Retrospective Evaluation of POCD Data of Studies From KAI, Charité - Universitätsmedizin Berlin

Study Overview
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Brief Summary
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Data on prevention of perioperative neurocognitive disorders (pNCDs) are limited. The purpose of this monocentric parallel - grouped observational registry is to collect study data from studies with pNCDs as primary or secondary endpoint to estimate prevalence and incidence of pNCDs.

Detailed Description
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Perioperative cognitive trajectories (Perioperative neurocognitive disorders [pNCDs]) are described with formal cognitive testing (neurocognitive test battery). Definitions are based on current nomenclature recommendations (Evered et al.) according to DSM-V criteria including a multi-component cognitive test battery comparing baseline and postoperative follow-up testing of patients with cognitive test performance of non-surgical control groups.Cognitive concern and functional ability are described with items from questionnaires, e.g. IQCODE, MMQ, GDS, ADL/IADL and others specific to the respective study design. Repeated cognitive testing with a battery of computerized neuropsychological tests (Cambridge Neuropsychological Test Automated Battery [CANTAB®]) and non computerized (paper based)tests (e.g. trailmaking test, Grooved pegboard test, Stroop color word interference test, animal naming test, etc.) are performed at preoperative baseline, after 5-7 days and at three months follow up, 1 year, 2 years and 5 years follow-up according to the study design of the registered studies. Different calculation methods will be applied to the cognitive test data, primarily the dichotomousapproach established by Rasmussen et al. in the International Study on postoperative cognitive deficits (ISPOCD). This calculation method defines POCD as a reliable change in pre- and postoperative cognitive performance (difference scores) of each individual in the surgical patients cohort as compared to the changes in a non-surgical control group (reliable change index in either a composite score including cognitive test parameters from all tests in the cognitive test battery or in at least two of the chosen cognitive test parameters). Additional calculation methods like g-factor, GCP and arbitrary definitions e.g. 20.20- rule will be used for detailed methodologic evaluation. In two subprojects we plan to describe domain-specific changes in formal cognitive testing over the registered surgical cohorts. Subproject 1-Analyses will be performed in joint evaluation with Monument Therapeutics (Spin off Cambridge Cognition). The analyses aim to : Describe cognitive change based on raw cognitive data from the applied cognitive test battery (computerized tests with CANTAB eclipse, CANTAB research suite, CANTAB connect and non-computerized tests) Identify predisposing factors (e.g. patient characteristics, biomarkers, medications) predictive of cognitive decline following surgery Identify the cognitive domains most sensitive to neuropsychological change following surgery Subproject 2-Analyses will be performed in joint evaluation with Cambridge Cognition. The analyses aim to : Facilitate the use of data collected from non-surgical controls as normative material for future studies in the research area.

Official Title
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Retrospective Evaluation of POCD Data of Studies From the Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK) Charité - Universitätsmedizin Berlin

Conditions
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Postoperative Cognitive Dysfunction

Participation Criteria
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Eligibility Criteria
