Abstract
BackgroundPostoperative 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.MethodsThis 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).Results745 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.ConclusionsWe 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.Trial registration: ClinicalTrials.gov: NCT02265263.
Highlights
Postoperative delirium (POD) is a common and serious complication, presenting as an acute change in the mental state in terms of attention and other cognitive functions [1]
The incidence of POD and postoperative cognitive dysfunction (POCD) is related to a number of predisposing and precipitating risk factors [6, 7], and the condition can develop at any age, older patients are susceptible
Genome-wide association studies (GWAS) have so far been unable to identify a link between the cholinergic system and the development of POD and POCD [13, 14], numerous polymorphisms are located in the cholinergic system [15] and a connection to inflammation has already been established [16]
Summary
Postoperative delirium (POD) is a common and serious complication, presenting as an acute change in the mental state in terms of attention and other cognitive functions [1]. Results of a systematic review suggest that genetic factors are likely to influence the development of POD and POCD [9, 10]. Genome-wide association studies (GWAS) have so far been unable to identify a link between the cholinergic system and the development of POD and POCD [13, 14], numerous polymorphisms are located in the cholinergic system [15] and a connection to inflammation has already been established [16]. 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
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