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Background: Subjective cognitive decline (SCD) might occur at the early stages of dementia. Individuals with SCD have an increased risk of subsequent objective cognitive decline and greater rates of progression to dementia. Objective: We aimed to explore the associations between SCD and cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) pathology in cognitively normal individuals. Methods: A total of 1,099 cognitively normal elders with available data on CSF biomarkers of AD pathology (Aβ42, P-tau, and T-tau) were included in our analysis. Linear regression was used to examine the associations of SCD status and SCD severity with CSF biomarkers. Additionally, a review was conducted to discuss the associations between SCD and CSF biomarkers of AD pathology. Results: After adjustments for covariates, SCD and SCD severity showed significant associations with CSF Aβ42 (SCD: β= –0.0003, p = 0.0263; SCD severity: β= –0.0004, p = 0.0046), CSF T-tau/Aβ42 ratio (SCD: β= 0.1080, p = 0.0064; SCD severity: β= 0.1129, p = 0.0009) and CSF P-tau/Aβ42 ratio (SCD: β= 0.0167, p = 0.0103; SCD severity: β= 0.0193, p = 0.0006) rather than T-tau and P-tau compared with cognitively normal individuals. In the review, a total of 28 studies were finally included after reviewing 174 articles. CSF Aβ42 was lower in SCD than cognitively normal (CN) individuals, but higher than those with objective cognitive decline. However, CSF tau pathology showed no difference between SCD and CN. Conclusion: The results indicated that pathophysiological changes in CSF Aβ pathology occurred in individuals with SCD, which provide new insights into early intervention of AD.

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

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.

Background: Heart failure has been considered as a potential modifiable risk factor for cognitive impairment and dementia. Left ventricular ejection fraction (LVEF), an indicator of cardiac dysfunction, has also been associated with cognitive aging. However, the effect of LVEF on Alzheimer’s disease (AD) pathology is still less known. Objective: We aimed to investigate the associations of LVEF with cerebrospinal fluid (CSF) biomarkers for AD in cognitively normal elders. Methods: A total of 423 cognitively normal individuals without heart failure were included from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) study. Participants were divided into low LVEF group (50%≤LVEF

Background: Although social networks are deemed as moderators of incident Alzheimer’s disease (AD), few data are available on the mechanism relevant to AD pathology. Objective: We aimed to investigate whether social networks affect metabolism of cerebrospinal fluid (CSF) AD biomarkers during early stage and identify modification effects of genetic factor and subjective cognitive decline (SCD). Methods: We studied participants from the Chinese Alzheimer’s disease Biomarker and Lifestyle (CABLE) database who received cognition assessments and CSF amyloid-β (Aβ1–42 and Aβ1–40) and tau proteins (total-tau [T-tau] and phosphorylated-tau [P-tau]) measurements. The social networks were measured using self-reported questionnaires about social ties. Linear regression models were used. Results: Data were analyzed from 886 cognitively intact individuals aged 61.91 years (SD = 10.51), including 295 preclinical AD participants and 591 healthy controls. Social networks were mostly associated with CSF indicators of AD multi-pathologies (low P-tau/Aβ1–42 and T-tau/Aβ1–42 and high Aβ1–42/Aβ1–40). Significant differences of genetic and cognitive status were observed for CSF indicators, in which associations of social network scores with CSF P-tau and indicators of multi-pathologies appeared stronger in APOE 4 carriers (versus non-carriers) and participants with SCD (versus controls), respectively. Alternatively, more pronounced associations for CSF T-tau (β= –0.005, p

The relationship between depression and Alzheimer's disease (AD) is complex and still not well understood. We aimed to examine the roles of the AD core pathologies in modulating the associations of minimal depressive symptoms (MDSs) with cognitive impairments.A total of 721 participants who had measures of cognition, depressive symptoms, and cerebrospinal fluid AD biomarkers were included from the CABLE (Chinese Alzheimer's Biomarker and LifestylE) study. Causal mediation analyses with 10,000 bootstrapped iterations were conducted to explore the mediation effects of AD pathologies on cognition. The ADNI (Alzheimer's Disease Neuroimaging Initiative) was used 1) to replicate the mediation effects and 2) to examine the longitudinal relationships of MDSs with amyloid pathology and incident AD risk.In CABLE, MDSs were associated with poorer global cognition (p = .006) and higher amyloid burden as indicated by cerebrospinal fluid amyloid markers (p.0001). The influence of MDSs on cognition was partially mediated by amyloid pathology (a maximum of 85%). The mediation effects were replicated in 725 elderly persons without dementia (age, mean ± SD = 73.5 ± 6.9 years; 301 female subjects [42%]) in ADNI, such that the mediation percentage varied from 10% to 30% for general cognition, memory, and executive functions. Longitudinal analyses revealed a bidirectional relationship between MDSs and amyloid pathology (p = .01). MDSs were associated with 83% increased risk of developing AD dementia (hazard ratio = 1.83, p.01).Overall, amyloid pathology might partially mediate and magnify the influences of MDSs on cognitive impairments and AD risk.

BACKGROUND: Studies suggested that vascular dysfunction might increase the risk of developing Alzheimer’s disease (AD), but the underlying mechanisms still remain obscure. Objective: To evaluate the associations of vascular risk burden with AD core pathologies and investigate the effects of AD core pathologies on relationships between vascular risk burden and cognitive impairments. Design: The Chinese Alzheimer’s Biomarker and LifestyLE (CABLE) study was principally focusing on aging, as well as the risk factors and biomarkers of AD initiated in 2017. Setting: The CABLE study was a large cohort study established in Qingdao, China. Participants: A total of 618 non-demented elders were obtained from CABLE study. Measurements: The general vascular risk burden was assessed by the Framingham General Cardiovascular Risk Score (FGCRS). Multivariate linear regression analyses were performed to evaluate the associations of FGCRS with cerebrospinal fluid (CSF) AD biomarkers and cognition. Casual mediation analyses were performed to investigate the mediating effects of AD biomarkers on cognition. Results: Increased FGCRS was related to higher levels of CSF total tau (t-tau, p < 0.001), phosphorylated tau (p-tau, p < 0.001) as well as the ratio of t-tau and amyloid-β 42 (t-tau/Aβ42, p = 0.010), and lower Chinese-Modified Mini-Mental State Examination (CM-MMSE, p = 0.010) score. Stratified analysis indicated that age modified the associations, with FGCRS being significantly associated with tau pathology (p < 0.001 for t-tau and p-tau) in middle-aged group (

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.

