Mild Cognitive Impairment Classification Research Articles

Integrating Biomarkers From Virtual Reality and Magnetic Resonance Imaging for the Early Detection of Mild Cognitive Impairment Using a Multimodal Learning Approach: Validation Study.

Early detection of mild cognitive impairment (MCI), a transitional stage between normal aging and Alzheimer disease, is crucial for preventing the progression of dementia. Virtual reality (VR) biomarkers have proven to be effective in capturing behaviors associated with subtle deficits in instrumental activities of daily living, such as challenges in using a food-ordering kiosk, for early detection of MCI. On the other hand, magnetic resonance imaging (MRI) biomarkers have demonstrated their efficacy in quantifying observable structural brain changes that can aid in early MCI detection. Nevertheless, the relationship between VR-derived and MRI biomarkers remains an open question. In this context, we explored the integration of VR-derived and MRI biomarkers to enhance early MCI detection through a multimodal learning approach. We aimed to evaluate and compare the efficacy of VR-derived and MRI biomarkers in the classification of MCI while also examining the strengths and weaknesses of each approach. Furthermore, we focused on improving early MCI detection by leveraging multimodal learning to integrate VR-derived and MRI biomarkers. The study encompassed a total of 54 participants, comprising 22 (41%) healthy controls and 32 (59%) patients with MCI. Participants completed a virtual kiosk test to collect 4 VR-derived biomarkers (hand movement speed, scanpath length, time to completion, and the number of errors), and T1-weighted MRI scans were performed to collect 22 MRI biomarkers from both hemispheres. Analyses of covariance were used to compare these biomarkers between healthy controls and patients with MCI, with age considered as a covariate. Subsequently, the biomarkers that exhibited significant differences between the 2 groups were used to train and validate a multimodal learning model aimed at early screening for patients with MCI among healthy controls. The support vector machine (SVM) using only VR-derived biomarkers achieved a sensitivity of 87.5% and specificity of 90%, whereas the MRI biomarkers showed a sensitivity of 90.9% and specificity of 71.4%. Moreover, a correlation analysis revealed a significant association between MRI-observed brain atrophy and impaired performance in instrumental activities of daily living in the VR environment. Notably, the integration of both VR-derived and MRI biomarkers into a multimodal SVM model yielded superior results compared to unimodal SVM models, achieving higher accuracy (94.4%), sensitivity (100%), specificity (90.9%), precision (87.5%), and F1-score (93.3%). The results indicate that VR-derived biomarkers, characterized by their high specificity, can be valuable as a robust, early screening tool for MCI in a broader older adult population. On the other hand, MRI biomarkers, known for their high sensitivity, excel at confirming the presence of MCI. Moreover, the multimodal learning approach introduced in our study provides valuable insights into the improvement of early MCI detection by integrating a diverse set of biomarkers.

Classification of Mild Cognitive Impairment Using Functional Near-Infrared Spectroscopy-Derived Biomarkers With Convolutional Neural Networks.

To date, early detection of mild cognitive impairment (MCI) has mainly depended on paper-based neuropsychological assessments. Recently, biomarkers for MCI detection have gained a lot of attention because of the low sensitivity of neuropsychological assessments. This study proposed the functional near-infrared spectroscopy (fNIRS)-derived data with convolutional neural networks (CNNs) to identify MCI. Eighty-two subjects with MCI and 148 healthy controls (HC) performed the 2-back task, and their oxygenated hemoglobin (HbO2) changes in the prefrontal cortex (PFC) were recorded during the task. The CNN model based on fNIRS-derived spatial features with HbO2 slope within time windows was trained to classify MCI. Thereafter, the 5-fold cross-validation approach was used to evaluate the performance of the CNN model. Significant differences in averaged HbO2 values between MCI and HC groups were found, and the CNN model could better discriminate MCI with over 89.57% accuracy than the Korean version of the Montreal Cognitive Assessment (MoCA) (89.57%). Specifically, the CNN model based on HbO2 slope within the time window of 20-60 seconds from the left PFC (96.09%) achieved the highest accuracy. These findings suggest that the fNIRS-derived spatial features with CNNs could be a promising way for early detection of MCI as a surrogate for a conventional screening tool and demonstrate the superiority of the fNIRS-derived spatial features with CNNs to the MoCA.

