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. 2013 Nov;73(5):791-6; discussion 796.
doi: 10.1227/NEU.0000000000000085.

Phosphodiesterase 4D single-nucleotide polymorphism 83 and cognitive dysfunction in carotid endarterectomy patients

Eric J Heyer  1 , Joanna L Mergeche, Justin T Ward, Hani R Malone, Christopher Kellner, Samuel S Bruce, E Sander Connolly
Affiliations

Phosphodiesterase 4D single-nucleotide polymorphism 83 and cognitive dysfunction in carotid endarterectomy patients

Eric J Heyer et al. Neurosurgery. 2013 Nov.

Expression of concern in

  • Editorial Expression of Concern.
    [No authors listed] [No authors listed] Neurosurgery. 2023 Aug 1;93(2):489. doi: 10.1227/neu.0000000000002565. Epub 2023 Jun 9. Neurosurgery. 2023. PMID: 37293834 No abstract available.

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.

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Figures

FIGURE
FIGURE
Incidence of cognitive dysfunction at 1 day and 1 month. Bar graph of the incidence of cognitive dysfunction at 1 day and 1 month in patients with each SNP 83 genotype. Error bars are 95% confidence intervals. Patients with the C/C genotype 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. The comparisons at 1 month are not significantly different. PDE4D, phosphodiesterase 4D; SNP, single-nucleotide polymorphism.
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References

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