Process approach as a cognitive biomarker related to gray matter volume in mild cognitive impairment and Alzheimer's disease.

BACKGROUND: Process approach is valuable for memory assessment in Alzheimer's disease (AD) and mild cognitive impairment (MCI), yet its underlying mechanisms remain elusive. This study aims to synergize the process approach with brain structure analysis to explore both the discriminative capacity and potential mechanisms underlying the process approach. METHODS: 37 subjects of MCI, 35 subjects of AD and 38 subjects of healthy control (HC) were included. The process approach in Auditory Verbal Learning Test (AVLT), including discriminability (A'), response bias (B"D), semantic clustering (LBCsem) and serial clustering (LBCser) was performed. The gray matter volume (GMV) was analyzed by voxel-based morphometry. Receiver operating characteristic (ROC) analysis and partial correlations were conducted to explore the value of the process approach and investigate the relationship between the process approach, traditional indices of AVLT and GMV. RESULTS: ROC analysis showed the value of A', B"D and LBCser in differentiating MCI and AD. Combining AVLT-Immediately Recall (AVLT-IR) and LBCser showed a higher value in diagnosing MCI. Partial correlations revealed that in the MCI group, A' and B"D were mainly positively associated with GMV of the hippocampus and temporal lobe. CONCLUSION: This study indicated that the process approach is a promising cognitive biomarker to detect MCI and AD.

[Changes in Plasma Amyloid-ß Level and Their Relationship With White Matter Microstructure in Patients With Mild Cognitive Impairment].

Objective To investigate the changes in plasma amyloid-ß (Aß) level and their relationship with white matter microstructure in the patients with amnesic mild cognitive impairment(aMCI) and vascular mild cognitive impairment (vMCI).Methods A total of 36 aMCI patients,20 vMCI patients,and 34 sex and age matched healthy controls (HC) in the outpatient and inpatient departments of the First Affiliated Hospital of Anhui Medical University were enrolled in this study.Neuropsychological scales,including the Mini-Mental State Examination,the Montreal Cognitive Assessment,and the Activity of Daily Living Scale,were employed to assess the participants.Plasma samples of all the participants were collected for the measurement of Aß42 and Aß40 levels.All the participants underwent magnetic resonance scanning to obtain diffusion tensor imaging (DTI) data.The DTI indexes of 48 white matter regions of each individual were measured (based on the ICBM-DTI-81 white-matter labels atlas developed by Johns Hopkins University),including fractional anisotropy (FA) and mean diffusivity (MD).The cognitive function,plasma Aß42,Aß40,and Aß42/40 levels,and DTI index were compared among the three groups.The correlations between the plasma Aß42/40 levels and DTI index of aMCI and vMCI patients were analyzed.Results The Mini-Mental State Examination and the Montreal Cognitive Assessment scores of aMCI and vMCI groups were lower than those of the HC group (all P<0.001).There was no significant difference in the Activity of Daily Living Scale score among the three groups (P=0.654).The plasma Aß42 level showed no significant difference among the three groups (P=0.227).The plasma Aß40 level in the vMCI group was higher than that in the HC group (P=0.014),while it showed no significant difference between aMCI and HC groups (P=1.000).The plasma Aß42/40 levels in aMCI and vMCI groups showed no significant differences from that in the HC group (P=1.000,P=0.105),while the plasma Aß42/40 level was lower in the vMCI group than in the aMCI group (P=0.016).The FA value of the left anterior limb of internal capsule in the vMCI group was lower than those in HC and aMCI groups (all P=0.001).The MD values of the left superior corona radiata,left external capsule,left cingulum (cingulate gyrus),and left superior fronto-occipital fasciculus in the vMCI group were higher than those in HC (P=0.024,P=0.001,P=0.003,P<0.001) and aMCI (P=0.015,P=0.004,P=0.019,P=0.001) groups,while the MD values of the right posterior limb of internal capsule (P=0.005,P=0.001) and left cingulum (hippocampus) (P=0.017,P=0.031) in the aMCI and vMCI groups were higher than those in the HC group.In the aMCI group,plasma Aß42/40 level was positively correlated with FA of left posterior limb of internal capsule (r=0.403,P=0.015) and negatively correlated with MD of the right fonix (r=-0.395,P=0.017).In the vMCI group,plasma Aß42/40 level was positively correlated with FA of the right superior cerebellar peduncle and the right anterior limb of internal capsule (r=0.575,P=0.008;r=0.639,P=0.002),while it was negatively correlated with MD of the right superior cerebellar peduncle and the right anterior limb of internal capsule (r=-0.558,P=0.011;r=-0.626,P=0.003).Conclusions Plasma Aß levels vary differently in the patients with aMCI and vMCI.The white matter regions of impaired microstructural integrity differ in the patients with different dementia types in the early stage.The plasma Aß levels in the patients with aMCI and vMCI are associated with the structural integrity of white matter,and there is regional specificity between them.

