Differential DNA Methylation and Delirium After Anesthesia and Surgery

Area of Science:

• Epigenetics
• Molecular Biology
• Neuroscience

Background:

• DNA methylation is a key epigenetic mechanism regulating gene expression.
• Environmental factors can influence DNA methylation patterns.
• Postoperative delirium (POD) and postoperative neurocognitive disorder (PNCD) are significant complications following surgery.

Purpose of the Study:

• To investigate differential DNA methylation levels in blood before and after general anesthesia and surgery.
• To identify DNA methylation signatures associated with the development of POD and PNCD.

Main Methods:

• Prospective blood sampling, delirium assessment, and cognitive testing in 94 participants before and at 24 hours and 6 weeks after non-cardiac, non-neurologic surgery.
• DNA methylation analysis using the Illumina Infinium MethylationEPIC Beadchip.
• Comparison of methylation levels between participants with and without POD/PNCD.

Main Results:

• 132 differentially methylated positions (DMPs) and 198 differentially methylated genes (DMGs) were identified 24 hours after surgery compared to baseline.
• Differential DNA methylation at baseline and 24 hours post-surgery distinguished participants who developed POD.
• No significant DMPs were found between baseline and 6 weeks post-surgery, nor between patients with and without PNCD at 6 weeks.

Conclusions:

• Significant genome-wide DNA methylation changes occur 24 hours after anesthesia and surgery.
• Pre-operative and early post-operative DNA methylation patterns can serve as biomarkers for predicting POD.
• DNA methylation differences were not identified as predictors for PNCD in this study.