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 P P 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).

Background: Green tea has been widely recognized in ameliorating cognitive impairment and Alzheimer’s disease (AD), especially the progression of cognitive dysfunction. But the underlying mechanism is still unclear. Objective: This study was designed to determine the role of green tea consumption in the association with cerebrospinal fluid (CSF) biomarkers of AD pathology and to ascertain whether specific population backgrounds showed the differences toward these relationships. Methods: Multivariate linear models analyzed the available data on CSF biomarkers and frequency of green tea consumption of 722 cognitively intact participants from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database, and we additionally detected the interaction effects of tea consumption with APOE ɛ4 status and gender using a two-way analysis of covariance. Results: Frequent green tea consumption was associated with a decreased level of CSF total-tau protein (t-tau) (p = 0.041) but not with the levels of CSF amyloid-β 42 (Aβ42) and CSF phosphorylated tau. The more pronounced associations of green tea consumption with CSF t-tau (p = 0.007) and CSF t-tau/Aβ42 (p = 0.039) were observed in individuals aged 65 years or younger. Additionally, males with frequent green tea consumption had a significantly low level of CSF t-tau/Aβ42 and a modest trend toward decreased CSF t-tau. There were no interaction effects of green tea consumption with APOE ɛ4 and gender. Conclusion: Collectively, our findings consolidated the favorable effects of green tea on the mitigation of AD risk. The constituents of green tea may improve abnormal tau metabolism and are promising targets in interventions and drug therapies.

It was unclear whether sex hormone-binding globulin (SHBG) was a circulating biomarker of Alzheimer’s disease (AD). We tested the cross-sectional relationships between plasma SHBG and cerebrospinal fluid (CSF) AD biomarkers in 707 non-demented adults. Next, the influences of plasma SHBG on dynamic changes of CSF Aβ42, hippocampus volume, brain metabolism, and cognition were explored in 448 non-demented adults from the Alzheimer’s disease Neuroimaging Initiative (ADNI). Finally, the predictive and diagnostic values of plasma SHBG in AD were explored. A positive correlation was found between SHBG levels in plasma and CSF. Individuals with higher plasma SHBG levels had lower CSF Aβ42 (p < 0.005), after adjusting for age, gender, education, APOE4 allele, and cognitive scores. Though no significant difference of plasma SHBG was observed between mild AD dementia and healthy normal, plasma SHBG could contribute to accelerated rates of CSF Aβ42 decrease (p < 0.0005), decline in brain metabolism (p < 0.05), and hippocampus atrophy (p < 0.01), cognitive decline (p < 0.01), as well as higher risk of AD dementia (p < 0.05). These findings indicated plasma SHBG could be a prodromal biomarker to predict disease progression in AD.

Background: Although cigarette smoking is an important modifiable factor of cognitive impairment, the roles of the Alzheimer’s disease (AD) core pathologies in modulating this process have not been fully delineated. Objective: This study aimed to explore associations of cigarette smoking with cognition and cerebrospinal fluid (CSF) AD biomarkers. Methods: A total of 1,079 non-demented participants were included from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) study. Associations of cigarette smoking with cognition and CSF AD biomarkers were explored by multiple linear regression models. The mediation analyses with 10,000 bootstrapped iterations were conducted to explore the mediation effects. Results: Heavy cigarette smokers (pack-years > 20) had poorer global cognition as well as higher levels of CSF p-tau and t-tau compared with the non-smokers (p

Objectives To compare differential expression protein in hippocampal tissues from mice of perioperative neurocognitive disorder (PND) and normal control mice and to explore the possible mechanism of PND. Methods Mice were randomly divided into a PND group (n = 9) and a control group (n = 9).The mice in the PND group were treated with open tibial fracture with intramedullary fixation under isoflurane anesthesia, while the mice in the control group received pure oxygen without surgery. The cognitive functions of the two groups were examined using Morris water maze experiment, Open field test and Fear conditioning test. The protein expression of the hippocampus of mice was analyzed by high-performance liquid chromatography–mass spectrometry (HPLC–MS/MS). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore the principal functions of dysregulated proteins. Results A total of 21 proteins were differentially expressed between PND and control mice on days 1, 3, and 7 after the operation. These proteins were involved in many pathological processes, such as neuroinflammatory responses, mitochondrial oxidative stress, impaired synaptic plasticity, and neuronal cell apoptosis. Also, the dysregulated proteins were involved in MAPK, AMPK, and ErbB signaling pathways. Conclusion The occurrence of PND could be attributed to multiple mechanisms.

Background: The associations between sleep characteristics and cognition are complicated. Alzheimer’s disease (AD) pathologies have been proven to be associated with sleep characteristics. Objective: We aimed to investigate the associations between sleep characteristics and cognitive function and examine the roles of AD pathologies in modulating the association of sleep duration with cognition. Methods: A total of 974 participants who had measurements of cerebrospinal fluid (CSF) amyloid-β (Aβ), phosphorylated tau (P-tau), total tau proteins (T-tau), cognitive function, and sleep characteristics were included from the Chinese Alzheimer’s Biomarker and Lifestyle (CABLE) study. Linear regression analyses were utilized to explore the associations of sleep characteristics with cognition. Non-linear regression analyses were utilized to explore the associations of sleep habits with cognition. Causal mediation analyses were conducted to explore the mediation effects of AD pathologies on cognition. Results: The Pittsburgh Sleep Quality Index (PSQI) total score was significantly negatively correlated with Montreal Cognitive Assessment (MoCA) score (p = 0.0176). Long latency (p = 0.0054) and low efficiency (p = 0.0273) were associated with cognitive impairment. Habitual nap behavior was associated with lower MoCA scores (p = 0.0045). U-shaped associations were observed between sleep habits (bedtime and nocturnal sleep duration) and cognition. A causal mediation analysis indicated that P-tau/Aβ42 mediated the association of sleep duration with cognition. Conclusion: These findings showed sleep characteristics were associated with cognitive functions. Sleep habits (duration, bedtime) had U-shaped associations with cognition. AD core pathologies might partially mediate the influence of sleep duration on cognitive impairments.