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Study Group Inclusion Criteria: Age 18 -100 years Male or female patients undergoing elective surgery expected to last at least 60 min, screened at the Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité - Universitätsmedizin Berlin, Berlin, Germany Written informed consent to participate after having been properly instructed Exclusion Criteria: Lacking willingness to take part in the study, or to have relevant study data collected, saved and analyzed for the purpose of the study Accommodation in an institution due to an official or judicial order Insufficient knowledge of German language Members of the hospital staff Homelessness or other conditions that disable reachability for postoperative assessment by post or telephone Illiteracy Patients who had a history of neurologic deficits (e.g. stroke, history of seizures, etc.) Hearing impairment that severely affects the neuropsychological testing. Visual impairment that severely affects the neuropsychological testing. Participation in other prospective clinical interventional trials Control Group Inclusion Criteria: Age 18 - 100 years Male or female patients (ASA Status I, II+III) No planned surgery during the next 3 months No surgery during the past 6 months before study inclusion Written informed consent to participate after having been properly instructed Exclusion Criteria: Insufficient knowledge of German language Lacking willingness to take part in the study, or to have relevant study data collected, saved and analyzed for the purpose of the study Neuropsychiatric conditions that severely affect the neuropsychological testing Hearing impairment that severely affects the neuropsychological testing Visual impairment that severely affects the neuropsychological testing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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>POCD data of study patients of the following studies: Phydelio - Eudract.-No.: 2008-007237-47 - 08/0618 ZS EK11 Neuprodex - Eudract-No.: 2013 -000823-15 - 13/0491 ZSEK11 BioCog - EA2/092/14 Cognitive Outcome after two stage liver operation - EA1/296/12 ReCosa - EA1/056/13 Hypnoc - EA1/273/11 Sudoco - EA1/242/08 Peratecs - EA1/241/08 Hipster - Eudract.-No.: 2009-016043-19 100/10 ZS EK15 Pain-Long-EA2/041/17 PCI - EA2/024/18 PODSPA - EA4/138/18, PRÄP-GO -EA1/225/19, ANA-PRÄP-Go (EA1/266/20) Further studies from the Department of Anesthesiology and Operative Intensive Care Medince (CCM/CVK), Charité - Universitätsmedizin Berlin | |
| Control group I<br>POCD data of prospective control subjects/patients (ASA I+II+III) and POCD data of control subjects/patients of the following studies: Neuprodex - Eudract-No.: 2013 -000823-15 - 13/0491 ZSEK11 Phydeliostudie - Eudract.-No.: 2008-007237-47 - 08/0618 ZS EK11 BioCog - EA2/092/14 Cognitive Outcome after two stage liver operation - EA1/296/12 Hypnoc - EA1/273/11 Sudoco - EA1/242/08 Peratecs - EA1/241/08 Hipster - Eudract.-No.: 2009-016043-19 100/10 ZS EK15 BioCog-Studie - EA2/092/14 REACT-Studie - EA2/091/15 PAINLONG-Studie - EA2/041/17 PCI - EA2/024/18 PODSPA - EA4/138/18, PRÄP-GO -EA1/225/19, ANA-PRÄP-Go (EA1/266/20) Further studies from the Department of Anesthesiology and Operative Intensive Care Medince (CCM/CVK), Charité - Universitätsmedizin Berlin | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurocognitive Disorder (NCD) | Mild / major neurocognitive disorder 3 (mild / major NCD 'Postoperative cognitive dysfunction (POCD)') and 12 months (mild / major NCD) postoperatively. | Up to 1 year | 
| Postoperative cognitive dysfunction (POCD) | Postoperative cognitive dysfunction (POCD) is defined as relevant change in postoperative cognitive performance compared to baseline (preoperative) cognitive performance. | Up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Suspected neurocognitive disorder due to MiniCog | The MiniCog is used for cognitive screening. A cut-off value of <3 points is interpreted possible mild / major NCD. The Mini-Cog consists of a sub-test for word memory skills and a clock drawing test. | Up to 5 years | 
| Suspected dementia from MOCA | The Montreal Cognitive Assessment (MOCA) with cut-offs according to normative age-adjusted values is used as dementia screening. The MOCA consists of 13 items, which are rated on a scale from 0 to 30 points. | Up to 5 years | 
| Neurocognitive Disorder (NCD) | Mild / major neurocognitive disorder (mild / major NCD) 60months postoperatively. | Up to 5 years | 
| Suspected postoperative neurocognitive disorder (mild / major NCD 'POCD') | The non-computerized neuropsychological trail making test is used as an indicator screening test for relevant cognitive changes after the operation. The cut-off is an increase in TMT-B test performance of> 55 seconds three and / or 12 months after the operation compared to the baseline value. | Up to 5 years | 
