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Purpose: We investigated the volumetric changes in the components of the cholinergic pathway for patients with early mild cognitive impairment (EMCI) and those with late mild cognitive impairment (LMCI). The effect of patients' apolipoprotein 4 (APOE-ε4) allele status on the structural changes were analyzed. Methods: Structural magnetic resonance imaging data were collected. Patients' demographic information, plasma data, and validated global cognitive composite scores were included. Relevant features were extracted for constructing machine learning models to differentiate between EMCI (n = 312) and LMCI (n = 541) and predict patients' neurocognitive function. The data were analyzed primarily through one-way analysis of variance and two-way analysis of covariance. Results: Considerable differences were observed in cholinergic structural changes between patients with EMCI and LMCI. Cholinergic atrophy was more prominent in the LMCI cohort than in the EMCI cohort (P < 0.05 family-wise error corrected). APOE-ε4 differentially affected cholinergic atrophy in the LMCI and EMCI cohorts. For LMCI cohort, APOE-ε4 carriers exhibited increased brain atrophy (left amygdala: P = 0.001; right amygdala: P = 0.006, and right Ch123, P = 0.032). EMCI and LCMI patients showed distinctive associations of gray matter volumes in cholinergic regions with executive (R2 = 0.063 and 0.030 for EMCI and LMCI, respectively) and language (R2 = 0.095 and 0.042 for EMCI and LMCI, respectively) function. Conclusions: Our data confirmed significant cholinergic atrophy differences between early and late stages of mild cognitive impairment. The impact of the APOE-ε4 allele on cholinergic atrophy varied between the LMCI and EMCI groups. [ABSTRACT FROM AUTHOR]

Deep Auto-Encoders (DAE) have been widely used in dimensionality reduction and feature extraction of brain functional networks. However, the features in aggregation matrices of functional networks obtained by DAE dimensionality reduction might lose part of time-varying information, so that DAE cannot learn the distribution of original features well. To solve these problems, we extracted and analyzed brain functional statuses for early Mild Cognitive Impairment (eMCI) based on Variational Auto-Encoder (VAE). The high dimensions of features in aggregation matrices of dynamic functional networks were reduced by VAE to obtain the corresponding hidden variable matrices. Gaussian Mixture Model (GMM) was used to cluster the features in the hidden variable matrices to form several Common Functional Networks (CFNs) representing different functional statuses. We analyzed the similarities and differences of functional statuses between eMCI subjects and normal subjects in different sub-segments, as well as the switching of functional statuses in the entire time series. The experimental results show that there are similarities between the most frequent functional statuses of the two types of subjects and differences between the least frequent functional statuses. The proposed method can more significantly reveal the similarity and difference of functional statuses between eMCI subjects and normal subjects than the comparable methods, and the switching rule of functional statuses can help better understand the dynamic characteristics of brain functional networks for eMCI patients. [ABSTRACT FROM AUTHOR]

Dementia is a term used to describe a variety of symptoms related to cognitive impairment in which Alzheimer disease represents 60% – 70% of the cases. As of today, there is no cure for this disease and the only way to prevent any associated medical, economic, and financial impacts or losses is to detect the disease early and work closely with suspected patients to prevent any further progress. In this research, a methodology consisting of 4 modules is proposed: (1) preprocessing, exemplar pyramid along with bi-linear interpolation followed by (2) feature extraction using Gray Level Co-Occurrence Matrix and Local Binary Pattern then (3) concatenation of all extracted features and finally (4) classification of Alzheimer disease stage using deep learning, Multi-Layer Perceptron, in particular. Our proposed method was tested using the MPRAGE structural MRI dataset from Alzheimer Disease Neuro Imaging Initiative (ADNI), and it outperformed other techniques used in the literature review. An accuracy result of 89.80 was reported for multi-class classification of 4 stages of Alzheimer disease (Cognitive Normal, Early Mild Cognitive Impairment, Late Mild Cognitive Impairment and Alzheimer Disease) for both Gray Matter (GM) and White Matter (WM). In term of binary-class classification, we were able to achieve very good results using both GM and WM. By using GM, we were able to distinguish between CN vs EMCI, EMCI vs AD and LMCI vs AD with accuracy results of 96.43%, 90.91% and 95.24% respectively. And using WM, we were able to distinguish between CN vs LMCI with 100% accuracy and EMCI vs LMCI with 95.65% accuracy. While we achieved the same accuracy result of 96.15 using both WM and GM.

