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

Neurocognitive Disorders Clinical Trial

Official title:

Evaluation of POCD-Census Prospective, International Observation Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03540433
• Other study ID #: PCI
• Status: Active, not recruiting
• Start date: June 8, 2018
• Est. completion date: December 2024

Study information

• Verified date: March 2024
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 173
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 70 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Cognition Disorders
• Cognitive Dysfunction
• Neurocognitive Disorders
• Postoperative Cognitive Deficit (POCD)

Locations

Country	Name	City	State
Germany	Arbeitsbereich Physikalische Medizin	Berlin
Germany	Department of Anesthesiology and Intensive Care Medicine Berlin (CCM/CVK), Charité - Universitätsmedizin Berlin	Berlin
Germany	Internistische Hausarztpraxis	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Obesity 1	Obesity is measured by body mass index (BMI)	At the beginning of the observation
Other	Obesity 2	Obesity is measured by waist to hip ratio	At the beginning of the observation
Other	Variables of adjusting	Reading / writing weakness, hendedness, native speaker	At the beginning of the observation
Other	Frailty	Frailty will be measured by Fried's criteria (Physical Frailty Phenotype), Fried et al: Frailty in older adults: evidence for a phenotype. J.Gerontol.A Biol.Sci.Med.Sci. 2001; 56: M146-M156 and evaluated in a short comprehensive geriatric assessment as decribed by Birkelbach, O. et al. Warum und wie sollte ich Frailty erfassen? - ein Ansatz für die Anästhesieambulanz. Anasthesiol. Intensivmed. Notfallmedizin Schmerztherapie 52, 765-776 (2017).	At the beginning of the observation
Other	Cognitive Reserve	Level of education (years of formal training, last occupation, ISCED-2011 and crystalline intelligence [IQ-variable calculated with NART/MWT-A or other national equivalent ] will be used to evaluate cognitive reserve.	At the beginning of the observation
Other	Crystalline Intelligence	Mehrfachwahl-Wortschatz-Intelligenztest (MWT-A) and National Adult Reading Test (NART)	At the beginning of the observation
Other	Previous professional activity	Interview guide employment situation and previous professional activity adapted to Engstler (2017); Classification according to ISCO 08; Workload indices according to Kroll (2011)	At the beginning of the observation
Other	Delusion proneness	Delusion proneness is measured by Peter's Delusion Inventory	At the beginning of the observation
Other	Physical activity	History of physical activity less than 30 minutes / day (i.e. moderate increase in heart rate due to fast walking, cycling or other exercise)	At the beginning of the observation
Other	Pre-operative electroencephalography (EEG) spectral analysis with band power	Spectral analysis with band power are measured by EEG	At the beginning of the observation
Other	Preoperative Cognitive Impairment (PreCI)	Preoperative Cognitive Impairment (PreCI) is measured by computerized and paper pencil tests	At the beginning of the observation
Primary	Incidence of postoperative cognitive dysfunction (POCD)	Neuropsychological testing	Up to 1 year
Secondary	Incidence of postoperative cognitive dysfunction (POCD)	Neuropsychological testing	Up to 5 years
Secondary	Positive cognitive screening	Short neuropsychological testing	Up to 5 years
Secondary	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
Secondary	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
Secondary	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
Secondary	Blood biomarker for diagnosing dementia	Patients consented on blood sampling receive biomarker analysis from blood (Apolipoprotein E).	Up to five years
Secondary	Findings of memory consultation session		Up to five years
Secondary	Comorbidities	Comorbidities will be quantified by use of Charlson Comorbidity index	Up to five years
Secondary	Nutritional status	Changes in the nutritional status after elective surgery are measured by a questionnaire.	Up to five years
Secondary	Malnutrition 1	Malnutrition is measured by the Body mass index	Up to five years
Secondary	Malnutrition 2	Malnutrition is measured by weight	Up to five years
Secondary	Malnutrition 3	Malnutrition is measured by weight	Up to five years
Secondary	Dental health	The dental status is determined by tooth doctors	Up to five years
Secondary	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
Secondary	Calf circumference	Calf circumference is measured in a standardized position and documented in centimeter.	Up to five years
Secondary	Arm circumference	Arm circumference is measured in a standardized position and documented in centimeter.	Up to five years
Secondary	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
Secondary	Nutrition in the hospital	Participants will be followed for the duration of hospital stay, an expected average of 7 days	Up to five years
Secondary	Physical activity	Physical activity is evaluated by interviewing the Patient.	At the beginning of the observation
Secondary	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
Secondary	Anaesthesiological Risk 1	Anaesthesiological risk will be described by American Society of Anesthesiologists Classification (ASA Class)	At the beginning of the observation
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Duration of Delirium	Duration of postoperative delirium, defined according to medical evaluation, measured in days	Participants will be followed for the duration of hospital stay, an expected average of 7 days
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Perioperative Anxiety	Perioperative anxiety will be measured with APAIS preoperatively and the Faces Anxiety Scale (FAS) and during hospital stay.	Up to 5 days
Secondary	Perception of stress	Stress is measured by Perceived Stress Questionnaire 20	Up to 5 days
Secondary	Stress level	Stress level is measured by stress thermometer	Up to 5 days
Secondary	Generalized anxiety	Anxiety will be measured with the Generalized Anxiety Disorder 7-Item Scale (GAD-7)	Up to 5 days
Secondary	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
Secondary	Quality of sleep	Quality of sleep is measured by the Insomnia Severity Index.	Up to 5 years
Secondary	Routine laboratory		Up to hospital discharge, an expected average of 7 days
Secondary	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
Secondary	Subjective/By proxy assessment of cognitive impairment		Up to five years
Secondary	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
Secondary	Quality of life	Quality of life will be measured with the EQ-5D-5L	Up to 5 years
Secondary	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
Secondary	Plausibility check variables	Variables affecting performance of cognitive testings	Up to 5 years
Secondary	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
Secondary	Revison surgery	Surgery performed to replace or compensate for a failed implant or to correct undesirable sequelae of previous surgery.	Up to 5 years
Secondary	Outpatient treatment	Treatment outside of the hospital in an associated facility for diagnosis or treatment.	Up to 5 years
Secondary	Mortality	The number of deaths in a given period.	Up to 5 years
Secondary	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
Secondary	Motivational incongruence	The incongruence questionnaire (Der Inkongruenzfragebogen)	Up to five years
Secondary	Leisure behavior	Questionnaire on frequency of cognitively stimulating leisure activities	Up to five years
Secondary	Demographic variables		Up to five years
Secondary	Living conditions		Up to five years
Secondary	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
Secondary	Evaluation of pain	Pain is measured with dolosys paintracker	Up to three months
Secondary	Loneliness	Loneliness is measured with the UCLA-Loneliness-Scale (3 items)	Up to five years
Secondary	Social support	Social support is measured with the Berliner Social-Support Skalen BSSS-17	Up to five years
Secondary	Living situation	Living situation is measured with te question: How do you live?	Up to five years