PSEN1 and Cognitive impairment: Hippocampal hyperactivation has been detected by fMRI during memory-encoding tasks in people with mild cognitive impairment (MCI), a prodromal stage of AD, as well as in pre-symptomatic individuals carrying the E280A presenilin-1 (PS1) mutation, the most common cause of early-onset familial AD (Dickerson et al., 2005; Celone et al., 2006; Quiroz et al., 2010; Bakker et al., 2012; Sepulveda-Falla et al., 2012) (Table 1).