Longitudinal Neuropsychological Study of Presymptomatic c.709-1G>A Progranulin Mutation Carriers

Objective: The assessment of individuals from families affected by familial frontotemporal dementia (FTD) allows the evaluation of preclinical or pre-diagnosis disease markers. The current work aims to investigate the existence of a cognitive phase in GRN mutation carriers before overt clinical symptoms begin. Methods: We performed a longitudinal neuropsychological analysis (three assessments in 4 years) in a group of presymptomatic c.709-1G>A progranulin (GRN) (n=15) mutation carriers and non-carrier relatives (n=25) from seven FTD families. Results: GRN mutation carriers showed subtle decline over the longitudinal follow-up in several different domains (namely, attention, facial affect recognition, decision-making, language, and memory). The differences between groups were most marked in the facial affect recognition test, with improvement in the non-carrier group and decline in the GRN mutation carrier group, with very large effect sizes. Conclusions: Facial affect recognition may decline before clinical diagnosis and makes the adapted version of the Picture of Facial Affect a potential candidate for early detection of GRN-associated FTD. (JINS, 2019, 25, 39-47)