Background: Loss of function of triggering receptor expressed on myeloid cell 2 (TREM2), a key receptor selectively expressed by microglia in the brain, contributes to the development of Alzheimer’s disease (AD). Whether TREM2 levels are pathologically altered during the preclinical phase, and whether cerebrospinal fluid (CSF) soluble TREM2 protein (sTREM2) has a relationship with major pathological processes including Aβ and tau deposition are still unclear. Methods: According to the NIA-AA criteria, 659 cognitively normal participants from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) cohort were divided into four groups, stage 0 (normal Aβ_1–42, T-tau and P-tau), stage 1 (low Aβ_1–42, normal T-tau and P-tau), stage 2 (low Aβ_1–42 and high T-tau or P-tau), and suspected non-AD pathology (SNAP) (normal Aβ_1–42 and high T-tau or P-tau), to examine changes of CSF sTREM2 in the preclinical AD. Biomarker cut-off was based on the assumption that one-third of adults with normal cognition have AD pathology. Results: The level of CSF sTREM2 in the stage 1 decreased compared with the stage 0 (P < 0.001), and then increased in the stage 2 (P = 0.008). SNAP individuals also had significantly increased CSF sTREM2 (P < 0.001). Results of multiple linear regressions also showed positive correlations of CSF sTREM2 with Aβ_1–42 (β = 0.192, P < 0.001), T-tau (β = 0.215, P < 0.001) and P-tau (β = 0.123, P < 0.001). Conclusion: CSF sTREM2 levels are dynamic in preclinical AD. Aβ pathology is associated with a decrease in CSF sTREM2 in the absence of tau deposition and neurodegeneration. However, tau pathology and neurodegeneration are associated with an increase in CSF sTREM2.

Background: Postoperative delirium (POD) is a frequent complication after surgery and its occurrence is associated with poor outcomes. The neuropathology of this complication is unclear, but it is important to evaluate relevant biomarkers for postoperative status. The purpose of this study is to explore the relationship between expression levels of cholinergic biomarkers in cerebrospinal fluid (CSF) and the occurrence and development of POD in elderly patients. Methods: Four hundred and ninety-two elderly patients aged 65 years old or older with elective total hip/knee replacement received combined spinal-epidural anesthesia. Preoperative baseline cognitive function was assessed using the Mini-Mental State Examination (MMSE) before surgery. Each patient was interviewed in post-anesthesia care unit (PACU) and on the first, second, third and seventh (or before discharge) postoperative days. POD was diagnosed using the Confusion Assessment Method (CAM), and POD severity was measured using the Memorial Delirium Assessment Scale (MDAS). Preoperative CSF and plasma choline acetyltransferase (ChAT), acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were determined by ELISA. The levels of ChAT, AChE and BuChE activities were determined by spectrophotometry. Results: POD was detected in 11.4% (51/447) of the patients. AChE, BuChE, ChAT, TNF-α and IL-6 concentrations in CSF and plasma have higher consistency. In preoperative CSF and preoperative and postoperative plasma, down-regulation of the concentration and activity of AChE and BuChE as well as up-regulation of the concentration and activity of ChAT and the concentrations of IL-6 and TNF-α were observed in patients who developed POD, and the decrease in BuChE was the most obvious. Logistic analysis showed the activities of ChAT, AChE and BuChE in CSF were still related to POD after adjusting for related factors such as sex, age, years of education, height, weight, body mass index (BMI), and American Society of Anesthesiologists (ASA) class. Receiver Operating Characteristic (ROC) curve analysis was conducted to determine the Area Under Curve (AUC) of AChE, BuChE and ChAT activity in CSF was 0.679 (P < 0.01), 0.940 (P < 0.01) and 0.819 (P < 0.01) respectively and found that BuChE activity had the most accurate diagnostic value. Conclusion: The changes in preoperative activity of AChE, BuChE and ChAT in CSF were associated with the development of POD in elderly patients, and BuChE activity had the greatest diagnostic value, which may be related to central cholinergic degradation. These cholinergic biomarkers might participate in the neuropathology of POD, pending further investigations. Trial registration: This study was registered at Chictr.org.cn (NO. ChiCTR1900023729) June 9th, 2019. (Retrospectively registered).

