Abstract

Cortical thinning is a potentially important biomarker, but the pathophysiology in cerebrovascular disease is unknown. We investigated the association between regional cortical blood flow and regional cortical thickness in patients with asymptomatic unilateral high-grade internal carotid artery disease without stroke. Twenty-nine patients underwent high resolution anatomical and single-delay, pseudocontinuous arterial spin labeling magnetic resonance imaging with partial volume correction to assess gray matter baseline flow. Cortical thickness was estimated using Freesurfer software, followed by co-registration onto each patient’s cerebral blood flow image space. Paired t-tests assessed regional cerebral blood flow in motor cortex (supplied by the carotid artery) and visual cortex (indirectly supplied by the carotid) on the occluded and unoccluded side. Pearson correlations were calculated between cortical thickness and regional cerebral blood flow, along with age, hypertension, diabetes and white matter hyperintensity volume. Multiple regression and generalized estimating equation were used to predict cortical thickness bilaterally and in each hemisphere separately. Cortical blood flow correlated with thickness in motor cortex bilaterally (p = 0.0002), and in the occluded and unoccluded sides individually; age (p = 0.002) was also a predictor of cortical thickness in the motor cortex. None of the variables predicted cortical thickness in visual cortex. Blood flow was significantly lower on the occluded versus unoccluded side in the motor cortex (p<0.0001) and in the visual cortex (p = 0.018). On average, cortex was thinner on the side of occlusion in motor but not in visual cortex. The association between cortical blood flow and cortical thickness in carotid arterial territory with greater thinning on the side of the carotid occlusion suggests that altered cerebral hemodynamics is a factor in cortical thinning.

Highlights

  • Thinning of the cortex in the brain has been linked to cognitive impairment in neurodegenerative dementias[1,2,3,4] and vascular disease[5,6,7], making the radiographic assessment of cortical thickness a potentially valuable biomarker for cognitive decline.[8]

  • In the present study, using the same cohort, we investigated the relationship between cortical thinning and regional cortical blood flow

  • The motor cortex was thinner on the side of the occluded carotid artery where the blood flow was significantly lower, whereas no such asymmetry in cortical thickness was found in the visual cortex, despite a similar asymmetry in blood flow

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Summary

Introduction

Thinning of the cortex in the brain has been linked to cognitive impairment in neurodegenerative dementias[1,2,3,4] and vascular disease[5,6,7], making the radiographic assessment of cortical thickness a potentially valuable biomarker for cognitive decline.[8]. In patients with cardiovascular disease, it has been reported that chronic hypertension[9], diabetes[10, 11] and heart failure[12] confer risk for generalized cortical thinning. Cortical thinning has been associated with clinically and radiographically apparent cerebral ischemic injury, both in small-vessel and large-vessel infarction, and in association with white matter hyperintensity volumes (WMHV).[13, 14] Yet despite correlative studies in these populations there has not been an adequate way to investigate the hemodynamic variables that contribute to cortical thinning. Asymptomatic, unilateral high grade internal carotid artery (ICA) stenosis may provide a model for one potential factor—altered cerebral blood flow—because intra-subject assessments can be made, comparing blood flow in the occluded vs non-occluded side, and carotid vs non-carotid territory

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