Functional redundancy of the posterior hippocampi is selectively disrupted in non-demented older adults with β-amyloid deposition

Several neural mechanisms underlying resilience to Alzheimer's disease (AD) have been proposed, including redundant neural connections between the posterior hippocampi and all other brain regions, and global functional connectivity of the left frontal cortex (LFC). Here, we investigated if functional redundancy of the hippocampus (HC) and LFC underscores neural resilience in the presence of early AD pathologies. From the ADNI database, cognitively normal older adults (CN) (N = 220; 36 % A<i>β</i>+) and patients with Mild Cognitive Impairment (MCI) (N = 143; 51 % A<i>β</i>+) were utilized. Functional redundancy was calculated from resting state fMRI data using a graph theoretical approach by summing the direct and indirect paths (path lengths = 1-4) between each region of interest and its 263 functional connections. Posterior HC, but not anterior HC or LFC, redundancy was significantly lower in A<i>β</i>+ than A<i>β</i>-groups, regardless of diagnosis. Posterior HC redundancy related to higher education and better episodic memory, but it did not moderate the A<i>β</i>-cognition relationships across the diagnostic groups. Together, these findings suggest that posterior HC redundancy captures network disruption that parallels selective vulnerability to A<i>β</i> deposition. Further, our findings indicate that functional redundancy may underscore a network metric different from global functional connectivity of the LFC.