International Observational Study on Perioperative Cognitive Trajectories (POCD Census International/PCI)

Study Overview
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Brief Summary
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The purpose of this international, multi-centre observational study is to describe perioperative cognitive changes (pre-existing neurocognitive disorder [NCD], postoperative delirium [POD] and Postoperative Cognitive Dysfunction [POCD]) up to five years after elective surgery in a mixed cohort. Measurements and definitions of cognitive outcomes will be based on current consensus and used for further harmonization in future clinical studies on perioperative cognitive trajectories. This is a feasibility approach to identify an effective screening procedure and estimate loss to follow up rates for the planning of future intervention studies. Data from this trial may also serve to facilitate and implement time effective cognitive screening and risk stratification concerning postoperative cognitive decline in the anaesthesiological preoperative assessment.

Detailed Description
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This international observational study on perioperative cognitive trajectories (POCD census international/PCI) has been designed as a pilot study to allow a peer reviewed process of four international test centres on measurement of perioperative acute and long-term cognitive outcome. Data from standard clinical treatment of 500 patients age ≥ 70 years scheduled for elective surgery (stratified according to preoperative assessment of frailty and monitored by intraoperative depth of anaesthesia) will be supplemented by guideline conform delirium- analgesia- and sedation screening until day 5 after surgery, I-Pad based neuropsychological testing [Cambridge Neuropsychological Test Automated Battery - CANTAB connect] pre-operatively, 3 months, 1- 2- and 5 years after surgery, a paper-based verbal fluency test (animal naming test from Addenbrooke's Cognitive Examination Revised (ACE-R)), a paper based test on executive function (Trailmaking Test), cognitive screening tests (Montreal Cognitive Assessment (MOCA) and Mini-Cog), and concomitant questionnaires to assess functional status, self- and by proxy rating of cognitive performance, psychological factors (depression, perioperative anxiety, stress, resilience and coping), social support, perioperative anxiety, stress, resilience and coping, as well as risk consumption of alcohol and tobacco. A non-surgical control group of 100 study participants who are not scheduled for surgery will be followed up at the same time points as the surgical cohort for scaling of cognitive data and definition of cut off values to define significant cognitive decline. Secondary outcome measures of this trial comprise levels and changes in molecular biomarkers involved in Alzheimer's dementia etiology sampled from spinal fluid on induction of spinal anaesthesia and sampled from blood in all patients. Retrospective comparison collective (01/01/2017 to 01/01/2022): A group of around 8000 surgical patients aged 65 and older at the Charité will be examined as control group. This control group is required for various questions, especially influencing factors with regard to the postoperative outcome of delirium, and aims to test the predictive ability of clinical routine data with regard to postoperative delirium. As part of the multimodality of this retrospective comparative cohort study, in cooperation with PD. Dr Scheel and in collaboration with Prof. Dr. Finke, cranial MRI scans analyzing routine data from the Institute of Neuroradiology. The subject of the investigation is initially the entire electronic routine data of the control group, including the existing cranial MRI scans.

Official Title
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Evaluation of POCD-Census Prospective, International Observation Study

Conditions
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Postoperative Cognitive Deficit (POCD), Neurocognitive Disorders

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Surgical patients at Campus Virchow- Klinikum and Campus Charité Mitte Aged ≥ 70 years Informed consent Exclusion Criteria: Manifest dementia Lack of willingness to store and disseminate pseudonymized disease data as part of the clinical trial Lack of readiness to participate in the follow-up examinations and contact to make an appointment Placement in an institute under judicial or official orders (according to German drug Law §40 (1) 4) Persons without a permanent residence or other circumstances that call into question the availability by telephone or post for postoperative examination Employees of the respective study centers illiteracy Patients with a neuropsychiatric condition that limits the performance of neurocognitive testing Patients with hearing and / or vision problems that limit the performance of neuro-cognitive testing Simultaneous participation in a prospective clinical intervention study (apart from the desired parallel participation in the anaesthesiological study Praep-Go, EA1/225/19)

