Functional Redundancy of the Posterior Hippocampi, but not Anterior Hippocampi or Left Frontal Cortex, is Disrupted in Pathological Brain Aging

As prevalence rates of Alzheimers disease (AD), the leading cause of dementia, are projected to more than double by 2050, emphasis has been placed on early intervention strategies that target resilience mechanisms to delay or prevent the onset of clinical symptoms. Several neural mechanisms underlying brain resilience to AD have been proposed, including redundant neural connections between the posterior hippocampi (HC) and all other brain regions, and global functional connectivity of the left frontal cortex (LFC). It remains unknown, however, if regional redundancy of the HC and LFC underscores neural resilience in the presence of AD pathologies. From the ADNI database, 363 cognitively normal older adults (CN) (N = 220; 36% A{beta}+) and patients with Mild Cognitive Impairment (MCI) (N = 143; 51% A{beta}+) were utilized. Regional 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 ROI and its 262 functional connections. The results showed that A{beta}-status significantly disrupted posterior HC, but not anterior HC or LFC, redundancy. A{beta}- groups showed higher redundancy of the bilateral posterior HC than A{beta}+. In regard to redundancy-cognition relationships, higher posterior HC redundancy was related to better episodic memory performance, an effect which was primarily driven by the A{beta}- group. Despite the positive relationship between posterior HC redundancy and cognition, we did not find compelling evidence that redundancy of the posterior HC serves in a resilience manner, as posterior HC redundancy did not moderate the potentially deleterious relationship between A{beta} deposition and cognition. No relationships were found between anterior HC or LFC redundancy and cognitive performance. Together, these findings suggest that redundancy of the LFC does not underpin its role in resilience and that posterior HC redundancy may capture disruptions to network connectivity that occur as a result of A{beta} deposition.