Ahead of Print: PDE4D and Cognitive Dysfunction

Background: Phosphodiesterase 4D (PDE4D), through regulation of cyclic-AMP, modulates inflammation and other processes that affect atherosclerosis and stroke. A PDE4D polymorphism, SNP 83 (rs966221), is associated with ischemic stroke. The association of SNP 83 with post-operative 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=0.008) and T/T (12.7%, P=0.01) genotypes. In a multivariate logistic regression model, C/T and T/T genotypes were both associated with significantly decreased odds of cognitive dysfunction compared to the C/C genotype (OR: 0.45 [0.24-0.83], P=0.01 and OR: 0.33 [0.12-0.77], P=0.02). 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 compared to 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 elevated inflammatory states may be partially responsible for the development of cognitive dysfunction after CEA, but more investigation is required.

From: Phosphodiesterase 4D Single Nucleotide Polymorphism 83 and Cognitive Dysfunction in Carotid Endarterectomy Patients by Heyer et al.

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