Neuroinflammation in Cognitive Decline Post-cardiac Surgery

Systemic inflammation can activate the innate immune cells of the brain inducing neuroinflammation, which plays an important role in the pathogenesis of neurodegenerative disease. Major cardiovascular surgery induces a severe systemic inflammatory response.There is growing support that neuroinflammation is a pivotal factor in the development of postoperative cognitive decline (POCD) due to surgery-related systemic inflammation.

Although the neuroinflammatory hypothesis is scientifically accepted, in vivo human data supporting the role of neuroinflammation in severe systemic inflammation such as major surgery are still lacking. In the last decades, several nuclear imaging tracers have been developed that can quantitatively measure microglial and astrocytic activation in vivo, by targeting the mitochondrial 18kDa translocator protein (TSPO).

The investigators hypothesize that cardiac surgery induces a neuroinflammatory response and that its presence is related to acute and long term brain dysfunction postoperatively. This will be studied by pre- and postoperative PET brain imaging using a 18F-DPA-714 tracer targeting TSPO, combined with longitudinal neuropsychological examinations. Structural changes in the brain will be recorded on MRI prior to and after cardiac surgery to enable us to correct for the potentially confounding effects of neurovascular events on cognitive outcomes after CABG surgery.

Inclusion criteria

• Age > 50 years
• Planned for on-pump coronary artery bypass grafting surgery
• High-affinity binder or mixed-affinity binders based on rs6971 polymorphism for TSPO
• Chronic use of statins (defined as pre-hospital use)

Exclusion criteria

• Previous cardiac surgery.
• Pregnancy or wish to become pregnant within 2 weeks after PET-CT scan
• Contra-indication to undergo a PET/CT or MRI scan, including claustrophobia.
• Low-affinity binder based on rs6971 polymorphism for TSPO, or unable to determine rs6971 polymorphism.
• Patients with cognitive disorders that have not recovered enough to be able to understand the study leaflets and information for participation.
• Brain or spinal surgery within the last 6 months.
• Meningitis or brain infection within the last 6 months.
• Pre-existing dementia or neurodegenerative disease or cognitive impairment interfering with the ability to understand informational material about this research project.
• Presence of a CSF catheter or shunt.
• Patients with known brain tumors.
• Patients with brain injury (e.g. acute stroke, or subarachnoid hemorrhage) within the last 6 months.
• Severe brain trauma in previous medical history.
• Chronic (>2 weeks) use of immunosuppressive agents (see table 3.3.A).
• Concomitant diseases resulting in severe immunosuppression (e.g. HIV).
• Auto-immune or auto-inflammatory disease
• Active infection < 2 weeks prior to inclusion (defined as fever >38.5 or antibiotic treatment)
• Kidney failure, defined by a MDRD-GFR<15 ml/min/1.73m2
• Known contrast allergy for gadolinium
• Chronic use of neuroleptics, defined as pre-hospital use.
• Patients that do not speak Dutch or have disabilities that prevent accurate delirium diagnosis.
• Analphabetic patients.
• No written informed consent obtained.