The complex interaction of genetics and delirium: a systematic review and meta-analysis

Sepúlveda, Esteban; Adamis, Dimitrios; Vásquez, José Gabriel Franco; Meagher, David; Aranda, Selena; Vilella, Elisabet

doi:10.1007/s00406-021-01255-x

Cited by 7 publications

(10 citation statements)

References 56 publications

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“…However, they included only few studies and being interfered by one study with predominant patient number included and there are additional studies being published afterwards [23][24][25]. Previous meta-analyses have reported no association between APOE4 and delirium [26,27]. However, no meta-analysis has examined the relationship between APOE4 and POD.…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein E4 allele is genetically associated with risk of the short- and medium-term postoperative cognitive dysfunction: A meta-analysis and trial sequential analysis

et al. 2023

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The aim of systematic review and meta-analysis was to investigate whether APOE4 was associated with postoperative neurologic dysfunction occurrence in short- or medium-term among surgical patients and to study the potential genetic association among these two entities. We searched electronic databases for reserch studies to evaluate the association of APOE4 with postoperative delirium (POD) or short- and medium term postoperative cognitive dysfunction (POCD). Twenty-two trials (16 prospective and six retrospective) with 6734 patients were included. APOE4 alleles was shown significantly associated with POCD within 1 week (odds ratio, OR, 1.89, 95% confidence interval, CI, 1.36 to 2.6278, p < 0.01) in the random-effects model. A significant association was also noted between APOE4 and POCD in medium-term, 1–3 months, after surgery (OR: 1.67, 95% CI: 1.003–2.839, p = 0.049). However, APOE4 was not significantly associated with POCD 1 year after surgery (OR: 0.98, 95% CI: 0.57–1.70, p = 0.9449) and POD (OR: 1.28, 95% CI: 0.85–1.91, p = 0.23). In conclusion, APOE4 alleles was genetically associated with short- and medium-term postoperative neurological dysfunction and future screening or preventive strategies derived is highly potential to improve outcomes.

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Section: Introductionmentioning

confidence: 99%

Apolipoprotein E4 allele is genetically associated with risk of the short- and medium-term postoperative cognitive dysfunction: A meta-analysis and trial sequential analysis

et al. 2023

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Section: Introductionmentioning

confidence: 99%

“…The hypothesized mechanisms of delirium include neurotransmitters, 13 inflammation, 14 physiologic stressors, 15 metabolic derangements, 16 electrolyte disorders, 17 and genetic factors. 18 This present study was conducted to explore possible biomarkers of POD in PD patients after DBS surgery. The findings might provide valuable scientific clues for the early detection and treatment of POD in PD patients after DBS surgery.…”

Section: Introductionmentioning

confidence: 99%

Detection Analysis of Perioperative Plasma and CSF Reveals Risk Biomarkers of Postoperative Delirium of Parkinson’s Disease Patients Undergoing Deep Brain Stimulation of the Subthalamic Nuclei

Zhou¹,

Ma²,

Yu³

et al. 2022

CIA

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Objective This study aimed to explore possible biomarkers of postoperative delirium (POD) of Parkinson’s disease (PD) patients received deep brain stimulation (DBS) of the subthalamic nuclei. Materials and methods This nested case control study analyzed perioperative plasma and cerebral spinal fluid (CSF) of patients (n = 40) who developed POD undergone DBS surgery (n = 10) and those who did not (n = 30). Blood sample was collected before surgery and on the first day postoperative, CSF sample was collected at the beginning of the operation. POD was assessed by the Confusion Assessment Method (CAM) twice a day between 7:00 am and 7:00 pm after the surgery until discharge. Plasma and CSF sample from the two groups were analyzed to investigate possible biomarkers for POD in PD patients. Results There was no difference between POD and Non-POD groups on the concentration of Interleukin 6 and Tumor Necrosis Factor-α in CSF, preoperative plasma and postoperative plasma. There was no difference between POD and Non-POD groups on the concentration of S100 calcium-binding protein β protein (S100β) and Neurofilament light chain (NFL) in preoperative plasma and postoperative plasma. The concentration of C-reactive protein (CRP), NFL and S100β were significant higher in POD group than non-POD group in CSF. The concentration of CRP was significantly higher in POD group than non-POD group in preoperative plasma and postoperative plasma. CSF concentration of S100β might be a potential biomarker for POD via the receiver operating characteristic curve analysis and the area under the curve value of 0.973. Conclusion For PD patients received DBS surgery, CSF S100β might be a marker for aiding detection of high-risk patients with delirium. This requires further confirmation in clinical trials.

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“…It is unknown to what extent POD and POCD are subject to genetic factors [ 8 ]. However, results of a systematic review suggest that genetic factors are likely to influence the development of POD and POCD [ 9 , 10 ]. Neurotransmitter imbalance, in addition to neuroinflammation is one of the leading hypotheses for the development of delirium [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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. Trial registration: ClinicalTrials.gov: NCT02265263.

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The complex interaction of genetics and delirium: a systematic review and meta-analysis

Cited by 7 publications

References 56 publications

Apolipoprotein E4 allele is genetically associated with risk of the short- and medium-term postoperative cognitive dysfunction: A meta-analysis and trial sequential analysis

Apolipoprotein E4 allele is genetically associated with risk of the short- and medium-term postoperative cognitive dysfunction: A meta-analysis and trial sequential analysis

Detection Analysis of Perioperative Plasma and CSF Reveals Risk Biomarkers of Postoperative Delirium of Parkinson’s Disease Patients Undergoing Deep Brain Stimulation of the Subthalamic Nuclei

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

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