Clinical Study Of Correlation Between Cerebrospinal Fluid Cholinergic Biomarkers In Elderly Patients And Postoperative Cognitive Dysfunction

Background:Postoperative cognitive dysfunction(POCD)is a decline in cognitive function especially memory,attention after anesthesia and surgery.Concern has been growing regarding that POCD as an important complication of patients after surgery.Elderly patients in particular are vulnerable to memory disturbances and other types of cognitive impairment after surgical operations.The aging of the population and new developments in medicine both imply the number of elderly patients undergoing surgery and anesthesia will keep rising.This is an important issue in perioperative care.POCD has received more and more attention from scholars.Although aging is regarded as the only one clear risk of POCD,the causes of higher POCD morbidity in aging is still unclear.The central cholinergic system plays an important role on regulating cognitive function such as learning and memory.The degeneration of cholinergic system during aging could decrease the ability of resisting Central nociceptive response.Severe degeneration of central cholinergic system can lead to senile dementia.Whether the degree of the central cholinergic degeneration of the patient is the cause of the high incidence of POCD in elderly patients? Studies have shown that the cerebrospinal fluid cholinergic biomarkers including acetylcholine(ACh),choline acetyltransferase(ChAT)and acetylcholinesterase(AChE)can reflect the state of central cholinergic system,So as to indirectly assess the degree of degeneration of the central cholinergic system.Therefore,the aim of this study was to investigate correlation between preoperative cerebrospinal fluid cholinergic biomarkers including ACh,ChAT and AChE in elderly patients and POCD,in order to provide clinical evidence for the research on the mechanism of POCD,so as to provide clues for the prevention and treatment of POCD.Purpose:To evaluate the correlation between preoperative cerebrospinal fluid cholinergic biomarkers and POCD in elderly patients.To determinate the incidence and potential risk factors of POCD at 7 days and 2 months after the surgery in patients aged at least 60 years undergoing hip or knee replacement.Methods:A total of 157 patients aged at least 60 years undergoing hip or knee replacement were enrolled in this prospective study,99 patients finally completed the study.A battery of neurocognitive tests were performed with these participants at 1-3 days before and at 7 days and 2 months after the surgery.The cognitive tests included mini-mental state examination(MMSE),visual reproduction test(VRT),digit symbol test,digit span test,color trails test(CTT),stroop color and word test(SCWT).Patients' general information were documented before surgery.During the surgery,we documented the type of surgery,the duration of surgery,estimated blood loss,anesthetic agents,the patient's vital signs and a variety of adverse events.we documented postoperative any complications and the adverse events until hospital discharge.The incidence of POCD was calculated using the Z-score method.A multivariable logistic regression model stepwise was used to identify risk factors for POCD.The CSF samples was obtained during the administration of spinal anesthesia.CSF ACh was assayed with Liquid chromatography tandem mass Spectrometry method(LC-MS/MS).CSF Choline acetyltransferase(ChAT),Acetylcholinesterase(AChE)were assayed with enzymelinked immunosorbent assay(ELISA)Kits.We then examined the correlation between preoperative CSF ACh,ChAT or AChE and POCD.Results:157 eligible participants were screened,99 patients completed a total of three times Cognitive tests before and after surgery and CSF samples collected,Because of the reason for the preservation of CSF,only 66 of 99 patients' CSF ACh,90 of 99 patients' CSF ChAT and AChE were assayed.1.Incidence and risk factors of POCD at 7 days 21 of 99 patients demonstrated POCD at 7 days,the incidence of POCD was 21.21%(95%CI,13 to 30%).The incidence of POCD after hip replacement was 20.90%(14/67),after knee replacement was 21.87%(7/32),differences in the incidence of POCD nonstatistically significant(P>0.05).Multiple factors Logistic stepwise regression analysis showed that age(OR=1.119,95%CI,1.020 to 1.227,P<0.05),estimated blood loss(OR=1.003,95%CI,1.000 to 1.005,P<0.05),intraoperative ephedrine dosage(OR=1.045,95%CI,1.000 to 1.091,P<0.05)were risk factors for POCD at7 days.2.Incidence and risk factors of POCD at 2 months 12 of 99 patients demonstrated POCD at 2 months,the incidence of POCD was 12.12%(95%CI,2 to 20%).The incidence of POCD after hip replacement was 13.43%(9/67),after knee replacement was 3/32,differences in the incidence of POCD nonstatistically significant(P>0.05).Patients who demonstrated POCD at 7 days is risk factor for POCD at 2 months(OR=4.801,95%CI,1.361 to 16.941,P<0.05).3.Preoperative CSF ACh was negatively correlated with Z score of postoperative function of CTT2 at 7 days(-0.9588;P = 0.0102).Preoperative CSF ACh was negatively correlated with Z score of postoperative function of CTT2 at 2 months(-0.9562;P = 0.0335).Preoperative CSF ACh was positively correlated with Z score of postoperative function of Total at 2 months(0.2524;P = 0.0270).Preoperative CSF ChAT was positively correlated with Z score of postoperative function of VRT at 7 days(2.4131;P = 0.0400).Preoperative CSF ChAT was positively correlated with Z score of postoperative function of Total at 7 days(0.8167;P = 0.0205).Patients with POCD had a significantly lower CSF ChAT when compared with the Non-POCD group(P = 0.0495).Preoperative CSF AChE was positively correlated with Z score of postoperative function of CTT2 at 7 days(0.1348;P = 0.0390).Preoperative CSF AChE was negatively correlated with Z score of postoperative function of Total at 2 months(-0.0337;P = 0.0422).Conclusions: 1.The incidence of POCD was 21.21% at 7 days,risk factors for POCD in these patients were age,estimated blood loss and intraoperative ephedrine dosage.2.The incidence of POCD was 12.12% at 2 months,patients who demonstrated POCD at 7 days is risk factor for POCD at 2 months.3.We have found correlation between preoperative CSF ACh,ChAT and AChE and postoperative changes.Reflected in the CSF cholinergic biomarkers represent a functional degeneration of the cholinergic nervous system may identify patients at higher risk for POCD.