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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.
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…).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients with orthopedic surgery | Experimental | 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Determination of apelin and inflammatory cytokines | Other | A blood sample will be conducted at baseline, on day 1 and day 7 post operative to meter inflammatory cytokines (IL1B, IL1-ra, IL6) and apelin. |
| Measure | Description | Time Frame |
|---|---|---|
| Postoperative delirium occurrence. | Evaluation of the occurrence of postoperative delirium evaluated by the Confusion Assessment Method (CAM) | day1 to day 7 post-operation |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluation of postoperative cognitive functions. | Evaluation with IQCODE questionary (Informant Questionary on Cognitive Decline in the Elderly) | day 1 to day 7 and 3 month after post-operation |
| Assessment of the autonomy. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Vincent MINVILLE, MD | University Hospital, Toulouse | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU Toulouse, service d'orthopédie et traumatologie | Toulouse | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17325520 | Background | Silverstein JH, Timberger M, Reich DL, Uysal S. Central nervous system dysfunction after noncardiac surgery and anesthesia in the elderly. Anesthesiology. 2007 Mar;106(3):622-8. doi: 10.1097/00000542-200703000-00026. No abstract available. | |
| 20007989 | Background | Deiner S, Silverstein JH. Postoperative delirium and cognitive dysfunction. Br J Anaesth. 2009 Dec;103 Suppl 1(Suppl 1):i41-46. doi: 10.1093/bja/aep291. |
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| Assessment of cognitive functions | Other | Evaluation of preoperative cognitive performance by achieving a IQCODE, an MMS and an IADL scale. |
|
| Liquid sampling cerebrospinal | Other | Determination of the concentrations of inflammatory cytokines and apelin in cerebrospinal fluid perioperatively. |
|
| Postoperative delirium research | Other | Using the scale Confusion Assessment Method (CAM) for screening and delirium diagnosis. This research will be daily lasted, during the first 7 days postoperative. |
|
| Residual cognitive dysfunction research | Other | Evaluation of postoperative cognitive performance by achieving a IQCODE, an MMS and an IADL scale realised on day 1 and day 7 postoperative. Realization of the IQCODE and IADL three months after the operation in a telephone interview. |
|
Evaluation with IADL scale (Instrumental Activities Scale of Everyday Life)
| day 1 to day 7 and 3 month after post-operation |
| 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 |
| Concentration of inflammatory cytokines and apelin in the cerebrospinal fluid. | day 0 (operation day) |
| 18156877 | Background | Price CC, Garvan CW, Monk TG. Type and severity of cognitive decline in older adults after noncardiac surgery. Anesthesiology. 2008 Jan;108(1):8-17. doi: 10.1097/01.anes.0000296072.02527.18. |
| 22762316 | Background | Saczynski JS, Marcantonio ER, Quach L, Fong TG, Gross A, Inouye SK, Jones RN. Cognitive trajectories after postoperative delirium. N Engl J Med. 2012 Jul 5;367(1):30-9. doi: 10.1056/NEJMoa1112923. |
| 20818791 | Background | Cibelli M, Fidalgo AR, Terrando N, Ma D, Monaco C, Feldmann M, Takata M, Lever IJ, Nanchahal J, Fanselow MS, Maze M. Role of interleukin-1beta in postoperative cognitive dysfunction. Ann Neurol. 2010 Sep;68(3):360-8. doi: 10.1002/ana.22082. |
| 37649978 | Result | Labaste F, Delort F, Ferre F, Bounes F, Reina N, Valet P, Dray C, Minville V. Postoperative delirium is a risk factor of institutionalization after hip fracture: an observational cohort study. Front Med (Lausanne). 2023 Aug 15;10:1165734. doi: 10.3389/fmed.2023.1165734. eCollection 2023. |
| ID | Term |
|---|---|
| D003693 | Delirium |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D003221 | Confusion |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D010335 | Pathologic Processes |
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