Hydrogen Bond Boosted Ferroelectric Polarization Enables High Rate Capability Lithium Metal Batteries.

Lithium metal is considered as a promising anode material for next generation lithium-based batteries due to its highest specific capacity and lowest reduction potential. However, irreversible lithium stripping/depositing gives rise to severe dendritic growth and countless dead lithium, which lead to rapid electrochemical performance degradation and increased safety hazards, and thus limit its large-scale application. Herein, this work demonstrates a universal hydrogen-bond-induced strategy to in situ form a highly polarized ferroelectric polyvinylidene fluoride (PVDF) coating on the anode current collector. The localized electric field induced by the polarized ferroelectric PVDF can accelerate the migration of lithium ions and alleviate the shortage of lithium ions and uneven ion/electron distribution and transfer at the anode/electrolyte interface, thus promoting uniform deposition and stripping of Li+ at high-rate situations. As a result, the symmetrical Li || Li batteries with polarized PVDF coating exhibit a long cycling lifespan over 900 h under 2 mA cm-2 with marginal voltage polarization, and an ultra-high-rate performance up to 8.85 mA cm-2 . The full cells using LiFePO4 cathode also display enhanced electrochemical performance. The innovative strategy of ferroelectric polarization sheds light on interface engineering to circumvent Li dendrite growth in lithium metal batteries (LMBs).

Increased Peripheral CD137 Expression in a Mouse Model of Permanent Focal Cerebral Ischemia.

Various studies demonstrate that CD137 (TNFRSF9, 4-1BB) promotes atherosclerosis and vascular inflammation in experimental models via interactions with the CD137 ligand (CD137L). However, the exact role of CD137 in ischemic stroke remains unclear. In this study, we analyzed dynamic changes of peripheral CD137 expression on T cells in a mouse model of cerebral ischemia-middle cerebral artery occlusion (MCAO), as well as alternation of neurological function, infarct size and cerebral inflammatory status after inhibition of the CD137/CD137L pathway using an anti-CD137L monoclonal antibody. MCAO mice showed elevated surface expression of CD137 on T cells in both peripheral blood and lymphoid tissues during early cerebral ischemia. Remarkably, blockade of the CD137/CD137L pathway reduced the post-ischemic brain damage. Our findings indicate that enhanced CD137 costimulation occurs in early cerebral ischemia and promotes T cell activation, which in turn upregulates inflammatory immune response and possibly exerting deleterious effects on cerebral ischemia.

[Design and experiment of a multi-modal electroencephalogram-near infrared spectroscopy helmet for simultaneously acquiring at the same brain area].

Multi-modal brain-computer interface and multi-modal brain function imaging are developing trends for the present and future. Aiming at multi-modal brain-computer interface based on electroencephalogram-near infrared spectroscopy (EEG-NIRS) and in order to simultaneously acquire the brain activity of motor area, an acquisition helmet by NIRS combined with EEG was designed and verified by the experiment. According to the 10-20 system or 10-20 extended system, the diameter and spacing of NIRS probe and EEG electrode, NIRS probes were aligned with C3 and C4 as the reference electrodes, and NIRS probes were placed in the middle position between EEG electrodes to simultaneously measure variations of NIRS and the corresponding variation of EEG in the same functional brain area. The clamp holder and near infrared probe were coupled by tightening a screw. To verify the feasibility and effectiveness of the multi-modal EEG-NIRS helmet, NIRS and EEG signals were collected from six healthy subjects during six mental tasks involving the right hand clenching force and speed motor imagery. These signals may reflect brain activity related to hand clenching force and speed motor imagery in a certain extent. The experiment showed that the EEG-NIRS helmet designed in the paper was feasible and effective. It not only could provide support for the multi-modal motor imagery brain-computer interface based on EEG-NIRS, but also was expected to provide support for multi-modal brain functional imaging based on EEG-NIRS.

Influence of age-related learning and memory capacity of mice: different effects of a high and low caloric diet.

