Recent studies showed the presence of task-based fMRI hyperactivation prior to overt clinical symptomatology, for instance in individuals with normal cognition but presenting with subjective cognitive decline (SCD)27-31 and/or with in vivo evidence of Alzheimer’s disease pathology.17,32-37 The advent of PET ligands detecting Alzheimer’s pathology allowed for the assessment of close, yet complex associations between hyperactivation and the topology of Aβ plaques and tau across disease stages. This evidence concerns the gene MAPT and early-onset autosomal dominant Alzheimer disease.