Abstract
Background and purposeThe 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.MethodsSeventy‐one participants with a recent cerebrovascular event and with written informed consent underwent resting‐state functional magnetic resonance imaging 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, their associations with microstructural damage of related white matter tracts and cognitive performance were investigated, followed by mediation analysis.ResultsParticipants 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 whilst patients with memory loss demonstrated low FC in both the CEN and the 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 ACE‐R and CEN–DMN FC. The cingulum MD–cognition association was partially mediated by CEN–DMN FC.ConclusionsLong‐range functional disconnection of the 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, and highlight a mediation role of functional disconnection to explain associations between microstructural white matter tract damage and cognitive impairment.
Highlights
Vascular cognitive disorder (VCD) is common in people 65 years of age and older [1] and encompasses a range of cognitive disorders that have a presumed vascular cause which may be small vessel disease, territorial infarctions or haemorrhage
Long-range functional connectivity (FC) alterations were characterized in relation to cognition and microstructural white matter tracts (WMTs) injuries in patients with symptomatic carotid artery disease
Functional disconnection of the central executive network (CEN) including its inter-hemispheric desynchronization was the main abnormality in support of long-range connectivity diaschisis in VCD
Summary
Vascular cognitive disorder (VCD) is common in people 65 years of age and older (prevalence from 2.2%to 16.3%) [1] and encompasses a range of cognitive disorders that have a presumed vascular cause which may be small vessel disease, territorial infarctions or haemorrhage. The functional architecture of the brains of people with symptomatic carotid artery disease with and without cognitive impairment was characterized and compared using established network metrics. The nature of the interrelation between functional disconnection, mean diffusivity (MD) of white matter tracts (WMTs) and cognition was investigated. In order to explore the nature of FC changes, their associations with microstructural damage of related white matter tracts and cognitive performance were investigated, followed by mediation analysis. Conclusions: Long-range functional disconnection of the 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, and highlight a mediation role of functional disconnection to explain associations between microstructural white matter tract damage and cognitive impairment
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