The American Journal of Geriatric Psychiatry · Sep 22, 2026

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

By Roberts A, Andreescu C, Cohen A et al.

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.

doi.org/10.1016/j.jagp.2026.09.003 Open access PubMed 42888083 Mechanisms