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Updated: Oct 18, 2026

Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
Published on: November 14, 2017
Altered Resting State Hippocampal Connectivity Associated With Amyloid and Tau in Older Adults Without Dementia From
Anna Roberts1, Carmen Andreescu1, Ann Cohen1
1Department of Psychiatry (AR, CA, AC, BS, HTK), University of Pittsburgh School of Medicine, Pittsburgh, PA.
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.
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