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Dopaminergic sub-network connectivity alterations are associated with postoperative cognitive dysfunction: Results
Florian Lammers-Lietz1, Friedrich Borchers, Insa Feinkohl
1From the Department of Anesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin (FL-L, FB, CK, HK, JS, CS, GW), Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Epidemiology Research Group, Faculty of Health Sciences Brandenburg, University of Potsdam, Potsdam, Germany (IF), Molecular Epidemiology Research Group, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany (IF), Molecular Physiology & Cell Biology, Leibniz-Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP), Berlin (CK), Department of Anesthesiology, Intensive Care, Emergency and Pain Medicine, Universitätsmedizin Greifswald, Greifswald (GL), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Biometry and Clinical Epidemiology (JW), Berlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Metabolomics Platform (JW), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) (MW), Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin (MW, FP), Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin (MW, FP), Pharmaimage Biomarker Solutions GmbH, Berlin, Germany (GW), and Pharmaimage Biomarker Solutions Inc., Cambridge, Massachusetts, USA (GW).
Background:
Postoperative cognitive dysfunction (POCD) is a detrimental complication after surgery with lasting impact on patients' daily lives. It is most common after postoperative delirium. While dopaminergic dysfunction has been suggested to play a role in delirium, little knowledge exists regarding its relevance for POCD.
Objective:
We hypothesised that POCD is associated with altered resting-state functional connectivity (FC) of the ventral tegmental area (VTA) and the substantia nigra pars compacta (SNc) in functional magnetic resonance imaging (fMRI).
Setting:
Tertiary care centre, Germany.
Patients:
Patients aged at least 65 years with a Mini-Mental Status Examination (MMSE) at least 24 points presenting for elective major surgery were eligible for this study. Of 747 included patients, 214 patients with POCD assessment and at least one preoperative fMRI dataset were analysed.
Investigations:
Resting-state fMRI and neuropsychological assessment before surgery and at follow-up 3 months later.
Main Outcome:
POCD after 3 months after surgery was determined as the Reliable Change Index (RCI). Connectivity between VTA or SNc and 132 regions was calculated.
Results:
Twenty-six patients (12%) developed POCD. Four components for VTA-FC and SNc-FC were selected for further analysis with principal component analysis. For both VTA and SNc connectivity, one component was significantly associated with POCD. Postoperative alterations of dopaminergic networks were observed in an exploratory voxelwise analysis in a left temporal cluster.
Conclusion:
Higher dopaminergic connectivity to regions associated with spatial perceptive processes and lower connectivity to cognitive control-related areas may predispose to POCD.
Trial Registration:
Clinicaltrials.gov, NCT02265263.
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