ObjectivesTo systematically review the efficacy and safety of butylphthalide soft capsule with routine treatment for Alzheimer’s disease (AD).MethodsDatabases including CNKI, WanFang Data, VIP, CBM, PubMed, EMbase, and The Cochrane Library were electronically searched from September 2002 to July 2018 to collect randomized controlled trials of butylphthalide soft capsule with routine treatment for Alzheimer’s disease. The trial was screened based on inclusion and exclusion criteria, and the methodological quality of the included trial was assessed. Meta-analysis was then performed by Revman 5.3 software.ResultsA total of 8 studies involving 576 patients were included. The butylphthalide soft capsule group included 283 patients and the control group included 293 patients. The result of meta-analysis showed that butylphthalide soft capsule with routine treatment (Donepezil hydrochloride or Memantine or EGb761) significantly improved the score of mini-mental state examination (MMSE) (MD=3.19, 95% CI 2.69 to 3.69, P<0.001) and clinical efficacy (RR=1.36, 95%CI 1.21 to 1.53, P<0.001). There was no significant difference in number of adverse events between the butylphthalide group and the control group (RR=1.13, 95%CI 0.77 to 1.67, P=0.52).ConclusionsBased on the routine treatment, combining with butylphthalide soft capsule can further facilitate cognitive function of AD and improve clinical efficacy. At the same time, no increase in adverse reactions has been found. However, due to the low quality of the included studies, more high quality randomized controlled trials are required to verify the results.
Objective To generate eukaryotic expression vector of pcDNA3.1-β-site amyloid precursor protein cleaving enzyme (BACE) and obtain its transient expression in COS-7 cells. Methods A 1.5 kb cDNA fragment was amplified from the total RNA of the human neuroblastoma cells by the RT-PCR method and was cloned into the plasmid pcDNA3.1. The vector was identified by the double digestion with restriction enzymes BamHI and XhoI and was sequenced by the Sanger-dideoxy-mediated chain termination. The expression of the BACE gene was detected by immunocytochemistry. Results The results showed that the cDNA fragment included 1.5 kb total coding region. The recombinant eukaryotic cell expression vector of pcDNA3.1-BACE was constructed successfully, and the sequence of insert was identical to the published sequence. The COS-7 cells transfected with the pcDNA3.1BACE plasmid expressed a high level of the BACE protein in the cytoplasm. Conclusion The recombinant plasmid pcDNA3.1-BACE can provide a very useful tool for the research on the cause of Alzheimer’s disease and lay an important foundation for preventing Alzheimer’s disease.
Krüppel-like factor 4 (KLF4) is a member of the sample Kruppel transcription factor protein family, is an evolutionary conservative contain zinc finger transcription factors, involved in regulating many cellular processes, such as cell growth, proliferation, differentiation and invasion, KLF4 expression in a variety of tissues and cells in the body, has widely in many physiological and pathological conditions. Many studies have shown that KLF4 is involved in neurobiological processes such as neuroinflammation, oxidative stress, apoptosis and axon regeneration, and is closely related to a variety of nervous system diseases such as epilepsy, stroke, and Alzheimer’s disease. Now KLF4 in its role in the development of nervous system diseases were reviewed, help to understand the pathogenesis of the disease and clinical treatment for diseases of the nervous system to provide potential targets.
Objective To evaluate the relationship between genetic polymorphism of ApoE and Alzheimer’s disease in Chinese population. Methods Such databases as PubMed, EBSCO, CNKI, CBM, and WangFang Data were searched from their establishment to December 2010 to collect the literature about the relationship between genetic polymorphism of ApoE and Alzheimer’s disease in Chinese population. RevMan 5.0 was adopted to conduct consistency check and data merging, and to evaluate publication bias. Results ApoEε4 was the risky allele (Plt;0.05) in Chinese population, and its pooled odds ratios and 95%CI was 3.53 (2.49 to 5.00). ApoEε3 was the protective alleles (Plt;0.05) in Chinese population, and its pooled odds ratios and 95%CI was 0.52 (0.40 to 0.68). ApoEε4/ε4, ApoEε4/ε3, and ApoEε4/ε2 were the risky genotypes (all Plt;0.05) in Chinese population, and their pooled odds ratios and 95%CI were 10.17 (4.25 to 24.19), 2.57 (2.04 to 3.25), and 1.94 (1.13 to 3.34), respectively. ApoEε3/ε3 was the protective genotype (Plt;0.05) in Chinese population, and its pooled odds ratios and 95%CI was 0.67 (0.57 to 0.77). Conclusion In Chinese population, some ApoE alleles and genotypes are associated with Alzheimer’s disease.
Caveolin-1 (Cav-1) protein plays a very important role in the central nervous system, and is closely related to Alzheimer’s disease (AD). Through literature review, this article summarizes the present research status of Cav-1 protein in the field of AD from three aspects: the relationship between Cav-1 gene and AD; the relationship of Cav-1 protein with learning and memory; the relationship of Cav-1 protein with amyloid β-protein and Tau protein. And the aim of this paper is to provide a new thought and evidence for exploring the mechanism of AD via Cav-1 protein.
