CREST-2 Substudy: Revascularization Does Not Improve Cognition in Asymptomatic Carotid Disease

Findings from a CREST-2 substudy presented at ISC 2026 show that revascularization did not improve cognitive outcomes in patients with asymptomatic carotid artery disease. The study evaluated stroke rates in patients randomly assigned to intensive medical management alone, intensive medical management with carotid endarterectomy, or intensive medical management with stenting. A substudy of the CREST-2 trial used a "cognitive core" to measure cognitive performance from baseline for up to 4 years.

Overall, findings demonstrated no differences in cognitive outcomes between participants who underwent revascularization and those receiving medical therapy alone. Notably, cognitive decline occurred only in patients who experienced a stroke, supporting the sensitivity of the cognitive assessments to neurologic changes. The data show that prior to revascularization there is cognitive decline beforehand, presumably as a result of flow failure across the stenosis. The notion is that, based on the work in stroke, where reperfusion therapy results in significant improvement in neurologic function, revascularization might not only reduce the risk of stroke in these individuals but improve cognition as well.

Carotid artery stenosis, a narrowing of the neck's carotid arteries typically caused by plaque buildup, is generally managed with intensive medical therapy, including antiplatelet agents, medications for blood pressure or cholesterol control, and lifestyle modifications. The lead author, a professor of neurology and neurobiology at the University of Alabama at Birmingham, noted that the study used a structured, longitudinal approach to assess cognitive function over time. He explained that the findings highlighted key considerations regarding cognitive performance and the impact of different treatment strategies, as well as the relationship between vascular events and changes in brain function.