INTRODUCTION: There are no reports regarding a pregnant woman with fulminant myocarditis underwent Extracorporeal Membrane Oxygenation (ECMO). Hence, we report a case of successful ECMO treatment of fulminant myocarditis puerpera. CASE PRESENTATION: A 32-year-old puerpera was admitted to our hospital with menopause for 7 months, fetal movement for 3 months and fever for 1 day. After admission, the patient's body temperature increased repeatedly, heart rate increased, and the whole process C-reactive protein increased rapidly. Considered a diagnosis of fulminant myocarditis. After antiviral and cardioprotective treatment, the heart function progressively worsened. Pregnancy was terminated, the newborn was intubated in the neonatal room for rescue after surgery, and ECMO treatment was given after the puerpera was transferred to the intensive care unit. Finally, the patient and the baby have been safely discharged from hospital. DISCUSSION: ECMO can provide cardiac and respiratory support. Fulminant myocarditis is common in children, adolescents and particularly pregnant women who had the highest mortality rate. In the pregnant woman with fulminant myocarditis described in this report, antiviral treatment only transiently improved heart function and then heart function progressively worsened. After receiving ECMO therapy, the patient's cardiac function has improved markedly. The patient was then successfully weaned from ECMO. To our knowledge, this is the first report of pregnant woman in whom ECMO was part of the treatment for fulminant myocarditis. CONCLUSION: We report a case of successful ECMO treatment of fulminant myocarditis puerpera. ECMO can be the treatment of choice for pregnant women with fulminant myocarditis.

The associations between obesity and Alzheimer's disease (AD) at different ages have been debated. Recent evidence implied the protective effects of metabolically healthy obesity on AD. We hypothesized that obesity and lipids could mitigate the detrimental impacts of AD pathological changes among metabolically healthy individuals in late life. In this study, a total of 604 metabolically healthy participants with normal cognition were included from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) database. Multiple linear regression models were used to test the associations of body mass index (BMI) or lipids with cerebrospinal fluid (CSF) biomarkers after adjustment for age, gender, education, and Apolipoprotein E-ɛ4 (APOE-ɛ4). The results showed the lower CSF levels of total tau protein (t-tau: p = .0048) and phosphorylated tau protein (p-tau: p = .0035) in obese participants than in non-obese participants, even after correcting for covariates. Moreover in late life, higher BMI was associated with decreased CSF t-tau (β: -0.15, p = .0145) and p-tau (β: -0.17, p = .0052). As for lipids, higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were associated with decreased CSF t-tau (TC: β: -0.16, p = .0115; LDL-C: β: -0.16, p = .0082) and p-tau (TC: β: -0.15, p = .0177; LDL-C: β: -0.14, p = .0225) in obese participants. Furthermore, these associations were only significant in participants with late-life obesity and APOE-ɛ4 non-carriers. Overall, in a cognitively normal population, we found metabolically healthy obesity and lipids in late life might be protective factors for neurodegenerative changes.

Background: The relationship between alcohol consumption and Alzheimer’s disease (AD) pathology is unclear. Amyloid-β (Aβ) and tau biomarkers in cerebrospinal fluid (CSF) have been proven valuable in establishing prognosis in pre-clinical AD. Objective: We sought to examine the associations between alcohol consumption and CSF AD biomarkers in cognitive intact subjects. Methods: A total of 806 cognitively intact participants who had measurements of CSF Aβ, pTau, and total Tau proteins and drinking characteristics were included from the Chinese Alzheimer’s Biomarker and Lifestyle (CABLE) study. Linear and logistic regression analyses were utilized to explore the associations of alcohol consumption with CSF AD biomarkers. We examined the interaction effects of age, gender, and apolipoprotein epsilon (APOE) ɛ4 status on the relationships between the frequency of drinking and CSF biomarkers. Results: The multiple linear regression analyses revealed significant differences in CSF AD biomarkers between infrequent drinking ( 65 years) participants. Conclusion: The present study showed significant associations between drinking frequency and CSF AD biomarkers in cognitively intact older adults. Alcohol consumption may have an influence on AD by modulating amyloid deposition and tau phosphorylation in the preclinical stage.

Xu Lin,1,* Pei Wang,1 Ding-Wei Liu,2 Yu-Wei Guo,1 Chun-Hui Xie,3 Bin Wang,1,* Rui Dong,4 Li-Xin Sun,1 Ming-Shan Wang,1 Yan-Lin Bi1 1Department of Anesthesiology, Qingdao Municipal Hospital Affiliated to Qingdao University, Qingdao, People’s Republic of China; 2Department of Laboratory, Qingdao Municipal Hospital Affiliated to Qingdao University, Qingdao, People’s Republic of China; 3Department of Anesthesiology, Weifang Medical University, Weifang, People’s Republic of China; 4Department of Anesthesiology, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan-Lin Bi; Ming-Shan WangDepartment of Anesthesiology, Qingdao Municipal Hospital Affiliated to Qingdao University, Qingdao, People’s Republic of ChinaTel +86 186 6167 5610; +86 186 61675608Email yanlinbi68@sina.cn; wmsqingdao@163.comPurpose: 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 (PETCO2), 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.Keywords: intraoperative oxygen concentration, postoperative delirium, malignancy