Prediction Of Mild Cognitive Impairment to Alzheimer’s Disease Conversion Via Machine Learning

Alzheimer’s Disease (AD) is a progressive neurodegenerative condition characterized by deterioration of cognitive functions. Although there does not exist a cure for AD, early diagnosis and intervention during stages of Mild Cognitive Impairment (MCI) can be incredibly beneficial in slowing its development. However, predicting the conversion from MCI to AD remains a challenging task. This paper aims to provide an overview of the current research on predicting MCI to AD conversion, with a focus on machine learning methodologies to aid feature extraction and classification. Through a literature review, we aim to offer insights into the latest state-of-the-art techniques to predict MCI to AD conversion as well as prevailing trends in this field including deep learning, transfer learning, contrastive learning, and graph neural networks. We conclude from our study that utilizing AD/HC classes for feature extraction is a promising approach for generating discriminative features for stable MCI and progressive MCI classification. In addition, employing multi-modality models is instrumental in attaining a robust validation framework for the early diagnosis of AD.

A deep feature fusion network with global context and cross-dimensional dependencies for classification of mild cognitive impairment from brain MRI

Background and objectives:The accurate identification of people with Mild Cognitive Impairment (MCI) who may develop Alzheimer's disease (AD) holds significant importance in facilitating timely intervention and treatment. However, current classification methods have yet to be effective due to the subtle nature of the features involved. This research aims to improve the performance of the MCI classification by enhancing the feature representation in brain MRI. MethodsWe propose an integrated model that combines Group Shuffle Depth-wise Convolution (GSDW), Global Context Network (GCN), Hybrid Multi-Focus Attention Block (HMAB), and EfficientNet-B0 architecture for MCI classification. This model extracts fine-grained features, contextual information, and long-range dependencies and aggregates low-level details with high-level context information to learn discriminative features. ResultsOur comprehensive evaluation demonstrates significant improvements in the classification performance for both progressive MCI (pMCI) and stable MCI (sMCI), surpassing existing approaches. The proposed model achieved a notable accuracy of 77.2%. ConclusionsThis study introduces a novel feature fusion technique that combines global contextual representations and cross-dimensional dependencies to enhance classification results. These findings highlight the potential of the proposed framework for early identification and intervention in individuals at risk of cognitive decline.

Categorization of Alzheimer's disease stages using deep learning approaches with McNemar's test.

Early diagnosis is crucial in Alzheimer's disease both clinically and for preventing the rapid progression of the disease. Early diagnosis with awareness studies of the disease is of great importance in terms of controlling the disease at an early stage. Additionally, early detection can reduce treatment costs associated with the disease. A study has been carried out on this subject to have the great importance of detecting Alzheimer's disease at a mild stage and being able to grade the disease correctly. This study's dataset consisting of MRI images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) was split into training and testing sets, and deep learning-based approaches were used to obtain results. The dataset consists of three classes: Alzheimer's disease (AD), Cognitive Normal (CN), and Mild Cognitive Impairment (MCI). The achieved results showed an accuracy of 98.94% for CN vs AD in the one vs one (1 vs 1) classification with the EfficientNetB0 model and 99.58% for AD vs CNMCI in the one vs All (1 vs All) classification with AlexNet model. In addition, in the study, an accuracy of 98.42% was obtained with the EfficientNet121 model in MCI vs CN classification. These results indicate the significant potential for mild stage Alzheimer's disease detection of Alzheimer's disease. Early detection of the disease in the mild stage is a critical factor in preventing the progression of Alzheimer's disease. In addition, a variant of the non-parametric statistical McNemar's Test was applied to determine the statistical significance of the results obtained in the study. Statistical significance of 1 vs 1 and 1 vs all classifications were obtained for EfficientNetB0, DenseNet, and AlexNet models.