| Findings from outpatient neurocognitive evaluation (memory clinic) | Results from patient neurocognitive assessment in a memory clinic are evaluated. | Up to 1 year | 
| Neuroimaging | Technique to image the nervous system. | Up to 5 years | 
| Normative database | Establishment of a norm database for deriving normative data in a cooperation between the Clinial Research Unit Berlin/Institute of Health (BIH), the Department of Anesthesiology and Operative Intensive Care Medicine (CCM/CVK) at Charité Universitätsmedizin Berlin and Cambridge Cognition. | Up to 5 years | 
| Perioperative cognitive disorders | Perioperative cognitive disorders for different surgical cohorts are evaluated to describe domain-specific changes over time in formal cognitive tests. These analyzes are carried out in a joint evaluation with Monument Therapeutics as part of a cooperation agreement | Up to 5 years | 
| Computerized cognitive data | Computerized cognitive data from CANTAB-research suite, CANTAB eclipse and CANTAB connect | Up to 5 years | 
| Paper-based, non-computerized, cognitive test data | Paper-based, non-computerized, cognitive test data are data from such as IQ equivalent (e.g. MWT-A), MMSE, MOCA, MMQ, Mini-Cog, etc. | Up to 5 years | 
| Socio-economic Information 1 | Soci-economic information is collected by FIMA | Up to 5 years | 
| Socio-economic Information 2 | Soci-economic information is collected by a questionnaire according to Nikolaus 1. Subscale | Up to 5 years | 
| Comorbidities | Comorbidities are new diagnoses from hospital records. | Up to 5 years | 
| Charlson comorbidity index | Comorbidity scores | Up to 5 years | 
| Lifestyle Risks 1 | Consumption of alcohol per week. | Up to 5 years | 
| Lifestyle Risks 2 | Consumption of tobacco and nicotine is measured by Fagerström Test for Cigarette Dependence (FTCD). Questionnaire scored 0-10 points with Total Score equal to the sum of all points | Up to 5 years | 
| Level of education | Level of education is measured by ISCED | Up to 5 years | 
| Incidence of postoperative delirium | Incidence of postoperative delirium is measured by DDS, DSM-V, CAM/CAM-ICU, NuDESC and Chart review | Up to 5 years | 
| Duration of postoperative delirium | The Duration of postoperative Delirium is measured in days | Up to 5 years | 
| Severity of postoperative delirium 1 | Severity of delirium 1 is measured by Delirium Detection Score (DDS). The DDS is composed of eight criteria (orientation, hallucination, agitation, anxiety, seizures, tremor, paroxysmal sweating, and altered sleep- wake rhythm). Each item is cored 0,1,4, or 7 points for a possible total score of 0 to 56). Positive if >7. | Up to 5 years | 
| Severity of postoperative delirium 2 | Severity of delirium 2 is measured by Confusion assessment method-short (CAM-S). This is a CAM-based scoring system for delirium severity. The CAM-S uses the same items as the original CAM and rates each symptom 0 for absent, 1 for mild, or 2 for marked; acute onset of fluctuation receives 0 (absent) or 1 (present) (scored 0-10, higher worse). | Up to 5 years | 
| Severity of postoperative delirium 3 | Severity of delirium 3 is measured by DSR-R-98. DRS-R-98 is 16 items clinician rated scale. Total Item: 16 = 3 (for diagnosis) + 13 (for severity). | Up to 5 years | 
| Severity of postoperative delirium 4 | Severity of delirium 4 is measured by ICDSC. Give a score of 1 to each of the 8 items below if the patient clearly meets the criteria defined in the scoring instructions. Give a score of 0 if there is no manifestation orunable to score. If the patient scores >4, notify the physician. The diagnosis of delirium is made following clinical assessment. assessment. | Up to 5 years | 
| Severity of postoperative delirium 5 | Severity of delirium 5 is measured by Nursing Delirium Screening Scale (Nu-DESC). The Nu-DESC is a scale that evaluates the severity of the 5 delirium characteristics on a scale of 0 (not present) to 2 (severe) and takes only 1-2 min to complete, based on the nurses' observations of the patient's behavior during their shifts. | Up to 5 years | 
| Length of hospital stay | Participants will be followed for the duration of hospital stay, an expected average of 7 days | Up to 5 years | 
| Quality of life - relatives | Quality of life is measured by CarerQoL | Up to 5 years | 
