Preliminary Study Of Association Between Systemic Biomarkers And Postoperative Cognitive Decline In Elderly Patients

ObjectivesIn order to investigate the changes in the plasma levels of SOD1,SOD2,Osteopontin,Kallikrein-6,and Contactin-1 at preoperation(PREOP),postoperation day 1(POD1),and postoperation day 3(POD3)in patients undergoing elective surgeries between group NPOCD and POCD,respectively.The differences of the five biomarkers above in each group at different time points were also measured and compared,respectively.Our current program was aimed to determine the relationship between the these biomarkers above and the development or progression of POCD,which will provide potential mechanisms and new sights for early clinical diagnosis,prevention and therapy for POCD.MethodsAged patients who received elective hip and knee replacement surgery in department of anesthesiology of Changhai Hospital between December,2015 and April,2016 were enrolled into the current prospective clinical study.The study was approved by Special Committee on Ethics of Biomedicine Research of Second Military Medical University and written informed consent was obtained from all participants.Patients with more than 65 years old,ASA physical status?-?,educational level above primary school,a negative Clock-Drawing Test(CDT),and MMSE score ?22 points were included.Patients with ASA physical status > ?,a history of neurological disorders,stroke,Malignant tumors,long-term use of psychiatric drugs,preoperative severe anxiety,and delirium were excluded.Patients if loss to follow-up were also excluded.Patients enrolled in this study were then divided into two groups,i.e.,group NPOCD and group POCD.Characteristics of patients were recorded,including age,sex,height,weight,body mass index(BMI),the medical history(comorbidity such as hypertension,hyperlipidemia,diabetes mellitus,and coronary heart disease),educational level(primary school,junior high school,or college),operative duration and basal MMSE scores,preoperative anxiety score,postoperative pain score.We used SAS/SDS and CAM-ICU scale to exclude patients with severe anxiety,depression and delirium before surgery,respectively.The patients' based cognitive function was determined with MMSE and CDT.We eliminated delirium by CAM-ICU scale at POD1 and POD3.And the visual analogue scale(VAS)was used to evaluate thepatients' pain after the operation.Blood samples were collected from all participants at three time points: PREOP,POD1 and POD3.The plasma levels of these biomarkers were measured using The MILLIPLEX? MAP Human Neurological Disorders Panel 3 kits according to the manufacturer's instructions(Millipore,Billerica,Massachusetts).Measurement data were expressed as mean±SD,and enumeration data were expressed as frequency or percentage.All data were analyzed through SPSS 19.0 statistical program.Categorical and continuous demographic characteristics were compared between groups with Pearson Chi-Square and t-tests.Unified comparisons of biomarkers levels were analyzed using repeated measure ANOVA,and comparisons of biomarkers levels between two time points intra-group were performed with LSD-t.Comparisons of biomarkers levels between two groups at the same time point were performed with Student's t test.A p value<0.05 was considered significant.Results1.Forty-five patients were enrolled into our current study,with 18(40%)patients' MMSE score was lower at POD1 and POD3 than that at PREOP and 18 patients developed POCD at POD3,and there was no significant difference in the characteristics of patients in two groups(p>0.05).2.There was no significant difference in the basal level of Kallikrein-6 in plasma between the two groups(p>0.05)at PREOP.The plasma level of Kallikrein-6 of POCD group at POD1 was significant lower(p<0.05)than that of NPOCD group,and the plasma level of Kallikrein-6 of POCD group at POD3 was significant lower(p<0.01)than that of NPOCD group.While the plasma levels of Kallikrein-6 at POD1 and POD3 were significant lower(p<0.05)than that at PREOP,respectively in POCD group.3.There was no significant difference in the basal level of ln(SOD1),ln(SOD2),ln(Osteopontin)and Contactin-1 in plasma between the two groups(p>0.05).The plasma levels of ln(SOD1)at POD3 were significant lower(p<0.05)than that at PREOP in POCD group,and the plasma levels of ln(Osteopontin)at POD1 and POD3 were significant higher(p<0.05)than that at PREOP respectively in POCD group,while the plasma levels of contactin-1 at POD1 and POD3 were significant lower(p<0.01)than that at PREOP respectively in POCD group.However,there was no significant difference in the plasma level of ln(SOD2)at POD1 and POD3 compared with PREOP in POCD group(p>0.05).ConclusionOur study showed that 18(40%)patients' MMSE score was lower at POD1 and POD3 than that at PREOP and 18 patients developed POCD at POD3,and there was no significant difference in the characteristics of patients in two groups.The plasma level of Kallikrein-6 after operation may be related to the development or progression of POCD in elderly patients,and the expression level of plasma biomarkers(SOD1,Osteopontin,Kallikrein-6,Contactin-1)in POCD group may change accompanied by cognitive decline after surgery.