With the exacerbation of aging population in China, the number of patients with Alzheimer's disease (AD) is increasing rapidly. AD is a chronic but irreversible neurodegenerative disease, which cannot be cured radically at present. In recent years, in order to intervene in the course of AD in advance, many researchers have explored how to detect AD as early as possible, which may be helpful for effective treatment of AD. Imaging genomics is a kind of diagnosis method developed in recent years, which combines the medical imaging and high-throughput genetic omics together. It studies changes in cognitive function in patients with AD by extracting effective information from high-throughput medical imaging data and genomic data, providing effective guidance for early detection and treatment of AD patients. In this paper, the association analysis of magnetic resonance image (MRI) with genetic variation are summarized, as well as the research progress on AD with this method. According to complexity, the objects in the association analysis are classified as candidate brain phenotype, candidate genetic variation, genome-wide genetic variation and whole brain voxel. Then we briefly describe the specific methods corresponding to phenotypic of the brain and genetic variation respectively. Finally, some unsolved problems such as phenotype selection and limited polymorphism of candidate genes are put forward.
We in the present research proposed a classification method that applied infomax independent component analysis (ICA) to respectively extract single modality features of structural magnetic resonance imaging (sMRI) and positron emission tomography (PET). And then we combined these two features by using a method of weight combination. We found that the present method was able to improve the accurate diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI). Compared AD to healthy controls (HC): the study achieved a classification accuracy of 93.75%, with a sensitivity of 100% and a specificity of 87.64%. Compared MCI to HC: classification accuracy was 89.35%, with a sensitivity of 81.85% and a specificity of 99.36%. The experimental results showed that the bi-modality method performed better than the individual modality in comparison to classification accuracy.
Objective To observe the changes of retinal nerve fiber layer (RNFL) thickness in patients with Alzheimer's disease (AD). Methods Twenty eyes of 40 patients with mild and (or) moderate AD confirmed by clinical examination (AD group) were included in the study. There were 11 males and 9 females with an average age of (72.75±8.25) years. Age and gender-matched normal 20 objectives were in the normal control group. Among them, there were 11 males and 9 females with a mean age of (71.05±7.08) years. There was no significant difference in gender composition, age and intraocular pressure between the two groups (P＞0.05). There were significant differences in visual acuity, cup disc ratio and mini-mental state examination score (P＜0.05). All eyes underwent high-resolution optical coherence tomography (OCT) examination. With a diameter of 3.4 mm and a center on the center of the optic disc, circular fast scans on optic disc were performed to obtain an average disc RNFL thickness, signal threshold ＞6. Computer image analysis system was used to measure the RNFL thickness from superior, inferior, temporal and nasal quadrants, and the average RNFL thickness. The changes of RNFL thickness between the two groups and between different eyes of the same group were compared. Results Compared with the normal control group, the average (t=5.591), superior (t=8.169, 8.053) and inferior (t=12.596, 11.377) thickness of RNFL in both eyes in AD group were thinner, the differences were significant (P＜0.05); the temporal (t=1.966, 0.838）and nasal (t=2.071, 0.916) thickness of RNFL in both eyes of AD group were thinner, but the difference was not statistically significant (P＞0.05). There was no significant difference of the mean and different quadrant RNFL thickness between different eyes in AD group and normal control group (AD group: t=0.097, 0.821, 0.059, 0.020, 0.116; normal control group: t=0.791, 1.938, 1.806, 2.058, 1.005; P＞0.05). Conclusion The RNFL thickness around the optic disc in AD patients is thinner; This occurs first in superior and inferior quadrants of the optic disc.
This study aims to explore the diagnosis in patients with Alzheimer's disease (AD) based on magnetic resonance (MR) images, and to compare the differences of bilateral hippocampus in classification and recognition. MR images were obtained from 25 AD patients and 25 normal controls (NC) respectively. Three-dimensional texture features were extracted from bilateral hippocampus of each subject. The texture features that existed significant differences between AD and NC were used as the features in a classification procedure. Back propagation (BP) neural network model was built to classify AD patients from healthy controls. The classification accuracy of three methods, which were principal components analysis, linear discriminant analysis and non-linear discriminant analysis, was obtained and compared. The correlations between bilateral hippocampal texture parameters and Mini-Mental State Examination (MMSE) scores were calculated. The classification accuracy of nonlinear discriminant analysis with a neural network model was the highest, and the classification accuracy of right hippocampus was higher than that of the left. The bilateral hippocampal texture features were correlated to MMSE scores, and the relative of right hippocampus was higher than that of the left. The neural network model with three-dimensional texture features could recognize AD patients and NC, and right hippocampus might be more helpful to AD diagnosis.