BACKGROUND: Recent studies indicate that consumption of the different calorie diet may be an important way to accelerate or slow the neurodegenerative disorder related to age. Long-term consumption of a high-calorie diet affects the brain and increase the risk of neurodegenerative disorders. And consumption of a low-calorie diet (caloric restriction, CR) could delay aging, and protect the central nervous system from neurodegenerative disorders. The underlying mechanisms have not yet been clearly defined. METHOD: Thirty 6-week-old C57/BL6 mice were randomly assigned to a NC group (fed standard diet, n = 10), a CR group (fed a low-calorie diet, n = 10) or a HC group (fed a high-calorie diet, n = 10) for 10 months. Body weight was measured monthly. Learning and memory capacity were determined by Morris water maze. Pathological changes of the hippocampus cells were detected with HE and Nissl staining. The expression of GFAP was determined by immunofluorescence and western blot. The expression of mTOR, S6K and LC3B in the hippocampus was determined by immunofluorescence. RESULTS: After feeding for 10 months, compared with mice in the NC group, mean body weight was significantly higher in the HC group and significantly lower in the CR group. The result of Morris water maze showed that compared with mice in the NC group, the learning and memory capacity was significantly increased in the CR group, and significantly decreased in the HC group. HE and Nissl staining of the hippocampus showed cells damaged obviously in the HC group. In the hippocampus, the expression of GFAP, mTOR and S6K was increased in the HC group, and decreased in the CR group. The expression of LC3B was decreased in the HC group, and increased in the CR group. CONCLUSIONS: Long-term consumption of a high-calorie diet could inhibit autophagy function, and facilitate neuronal loss in the hippocampus, which in turn aggravate age-related cognition impairment. And consumption of a low-calorie diet (caloric restriction, CR) could enhance the degree of autophagy, protect neurons effectively against aging and damage, and keep learning and memory capacity better.

The ß-amyloid precursor protein analog P165 improves impaired insulin signal transduction in type 2 diabetic rats.

This study was performed to understand whether P165 improves learning and memory by restoring insulin action using a diabetes mellitus (DM) rat model. A total of 34 male Sprague-Dawley rats were randomly divided into four groups: control group (n = 8), DM group (n = 8), DM group treated with a low dose of P165 (n = 9), and DM group treated with a high dose of P165 (n = 9). After 8 weeks of treatment, the animals were killed and the expression of insulin signaling-related proteins was examined in the hippocampus by Western blot and immunohistochemical staining. Administration of P165 in diabetic rats did not induce a significant effect on the fasting blood glucose level. The expression of IR, IRS-1, AKT, p-CREB, and Bcl-2 proteins was significantly enhanced in the hippocampus in diabetic rats. Treatment of diabetic rats with P165 at both low and high doses significantly attenuated the expression levels of these proteins. Moreover, immunohistochemistry staining showed that IR, IRS-1, AKT, p-CREB, and Bcl-2 were abundantly expressed in the CA1 region of the hippocampus. The number of cells positively stained for the above proteins was significantly higher in diabetic tissues compared to control tissues, whereas P165 treatments induced a significant reduction in the expression of these proteins. The expression of IR, IRS-1, AKT, p-CREB, and Bcl-2 was enhanced in DM rats, and administration of P165 normalized the expression of these molecules, suggesting that P165 can improve impaired insulin signal transduction.

Classification of hemodynamic responses associated with force and speed imagery for a brain-computer interface.

Functional near-infrared spectroscopy (fNIRS) is an emerging optical technique, which can assess brain activities associated with tasks. In this study, six participants were asked to perform three imageries of hand clenching associated with force and speed, respectively. Joint mutual information (JMI) criterion was used to extract the optimal features of hemodynamic responses. And extreme learning machine (ELM) was employed to be the classifier. ELM solved the major bottleneck of feedforward neural networks in learning speed, this classifier was easily implemented and less sensitive to specified parameters. The 2-class fNIRS-BCI system was firstly built with an average accuracy of 76.7%, when all force and speed tasks were categorized as one class, respectively. The multi-class systems based on different levels of force and speed attempted to be investigated, the accuracies were moderate. This study provided a novel paradigm for establishing fNIRS-BCI system, and provided a possibility to produce more degrees of freedom in BCI system.

Caloric restriction can improve learning ability in C57/BL mice via regulation of the insulin-PI3K/Akt signaling pathway.

