Genome-Wide DNA Methylation Profiles of Long-Term Cognitive Decline after Delirium in Intensive Care Unit Patients.

Abstract

BACKGROUND To date, no studies have reported on the differences in genome-wide DNA methylation (DNAm) profiles between delirium patients with and without long-term cognitive decline (LTCD). This study aimed to identify epigenetic markers associated with LTCD after delirium using blood samples from intensive care unit (ICU) patients. METHODS Blood DNA samples from 104 patients (86 delirium patients and 18 nondelirium patients) were analyzed using the Illumina EPIC array genome-wide platform. We investigated the differences in DNAm related to the presence or absence of LTCD among delirium patients, nondelirium patients, and the entire cohort. Enrichment analyses were conducted using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome terminology (KEGG). RESULTS Among the 20 top hits of differentially methylated cytosine-phosphate-guanine (CpG) sites associated with LTCD in patients with delirium, CpG located within the major histocompatibility complex (MHC) region on chromosome 6 (cg11103845) was significantly associated after false discovery rate (FDR) correction (FDR-adjusted P = .034). Enrichment analysis revealed immune-related pathways associated with LTCD. Although not statistically significant, MHC class II-related pathways, such as "MHC class II receptor activity" and "MHC class II protein complex assembly," were also ranked among the top hits. CONCLUSIONS This genome-wide DNAm analysis focused on LTCD after delirium highlights differentiating epigenetic signals related to MHC class II and immune processes. These findings provide initial evidence that epigenetic processes may play a crucial role in the pathophysiological mechanisms underlying LTCD after delirium.