Project Summary: Complete occlusion of the internal carotid artery (COICA) by atherosclerotic disease causes approximately 15%–25% of ischemic strokes in the carotid artery distribution. Additionally, 40% of subjects with COICA who present with transient ischemic attacks and 70% of COICA who present with stroke have cognitive decline with significantly increased risk of vascular dementia and Alzheimer's' disease with time. Our group and others have used an alternative approach to revascularize subjects with COICAs. These studies showed the feasibility and safety of using endovascular angioplasty and stenting (EAS) and/or hybrid of both carotid enterectomy (CEA) and EAS to restore cerebral flow to the ipsilateral hemisphere of the COICA. Furthermore, our group devised a new angiographic and anatomic classification to upfront predict the success of revascularization using these techniques. This classification was tested in 2 pilot studies and the results showed robust plausibility to predict upfront the percentage of success anticipated in revascularizing these lesions using these techniques. In addition, 3 groups including ours showed that revascularization using these techniques restored cerebral blood flow to the ipsilateral hemisphere of the COICA evident of normalization of mean transient time (MTT) on CT perfusion (CTP) and significant improvement in the cognitive function. EAS and hybrid technique restore the caliber of the cervical ICA and therefore, the blood flow to all involved vessels with clear evidence of complete resolution of penumbra and normalization of MTT on CTP. This could provide an explanation for the marked improvement of cognitive function. Best medical management for this cohort maybe sufficient to reduce the risk of recurrent strokes and/or TIAs but not enough to improve executive and cognitive function and minimize the accelerated risk of vascular dementia and AD with time. This creates a clinical gap and a must need of an alternative approach to help this cohort. Therefore, we leverage our data and others to test the primary hypothesis below: Primary Hypothesis: Revascularizing symptomatic COICA using endovascular techniques (or Hybrid of carotid endarterectomy and endovascular techniques) will significantly improve cognitive outcome. To test this hypothesis we will examine these objectives: Primary Objective: To test the hypothesis that endovascular revascularization of COICA improves significantly cognitive function measured by Montreal Cognitive Assessment (MoCA) test. Secondary Objectives: To test the hypothesis that subjects with symptomatic COICAs and mild/moderate cognitive dysfunction have the following biomarkers: A) Large penumbra (≥50 ml) measured by mismatch volume of cerebral blood flow (CBF) & MTT on CTP, B) Presence of lactate and decreased N-acetylaspartate to creatine (Naa/Cr) in the watershed area (specifically centrum semiovale) on MRI-spectroscopy, and C) Decreased volumes of the hippocampus and amygdala on MRI.

Project Narrative: Subjects with complete occlusion of the ICA by atherosclerotic disease (COICA) have increased risk of cognitive decline and dementia and Alzheimer's' disease with time. Our group and others have showed the feasibility and safety of using endovascular angioplasty and stenting (EAS) and/or hybrid of both carotid enterectomy (CEA) and EAS to restore cerebral flow to the ipsilateral hemisphere of the COICA and improve cognitive outcome. Our proposal aims to test specific biomarkers to identify subject with COICA and cognitive impairment and assess the efficacy of using endovascular techniques in this cohort to reverse the natural history of rapid progression to vascular dementia and Alzheimer's' disease with time.