To identify the molecular mechanism underlying improved spatial learning ability of C57/BL mice on a caloric restricted (CR) diet. Seven-week-old male C57/BL mice were randomly divided into three groups: normal control group (NC group, n = 10), high energy group (n = 10), and low energy group (CR group, n = 10). Body mass and levels of blood glucose were measured every 2 weeks over the course of 30 weeks. After 30 weeks, metabolic parameters, serum total cholesterol, and insulin-like growth factor 1 (IGF-1) were measured, and learning and memory ability of animals were tested using the Morris water maze. The expression of insulin signaling pathway-related proteins in the brain tissues also were tested for molecular mechanism. When compared with the NC group, body weight, and levels of serum glucose decreased in the CR group and increased in the high energy group at all time points tested. Average escape latency and swimming distance were lower in the CR group as compared to the control group after 30 weeks. The serum cholesterol level of the high energy group was significantly higher than that of the control group. The expressions of IGF-1, IR, IRS-1, PI3K, Akt/PKB, and p-CREB protein in the CR group were significantly lower and the expressions of PI3K and Akt/PKB protein in the high energy group were significantly lower than those of the control group at post 30 weeks treatment. Our findings demonstrate that the low energy diet may improve hippocampus-dependent spatial learning ability in C57/BL mice, possibly through a regulatory mechanism of the insulin-PI3K/Akt signaling pathway.

Effects of analog P165 of amyloid precursor protein 5-mer peptide on learning, memory and brain insulin receptors in the rat model of cognitive decline.

We aim to study the therapeutic efficacy of analog P165 of amyloid precursor protein 5-mer peptide in streptozotocin (STZ)-induced cognitive decline model. Rats were divided into four groups: control, STZ, STZ+P165, and STZ+rosiglitazone (RSG). STZ model was established by intracerebroventricular injection of STZ. Three weeks following surgery, rats received daily gavage administration of distilled water (control and STZ groups), P165 (STZ+P165), or RSG (STZ+RSG) for four consecutive weeks. Learning and memory abilities were assessed with the Morris water maze test. Insulin-like growth factor-1 (IGF-1) was detected by ELISA. Expressions of insulin receptor-ß (IR-ß), insulin receptor substrate-1 (IRS-1), serine/threonine kinase (Akt), and phosphorylation of CREB (p-CREB) were observed by immunohistochemistry. Both P165 and RSG significantly reduced the escape latency relative to the STZ group (P165, P < 0.05; RSG, P < 0.01). STZ model rats had reduced levels of IGF-1 relative to control, and this deficit was attenuated in the STZ+P165 group (P < 0.01). IR and IRS-1 were elevated in STZ rats, and these levels were restored to near control in the STZ+P165 and STZ+RSG groups (P < 0.01). Our findings demonstrate that P165 and RSG improved hippocampus-dependent spatial learning and memory in STZ rats by regulating the insulin signaling pathway.

Enhanced performance by time-frequency-phase feature for EEG-based BCI systems.

We introduce a new motor parameter imagery paradigm using clench speed and clench force motor imagery. The time-frequency-phase features are extracted from mu rhythm and beta rhythms, and the features are optimized using three process methods: no-scaled feature using "MIFS" feature selection criterion, scaled feature using "MIFS" feature selection criterion, and scaled feature using "mRMR" feature selection criterion. Support vector machines (SVMs) and extreme learning machines (ELMs) are compared for classification between clench speed and clench force motor imagery using the optimized feature. Our results show that no significant difference in the classification rate between SVMs and ELMs is found. The scaled feature combinations can get higher classification accuracy than the no-scaled feature combinations at significant level of 0.01, and the "mRMR" feature selection criterion can get higher classification rate than the "MIFS" feature selection criterion at significant level of 0.01. The time-frequency-phase feature can improve the classification rate by about 20% more than the time-frequency feature, and the best classification rate between clench speed motor imagery and clench force motor imagery is 92%. In conclusion, the motor parameter imagery paradigm has the potential to increase the direct control commands for BCI control and the time-frequency-phase feature has the ability to improve BCI classification accuracy.

Helicobacter pylori infection is a risk factor for constipation in patients with Parkinson's disease: A multicenter prospective cohort study.

