Asymptomatic Carotid Stenosis: Cognitive Function and Plaque Correlates - 2

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Vascular cognitive impairment is an insidious disease resulting from accumulated ischemic injury to the brain. Our VA Merit-funded Asymptomatic Carotid Stenosis and Cognitive Function (ACCOF) found that in the setting of carotid stenosis, alterations of behavior can occur in the absence of physical manifestations of stroke. Otherwise asymptomatic patients with carotid stenosis had worse cognitive performance than controls. In addition, approximately 40% of patients with stenosis had cerebral hemodynamic compromise at baseline; and hemodynamic compromise correlated with cognitive impairment. Not all patients with carotid stenosis have reduced cerebral perfusion. The geometry of the plaque (degree of stenosis, length and shape of the plaque) and, as we have demonstrated, the extent of intra-cerebral collateralization across the Circle of Willis, influence cerebral perfusion. The implication of these findings is that a subset of carotid stenosis patients has hemodynamic compromise, and that reversal of the hemodynamic abnormalities by removing the stenosis may ameliorate the associated cognitive impairment. Therefore, treatment for carotid stenosis might need to be broadened to include preservation of cognition-related Quality of Life (QoL). The demonstration that some patients with carotid stenosis are living with reversible cognitive impairment would have important public-health implications. Carotid stenosis affects 2-12% of people. With 23 million Veterans in the country, approximately 1 million (4.3%) will have a stenosis. ACCOF shows that these patients are at risk for cognitive impairment which, with intervention, might be reversible. We propose a longitudinal controlled observational study that assesses whether carotid revascularization improves cognitive dysfunction in patients with cerebral hemodynamic compromise. Proof of concept (followed by a clinical trial) is necessary before a shift in clinical practice is considered. If cognitive decline can be reversed in these patients, we will have established a new indication for carotid revascularization independent of stroke prevention. We will enroll 138 patients with asymptomatic high-grade (≥70%) carotid stenosis undergoing planned carotid endarterectomy. Approximately 40% (n=55 patients) of patients are anticipated to have compromised cerebral perfusion at baseline (study group); the remaining 60% (n=83) will have carotid stenosis but will not have compromised perfusion (control group). Our Primary Aim will determine if carotid revascularization improves cognitive performance at 1 year in patients with cerebral hemodynamic compromise at baseline. We hypothesize that among patients with asymptomatic carotid stenosis undergoing carotid endarterectomy, cognitive performance will improve more in those with impaired cerebral perfusion at baseline versus those with normal baseline perfusion. Our Secondary Aim 1 will determine whether cerebral hemodynamic compromise is the result of pressure drop across the carotid artery stenosis. We hypothesize that among all patients enrolled, the degree of PWI-TTP delay at baseline will correlate with the degree of pressure drop across the carotid stenosis. Pressure drop will be measured by patient-specific computational fluid dynamic modeling based on 3D imaging of carotid luminal geometry, flow measurements, and analysis of the circulation in the Circle of Willis. Secondary Aim 2 will determine whether cognitive improvement after revascularization is the result of improved cerebral hemodynamics. We hypothesize that among patients with delayed PWI-TTP at baseline, the degree of improvement in cognition after revascularization will correlate with the improvement in pressure drop. Secondary Aim 3 will determine whether differences in cognitive outcome between the two groups impact quality of life. We hypothesize that 1 year after revascularization, quality of life will improve more in patients with impaired baseline cerebral perfusion versus those without impairment.