Influence of Apelin Levels on Postoperative Cognitive Disorders After Orthopedic Surgery in Elderlies (APOCOGNIT)

Not Applicable

Completed

• Conditions: Delirium
• Interventions: Other: Determination of apelin and inflammatory cytokines; Other: Assessment of cognitive functions; Other: Liquid sampling cerebrospinal; Other: Postoperative delirium research; Other: Residual cognitive dysfunction research

• Registration Number: NCT02574234
• Lead Sponsor: University Hospital, Toulouse

Brief Summary

No successful strategy is proposed to patients submitted to important surgery to reduce the incidence of postoperative cognitive disorders (POCD) onset. This project propose to measure plasma levels of apelin in wide population submitted to orthopedic surgery. Apelin could be involved in anti-inflammatory processes. Apelin levels before and after surgery correlated to postoperative cognitive disorders symptom measured by PET-Scan could be an important predictive or diagnostic marker to adapt therapeutic strategy to fight against postoperative cognitive disorders.

Detailed Description

It has been now clearly shown that important surgery with general anesthesia could be strongly associated to postoperative cognitive disorders few months after the intervention especially in elderlies. No strategy is really efficient to fight against this phenomenon that could lead to Alzheimer disease development. In order to prognosticate and characterize the potential risk to develop cognitive troubles after a surgery, this study propose to evaluate the potential predictive capacity of apelin in a cohort of young and old adult undergoing an orthopedic surgery. Apelin is a peptide involved in different physiological as well physiopathological pathways. This peptide, involved in osteogenesis and inflammatory processes, has also been described to be neuroprotective. Yet, hippocampic neuroinflammation has been related in case of postoperative cognitive disorders in human as well as in mice model of surgery. Taken together, these results seem to indicate that apelin could be a therapeutic target and be predictive of the postoperative cognitive disorders onset.

This study will measure plasma apelin levels in young and old adult one day before and after a programed orthopedic surgery. Moreover, to correlate apelin amounts with inflammation processes, protocol will quantify inflammatory cytokines in plasma (IL6, IL1, TNFα). These results will be compared to measures of brain b-amyloid deposit assessed by PET-Scan technology.

The follow-up of the patients will be done during 3 months in order to evaluate the postoperative cognitive disorders or the cognitive troubles associated to surgery (memory fail, decrease of cognitive reserve...).

Study Timeline

• Study First Submitted: 2015-08-26
• Study First Submitted QC: 2015-10-09
• Study First Posted: 2015-10-12
• Study Start: 2016-03-30
• Primary Completion: 2018-03
• Study Completion: 2018-03-12
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-23
• Last Update Posted: 2024-02-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 88

Inclusion Criteria

• Patients submitted to a programed orthopedic surgery
• Patients with pre- and post-surgery check-up.