The role of perfusion, grey matter volume and behavioural phenotypes in the data-driven classification of cognitive syndromes

BackgroundThe use of structural and perfusion brain imaging in combination with behavioural information in the prediction of cognitive syndromes using a data-driven approach remains to be explored. Here, we thus examined the contribution of brain structural and perfusion imaging and behavioural features to the existing classification of cognitive syndromes using a data-driven approach.MethodsStudy participants belonged to the community-based Biomarker and Cognition Cohort Study in Singapore who underwent neuropsychological assessments, structural-functional MRI and blood biomarkers. Participants had a diagnosis of cognitively normal (CN), subjective cognitive impairment (SCI), mild cognitive impairment (MCI) and dementia. Cross-sectional structural and cerebral perfusion imaging, behavioural scale data including mild behaviour impairment checklist, Pittsburgh Sleep Quality Index and Depression, Anxiety and Stress scale data were obtained.ResultsThree hundred seventy-three participants (mean age 60.7 years; 56% female sex) with complete data were included. Principal component analyses demonstrated that no single modality was informative for the classification of cognitive syndromes. However, multivariate glmnet analyses revealed a specific combination of frontal perfusion and temporo-frontal grey matter volume were key protective factors while the severity of mild behaviour impairment interest sub-domain and poor sleep quality were key at-risk factors contributing to the classification of CN, SCI, MCI and dementia (p < 0.0001). Moreover, the glmnet model showed best classification accuracy in differentiating between CN and MCI cognitive syndromes (AUC = 0.704; sensitivity = 0.698; specificity = 0.637).ConclusionsBrain structure, perfusion and behavioural features are important in the classification of cognitive syndromes and should be incorporated by clinicians and researchers. These findings illustrate the value of using multimodal data when examining syndrome severity and provide new insights into how cerebral perfusion and behavioural impairment influence classification of cognitive syndromes.

Machine learning-based prediction of mild cognitive impairment among individuals with normal cognitive function.

Previous studies mainly focused on risk factors in patients with mild cognitive impairment (MCI) or dementia. The aim of the study was to provide basis for preventing MCI in cognitive normal populations. The data came from a longitudinal retrospective study involving individuals with brain magnetic resonance imaging scans, clinical visits, and cognitive assessment with interval of more than 3 years. Multiple machine-learning technologies, including random forest, support vector machine, logistic regression, eXtreme Gradient Boosting, and naïve Bayes, were used to establish a prediction model of a future risk of MCI through a combination of clinical and image variables. Among these machine learning models; eXtreme Gradient Boosting (XGB) was the best classification model. The classification accuracy of clinical variables was 65.90%, of image variables was 79.54%, of a combination of clinical and image variables was 94.32%. The best result of the combination was an accuracy of 94.32%, a precision of 96.21%, and a recall of 93.08%. XGB with a combination of clinical and image variables had a potential prospect for the risk prediction of MCI. From clinical perspective, the degree of white matter hyperintensity (WMH), especially in the frontal lobe, and the control of systolic blood pressure (SBP) were the most important risk factor for the development of MCI. The best MCI classification results came from the XGB model with a combination of both clinical and imaging variables. The degree of WMH in the frontal lobe and SBP control were the most important variables in predicting MCI.

A Transformer Approach for Cognitive Impairment Classification and Prediction.

Early classification and prediction of Alzheimer disease (AD) and amnestic mild cognitive impairment (aMCI) with noninvasive approaches is a long-standing challenge. This challenge is further exacerbated by the sparsity of data needed for modeling. Deep learning methods offer a novel method to help address these challenging multiclass classification and prediction problems. We analyzed 3 target feature-sets from the National Alzheimer Coordinating Center (NACC) dataset: (1) neuropsychological (cognitive) data; (2) patient health history data; and (3) the combination of both sets. We used a masked Transformer-encoder without further feature selection to classify the samples on cognitive status (no cognitive impairment, aMCI, AD)-dynamically ignoring unavailable features. We then fine-tuned the model to predict the participants' future diagnosis in 1 to 3 years. We analyzed the sensitivity of the model to input features via Feature Permutation Importance. We demonstrated (1) the masked Transformer-encoder was able to perform prediction with sparse input data; (2) high multiclass current cognitive status classification accuracy (87% control, 79% aMCI, 89% AD); (3) acceptable results for 1- to 3-year multiclass future cognitive status prediction (83% control, 77% aMCI, 91% AD). The flexibility of our methods in handling inconsistent data provides a new venue for the analysis of cognitive status data.

