APOE ε4 positivity predicts centrality of episodic memory nodes in patients with mild cognitive impairment: A cohort-based, graph theory-informed study of cognitive networks

Published research reports inconsistent links between APOE-ε4 and cognition. We hypothesised that these links can be reliably captured by graph-theory analyses.Cognitive networks were calculated in 8,118 controls, 3,482 MCI patients and 4,573 Alzheimer’s dementia patients, recruited as part of the National Alzheimer’s Coordinating Center (NACC) database. Differences in nodal centrality were tested in two independent NACC sub-cohorts between ε4-carriers and non-carriers.A significant APOE-dependant effect emerged from the analysis of the Logical-Memory nodes in MCI patients in both sub-cohorts. While non-carriers showed equal centrality in immediate and delayed recall, the latter was significantly less central among carriers. These findings were replicated in the sub-groups of sole amnestic-MCI patients (n = 2,971). No effects were found in the other two diagnostic groups.APOE ε4 influences nodal properties of cognitive networks at the MCI stage. This highlights the importance of characterising the impact of risk factors on the entire cognitive network.