Exclusion Criteria

• Non programed orthopedic surgery (emergency)
• Patients with sepsis
• Patients submitted to orthopedic surgery but with ambulatory management.
• Existence of justice backup, curators or supervision.
• Absence of indication for a pre- or post-surgery check-up.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Patients with orthopedic surgery	Determination of apelin and inflammatory cytokines	Patients will be included in the consultation of anesthesia. The usual laboratory tests will be carried out and a determination of apelin and inflammatory cytokines. Assessment of cognitive functions using the Informant Questionnaire on Cognitive Decline in the Elderly (ICQODE), Mini Mental State examination (MMS) and the scale of Instrumental activities of daily living (IADL). Day of surgery: liquid sampling cerebrospinal. Day 1 to day 7 postoperatively: determination of inflammatory cytokines and apelin, postoperative delirium research (Confusion Assessment Method (CAM)), residual cognitive dysfunction research (MMS, IADL, IQCODE). 3 months after operation: evaluation of cognitive performance (IQCODE, IADL)
Patients with orthopedic surgery	Liquid sampling cerebrospinal	Patients will be included in the consultation of anesthesia. The usual laboratory tests will be carried out and a determination of apelin and inflammatory cytokines. Assessment of cognitive functions using the Informant Questionnaire on Cognitive Decline in the Elderly (ICQODE), Mini Mental State examination (MMS) and the scale of Instrumental activities of daily living (IADL). Day of surgery: liquid sampling cerebrospinal. Day 1 to day 7 postoperatively: determination of inflammatory cytokines and apelin, postoperative delirium research (Confusion Assessment Method (CAM)), residual cognitive dysfunction research (MMS, IADL, IQCODE). 3 months after operation: evaluation of cognitive performance (IQCODE, IADL)
Patients with orthopedic surgery	Assessment of cognitive functions	Patients will be included in the consultation of anesthesia. The usual laboratory tests will be carried out and a determination of apelin and inflammatory cytokines. Assessment of cognitive functions using the Informant Questionnaire on Cognitive Decline in the Elderly (ICQODE), Mini Mental State examination (MMS) and the scale of Instrumental activities of daily living (IADL). Day of surgery: liquid sampling cerebrospinal. Day 1 to day 7 postoperatively: determination of inflammatory cytokines and apelin, postoperative delirium research (Confusion Assessment Method (CAM)), residual cognitive dysfunction research (MMS, IADL, IQCODE). 3 months after operation: evaluation of cognitive performance (IQCODE, IADL)
Patients with orthopedic surgery	Postoperative delirium research	Patients will be included in the consultation of anesthesia. The usual laboratory tests will be carried out and a determination of apelin and inflammatory cytokines. Assessment of cognitive functions using the Informant Questionnaire on Cognitive Decline in the Elderly (ICQODE), Mini Mental State examination (MMS) and the scale of Instrumental activities of daily living (IADL). Day of surgery: liquid sampling cerebrospinal. Day 1 to day 7 postoperatively: determination of inflammatory cytokines and apelin, postoperative delirium research (Confusion Assessment Method (CAM)), residual cognitive dysfunction research (MMS, IADL, IQCODE). 3 months after operation: evaluation of cognitive performance (IQCODE, IADL)
Patients with orthopedic surgery	Residual cognitive dysfunction research	Patients will be included in the consultation of anesthesia. The usual laboratory tests will be carried out and a determination of apelin and inflammatory cytokines. Assessment of cognitive functions using the Informant Questionnaire on Cognitive Decline in the Elderly (ICQODE), Mini Mental State examination (MMS) and the scale of Instrumental activities of daily living (IADL). Day of surgery: liquid sampling cerebrospinal. Day 1 to day 7 postoperatively: determination of inflammatory cytokines and apelin, postoperative delirium research (Confusion Assessment Method (CAM)), residual cognitive dysfunction research (MMS, IADL, IQCODE). 3 months after operation: evaluation of cognitive performance (IQCODE, IADL)

Primary Outcome Measures

Name	Time	Method
Postoperative delirium occurrence.	day1 to day 7 post-operation	Evaluation of the occurrence of postoperative delirium evaluated by the Confusion Assessment Method (CAM)

Secondary Outcome Measures

Name	Time	Method
Concentration of inflammatory cytokines and apelin in the cerebrospinal fluid.	day 0 (operation day)
Assessment of the autonomy.	day 1 to day 7 and 3 month after post-operation	Evaluation with IADL scale (Instrumental Activities Scale of Everyday Life)
Evaluation of postoperative cognitive functions.	day 1 to day 7 and 3 month after post-operation	Evaluation with IQCODE questionary (Informant Questionary on Cognitive Decline in the Elderly)
Plasma concentration of apelin.	day 1 to day 7 post operation
Plasma concentration of inflammatory cytokines.	24 hours before operation, day 1 to day 7 post operation

Trial Locations

Locations (1)

CHU Toulouse, service d'orthopédie et traumatologie; 🇫🇷 Toulouse, France