Objective: Subjective cognitive decline (SCD) is associated with an increased risk of clinical cognitive disorders. Post-operative delirium (POD) is a common complication after total hip replacement. We aimed to investigate the relationship between SCD and POD in patients undergoing total hip replacement.Methods: Our study recruited 214 cognitively intact individuals from the Perioperative Neurocognitive Disorder And Biomarker Lifestyle (PNDABLE) study in the final analysis. SCD was diagnosed with Subjective Cognitive Decline Scale (SCDS), Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA). 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). Preoperative cerebrospinal fluid (CSF) Aβ40, Aβ42, T-tau, and P-tau levels were measured by enzyme-linked immune-sorbent assay (ELISA).Results: Overall, the incidence of POD was 26.64% (57/214), including 32.43% (36/111) in the SCD group and 20.39% (21/103) in the NC group. With the increase of age, the incidence of POD in all age groups increased (P < 0.05). Logistic regression analysis showed that after adjusting for SCD, Aβ42, Aβ40, P-tau, and T-tau, SCD (OR 2.32, CI 1.18–4.55, P = 0.01) and the increased CSF level of P-tau (OR 1.04, CI 1.01–1.06, P < 0.001) were risk factors for POD, while the level of aβ42 (OR 0.99, CI 0.99–1.00, P < 0.001) was a protective factor for POD.Conclusion: SCD is one of the preoperative risk factors for POD.Clinical Trial Registration: This study was registered at China Clinical Trial Registry (Chictr200033439).

Background: Postoperative delirium (POD) represents a serious complication following anesthesia and surgical procedures for patients undergoing surgical intervention. At present, there is no effective index to predict the occurrence of POD ,so the aim of this study was to validate whether cerebrospinal fluid (CSF) PGRN could predict the occurrence of POD.Methods: We conducted a prospective nested case-control and 1:1 matched (on age, diagnosis, American Society of Anesthesiologist’ (ASA) physical status, duration of surgery, and intraoperative blood loss) study. A total of 600 Han Chinese patients over the age of 65~ 90 who underwent unilateral total knee arthroplasty were included in the PNDABLE study from June 2020 to November 2020. POD cases and non-POD controls were selected from using Confusion Assessment Method (CAM) on the first, second, third and seventh (or before discharge) postoperative days. Delirium severity was measured by the Memorial Delirium Assessment Scale (MDAS). In the six month, cognitive function was assessed with the modified Telephone Interview for Cognitive Status (TICS-m) and the World Health Organization Quality of Life brief version (WHOQOLBREF). CSF PGRN and core biomarkers were measured by ELISA using the microplate reader. The associations of CSF PGRN levels with POD risk and CSF core biomarkers (Aβ1–42, Aβ1–40 ,T-tau and P-tau)were assessed. The effect of CSF PGRN on predicting POD occurrence was evaluated with the area under the receiver operating characteristic (ROC) curve (AUC).Results: POD incidence was 9.7% (53/545). There were significant differences in preoperative CSF PGRN concentration between POD patients and non-POD (P1–42 (β = 0.756, P < 0.001) , Aβ1–40 (β =0.637, P < 0.001) and negative associations of CSF PGRN with T-tau (β = -0.716, P < 0.001) and P-tau (β = -0.739, P < 0.001) in POD patients. The ROC curve analysis of PGRN showed that PGRN concentrations had high diagnostic value for POD.Conclusions: Aβ pathology is associated with increasing in CSF PGRN whereas Tau pathology and neurodegeneration is associated with decreasing in CSF PGRN in POD patients.CSF PGRN can predict the occurrence of POD in elderly patients．Clinical Trial Registration: www.clinicaltrials.gov, identifier ChiCTR2000033439.

Background: Serum uric acid (SUA) affects the reaction of oxidative stress and free radicals in the neurodegenerative processes. However, whether SUA impacts Alzheimer’s disease (AD) pathology remains unclear. Objective: We aimed to explore whether high SUA levels can aggravate the neurobiological changes of AD in preclinical AD. Methods: We analyzed cognitively intact participants (n = 839, age 62.16 years) who received SUA and cerebrospinal fluid (CSF) biomarkers (amyloid-β [Aβ], total tau [t-Tau], and phosphorylated tau [p-Tau]) measurements from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database using multivariable-adjusted linear models. Results: Levels of SUA in the preclinical AD elevated compared with the healthy controls (p = 0.007) and subjects with amyloid pathology had higher concentration of SUA than controls (p = 0.017). Roughly, equivalent levels of SUA displayed among cognitively intact individuals with or without tau pathology and neurodegeneration. CSF Aβ1 - 42 (p = 0.019) and Aβ1 - 42/Aβ1 - 40 (p = 0.027) were decreased and CSF p-Tau/Aβ1 - 42 (p = 0.009) and t-Tau/Aβ1 - 42 (p = 0.043) were increased with the highest (> 75th percentile) SUA when compared to lowest SUA, implying a high burden of cerebral amyloidosis in individuals with high SUA. Sensitivity analyses using the usual threshold to define hyperuricemia and precluding drug effects yielded robust associations. Nevertheless, the quadratic model did not show any U-shaped relationships between them. Conclusion: SUA may aggravate brain amyloid deposition in preclinical AD, which corroborated the detrimental role of SUA.

BackgroundPostoperative delirium (POD) represents a serious complication following anesthesia and surgical procedures for patients undergoing surgical intervention (1). Little is known about the mechanisms underlying similarities in the core features between postoperative delirium (POD) and progranulin (PGRN)-related cognitive disorders. We herein investigated the relationship between preoperative CSF PGRN concentration and POD occurrence in the Han Chinese patients undergoing unilateral total knee arthroplasty.MethodsWe conducted an observational, prospective, and 1:1 matched (on age older than 65, the unilateral total knee arthroplasty, American Society of Anesthesiologist’ (ASA) physical status, duration of surgery, and intraoperative bleeding) case-control study. POD cases and non-POD controls were selected from the overall cohort using Confusion Assessment Method (CAM). Delirium severity was measured by the Memorial Delirium Assessment Scale (MDAS). CSF PGRN and core biomarkers were measured by ELISA using the microplate reader. The associations of CSF PGRN levels with POD risk and CSF core biomarkers were assessed.ResultsPOD incidence was 9.7% (53/545). There were significant differences in preoperative CSF PGRN concentration between POD patients and controls (P1–42 (β = -0.576, P < 0.001), Aβ1–40 (β = -0.488, P < 0.001), Aβ42/p-tau (β = -0.422, P < 0.001), and Aβ42 / T- tau (β = -0.395, P < 0.001) in POD patients. The ROC curve analysis of PGRN showed that PGRN concentrations had high diagnostic value for POD.ConclusionsCSF PGRN may be associated with the POD. Aβ pathology is associated with a decrease in CSF PGRN in the absence of tau deposition and neurodegeneration, whereas tau pathology and neurodegeneration is associated with an increase in CSF PGRN.Clinical Trial Registrationwww.clinicaltrials.gov, identifier ChiCTR2000033439.