Epidemiology of gaming disorder and its effect on anxiety and insomnia in Chinese ethnic minority adolescents.

BACKGROUND: The growing popularity and frequency of online game use have resulted in a large number of studies reporting various mental problems associated with game abuse in adolescents. In this article, we examined the prevalence of gaming disorder (GD) and explored the associations of GD with anxiety and insomnia symptoms in minority youth in China. METHODS: A total of 1494 students completed the Problematic Online Gaming Questionnaire Short-Form (POGQ-SF), the Generalized Anxiety Disorder 7-item questionnaire (GAD-7), and Athens Insomnia Scale (AIS). Chi-square and binary logistic regression analyses were used to explore the associations between gaming disorder and anxiety/insomnia. RESULTS: A total of 356 (23.83%) respondents reported that they had gaming disorder. Chi-square analysis showed that gender, grade, marital status of parents and exercise situation were significantly associated with GD. Binary logistic regression analysis showed that those who had GD were at significantly higher risk for anxiety and insomnia than those without GD. CONCLUSION: We found a high incidence of GD and a positive association among anxiety, insomnia and GD. Thus, special attention should be paid to those who have suffered from GD. It is worth addressing the adverse effects of GD on anxiety and insomnia.

Space-Confined Seeded Growth of Black Silver Nanostructures for Solar Steam Generation.

Plasmonic metal nanostructures have attracted considerable attention for solar energy harvesting due to their capability in photothermal conversion. However, the narrow resonant band of the conventional plasmonic nanoparticles greatly limits their application as only a small fraction of the solar energy can be utilized. Herein, a unique confined seeded growth strategy is developed to synthesize black silver nanostructures with broadband absorption in the visible and near-infrared spectrum. Through this novel strategy, assemblages of silver nanoparticles with widely distributed interparticle distances are generated in rod-shaped tubular spaces, leading to strong random plasmonic coupling and accordingly broadband absorption for significantly improved utilization of solar energy. With excellent efficiency in converting solar energy to heat, the resulting black Ag nanostructures can be made into thin films floating at the air/water interface for efficient generation of clean water steam through localized interfacial heating.

Effects of a diet with or without physical activity on angiopoietin-like protein 8 concentrations in overweight/obese patients with newly diagnosed type 2 diabetes: a randomized controlled trial.

Angiopoietin-like protein 8 (ANGPTL8) is a newly discovered adipokine plays an important role in energy homoeostasis, obesity and type 2 diabetes (T2D). Although lifestyle modification in obesity and T2D is known to offer metabolic benefits, there is paucity of comprehensive data on change in ANGPTL8. We investigated the effect of lifestyle intervention on ANGPTL8 concentrations. 384 obese/overweight adults with newly diagnosed T2D were randomly assigned (1:1:1) to diet (n = 128), diet + activity (n = 128) or usual care (control, n = 128) groups. All patients received usual care. Besides, the diet group received a calorie-restricted diet aiming for a weight loss of 5-10%. The diet + activity group additionally received a pedometer-based walking program. Primary outcome was change in ANGPTL8 concentration at 6 months. Data were analyzed according to intention-to-treat. From baseline to 6 months, the median ANGPTL8 level changed from 804.38 pg/mL to 792.86 pg/mL in control group. Compared with control, ANGPTL8 decreased with diet (baseline-adjusted between-group difference was -121.00 pg/mL, 95% CI -177.47 to -64.53; p < 0.0001) and diet + activity (-126.16 pg/mL, -181.21 to -71.11; p < 0.0001). There was no greater effect of diet + activity compared with diet (-5.16 pg/mL, -53.63 to 43.31; p = 0.8348). Both effects disappeared after adjusting for change in body fat, but did not differ significantly when adjusting for physical activity. A 6-month intervention inducing weight loss by a calorie-restricted diet or diet + activity, resulted in significant decrease on ANGPTL8 concentration. These effects were established by change in total body fat, and not by change in physical activity.

