Salience Network Segregation Mediates the Effect of Tau Pathology on Mild Behavioral Impairment

Abstract

STRUCTURED ABSTRACTINTRODUCTIONA recently developed mild behavioral impairment (MBI) diagnostic framework standardizes the early characterization of neuropsychiatric symptoms in older adults. However, the links between MBI, brain function, and Alzheimer’s disease (AD) biomarkers are unclear.METHODSUsing data from 128 participants with diagnosis of amnestic mild cognitive impairment and mild dementia – Alzheimer’s type, we test a novel model assessing direct relationships between AD biomarker status and MBI symptoms, as well as mediated effects through segregation of the salience and default-mode networks.RESULTSWe identified a mediated effect of tau positivity on MBI through functional segregation of the salience network from the other high-level, association networks. There were no direct effects of AD biomarkers status on MBI.DISCUSSIONOur findings suggest an indirect role of tau pathology in MBI through brain network dysfunction and emphasize the role of the salience network in mediating relationships between neuropathological changes and behavioral manifestations.