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Salience Network Segregation Mediates the Effect of Tau Pathology on Mild Behavioral Impairment
Alexandru D Iordan1, Robert Ploutz-Snyder2, Bidisha Ghosh2
1Research Program on Cognition and Neuromodulation Based Interventions (RP-CNBI), Department of Psychiatry, University of Michigan, 4251 Plymouth Rd., Ann Arbor, MI, 48105, USA.
Introduction:
A 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.
Methods:
Using 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.
Results:
We 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.
Discussion:
Our 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.
Insights
Mild behavioral impairment (MBI) is indirectly linked to Alzheimer's disease (AD) tau pathology via brain network dysfunction. The salience network plays a key role in this relationship, impacting neuropsychiatric symptoms in older adults.
Area of Science:
- Neuroscience
- Neurology
- Geriatrics
Background:
- A standardized framework for mild behavioral impairment (MBI) in older adults exists.
- The relationship between MBI, brain function, and Alzheimer's disease (AD) biomarkers requires further clarification.
Purpose of the Study:
- To investigate the direct and mediated effects of AD biomarker status on MBI symptoms.
- To explore the role of salience and default-mode network segregation in mediating these relationships.
Main Methods:
- Analysis of data from 128 participants diagnosed with amnestic mild cognitive impairment or mild dementia due to AD.
- Testing a novel model of AD biomarkers, MBI symptoms, and network functional segregation.
Main Results:
- Tau positivity showed a mediated effect on MBI through the functional segregation of the salience network.
- No direct association was found between AD biomarker status and MBI symptoms.
Conclusions:
- Tau pathology indirectly influences MBI through disruptions in brain network function.
- The salience network is crucial in mediating the link between neuropathology and behavioral symptoms in AD.