Objective To investigate the effect of continuous positive airway pressure (CPAP) on sleep disorder and neuropsychological characteristics in patients with early Alzheimer’s disease (AD) combined with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods A total of forty-two early AD patients with OSAHS were randomly divided into a CPAP combined treatment group (20 cases) and a simple medicine treatment group (22 cases). The changes of neurocognitive function were assessed by Montreal Cognitive Assessment (MoCA), Mini-mental State Examination (MMSE) and Hopkins Verbal Learning Test-revised (HVLT). Patient Health Questionnaire-9 (PHQ9) was used to evaluate the depression mood changes. The sleep characteristics and respiratory parameters were evaluated by polysomnography. The changes of the patients’ sleep status were assessed by Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI). The changes of sleep status, cognitive function and mood in the CPAP combined treatment group were compared before and three months after CPAP treatment, and with the simple medicine treatment group. Results After three months of CPAP treatment, the ESS, PSQI and PHQ9 scores in the CPAP combined treatment group were significantly decreased compared with those before treatment, whereas MoCA, MMSE and HVLT (total scores and recall ) in the CPAP combined treatment group were increased compared with those before treatment (P<0.05). After CPAP treatment, the respiratory parameters apnea hypopnea index in the CPAP combined treatment group was significantly lower than that before treatment (P<0.05), and the minimum blood oxygen saturation was significantly higher than that before treatment (P<0.05). However, the sleep characteristics and parameters did not show statistically significant changes compared with those before treatment (P>0.05). The ESS, PSQI and PHQ9 scores were significantly reduced in the CPAP combined treatment group compared with the simple medicine treatment group (P<0.05), while there was no statistically significant changes of cognitive scores between the two groups (P>0.05). Conclusions The degree of low ventilation and hypoxia is alleviated, and the daytime sleepiness and depression is improved in early AD patients with OSAHS after three-month continuous CPAP treatment. Cognitive function is significantly improved, whereas there is no significant change in sleep structure disorder.
Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder that damages patients’ memory and cognitive abilities. Therefore, the diagnosis of AD holds significant importance. The interactions between regions of interest (ROIs) in the brain often involve multiple areas collaborating in a nonlinear manner. Leveraging these nonlinear higher-order interaction features to their fullest potential contributes to enhancing the accuracy of AD diagnosis. To address this, a framework combining nonlinear higher-order feature extraction and three-dimensional (3D) hypergraph neural networks is proposed for computer-assisted diagnosis of AD. First, a support vector machine regression model based on the radial basis function kernel was trained on ROI data to obtain a base estimator. Then, a recursive feature elimination algorithm based on the base estimator was applied to extract nonlinear higher-order features from functional magnetic resonance imaging (fMRI) data. These features were subsequently constructed into a hypergraph, leveraging the complex interactions captured in the data. Finally, a four-dimensional (4D) spatiotemporal hypergraph convolutional neural network model was constructed based on the fMRI data for classification. Experimental results on the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database demonstrated that the proposed framework outperformed the Hyper Graph Convolutional Network (HyperGCN) framework by 8% and traditional two-dimensional (2D) linear feature extraction methods by 12% in the AD/normal control (NC) classification task. In conclusion, this framework demonstrates an improvement in AD classification compared to mainstream deep learning methods, providing valuable evidence for computer-assisted diagnosis of AD.
Alzheimer’s disease (AD) is a chronic central neurodegenerative disease. The pathological features of AD are the extracellular deposition of senile plaques formed by amyloid-β oligomers (AβOs) and the intracellular accumulation of neurofibrillary tangles formed by hyperphosphorylated tau protein. In this paper, an in vitro pathological model of AD based on neuronal network chip and its real-time dynamic analysis were presented. The hippocampal neuronal network was cultured on the microelectrode array (MEA) chip and induced by AβOs as an AD model in vitro to simultaneously record two firing patterns from the interneurons and pyramidal neurons. The spatial firing patterns mapping and cross-correlation between channels were performed to validate the degeneration of neuronal network connectivity. This biosensor enabled the detection of the AβOs toxicity responses, and the identification of connectivity and interactions between neuronal networks, which can be a novel technique in the research of AD pathological model in vitro.
Alzheimer’s disease (AD) is a common elderly illness, and the hand movement abilities of patients differ from those of normal individuals. Focusing on the utilization of RGB, optical flow, and hand skeleton as tri-modal image information for early AD recognition, a method for early AD recognition via multi-modal hand motion quality assessment (EADR) is proposed. First, a hybrid modality feature encoder incorporating global contextual information was designed to integrate the global contextual information of features from three specific modality branches. Subsequently, a fusion modality feature decoder network incorporating specific modality features was proposed to decode the overlooked information in the fusion modality branch from specific modality features, thereby enhancing feature fusion. Experiments demonstrated that EADR effectively could capture high-quality hand motion features and excelled in hand motion quality assessment tasks, outperforming existing models. Based on this, the action quality scoring regression model trained using the k-nearest neighbors algorithm demonstrated the best recognition performance for AD patients, with Spearman’s rank correlation coefficient and Kendall’s rank correlation coefficient reaching 90.98% and 83.44%, respectively. This indicates that the assessment of hand motor ability may serve as a potential auxiliary tool for early AD identification.
ObjectiveTo systematically review the diagnostic value of miRNAs for Alzheimer’s disease (AD).MethodsPubMed, Web of Science, EMbase, The Cochrane Library, CNKI, WanFang Data, VIP, and CBM databases were electronically searched to collect diagnostic tests of miRNAs for AD from inception to October 31, 2020. Two researchers independently screened literature, extracted data, and assessed the risk of bias of the included studies. RevMan 5.3 and Stata 14.0 software were used for meta-analysis. ResultsA total of 22 studies involving 4 006 subjects were included. The meta-analysis results showed that the pooled sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and the areas under the working characteristic curve of miRNA in AD diagnosis were 0.83 (95%CI 0.79 to 0.87), 0.80 (95%CI 0.76 to 0.83), 4.07 (95%CI 3.37 to 4.92), 0.21 (95%CI 0.17 to 0.27), 19.20 (95%CI 12.96 to 28.48) and 0.88 (95%CI 0.85 to 0.90), respectively. ConclusionThe current evidence shows that miRNAs have a high diagnostic value for AD. However, because of the limited quality and quantity of the included studies, more high-quality studies are required to verify the above conclusion.