ß-Catenin Cooperates with CREB Binding Protein to Promote the Growth of Tumor Cells.

BACKGROUND/AIMS: ß-catenin is an integral component of the canonical Wnt signaling pathway, and its mutations are an autosomal recessive cause of colorectal cancer (CRC), medulloblastoma (MDB), and ovarian cancer. Nevertheless, little is known about its function in lung cancers. METHODS: We first knocked down ß-catenin by siRNA to investigate its effects on lung cancer cell proliferation, migration and apoptosis. Then we verified the interaction between ß-catenin and CREB binding protein (CBP) by immunofluoresence and co-immunoprecipition assays. Finally, the expression of ß-catenin and CBP in human lung adenocarcinoma specimens were analyzed by immunohistochemistry assay. RESULTS: ß-catenin knockdown inhibited cell proliferation, promoted apoptosis and suppressed cell migration in A549 and H460 cells accompanied by the decreased expression of Myc, PCNA, VEGF, CD44, MMP-9, MMP-13 and activated bax/caspase-3 pathway. Furthermore, co-immunoprecipition and immunofluoresence analyses revealed that CBP interacted with ß-catenin and contributed to ß-catenin-mediated lung cancer cell growth. Abolishment of their interaction by the Wnt/ß-catenin inhibitor ICG-001 remarkably suppressed cell proliferation. Immunohistochemistry assay of tissue microarrays from patients with lung cancer indicated that both CBP and ß-catenin were highly expressed in tumor tissues and predicted poor prognosis in lung adenocarcinoma patients. CONCLUSIONS: Our study has provided new evidence for the role of ß-catenin in promoting the growth of lung cancer cells through cooperation with CBP, and suggested that dual targeting of ß-catenin and CBP could be a potential therapeutic strategy in lung cancer treatment.

[Effects of transcription factor sterol regulatory element binding protein-1c in palmitate acid-induced L6 cells insulin resistance and its mechanism].

OBJECTIVE: Sterol regulatory element binding protein-1c (SREBP-1c) is a master regulator of fatty acid synthase and controls lipogenesis. And insulin receptor substrate-1 (IRS-1) is a key insulin signaling mediator in skeletal muscle. The present study was conducted to explore the mechanism of SREBP-1c in the regulation of IRS-1 in skeletal muscle cells and elucidate the role of SREBP-1c in high fat-induced skeletal muscle insulin resistance. METHODS: L6 cells differentiated into myotubes in differentiation medium with 2%FBS. An in vitro insulin resistant model in L6 myotubes was established by 500 µmol/L of palmitate acid (PA). SREBP-1c, p-IRS-1(Tyr608/612), IRS-1, p-AKT (Ser473) and AKT were detected by Western blot after incubating L6 myobutes with 500 µmol/L of PA for 0.5, 1, 3, 6, 12, 18 or 24 h.SREBP-1c, FAS and molecules related to insulin signaling pathway were detected by Western blot when L6 myotubes over-expressed SREBP-1c or after a treatment of liver X receptor (LXR) agonist (TO901317, 5 µmol/L). The regulatory effects of transcription factor SREBP-1c on promoter region of IRS-1 were assessed by dual-luciferase reporter assay. RESULTS: SREBP-1c protein expression increased significantly after 1-hour exposure to PA. The protein levels of p-IRS-1(Tyr608/612),IRS-1 and p-AKt (Ser473) decreased significantly after a 6-hour incubation of PA. However AKT protein levels were unaffected. The protein expressions of SREBP-1c and FAS were up-regulated by LXR agonist treatment versus controls. By contrast, LXR agonist treatment led to decreased expressions of IRS-1, p-IRS-1(Tyr608/612) and p-AKt (Ser473)/AKT proteins versus controls. The expressions of related proteins were similar to the observations made with LXR agonist intervention. The results of dual-luciferase reporter assay indicated that IRS-1 promoter activity was repressed significantly by SREBP-1c over-expression or TO901317 treatment whereas the dominant negative form of SREBP-1c (a mutant of Tyr320Ala lacking the ability of binding DNA) had no effect. CONCLUSION: SREBP-1c may suppress IRS-1 expression and the subsequent insulin signaling pathway. And it plays a key role in PA-induced insulin resistance of skeletal muscle.