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study group<br>Surgical patients aged ≥70 years | |
| Control group<br>Healthy subjects, aged ≥70 years, American Society of Anesthesiologists (ASA) I+II+III, no surgery | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of postoperative cognitive dysfunction (POCD) | Neuropsychological testing | Up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of postoperative cognitive dysfunction (POCD) | Neuropsychological testing | Up to 5 years | 
| Positive cognitive screening | Short neuropsychological testing | Up to 5 years | 
| Mild Neurocognitive Disorder | Definition according to DSM-V as proposed in Evered L et al. Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery. Br J Anaesth, Anesthesiology, Can J Anesth, Anesth Analg, J Alz Dis, acta scandinavica anaesthesiologica (Joint Publication) 2017; Accepted, In Press. We will use an I-pad based neuropsychological test battery (CANTAB connect), and cognitive screening instruments (MOCA, Mini-Cog™ and Animal naming test on verbal fluency from ACE-R) for assessment of cognitive function, MMQ and IQ-code for self- or by proxy reported cognitive concern and ADL/IADL for assessment of functional status. Mild/major Neurocognitive Disorder measured at baseline (pre-existing NCD) 3 months and 1 year (with specifier 'POCD'), 2- and 5 years after surgery | Up to five years | 
| Major Neurocognitive Disorder | Definition according to DSM-V as proposed in Evered L et al. Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery. Br J Anaesth, Anesthesiology, Can J Anesth, Anesth Analg, J Alz Dis, acta scandinavica anaesthesiologica (Joint Publication) 2017; Accepted, In Press. We will use an I-pad based neuropsychological test battery (CANTAB connect), and cognitive screening instruments (MOCA, Mini-Cog™ and Animal naming test on verbal fluency from ACE-R) for assessment of cognitive function, MMQ and IQ-code for self- or by proxy reported cognitive concern and ADL/IADL for assessment of functional status. Mild/major Neurocognitive Disorder measured at baseline (pre-existing NCD) 3 months and 1 year (with specifier 'POCD'), 2- and 5 years after surgery | Up to five years | 
| Cerobrospinal fluid biomarker for diagnosing dementia | Patients for spinal anesthesia who consented on lumbar puncture receive biomarkers analysis from spinal fluid (beta Amyloid 1-40, beta-Amyloid 1-42, beta-Amyloid Ratio (42/40*10), phospho-TAU, Protein 14-3-3, PRPSc, TAU (Gesamt-Tau)). | Up to five years | 
| Blood biomarker for diagnosing dementia | Patients consented on blood sampling receive biomarker analysis from blood (Apolipoprotein E). | Up to five years | 
| Findings of memory consultation session |  | Up to five years | 
| Comorbidities | Comorbidities will be quantified by use of Charlson Comorbidity index | Up to five years | 
| Malnutrition 1 | Malnutrition is measured by the Mini Nutritional Assessment - Short Form (MNA®-SF) | Up to five years | 
| Malnutrition 2 | Malnutrition is measured by the Body mass index | Up to five years | 
| Malnutrition 3 | Malnutrition is measured by weight | Up to five years | 
| Malnutrition 4 | Malnutrition is measured by weight | Up to five years | 
| Dental health | The dental status is determined by tooth doctors | Up to five years | 
| Sarcopenia | The composite outcome measure Sarcopenia is defined by the following three criteria: 1) low muscle strength (hand grip strength), 2) low muscle quantity (calf circumference and 3) low physical performance (gait speed). Criterion (1) identifies probable sarcopenia, additional documentation of criterion (2) confirms sarcopenia diagnosis, and if all criteria (1), (2) and (3) are met, sarcopenia is considered severe. | Up to five years | 
| Calf circumference | Calf circumference is measured in a standardized position and documented in centimeter. | Up to five years | 
| Arm circumference | Arm circumference is measured in a standardized position and documented in centimeter. | Up to five years | 
| Adherence to Mediterranean diet (MD) | Adherence to Mediterranean diet (MD) is measured with a German Mediscore, could range from 0 to 9, with higher scores (6-9) indicating greater MD adherence. | Up to five years | 
| Nutrition in the hospital | Participants will be followed for the duration of hospital stay, an expected average of 7 days | Up to five years | 
| Physical activity | Physical activity is evaluated by interviewing the Patient. | At the beginning of the observation | 
| Surgical risk | Surgical risk will be described by type and length of surgery and perioperative cardiac risk estimation as described in Anästh Intensivmed 2017; 58:349-364. | Participants will be followed up during surgery, an estimated duration of 1 hour | 
| Anaesthesiological Risk 1 | Anaesthesiological risk will be described by American Society of Anesthesiologists Classification (ASA Class) | At the beginning of the observation | 
| Anaesthesiological Risk 2 | Anaesthesiological risk will be measured by length of anesthesia | Participants will be followed up during surgery, an estimated duration of 1 hour | 
| Anaesthesiological Risk 3 | Anaesthesiological risk will be measured by type of anaesthesia | Participants will be followed up during surgery, an estimated duration of 1 hour | 
| Intraoperative depth of anaesthesia | Intraoperative depth of sedation will be monitored with changes in the pattern and power spectrum of EEG-raw data measured with the Masimo SedLine® brain function monitoring for Root®, Narcotrend®, BIS™ and additionally quantified by indices [e.g. PSI or BIS-index] and burst suppression ratio. | Participants will be followed up during surgery, an estimated duration of 1 hour | 
| Depth of sedation on the Intensive Care Unit | Sedation is measured by Richmond Agitation Sedation Scale. | Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days | 
