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.
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.
ObjectiveTo systematically review the data of peripheral inflammatory markers in patients with Alzheimer’s disease (AD) and vascular dementia (VaD) to further indicate pathogenesis and antidiastole.MethodsPubMed, EMbase, The Cochrane Library, CNKI, WanFang Data and VIP databases were electronically searched to collect studies on peripheral inflammatory markers in patients with AD and VaD from inception to July 2020. Two reviewers independently screened literature, extracted data, and assessed risk of bias of included studies, and meta-analysis was performed by using Stata 15.1SE software.ResultsA total of 30 studies involving 2 377 patients were included. The results of meta-analysis showed that the IL-6 level was higher in VaD group than that in AD group (SMD=−0.477, 95%CI −0.944 to −0.009, P=0.046). However, there were no statistical difference in peripheral IL-1β (SMD=−0.034, 95%CI −0.325 to 0.257, P=0.818), TNF-α (SMD=0.409, 95%CI −0.152 to 0.970, P=0.153) or CRP (SMD=0.277, 95%CI −0.228 to 0.782, P=0.282) levels.ConclusionsThese findings suggest that IL-6 may be sensitive markers to distinguish AD from VaD. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify the conclusions.
ObjectiveTo systematically review the diagnostic value of FDG-PET, Aβ-PET and tau-PET for Alzheimer ’s disease (AD).MethodsPubMed, EMbase, The Cochrane Library, CNKI, WanFang Data, VIP and CBM databases were electronically searched to collect diagnostic tests of FDG-PET, Aβ-PET and tau-PET for AD from January 2000 to February 2020. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies; then, meta-analysis was performed by Meta-Disc 1.4 and Stata 14.0 software.ResultsA total of 31 studies involving 3 718 subjects were included. The results of meta-analysis showed that, using normal population as control, the sensitivity/specificity of FDG-PET and Aβ-PET in diagnosing AD were 0.853/0.734 and 0.824/0.771, respectively. Only 2 studies were included for tau-PET and meta-analysis was not performed.ConclusionsFDG-PET and Aβ-PET can provide good diagnostic accuracy for AD, and their diagnostic efficacy is similar. Due to limited quality and quantity of the included studies, more high quality studies are required to verify the above conclusions.
In order to solve the problem of early classification of Alzheimer’s disease (AD), the conventional linear feature extraction algorithm is difficult to extract the most discriminative information from the high-dimensional features to effectively classify unlabeled samples. Therefore, in order to reduce the redundant features and improve the recognition accuracy, this paper used the supervised locally linear embedding (SLLE) algorithm to transform multivariate data of regional brain volume and cortical thickness to a locally linear space with fewer dimensions. The 412 individuals were collected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) including stable mild cognitive impairment (sMCI, n = 93), amnestic mild cognitive impairment (aMCI, n = 96), AD (n = 86) and cognitive normal controls (CN, n = 137). The SLLE algorithm used in this paper is to calculate the nearest neighbors of each sample point by adding the distance correction term, and the locally linear reconstruction weight matrix was obtained from its nearest neighbors, then the low dimensional mapping of the high dimensional data can be calculated. In order to verify the validity of SLLE in the task of classification, the feature extraction algorithms such as principal component analysis (PCA), Neighborhood MinMax Projection (NMMP), locally linear mapping (LLE) and SLLE were respectively combined with support vector machines (SVM) classifier to obtain the accuracy of classification of CN and sMCI, CN and aMCI, CN and AD, sMCI and aMCI, sMCI and AD, and aMCI and AD, respectively. Experimental results showed that our method had improvements (accuracy/sensitivity/specificity: 65.16%/63.33%/67.62%) on the classification of sMCI and aMCI by comparing with the combination algorithm of LLE and SVM (accuracy/sensitivity/specificity: 64.08%/66.14%/62.77%) and SVM (accuracy/sensitivity/specificity: 57.25%/56.28%/58.08%). In detail the accuracy of the combination algorithm of SLLE and SVM is 1.08% higher than the combination algorithm of LLE and SVM, and 7.91% higher than SVM. Thus, the combination of SLLE and SVM is more effective in the early diagnosis of Alzheimer’s disease.