Role for sterol regulatory element binding protein-1c activation in mediating skeletal muscle insulin resistance via repression of rat insulin receptor substrate-1 transcription.

AIMS/HYPOTHESIS: Sterol regulatory element binding protein-1c (SREBP-1c) is a master regulator of fatty acid synthase and controls lipogenesis. IRS-1 is the key insulin signalling mediator in skeletal muscle. In the present study, we investigated the role of SREBP-1c in the regulation of IRS-1 in skeletal muscle cells. METHODS: L6 muscle cells were treated with palmitic acid (PA) or metformin. Adenovirus vectors expressing Srebp-1c (also known as Srebf1) and small interfering RNA (siRNA) against Srebp-1c were transfected into the L6 cells. Protein-DNA interactions were assessed by luciferase reporter analysis, electrophoretic mobility shift assay and chromatin immunoprecipitation assay. RESULTS: We found that both gene and protein expression of SREBP-1c was increased in contrast to IRS-1 expression in PA-treated L6 cells. SREBP-1c overproduction decreased Irs-1 mRNA and IRS-1 protein expression in a dose-dependent manner, and suppressed the resultant insulin signalling, whereas SERBP-1c knockdown by Serbp-1c siRNA blocked the downregulation of IRS-1 induced by PA. Protein-DNA interaction studies demonstrated that SREBP-1c was able to bind to the rat Irs-1 promoter region, thereby repressing its gene transcription. Of particular importance, we found that metformin treatment downregulated Srebp-1c promoter activity, decreased the specific binding of SREBP-1c to Irs-1 promoter and upregulated Irs-1 promoter activity in PA-cultured L6 cells. CONCLUSIONS/INTERPRETATION: Our data indicate for the first time that SREBP-1c activation participates in skeletal muscle insulin resistance through a direct effect of suppressing Irs-1 transcription. These findings imply that SREBP-1c could serve as an attractive therapeutic target for insulin resistance.

[SAR of benzoyl sulfathiazole derivatives as PTP1B inhibitors].

Protein tyrosine phosphatase (PTP) 1B is a potential target for the treatment of diabetes and obesity. We have previously identified the benzoyl sulfathiazole derivative II as a non-competitive PTP1B inhibitor with in vivo insulin sensitizing effects. Preliminary SAR study on this compound series has been carried out herein, and thirteen new compounds have been designed and synthesized. Among them, compound 10 exhibited potent inhibition against human recombinant PTP1B with the IC50 value of 3.97 micromol x L(-1), and is comparable to that of compound II.

Synergistic effect of folate and MTHFR C677T on hippocampal subfields and perfusion in Alzheimer's disease.

