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Eur J Neurol. 2019 Sep 10. doi: 10.1111/ene.14084. [Epub ahead of print]

Large-scale network dysfunction in vascular cognitive disorder supports connectional diaschisis in advanced arteriosclerosis.

Meng D1,2,3, Hosseini AA1, Simpson RJ1,2,3,4, Welton T1,2, Dineen RA1,2,3, Auer DP1,2,3.

Author information

Radiological Sciences, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Queen's Medical Centre, Derby Road, Nottingham, UK, NG7 2UH.
Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham, University Park, Nottingham, UK, NG7 2RD.
NIHR Nottingham Biomedical Research Centre, Queen's Medical Centre, University of Nottingham, Nottingham, UK, NG7 2UH.
Department of Vascular Surgery, Nottingham University Hospitals NHS Trust, Queen's Medical Centre, Derby Road, Nottingham, UK, NG7 2UH.



The interrelation of cognitive performance, cerebrovascular damage and brain functional connectivity (FC) in advanced arteriosclerosis remains unclear. Our aim was to investigate the associations between FC, white matter damage and cognitive impairment in carotid artery disease.


Seventy-one participants with recent cerebrovascular event and with written informed consent underwent resting-state functional MRI (fMRI) and the Addenbrooke's Cognitive Examination-Revised (ACE-R). Network and inter-hemispheric FC metrics were compared between cognitively normal and impaired subjects, and interrelated with cognition. In order to explore the nature of FC changes, we investigated their associations with microstructural damage of related white matter tracts and cognitive performance, followed by mediation analysis.


Participants with global cognitive impairment showed reduced FC compared to the cognitively intact subjects within the central executive network (CEN), and between hemispheres. Patients with executive dysfunction had decreased CEN FC while patients with memory loss demonstrated low FC in both CEN and default mode network (DMN). Global performance correlated with connectivity metrics of the CEN hub with DMN nodes, and between hemispheres. Cingulum mean diffusivity (MD) was negatively correlated with the ACE-R and CEN-DMN FC. The cingulum MD-cognition association was partially mediated by CEN DMN FC.


Long-range functional disconnection of CEN with DMN nodes is the main feature of cognitive impairment in elderly subjects with symptomatic carotid artery disease. Our findings provide further support for the connectional diaschisis concept of vascular cognitive disorder (VCD), and highlight a mediation role of functional disconnection to explain associations between microstructural white matter tract damage and cognitive impairment.


Vascular dementia; cohort study; functional magnetic resonance imaging (fMRI); s


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