RT Journal Article
SR Electronic
T1 Apathy is associated with large-scale white matter network disruption in small vessel disease
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP e1157
OP e1167
DO 10.1212/WNL.0000000000007095
VO 92
IS 11
A1 Tay, Jonathan
A1 Tuladhar, Anil M.
A1 Hollocks, Matthew J.
A1 Brookes, Rebecca L.
A1 Tozer, Daniel J.
A1 Barrick, Thomas R.
A1 Husain, Masud
A1 de Leeuw, Frank-Erik
A1 Markus, Hugh S.
YR 2019
UL http://n.neurology.org/content/92/11/e1157.abstract
AB 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.AAL=Automated Anatomical Labeling; AES=Apathy Evaluation Scale; ANCOVA=analysis of covariance; CESD=Centre for Epidemiological Studies Depression Scale; DSM-IV-TR=Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision; EPI=echo-planar imaging; FLAIR=fluid-attenuated inversion recovery; LI=lacunar infarct; MCG=middle cingulate gyrus; NBS=Network Based Statistic; RUN DMC=Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort; SMA=supplementary motor area; SVD=small vessel disease; TE=echo time; TI=inversion time; TR=repetition time; WMH=white matter hyperintensities