Deep Fusion of Multi-Template Using Spatio-Temporal Weighted Multi-Hypergraph Convolutional Networks for Brain Disease Analysis.

Conventional functional connectivity network (FCN) based on resting-state fMRI (rs-fMRI) can only reflect the relationship between pairwise brain regions. Thus, the hyper-connectivity network (HCN) has been widely used to reveal high-order interactions among multiple brain regions. However, existing HCN models are essentially spatial HCN, which reflect the spatial relevance of multiple brain regions, but ignore the temporal correlation among multiple time points. Furthermore, the majority of HCN construction and learning frameworks are limited to using a single template, while the multi-template carries richer information. To address these issues, we first employ multiple templates to parcellate the rs-fMRI into different brain regions. Then, based on the multi-template data, we propose a spatio-temporal weighted HCN (STW-HCN) to capture more comprehensive high-order temporal and spatial properties of brain activity. Next, a novel deep fusion model of multi-template called spatio-temporal weighted multi-hypergraph convolutional network (STW-MHGCN) is proposed to fuse the STW-HCN of multiple templates, which extracts the deep interrelation information between different templates. Finally, we evaluate our method on the ADNI-2 and ABIDE-I datasets for mild cognitive impairment (MCI) and autism spectrum disorder (ASD) analysis. Experimental results demonstrate that the proposed method is superior to the state-of-the-art approaches in MCI and ASD classification, and the abnormal spatio-temporal hyper-edges discovered by our method have significant significance for the brain abnormalities analysis of MCI and ASD.

Comparing neuropsychological, typical, and ADNI criteria for the diagnosis of mild cognitive impairment in Vietnam-era veterans.

Neuropsychological criteria for mild cognitive impairment (MCI) more accurately predict progression to Alzheimer's disease (AD) and are more strongly associated with AD biomarkers and neuroimaging profiles than ADNI criteria. However, research to date has been conducted in relatively healthy samples with few comorbidities. Given that history of traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are risk factors for AD and common in Veterans, we compared neuropsychological, typical (Petersen/Winblad), and ADNI criteria for MCI in Vietnam-era Veterans with histories of TBI or PTSD. 267 Veterans (mean age = 69.8) from the DOD-ADNI study were evaluated for MCI using neuropsychological, typical, and ADNI criteria. Linear regressions adjusting for age and education assessed associations between MCI status and AD biomarker levels (cerebrospinal fluid [CSF] p-tau181, t-tau, and Aβ42) by diagnostic criteria. Logistic regressions adjusting for age and education assessed the effects of TBI severity and PTSD symptom severity simultaneously on MCI classification by each criteria. Agreement between criteria was poor. Neuropsychological criteria identified more Veterans with MCI than typical or ADNI criteria, and were associated with higher CSF p-tau181 and t-tau. Typical and ADNI criteria were not associated with CSF biomarkers. PTSD symptom severity predicted MCI diagnosis by neuropsychological and ADNI criteria. History of moderate/severe TBI predicted MCI by typical and ADNI criteria. MCI diagnosis using sensitive neuropsychological criteria is more strongly associated with AD biomarkers than conventional diagnostic methods. MCI diagnostics in Veterans would benefit from incorporation of comprehensive neuropsychological methods and consideration of the impact of PTSD.

Multimodal classification of Alzheimer's disease and mild cognitive impairment using custom MKSCDDL kernel over CNN with transparent decision-making for explainable diagnosis