BACKGROUND: Low folate intake and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism have been suggested to increase the risk of Alzheimer's disease (AD). However, the synergistic effects and their impact on brain structure and perfusion remain unclear. METHODS: This study explored the effects of dietary and genetic deficiencies in folate metabolism on the volume of the hippocampal subregions, cerebral perfusion, and cognitive decline in 71 cognitively unimpaired (CU) individuals and 102 patients with mild cognitive impairment (MCI) due to AD or AD. All participants underwent magnetic resonance imaging, laboratory examinations, and neuropsychological assessments. The hippocampal subfields were segmented using Freesurfer, and arterial spin labeling was used to measure the cerebral blood flow. RESULTS: We found a significant group-by-MTHFR interaction effect on folate. Patients with AD and the 677 T allele showed hypoperfusion in the left precuneus compared to patients without this mutation, which mediated the relationship between low folate level and cognitive decline in patients carrying the 677 T allele. Moreover, a synergistic effect was observed for the combination of decreased folate concentrations and the presence of the MTHFR 677 T allele on the atrophy of specific hippocampal subregions in patients with AD. CONCLUSIONS: In addition to offering insights into the neuronal mechanism underlying gene-dependent folate-induced cognitive impairment in AD, these findings may have clinical significance for the allocation of auxiliary folate supplementation therapy in patients with AD with low folate levels and carrying the MTHFR 677 T allele and may eventually promote the selection of early individualized AD drug therapy.

The Hippocampal Subfield Volume Reduction and Plasma Biomarker Changes in Mild Cognitive Impairment and Alzheimer's Disease.

Background: The hippocampus consists of histologically and functionally distinct subfields, which shows differential vulnerabilities to Alzheimer's disease (AD)-associated pathological changes. Objective: To investigate the atrophy patterns of the main hippocampal subfields in patients with mild cognitive impairment (MCI) and AD and the relationships among the hippocampal subfield volumes, plasma biomarkers and cognitive performance. Methods: This cross-sectional study included 119 patients stratified into three categories: normal cognition (CN; N = 40), MCI (N = 39), and AD (N = 40). AD-related plasma biomarkers were measured, including amyloid-ß (Aß)42, Aß40, Aß42/Aß40 ratio, p-tau181, and p-tau217, and the hippocampal subfield volumes were calculated using automated segmentation and volumetric procedures implemented in FreeSurfer. Results: The subiculum body, cornu ammonis (CA) 1-head, CA1-body, CA4-body, molecular_layer_HP-head, molecular_layer_HP-body, and GC-ML-DG-body volumes were smaller in the MCI group than in the CN group. The subiculum body and CA1-body volumes accurately distinguished MCI from CN (area under the curve [AUC] = 0.647-0.657). The subiculum-body, GC-ML-DG-body, CA4-body, and molecular_layer_HP-body volumes accurately distinguished AD from MCI (AUC = 0.822-0.833) and AD from CN (AUC = 0.903-0.905). The p-tau 217 level served as the best plasma indicator of AD and correlated with broader hippocampal subfield volumes. Moreover, mediation analysis demonstrated that the subiculum-body volume mediated the associations between the p-tau217 and p-tau181 levels, and the Montreal Cognitive Assessment and Auditory Verbal Learning Test recognition scores. Conclusions: Hippocampal subfields with distinctive atrophy patterns may mediate the effects of tau pathology on cognitive function. The subiculum-body may be the most clinically meaningful hippocampal subfield, which could be an effective target region for assessing disease progression.

Disrupted dynamic network attribution associated with gait disorder in cerebral small vessel disease.

BACKGROUND AND AIMS: Previous research has focused on static functional connectivity in gait disorders caused by cerebral small vessel disease (CSVD), neglecting dynamic functional connections and network attribution. This study aims to investigate alterations in dynamic functional network connectivity (dFNC) and topological organization variance in CSVD-related gait disorders. METHODS: A total of 85 patients with CSVD, including 41 CSVD patients with gait disorders (CSVD-GD), 44 CSVD patients with non-gait disorders (CSVD-NGD), and 32 health controls (HC) were enrolled in this study. Five networks composed of 10 independent components were selected using independent component analysis. Sliding time window and k-means clustering methods were used for dFNC analysis. The relationship between alterations in the dFNC properties and gait metrics was further assessed. RESULTS: Three reproducible dFNC states were determined (State 1: sparsely connected, State 2: intermediate pattern, State 3: strongly connected). CSVD-GD showed significantly higher fractional windows (FW) and mean dwell time (MDT) in State 1 compared to CSVD-NGD. Higher local efficiency variance was observed in the CSVD-GD group compared to HC, but no differences were found in the global efficiency comparison. Both the FW and MDT in State 1 were negatively correlated with gait speed and step length, and the relationship between MDT of State 1 and gait speed was mediated by overall cognition, information processing speed and executive function. CONCLUSIONS: Our study uncovered abnormal dFNC indicators and variations in topological organization in CSVD-GD, offering potential early prediction indicators and freshening insights into the underlying pathogenesis of gait disturbances in CSVD.

