Search

Abstract Purpose Postoperative delirium (POD) is a usual complication after total hip/knee replacement, which may be affected by sleep characteristics. However, up to now, preoperative sleep characteristics have not been evaluated as risk factors of POD. The relationship between self‐reported sleep characteristics and POD in patients has been investigated in this study. Patients and Methods We recruited 495 cognitively intact individuals in the final analysis from the Perioperative Neurocognitive Disorder and Biomarker Lifestyle study. Sleep characteristics were tested by the Pittsburgh Sleep Quality Index (PSQI). Mini‐mental state examination was applied to assess preoperative mental status of patients. Postoperatively, we used confusion assessment method and memorial delirium assessment scale to evaluate the incidence of POD and POD severity, respectively. The cerebrospinal fluid (CSF) levels of T‐tau, P‐tau, Aβ40, and Aβ42 were detected by enzyme‐linked immune‐sorbent assay before the operation. Logistic regression, multiple linear regression, and mediation effects were performed to analyze the relationship between self‐reported sleep characteristics and POD. Results POD was detected in 11.31% (56/495) of the patients, with logistic regression analysis showing that daytime dysfunction, P‐tau, and T‐tau were risk factors of POD, and Aβ42 was a protective factor of POD. Multiple linear regression analysis confirmed that daytime dysfunction was positively correlated with P‐tau in patients with POD. Meanwhile, compared to the patients with no postoperative delirium, the CSF levels of P‐ and T‐tau were higher in patients with POD. Furthermore, mediation analysis showed that it was probable that daytime dysfunction mediated POD through P‐tau (proportion: 12.90%) partially. Conclusion Daytime dysfunction is a risk factor of POD preoperatively. To sum up, CSF P‐tau protein might partially mediate the influence of daytime dysfunction on POD. Clinical trial registration This study was registered at Chinese Clinical Trial Registry (ChiCTR2000033439).

Abstract Introduction This study sought to explore the association between Life’s Simple 7 (LS7) and cerebrospinal fluid (CSF) Alzheimer’s disease (AD) pathological biomarkers in the cognitively normal northern Chinese population. Methods From the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) study, 1106 cognitively normal participants were enrolled. The mean age was 62.34 years, and 39.6% were female. LS7 scores were summed with each metric assigned 0, 1, or 2 scores. The multiple linear regression models were used to investigate the association between LS7 scores and CSF AD biomarkers. Results We found that LS7 scores were significantly associated with CSF AD pathologies, including Aβ42/40 (β = 0.034, P = .041), p-tau181 (β = − 0.043, P = .006), and t-tau (β = − 0.044, P = .003). In subscales, the biological metrics (blood pressure, cholesterol, glucose) were significantly related to CSF tau-related biomarkers. These associations were observed in the APOE ε4 allele non-carriers, yet not in carriers. The relationship of behavior metrics was found in the middle age and males. Conclusion Improving LS7 scores might do a favor to alleviate the pathology of AD in the preclinical stage, especially among the APOE ε4 allele non-carriers.

Abstract Background Anaemia has been reported to be associated with cognitive decline and Alzheimer’s disease (AD), but the associations between anaemia and cerebrospinal fluid (CSF) AD biomarkers are still unknown. This study aimed to investigate the associations between anaemia and CSF AD biomarkers. Methods Participants were included from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) study. The associations of anaemia and its severity with CSF AD biomarkers including β-amyloid 1–42 (Aβ42), total tau (t-tau) and phosphorylated tau (p-tau) were analysed by multiple linear regression models. Adjusted for age, gender, educational levels, APOE ε4 alleles, comorbidities (history of coronary heart disease, history of stroke, hypertension, diabetes mellitus, dyslipidaemia) and glomerular filtration rate. Results A total of 646 cognitively normal older adults, consisting of 117 anaemia patients and 529 non-anaemia individuals, were included in this study. Anaemia patients had lower levels of CSF Aβ42 than individuals without anaemia (p = 0.035). Besides, participants with more severe anaemia had lower CSF Aβ42 levels (p = 0.045). No significant association of anaemia with CSF t-tau and p-tau levels was found. Conclusion Cross-sectionally, anaemia was associated with lower CSF Aβ42 levels. These findings consolidated the causal close relationship between anaemia and AD.

Abstract Increasing evidences supported that subjective cognitive decline (SCD) might be a potential first symptomatic manifestation of Alzheimer’s disease (AD). The rapidly growing number of SCD individuals who seek medical help and advice also makes it urgent to develop more precise strategy for SCD. Therefore, this study aimed to explore the risk factors for SCD. Logistics and linear regression models were performed to investigate 41 factors for SCD in 1165 participants without objective cognitive impairment. Cochran-Armitage trend test was used to confirm the constant trend toward higher prevalence of SCD with an increasing number of risk factors. A high overall prevalence of SCD was found in total participants (42%). Eight factors were eventually identified as risk factors for SCD, including four stable factors associated with both SCD statues and severity (older age, thyroid diseases, minimal anxiety symptoms, and day time dysfunction; odds ratio (OR) ranging from 1.74 to 2.29) as well as four suggestive factors associated with either SCD statues or severity (female sex, anemia, lack of physical exercises, and living alone; OR ranging from 1.30 to 2.29). The prevalence of SCD gradually increased with the number of risk factors clustering increased in individuals (p for trend