The study presents an innovative diagnostic framework that synergises Convolutional Neural Networks (CNNs) with a Multi-feature Kernel Supervised within-class-similar Discriminative Dictionary Learning (MKSCDDL). This integrative methodology is designed to facilitate the precise classification of individuals into categories of Alzheimer's Disease, Mild Cognitive Impairment (MCI), and Cognitively Normal (CN) statuses while also discerning the nuanced phases within the MCI spectrum. Our approach is distinguished by its robustness and interpretability, offering clinicians an exceptionally transparent tool for diagnosis and therapeutic strategy formulation. We use scandent decision trees to deal with the unpredictability and complexity of neuroimaging data. Considering that different people's brain scans are different, this enables the model to make more detailed individualised assessments and explains how the algorithm illuminates the specific neuroanatomical regions that are indicative of cognitive impairment. This explanation is beneficial for clinicians because it gives them concrete ideas for early intervention and targeted care. The empirical review of our model shows that it makes diagnoses with a level of accuracy that is unmatched, with a classification efficacy of 98.27%. This shows that the model is good at finding important parts of the brain that may be damaged by cognitive diseases.

Mild cognitive impairment prediction and cognitive score regression in the elderly using EEG topological data analysis and machine learning with awareness assessed in affective reminiscent paradigm.

The main objective of this study is to evaluate working memory and determine EEG biomarkers that can assist in the field of health neuroscience. Our ultimate goal is to utilize this approach to predict the early signs of mild cognitive impairment (MCI) in healthy elderly individuals, which could potentially lead to dementia. The advancements in health neuroscience research have revealed that affective reminiscence stimulation is an effective method for developing EEG-based neuro-biomarkers that can detect the signs of MCI. We use topological data analysis (TDA) on multivariate EEG data to extract features that can be used for unsupervised clustering, subsequent machine learning-based classification, and cognitive score regression. We perform EEG experiments to evaluate conscious awareness in affective reminiscent photography settings. We use EEG and interior photography to distinguish between healthy cognitive aging and MCI. Our clustering UMAP and random forest application accurately predict MCI stage and MoCA scores. Our team has successfully implemented TDA feature extraction, MCI classification, and an initial regression of MoCA scores. However, our study has certain limitations due to a small sample size of only 23 participants and an unbalanced class distribution. To enhance the accuracy and validity of our results, future research should focus on expanding the sample size, ensuring gender balance, and extending the study to a cross-cultural context.

Personalized modeling of Alzheimer's disease progression estimates neurodegeneration severity from EEG recordings.

Early identification of Alzheimer's disease (AD) is necessary for a timely onset of therapeutic care. However, cortical structural alterations associated with AD are difficult to discern. We developed a cortical model of AD-related neurodegeneration accounting for slowing of local dynamics and global connectivity degradation. In a monocentric study we collected electroencephalography (EEG) recordings at rest from participants in healthy (HC, n=17), subjective cognitive decline (SCD, n=58), and mild cognitive impairment (MCI, n=44) conditions. For each patient, we estimated neurodegeneration model parameters based on individual EEG recordings. Our model outperformed standard EEG analysis not only in discriminating between HC and MCI conditions (F1 score 0.95vs 0.75) but also in identifying SCD patients with biological hallmarks of AD in the cerebrospinal fluid (recall 0.87vs 0.50). Personalized models could (1) support classification of MCI, (2) assess the presence of AD pathology, and (3) estimate the risk of cognitive decline progression, based only on economical and non-invasive EEG recordings. Personalized cortical model estimating structural alterations from EEG recordings.Discrimination of Mild Cognitive Impairment (MCI) and Healthy (HC) subjects (95%)Prediction of biological markers of Alzheimer's in Subjective Decline (SCD) Subjects (87%)Transition correctly predicted for 3/3 subjects that converted from SCD to MCI after 1y.

A multiclass extreme gradient boosting model for evaluation of transcriptomic biomarkers in Alzheimer’s disease prediction