Discovery of novel PTP1B inhibitors via pharmacophore-oriented scaffold hopping from Ertiprotafib.

An integrated molecular design strategy combining pharmacophore recognition and scaffold hopping was exploited to discover novel PTP1B inhibitors based on the known PTP1B inhibitor Ertiprotafib. A composite pharmacophore model was proposed from the interaction mode of Ertiprotafib, and 21 diverse molecules from five distinct structural classes were designed and synthesized accordingly. New compounds with considerable inhibition against PTP1B were identified from each series, and the most active compound 3a showed IC50 value of 1.3 µmol L(-1) against human recombinant PTP1B. Docking study indicated that the new inhibitors assumed binding modes similar to that of Ertiprotafib.

Synthetic route to metal nitrides: high-pressure solid-state metathesis reaction.

We report a general synthetic route to well-crystallized metal nitrides through a high-pressure solid-state metathesis reaction (HPSSM) between boron nitride (BN) and ternary metal oxide A(x)M(y)O(z) (A = alkaline or alkaline-earth metal and M = main group or transition metal). On the basis of the synthetic metal nitrides (Fe3N, Re3N, VN, GaN, CrN, and W(x)N) and elemental products (graphite, rhenium, indium, and cobalt metals), the HPSSM reaction has been systematically investigated with regard to its general chemical equation, reaction scheme, and characteristics, and its thermodynamic considerations have been explored by density functional theory (DFT) calculations. Our results indicate that pressure plays an important role in the synthesis, which involves an ion-exchange process between boron and the metal ion, opening a new pathway for material synthesis.

Nanoparticle core size and spacer coating thickness-dependence on metal-enhanced luminescence in optical oxygen sensors.

Metal-enhanced luminescence (MEL) originated from near field interactions of luminescence with the surface plasmon resonance (SPR) of nearby metallic nanoparticles (NPs) is an effective strategy to increase luminescence detection sensitivity in oxygen sensors. Once the excitation light induces SPR, the generated enhanced local electromagnetic filed will result in an enhanced excitation efficiency and an increased radiative decay rates of luminescence in close proximity. Meanwhile, the nonradioactive energy transfer from the dyes to the metal NPs, leading to emission quenching, can also be affected by their separation. The extent of the intensity enhancement depends critically on the particle size, shape and the separation distance between the dye and the metal surface. Here, we prepared core-shell Ag@SiO2 with different core sizes (35 nm, 58 nm and 95 nm) and shell thickness (5-25 nm) to investigate the size and separation dependence on the emission enhancement in oxygen sensors at 0-21% oxygen concentration. Intensity enhancement factors of 4-9 were observed with a silver core size of 95 nm and silica shell thickness of 5 nm at 0-21% O2. In addition, the intensity enhancement factor increases with increasing core size and decreasing shell thickness in the Ag@SiO2-based oxygen sensors. Using Ag@SiO2 NPs result in brighter emission throughout the 0-21% oxygen concentration. Our fundamental understanding of MEP in the oxygen sensors provides us the opportunity to design and control efficient luminescence enhancement in oxygen and other sensors. .

Metabolic syndrome-related cognitive impairment with white matter hyperintensities and functional network analysis.

