathologies do not yet exist for FTD. The prodromal phase is defined by the onset of mild symptoms. Recent work has highlighted the wide phenotypic spectrum that occurs, with the concept of mild cognitive ± behavioural ± motor impairment (MCBMI) being put forward, and additions to scales such as the CDR plus NACC FTLD now incorporating neuropsychiatric and motor symptoms.

It will be important to better characterize the presymptomatic period moving forward and develop robust biomarkers that can be used both for stratification and outcome measures in prevention trials. The work of the FTD Prevention Initiative aims to facilitate this by bringing together data from natural history studies across the world.