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[Preprint]. 2024 May 27:2024.05.26.24307943.
doi: 10.1101/2024.05.26.24307943.

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

Alexandru D Iordan  1 , Robert Ploutz-Snyder  2 , Bidisha Ghosh  2 , Annalise Rahman-Filipiak  1 , Robert Koeppe  3 , Scott Peltier  4   5 , Bruno Giordani  1   6 , Roger L Albin  6   7 , Benjamin M Hampstead  1   8
Affiliations

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

Alexandru D Iordan et al. medRxiv. .

Update in

Abstract

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.

Keywords: biomarkers; brain connectivity; functional magnetic resonance imaging (fMRI); network analysis; neuropsychiatric symptoms; positron emission tomography (PET); resting state.

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Conflict of interest statement

CONFLICTS No authors associated with this study reported conflicts of interest that would impact the reported results.

Figures

Figure 1.
Figure 1.. Main model.
The overall segregation of the salience network (SaN) from the other association networks mediates the effect of Aβ positive/tau positive (Aβ+/tau+) biomarker status on MBI (indirect effect: β=0.07, p=0.044). There is no direct path from AD biomarkers to MBI. Solid and dashed arrows indicate significant and non-significant relationships, respectively (see Table 2). Abbreviations: AD: Alzheimer’s disease; Aβ-/tau-: AD biomarker negative; Aβ+/tau-: Aβ positive/tau negative; Aβ+/tau+: Aβ positive/tau positive; SaN: salience network; DMN: default-mode network; MBI: mild behavioral impairment; MoCA: Montreal Cognitive Assessment; GM: grey matter.
Figure 2.
Figure 2.. Alternative model.
Similar to our main model, only the overall segregation of the salience network (SaN) from the other association networks mediates the effect of Aβ and tau positivity (Aβ+/tau+) on MBI (indirect effect: β=0.08, p=0.039). There is no direct path from AD biomarkers to MBI. Solid and dashed arrows indicate significant and non-significant relationships, respectively (see Table 3). Abbreviations: AD: Alzheimer’s disease; Aβ-/tau-: AD biomarker negative; Aβ+/tau-: Aβ positive/tau negative; Aβ+/tau+: Aβ positive/tau positive; SaN: salience network; DMN: default-mode network; MBI: mild behavioral impairment; MoCA: Montreal Cognitive Assessment; GM: grey matter.
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