There is no cognitive benefit from carotid revascularization compared with intensive medical therapy alone in patients with asymptomatic carotid stenosis.

Results from the landmark Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis (CREST-2) randomized trial showed no differences in cognitive trajectories among patients assigned to carotid endarterectomy (CEA) or carotid stenting plus intensive medical management compared with intensive medical therapy alone over a mean follow-up of nearly 3 years.

Restoring cerebral perfusion through carotid revascularization has long been thought to improve cognition in patients with asymptomatic carotid artery disease and was cited by some clinicians as a justification for intervention, lead study author Ronald M. Lazar, PhD, professor of neurology and neurobiology at The University of Alabama at Birmingham, told Medscape Medical News.

However, these new findings from CREST-2 should change the way clinicians counsel patients about these procedures, he said.

“From a clinical point of view, doctors can no longer tell these patients that opening their carotid artery may not only prevent stroke but improve their cognition,” he said.

The study was presented on February 4 at International Stroke Conference (ISC) 2026.

Answering a Key Question

Carotid artery stenosis is a major risk factor for ischemic stroke, accounting for approximately 8% of stroke. Prior studies suggest severe asymptomatic stenosis may impair cognitive function, but whether revascularization improves cognition is unclear.

Interest in cognitive outcomes has grown as awareness increases around the importance of preserving cognition in an aging population. Lazar said many patients place a higher priority on maintaining cognitive function than avoiding physical disability.

That concern was reinforced by a 2025 study by Lazar and colleagues showing that patients enrolled in CREST-2 had below-normal cognitive performance at baseline — before any intervention — particularly in memory compared with a matched population-based cohort after adjustment for demographic and cardiovascular risk factors.

These findings led investigators to hypothesize that carotid revascularization might improve cognitive function in patients with asymptomatic carotid stenosis.

To determine whether the procedure improves cognitive outcomes compared with intensive medical therapy alone in this patient population, the researchers conducted a large, multicenter randomized controlled trial with longitudinal cognitive assessment.

CREST-2 incorporated serial cognitive testing at baseline and annually for up to 4 years, making it the first, large, randomized trial in carotid stenosis to include cognition as a major outcome.

No Between Group Differences

The study included 2165 asymptomatic CREST-2 participants with severe carotid stenosis, defined as greater than 70% arterial narrowing. Previous research indicates that approximately 75%-80% of patients in the US who undergo carotid artery stenting (CAS) or endarterectomy are asymptomatic.

A total of 7060 cognitive assessments were administered by telephone at baseline — after randomization but before initiation of assigned treatment — and annually thereafter for up to 4 years.

The test battery assessed multiple cognitive domains, including learning (Word List Learning), attention (Digit Span forward and backward), memory (Word List Delayed Recall), and executive function (Animal Naming [verbal fluency] and Letter Fluency [F, A, and S]).

The cognitive battery was developed and validated in the population-based Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.

Researchers calculated Z scores for each individual cognitive test within treatment groups of the CAS and CEA trials and averaged these scores to generate a composite measure of overall cognitive performance.

Analyses were adjusted for demographic variables — age, race, and education — as well as major cardiovascular risk factors associated with cognitive performance, including hypertension, diabetes, dyslipidemia, and smoking.

Results showed “there was absolutely no difference between therapy and revascularization, for any of the tests,” said Lazar.

Given the hypothesis that improved cerebral perfusion would enhance cognition, the findings were somewhat unexpected, Lazar said. “This makes us realize that chronic hypoperfusion to the brain may cause irreversible damage.”

Investigators also examined participants with the lowest baseline cognitive performance and again found no differences in cognitive outcomes among the treatment groups.

“[Patients] received no benefit getting revascularization vs medical therapy, even though they had the most to gain from the intervention.”

A ‘True Finding’

Researchers also examined a subset of 118 participants who experienced a stroke during follow-up and found that cognitive testing detected a significant deterioration in cognitive function.

The observed cognitive decline after stroke reassured investigators that the test battery was sufficiently sensitive to detect meaningful neurologic change and supported the conclusion that the lack of cognitive differences between treatment groups reflected a true finding, Lazar said.

The new results suggest there’s a need to investigate other features of carotid stenosis that might contribute to cognition, he added.

Lazar suggested that in some cases, embolic particles may originate from the stenosis itself, or that chronic cerebral hypoperfusion could lead to cortical thinning. “Maybe those are treatment targets we could look at.”

He also noted that although cognition did not improve among study participants, it did not appear to worsen either. “Perhaps there’s a protective effect [of the intervention], but we can’t assert that based on the data we obtained.”

Lazar noted the brain’s “remarkable ability to maintain its function even as the narrowing of the vessel takes place,” emphasizing that participants in the study were asymptomatic.

“You could have 60%-70% narrowing of the vessel and there’s no clinical impact whatsoever, so the brain is really extraordinary in how it accommodates these changes in perfusion.”

The study had several limitations. Cognitive testing was conducted by telephone, which precluded assessment of visuospatial abilities and the full range of executive functions, and the analysis was limited to English-speaking participants.

Experts Weigh In

Commenting for Medscape Medical News, Rodica Di Lorenzo, MD, PhD, Cerebrovascular Center, Neurological Institute, Cleveland Clinic, Cleveland, said the CREST-2 Cognitive Sub-study provided some lessons for clinicians. Importantly, it showed that while CAS prevents stroke, it does not prevent cognitive decline.

“The findings suggest that cognitive impairment in patients with severe carotid artery stenosis likely reflects irreversible neurological injury rather than ongoing hypoperfusion that can be reversed with revascularization.”

In a press release, Mitchell Elkind, MD, chief science officer for brain health and stroke at American Heart Association, said the findings reflect the complexity of cognitive decline associated with aging.

“Restoration of blood flow through the large vessels alone may not be sufficient to address the many other pathways to decline, such as inflammation, neurodegeneration and small vessel disease.”

He added more research is needed on how to mitigate cognitive decline and reduce dementia risk.

CREST-2 received funding from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Centers for Medicare and Medicaid Services, Department of Health and Human Services, and StrokeNet.

Lazar and Di Lorenzo reported having no relevant conflicts of interest.