An introduction to GENFI and the development of novel behavioural and cognitive measures for genetic FTD. (20th December 2022) - Rohrer, Jonathan D.
Abstract: Background: The Genetic FTD Initiative (GENFI) is the largest familial FTD cohort study worldwide and over its initial ten years has created a network of nearly 30 research centres across Europe and Canada, and a cohort of over 1000 participants. Method: GENFI was established to develop robust biomarkers that could be used in clinical trials. In terms of clinical and cognitive measures, the study has used a set of novel symptom scales as well as a detailed neuropsychological battery, all harmonized across the network, to identify new rating scales and composite measures. Result: The study has characterized behavioural and neuropsychological changes across the different genetic forms of FTD, highlighting the earliest prodromal changes that occur in different domains, including emotion recognition, semantic knowledge and executive dysfunction. GENFI data has also been used to validate two core clinical/cognitive scales, highlighting their utility for clinical trials in genetic FTD: the CDR plus NACC FTLD and the FTD Rating Scale (FRS). An extension to the CDR plus NACC FTLD with motor and neuropsychiatric domains highlights the contribution of symptoms outside of classical behavioural and language domains to accurately measuring disease progression. The study has also combined neuropsychological measures to create a cognitive composite measure (GENFI‐Cog), individualized to each genetic group, which greatly reduces sample sizes required for clinical trials. Conclusion: The GENFI study has developed and validated a number of clinical and cognitive measures that are now being implemented in clinical trials for novel therapeutics in familial FTD. Future studies in GENFI will help to refine these even further.