Abstract Objective We aimed to investigate the associations between healthy lifestyles and Alzheimer’s disease (AD) biomarkers in cerebrospinal fluid (CSF). Methods A total of 1108 cognitively intact individuals from Chinese Alzheimer’s Biomarker and LifestylE (CABLE) study were examined to evaluate the associations of AD biomarkers with healthy lifestyle factors, including no current smoking, no harmful drinking, absence of social isolation, and regular physical activity. The participants were categorized into groups of favorable, intermediate, and unfavorable lifestyles according to the lifestyle factors. The associations between overall lifestyle and CSF biomarkers were also analyzed. Results Among cognitively intact older adults, those having more social engagement had lower CSF tau (p = 0.009) and p-tau (p

Abstract The bridging integrator 1 (BIN1) gene is the second most important susceptibility gene for late-onset Alzheimer’s disease (LOAD) after apolipoprotein E (APOE) gene. To explore whether the BIN1 methylation in peripheral blood changed in the early stage of LOAD, we included 814 participants (484 cognitively normal participants [CN] and 330 participants with subjective cognitive decline [SCD]) from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database. Then we tested associations of methylation of BIN1 promoter in peripheral blood with the susceptibility for preclinical AD or early changes of cerebrospinal fluid (CSF) AD-related biomarkers. Results showed that SCD participants with significant AD biological characteristics had lower methylation levels of BIN1 promoter, even after correcting for covariates. Hypomethylation of BIN1 promoter were associated with decreased CSF Aβ42 (p = 0.0008), as well as increased p-tau/Aβ42 (p = 0.0001) and t-tau/Aβ42 (p

Abstract Objective To examine whether apolipoprotein B (ApoB), apolipoprotein A‐1 (ApoA1), or their ratio (ApoB/A1) were associated with early changes in cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) pathology in elderly adults with subjective cognitive decline (SCD). Methods This study included 507 objective cognitive normal participants from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database including 288 cognitive normal participants (CN) and 219 SCD. Multiple linear regression models were used to examine the associations of apolipoproteins with CSF AD biomarkers. Results Compared with control group, SCD participants with significant AD biological characteristics had lower ApoB levels (P = 0.0461). In total participants, lower level of serum ApoB was associated with decreases in CSF Aβ42 (P = 0.0015) and Aβ42/40 (P = 0.0081) as well as increases in CSF p‐tau/Aβ42 (P

Abstract Objective Sleep disorders as a preclinical symptom of synucleinopathies become more prevalent in older adults. Synucleinopathies might be caused by the abnormal aggregation of alpha‐synuclein in the brain, which was indicated by alpha‐synuclein levels in cerebrospinal fluid (CSF). We aimed to investigate associations of sleep characteristics with CSF alpha‐synuclein in older adults. Methods Our study recruited 536 cognitively intact individuals (aged between 40 and 90 years old) from the Chinese Alzheimer’s Biomarker and Lifestyle study. Sleep behaviors were assessed by Pittsburgh Sleep Quality Index and total alpha‐synuclein in CSF was measured by enzyme‐linked immune‐sorbent assay. We used multiple linear and non‐linear regression models for research. Results Significant non‐linear associations of CSF alpha‐synuclein with sleep time and duration were revealed. Individuals who went to bed and fell asleep too early or late tended to have lower CSF alpha‐synuclein (reflection point for time to bed and fall asleep were 10:26 p.m. and 10:40 p.m.). Lower CSF alpha‐synuclein was also observed in individuals with either excessive or insufficient sleep duration (reflection point: 7.24 hours). Besides, overall poor sleep quality (β = −0.0621; P = 0.0242), longer sleep latency (β = −0.0415; P = 0.0174) and lower sleep efficiency (β = 0.0036; P = 0.0017) showed linear associations with lower CSF alpha‐synuclein. Sleep disturbances and daytime dysfunction were not significantly associated with CSF alpha‐synuclein. Interpretation Poor sleep was associated with lower levels of CSF alpha‐synuclein in older adults, which may provide new insight into the prevention of synucleinopathies.

Abstract 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 Aβ1–42, T-tau and P-tau), stage 1 (low Aβ1–42, normal T-tau and P-tau), stage 2 (low Aβ1–42 and high T-tau or P-tau), and suspected non-AD pathology (SNAP) (normal Aβ1–42 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

