Is Hemispheric Hypoperfusion a Treatable Cause of Cognitive Impairment?

  • Amani M. Norling
  • Randolph S. Marshall
  • Marykay A. Pavol
  • George Howard
  • Virginia Howard
  • David Liebeskind
  • John HustonIII
  • Brajesh K. Lal
  • Thomas G. Brott
  • Ronald M. LazarEmail author
Stroke (JF Meschia, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Stroke


Purpose of Review

To review the current literature that supports the notion that cerebral hemodynamic compromise from internal carotid artery stenosis may be a cause of vascular cognitive impairment that is amenable to treatment by revascularization.

Recent Findings

Converging evidence suggests that successful carotid endarterectomy and carotid artery stenting are associated with reversal of cognitive decline in many patients with severe but asymptomatic carotid artery stenosis. Most of these findings have been derived from cohort studies and comparisons with either normal or surgical controls. Failure to find treatment benefit in a number of studies appears to have been the result of patient heterogeneity or confounding from concomitant conditions independently associated with cognitive decline, such as heart failure and other cardiovascular risk factors, or failure to establish pre-procedure hemodynamic failure.


Patients with severe carotid artery stenosis causing cerebral hemodynamic impairment may have a reversible cause of cognitive decline. None of the prior studies, however, were done in the context of a randomized clinical trial with large numbers of participants. The ongoing CREST-2 trial comparing revascularization with medical therapy versus medical therapy alone, and its associated CREST-H study determining whether cognitive decline is reversible among those with hemodynamic compromise may address this question.


Severe carotid artery stenosis Revascularization Carotid endarterectomy Carotid artery stenting Cerebral hemodynamic impairment Cognition 


Funding Information

This manuscript was funded in part by NIGMS 5T32 GM109780-4 (AMN), NINDS R01 NS097876 (RML, RSM, DSL), U01 NS080168 (TGB, JFM, BKL, RML), and U01 NS080165 (GH,VH). Additional support comes from NIH StrokeNet U01 NS06872 (RSM) and NIH StrokeNet U24NS107223 (RML).

Compliance with Ethical Standards

Conflict of Interest

Amani M. Norling, Randolph S. Marshall, Marykay A. Pavol, George Howard, Virginia Howard, John Huston, III, Brajesh K. Lal, Thomas G. Brott, and Ronald M. Lazar declare that they have no conflict of interest.

David Liebeskind reports being a consultant as Imaging Core Lab for Stryker and Medtronic.

Human and Animal Rights and Informed Consent

This article does not contain any studies with animal subjects performed by any of the authors. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Amani M. Norling
    • 1
  • Randolph S. Marshall
    • 2
  • Marykay A. Pavol
    • 2
  • George Howard
    • 3
  • Virginia Howard
    • 4
  • David Liebeskind
    • 5
  • John HustonIII
    • 6
  • Brajesh K. Lal
    • 7
  • Thomas G. Brott
    • 8
  • Ronald M. Lazar
    • 1
    Email author
  1. 1.Department of NeurologyUniversity of Alabama at BirminghamBirminghamUSA
  2. 2.Department of NeurologyColumbia University Medical CenterNew YorkUSA
  3. 3.Department of Biostatistics (GH)University of Alabama at BirminghamBirminghamUSA
  4. 4.Department of Epidemiology (VH)University of Alabama at BirminghamBirminghamUSA
  5. 5.Department of NeurologyUniversity of CaliforniaLos AngelesUSA
  6. 6.Department of Neuroradiology (JH)Mayo ClinicRochesterUSA
  7. 7.Department of Vascular Surgery (BKL)University of MarylandBaltimoreUSA
  8. 8.Department of NeurologyMayo ClinicJacksonvilleUSA

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