Purpose: Postoperative delirium (POD) is common in elderly patients undergoing laparoscopic surgery for gastric and colorectal malignancies. POD may be affected by different fraction of inspired oxygen (FiO₂). The purpose of this study was to compare the effects of different FiO₂ on POD. Patients and Methods: A randomized, double-blind controlled trial was performed in Qingdao Municipal Hospital Affiliated to Qingdao University. A total of 662 patients aged 65 to 85 years old underwent isolated laparoscopic radical gastrectomy, radical resection of colon cancer, or radical resection of rectal cancer only. A random number table method was used to divide the patients into two groups: 40% FiO₂ (group A) and 80% FiO₂ (group B). The primary endpoint was the incidence of POD, which was assessed by the Confusion Assessment Method (CAM) twice daily during the first 7 postoperative days, and POD severity was measured by the Memorial Delirium Assessment Scale (MDAS). The secondary endpoints were the intraoperative regional cerebral oxygen saturation (rSO₂), Bispectral (BIS) index, invasive arterial blood pressure (IABP), oxygen saturation (SpO₂), end-tidal carbon dioxide partial pressure (P_ETCO₂), the number of atelectasis cases and visual analogue scale (VAS) scores on days 1– 7 after surgery. Results: The incidence of POD was 19.37% (122/630), including 20.38% (64/314) in group A and 18.35% (58/316) in group B. No statistical significance was found in the incidence of POD between the two groups (P > 0.05); compared with group B, SpO₂, rSO₂ and PaO₂ decreased at T₂ to T₄ time point (P < 0.01), and the incidence of postoperative atelectasis decreased (P < 0.05) in group A. Conclusion: The incidence of POD was not significantly affected by different FiO₂ and the incidence of postoperative atelectasis was decreased at low FiO₂.

Purpose: We aimed to investigate the relevance of body mass index (BMI) to postoperative delirium (POD), and to test whether the influences of BMI on POD were mediated by cerebrospinal fluid (CSF) biomarkers.Patients and methods: Our study recruited 682 and 761 cognitively intact individuals from the perioperative neurocognitive disorder risk factor and prognosis (PNDRFAP) study and the perioperative neurocognitive disorder and biomarker lifestyle (PNDABLE) study, respectively. The incidence of POD was evaluated by using Confusion Assessment Method (CAM), and POD severity was measured by using the Memorial Delirium Assessment Scale (MDAS). Logistic regression was used to analyze the relationship between BMI and POD. The levels of Aβ40, Aβ42, T‐tau, and P‐tau in preoperative CSF were measured by enzyme‐linked immune‐sorbent assay (ELISA) in the PNDABLE study. Mediation analysis with 5000 bootstrapped iterations was used to explore the mediation effects.Results: In the PNDRFAP study, the incidence of POD was 16.3%, with logistic regression analysis showing that BMI (odds ratio [OR] = 0.900, 95% confidence interval [CI] 0.823–0.985, p = .022) is a protective factor of POD. In the PNDABLE study, the incidence of POD was 18.7%, and regression analysis confirmed that BMI (OR = 0.832, 95% CI 0.761–0.910, p < .001) is a protective factor of POD, while T‐tau (OR = 1.005, 95% CI 1.003–1.006, p < .001) and P‐tau (OR = 1.037, 95% CI 1.024–1.050, p < .001) were risk factors of POD. Mediation analyses revealed that the association between BMI and POD was partially mediated by T‐tau (proportion: 36%) and P‐tau (proportion: 24%).Conclusion: Higher BMI mediated protective effects on POD through CSF biomarkers (T‐tau and P‐tau).