Introduction: Amnestic mild cognitive impairment (MCI) can be classified as either early MCI (EMCI) or late MCI (LMCI) according to the severity of memory impairment. The aim of this study was to compare the prognosis and clinical course between EMCI and LMCI. Methods: Between January 2009 and December 2017, a total of 418 patients with MCI and 146 subjects with normal cognition were recruited from a memory clinic. All the patients received at least two series of neuropsychological evaluations each year and were categorized as either EMCI or LMCI according to Alzheimer's Disease Neuroimaging Initiative 2 (ADNI2) criteria. Results: In total, our study included 161 patients with EMCI, 258 with LMCI, and 146 subjects with normal cognition as controls (NCs). The mean follow-up duration was 3.55 ± 2.18 years (range: 1–9). In a first-year follow-up assessment, 54 cases (32.8%) of EMCI and 16 (5%) of LMCI showed a normal cognitive status. There was no significant difference between the first year EMCI reverter and NCs in terms of dementia-free survival and further cognitive decline. However, first-year LMCI reverters still had a higher risk of cognitive decline during the following evaluations. Until the last follow-up, annual dementia conversion rates were 1.74, 4.33, and 18.6% in the NC, EMCI, and LMCI groups, respectively. The EMCI and LMCI groups showed a higher rate of progression to dementia (log-rank test, p < 0.001) than normal subjects. Compared with NCs, patients in the LMCI group showed a significantly faster annual decline in global cognition [annual rate of change for the mini-mental status examination (MMSE) score: −1.035, p < 0.001]) and all cognitive domains, while those in the EMCI group showed a faster rate of decline in global cognitive function (annual rate of change for the MMSE score: −0.299, p = 0.001). Conclusion: It is important to arrange follow-up visits for patients with MCI, even in the EMCI stage. One-year short-term follow-up may provide clues about the progression of cognitive function and help to identify relatively low-risk EMCI subjects. [ABSTRACT FROM AUTHOR]

IntroductionAmnestic mild cognitive impairment (MCI) can be classified as either early MCI (EMCI) or late MCI (LMCI) according to the severity of memory impairment. The aim of this study was to compare the prognosis and clinical course between EMCI and LMCI.MethodsBetween January 2009 and December 2017, a total of 418 patients with MCI and 146 subjects with normal cognition were recruited from a memory clinic. All the patients received at least two series of neuropsychological evaluations each year and were categorized as either EMCI or LMCI according to Alzheimer's Disease Neuroimaging Initiative 2 (ADNI2) criteria.ResultsIn total, our study included 161 patients with EMCI, 258 with LMCI, and 146 subjects with normal cognition as controls (NCs). The mean follow-up duration was 3.55 ± 2.18 years (range: 1–9). In a first-year follow-up assessment, 54 cases (32.8%) of EMCI and 16 (5%) of LMCI showed a normal cognitive status. There was no significant difference between the first year EMCI reverter and NCs in terms of dementia-free survival and further cognitive decline. However, first-year LMCI reverters still had a higher risk of cognitive decline during the following evaluations. Until the last follow-up, annual dementia conversion rates were 1.74, 4.33, and 18.6% in the NC, EMCI, and LMCI groups, respectively. The EMCI and LMCI groups showed a higher rate of progression to dementia (log-rank test, p < 0.001) than normal subjects. Compared with NCs, patients in the LMCI group showed a significantly faster annual decline in global cognition [annual rate of change for the mini-mental status examination (MMSE) score: −1.035, p < 0.001]) and all cognitive domains, while those in the EMCI group showed a faster rate of decline in global cognitive function (annual rate of change for the MMSE score: −0.299, p = 0.001).ConclusionIt is important to arrange follow-up visits for patients with MCI, even in the EMCI stage. One-year short-term follow-up may provide clues about the progression of cognitive function and help to identify relatively low-risk EMCI subjects.

Currently, it remains one of the most challenging issues to distinguish brain functional networks of early mild cognitive impairment subjects (eMCIs) and normal control subjects (NCs). Unlike images, functional networks are non‐Euclidean data and not easily classified by dilated convolutional neural network (DCNN). To address this problem, we developed a sparse structure deep network embedding (SSDNE) method which transforms brain functional networks into a double‐channel image in eMCI classification. First, the eigenvector of each node in the functional network was obtained by SSDNE, and principal component analysis (PCA) was employed to sort the importance of eigenvectors. Next, two eigenvector groups with the highest contribution rate were extracted in turn and divided into several equal‐length intervals along its direction respectively, and the numbers of nodes that fall into the intervals were counted to obtain the corresponding two‐dimensional histograms. Then, the both histograms were stacked up and down into a double‐channel image. Finally, a double‐channel image was input into DCNN for feature learning to achieve final classification results. Experimental results show that, SSDNE performed better in maintaining the original structure of brain functional networks, and the transformed double‐channel image achieved comparably identifying results on eMCI classification compared with other network embedding algorithms. This novel method solved the problem that brain functional networks cannot be directly applied to convolutional neural networks for feature extraction and classification. Meanwhile, it can provide a reference for the early auxiliary diagnosis of Alzheimer's disease (AD). [ABSTRACT FROM AUTHOR]

People suffering from mild cognitive impairment (MCI) are at an increased risk of developing Alzheimer's disease (AD) or another dementia. High prevalence will possibly be reduced if early interventions could be applied to the stage of early MCI (eMCI). In network-based classification, brain functional networks are often constructed, relying on the entire time series. It can lead to the neglect of the complex and dynamic interaction relationships among brain regions. As a result, the features derived from this type of functional network may fail to serve as an effective disease biomarker. To address this problem, we proposed a multi-scale feature combination framework for the eMCI classification. In this framework, global static features, time-varying features, and more refined features could be able to flexibly extract from static functional networks, dynamic functional networks, and high-order functional networks, respectively. Then, they are utilized to train and test the classification model in the form of feature combination. The experimental results have verified that the proposed method achieves superior classification accuracy than other competed methods in the eMCI classification, indicating a great potential in understanding the dysfunction of the brain regions.

