Carotid Revascularization Shows No Cognitive Gain in CREST-2

Carotid revascularization did not improve cognitive function in patients with severe asymptomatic carotid artery stenosis, according to a secondary-outcomes analysis of the CREST-2 randomized clinical trials published in JAMA. The study, led by Ronald M. Lazar, PhD, of the University of Alabama at Birmingham , examined whether procedural treatment offers a cognitive advantage over medical therapy alone.

Prior research has linked asymptomatic carotid stenosis to diminished cognition, but whether revascularization reverses that association had not been established. CREST-2 consisted of two parallel trials comparing carotid artery stenting plus intensive medical management (CAS + IMM) and carotid endarterectomy plus intensive medical management (CEA + IMM), each against intensive medical management (IMM) alone, in patients 35 years or older with 70% or greater asymptomatic carotid stenosis. Enrollment ran from December 2014 through July 2024, with follow-up ending July 2025.

Across 146 clinical sites, five cognitive tests assessing learning, memory, executive function, attention, and processing speed were administered before treatment and annually for up to four years, with blinded central assessment by telephone. Among 2366 US participants, 2165 (91.5%) completed cognitive assessments—1078 in the CAS trial and 1087 in the CEA trial; mean age was 70.1 years, and 37.8% were female.

At four years, adjusted composite cognitive z scores were similar between groups in both trials: 0.22 vs 0.18 for CAS + IMM vs IMM alone, and 0.25 vs 0.23 for CEA + IMM vs IMM alone, with between-group differences that were not statistically significant. No individual cognitive test showed a significant treatment-related difference. A total of 4954 test batteries were administered over a mean of 2.24 follow-up years.

The investigators concluded that, in patients with severe asymptomatic carotid artery stenosis, revascularization with either CAS or CEA plus IMM did not significantly improve cognitive function compared with IMM alone through four years of follow-up.

Source: Lazar RM, Meschia JF, Edwards LJ, et al. Revascularization of asymptomatic carotid artery stenosis: cognitive results of the CREST-2 randomized trials. JAMA. Published online September 16, 2026.doi:10.1001/jama.2026.14703