Delirium is a severe postoperative complication associated with poor overall and especially neurocognitive prognosis. Altered brain mineralization is found in neurodegenerative disorders but has not been studied in postoperative delirium and postoperative cognitive decline. We hypothesized that mineralization-related hypointensity in susceptibility-weighted magnetic resonance imaging (SWI) is associated with postoperative delirium and cognitive decline. We analyzed a subsample of cognitively healthy patients ≥65 years presenting for elective major surgery who underwent SWI before (N=65) and three months after surgery (N=33) as part of a subproject in the BioCog study. We measured relative SWI intensities in basal ganglia, hippocampus, and posterior basal forebrain cholinergic system (pBFCS). A post-hoc analysis of two pBFCS subregions (Ch4, Ch4p) was conducted. Patients were screened for delirium until the seventh postoperative day. Cognitive testing was performed before and three months after surgery. Preoperative relative SWI hypointensities in the basal ganglia and pBFCS were associated with increased risk for postoperative delirium after adjustment for surgery duration. After additional adjustment for age, sex, preoperative MMSE and region volume, only the association of pBFCS hypointensity and postoperative delirium remained significant. Adjusted for surgery duration, perioperative change in relative SWI intensities of the pBFCS was associated with cognitive decline three months after surgery. This association remained at a trend level after adjustments for age, sex, and region volume, but a significant independent association especially with pBFCS-subregion Ch4p was found in a post-hoc analysis. Brain mineralization, particularly in the cerebral cholinergic system, could be a pathomechanism in postoperative delirium and cognitive decline.

Florian Lammers-Lietz, MD, received personal fees from PI Health Solutions GmbH during the conduct of the study. Friedrich Borchers, MD: none Stefan Hetzer, PhD: none Insa Feinkohl, PhD: none Cicek Kanar, BSc: none Gunnar Lachmann, MD, PhD: none Claudia Paarmann-Chien, PhD, received research funding from Novartis and Alexion, unrelated to this study and is a Standing Committee on Science Member for the Canadian Institutes of Health Research (CIHR). Claudia Spies, MD, PhD, received grants from the European Commission during the conduct of the study. During the past 36 months, Prof. Spies received grants from Deutsche Forschungsgemeinschaft, Deutsches Zentrum fuer Luft- und Raumfahrt e.V., Einstein Stiftung Berlin, Federal Joint Committee (GBA Innovationsfond), inner university grants, Projekttraeger im DLR, Stifterverband, Federal Ministry for Economic Affairs and Climate Action, payments by the Georg Thieme Verlag, sponsoring from Dr. F. Koehler Chemie GmbH, Sintetica GmbH, Federal Joint Committee (GBA Innovationsfond), Max-Planck-Gesellschaft zur Foerderung der Wissenschaften e.V., Stifterverband fuer die deutsche Wissenschaft, Philipps Electronics Nederland BV, Federal Ministry of Education and Research, Robert-Koch-Institut and the European Commission. Prof. Spies is involved in patents 15753 627.7 (issued), PCT/EP 2015/067731 (issued), 3 174 588 (issued), 10 2014 215 211.9, 10 2018 114 364.8, 10 2018 110 275.5, 50 2015 010 534.8, 50 2015 010 347.7, 10 2014 215 212.7. She participates in or is member of the Association of the Scientific Medical Societies in Germany (AWMF), Deutsche Forschungsgemeinschaft and the German National Academy of Sciences (Leopoldina) without receiving payments. Georg Winterer, MD, PhD: grants from the European Commission during the conduct of the study. CEO of PharmaImage Biomarker Solutions GmbH Berlin (Germany) and President of its subsidiary Pharmaimage Biomarkers Incl. (Cambridge, MA, USA) and PI Health Solutions GmbH Berlin (Germany). Grants from the Deutsche Forschungsgemeinschaft/German Research Society and from the German Ministry of Health. Laszlo Zaborszky, PhD: none Norman Zacharias, PhD: none Friedemann Paul, MD, PhD: none

https://classic.clinicaltrials.gov/ct2/show/NCT02265263

The BioCog Project was funded by the European Union Seventh Framework Program [FP7/2007-2013] under grant agreement no. 602461. Gunnar Lachmann was participant in the BIH Charite Clinician Scientist Program funded by the Charite-Universitaetsmedizin Berlin, and the BIH at Charite.

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All study procedures were conducted in line with the declaration of Helsinki with approval by the local medical ethics committees of the study centres in Berlin, Germany (Charite-Universitaetsmedizin Berlin, EA2/092/14) and Utrecht, Netherlands (University Medical Center, 14-469).

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Data sharing is not applicable to this article as no new data were created or analyzed in this study. Data from the BioCog study are not publicly available due to constraints imposed in the consent forms. An anonymized version is available from the authors on reasonable request.