BACKGROUND AND AIMS: Constipation is one of the most common nonmotor symptoms (NMSs) of Parkinson's disease (PD). The infection rate of Helicobacter pylori (HP) is greater in PD patients. This study was a multicenter prospective cohort study in which propensity score matching (PSM) was used to determine whether HP infection was a risk factor for constipation in patients with PD. METHODS: A total of 932 PD patients with 13C-urea breath test for HP were included in the study. The PSM was estimated with the use of a nonparsimonious multivariate logistic regression model, with HP infection as the dependent variable and all the baseline characteristics as covariates. A total of 697 patients composed the study cohort, including 252 (36.2 %) patients in the HP-positive (HPP) group and 445 (63.8 %) patients in the HP-negative (HPN) group. Before PSM, there were differences in several of the baseline variables between the two groups. After PSM, 250 HPP patients were matched with 250 HPN patients and the standardized differences were less than 0.1 for all variables. RESULTS: The present results demonstrate that HP infection is a risk factor for constipation in patients with PD [RR (95 % CI) 1.412 (1.155-1.727), P < 0.001]. Subgroup analyses revealed that HP infection was both a risk factor for constipation in Hoehn-Yahr scale (1,1.5) group and Hoehn-Yahr scale (2-5) group [OR (95 % CI) 1.811 (1.079-3.038), P < 0.025; OR (95 % CI) 2.041 (1.177-3.541), P < 0.011]. CONCLUSIONS: The results of our prospective cohort study suggest that Helicobacter pylori infection is a risk factor for constipation in patients with PD. TRIAL REGISTRATION: ChiCTR2300071631.

Effect of acute levodopa challenge test on cerebral blood flow in Parkinson's disease with the supine-to-standing transcranial Doppler test.

BACKGROUND: Levodopa, a common drug that improves symptoms of Parkinson's disease (PD), can induce a reduction in blood pressure (BP); however, the effect of levodopa on cerebral blood flow (CBF) remains unclear. OBJECTIVES: To observe the changes in BP and CBF during active standing before and after the acute levodopa challenge test (ALCT) and analyse the influencing factors of CBF in patients with PD. METHODS: BP and CBF velocity were simultaneously recorded by continuous beat-to-beat non-invasive BP monitoring and transcranial Doppler at supine and orthostatic positions twice, before and after ALCT. The patients were divided into two groups according to those with increased and decreased CBF at baseline after ALCT to analyse the influencing factors. RESULTS: We examined 64 patients with PD (59.2 ± 11.6 years, 33 males). BP decreased at all timepoints after ALCT, while there was no significant change in the magnitude of the drop in BP induced by standing. CBF was reduced after ALCT, especially within 15 s to 1 min of standing (15 s: 48.95 ± 13.50 vs. 44.93 ± 13.26, p < 0.001; 30 s: 52.46 ± 12.06 vs. 50.11 ± 12.56, p = 0.033; 1 min: 52.19 ± 11.83 vs. 50.17 ± 13.21, p = 0.044). Lower body mass index (ß = -0.280, p = 0.027) was an independent factor associated with CBF reduction after ALCT. CONCLUSIONS: Additional attention should be paid to changes in CBF and BP within 1 min after standing in patients with PD taking levodopa, especially in those with low bodyweight.

Orderly Arranged Dipoles Regulate Anion-Derived Solid-Electrolyte Interphase for Stable Lithium Metal Chemistry.

Lithium (Li) metal batteries are considered the most promising high-energy-density electrochemical energy storage devices of the next generation. However, the unstable solid-electrolyte interphase (SEI) derived from electrolytes usually leads to high impedance, Li dendrites growth, and poor cyclability. Herein, the ferroelectric BaTiO3 with orderly arranged dipoles (BTOV) is integrated into the polypropylene separator as a functional layer. Detailed characterizations and theoretical calculations indicate that surface oxygen vacancies drive the phase transition of BaTiO3 materials and promote the ordered arrangement of dipoles. The strong dipole moments in BTOV can adsorb TFSI- and NO3 - anions selectively and promote their preferential reduction to form a SEI film enriched with inorganic LiF and LiNxOy species, thus facilitating the rapid transfer of Li+ and restraining the growth of Li dendrites. As a result, the Li-Li cell with the BTOV functional layer exhibits enhanced Li plating/stripping cycling with an ultra-long life of over 7000 h at 0.5 mA cm-2/1.0 mAh cm-2. The LiFePO4 || Li (50 µm) full cells display excellent cycling performance exceeding 1760 cycles and superior rate performance. This work provides a new perspective for regulating SEI chemistry by introducing ordered dipoles to control the distribution and reaction of anions.

Alzheimer's Disease Related Biomarkers Were Associated with Amnestic Cognitive Impairment in Parkinson's Disease: A Cross-Sectional Cohort Study.