Postoperative cognitive dysfunction (POCD) is a serious complication following anesthesia and operations in aged patients undergoing surgical intervention. It is characterized by temporary or permanent cognitive decline, memory impairment and deterioration in language comprehension and social adaption ability. Therefore, the development of POCD prevention and treatment tools has become an area of interest. The current study assessed the therapeutic effects of insulin-like growth factor-1 (IGF-1) on POCD in aged rats and explored the underlying mechanisms. Model rats underwent splenectomy under 1.5-2% isoflurane and mechanical ventilation. IGF-1 (50 µg/kg) was diluted in normal saline and administered by abdominal hypodermic injection daily from the operation to day 7 post-operation. Following splenectomy, the animals showed marked cognitive impairment as determined by the Morris water maze test. Hippocampal protein levels of amyloid precursor protein (APP), β-site APP-cleaving enzyme-1 (BACE-1), amyloid-β (Aβ), capase3, Bax and Bcl-2 were assessed by immunoblotting. Neuronal apoptosis in the hippocampus was analyzed using a TUNEL assay. The results demonstrated that the levels of APP, BACE-1, Aβ, caspase3 and Bax were increased following splenectomy, while the levels of Bcl2 were reduced at days 1, 3 and 7 post-operation in aged rats. However, IGF-1 downregulated APP, BACE-1, Aβ, capase3 and Bax, and upregulated Bcl2 at these time points following splenectomy. TUNEL staining revealed that administration of IGF-1 significantly reduced neuronal apoptosis in the hippocampal CA1 region following splenectomy. These results indicated that IGF-1 decreased Aβ-protein production and inhibited neuronal apoptosis in the hippocampus following splenectomy, subsequently alleviating POCD.

As brain insults, sleep disorders could enhance microglial activation and aggravate neuroinflammation. Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) serves as a readout for TREM2-associated microglial responses. We aimed to study the association of sleep characteristics with CSF sTREM2 in cognitively normal (CN) older adults. Linear and non-linear regression analyses were conducted in 830 participants with measurements of sleep characteristics and CSF sTREM2, after adjusting for age, sex, education, the Chinese-Modified Mini-Mental State Examination (CM-MMSE) scores, and APOE4 status. These analyses were also performed in amyloid-negative (A −) and amyloid-positive (A +) individuals. Linear relationships between sleep characteristics and CSF sTREM2 were found. In all the participants, sleep efficiency score in Pittsburgh Sleep Quality Index (PSQI) (p = 0.037) showed a positive linear association with CSF sTREM2. In A + individuals, the grade of PSQI total score (p = 0.011) as well as subjective sleep quality score (p = 0.048) and sleep efficiency score (p

Cerebrospinal fluid (CSF) progranulin (PGRN) is related to various neurodegeneration diseases. And sleep problems can cause abnormality in protein metabolism in vivo. We aim to explore the potential associations between the self-reported sleep characteristics and CSF PGRN in cognitively intact older adults. Our study recruited 747 participants (mean (standard deviation (SD)) age, 61.99 (10.52) years, 329 (42.89%) females) who had normal cognition from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) study with CSF PGRN and sleep characteristics measured. The multiple linear regression and nonlinear regression adjusted for age, gender, education, and apolipoprotein E-epsilon 4 gene (APOE4) status were used to assess the associations between sleep characteristics and PGRN. Interaction effects were explored between APOE4 status and sleep characteristics on CSF PGRN level. Sleep disturbances indicated lower CSF PGRN (β = − 0.0186, p = 0.0160). For detailed items in sleep disturbances, lower CSF PGRN was found in males who woke up during sleep (β = − 0.0121, p = 0.0062) and in females who had breathing difficulties (β = − 0.0258, p = 0.0271). Meanwhile, sleep efficiency was associated with CSF PGRN (β = − 0.0512, p = 0.0497). No significant interaction effects between sleep characteristics and APOE4 status were found. Meanwhile, we did not find a nonlinear relationship between nocturnal sleep duration and CSF PGRN. Sleep problems may influence the metabolism of PGRN, thus attenuating the protective effects of PGRN on neurodegeneration diseases.

Background Accumulating reports have suggested that α-synuclein is involved in the pathogenesis of Alzheimer’s disease (AD). As the cerebrospinal fluid (CSF) α-synuclein has been suggested as a potential biomarker of AD, this study was set out to test whether CSF α-synuclein is associated with other AD biomarkers and could predict neurodegeneration and clinical progression in non-demented elders. Methods The associations between CSF α-synuclein and other AD biomarkers were investigated at baseline in non-demented Chinese elders. The predictive values of CSF α-synuclein for longitudinal neuroimaging change and the conversion risk of non-demented elders were assessed using linear mixed effects models and multivariate Cox proportional hazard models, respectively, in the Alzheimer’s disease Neuroimaging Initiative (ADNI) database. Results The CSF α-synuclein levels correlated with AD-specific biomarkers, CSF total tau and phosphorylated tau levels, in 651 Chinese Han participants (training set). These positive correlations were replicated in the ADNI database (validation set). Using a longitudinal cohort from ADNI, the CSF α-synuclein concentrations were found to increase with disease severity. The CSF α-synuclein had high diagnostic accuracy for AD based on the “ATN” (amyloid, tau, neurodegeneration) system (A + T+ versus A − T − control) (area under the receiver operating characteristic curve, 0.84). Moreover, CSF α-synuclein predicted longitudinal hippocampus atrophy and conversion from MCI to AD dementia. Conclusions CSF α-synuclein is associated with CSF tau levels and could predict neurodegeneration and clinical progression in non-demented elders. This finding indicates that CSF α-synuclein is a potentially useful early biomarker for AD.