BackgroundPatients with young-onset Alzheimer's disease (AD) (before the age of 50 years old) often lack obvious imaging changes and amyloid protein deposition, which can lead to misdiagnosis with other cognitive impairments. Considering the association between immunological dysfunction and progression of neurodegenerative disease, recent research has focused on identifying blood transcriptomic signatures for precise prediction of AD. MethodsIn this study, we extracted blood biomarkers from large-scale transcriptomics to construct multiclass eXtreme Gradient Boosting models (XGBoost), and evaluated their performance in distinguishing AD from cognitive normal (CN) and mild cognitive impairment (MCI). ResultsIndependent testing with external dataset revealed that the combination of blood transcriptomic signatures achieved an area under the receiver operating characteristic curve (AUC of ROC) of 0.81 for multiclass classification (sensitivity = 0.81; specificity = 0.63), 0.83 for classification of AD vs. CN (sensitivity = 0.72; specificity = 0.73), and 0.85 for classification of AD vs. MCI (sensitivity = 0.77; specificity = 0.73). These candidate signatures were significantly enriched in 62 chromosome regions, such as Chr.19p12-19p13.3, Chr.1p22.1-1p31.1, and Chr.1q21.2-1p23.1 (adjusted p < 0.05), and significantly overrepresented by 26 transcription factors, including E2F2, FOXO3, and GATA1 (adjusted p < 0.05). Biological analysis of these signatures pointed to systemic dysregulation of immune responses, hematopoiesis, exocytosis, and neuronal support in neurodegenerative disease (adjusted p < 0.05). ConclusionsBlood transcriptomic biomarkers hold great promise in clinical use for the accurate assessment and prediction of AD.

EEG‐based neural biomarker for diagnosis and assessment of mild cognitive impairment and Alzheimer’s disease

AbstractBackgroundElectroencephalogram (EEG) has emerged as a non‐invasive tool to detect the aberrant neuronal activity related to different stages of Alzheimer’s disease (AD). However, the effectiveness of EEG in the precise diagnosis and prediction of AD and its preclinical stage, mild cognitive impairment (MCI), has yet to be fully elucidated. In this study, we aimed to identify key EEG biomarkers that are effective in distinguishing patients at the early stage of AD and monitoring the progression of AD.MethodA total of 890 participants, including 189 patients with MCI, 330 patients with AD, 125 patients with other dementias (frontotemporal dementia, dementia with Lewy bodies, and vascular cognitive impairment), and 246 healthy controls (HC) were enrolled. Biomarkers were extracted from resting‐state EEG recordings for a three‐level classification of HC, MCI, and AD. The optimal EEG biomarkers were then identified based on the classification performance. Random forest regression was used to train a series of predictive models by combining participants’ EEG biomarkers, demographic information (i.e., sex, age), CSF biomarkers, and APOE phenotype for predicting the disease progression and individual’s cognitive function.ResultThe identified EEG biomarkers achieved over 70% accuracy in the three‐level classification of HC, MCI, and AD. Among all six groups, the most prominent effects of AD‐linked neurodegeneration on EEG metrics were localized at parieto‐occipital regions. Noteworthy, the absolute theta power of channel O2 was negatively correlated with Aβ42 (r = ‐0.358, p &lt; 0.001) and positively correlated with p‐tau (r = 0.442, p &lt; 0.001). In terms of cognitive assessment, the Hjorth mobility of channel O1, O2 and P4 were found to be positively associated with MMSE and MoCA scores (r = 0.416‐0.464, all p &lt; 0.001). In the predictive analyses, the optimal EEG features were more effective than the CSF + APOE biomarkers in predicting the age of onset and disease course, whereas the combination of EEG + CSF + APOE measures achieved the best performance for all targets of prediction.ConclusionOur study indicates that EEG can be used as a useful screening tool for the diagnosis and disease progression evaluation of MCI and AD.

Sense of Purpose in Life Predicts Reduced Risk for and Delayed Onset of Mild Cognitive Impairment: A Multistate Survival Model