Objectives: This study aimed to reveal the relationship between alcohol consumption and Postoperative delirium (POD) in the elderly. Methods: We selected 252 patients from the Perioperative Neurocognitive Disorder And Biomarker Lifestyle (PNDABLE ) study. Patients in the PNDABLE database have been measured for Alzheimer-related biomarkers in CSF (Aβ₄₀, Aβ₄₂, P-tau, and tau protein). Mini-Mental State Examination (MMSE) was used to assess the preoperative mental status of patients. POD was diagnosed using the Confusion Assessment Method (CAM) and assessed for severity using the Memorial Delirium Assessment Scale (MDAS). Logistic regression analysis was utilized to explore the association of alcohol consumption with POD. Linear regression analysis was used to study the relationship between alcohol consumption and CSF biomarkers. Mediation analyses with 10,000 bootstrapped iterations were used to explore the mediation effects. Finally, we constructed the receiver operating characteristic (ROC) curve and the nomogram model to evaluate the efficacy of alcohol consumption and CSF biomarkers in predicting POD. Result: The incidence of POD was 17.5%. Logistic regression showed that alcohol consumption (OR = 1.016, 95%CI 1.009–1.024, P < 0.001) is a risk factor for POD. What’s more, Aβ₄₂ is a protective factor for POD (OR = 0.993, 95%CI 0.989–0.997, P < 0.05), and P-Tau was a risk factor for POD (OR = 1.093, 95%CI 1.022–1.168, P < 0.05). Linear regression analysis revealed that alcohol consumption was negatively associated with CSF Aβ₄₂ (β = -0.638, P < 0.001) in POD patients. Mediation analyses showed that alcohol consumption is likely to partially mediate POD through Aβ42 (proportion:14.21%). ROC curve showed that alcohol consumption (AUC = 0.904; P < 0.001) exhibited a relatively better discriminatory ability in POD prediction compared to Aβ₄₂ (AUC = 0.798; P < 0.001). The calibration curve indicated a good nomogram prediction (P = 0.797). Conclusion: Alcohol consumption is a risk factor for POD (particularly for those with > 24 g a day on average) in the elderly, and contributes to POD through the mediation of Aβ₄₂.

Objective: We aimed to investigate the relationship between preoperative lipid level and postoperative delirium (POD) and explore whether lipid’s effect on POD is mediated by POD core protein.Methods: A total of 635 patients who were planned to undergo knee/hip arthroplasty under combined spinal-epidural anesthesia, regardless of gender, were selected. The patients were aged 40–90 years with American Society of Anesthesiologists physical status I II. The Mini-Mental State Examination (MMSE) was completed 1 day before the operation. Five milliliter elbow venous blood was taken from the patients before anesthesia, and serum levels of total cholesterol (TG), triglyceride (TC), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C) were detected. Cerebrospinal fluid (CSF) was extracted after successful spinal-epidural combined puncture, and amyloid beta₄₀ (Aβ₄₀), amyloid beta₄₂ (Aβ₄₂), total Tau (t-Tau), and phosphorylated Tau (p-Tau) in the CSF were measured by enzyme-linked immunosorbent assays (ELISA). After the operation, the occurrence and severity of POD were assessed using the Confusion Assessment Method and the Memorial Delirium Assessment Scale (MDAS), respectively. Patients were categorized into POD group and NPOD group. Logistic regression was used to analyze the relationship between POD and TC, TG, LDL-C, and HDL-C, and the mediating effect was used to analyze the role of POD core proteins in the relationship between lipid and MDAS. We used the receiver operating characteristic (ROC) and the precision-recall curve (PRC) analysis to assess the ability of TC, TG, LDL-C, and HDL-C ability to predict POD. Finally, we performed a sensitivity analysis to assess the stability of the results.Results: A total of 562 patients were finally enrolled in this study, and 66 patients developed POD, with an incidence of 11.7%. Logistic regression analysis showed that high concentration of TC (OR = 3.148, 95%CI 1.858∼5.333, P < 0.001), TG (OR = 2.483, 95%CI 1.573∼3.918, P < 0.001), and LDL-C (OR = 2.469, 95%CI 1.310∼4.656, P = 0.005) in serum were risk factors for POD. A high concentration of HDL-C (OR = 0.258, 95%CI 0.112∼0.594, P = 0.001) was a protective factor for POD after adjusted for age, sex, education, and MMSE score. ROC curves showed that HDL-C have the highest sensitivity and specificity in predicting POD. For these four lipid markers, the PRC range from 0.602 to 0.731, respectively. The mediating analysis showed that POD core proteins could partially mediate the relationship between lipid and POD (effect value: 16.19∼91.04%). The results were barely changed in the sensitivity analysis, and the sensitivity analysis has shown that the results were stable.Conclusion: The increase of serum TG, TC, and LDL-C concentration is a risk factor for POD development, while high HDL-C concentration is a protective factor for POD, and the occurrence of POD is caused by hyperlipidemia may be caused by POD core proteins.Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [Chictr200033439].