BackgroundAccumulating reports suggest that α-synuclein is involved in Alzheimer disease (AD) pathogenesis. Cerebrospinal fluid (CSF) α-synuclein could be a potential biomarker of AD. We sought to test whether CSF α-synuclein is associated with other AD biomarkers and could predict neurodegeneration and clinical progression in prodromal AD. MethodsAssociations were investigated between CSF α-synuclein and other AD biomarkers at baseline in prodromal AD stage Chinese elders. The predictive values of CSF α-synuclein in longitudinal change in clinical outcomes and conversion risk of prodromal AD stage subjects were assessed using linear mixed effects models and multivariate Cox proportional hazard models, respectively, in Alzheimer's disease Neuroimaging Initiative (ADNI) database.ResultsAmong individuals in prodromal AD stage, we detected that CSF α-synuclein levels correlated with AD-specific biomarkers CSF total tau and phosphorylated tau levels in 651 Chinese Han participants (training set). These positive correlations were replicated in ADNI database (validation set). Using a longitudinal cohort from ADNI, CSF α-synuclein concentrations increased with disease severity. CSF α-synuclein had high diagnostic accuracy for AD based on the “ATN” system (A+T+) vs controls (A-T-) (area under the receiver operating characteristic curve, 0.84). Moreover, CSF α-synuclein predicted longitudinal hippocampus atrophy and conversion from MCI to AD dementia.ConclusionsCSF α-synuclein is associated with CSF tau levels and could predict neurodegeneration and clinical progression in prodromal AD. This finding indicates CSF α-synuclein is a potentially useful, early biomarker for AD.

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

Background Postoperative Cognitive Dysfunction (POCD) has received considerable attention as one of the main postoperative complications. The underlying mechanism of POCD in elderly subjects has not been fully elucidated to date. The Central Nervous System (CNS) is isolated from the bloodstream by the Blood Brain Barrier (BBB) that consists of endothelial cells, capillary blood vessels and tight junctions. The tight junctions carry out significant biological functions that are associated with the CNS and blood circulation. Methods In this review, I present a hypothesis that blood-brain barrier disruption leads to postoperative cognitive dysfunction. A total of 81 healthy male Wistar rats were used for the present study. All the experimental animals were randomly divided into 3 groups: normal control group, isoflurane group and splenectomy group. The control group was not subjected to any form of treatment. The rats in isoflurane group were given 1.5-2% isoflurane under intubation and mechanical ventilation. The rats in splenectomy group underwent splenectomy under the same anesthesia as the isoflurane group. The Morris water maze was used to examine the learning and memory ability of the animals. The expression of the Tight Junctions Proteins (TJPs) in the hippocampus was analyzed using Western blotting. The concentration of Evans Blue (EB) in the supernatant was analyzed using UV spectroscopy. Ultrastructure changes in the basal laminas, the Tight Junctions (TJs), mitochondria and the endoplasmic reticulum surrounding the capillaries were assessed by Transmission Electron Microscopy (TEM). Results Following splenectomy, the rats displayed concomitant significant cognitive deficits in the Morris water maze test. Taken together, the results indicate that the expression levels of occludin (65KD) following splenectomy were reduced on days one and three in aged rats. No significant difference was noted in the expression levels of claudin-5, except for a reduction after surgery on day one. The leakage of EB was higher following splenectomy than control group and isoflurane group. The ultrastructure of the neurovascular unit was monitored on the day prior to surgery and on the 1st, 3rd and 7th day following surgery using a transmission electronmicroscope. Conclusion The alterations in the levels of tight junction proteins following splenectomy may contribute to the BBB permeability increase, which in turn will induce postoperative cognitive dysfunction.

Background: The preclinical stage of Alzheimer's disease (AD) has become a key target stage for future AD prevention trials. Serum apolipoprotein, an important lipid-related factor, has been found to be involved in the pathogenesis of AD. This study was to examine whether apolipoprotein B (ApoB), apolipoprotein A-1 (ApoA1) or the ratio of ApoB and ApoA1 (ApoB/A1) were associated with early changes of cerebrospinal fluid (CSF) AD biomarkers in elderly adults with subjective cognitive decline.Methods: This study included 201 cognitive normal (CN) elderly adults and 101 participants with subjective cognitive decline (SCD) from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database. The Kruskall-Wallis test and Chisquare test were applied in the intergroup comparisons. Multiple linear regression models were used to examine the cross-sectional associations of serum ApoB, ApoA1 and ApoB/A1 levels with CSF AD-related biomarkers.Results: Compared with the control group, SCD participants with significant AD biological characteristics had lower ApoB levels. In the total participants, higher level of serum ApoB was associated with increases in CSF Aβ42 (p = 0.0009) and Aβ42/40 (p = 0.0038) as well as decreases in CSF t-tau/Aβ42 (p < 0.0001) and p-tau/Aβ42 (p < 0.0001), independent of APOEɛ4 status. In the further subgroup analysis, these associations were much more significant in the SCD participants. In addition, higher levels of serum ApoB were also found associated with decreases in CSF t-tau (p = 0.0224), p-tau (p = 0.0086) and Aβ40 (p = 0.0297) in the SCD subgroup. Furthermore, we found that these protective associations between serum ApoB and CSF AD core biomarkers were much more significant in the overweight participants. Results showed no association between ApoA1 and all CSF biomarkers in either total participants or subgroups. Conclusions: This study is the first to find protective associations of serum ApoB, but not ApoA1, with CSF AD core biomarkers in elderly adults, and these associations were more significant in SCD individuals. This finding indicated that ApoB may play a protective role in the preclinical stage of AD. Identifying the underlying mechanisms may contribute to the discovery of new pathogenic mechanisms and therapeutic targets.