Alzheimer's disease is a common neuro-degenerative disease. The clinical diagnosis mainly depends on the patient's complaint, the score of mini-mental state examination and Montreal cognitive assessment scale, and the comprehensive judgment of MRI and other imaging examinations. Retina is homologous to brain tissue, and their vascular systems have similar physiological characteristics to small blood vessels in the brain. Numerous studies found that the thickness of retinal nerve fiber layer, visual function, retinal blood vessels and retinal oxygen saturation were changed in AD patients to different degrees. To explore the formation mechanism and significance of ocular fundus changes in AD patients will be helpful to select specific, sensitive and simple methods for early observation and evaluation of AD.
ObjectiveTo obverse the changes of macular choroidal thickness (CT) in patients with mild to moderate Alzheimer’s disease (AD).MethodsThis was a case-control study. Twenty-one patients with mild to moderate AD confirmed by Neurology Department of Jinhua Central Hospital from November 2016 to June 2018 and 21 age-matched control subjects were concluded in the study. There was no significant difference in age (t=0.128), intraocular pressure (t=0.440) and axial length (t=1.202) between the two groups (P＞0.05). There was significant difference in mini-mental state examination score (t=8.608, P＜0.05). CT was measured by OCT with enhanced depth imaging technique in the subfoveal choroid, at 0.5 mm and 1.0 mm from the center of the fovea nasal (NCT0.5, 1.0 mm), temporal (TCT0.5, 1.0 mm), superior (SCT0.5, 1 .0 mm), and inferior (ICT0.5, 1.0 mm). Independent-samples t test was used to compare the results obtained from these two groups.ResultsSFCT (t=2.431), NCT0.5, 1.0 mm (t=3.341, 2.640), TCT0.5, 1.0 mm (t=3.340, 2.899), SCT0.5, 1.0 mm (t=3.576, 3.751) and ICT0.5, 1.0 mm (t=2.897, 2.903) were significantly thinner in AD eyes than those in control eyes.ConclusionCompared with healthy subjects, patients with mild to moderate AD showed a significant reduction in CT.
Wavelet entropy is a quantitative index to describe the complexity of signals. Continuous wavelet transform method was employed to analyze the spontaneous electroencephalogram (EEG) signals of mild, moderate and severe Alzheimer's disease (AD) patients and normal elderly control people in this study. Wavelet power spectrums of EEG signals were calculated based on wavelet coefficients. Wavelet entropies of mild, moderate and severe AD patients were compared with those of normal controls. The correlation analysis between wavelet entropy and MMSE score was carried out. There existed significant difference on wavelet entropy among mild, moderate, severe AD patients and normal controls (P<0.01). Group comparisons showed that wavelet entropy for mild, moderate, severe AD patients was significantly lower than that for normal controls, which was related to the narrow distribution of their wavelet power spectrums. The statistical difference was significant (P<0.05). Further studies showed that the wavelet entropy of EEG and the MMSE score were significantly correlated (r=0.601-0.799, P<0.01). Wavelet entropy is a quantitative indicator describing the complexity of EEG signals. Wavelet entropy is likely to be an electrophysiological index for AD diagnosis and severity assessment.
The pathogenesis of Alzheimer's disease (AD), a common neurodegenerative disease, is still unknown. It is difficult to determine the atrophy areas, especially for patients with mild cognitive impairment (MCI) at different stages of AD, which results in a low diagnostic rate. Therefore, an early diagnosis model of AD based on 3-dimensional convolutional neural network (3DCNN) and genetic algorithm (GA) was proposed. Firstly, the 3DCNN was used to train a base classifier for each region of interest (ROI). And then, the optimal combination of the base classifiers was determined with the GA. Finally, the ensemble consisting of the chosen base classifiers was employed to make a diagnosis for a patient and the brain regions with significant classification capability were decided. The experimental results showed that the classification accuracy was 88.6% for AD vs. normal control (NC), 88.1% for MCI patients who will convert to AD (MCIc) vs. NC, and 71.3% for MCI patients who will not convert to AD (MCInc) vs. MCIc. In addition, with the statistical analysis of the behavioral domains corresponding to ROIs (i.e. brain regions), besides left hippocampus, medial and lateral amygdala, and left para-hippocampal gyrus, anterior superior temporal sulcus of middle temporal gyrus and dorsal area 23 of cingulate gyrus were also found with GA. It is concluded that the functions of the selected brain regions mainly are relevant to emotions, memory, cognition and the like, which is basically consistent with the symptoms of indifference, memory losses, mobility decreases and cognitive declines in AD patients. All of these show that the proposed method is effective.
