Asymptomatic Carotid Stenosis Linked to Cognitive Impairment

Daniel M. Keller, PhD

April 30, 2014

PHILADELPHIA — A new study of people with at least 50% carotid narrowing but no obvious neurologic deficit finds that they have greater cognitive impairment than people with similar vascular and other risk factors but no carotid stenosis.

"The key finding is that we've identified for the first time unequivocally that a plaque in the carotid artery of a patient that has never suffered a stroke before in and of itself can result in cognitive impairment," principal investigator Brajesh Lal, MD, chief of vascular surgery at the Baltimore Veterans Affairs Medical Center and professor of vascular surgery at the University of Maryland School of Medicine in Baltimore, told Medscape Medical News.

He said that a significantly large percentage of the older population may be suffering, "and it's flying under the radar screen because nobody has really focused on this."

The study is being presented as a poster and a "data blitz" talk here at the American Academy of Neurology (AAN) 66th Annual Meeting by first author Moira Dux, PhD.

Carotid Disease

US and European trials carried out in the 1990s and early 2000s have produced controversial results in terms of the best ways to manage mild to moderate carotid artery occlusive disease. For high-grade stenosis, carotid endarterectomy has been shown to be a moderately better alternative than optimal medical management.

The present study sought to determine whether a blood flow limitation or microembolization from disruption of unstable plaques injures parts of the brain that are not immediately expressive.

"There's a whole lot of brain material between the sensory and motor cortices, and if we are hurting that, should we be testing for it in order to identify whether there is injury that is ongoing?" Dr. Lal asked.

This cross-sectional study compared patients who had asymptomatic carotid stenosis with patients who had vascular risk factors but no visible plaque in the carotid artery on duplex ultrasonography, which was also used to assess patency of the circle of Willis. The patients with stenosis had 50% or greater unilateral stenosis. Patients with a history of stroke in either hemisphere, operation on either carotid artery, or an occlusion on the contralateral side were excluded.

The researchers administered well-validated neuropsychological measures to each group. The 67 patients with stenosis had an average age of 68.9±7 years vs 66.1±7 years for controls. Both groups comprised more than 90% men. White patients made up 80% of the stenosis group and 50% of the controls. The remainder of each group was African American. Educational attainment was approximately the same for each group.

Groups did not significantly differ in the prevalence of diabetes, hypertension, dyslipidemia, peripheral vascular disease, symptomatic coronary artery disease, or smoking.

The researchers conducted tests of learning and memory, motor/processing speed, executive function, attention/working memory, and language.

T-scores indicated the proportion of patients above or below the 50th percentile, after adjustment of the scores for age, sex, education, and race. From these results the researchers calculated Cohen's d score, a measure of clinically (not just statistically) significant differences between groups. Cohen's d scores of 0 to 0.4 are considered to indicate a mildly important clinical difference; 0.4 to 0.6, a moderately important clinical difference; and 0.6 and greater, a pathologic difference.

Moderate to severe clinically significant differences occurred on tests of learning/memory, motor/processing speed, and the neurocognitive composite score.

Table. Neuropsychological Performance

Neuropsychological Battery Adjusted T-Score in Controls Adjusted T-Score in Patients With Stenosis P Value Cohen's d Score
Learning/memory 48 44 ≤.05 .48
Motor/processing speed 49 43 ≤.01 .69
Executive function 44 40 ≤.07 .35
Attention/working memory 49 46 ≤.15 .26
Language 50 50 NS
Neurocognitive composite 48 45 ≤.01 .52

NS, not statistically significant.


Dr. Lal said a remaining question is the mechanism of injury: reduced blood flow, microembolization, or both. He is following patients and measuring cerebral blood flow with transcranial Doppler ultrasonography and microinfarctions with MRI. The answer to this question will inform a second one, namely whether aggressive medical therapy to stabilize plaque, cognitive rehabilitation to reverse some of the impairment, or revascularization should be tested.

He and colleagues will follow each patient in the study for at least 2 years with imaging and cognitive testing to see whether there is continued cognitive deterioration in the patients with stenosis compared with controls and to look at mechanisms.

He pointed out that the Agency for Healthcare Research and Quality (AHRQ) has no recommendation for screening but that maybe it should consider one. The Society for Vascular Surgery and the American Heart Association differ from AHRQ, he said, in that both organizations recommend selective screening for carotid stenosis in individuals with risk factors for atherosclerosis.

I think one could argue that this has equal if not more impact than even a stroke. Dr. Brajesh Lal

The study findings could have large public health implications. "Based on the number of individuals that are potentially impacted, and based on the fact that this degree of impairment will clearly have an effect on the ability of people to perform their jobs if they're relatively younger or their activities of daily living if they are older and retired, I think one could argue that this has equal if not more impact than even a stroke," Dr. Lal predicted, based on the much smaller number of strokes associated with carotid stenosis, which is around 10% of all strokes.

Mechanism Unclear

Sana Bloch, MD, clinical professor of neurology at Albert Einstein College of Medicine in Bronx, New York, wondered, "Why would stenosis of only 50% cause a person to have cognitive impairment?" He commented to Medscape Medical News that the study is not large enough or sufficiently powered to answer that question.

"I'd like to hope that there is some sort of correlation, but I can't figure out physiologically why that would occur unless you say that anybody who already has carotid stenosis has small-vessel disease in addition that's not being seen in the analysis," he said, with the implication that carotid stenosis is a predictor or marker of cerebrovascular disease or cognitive impairment "as opposed to the fact that's it a flow phenomenon."

David Knopman, MD, a neurologist at the Mayo Clinic in Rochester, Minnesota, also expressed some skepticism about the claim that asymptomatic carotid stenosis was associated with worse cognition because part of the basis of such a claim would depend on having a comparable control group — and the "poster says nothing about the control group." So he suggested 2 possible scenarios.

"If the control group was matched for cardiovascular risk factors and other relevant covariates, then it could be the case that the authors' claims are supportable," he said. However, if the control group was not comparable in terms of cardiovascular risk factors, "then I would assert that their claim is seriously compromised, because persons with diabetes, hypertension, and significant vascular disease are generally known to have more cognitive impairment than their peer without those risk factors."

Dr. Knopman noted that most prior studies of large-vessel (carotid) disease found no or very modest associations with cognition.

The study was funded by the Research and Development Department of the Department of Veterans Affairs. Dr. Lal and Dr. Bloch have disclosed no relevant financial relationships. Dr. Knopman has received personal compensation for activities with Lundbeck Pharmaceuticals.

American Academy of Neurology (AAN) 66th Annual Meeting. Emerging Science Platform Session. Abstract 003. Presented April 30, 2014.


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