Background The preclinical stage of Alzheimer's disease (AD) has become a key target stage for future AD prevention trials. Serum apolipoprotein, an important lipid-related factor, has been found to be involved in the pathogenesis of AD. This study was to examine whether apolipoprotein B (ApoB), apolipoprotein A-1 (ApoA1) or the ratio of ApoB and ApoA1 (ApoB/A1) were associated with early changes of cerebrospinal fluid (CSF) AD biomarkers in elderly adults with subjective cognitive decline. Methods This study included 201 cognitive normal (CN) elderly adults and 101 participants with subjective cognitive decline (SCD) from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database. The Kruskall-Wallis test and Chisquare test were applied in the intergroup comparisons. Multiple linear regression models were used to examine the cross-sectional associations of serum ApoB, ApoA1 and ApoB/A1 levels with CSF AD-related biomarkers. Results Compared with the control group, SCD participants with significant AD biological characteristics had lower ApoB levels. In the total participants, higher level of serum ApoB was associated with increases in CSF Aβ42 (p = 0.0009) and Aβ42/40 (p = 0.0038) as well as decreases in CSF t-tau/Aβ42 (p < 0.0001) and p-tau/Aβ42 (p < 0.0001), independent of APOEɛ4 status. In the further subgroup analysis, these associations were much more significant in the SCD participants. In addition, higher levels of serum ApoB were also found associated with decreases in CSF t-tau (p = 0.0224), p-tau (p = 0.0086) and Aβ40 (p = 0.0297) in the SCD subgroup. Furthermore, we found that these protective associations between serum ApoB and CSF AD core biomarkers were much more significant in the overweight participants. Results showed no association between ApoA1 and all CSF biomarkers in either total participants or subgroups. Conclusions This study is the first to find protective associations of serum ApoB, but not ApoA1, with CSF AD core biomarkers in elderly adults, and these associations were more significant in SCD individuals. This finding indicated that ApoB may play a protective role in the preclinical stage of AD. Identifying the underlying mechanisms may contribute to the discovery of new pathogenic mechanisms and therapeutic targets.

BackgroundThe preclinical stage of Alzheimer's disease (AD) has become a key target stage for future AD prevention trials. Plasma apolipoprotein, an important lipid-related factor, has been found to be involved in the pathogenesis of AD. This study was to examine whether apolipoprotein B (ApoB), apolipoprotein A-1 (ApoA1) or the ratio of ApoB and ApoA1 (ApoB/A1) were associated with early changes of cerebrospinal fluid (CSF) AD biomarkers in elderly adults with subjective cognitive decline.MethodsThis study finally included 201 cognitive normal (CN) elderly adults and 101 participants with subjective cognitive decline (SCD) from the Chinese Alzheimer’s Biomarker and Lifestyle (CABLE) database. The One-way analysis of variance, t-test, Kruskall-Wallis test and Chisquare test were applied in the intergroup comparisons. Multiple linear regression models were used to examine the cross-sectional associations of plasma ApoB, ApoA1 and ApoB/A1 levels with CSF AD-related biomarkers.ResultsCompared with the control group, SCD participants with significant AD biological characteristics had lower ApoB levels. In the total participants, higher level of plasma ApoB was associated with increases in CSF Aβ42 (p = 0.0009) and Aβ42/40 (p = 0.0038) as well as decreases in CSF t-tau/Aβ42 (p < 0.0001) and p-tau/Aβ42 (p < 0.0001), independent of APOEɛ4 status. In the further subgroup analysis, these associations were much more significant in the SCD participants. In addition, higher levels of plasma ApoB were also found associated with decreases in CSF t-tau (p = 0.0224), p-tau (p = 0.0086) and Aβ40 (p = 0.0297) in the SCD subgroup. Furthermore, we found that these protective associations between plasma ApoB and CSF AD core biomarkers were much more significant in the overweight participants. Results showed no association between ApoA1 and all CSF biomarkers in either total participants or subgroups. ConclusionsThis study is the first to find protective associations of plasma ApoB, but not ApoA1, with CSF AD core biomarkers in elderly adults, and these associations were more significant in SCD individuals. This finding indicated that ApoB may play a protective role in the preclinical stage of AD. Identifying the underlying mechanisms may contribute to the discovery of new pathogenic mechanisms and therapeutic targets.

Background: Sex hormone-binding globulin (SHBG) in plasma has been found to be significantly elevated in subjects with AD. We aimed to investigate whether plasma SHBG was associated with AD biomarkers and could predict neurodegeneration and clinical progression in prodromal AD.Methods: The study tested the cross-sectional relationship between plasma SHBG and CSF AD biomarkers in 707 non-demented adults. Next, the longitudinal influences of plasma SHBG at baseline on dynamic changes of CSF Aβ42, hippocampus volume, brain metabolism, and cognition were explored in 448 non-demented adults from the Alzheimer’s disease Neuroimaging Initiative (ADNI). Finally, the influence of plasma SHBG on the risk of incident AD was explored. Results: This study included 707 participants (mean [SD] age, 62.5 [10.5] years, 416 [58.8%] female) from CABLE and 448 from ADNI-1 (mean [SD] age, 74.8 [7.2] years, 166 [37.5%] female). A positive correlation was found for SHBG levels in plasma and CSF (p = 2.12 × 10 -10, r = 0.44). Cross-sectional analyses indicated that individuals with higher plasma SHBG had lower levels of CSF Aβ42 (p < 0.005), after adjusting for age, gender, education, APOE4 allele, and cognitive scores. The longitudinal data showed that higher levels of plasma SHBG contribute to accelerated CSF Aβ42 decrease (p < 0.0005), brain metabolism decline (p < 0.05), hippocampus atrophy (p < 0.01), cognitive decline (p < 0.01), and higher risk of AD dementia (p < 0.05).Conclusions: Plasma SHBG is associated with CSF Aβ42 levels and could predict neurodegeneration and clinical progression in prodromal AD. This finding indicates plasma SHBG is a potentially useful, early biomarker for AD.

