CREST-2 Substudy Shows No Cognitive Benefit From Carotid Revascularization Versus Medical Therapy Alone

February 9, 2026—Carotid revascularization did not lead to better cognitive performance compared with intensive medical therapy alone, according to late-breaking data from a CREST-2 substudy presented at the American Stroke Association’s International Stroke Conference 2026.

The findings come from a cognitive substudy of CREST-2, a randomized controlled trial evaluating strategies to reduce stroke risk in patients with asymptomatic carotid stenosis. More than 2,000 adults were enrolled across the parent trial, which compared intensive medical management alone with intensive management plus carotid endarterectomy or carotid artery stenting.

According to the press release from the American Stroke Association, the cognitive substudy assessed whether restoring blood flow through revascularization translated into improvements in thinking or memory. Cognitive testing was performed at baseline and annually for up to 4 years. With a mean follow-up of 2.8 years, investigators found no differences in cognitive trajectories among patients treated with surgery, stenting, or medical therapy alone.

“Whether patients undergo a procedure to remove plaque in the carotid artery, stenting to insert a flexible tube to hold open the narrowed part of the artery, or a combination of medications and lifestyle guidance without a procedure, there should be no expectation that cognition will improve after the treatment,” said lead author Ronald M. Lazar, PhD, FAHA, a professor of neurology and neurobiology at the University of Alabama at Birmingham (UAB) and Director of the UAB McKnight Brain Institute.

Earlier CREST-2 analyses, published in 2021, showed that patients with severe asymptomatic stenosis entered the trial with lower cognitive scores than matched controls, particularly in memory domains. However, the current results indicate that revascularization does not alter cognitive outcomes, even among participants with the lowest baseline performance.

Cognitive decline was observed in participants who experienced a stroke during follow-up, supporting the sensitivity of the testing methods. Investigators noted that worsening cognition over time may still serve as a clinical signal prompting reassessment of management strategies.

Limitations include telephone-based testing, which precluded assessment of visuospatial and some executive functions, and enrollment was limited to English-speaking participants. The findings are based on an abstract presented at a scientific meeting and have not yet undergone peer review, noted the press release.