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Phosphodiesterase 4D Single-Nucleotide Polymorphism 83 and Cognitive Dysfunction in Carotid Endarterectomy Patients

Heyer, Eric J. MD, PhD*,‡; Mergeche, Joanna L. BA*; Ward, Justin T. BS*; Malone, Hani R. MD§; Kellner, Christopher MD§; Bruce, Samuel S. MA§; Connolly, E. Sander MD‡,§

Neurosurgery:
doi: 10.1227/NEU.0000000000000085
Research-Human-Clinical Studies
Abstract

BACKGROUND: Phosphodiesterase 4D (PDE4D), through the regulation of cyclic AMP, modulates inflammation and other processes that affect atherosclerosis and stroke. A PDE4D polymorphism, single-nucleotide polymorphism (SNP) 83 (rs966221), is associated with ischemic stroke. The association of SNP 83 with postoperative cognitive dysfunction has never been investigated.

OBJECTIVE: To determine whether SNP 83 is associated with cognitive dysfunction 1 day and 1 month following carotid endarterectomy (CEA).

METHODS: Three hundred fourteen patients with high-grade carotid stenosis scheduled for CEA consented to participate in this single-center cohort study of cognitive dysfunction.

RESULTS: Patients with the C/C genotype of SNP 83 exhibited significantly more cognitive dysfunction at 1 day (29.7%) than the C/T (15.8%, P = .008) and T/T (12.7%, P = .01) genotypes. In a multivariate logistic regression model, C/T and T/T genotypes were both associated with significantly decreased odds of cognitive dysfunction compared with the C/C genotype (odds ratio, 0.45 [0.24-0.83], P = .01 and odds ratio, 0.33 [0.12-0.77], P = .02). There were no significant associations at 1 month.

CONCLUSION: The C/C genotype of SNP 83 is significantly associated with the highest incidence of cognitive dysfunction 1 day following CEA in comparison with the C/T and T/T genotypes. This PDE4D genotype may lead to accelerated cyclic AMP degradation and subsequently elevated inflammation 1 day after CEA. These observations, in conjunction with previous studies, suggest that elevated inflammatory states may be partially responsible for the development of cognitive dysfunction after CEA, but more investigation is required.

ABBREVIATIONS: CEA, carotid endarterectomy

PDE4D, phosphodiesterase 4D

SNP, single-nucleotide polymorphism

Author Information

*Department of Anesthesiology, Columbia University, New York, New York;

Department of Neurology, Columbia University, New York, New York;

§Department of Neurological Surgery, Columbia University, New York, New York

Correspondence: Eric J. Heyer, MD, PhD, 630 W 168th St, P&S Box 46, New York, NY 10032. E-mail: ejh3@columbia.edu.

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Received January 16, 2013

Accepted July 09, 2013

Copyright © by the Congress of Neurological Surgeons