Altered resting state hippocampal connectivity associated with amyloid and tau in older adults without dementia from a population-based cohort study

Structured Abstract Introduction : Default mode network (DMN) structures, including hippocampus, accumulate amyloid-beta and tau pathology in Alzheimer's disease (AD) and display connectivity changes prior to the onset of cognitive dysfunction. Methods : We recruited cognitively healthy older adults who underwent PiB and AV1451 imaging and resting state functional imaging. We evaluated non-linear associations between hippocampal DMN connectivity and amyloid-beta and tau in cross-sectional analyses. Results : Left and right anterior hippocampal to DMN intranetwork connectivity was greater with greater amyloid and was lower with even greater levels of amyloid (inverted U-shape association). We found that inter-network hippocampal connectivity was greater with greater amyloid and tau. Greater intra and inter-DMN connectivity was associated with greater cognitive function especially memory and attention, consistent with protective association processes. Discussion : Intranetwork DMN connectivity was greater with low to moderate amyloid and was lower with greater amyloid and tau in preclinical AD – connectivity may help maintain cognitive function, especially memory. Functional connectivity may potentially offset the impact of early amyloid and tau accumulation and transitionally spare cognitive function.