OBJECTIVE: This study aimed to explore the relationship between white matter hyperintensities (WMHs) and cognitive impairment related to metabolic syndrome (MetS) and the underlying neural network mechanisms. METHODS: This cross-sectional study included 50 participants with MetS and WMHs (MetS-WMHs), 45 with MetS without WMHs, and 50 control participants. All participants underwent resting-state functional magnetic resonance imaging and a detailed cognitive evaluation. A graph theory analysis based on resting-state functional magnetic resonance imaging was conducted to calculate functional network properties. A mediation analysis was conducted to determine the relationship between WMHs and MetS-related cognitive impairment. RESULTS: Compared with the control group, the participants in the MetS-WMHs group displayed lower global efficiency, local efficiency, and nodal efficiency, mainly located in the regions of the salience network. Furthermore, a significant correlation was observed between functional network efficiency and cognitive performance. Mediation analysis indicated that WMHs served as a mediating variable between MetS and cognitive decline, affecting attention/executive function, language, and global cognitive function. CONCLUSIONS: WMHs mediated the association between MetS and cognitive function, with a decline in the efficiency of functional brain networks being a probable neural mechanism.

Bilateral Hippocampal Volume Mediated the Relationship Between Plasma BACE1 Concentration and Memory Function in the Early Stage of Alzheimer's Disease: A Cross-Sectional Study.

BACKGROUND: ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a key enzyme in the formation of amyloid-ß (Aß) protein. Increasing evidence suggests that BACE1 concentration is a potential biomarker for Alzheimer's disease (AD). OBJECTIVE: To evaluate the correlations between plasma BACE1 concentration, cognition, and hippocampal volume at different stages of the AD continuum. METHODS: Plasma BACE1 concentrations were measured in 32 patients with probable dementia due to AD (ADD), 48 patients with mild cognitive impairment (MCI) due to AD, and 40 cognitively unimpaired (CU) individuals. Memory function was evaluated using the auditory verbal learning test (AVLT), and voxel-based morphometry was used to analyze bilateral hippocampal volumes. Correlation and mediation analyses were performed to investigate the associations between plasma BACE1 concentration, cognition, and hippocampal atrophy. RESULTS: The MCI and ADD groups exhibited elevated BACE1 concentrations compared with the CU group after adjusting for age, sex, and apolipoprotein E (APOE) genotype. Increased BACE1 concentration was found in AD continuum patients who were APOE ɛ4 carriers (p < 0.05). BACE1 concentration was negatively associated with the scores of the subitems of the AVLT and hippocampal volume (p < 0.05, false discovery rate correction) in the MCI group. Moreover, bilateral hippocampal volume mediated the relationship between BACE1 concentration and recognition in the MCI group. CONCLUSION: BACE1 expression increased in the AD continuum, and bilateral hippocampal volume mediated the effect of BACE1 concentration on memory function in patients with MCI. Research has indicated that the plasma BACE1 concentration might be a biomarker at the early stage of AD.

Brain Gray Matter Volume Mediated the Correlation Between Plasma P-Tau and Cognitive Function of Early Alzheimer's Disease in China: A Cross-Sectional Observational Study.

BACKGROUND: The primary manifestations of Alzheimer's disease (AD) include cognitive decline and brain gray matter volume (GMV) atrophy. Recent studies have found that plasma phosphorylated-tau (p-tau) concentrations perform better in diagnosing, differentiating, and monitoring the progression of AD. However, the correlation between plasma p-tau, GMV, and cognition remains unclear. OBJECTIVE: To investigate whether GMV plays a mediating role in the association between plasma p-tau concentrations and cognition. METHODS: In total, 99 participants (47 patients with AD and 52 cognitively unimpaired [CU] individuals) were included. All participants underwent neuropsychological assessments, laboratory examinations, and magnetic resonance imaging scans. Plasma p-tau217 and p-tau181 concentrations were measured using an enzyme-linked immunosorbent assay kit. Voxel-based morphometry was performed to assess participants' brain GMV. Partial correlation and mediation analyses were conducted in AD group. RESULTS: Plasma p-tau concentrations were significantly higher in the AD group than in the CU group. Patients with AD had significant brain GMV atrophy in the right hippocampus, bilateral middle temporal gyrus, and right inferior temporal gyrus. In the AD group, there were significant correlations between plasma p-tau217 concentrations, GMV, and Mini-Mental State Examination (MMSE) scores. Brain GMV of the right hippocampus mediated the association between plasma p-tau217 concentrations and MMSE scores. A significant correlation between plasma p-tau181 and MMSE scores was not identified. CONCLUSION: The findings indicate that p-tau217 is a promising biomarker for central processes affecting brain GMV and cognitive function. This may provide potential targets for future intervention and treatment of tau-targeting therapies in the early stages of AD.