Objective To evaluate the efficacy and safety of memantine in the treatment of Alzheimer’s disease (AD). Methods The randomized controlled trials (RCTs) about memantine vs. donepezil for patients with AD from January 1989 to July 2011 were searched in CBM, CNKI, WanFang Data, MEDLINE, OVID, EMbase and The Cochrane Library. Two reviewers independently screened the literatures, extracted the data, and evaluated the methodological quality. Then meta-analyses were conducted by using RevMan 5.0 software. Results The total 12 RCTs were included. Among the 2 716 patients involved, 1 459 were in the memantine group, while the other 1 302 were in the donepezil group. The results of meta-analyses showed that the efficacy of the memantine group was superior to that of the donepezil group in MMSE (MD=0.53, 95%CI 0.21 to 0.85, P=0.001), CIBIC-Plus (MD= –0.19, 95%CI –0.31 to –0.07, P=0.002), NPI (MD= –2.9, 95%CI –4.57 to –1.22, P=0.000 7) and SIB (MD=3.12, 95%CI 0.57 to 5.67, P=0.02), with significant differences; but the efficacy of the two groups was similar in ADCS-ADL19 (MD=0.29, 95%CI –0.03 to 0.60, P=0.07). There was no significant difference between the two groups in incidence of side effects (RR=1.14, 95%CI 0.94 to 1.38, P=0.17), but the tolerability of the memantine group was much better (RR=0.78, 95%CI 0.63 to 0.97, P=0.03). Conclusion Based on the current studies, memantine is superior to donepezil in treating Alzheimer’s disease (AD) at present. Although the side effects are similar to donepezil, memantine has much better intolerability and is considered to be safe and effective. For the quality restrictions and possible publication bias of the included studies, more double blind RCTs with high quality are required to further assess the effects.
The electroencephalogram (EEG) signal is a general reflection of the neurophysiological activity of the brain, which has the advantages of being safe, efficient, real-time and dynamic. With the development and advancement of machine learning research, automatic diagnosis of Alzheimer’s diseases based on deep learning is becoming a research hotspot. Started from feedforward neural networks, this paper compared and analysed the structural properties of neural network models such as recurrent neural networks, convolutional neural networks and deep belief networks and their performance in the diagnosis of Alzheimer’s disease. It also discussed the possible challenges and research trends of this research in the future, expecting to provide a valuable reference for the clinical application of neural networks in the EEG diagnosis of Alzheimer’s disease.
Amyloid β-protein (Aβ) deposition is an important prevention and treatment target for Alzheimer’s disease (AD), and early detection of Aβ deposition in the brain is the key to early diagnosis of AD. Magnetic resonance imaging (MRI) is the perfect imaging technology for the clinical diagnosis of AD, but it cannot display the plaque deposition directly. In this paper, based on two feature selection modes-filter and wrapper, chain-like agent genetic algorithm (CAGA), principal component analysis (PCA), support vector machine (SVM) and random forest (RF), we designed six kinds of feature learning classification algorithms to detect the information (distribution) of Aβ deposition through magnetic resonance image pixels selection. Firstly, we segmented the brain region from brain MR images. Secondly, we extracted the pixels in the segmented brain region as a feature vector (features) according to rows. Thirdly, we conducted feature learning on the extracted features, and obtained the final optimal feature subset by voting mechanism. Finally, using the final optimal selected features, we could find and mark the corresponding pixels on the MR images to show the information about Aβ plaque deposition by elastic mapping. According to the experimental results, the proposed pixel features learning methods in this paper could extract and reflect Aβ plaque deposition, and the best classification accuracy could be as high as 80%, thereby showing the effectiveness of the methods. The proposed methods can precisely detect the information of the Aβ plaque deposition, thereby being helpful for improving classification accuracy of diagnosis of AD.
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.
Objective To analyze the characteristic and temporal trend in mortality and disease burden of Alzheimer’s disease (AD) and other forms of dementia in Guangzhou from 2008 to 2019, and estimate the disease burden attributable to smoking to provide evidence for promoting local health policy of prevention and intervention of dementia. Methods Based on the data of Guangzhou surveillance point of the National Mortality Surveillance System (NMSS), the crude mortality, standardized mortality, years of life lost (YLL) of AD and other dementia were calculated. The indirect method was used to estimate years lived with disability (YLD) and disability-adjusted life years (DALY).The distribution and changing trends of the index rates were compared from 2008 to 2019 using Joinpoint Regression Program. Based on the data of Guangzhou Chronic Disease and Risk Factors Monitoring System in 2013, the indexes of disease burden of AD and other forms of dementia attributable to smoking in 2018 was calculated. Results The standardized mortality rate, YLL rate, YLD rate and DALY rate of AD and other forms of dementia in Guangzhou increased from 0.45/100 000, 0.05‰, 0.02‰ and 0.07 ‰ in 2008 to 1.28/100 000, 0.15‰, 0.07‰ and 0.22‰ in 2019, respectively. The average annual changing trend was statistically significant (AAPC=11.30%, 13.09%, 13.09%, 13.09%, P<0.001）. In most years, the mortality and disease burden of women were higher than those of men, but men had higher growing trend than women in standardized mortality rate, YLL rate, YLD rate and DALY rate from 2008 to 2019, with a slower growing speed after the year 2012.The disease burden of dementia attributable to smoking in men was significantly higher than that in women. Conclusion The mortality and disease burden of AD and other forms of dementia in Guangzhou have dramatically increased over the past twelve years. Intervention against modifiable factors such as smoking, and prevention and screening for dementia in key populations should be strengthened. Support policies for dementia care management should be adopted to reduce the disease burden caused by premature death and disability.