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Apathy is associated with large-scale white matter network disruption in small vessel disease.

Published version
Peer-reviewed

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Authors

Tay, Jonathan 
Tuladhar, Anil M 
Hollocks, Matthew J 
Brookes, Rebecca L 
Tozer, Daniel J 

Abstract

OBJECTIVE: To investigate whether white matter network disruption underlies the pathogenesis of apathy, but not depression, in cerebral small vessel disease (SVD). METHODS: Three hundred thirty-one patients with SVD from the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC) study completed measures of apathy and depression and underwent structural MRI. Streamlines reflecting underlying white matter fibers were reconstructed with diffusion tensor tractography. First, path analysis was used to determine whether network measures mediated associations between apathy and radiologic markers of SVD. Next, we examined differences in whole-brain network measures between participants with only apathy, only depression, and comorbid apathy and depression and a control group free of neuropsychiatric symptoms. Finally, we examined regional network differences associated with apathy. RESULTS: Path analysis demonstrated that network disruption mediated the relationship between apathy and SVD markers. Patients with apathy, compared to all other groups, were impaired on whole-brain measures of network density and efficiency. Regional network analyses in both the apathy subgroup and the entire sample revealed that apathy was associated with impaired connectivity in premotor and cingulate regions. CONCLUSIONS: Our results suggest that apathy, but not depression, is associated with white matter tract disconnection in SVD. The subnetworks delineated suggest that apathy may be driven by damage to white matter networks underlying action initiation and effort-based decision making.

Description

Keywords

Aged, Apathy, Cerebral Small Vessel Diseases, Depression, Diffusion Tensor Imaging, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, White Matter

Journal Title

Neurology

Conference Name

Journal ISSN

0028-3878
1526-632X

Volume Title

92

Publisher

Ovid Technologies (Wolters Kluwer Health)
Sponsorship
Stroke Association (PPA 2015/02)