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

Overview

Journal Alzheimers Dement

Specialties Neurology
Psychiatry

Date 2024 Oct 4

PMID 39364768

Authors

Alexandru D Iordan

Robert Ploutz-Snyder

Bidisha Ghosh

Annalise Rahman-Filipiak

Robert Koeppe

Scott Peltier

Bruno Giordani

Roger L Albin

Benjamin M Hampstead

Affiliations

Soon will be listed here.

Abstract

Introduction: A recently developed mild behavioral impairment (MBI) diagnostic framework standardizes the early characterization of neuropsychiatric symptoms in older adults. However, the joint contributions of Alzheimer's disease (AD) pathology and brain function to MBI remain unclear.

Methods: 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, using data from 128 participants with diagnosis of amnestic mild cognitive impairment or mild dementia-AD type.

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 that tau pathology contributes to MBI primarily by disrupting salience network function and emphasize the role of the salience network in mediating relationships between neuropathological changes and behavioral manifestations.

Highlights: Network segregation mediates Alzheimer's disease (AD) pathology impact on mild behavioral impairment (MBI). The salience network is pivotal in linking tau pathology and MBI. This study used path analysis with AD biomarkers and network integrity. The study evaluated the roles of salience, default mode, and frontoparietal networks. This is the first study to integrate MBI with AD biomarkers and network functionality.

Citing Articles

Salience network segregation mediates the effect of tau pathology on mild behavioral impairment.

Iordan A, Ploutz-Snyder R, Ghosh B, Rahman-Filipiak A, Koeppe R, Peltier S Alzheimers Dement. 2024; 20(11):7675-7685.

PMID: 39364768 PMC: 11567810. DOI: 10.1002/alz.14229.

References

Dehaene S, Kerszberg M, Changeux J . A neuronal model of a global workspace in effortful cognitive tasks. Proc Natl Acad Sci U S A. 1998; 95(24):14529-34. PMC: 24407. DOI: 10.1073/pnas.95.24.14529. View

Murphy K, Birn R, Handwerker D, Jones T, Bandettini P . The impact of global signal regression on resting state correlations: are anti-correlated networks introduced?. Neuroimage. 2008; 44(3):893-905. PMC: 2750906. DOI: 10.1016/j.neuroimage.2008.09.036. View

Klunk W, Koeppe R, Price J, Benzinger T, Devous Sr M, Jagust W . The Centiloid Project: standardizing quantitative amyloid plaque estimation by PET. Alzheimers Dement. 2014; 11(1):1-15.e1-4. PMC: 4300247. DOI: 10.1016/j.jalz.2014.07.003. View

Royse S, Minhas D, Lopresti B, Murphy A, Ward T, Koeppe R . Validation of amyloid PET positivity thresholds in centiloids: a multisite PET study approach. Alzheimers Res Ther. 2021; 13(1):99. PMC: 8111744. DOI: 10.1186/s13195-021-00836-1. View

Gordon E, Chauvin R, Van A, Rajesh A, Nielsen A, Newbold D . A somato-cognitive action network alternates with effector regions in motor cortex. Nature. 2023; 617(7960):351-359. PMC: 10172144. DOI: 10.1038/s41586-023-05964-2. View

Baron R, Kenny D . The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. J Pers Soc Psychol. 1986; 51(6):1173-82. DOI: 10.1037//0022-3514.51.6.1173. View

Geerligs L, Renken R, Saliasi E, Maurits N, Lorist M . A Brain-Wide Study of Age-Related Changes in Functional Connectivity. Cereb Cortex. 2014; 25(7):1987-99. DOI: 10.1093/cercor/bhu012. View

Mortby M, Ismail Z, Anstey K . Prevalence estimates of mild behavioral impairment in a population-based sample of pre-dementia states and cognitively healthy older adults. Int Psychogeriatr. 2017; 30(2):221-232. DOI: 10.1017/S1041610217001909. View

Guan D, Rockwood K, Smith E, Ismail Z . Sex Moderates the Association between Frailty and Mild Behavioral Impairment. J Prev Alzheimers Dis. 2022; 9(4):692-700. DOI: 10.14283/jpad.2022.61. View

10.

Seeley W . The Salience Network: A Neural System for Perceiving and Responding to Homeostatic Demands. J Neurosci. 2019; 39(50):9878-9882. PMC: 6978945. DOI: 10.1523/JNEUROSCI.1138-17.2019. View

11.

Wang X, Ren P, Mapstone M, Conwell Y, Porsteinsson A, Foxe J . Identify a shared neural circuit linking multiple neuropsychiatric symptoms with Alzheimer's pathology. Brain Imaging Behav. 2017; 13(1):53-64. PMC: 5854501. DOI: 10.1007/s11682-017-9767-y. View

12.

Sun Y, Xu W, Chen K, Shen X, Tan L, Yu J . Mild behavioral impairment correlates of cognitive impairments in older adults without dementia: mediation by amyloid pathology. Transl Psychiatry. 2021; 11(1):577. PMC: 8580970. DOI: 10.1038/s41398-021-01675-2. View

13.

Greenberg T, Hoff M, Gilk T, Jackson E, Kanal E, McKinney A . ACR guidance document on MR safe practices: Updates and critical information 2019. J Magn Reson Imaging. 2019; 51(2):331-338. DOI: 10.1002/jmri.26880. View

14.

Zhou J, Seeley W . Network dysfunction in Alzheimer's disease and frontotemporal dementia: implications for psychiatry. Biol Psychiatry. 2014; 75(7):565-73. DOI: 10.1016/j.biopsych.2014.01.020. View

15.

Barrett L, Satpute A . Large-scale brain networks in affective and social neuroscience: towards an integrative functional architecture of the brain. Curr Opin Neurobiol. 2013; 23(3):361-72. PMC: 4119963. DOI: 10.1016/j.conb.2012.12.012. View

16.

Seeley W, Menon V, Schatzberg A, Keller J, Glover G, Kenna H . Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci. 2007; 27(9):2349-56. PMC: 2680293. DOI: 10.1523/JNEUROSCI.5587-06.2007. View

17.

Menon V . Large-scale brain networks and psychopathology: a unifying triple network model. Trends Cogn Sci. 2011; 15(10):483-506. DOI: 10.1016/j.tics.2011.08.003. View

18.

Matuskova V, Ismail Z, Nikolai T, Markova H, Cechova K, Nedelska Z . Mild Behavioral Impairment Is Associated With Atrophy of Entorhinal Cortex and Hippocampus in a Memory Clinic Cohort. Front Aging Neurosci. 2021; 13:643271. PMC: 8180573. DOI: 10.3389/fnagi.2021.643271. View

19.

Behzadi Y, Restom K, Liau J, Liu T . A component based noise correction method (CompCor) for BOLD and perfusion based fMRI. Neuroimage. 2007; 37(1):90-101. PMC: 2214855. DOI: 10.1016/j.neuroimage.2007.04.042. View

20.

Ismail Z, Smith E, Geda Y, Sultzer D, Brodaty H, Smith G . Neuropsychiatric symptoms as early manifestations of emergent dementia: Provisional diagnostic criteria for mild behavioral impairment. Alzheimers Dement. 2015; 12(2):195-202. PMC: 4684483. DOI: 10.1016/j.jalz.2015.05.017. View