Discovery for Biomarkers and Risk Factors for Postoperative Delirium in Elderly Patients With Spine Surgery

Study Overview
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Brief Summary
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Introduction: With the increase of the elderly population, the number of elderly patients undergoing surgery is increasing, and postoperative delirium is 11-51% depending on the type of surgery. In recent cohort studies have shown that delirium might reduce cognitive function and develop dementia. Since delirium is difficult to treat, the key to treatment is prevention, and about 40% is prevented when prophylactic intervention is applied. However, delirium is difficult to diagnose and difficult to predict, therefore, biomarkers are needed to diagnose and prevention. Exosome and brain efficiency test(electroencephalogram, and pulse wave test) have the potential of simple biomarkers that can diagnose postoperative delirium and predict cognitive decline. Purpose: The purpose of this study is to investigate the risk factors affecting delirium in the elderly who have spinal surgery and to search for biomarkers of delirium for early detection and prevention of delirium.

Detailed Description
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Method: Study design: This study is a prospective investigation that identifies risk factors for postoperative delirium and searches for predictive biomarkers of delirium. Inclusion criteria / Exclusion Criteria Inclusion criteria Elderly patients over 70 Eligible Surgeries: lumbar spine fusion surgery, posterior cervical spine fusion surgery, or anterior cervical spine fusion surgery Exclusion Criteria Patients with cognitive decline according to MMSE-DS outcome criterion Patients diagnosed with malignant or benign tumors If surgery is scheduled within 2 hours(micro surgery) In case of difficulty in communication History of brain neurological diseases (brain hemorrhage, stroke, dementia, Parkinson's, cognitive impairment diagnosis, etc.) Patients diagnosed with alcoholism or drug addiction Patients with surgical complications (post-operative bleeding, high fever over 39 degrees, etc.) Patients undergoing re-operation due to surgery-related complications Outcome Primary outcome: Urinary and Blood exosome, stool Secondary outcome: brain function test(electroencephalogram, pulse wave test, and cognitive test) Measurement Delirium: Confusion Assessment Method(CAM), Korean-Delirium Rating Scale-R-98(K-DRS-R-98), Korean Nusing Delirium Scale(Nu-DESC) Cognitive function test: Mini-Mental State Examination-Dementia Screening(MMSE-DS), Montreal Cognitive Assessment(MoCA), Telephone interview for Cognitive Status(TICS) Depression: Geriatric Depression Scale Short Form Version (GDSSF-K) Activity Daily of Living: K-ADL, K-IADL Frail: Korean version of the FRAIL scale Nutrition: Mini Nutritional Assessment-Short Form patient-reported outcomes ; PROMIS-29

Official Title
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Discovery for Biomarkers and Risk Factors for Postoperative Delirium in Elderly Patients With Spine Surgery

Conditions
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Spinal Disease

Intervention / Treatment
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* Procedure: Spine surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Elderly patients over 70 Eligible Surgeries: lumbar spine fusion surgery, posterior cervical spine fusion surgery, or anterior cervical spine fusion surgery Exclusion Criteria: Patients with cognitive decline according to MMSE-DS outcome criterion Patients diagnosed with malignant or benign tumors If surgery is scheduled within 2 hours(micro surgery) In case of difficulty in communication History of brain neurological diseases (brain hemorrhage, stroke, dementia, Parkinson's, cognitive impairment diagnosis, etc.) Patients diagnosed with alcoholism or drug addiction Patients with surgical complications (post-operative bleeding, high fever over 39 degrees, etc.) Patients undergoing re-operation due to surgery-related complications

