“The one thing you could say, looking at these data, is that hyperperfusion, or subclinical hyperperfusion, probably explains about 50% of the cognitive deficits in this patient population, but the other 50% remain unexplained,” Dr. Connolly remarked.
“In terms of carotid stenting, the vast majority of the data leads us to believe that unlike endarterectomy, microemboli may play a bigger role in this population,” said Dr. Connolly, who has a paper in press evaluating the degree to which microembolic signals correlate with cognitive dysfunction in this patient population. “What hasn’t been looked at in this population yet is the degree to which hyperperfusion may also play a role,” he said.
Risk Factors for Cognitive Dysfunction
According to Dr. Connolly, data on predictors of cognitive dysfunction in patients with carotid stenotic disease are more abundant for those undergoing endarterectomy, compared with stenting. For patients undergoing stenting, “the only thing that we’ve been able to come up with is the current use of statins,” he said. “Patients who are not on statins have a much higher incidence of injury than those patients who are on statins, and this may have something to do with plaque stability and microembolic phenomenon.”
On the other hand, for patients undergoing endarterectomy, much more data are available. Risk factors for cognitive dysfunction include diabetes, extremes of age, obesity, preoperative monocyte count, apolipoprotein E ε4 polymorphisms, polymorphisms in a complement mannan-binding lectin pathway, and inducible nitric oxide synthase polymorphisms.
Ongoing Research in Patients With Carotid Stenotic Disease
Dr. Connolly noted that he and his colleagues are currently conducting biomarker and genetic studies to identify additional risk factors that might predispose an individual to cognitive injury.
Other ongoing research efforts include modifying endovascular techniques, through the use of various devices, to reduce the incidence of cognitive injury resulting from microembolic phenomenon, as well as studying diabetic patients to determine whether improving regional flow reduces the incidence of cognitive injury following endarterectomy.
Dr. Connolly’s team is also working on determining the ability of neuroprotective drugs to reduce incidence of cognitive injury in nondiabetic patients undergoing endarterectomy. In one such study, published in the February 6 online Journal of Neurosurgery, the researchers found that both high and low intraoperative magnesium dosing appears to be protective at 24 hours postsurgery, especially in patients receiving low-dose magnesium.
“Understanding cognitive dysfunction following carotid endarterectomy and stenting may offer a means to improve both procedures, as well as develop a better understanding of the pathophysiology of cerebral ischemia and injury in humans, especially in the aging population,” concluded Dr. Connolly.
—Karen L. Spittler