Background Although incidence rates of postoperative neurocognitive disorder (PND) in aged individuals following noncardiac major surgery are rising as individuals are living longer, the mechanism of PND remains poorly understood. We wondered if mammalian target of rapamycin (mTOR) signaling might be associated with PND since mTOR controls some essential intracellular events. Objective To investigate whether surgery activates the mTOR signaling pathway in aged rats, leading to PND, and whether the mTOR inhibitor, rapamycin, can be used to alleviate PND. Methods We randomly assigned aged rats to four groups: normal control (C), isoflurane (I), surgery (S), and rapamycin (R). Then, we anesthetized Groups I, S, and R, following which, Groups S and R underwent a splenectomy. After surgery, Group R was administered rapamycin. We used the Morris water maze to test the rats' spatial learning and memory after surgery. Results In Group S, escape latency (ie, the time to find the platform) was markedly higher, and the ratio of swimming time in the target quadrant was lower, compared to the other groups. In Group R, escape latency was markedly lower as compared with Group S, and the ratio of swimming time in the target quadrant was higher. Conclusions Our results indicate that an altered mTOR signaling pathway after a splenectomy causes PND in aged rats, which can be alleviated by rapamycin.

Background: Alzheimer's disease, the most common form of dementia, has tremendous social and economic impact worldwide. This study aimed to analyze global trends in Alzheimer's disease research and to investigate China's contribution to this research. Methods: The quantity and influence of publications related to Alzheimer's disease in China and elsewhere were compared. The Web of Science (WOS) and PubMed databases were searched from 1988 to 2017 using the terms “Alzheimer's disease” or “Alzheimers disease.” Global Alzheimer's disease publications were classified and analyzed. Keywords, countries, and institutions publishing articles on Alzheimer's disease were analyzed, and citations of these articles were examined. Results: A total of 181,116 articles regarding Alzheimer's disease research were identified and analyzed. Neuroscience and neurology were the main research categories both globally and in China. Basic research dominated Alzheimer's publications, accounting for 30.93% of global publications and 95.31% of publications in China. A total of 8,935 journals published articles related to Alzheimer's disease. The journal Neurobiology of Aging published the most Alzheimer's disease-related articles, numbering 5,206 over the time period examined. The National Institutes of Health, the National Institute on Aging, and the Department of Health and Human Services jointly sponsored 11,809 articles, ranking first in the world. The National Natural Science Foundation of China funded the largest number of studies on Alzheimer's disease in China and recognized the importance of traditional Chinese medicine in Alzheimer's disease research. Conclusions: The present study provides data for global researchers to understand research perspectives and develop future research directions. In recent years, Chinese researchers have contributed significantly to global Alzheimer's research. Still, strengthening international cooperation could improve the quality and number of publications regarding Alzheimer's disease.

The triggering receptor expressed on myeloid cells 2 (TREM2) gene has been reported to increase the risk of Alzheimer's disease (AD). The soluble TREM2 protein (sTREM2) in cerebrospinal fluid (CSF) was also associated with AD. However, the role of sTREM2 in AD and its genetic modifiers remain unclear. We carried out a genome-wide association study for CSF sTREM2 levels using participants from the Alzheimer's Disease Neuroimaging Initiative and validated the significant association in an independent cohort from Chinese Alzheimer's Biomarker and LifestylE study. rs7232 in membrane spanning 4-domains A6A (MS4A6A) gene was associated with CSF sTREM2 levels at genome-wide significance (p = 1.42 × 10−15). The locus influences CSF sTREM2 levels especially in nondemented individuals. And the association was replicable in the validation cohort from Chinese Alzheimer's Biomarker and LifestylE study (p = 0.0106). Besides, the expressions of MS4A6A and TREM2 were correlated in brain regions (p

To explore the effect of Scalp acupuncture on serum neuron specific enolase (NSE) and S-100β concentrations, and incidence rates of postoperative delirium (POD) and postoperative cognitive function (POCD) of elderly patients undergoing hip replacement.Eighty-four patients undergoing scheduled hip replacement under combined spinal-epidural anesthesia (CSEA) were assigned to the control group (group C) and the scalp acupuncture group (group S) according to random digit table, 42 cases in each group. In group S, scalp acupuncture was additionally performed according to International Standardized Scheme for Scalp Acupuncture. Scalp acupuncture was performed during the operation from the MS1 middle line of forehead [1 cun before Shenting (GV24), including Shenting (GV24)] and MS5 middle line of vertex [from Baihui (DU20) to Qianding (DU21), including Baihui (DU20) and Qianding (DU21)]. The operation time and post-operative length of stay were observed. The midazolam dosage, hemorrhage amount, fluid transfusion amount, urine amount, use rates of ephedrine and atropine during the operation were also observed and compared between the two groups. The occurrence rate of POD and POCD at post-operative day 3 (T₁), week 1 (T₂), month 3 (T₃), and month 6 (T₄) were measured. Eighteen patients were randomly selected to collect blood from internal jugular vein before anesthesia t₀), immediately after ending the surgery (t₁), 6 h after operation (t₂), 24 h after operation (t₃), and 48 h after operation (t₄), respectively. Serum levels of NSE and S-100β were correspondingly measured.There was no statistical difference in the operation time, midazolam dosage used during the operation, hemorrhage amount, fluid transfusion amount, urine amount, use rates of ephedrine and atropine (P0.05). Compared with group C, the post-operative length of stay was shortened in group S (P0.05). The incidence rate of POD and that of POCD at each time point were lower in group S (P0.05). The expression level of NSE decreased at t₂, t3, and t₄, and the expression level of S100β also decreased at t₁, t₂, t₃, and t₄(P0.05). There was no statistical difference in expression levels of NSE or S100β between the two groups at other time points (P0.05).Scalp acupuncture could attenuate central nervous system lesion and improve POCD of elderly patients undergoing hip replacement.