The research leading consortium to these results has received funding from the European Union Seventh Framework Programme [FP7/2007-2013] under grant agreement no 602461 (www.biocog.eu).

The investigators will establish valid biomarkers panels (neuroimaging and molecular) for risk and clinical outcome prediction of postoperative delirium (POD)/postoperative cognitive deficit (POCD) in elective surgical patients (Age ≥ 65 years) in study centers in Berlin,Germany (data collection within 2 years after initial hospital stay) and Utrecht, The Netherlands (data collection within 1 year after initial hospital stay), thereof cerebrospinal fluid (only once on day of surgery in patients with planned spinal anesthesia/combined spinal epidural analgesia in patients, only in Berlin).

A control group of ASA II/III- patients is collected for measuring the learning experience during the cognitive testings. The participants are matched on age, education, and gender to the study patients. The ASA II/III- control patients receive additionally MRI-scan (3 Tesla) at baseline, after 3 months and after 1 (Utrecht) and 2 years (Berlin).

To analyze scanner variability we additionally measure at maximum 20 subjects (Age ≥ 65 years, ASA I and II) from Utrecht in the MRI scanner (3-Tesla) in Berlin and vice versa.

A study group at maximum (n= 80) and is collected for measuring 7 Tesla MRI at two timepoints (Baseline and 90 days).The primary endponit of this substudy is gamma amino-butyric acid concentration in CNS after 3-months (measured by MRI). A retrospective comparison group (extracting 8000 intensive care unit patient data from the patient data management system during the BioCog study period in 2016) to analyse economic effects that are caused by the implementation of quality indicators in health care.

An interim-analysis is performed on the primary endpoint after 400 included patients.

The resulting (multivariate) expert system is expected: 1) to support clinical decision-making in patient care, e.g. to balance the individual POD/POCD risk against the expected overall clinical outcome of an (elective) surgical intervention, 2) to allow the design of more sophisticated and hypothesis-driven clinical studies and drug trials (translational research) in the future. The latter will be possible on the basis of biomarker-based sub-grouping of patients and a better understanding of relevant pathophysiological processes.

Furthermore, a state-of-the art clinical database and biobank will be created that does not yet exist worldwide. Both the expert system and the reference database/biobank will expand the leadership of the contributing academic institutions in this particular research area. In addition, the newly created biobank will become an integral part of the European Biobanking and Biomolecular Resources Research Infrastructure (BBMRI) which allows top address specific and hypothesis-driven research questions.

Most notably, the developed (multivariate) expert system also has the potential for commercialization. Possible customers are: 1) physicians and hospital departments being involved in pre-surgical decision making, 2) pharmaceutical industry intending to conduct biomarker-based drug trials in POD/POCD.

Study Group (Berlin/Utrecht):

Inclusion Criteria:

• Male and female patients aged ≥ 65 years, of European descent (Caucasian)
• Elective surgery with an expected operative time ≥ 60 minutes
• Ability to give informed consent after receiving spoken and written information of the study
• Eligibility for magnetic resonance Imaging

Exclusion Criteria:

• Mini-Mental-State-Examination ≤ 23 points
• Homelessness or other circumstances where the patient would not be reachable by phone or postal services during follow-up.
• Participation in another prospective interventional clinical study during participation in this clinical study during hospital stay
• Accommodation in an institution due to an official or judicial order
• Missing informed consent for saving and hand out pseudonymous data
• Neuropsychiatric morbidity, which limits the conduction of the neurocognitive testing
• Anacusis or Hypoacusis, which limits the conduction of the neurocognitive testing

Intraoperative clectroencephalography - examinations (Study Group Berlin):

Exclusion criteria:

• Neurological preconditions
• Proposed neurological surgery

Control Group (Berlin/Utrecht):

Inclusion criteria:

• Male and female patients aged ≥ 65 years, of European descent (Caucasian)
• ASA II and III patients
• No operation in the last half year before study inclusion
• Eligibility for magnetic resonance Imaging

Exclusion Criteria:

• Mini-Mental-State-Examination ≤ 23 Points
• Missing informed consent for saving and hand out pseudonymous data
• Neuropsychiatric morbidity, which limits the conduction of the neurocognitive testing
• Anacusis or Hypoacusis, which limits the conduction of the neurocognitive testing
• Taking psychothropic drugs (including sleep-inducing drug and benzodiazepine) on a regular basis and substances, which limit the conduction of the neurocognitive testing

Control Group (Utrecht) - Scannervariability:

Inclusion criteria:

• Male and female patients aged ≥ 65 years, of European descent (Caucasian)
• ASA I and II patients
• No operation in the last half year before study inclusion
• Eligibility for magnetic resonance Imaging

Study Group (Berlin) - 7 Tesla MRI:

Criteria as of the 3-Tesla- study group and additionally:

Exclusion criteria:

• absolute 7 - Tesla MRI-contraindications
• relative 7 - Tesla MRI-contraindications

Surgical patients, 65 years or above (Berlin/Utrecht) ASA I and II patients, 65 years or above (Utrecht) ASA II and III patients, 65 years or above (Berlin/Utrecht)