Telemedicine management of type 2 diabetes mellitus in obese and overweight young and middle-aged patients during COVID-19 outbreak: A single-center, prospective, randomized control study.

OBJECTIVE: The coronavirus disease-2019 (COVID-19) pandemic severely affected the disease management of patients with chronic illnesses such as type 2 diabetes mellitus (T2DM). This study aimed to assess the effect of telemedicine management of diabetes in obese and overweight young and middle-aged patients with T2DM during the COVID-19 pandemic. METHODS: A single-center randomized control study was conducted in 120 obese or overweight (body mass index [BMI] ≥ 24 kg/m2) young and middle-aged patients (aged 18-55 years) with T2DM. Patients were randomly assigned to the intervention (telemedicine) or control (conventional outpatient clinic appointment) group. After baseline assessment, they were home isolated for 21 days, received diet and exercise guidance, underwent glucose monitoring, and followed up for 6 months. Glucose monitoring and Self-Rating Depression Scale (SDS) scores were evaluated at 22 days and at the end of 3 and 6 months. RESULTS: Ninety-nine patients completed the 6-month follow-up (intervention group: n = 52; control group: n = 47). On day 22, the fasting blood glucose (FBG) level of the intervention group was lower than that of the control group (p < 0.05), and the control group's SDS increased significantly compared with the baseline value (p < 0.05). At the end of 3 months, glycated hemoglobin (HbA1c) and FBG levels in the intervention group decreased significantly compared with those in the control group (p < 0.01). At the end of 6 months, the intervention group showed a significant decrease in postprandial blood glucose, triglyceride, and low-density lipoprotein cholesterol levels as well as waist-to-hip ratio compared with the control group (p < 0.05); moreover, the intervention group showed lower SDS scores than the baseline value (p < 0.05). Further, the intervention group showed a significant reduction in BMI compared with the control group at the end of 3 and 6 months (p < 0.01). CONCLUSION: Telemedicine is a beneficial strategy for achieving remotely supervised blood glucose regulation, weight loss, and depression relief in patients with T2DM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04723550.

The Clustering Analysis of Time Properties in Patients With Cerebral Small Vessel Disease: A Dynamic Connectivity Study.

Purpose: This study aimed to investigate the dynamic functional connectivity (DFC) pattern in cerebral small vessel disease (CSVD) and explore the relationships between DFC temporal properties and cognitive impairment in CSVD. Methods: Functional data were collected from 67 CSVD patients, including 35 patients with subcortical vascular cognitive impairment (SVCI) and 32 cognitively unimpaired (CU) patients, as well as 35 healthy controls (HCs). The DFC properties were estimated by k-means clustering analysis. DFC strength analysis was used to explore the regional functional alterations between CSVD patients and HCs. Correlation analysis was used for DFC properties with cognition and SVD scores, respectively. Results: The DFC analysis showed three distinct connectivity states (state I: sparsely connected, state II: strongly connected, state III: intermediate pattern). Compared to HCs, CSVD patients exhibited an increased proportion in state I and decreased proportion in state II. Besides, CSVD patients dwelled longer in state I while dwelled shorter in state II. CSVD subgroup analyses showed that state I frequently occurred and dwelled longer in SVCI compared with CSVD-CU. Also, the internetwork (frontal-parietal lobe, frontal-occipital lobe) and intranetwork (frontal lobe, occipital lobe) functional activities were obviously decreased in CSVD. Furthermore, the fractional windows and mean dwell time (MDT) in state I were negatively correlated with cognition in CSVD but opposite to cognition in state II. Conclusion: Patients with CSVD accounted for a higher proportion and dwelled longer mean time in the sparsely connected state, while presented lower proportion and shorter mean dwell time in the strongly connected state, which was more prominent in SVCI. The changes in the DFC are associated with altered cognition in CSVD. This study provides a better explanation of the potential mechanism of CSVD patients with cognitive impairment from the perspective of DFC.