Brain functional networks constructed via regularization has been widely used in early mild cognitive impairment (eMCI) classification. However, few methods can properly reflect the similarities and differences of functional connections among different people. Most methods ignore some topological attributes, such as connection strength, which may delete strong functional connections in brain functional networks. To overcome these limitations, we propose a novel method to construct dynamic functional networks (DFN) based on weighted regularization (WR) and tensor low-rank approximation (TLA), and apply it to identify eMCI subjects from normal subjects. First, we introduce the WR term into the DFN construction and obtain WR-based DFNs (WRDFN). Then, we combine the WRDFNs of all subjects into a third-order tensor for TLA processing, and obtain the DFN based on WR and TLA (WRTDFN) of each subject in the tensor. We calculate the weighted-graph local clustering coefficient of each region in each WRTDFN as the effective feature, and use the t-test for feature selection. Finally, we train a linear support vector machine (SVM) classifier to classify the WRTDFNs of all subjects. Experimental results demonstrate that the proposed method can obtain DFNs with the scale-free property, and that the classification accuracy (ACC), the sensitivity (SEN), the specificity (SPE), and the area under curve (AUC) reach 87.0662% ± 0.3202%, 83.4363% ± 0.5076%, 90.6961% ± 0.3250% and 0.9431 ± 0.0023, respectively. We also achieve the best classification results compared with other comparable methods. This work can effectively improve the classification performance of DFNs constructed by existing methods for eMCI and has certain reference value for the early diagnosis of Alzheimer’s disease (AD).

• Developing a new probabilistic approach for obtaining the most relevant features from MRI and PET data. • Achieving higher accuracy in diagnosis of the EMCI from CN compared with the previous studies. • The proposed algorithm is able to rank the features based on their importance in every state of Alzheimer's disease. • Validating the results considering 896 subjects including 296 EMCI subjects as the first study to consider such a large number of EMCI. Diagnosis of early mild cognitive impairment (EMCI) as a prodromal stage of Alzheimer's disease (AD) with its delineation from the cognitively normal (CN) group remains a challenging but essential step for the planning of early treatment. Although several studies have focused on the MCI diagnosis, this study introduces the early stage of MCI to assess more thoroughly the earliest signs of disease manifestation and progression. We used random forest feature selection model with a Gaussian-based algorithm to perform method evaluation. This integrated method serves to define multivariate normal distributions in order to classify different stages of AD, with the focus placed on detecting EMCI subjects in the most challenging classification of CN vs. EMCI. Using 896 participants classified into the four categories of CN, EMCI, late mild cognitive impairment (LMCI) and AD, the results show that the EMCI group can be delineated from the CN group with a relatively high accuracy of 78.8% and sensitivity of 81.3%. The feature selection model and classifier are compared with some other prominent algorithms. Although higher accuracy has been achieved using the Gaussian process (GP) model (78.8%) over the SVM classifier (75.6%) for CN vs. EMCI classification, with 0.05 being the cutoff for significance, and based on student's t-test, it was determined that the differences for accuracy, sensitivity, specificity between the GP method and support vector machine (SVM) are not statistically significant. Addressing the challenging classification of CN vs. EMCI provides useful information to help clinicians and researchers determine essential measures that can help in the early detection of AD. [ABSTRACT FROM AUTHOR]

Brain functional networks constructed via regularization has been widely used in early mild cognitive impairment (eMCI) classification. However, few methods can properly reflect the similarities and differences of functional connections among different people. Most methods ignore some topological attributes, such as connection strength, which may delete strong functional connections in brain functional networks. To overcome these limitations, we propose a novel method to construct dynamic functional networks (DFN) based on weighted regularization (WR) and tensor low-rank approximation (TLA), and apply it to identify eMCI subjects from normal subjects. First, we introduce the WR term into the DFN construction and obtain WR-based DFNs (WRDFN). Then, we combine the WRDFNs of all subjects into a third-order tensor for TLA processing, and obtain the DFN based on WR and TLA (WRTDFN) of each subject in the tensor. We calculate the weighted-graph local clustering coefficient of each region in each WRTDFN as the effective feature, and use the t -test for feature selection. Finally, we train a linear support vector machine (SVM) classifier to classify the WRTDFNs of all subjects. Experimental results demonstrate that the proposed method can obtain DFNs with the scale-free property, and that the classification accuracy (ACC), the sensitivity (SEN), the specificity (SPE), and the area under curve (AUC) reach 87.0662% ± 0.3202%, 83.4363% ± 0.5076%, 90.6961% ± 0.3250% and 0.9431 ± 0.0023, respectively. We also achieve the best classification results compared with other comparable methods. This work can effectively improve the classification performance of DFNs constructed by existing methods for eMCI and has certain reference value for the early diagnosis of Alzheimer's disease (AD)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jiao, Ji, Zhang, Shi and Wang.)