ObjectiveTo conduct a meta-analysis comparing the accuracy of artificial intelligence (AI)-assisted diagnostic systems based on 18F-fluorodeoxyglucose PET/CT (18F-FDG PET/CT) and structural MRI (sMRI) in the diagnosis of Alzheimer's disease (AD). MethodsOriginal studies dedicated to the development or validation of AI-assisted diagnostic systems based on 18F-FDG PET/CT or sMRI for AD diagnosis were retrieved from the Web of Science, PubMed, and Embase databases. Studies meeting the inclusion criteria were collected, and the risk of bias and clinical applicability of the included studies were assessed using the PROBAST checklist. The pooled sensitivity, specificity, and area under the summary receiver operating characteristic (SROC) curve (AUC) were calculated using a bivariate random-effects model. ResultsTwenty-six studies met the inclusion criteria, yielding a total of 38 2×2 contingency tables related to diagnostic performance. Specifically, 24 contingency tables were based on 18F-FDG PET/CT to distinguish AD patients from normal cognitive (NC) controls, and 14 contingency tables were based on sMRI for the same purpose. The meta-analysis results showed that for 18F-FDG PET/CT, the AI-assisted diagnostic systems had a pooled sensitivity, specificity, and SROC-AUC of 89% (95%CI 88% to 91%), 93% (95%CI 91% to 94%), and 0.96 (95%CI 0.93 to 0.97), respectively. For sMRI, the AI-assisted diagnostic systems had a pooled sensitivity, specificity, and SROC-AUC of 88% (95%CI 85% to 90%), 90% (95%CI 87% to 92%), and 0.94 (95%CI 0.92 to 0.96), respectively. ConclusionAI-assisted diagnostic systems based on either 18F-FDG PET/CT or sMRI demonstrated similar performance in the diagnosis of AD, with both showing high accuracy.
ObjectiveTo systematically review the correlation between apolipoprotein E (ApoE) polymorphism and sporadic Alzheimer's disease (SAD) in Chinese population. MethodsThe case-control studies about the relationship between ApoE polymorphism and SAD in Chinese population were electronically retrieved in PubMed, EMbase, CBM, The Cochrane Library (Issue 8, 2013), CNKI, VIP, and WanFang Data from the date of their establishment to August 2013. Literature screening according to the inclusion and exclusion criteria, data extraction and methodological quality assessment of the included stuides were completed by two reviewers independently. Meta-analysis was then conducted using Stata 12.0 software. ResultsA total of 50 case-control studies invovling 3 396 cases and 4 917 controls were finally included. The results of meta-analysis showed that, in Chinese, the risk of SAD was 2.89 times higher in population with allele ε4 than in population with allele ε3 (OR=2.89, 95%CI 2.61 to 3.19, P < 0.001); 7.24 times higher in those with ε4/ε4 genotype than in those with ε3/ε3 genotype (OR=7.24, 95%CI 5.11 to 10.24, P < 0.001); 2.90 times higher in ε3/ε4 genotype than in ε3/ε3 genotype (OR=2.90, 95%CI 2.56 to 3.29, P < 0.001); 2.11 times higher in ε2/ε4 genotype than in ε3/ε3 genotype (OR=2.11, 95%CI 1.64 to 2.72, P < 0.001); and no statistic significance was found in the risk of SAD compared ε2/ε3, ε2/ε2 genotypes and ε2 allele with ε3/ε3 genotype and ε3 allele. ConclusionFor Chinese population, ApoE allele ε4 is significantly associated with the onset of SAD, and genotype ε4/ε4 is a high risk factor of SAD. While allele ε2 is not associated with the onset of SAD. Since a great deal of current studies failed to conduct stratified analysis, it is suggested to further conduct relevant relevant studies according to clinical classification of SAD and patients' characteristics.