| Quality of life - self 1 | Quality of life is measured by EQ-5D.An index calculated from the five EQ-5D (3L and 5L) dimensions by attaching specific weights to each severity level in each dimension. | Up to 5 years | 
| Quality of life - self 2 | Quality of life is measured by WHO-5. WHO-5 is a short and generic global rating scale measuring subjective well-being, the respondent is asked to rate how well each of the 5 statements applies to him or her when considering the last 14 days. Each of the 5 items is scored from 5 (all of the time) to 0 (none of the time). The raw score ranges from 0 (absence of well-being) to 25 (maximal well-being). Scores are then converted to a percentage scale from 0 (absent) to 100 (maximal). Higher scores represent greater psychological well-being. | Up to 5 years | 
| Functional impairment (IADL) 1 | Instrumental Activities of Daily Living (IADLs) < 8 | Up to 5 years | 
| Functional impairment (ADL) 2 | Activities of Daily Living (ADLs) < 100 | Up to 5 years | 
| Depression 1 | Depression 1 is measured by PHQ-8 | Up to 5 years | 
| Depression 2 | Depression 2 is measured by GDS | Up to 5 years | 
| Anxiety scales | Anxiety is measured by GAD-7 | Up to 5 years | 
| Pain | Pain is measured by different scales, e.g. Numeric Rating Scale | Up to 5 years | 
| Depth of sedation | The sedation is emasured intraoperatively processed electroencephalogram (EEG) Full-brain EEG recording with surface electrodes, raw EEG analysis measured during the operation. | Up to 5 years | 
| Sedation | Sedation is measured by the Richmond Agitation Sedation Scale | Up to 5 years | 
| Type of operation | Type of operation is measured by OPS-Code. | Up to 5 years | 
| Type of anesthesia | There are four main categories of anesthesia used during surgery and other procedures: general anesthesia, regional anesthesia, sedation (sometimes called monitored anesthesia care), and local anesthesia. | Up to 5 years | 
| Type of concomitant medication | The medication administered during the hospital stay is documented. | Up to 5 years | 
| Anticholinergic Load | Measured by anticholinergic drug scale | Up to 5 years | 
| Frailty | Frailty is measured with a modified frailty score according to Fried´s frailty phenotype assessment. | Up to 5 years | 
| Number of participants with changes in laboratory values 1 | Laboratory results in the hospital including hemoglobin, lymphocytes, total neutrophils, platelet count, white blood cell (WBC) count and inflammatory markers from blood samples. | Up to 5 years | 
| Number of participants with changes in laboratory values 2 | Laboratory results in the hospital from serum samples | Up to 5 years | 
| Number of participants with changes in laboratory values 3 | Laboratory results in the hospital from urine samples | Up to 5 years | 
| Number of participants with changes in laboratory values 4 | Laboratory results in the hospital from stool samples | Up to 5 years | 
| Perioperative Electroencephalography | Electroencephalography (EEG)- Mapping with electrodes. | During hospital stay an expected avarage of 7 days | 
| Nutritional status 1 | Nutritional status 1 is measured by calf circumference | Up to five years | 
| Nutritional status 2 | Nutritional status 2 is measured by arm circumference | Up to five years | 
| Nutritional status 3 | Nutritional status 3 is measured by changes in weight | Up to five years | 
| Nutritional status 4 | Nutritional status 4 is measured by changes in body mass index | Up to five years | 
| Nutritional status 5 | Nutritional status 5 is measured by questions regarding microbiome | Up to five years | 
| Nutritional status 6 | Nutritional status 6 is measured by Medi-Score | Up to five years | 
| Nutritional status 7 | Nutritional status 7 is measured by MNA-SF | Up to five years | 
| Nutritional status 8 | Nutritional status 8 is measured by Sarcopenia, which is identified by criterion 1: low muscle strength, criterion 2: low muscle quantity and criterion 3: low physical performance. Probable sarcopenia is identified by Criterion 1. Diagnosis is confirmed by additional documentation of Criterion 2. If Criteria 1, 2 and 3 are all met, sarcopenia is considered severe. | Up to five years | 
| Inhospital diet | Inhospital diet is measured by patient record. | Up to five years | 
| Eating habits | Eating habits are measured by patient survey. | Up to five years |