In addition, extending the age range of participants, or using a longitudinal design, would further enable us to track how DN deactivation, PMC metabolites, AD pathology and episodic cognition may change with age in APOE E4 carriers (Foster et al., 2018) to give greater insight into the timeline of how and when APOE E4 possession may predispose to development of AD. Here, APOE is linked to Alzheimer disease.