BACKGROUND: Cognitive impairment is common in patients with Parkinson's disease (PD) and occurs through multiple mechanisms, including Alzheimer's disease (AD) pathology and the involvement of α-synucleinopathies. We aimed to investigate the pathological biomarkers of both PD and AD in plasma and neuronal extracellular vesicles (EVs) and their association with different types of cognitive impairment in PD patients. METHODS: A total of 122 patients with PD and 30 healthy controls were included in this cross-sectional cohort study between March 2021 and July 2023. Non-dementia PD patients were divided into amnestic and non-amnestic groups according to the memory domain of a neuropsychological assessment. Plasma and neuronal EV biomarkers, including α-synuclein (α-syn), beta-amyloid (Aß), total tau (T-tau), phosphorylated tau181 (p-tau181), and glial fibrillary acidic protein (GFAP), were measured using a single-molecule array and a chemiluminescence immunoassay, respectively. RESULTS: Neuronal EV but not plasma α-syn levels, were significantly increased in PD as compared to healthy controls, and they were positively associated with UPDRS part III scores and the severity of cognitive impairment. A lower plasma Aß42 level and higher neuronal EV T-tau level were found in the amnestic PD group compared to the non-amnestic PD group. CONCLUSIONS: The results of the current study demonstrate that neuronal EV α-syn levels can be a sensitive biomarker for assisting in the diagnosis and disease severity prediction of PD. Both AD and PD pathologies are important factors in cognitive impairment associated with PD, and AD pathologies are more involved in amnestic memory deficit in PD.

Age as a risk factor for orthostatic hypotension induced by the levodopa challenge test in patients with Parkinson's disease: Results from a single-center trial.

BACKGROUND: Hypotension can occur in patients receiving levodopa (L-dopa) treatment for parkinsonism. However, only few studies have focused on the characteristics of orthostatic hypotension (OH) induced by the L-dopa challenge test (LCT). This study aimed to investigate the characteristics and influencing factors of LCT-induced OH in a relatively large sample of patients with Parkinson's disease (PD). METHODS: Seventy-eight patients with PD without a previous diagnosis of OH underwent the LCT. Blood pressure (BP) in the supine and standing positions was measured before and 2 hours after the LCT. If diagnosed with OH, the patients' BP was monitored again 3 hours after the LCT. The clinical features and demographics of the patients were analyzed. RESULTS: Eight patients were diagnosed with OH 2 hours after the LCT (median dose of 375 mg L-dopa/benserazide; incidence = 10.3%). One patient without symptoms had OH 3 hours after the LCT. Compared with patients without OH, patients with OH had lower 1- and 3-minutes standing systolic BP and 1-minute standing diastolic BP at baseline and 2 hours after the LCT. Patients in the OH group were of older age (65.31 ± 4.17 years vs 59.74 ± 5.55years) and had lower Montreal Cognitive Assessment scores (17.5 vs 24) and higher L-dopa/benserazide levels (375 [250, 500] mg vs 250 [125, 500] mg). Older age markedly increased the odds of having LCT-induced OH (odds ratio, 1.451; 95% confidence interval, 1.055-1.995; P = .022). CONCLUSIONS: LCT increased the odds of OH in non-OH PD, causing symptomatic OH in 10.3% of patients in our study, thereby raising safety concerns. Increase in age was observed to be a risk factor for LCT-induced OH in PD patients. A study with a larger sample size is warranted to confirm our results. TRIAL REGISTRATION NUMBER: Clinical Trials Registry under ChiCTR2200055707. DATE OF REGISTRATION: January 16, 2022.

The differences of orthostatic hypotension in patients with Parkinson's disease and multiple system atrophy.