Ages Eligible for Study
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Minimum Age: 70 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Delirium group<br>Group of patients with postoperative delirium | Procedure: Spine surgery<br>* Eligible Surgeries: lumbar spine fusion surgery, posterior cervical spine fusion surgery, or anterior cervical spine fusion surgery<br>|
| Non delirium group<br>Group of patients without postoperative delirium | Procedure: Spine surgery<br>* Eligible Surgeries: lumbar spine fusion surgery, posterior cervical spine fusion surgery, or anterior cervical spine fusion surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exosomes in Urine: Differences in Gene Expression | - Gene expression and expression comparison in exosomes The gene expression difference is determined using the SAM tool and DEseq2, and the Gene Ontology (GO) Database (www.geneontology.org) and the KEGG database (www.genome.jp/kegg) are used to find the correlation between gene functions. In the case of miRNA, there will be a regulatory function of the coding gene, so for this purpose, an integrative analysis is performed to identify the mRNA-miRNA interaction | Just before surgery | 
| Exosomes in Urine: Differences in Gene Expression | - Gene expression and expression comparison in exosomes The gene expression difference is determined using the SAM tool and DEseq2, and the Gene Ontology (GO) Database (www.geneontology.org) and the KEGG database (www.genome.jp/kegg) are used to find the correlation between gene functions. In the case of miRNA, there will be a regulatory function of the coding gene, so for this purpose, an integrative analysis is performed to identify the mRNA-miRNA interaction | just before end of surgery | 
| Exosomes in Urine: Differences in Gene Expression | - Gene expression and expression comparison in exosomes The gene expression difference is determined using the SAM tool and DEseq2, and the Gene Ontology (GO) Database (www.geneontology.org) and the KEGG database (www.genome.jp/kegg) are used to find the correlation between gene functions. In the case of miRNA, there will be a regulatory function of the coding gene, so for this purpose, an integrative analysis is performed to identify the mRNA-miRNA interaction | Post operative day 1 (6 AM) | 
| Exosomes in Urine: Differences in Gene Expression | - Gene expression and expression comparison in exosomes The gene expression difference is determined using the SAM tool and DEseq2, and the Gene Ontology (GO) Database (www.geneontology.org) and the KEGG database (www.genome.jp/kegg) are used to find the correlation between gene functions. In the case of miRNA, there will be a regulatory function of the coding gene, so for this purpose, an integrative analysis is performed to identify the mRNA-miRNA interaction | Post operative day 1 (6 PM) | 
| Exosomes in Urine: Differences in Gene Expression | - Gene expression and expression comparison in exosomes The gene expression difference is determined using the SAM tool and DEseq2, and the Gene Ontology (GO) Database (www.geneontology.org) and the KEGG database (www.genome.jp/kegg) are used to find the correlation between gene functions. In the case of miRNA, there will be a regulatory function of the coding gene, so for this purpose, an integrative analysis is performed to identify the mRNA-miRNA interaction | immediately after onset of delirium | 
| Exosomes in Urine: Differences in Gene Expression | - Gene expression and expression comparison in exosomes The gene expression difference is determined using the SAM tool and DEseq2, and the Gene Ontology (GO) Database (www.geneontology.org) and the KEGG database (www.genome.jp/kegg) are used to find the correlation between gene functions. In the case of miRNA, there will be a regulatory function of the coding gene, so for this purpose, an integrative analysis is performed to identify the mRNA-miRNA interaction | 7 days after surgery, within hospitalization period | 
| Exosomes in Blood: Differences in Gene Expression | - Gene expression and expression comparison in exosomes The gene expression difference is determined using the SAM tool and DEseq2, and the Gene Ontology (GO) Database (www.geneontology.org) and the KEGG database (www.genome.jp/kegg) are used to find the correlation between gene functions. In the case of miRNA, there will be a regulatory function of the coding gene, so for this purpose, an integrative analysis is performed to identify the mRNA-miRNA interaction | Just before surgery | 
| Exosomes in Blood: Differences in Gene Expression | - Gene expression and expression comparison in exosomes The gene expression difference is determined using the SAM tool and DEseq2, and the Gene Ontology (GO) Database (www.geneontology.org) and the KEGG database (www.genome.jp/kegg) are used to find the correlation between gene functions. In the case of miRNA, there will be a regulatory function of the coding gene, so for this purpose, an integrative analysis is performed to identify the mRNA-miRNA interaction | just before end of surgery | 
| Fecal microbiota |  | just before surgery, on the day of discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain efficiency test(EEG) | - EEG test for brain efficiency Peak-MEF(intermediate rhythm of background EEG spectrum), Peak-Freq, Peak_power, Theta frequency band (4 or more and less than 8) of the left (Fp1) EEG power value (log scale), Left (Fp1) EEG alpha frequency band (8 or more and less than 12) Power value (log scale), Left (Fp1) EEG slow beta band (more than 12 and less than 15) power value (log scale), Left (Fp1) EEG mid-beta frequency band (more than 15 and less than 20) power value (log scale), Fast beta frequency band of the left (Fp1) brain waves (more than 20 and less than 30) power value (log scale), Gamma frequency band (30 or more and 50 or less) power value (log scale) of left (Fp1) brain waves, Peak amplitude of 125 Hz auditory stimulated brain potential (ERP); Left and right average of P2 (maximum) peak value difference based on N1 (minimum) peak. Peak amplitude mean of left (Fp1) auditory induced brain potentials (ERPs), Left and right EEG cross-correlation coefficient. | Before surgery (from 2 weeks before to the day before) | 