AbstractBackgroundWith no known cure for Alzheimer’s disease and related dementias, delaying the onset of cognitive decline represents a key target for future dementia research. Sense of purpose has been shown to be associated with high cognitive functioning, more supportive social ties, and greater intellectual activity, and may be valuable for mitigating cognitive impairment both before and following its onset.MethodLongitudinal data from the Health and Retirement Study (HRS, n = 10,542) and the Rush Memory and Aging Project (MAP, n = 10.48) were used to examine associations between sense of purpose and prospective transitions across normal cognition, mild cognitive impairment (MCI), dementia, and death over up to 12 and 19 years, respectively. Multistate survival modeling examined the impact of sense of purpose on risk for each transition, adjusting for age, sex, education, apolipoprotein‐E allele, and depressive symptoms. Multinomial regression was used to estimate life expectancy in each cognitive state.ResultMore purposeful older adults were found to have lower prospective risk of developing MCI in the HRS (HR = 0.93, 95% CI: 0.90, 0.97) and MAP (HR = 0.82, 95% CI: 0.69, 0.98) and had increased likelihood of improvement in cognitive functioning following MCI classification. In both samples, those higher in sense of purpose were found to have significantly longer overall life expectancy and life expectancy free of cognitive impairment (without MCI or dementia).ConclusionOlder adults higher in sense of purpose appear to live longer lives, with these differences in life expectancy attributable to increases in years lived without cognitive impairment. Replication of findings across longitudinal studies with disparate samples and measurement procedures provides robust support that having a strong sense of purpose in life contributes to cognitive reserve and resilience. Interventions aiming to promote older adult sense of purpose could extend the cognitive healthspan—the period in which individuals live in a cognitively healthy state free of impairment.

Education as Risk Factor of Mild Cognitive Impairment ‐ the Role of the Gut Microbiome

AbstractBackgroundResearch on social determinants of health has identified modifiable risk factors that contribute to an individual’s risk of developing dementia [1]. Individuals with mild cognitive impairment (MCI) present a group with highest potential of lifestyle interventions due to the risk of progressing to dementia [2]. The pathways from identified modifiable risk factors for dementia such as education have not been clarified, however understanding the relationships between risk factors and MCI could help identify mechanisms for intervention and reducing risk of progressing to dementia. Previous findings found taxonomic differences in dementia and MCI patients, and further education linked to indicators of gut dysbiosis [3–5]. We sought to test the possibly mediating role of gut dysbiosis and taxonomic differences in the relationship between modifiable risk factors and MCI, independent of genetic risk for developing dementia.MethodGut microbiome composition was ascertained with 16S rRNA gene amplicon sequencing. MCI classification was based on MoCA performance. Educational attainment in years was grouped. Mediation analysis [6] was conducted decomposing direct and indirect effects of educational attainment on MCI mediated by markers of dysbiosis (Chao1, Inverse Simpson, Shannon) while controlling for polygenic risk of Alzheimer’s Disease, Lewy Body Dementia and Parkinson’s Disease to account for different etiologic neurodegenerative pathways manifesting as MCI. Taxonomic differences across education groups were further tested (ANCOM‐BC, DESeq2) and PAM clustering based on relative abundance at Genus level was conducted to explore underlying signatures.ResultAfter exclusion of participants below age 50, or with missing data, n = 256 participants (n = 58 with MCI) of the Luxembourg Parkinson’s Study without Parkinson’s disease were eligible for analysis (M[SD] Age = 64.7[8.3] years). Higher vs lower educational attainment had a controlled direct effect (CDE) = 0.35 (P&lt;.01) on MCI, Chao1 included as mediator. We did not find significant indirect effects via any indicator of dysbiosis. Clusters with lower abundance of Bacteroides relative to Prevotella and Ruminococcus were at higher risk of MCI.ConclusionOur findings indicate direct effects of education not mediated by markers of dysbiosis. Taxonomic analysis suggests a signature linked to lower risk of dementia in higher educated individuals.

A New Approach for Multimodal Usage of Gene Expression and Its Image Representation for the Detection of Alzheimer's Disease.

Alzheimer's disease (AD) is a complex neurodegenerative disorder and the multifaceted nature of it requires innovative approaches that integrate various data modalities to enhance its detection. However, due to the cost of collecting multimodal data, multimodal datasets suffer from an insufficient number of samples. To mitigate the impact of a limited sample size on classification, we introduce a novel deep learning method (One2MFusion) which combines gene expression data with their corresponding 2D representation as a new modality. The gene vectors were first mapped to a discriminative 2D image for training a convolutional neural network (CNN). In parallel, the gene sequences were used to train a feed forward neural network (FNN) and the outputs of the FNN and CNN were merged, and a joint deep network was trained for the binary classification of AD, normal control (NC), and mild cognitive impairment (MCI) samples. The fusion of the gene expression data and gene-originated 2D image increased the accuracy (area under the curve) from 0.86 (obtained using a 2D image) to 0.91 for AD vs. NC and from 0.76 (obtained using a 2D image) to 0.88 for MCI vs. NC. The results show that representing gene expression data in another discriminative form increases the classification accuracy when fused with base data.