Background: Multiple system atrophy (MSA) and Parkinson's disease (PD) have similar clinical presentations in their early stages. Orthostatic hypotension (OH) is a common autonomic dysfunction associated with MSA and PD. Heart rate (HR) and systolic blood pressure (SBP) changes are measured in response to the active standing test, which is widely used to screen for cardiovascular autonomic function. Objectives and methods: Overall, 255 patients (67 MSA, 188 PD) underwent continuous beat-to-beat non-invasive BP monitoring and active standing test. The total standing time was 10 min, and the BP differences between both groups were compared to determine whether the ΔHR/ΔSBP can differentiate both conditions. Results: Classical orthostatic hypotension (COH) (52%) and initial OH (19%) were most common in MSA and PD, respectively. MSA had a higher HR (75.0 ± 9.7 vs. 71.0 ± 10.7, P = 0.008) than PD in the supine position. SBP (135.70 ± 15.68 mmHg vs. 127.31 ± 15.14 mmHg, P = 0.106), diastolic BP (78.45 ± 12.36 mmHg vs. 67.15 ± 13.39 mmHg, P = 0.009) and HR (73.94 ± 8.39 bpm vs. 71.08 ± 13.52 bpm, P = 0.389) at baseline were higher in MSA-COH than in PD-COH. After adjusting for age and disease duration, the ΔHR/ΔSBP-10 min significantly discriminated MSA-COH from PD-COH (P = 0.031). An ΔHR/ΔSBP-10 min of 0.517 showed a sensitivity of 67% and specificity of 84% (AUC = 0.77, 95% CI: 0.63-0.91). Conclusion: The SBP, diastolic BP, and HR were higher in the supine position; however, ΔHR and ΔSBP were lower after standing in MSA patients than in PD patients. The ΔHR/ΔSBP-10 min discriminated between MSA-COH and PD-COH with quiet acceptable accuracy.

Ginkgolide attenuates memory impairment and neuroinflammation by suppressing the NLRP3/caspase-1 pathway in Alzheimer's disease.

The NLRP3 inflammasome is involved in the neuroinflammatory pathway of Alzheimer's disease (AD). The aim of this study is to explore the roles and underlying mechanisms of ginkgolide (Baiyu®) on amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice and a murine microglial cell line, BV-2. In the present study, the APP/PS1 mice were administered with ginkgolide, followed by a Morris water maze test. The mice were then euthanized to obtain brain tissue for histological and Aß analysis. Additionally, BV-2 cells were pretreated with ginkgolide and then incubated with Aß1-42 peptide. NLRP3, ASC, and caspase-1 mRNA and protein expression in brain tissue of mice and BV-2 cells were quantified by real-time PCR and western blotting, as well as reactive oxygen species (ROS) production, interleukin (IL)-1ß and IL-18 levels by lucigenin technique and ELISA. Compared with the APP/PS1 mice, ginkgolide-treated mice demonstrated the shortened escape latency, reduced plaques, less inflammatory cell infiltration and neuron loss in the hippocampi of APP/PS1 mice. The levels of NLRP3, ASC, caspase-1, ROS, IL-1ß, and IL-18 were also decreased in the brain tissue of APP/PS1 mice or Aß1-42-treated BV-2 cells following ginkgolide treatment. Ginkgolide exerted protective effects on AD, at least partly by inactivating the NLRP3/caspase-1 pathway.

Feasibility and Validity of Cambridge Neuropsychological Test Automated Battery in Mild Cognitive Impairment Screening for Patients with Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with the worsening of cognitive function. Strategies that are both convenient and reliable for cognitive screening of AF patients remain underdeveloped. We aimed to analyze the sensitivity and specificity of computerized cognitive screening strategies using subtests from Cambridge Neuropsychological Test Automated Battery (CANTAB) in AF patients. METHODS: The Multitasking Test (MTT), Rapid Visual Information Processing (RVP), and Paired Associates Learning (PAL) subtests from CANTAB were performed in 105 AF patients. Traditional standard neuropsychological tests were used as a reference standard. Cognitive screening models using different CANTAB subtests were established using multivariable logistic regression. Further stepwise regression using the Akaike Information Criterion (AIC) was applied to optimize the models. Receiver operating characteristic curve analyses were used to study the sensitivity and specificity of these models. RESULTS: Fifty-eight (55%) patients were diagnosed with mild cognitive impairment (MCI). MTT alone had reasonable sensitivity (82.8%) and specificity (74.5%) for MCI screening, while RVP (sensitivity 72.4%, specificity 70.2%) and PAL (sensitivity 70.7%, specificity 57.4%) were less effective. Stepwise regression of all available variables revealed that a combination of MTT and RVP brought about higher specificity (sensitivity 82.8%, specificity 85.8%), while PAL was not included in the optimal model. Moreover, adding education to the models did not result in improved validity for MCI screening. CONCLUSION: The CANTAB subtests are feasible and effective strategies for MCI screening among AF patients independent of patients' education levels. Hence, they are practical for cardiologists or general practitioners.

Protective Effects of Ginkgolide on a Cellular Model of Alzheimer's Disease via Suppression of the NF-κB Signaling Pathway.