Abstract Purpose To clarify the effects of habitual tea consumption on postoperative delirium (POD) in elderly patients undergoing total hip/knee arthroplasty. Patients and Methods A prospective cohort study was carried out at Qingdao Municipal Hospital Affiliated to Qingdao University between June 2020 and June 2021. A total of 332 patients aged 65–85 years undergoing total hip/knee arthroplasty under combined spinal and epidural anesthesia were enrolled from the Perioperative Neurocognitive Disorder and Biomarker Lifestyle (PNDABLE) study in the final analysis, consisting of 168 patients with habitual tea consumption and 164 patients with infrequent tea consumption. The primary endpoint was the effects of habitual tea consumption on POD and 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 concentrations of caffeine and tea polyphenols in plasma and cerebrospinal fluid (CSF), which were detected by the enzyme‐linked immunosorbent assay. Results POD occurred in 61 of 332 patients (18.37%), among whom 19 had habitual tea consumption (5.72%) and 42 had infrequent tea consumption (12.65%). Habitual tea consumption (odds ratio [OR] = 0.370, 95% confidence interval [CI]: 0.205–0.670, P = .001) was significantly associated with POD in the logistic analysis, and then after adjusting for age and American Society of Anesthesiologists (ASA) physical status (OR = 0.353, 95% CI: 0.190–0.655, P = .001). Furthermore, caffeine in T0 plasma (OR = 0.834, 95% CI: 0.752–0.924, P = .001), T1 plasma (OR = 0.818, 95% CI: 0.738–0.908, P

Electroacupuncture preconditioning at acupoint Baihui (GV20) can reduce focal cerebral ischemia/reperfusion injury. However, the precise protective mechanism remains unknown. Mitochondrial fission mediated by dynamin-related protein 1 (Drp1) can trigger neuronal apoptosis following cerebral ischemia/reperfusion injury. Herein, we examined the hypothesis that electroacupuncture pretreatment can regulate Drp1, and thus inhibit mitochondrial fission to provide cerebral protection. Rat models of focal cerebral ischemia/reperfusion injury were established by middle cerebral artery occlusion at 24 hours after 5 consecutive days of preconditioning with electroacupuncture at GV20 (depth 2 mm, intensity 1 mA, frequency 2/15 Hz, for 30 minutes, once a day). Neurological function was assessed using the Longa neurological deficit score. Pathological changes in the ischemic penumbra on the injury side were assessed by hematoxylin-eosin staining. Cellular apoptosis in the ischemic penumbra on the injury side was assessed by terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling staining. Mitochondrial ultrastructure in the ischemic penumbra on the injury side was assessed by transmission electron microscopy. Drp1 and cytochrome c expression in the ischemic penumbra on the injury side were assessed by western blot assay. Results showed that electroacupuncture preconditioning decreased expression of total and mitochondrial Drp1, decreased expression of total and cytosolic cytochrome c, maintained mitochondrial morphology and reduced the proportion of apoptotic cells in the ischemic penumbra on the injury side, with associated improvements in neurological function. These data suggest that electroacupuncture preconditioning-induced neuronal protection involves inhibition of the expression and translocation of Drp1.

Abstract In this study, two new kaurane diterpenes (16, 17), together with 12 lignans (1–12), a triterpene (15), and two other compounds (13, 14) were isolated from the woods of Agathis dammara. The structure of the new compound was determined by HR ESIMS and 1D/2D NMR spectroscopy, and its absolute configuration was determined by electronic circular dichroism (ECD) exciton chirality method. Compounds 5, 11, 14 exhibit significant hypoglycaemic activity in zebrafish, and their mechanism of action is to enhance glucose uptake in zebrafish. Graphical Abstract

Introduction: This study delineated the interrelationships among blood pressure (BP), cerebrospinal fluid (CSF) core biomarkers of Alzheimer’s disease (AD), and cognition. Methods: The linear regression analyses were conducted in 1546 non-demented participants (mean age of 61.58 years, range 40 to 89 years; 40% female; average days of BP measurement, 9.10 days). Mediation analyses with 10,000 bootstrapped iterations were used to explore the mediation effects. Results: A clear age-related pattern of BP was delineated. Mid-life hypertension (especially systolic BP), late-life lower diastolic BP, as well as mid- and late-life higher pulse pressure were associated with cognitive impairment and tau-related biomarkers. BP variability was associated only with cognition but not with CSF biomarkers. Overall, the associations between BP and cognition were partially mediated (proportion: 11% to 30%) by tau pathologies, independently of amyloid pathology. Discussion: Tau pathologies might play important roles in the relationship between BP and cognition, with significant age- and BP-type dependences. [ABSTRACT FROM AUTHOR]

Many studies have confirmed that the human poliovirus receptor (PVR; CD155) is related to tumor cell migration, invasion, and thus tumor progression. A PVR receptor binds its ligand T cell Ig and the ITIM domain (TIGIT) to inhibit the function of T and NK cells, thereby allowing tumors to evade immune surveillance. In this study, two IgG1 monoclonal antibodies, anti-CD155 and anti-TIGIT, were expressed by the mammalian transient transfection system, then, antibody-dependent cell-mediated cytotoxicity, antibody-binding affinity, and antitumor efficacy were evaluated subsequently in vitro. In this work, protein A affinity chromatography was used for antibodies' purification. Analysis methods included Western blot, enzyme-linked immunosorbent assay, and flow cytometry. Our data suggested that both the two monoclonal antibodies have a purity of higher than 90%, and bound tightly to the antigen with dissociation constant (K d) and 50% effective concentrations (EC50) below micromolar range. Most notably, these antibodies promote antitumor activity of immune cells in vitro. Therefore, our study laid down the foundation for subsequent in vivo experiments for further evaluation.