EAMNet: an Alzheimer’s disease prediction model based on representation learning

Objective. Brain 18F-FDG PET images indicate brain lesions’ metabolic status and offer the predictive potential for Alzheimer’s disease (AD). However, the complexity of extracting relevant lesion features and dealing with extraneous information in PET images poses challenges for accurate prediction. Approach. To address these issues, we propose an innovative solution called the efficient adaptive multiscale network (EAMNet) for predicting potential patient populations using positron emission tomography (PET) image slices, enabling effective intervention and treatment. Firstly, we introduce an efficient convolutional strategy to enhance the receptive field of PET images during the feature learning process, avoiding excessive extraction of fine tissue features by deep-level networks while reducing the model’s computational complexity. Secondly, we construct a channel attention module that enables the prediction model to adaptively allocate weights between different channels, compensating for the spatial noise in PET images’ impact on classification. Finally, we use skip connections to merge features from different-scale lesion information. Through visual analysis, the network constructed in this article aligns with the regions of interest of clinical doctors. Main results. Through visualization analysis, our network aligns with regions of interest identified by clinical doctors. Experimental evaluations conducted on the ADNI (Alzheimer’s Disease Neuroimaging Initiative) dataset demonstrate the outstanding classification performance of our proposed method. The accuracy rates for AD versus NC (Normal Controls), AD versus MCI (Mild Cognitive Impairment), MCI versus NC, and AD versus MCI versus NC classifications achieve 97.66%, 96.32%, 95.23%, and 95.68%, respectively. Significance. The proposed method surpasses advanced algorithms in the field, providing a hopeful advancement in accurately predicting and classifying Alzheimer’s Disease using 18F-FDG PET images. The source code has been uploaded to https://github.com/Haoliang-D-AHU/EAMNet/tree/master.

Diagnostic performance of MRI radiomics for classification of Alzheimer's disease, mild cognitive impairment, and normal subjects: a systematic review and meta-analysis.

Alzheimer's disease (AD) is a debilitating neurodegenerative disease. Early diagnosis of AD and its precursor, mild cognitive impairment (MCI), is crucial for timely intervention and management. Radiomics involves extracting quantitative features from medical images and analyzing them using advanced computational algorithms. These characteristics have the potential to serve as biomarkers for disease classification, treatment response prediction, and patient stratification. Of note, Magnetic resonance imaging (MRI) radiomics showed a promising result for diagnosing and classifying AD, and MCI from normal subjects. Thus, we aimed to systematically evaluate the diagnostic performance of the MRI radiomics for this task. A comprehensive search of the current literature was conducted using relevant keywords in PubMed/MEDLINE, Embase, Scopus, and Web of Science databases from inception to August 5, 2023. Original studies discussing the diagnostic performance of MRI radiomics for the classification of AD, MCI, and normal subjects were included. Method quality was evaluated with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and the Radiomics Quality Score (RQS) tools. We identified 13 studies that met the inclusion criteria, involving a total of 5448 participants. The overall quality of the included studies was moderate to high. The pooled sensitivity and specificity of MRI radiomics for differentiating AD from normal subjects were 0.92 (95% CI [0.85; 0.96]) and 0.91 (95% CI [0.85; 0.95]), respectively. The pooled sensitivity and specificity of MRI radiomics for differentiating MCI from normal subjects were 0.74 (95% CI [0.60; 0.85]) and 0.79 (95% CI [0.70; 0.86]), respectively. Also, the pooled sensitivity and specificity of MRI radiomics for differentiating AD from MCI were 0.73 (95% CI [0.64; 0.80]) and 0.79 (95% CI [0.64; 0.90]), respectively. MRI radiomics has promising diagnostic performance in differentiating AD, MCI, and normal subjects. It can potentially serve as a non-invasive and reliable tool for early diagnosis and classification of AD and MCI.