| Brain efficiency test(pulse wave test) | - pulse wave test for brain efficiency HF (High Frequency) frequency band of heart rate variability (RRV) (0.15 or more and 0.4Hz or less), LF (Low Frequency) frequency band of heart rate variability (RRV) (0.04 or more and less than 0.15 Hz) absolute power, Relative percentage of LF to (LF + HF), Total power of heart rate variability (RRV), Heart rate variability (RRV) histogram; the histogram distribution area divided by the maximum value | Before surgery (from 2 weeks before to the day before) | 
| Cognitive test -MMSE |  | Before surgery (from 2 weeks before to the day before) | 
| Cognitive test -MOCA |  | Before surgery (from 2 weeks before to the day before) | 
| Cognitive test -TICS |  | Before surgery (from 2 weeks before to the day before) | 
| Brain efficiency test(EEG) | - EEG test for brain efficiency Peak-MEF(intermediate rhythm of background EEG spectrum), Peak-Freq, Peak_power, Theta frequency band (4 or more and less than 8) of the left (Fp1) EEG power value (log scale), Left (Fp1) EEG alpha frequency band (8 or more and less than 12) Power value (log scale), Left (Fp1) EEG slow beta band (more than 12 and less than 15) power value (log scale), Left (Fp1) EEG mid-beta frequency band (more than 15 and less than 20) power value (log scale), Fast beta frequency band of the left (Fp1) brain waves (more than 20 and less than 30) power value (log scale), Gamma frequency band (30 or more and 50 or less) power value (log scale) of left (Fp1) brain waves, Peak amplitude of 125 Hz auditory stimulated brain potential (ERP); Left and right average of P2 (maximum) peak value difference based on N1 (minimum) peak. Peak amplitude mean of left (Fp1) auditory induced brain potentials (ERPs), Left and right EEG cross-correlation coefficient. | 7 days after surgery, within hospitalization period | 
| Brain efficiency test(pulse wave test) | - pulse wave test for brain efficiency HF (High Frequency) frequency band of heart rate variability (RRV) (0.15 or more and 0.4Hz or less), LF (Low Frequency) frequency band of heart rate variability (RRV) (0.04 or more and less than 0.15 Hz) absolute power, Relative percentage of LF to (LF + HF), Total power of heart rate variability (RRV), Heart rate variability (RRV) histogram; the histogram distribution area divided by the maximum value | 7 days after surgery, within hospitalization period | 
| Cognitive test -MMSE |  | 7 days after surgery, within hospitalization period | 
| Cognitive test -MOCA |  | 7 days after surgery, within hospitalization period | 
| Cognitive test -TICS |  | 7 days after surgery, within hospitalization period | 
| Brain efficiency test(EEG) | - EEG test for brain efficiency Peak-MEF(intermediate rhythm of background EEG spectrum), Peak-Freq, Peak_power, Theta frequency band (4 or more and less than 8) of the left (Fp1) EEG power value (log scale), Left (Fp1) EEG alpha frequency band (8 or more and less than 12) Power value (log scale), Left (Fp1) EEG slow beta band (more than 12 and less than 15) power value (log scale), Left (Fp1) EEG mid-beta frequency band (more than 15 and less than 20) power value (log scale), Fast beta frequency band of the left (Fp1) brain waves (more than 20 and less than 30) power value (log scale), Gamma frequency band (30 or more and 50 or less) power value (log scale) of left (Fp1) brain waves, Peak amplitude of 125 Hz auditory stimulated brain potential (ERP); Left and right average of P2 (maximum) peak value difference based on N1 (minimum) peak. Peak amplitude mean of left (Fp1) auditory induced brain potentials (ERPs), Left and right EEG cross-correlation coefficient. | 1 month after surgery | 
| Brain efficiency test(pulse wave test) | - pulse wave test for brain efficiency HF (High Frequency) frequency band of heart rate variability (RRV) (0.15 or more and 0.4Hz or less), LF (Low Frequency) frequency band of heart rate variability (RRV) (0.04 or more and less than 0.15 Hz) absolute power, Relative percentage of LF to (LF + HF), Total power of heart rate variability (RRV), Heart rate variability (RRV) histogram; the histogram distribution area divided by the maximum value | 1 month after surgery | 
| Cognitive test -MMSE |  | 1 month after surgery | 
| Cognitive test -MOCA |  | 1 month after surgery | 
| Cognitive test -TICS |  | 1 month after surgery | 
| Brain efficiency test(EEG) | - EEG test for brain efficiency Peak-MEF(intermediate rhythm of background EEG spectrum), Peak-Freq, Peak_power, Theta frequency band (4 or more and less than 8) of the left (Fp1) EEG power value (log scale), Left (Fp1) EEG alpha frequency band (8 or more and less than 12) Power value (log scale), Left (Fp1) EEG slow beta band (more than 12 and less than 15) power value (log scale), Left (Fp1) EEG mid-beta frequency band (more than 15 and less than 20) power value (log scale), Fast beta frequency band of the left (Fp1) brain waves (more than 20 and less than 30) power value (log scale), Gamma frequency band (30 or more and 50 or less) power value (log scale) of left (Fp1) brain waves, Peak amplitude of 125 Hz auditory stimulated brain potential (ERP); Left and right average of P2 (maximum) peak value difference based on N1 (minimum) peak. Peak amplitude mean of left (Fp1) auditory induced brain potentials (ERPs), Left and right EEG cross-correlation coefficient. | 1 year after surgery | 
| Brain efficiency test(pulse wave test) | - pulse wave test for brain efficiency HF (High Frequency) frequency band of heart rate variability (RRV) (0.15 or more and 0.4Hz or less), LF (Low Frequency) frequency band of heart rate variability (RRV) (0.04 or more and less than 0.15 Hz) absolute power, Relative percentage of LF to (LF + HF), Total power of heart rate variability (RRV), Heart rate variability (RRV) histogram; the histogram distribution area divided by the maximum value | 1 year after surgery | 
| Cognitive test -MMSE |  | 1 year after surgery | 
| Cognitive test -MOCA |  | 1 year after surgery | 
| Cognitive test -TICS |  | 1 year after surgery |