Impairments in Cognitive Function and Brain Connectivity in Severe Asymptomatic Carotid Stenosis

Abstract

Background and Purpose-Severe asymptomatic carotid stenosis has been associated with cognitive impairment, but it is unknown whether this association is attributable to effects on brain connectivity. We present cognitive network abnormalities in a group of patients at a presymptomatic stage. Methods-Seventeen patients with Ն70% asymptomatic stenosis of unilateral internal carotid artery were compared with 26 healthy controls utilizing a comprehensive neuropsychological battery, the dizziness handicap inventory, and multimodality neuroimaging including diffusion tensor imaging and resting-state functional connectivity magnetic resonance imaging. Longitudinally, assessments were completed in a subgroup of 10 patients at 3 months after carotid artery stenting. Results-Compared with the healthy controls, the patients had worse dizziness scores, poorer memory, complex visuo-spatial performances, and lower whole-brain mean fractional anisotropy. The Scheltens scores of leukoaraiosis/ infarction were not different between groups. Their seed-based functional connectivity magnetic resonance imaging showed marked decrements of interhemispheric and intrahemispheric, ipsilaterally to carotid stenosis, functional connectivity in the frontoparietal network. In the default mode network, the intrahemispheric functional connectivity was bilaterally impaired. Importantly, the disrupted mean fractional anisotropy in the patients significantly correlated with the attention and verbal memory functions. After successful carotid artery stenting, small but measurable increments of the mean fractional anisotropy and little functional connectivity in the default mode network ipsilateral-to-carotid artery stenting were noted. Conclusions-We identified for the first time distinct patterns of network disruption that correlate with cognitive fragility in patients with asymptomatic carotid stenosis. Brain connectivity may provide early and useful biomarkers for brain ischemia and reperfusion. (Stroke. 2012;43:2567-2573.)Key Words: asymptomatic carotid stenosis Ⅲ cognitive impairment Ⅲ diffusion tensor imaging Ⅲ endovascular treatment Ⅲ functional connectivity magnetic resonance imaging Ⅲ resting state Ⅲ stent A symptomatic stenosis of the internal carotid artery (ICA) is described as significant atherosclerosis without stroke or transient ischemic attack in the brain or eyes. 1 Retrospective studies comparing asymptomatic subjects with and without ultrasound-assessed carotid stenosis have shown that subjects with carotid stenosis had significantly poorer performance in tests of attention, psychomotor speed, and memory. [2][3][4] Moreover, severe ICA stenosis (Ն50%) has been associated with a higher prevalence of silent cerebral infarcts and white matter hyperintensities, 3 indicating that "asymptomatic" carotid stenosis may not be truly asymptomatic. To understand the pathological changes after chronic cerebral hypoperfusion, experimental models of vascular cognitive impairment have been induced by bilateral 5 or unilateral 6 common carotid a...

Characteristics of Diffusional Kurtosis in Chronic Ischemia of Adult Moyamoya Disease: Comparing Diffusional Kurtosis and Diffusion Tensor Imaging

“…3 Detecting microstructural changes due to chronic ischemia potentially enables early identification of patients at risk of cognitive impairment. 3,20 However, detecting microstructural changes has been hampered by the limited sensitivity of DTI in fiber-crossing areas. 7 In this study, DKI demonstrated microstructural changes, predominantly in the dorsal part of the deep white matter, where conventional MR imaging frequently demonstrates ischemic lesions.…”

Intervention versus Aggressive Medical Therapy for Cognition in Severe Asymptomatic Carotid Stenosis

“…For DTI, voxelwise fractional anisotropy (FA) was analyzed after applying preprocessing with Tract-Based Spatial Statistics from the FMRIB Software Library (TBSS; http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/TBSS), as previously described. 12 We performed a paired t test for withingroup interval changes of the FA maps and then a 2-sample t test for between-group comparison of the interval changes with a significance set at P Ͻ .05 with family-wise error rate correction for multiple comparisons (random permutations, n ϭ 5000).…”

“…10,11 We previously demonstrated that patients with unilateral asymptomatic carotid stenosis of Ն70% had more dizziness/ unsteadiness and poorer verbal memory, executive function, and visuospatial perception than the healthy controls, accompanied by extensive widespread disruption of long-range structural and functional connectivity. 12,13 The mechanisms are likely attributed to microemboli from unstable carotid plaques 5 and/or chronic hypoperfusion. 14,15 Single-arm studies of carotid revascularization accomplished by either carotid endarterectomy or CAS reported the controversial results of cognitive enhancement in patients with asymptomatic carotid stenosis.…”

Cerebral Autoregulation and Brain Networks in Occlusive Processes of the Internal Carotid Artery

“…11,12 With regard to largescale networks, changes in white matter microstructure and RSFC may account for cognitive decline in these patients. 13 In neurodegenerative diseases, impaired cerebral hemodynamics indicate lower capacity to modulate resistance of cerebral vessels because of cerebral atrophy. 14 Recently, associations between cerebral hemodynamics and white matter hyperintensities have also been reported in older adults without extracranial artery stenoses.…”