| Sedation on the peripheral ward | Sedation is measured by Richmond Agitation Sedation Scale. | Participants will be followed for the duration of hospital stay, an expected average of 7 days | 
| Agitation on the peripheral ward | Agitation describes a clinical state in which the patient may be impulsive and attempt to get out of bed, to wander, and to fall (which may lead to further injury or death) and attempt to remove IV lines, tubes, or catheters. | Participants will be followed for the duration of hospital stay, an expected average of 7 days | 
| Incidence of postoperative delirium | Postoperative delirium rate, defined according to Diagnostic and Statistical Manual of Mental Disorders (DSM-V), CAM/CAM-ICU, Nu-DESC and Chart Review. | Up to 5 days | 
| Severity of postoperative delirium | Postoperative delirium rate, defined according to Confusion assessment method - severity(CAM-S); Delirium Rating Scale Revised (DSR-R-98), Intensive Care Delirium Screening Checklist (ICDSC) and Nursing Delirium Screening Scale (Nu-DESC). | Up to 5 days | 
| Duration of Delirium | Duration of postoperative delirium, defined according to medical evaluation, measured in days | Up to intensive care unit discharge, an expected average of 3 days. | 
| Pain scale for patients able of pain self-assessment | Pain during hospital stay will be measured with the Numeric Rating Scale (NRS-V). | Up to hospital discharge, an expected average of 5 days | 
| Pain scales for patients unable of pain self-assessment | For patients unable of pain self-assessment (e.g. ventilated patients, patients in delirious state or patients with stroke affecting language skills) observer-rated pain scales will be applied: Behavioural Pain Scale (BPS for ventilated) and BPS-NI (for non-ventilated) patients, Critical-Care Pain Observation Tool (CPOT) during hospital stay. | Up to hospital discharge, an expected average of 5 days | 
| Intensive care unit length of stay | Intensive care unit length of stay describes every day spent in an ICU bed. | Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days | 
| Hospital length of stay | Hospital length of stay describes every day spent in an hospital. | Participants will be followed for the duration of hospital stay, an expected average of 7 days | 
| Perioperative Anxiety | Perioperative anxiety will be measured with APAIS preoperatively and the Faces Anxiety Scale (FAS) and during hospital stay. | Up to 5 days | 
| Perception of stress | Stress is measured by Perceived Stress Questionnaire 20 | Up to 5 days | 
| Stress level | Stress level is measured by stress thermometer | Up to 5 days | 
| Generalized anxiety | Anxiety will be measured with the Generalized Anxiety Disorder 7-Item Scale (GAD-7) | Up to 5 days | 
| Depression | Depression is measured by PHQ-8. Scores represent:0-5 = mild, 6-10 = moderate, 11-15 = moderately severe, 16-20 = severe depression | Up to 5 years | 
| Quality of sleep | Quality of sleep is measured by the Insomnia Severity Index. | Up to 5 years | 
| Routine laboratory |  | Up to hospital discharge, an expected average of 7 days | 
| Organ dysfunctions | Organ dysfunctions are evaluated according to the Clavien-Dindo classification of surgical complications | Up to hospital discharge, an expected average of 7 days | 
| Subjective/By proxy assessment of cognitive impairment |  | Up to five years | 
| Medication | Prescribed regular drug intake from baseline at all follow ups including perioperative application of drugs, infusions and transfusions will be evaluated. | Up to 5 years | 
| Quality of life | Quality of life will be measured with the EQ-5D-5L | Up to 5 years | 
| Level of dependency | Level of dependency will be measured with with ADL/IADL, single items concerning patients' living situation and the BSSS-17 (Berlin Social Support Scales). | Up to 5 years | 
| Plausibility check variables | Variables affecting performance of cognitive testings | Up to 5 years | 
| Re-admission | Hospital readmission is an episode when a patient who had been discharged from a hospital is admitted again within a specified time interval. | Up to 5 years | 
| Revison surgery | Surgery performed to replace or compensate for a failed implant or to correct undesirable sequelae of previous surgery. | Up to 5 years | 
| Outpatient treatment | Treatment outside of the hospital in an associated facility for diagnosis or treatment. | Up to 5 years | 
| Mortality | The number of deaths in a given period. | Up to 5 years | 
| Dementia | Dementia reported as clinical diagnosis based on DSM-5 criteria for major NCD either through neuropsychological evaluation at a memory clinic or as a research diagnosis based on neuropsychological test values (CANTAB/MOCA), cognitive concern (MMQ/IQCODE) and functionality (ADL/IADL). | Up to 5 years | 
| Motivational incongruence | The incongruence questionnaire (Der Inkongruenzfragebogen) | Up to five years | 
| Leisure behavior | Questionnaire on frequency of cognitively stimulating leisure activities | Up to five years | 
| Demographic variables |  | Up to five years | 
| Living conditions |  | Up to five years | 
| Postoperative electroencephalography (EEG) spectral analysis with band power | Spectral analysis with band power are measured by EEG at third postoperative day and delirium dependent until postoperative day 7. | Up to seven days | 
| Evaluation of pain | Pain is measured with dolosys paintracker | Up to three months | 
| Loneliness | Loneliness is measured with the UCLA-Loneliness-Scale (3 items) | Up to five years | 
| Social support | Social support is measured with the Berliner Social-Support Skalen BSSS-17 | Up to five years | 
| Living situation | Living situation is measured with te question: How do you live? | Up to five years |