Evidence map›Paper›PMID 34674705›Full record

Observational studyBMC medical genomics2021

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

Maria Heinrich, Miriam Sieg, Jochen Kruppa, Peter Nürnberg, Peter H Schreier, Stefanie Heilmann-Heimbach, Per Hoffmann, Markus M Nöthen, Jürgen Janke, Tobias Pischon and 3 more

Registry-linked trialOpen access · goldAbstract readMulticenter StudyObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in BMC medical genomics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02265263 (Biomarker Development for Postoperative Cognitive Impairment in the Elderly), which is not on this map. Cited by 15 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 3 pooled it
3.2field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02265263 terminatednot on this map

Biomarker Development for Postoperative Cognitive Impairment in the Elderly (BioCog)

TypeobservationalSponsorCharite University, Berlin, GermanyRan2014 to 2019Enrolled1,054ConditionsPostoperative Delirium (POD), Postoperative Cognitive Deficit (POCD)
3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 3 syntheses or guidelines pooled it, 25 citations in OpenAlex.

  1. Pooled it
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  12. Perioperative Levels of IL8 and IL18, but not IL6, are Associated with Nucleus Basalis Magnocellularis Atrophy Three Months after Surgery.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 9 institutions in 4 countries.

Maria HeinrichUniversitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Berlin, Germany.
Miriam SiegBerlin Institute of Health at Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Jochen KruppaUniversitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Berlin, Germany.
Peter NürnbergInstitute of Genetics, University of Cologne, Cologne, Germany.
Peter H SchreierInstitute of Genetics, University of Cologne, Cologne, Germany.
Stefanie Heilmann-HeimbachInstitute of Human Genetics, School of Medicine and University Hospital Bonn, University of Bonn, Bonn, Germany.
Per HoffmannInstitute of Human Genetics, School of Medicine and University Hospital Bonn, University of Bonn, Bonn, Germany.
Markus M NöthenInstitute of Human Genetics, School of Medicine and University Hospital Bonn, University of Bonn, Bonn, Germany.
Jürgen JankeMDC/BIH Biobank, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
Tobias PischonBerlin Institute of Health at Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Arjen J C SlooterDepartment of Intensive Care Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Georg Winterer *Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Berlin, Germany.
Claudia D Spies *Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Berlin, Germany. claudia.spies@charite.de.
Humboldt-Universität zu Berlin · DEFreie Universität Berlin · DEUniversity Hospital Bonn · DEAtlas Biolabs (Germany) · DEBerlin Institute of Health at Charité - Universitätsmedizin Berlin · DEMax Delbrück Center · DEUniversity of Bonn · DEUniversity of Cologne · DEUtrecht University · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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 registrationClinicalTrials.gov: NCT02265263.

Indexed as

Genetic VariationAgedCognitive DysfunctionDeliriumFemaleGenome-Wide Association StudyHumansMalePolymorphism, Single NucleotidePostoperative ComplicationsProspective StudiesReceptors, CholinergicReceptors, CholinergicCHRM2CHRM4Genome-wide association studyNeurocognitive disorder

Identifiers

PMID34674705
PMCPMC8529799
OpenAlexW3207529716

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.