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Association between genetic variants of the cholinergic system and postoperative delirium and cognitive dysfunction in elderly patients

  • Background Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are frequent and serious complications after surgery. We aim to investigate the association between genetic variants in cholinergic candidate genes according to the Kyoto encyclopedia of genes and genomes - pathway: cholinergic neurotransmission with the development of POD or POCD in elderly patients. Methods This analysis is part of the European BioCog project (www.biocog.eu), a prospective multicenter observational study with elderly surgical patients. Patients with a Mini-Mental-State-Examination score ≤ 23 points were excluded. POD was assessed up to seven days after surgery using the Nursing Delirium Screening Scale, Confusion Assessment Method and a patient chart review. POCD was assessed three months after surgery with a neuropsychological test battery. Genotyping was performed on the Illumina Infinium Global Screening Array. Associations with POD and POCD were analyzed using logistic regression analysis, adjusted for age, comorbidities and duration of anesthesia (for POCD analysis additionally for education). Odds ratios (OR) refer to minor allele counts (0, 1, 2). Results 745 patients could be included in the POD analysis, and 452 in the POCD analysis. The rate of POD within this group was 20.8% (155 patients), and the rate of POCD was 10.2% (46 patients). In a candidate gene approach three genetic variants of the cholinergic genes CHRM2 and CHRM4 were associated with POD (OR [95% confidence interval], rs8191992: 0.61[0.46; 0.80]; rs8191992: 1.60[1.22; 2.09]; rs2067482: 1.64[1.10; 2.44]). No associations were found for POCD. Conclusions We found an association between genetic variants of CHRM2 and CHRM4 and POD. Further studies are needed to investigate whether disturbances in acetylcholine release and synaptic plasticity are involved in the development of POD.

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Author:Maria HeinrichORCiD, Miriam SiegORCiD, Jochen Kruppa-ScheetzORCiD, Peter NürnbergORCiD, Peter H. SchreierORCiD, Stefanie Heilmann-HeimbachORCiD, Per HoffmannORCiD, Markus M. NöthenORCiD, Jürgen JankeORCiD, Tobias PischonORCiD, Arjen J. C. SlooterORCiD, Georg WintererORCiD, Claudia SpiesORCiD
Title (English):Association between genetic variants of the cholinergic system and postoperative delirium and cognitive dysfunction in elderly patients
Parent Title (English):BMC Medical Genomics
Document Type:Article
Year of Completion:2021
Release Date:2024/04/23
Tag:CHRM2; CHRM4; Genome-wide association study; Neurocognitive disorder
Article Number:248
Page Number:10
Faculties:Fakultät AuL
DDC classes:600 Technik, Medizin, angewandte Wissenschaften / 610 Medizin, Gesundheit
Review Status:Veröffentlichte Fassung/Verlagsversion
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International