Longitudinal cognitive biomarkers predicting symptom onset in presymptomatic frontotemporal dementia

We performed 4-year follow-up neuropsychological assessment to investigate cognitive decline and the prognostic abilities from presymptomatic to symptomatic familial frontotemporal dementia (FTD). Presymptomatic MAPT (n = 15) and GRN mutation carriers (n = 31), and healthy controls (n = 39) underwent neuropsychological assessment every 2 years. Eight mutation carriers (5 MAPT, 3 GRN) became symptomatic. We investigated cognitive decline with multilevel regression modeling; the prognostic performance was assessed with ROC analyses and stepwise logistic regression. MAPT converters declined on language, attention, executive function, social cognition, and memory, and GRN converters declined on attention and executive function (p < 0.05). Cognitive decline in ScreeLing phonology (p = 0.046) and letter fluency (p = 0.046) were predictive for conversion to non-fluent variant PPA, and decline on categorical fluency (p = 0.025) for an underlying MAPT mutation. Using longitudinal neuropsychological assessment, we detected a mutation-specific pattern of cognitive decline, potentially suggesting prognostic value of neuropsychological trajectories in conversion to symptomatic FTD.