Altered Resting State Hippocampal Connectivity Associated With Amyloid and Tau in Older Adults Without Dementia From a Population-Based Cohort Study.

OBJECTIVE

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 nonlinear 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.

CONCLUSION

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.