SYNOPSIS: NF-κB signaling has been reported to play a key regulatory role in the pathogenesis of Alzheimer's disease (AD). The purpose of this study is to investigate the effects of ginkgolide on cell viability in an AD cellular model involving an APP/PS1 double gene-transfected HEK293 cell line (APP/PS1-HEK293) and further explore the mechanisms of action related to NF-κB signaling. The optimal time point and concentration of ginkgolide for cell proliferation were screened using a cell counting kit-8 assay. Based on the results, an in vitro study was performed by co-culture of APP/PS1-HEK293 with different dosages of ginkgolide, followed by an enzyme-linked immunosorbent assay to measure the levels of supernatant tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6, as well as western blotting and real-time polymerase chain reaction to detect intracellular protein and mRNA expression of NF-κB p65, IκBa, Bcl-2, and Bax. APP/PS1-HEK293 cells exhibited the highest cell viability at a concentration of 100 µg/ml after 48 h of treatment with ginkgolide. The supernatant levels of TNF-α, IL-1ß, and IL-6 in the high-dosage ginkgolide-treated groups were lower than those in the control group. Compared with the control group, there were decreased intracellular protein and mRNA expression of NF-κB p65 and Bax, but increased protein and mRNA expression of IκBa in both high-dosage and low-dosage groups. Ginkgolide may enhance cell viability, indicative of its neuroprotective effects on AD, at least partially via suppression of the NF-κB signaling pathway involving anti-apoptosis and anti-inflammation mechanisms. Therefore, ginkgolide might be a promising therapeutic agent against AD.

Validation of T-MoCA in the Screening of Mild Cognitive Impairment in Chinese Patients With Atrial Fibrillation.

Background: Atrial fibrillation (AF) is associated with a high risk of mild cognitive impairment (MCI) and dementia. However, feasible and simple instruments that facilitate the regular assessment of cognitive status in patients with AF remain underdeveloped. Methods: Cognitive function was first evaluated using telephone Montreal cognitive assessment (T-MoCA), and then patients were invited for an in-person interview for cognitive assessment using both Clinical Dementia Rating (CDR) and mini-mental status evaluation (MMSE). Using CDR = 0.5 as a reference standard, the ability of T-MoCA and MMSE to discriminate cognitive dysfunction, stratified by education level, was tested by receiver-operating curve (ROC) analysis. The net reclassification index was calculated for comparison between the performance of T-MoCA and MMSE. Results: One hundred and one patients completed both telephone and in-person interview. Thirty-five MCI patients were identified as MCI using the criteria of CDR = 0.5. The areas under the ROC curve of T-MoCA were 0.80 (0.71-0.89), 0.83 (0.71-0.95), and 0.85 (0.64-0.92) for all patients, patients with high educational level, and patients with low education level, respectively. The optimal threshold was achieved at 16/17 with a sensitivity of 85.7% and a specificity of 69.7% in overall patients, 15/16 with a sensitivity of 88.2% and a specificity of 64.5% in the low educational level patients, and 16/17 with a sensitivity of 77.8% and a specificity of 87.9% in the high educational level patients. Compared to the criterion MMSE ≤ 27 and MMSE norms for the elderly Chinese community, the stratified T-MoCA threshold improves correct classification by 23.7% (p = 0.033) and 30.3% (p = 0.020), respectively. Conclusion: T-MoCA is a feasible and effective instrument for MCI screening in patients with AF.

Case Report: Progressive Asymmetric Parkinsonism Secondary to CADASIL Without Dementia.

Parkinsonism is a rare phenotype of cerebral autosomal dominant arteriopathy with subcortical infarction and leukoencephalopathy (CADASIL), all of which involve cognitive decline. Normal cognition has not been reported in previous disease studies. Here we report the case of a 60-year-old female patient with a 2-year history of progressive asymmetric parkinsonism. On examination, she showed severe parkinsonism featuring bradykinesia and axial and limb rigidity with preserved cognition. Magnetic resonance imaging (MRI) revealed white matter hyperintensity in the external capsule and periventricular region. Dopaminergic response was limited. A missense mutation c.1630C>T (p.R544C) on the NOTCH3 gene was identified on whole-exome sequencing, which confirmed the diagnosis of vascular parkinsonism secondary to CADASIL. A diagnosis of CADASIL should be considered in asymmetric parkinsonism without dementia. Characteristic MRI findings support the diagnosis.