Neuroinflammation in cognitive decline post-cardiac surgery (the FOCUS study): an observational study protocol

Annemieke M Peters van Ton, Harmke B Duindam, Julia van Tuijl, Wilson Wl Li, Hendrik-Jan Dieker, Niels P Riksen, Fj Anton Meijer, Roy Pc Kessels, Nils Kohn, Johannes G van der Hoeven, Peter Pickkers, Mark Rijpkema, Wilson F Abdo, Annemieke M Peters van Ton, Harmke B Duindam, Julia van Tuijl, Wilson Wl Li, Hendrik-Jan Dieker, Niels P Riksen, Fj Anton Meijer, Roy Pc Kessels, Nils Kohn, Johannes G van der Hoeven, Peter Pickkers, Mark Rijpkema, Wilson F Abdo

Abstract

Introduction: Postoperative cognitive dysfunction occurs frequently after coronary artery bypass grafting (CABG). The underlying mechanisms remain poorly understood, but neuroinflammation might play a pivotal role. We hypothesise that systemic inflammation induced by the surgical trauma could activate the innate immune (glial) cells of the brain. This could lead to an exaggerated neuroinflammatory cascade, resulting in neuronal dysfunction and loss of neuronal cells. Therefore, the aims of this study are to assess neuroinflammation in vivo presurgery and postsurgery in patients undergoing major cardiac surgery and investigate whether there is a relationship of neuroinflammation to cognitive outcomes, changes to brain structure and function, and systemic inflammation.

Methods and analysis: The FOCUS study is a prospective, single-centre observational study, including 30 patients undergoing elective on-pump CABG. Translocator protein (TSPO) positron emission tomography neuroimaging will be performed preoperatively and postoperatively using the second generation tracer 18F-DPA-714 to assess the neuroinflammatory response. In addition, a comprehensive cerebral MRI will be performed presurgery and postsurgery, in order to discover newly developed brain and vascular wall lesions. Up to 6 months postoperatively, serial extensive neurocognitive assessments will be performed and blood will be obtained to quantify systemic inflammatory responses and peripheral immune cell activation.

Ethics and dissemination: Patients do not benefit directly from engaging in the study, but imaging neuroinflammation is considered safe and no side effects are expected. The study protocol obtained ethical approval by the Medical Research Ethics Committee region Arnhem-Nijmegen. This work will be published in peer-reviewed international medical journals and presented at medical conferences.

Trial registration number: NCT04520802.

Keywords: cardiac surgery; delirium & cognitive disorders; immunology; intensive & critical care; nuclear medicine.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

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