Posterior hippocampal redundancy: A marker of non‐pathological brain aging

Background Several neural mechanisms underlying brain resilience to Alzheimer’s disease (AD) have been proposed, including redundant neural connections between the posterior hippocampi and all other brain regions (pHipp‐redundancy), and global functional connectivity of the left frontal cortex (gLFC). It remains unclear whether these two mechanisms confer resilience to AD pathologies through similar or distinctive mechanisms. We examined if redundancy, measured through graph theory, underlies the neuroprotective effects of both pHipp‐redundancy and gLFC connectivity in the early stage of AD pathologies. Method From the ADNI database, 370 CN and MCI participants were utilized. Aβ‐positivity (Aβ+) was defined as PET AV45 SUVR normalized to cerebellum greater than 1.11. Resting state data were preprocessed using fMRIprep. Network graphs were constructed with 263 functional ROIs as nodes and z‐transformed correlations between each node as edges. Redundancy was calculated by summing the direct and indirect paths (path lengths=1‐4) between each hippocampal region (i.e., anterior and posterior hippocampal regions, bilaterally and LFC) and its 262 connections. Group differences (Aβ‐status, diagnosis) were computed in R using non‐parametric ANCOVA models with 10,000 permutations. Regression analyses were conducted to examine if Aβ‐status and diagnosis moderated the relationship between SUVR and redundancy. Models covaried for age, sex, education, and APOE4. Result Across CN and MCI, Aβ‐ had higher bilateral pHipp‐redundancy than Aβ+ (p’s