Randomized Clinical Trial Evaluates Revascularization vs Medical Therapy for Carotid Cognitive Impairment

Article Impact Level: HIGH
Data Quality: STRONG
Summary of  JAMA. https://doi.org/10.1001/jama.2026.13384 
Dr. Randolph S. Marshall et al.

Points

Columbia University researchers conducted the CREST H randomized clinical trial substudy evaluating two hundred ninety one patients with asymptomatic high grade carotid stenosis exceeding seventy percent.
Long term follow up data demonstrated that restoring cerebral blood flow via carotid stenting or endarterectomy provided no significant cognitive improvement over intensive medical management alone at one year.
Quantitative cognitive assessments confirmed equal minor performance gains across both surgical and medical treatment arms regardless of baseline cerebral perfusion status or initial cognitive impairment severity.
Primary CREST 2 parent trial data confirmed that carotid stenting combined with medical therapy halved overall stroke risk compared to medication alone changing clinical stroke prevention practices.
Authors concluded that carotid revascularization cannot be expected to reverse cognitive decline emphasizing aggressive lifestyle modification and primary prevention to avoid severe carotid artery stenosis.

Summary

This study evaluated the cognitive effects of carotid revascularization compared to intensive medical management (IMM) alone in patients with asymptomatic severe carotid artery stenosis and hemodynamic impairment. Published in JAMA as the CREST-H substudy of the larger CREST-2 clinical trial, the investigation was led by Columbia University Vagelos College of Physicians and Surgeons researchers. Given that chronic severe carotid stenosis and reduced cerebral blood flow are linked to cognitive decline, the study sought to determine whether restoring cerebral perfusion via carotid stenting or endarterectomy improves cognitive performance compared to medical therapy alone in patients with baseline cognitive dysfunction.

The multicenter randomized clinical trial substudy enrolled 291 patients with asymptomatic high-grade carotid stenosis (70% or greater) and verified cerebral hemodynamic impairment. Participants underwent baseline cognitive and cerebral perfusion assessments and were randomized to receive either carotid revascularization (stenting or endarterectomy) plus IMM or IMM alone, with serial cognitive testing performed at one year follow-up. While both treatment arms demonstrated slight, non-significant baseline-to-one-year cognitive score improvements, quantitative comparative analysis revealed no differential effect of revascularization versus IMM alone on cognitive trajectories (P > .05), regardless of baseline cerebral hemodynamic status or degree of initial cognitive impairment.

The authors conclude that carotid revascularization does not improve cognitive dysfunction by restoring cerebral blood flow in patients with chronic asymptomatic carotid stenosis. While parent CREST-2 findings demonstrated that stenting combined with medical management reduced stroke risk twofold compared to medication alone, revascularization should not be performed with the expectation of reversing cognitive decline. Clinicians should emphasize primary prevention and aggressive risk factor modification to prevent carotid stenosis and preserve long-term cognitive health.

Link to the article: https://jamanetwork.com/journals/jama/article-abstract/2854196

References

Marshall, R. S., Lazar, R. M., Meschia, J. F., Huston, J., Edwards, L. J., Brott, T. G., Lal, B. K., Howard, G., Mena-Hurtado, C., Heck, D., Sangha, N., Lanzino, G., Kashyap, V. S., Aronow, H. D., Sharafuddin, M., Voeks, J., Zhang, Y., Slane, K., & Liebeskind, D. S. (2026). Revascularization in asymptomatic carotid artery stenosis with hemodynamic impairment and cognitive outcomes: The crest-h substudy of the crest-2 randomized clinical trial. JAMA. https://doi.org/10.1001/jama.2026.13384