Spatial component analysis of MRI data for Alzheimer's disease diagnosis: a Bayesian network approach

This work presents a spatial-component (SC) based approach to aid the diagnosis of Alzheimer's disease (AD) using magnetic resonance images. In this approach, the whole brain image is subdivided in regions or spatial components, and a Bayesian network is used to model the dependencies between affected regions of AD. The structure of relations between affected regions allows to detect neurodegeneration with an estimated performance of 88% on more than 400 subjects and predict neurodegeneration with 80% accuracy, supporting the conclusion that modeling the dependencies between components increases the recognition of different patterns of brain degeneration in AD.This work was partly supported by the MICINN under the TEC2012-34306 project and the Consejería de Innovación, Ciencia y Empresa (Junta de Andaluca, Spain) under the Excellence Projects P09-TIC-4530 and P11-TIC-7103

Optimized One vs One approach in multiclass classification for early Alzheimer’s Disease and Mild Cognitive Impairment diagnosis

The detection of Alzheimer’s Disease in its early stages is crucial for patient care and drugs development. Motivated by this fact, the neuroimaging community has extensively applied machine learning techniques to the early diagnosis problem with promising results. The organization of challenges has helped the community to address different raised problems and to standardize the approaches to the problem. In this work we use the data from international challenge for automated prediction of MCI from MRI data to address the multiclass classification problem. We propose a novel multiclass classification approach that addresses the outlier detection problem, uses pairwise t-test feature selection, project the selected features onto a Partial-Least-Squares multiclass subspace, and applies one-versus-one error correction output codes classification. The proposed method yields to an accuracy of 67 % in the multiclass classification, outperforming all the proposals of the competition.Ministerio de Innovacion y Ciencia Project DEEP-NEUROMAPS RTI2018-098913-B100Consejeria de Economia, Innovacion, Ciencia, y Empleo of the Junta de Andalucia A-TIC-080-UGR18 TIC FRONTERAGerman Research Foundation (DFG) FPU 18/04902United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Neurological Disorders & Stroke (NINDS) U01 AG024904DOD ADNI Department of Defense W81XWH-12-2-001

Distinguishing Parkinson's disease from atypical parkinsonian syndromes using PET data and a computer system based on support vector machines and Bayesian networks

Differentiating between Parkinson's disease (PD) and atypical parkinsonian syndromes (APS) is still a challenge, specially at early stages when the patients show similar symptoms. During last years, several computer systems have been proposed in order to improve the diagnosis of PD, but their accuracy is still limited. In this work we demonstrate a full automatic computer system to assist the diagnosis of PD using 18F-DMFP PET data. First, a few regions of interest are selected by means of a two-sample t-test. The accuracy of the selected regions to separate PD from APS patients is then computed using a support vector machine classifier. The accuracy values are finally used to train a Bayesian network that can be used to predict the class of new unseen data. This methodology was evaluated using a database with 87 neuroimages, achieving accuracy rates over 78%. A fair comparison with other similar approaches is also provided.This work is part of a project approved by the Andalucía Talent Hub Program launched by the Andalusian Knowledge Agency, co-funded by the European Union's Seventh Framework Program, Marie Sklodowska-Curie actions (COFUND Grant Agreement no 291780) and the Ministry of Economy, Innovation, Science and Employment of the Junta de Andalucía. The work was also supported by the University of Granada (Spain), the University for Munich (Germany), the MICINN (Spain) under the TEC2012–34306 project and the Consejera de Innovacin, Ciencia y Empresa (Junta de Andaluca, Spain) under the P11–TIC–7103 excellence project

Autosomal Dominantly Inherited Alzheimer Disease: Analysis of genetic subgroups by Machine Learning

Despite subjects with Dominantly-Inherited Alzheimer's Disease (DIAD) represent less than 1% of all Alzheimer's Disease (AD) cases, the Dominantly Inherited Alzheimer Network (DIAN) initiative constitutes a strong impact in the understanding of AD disease course with special emphasis on the presyptomatic disease phase. Until now, the 3 genes involved in DIAD pathogenesis (PSEN1, PSEN2 and APP) have been commonly merged into one group (Mutation Carriers, MC) and studied using conventional statistical analysis. Comparisons between groups using null-hypothesis testing or longitudinal regression procedures, such as the linear-mixed-effects models, have been assessed in the extant literature. Within this context, the work presented here performs a comparison between different groups of subjects by considering the 3 genes, either jointly or separately, and using tools based on Machine Learning (ML). This involves a feature selection step which makes use of ANOVA followed by Principal Component Analysis (PCA) to determine which features would be realiable for further comparison purposes. Then, the selected predictors are classified using a Support-Vector-Machine (SVM) in a nested k-Fold cross-validation resulting in maximum classification rates of 72-74% using PiB PET features, specially when comparing asymptomatic Non-Carriers (NC) subjects with asymptomatic PSEN1 Mutation-Carriers (PSEN1-MC). Results obtained from these experiments led to the idea that PSEN1-MC might be considered as a mixture of two different subgroups including: a first group whose patterns were very close to NC subjects, and a second group much more different in terms of imaging patterns. Thus, using a k-Means clustering algorithm it was determined both subgroups and a new classification scenario was conducted to validate this process. The comparison between each subgroup vs. NC subjects resulted in classification rates around 80% underscoring the importance of considering DIAN as an heterogeneous entity

Statistical Agnostic Mapping: A framework in neuroimaging based on concentration inequalities

In the 1970s a novel branch of statistics emerged focusing its effort on the selection of a function for the pattern recognition problem that would fulfill a relationship between the quality of the approximation and its complexity. This theory is mainly devoted to problems of estimating dependencies in the case of limited sample sizes, and comprise all the empirical out-of sample generalization approaches; e.g. cross validation (CV). In this paper a data-driven approach based on concentration inequalities is designed for testing competing hypothesis or comparing different models. In this sense we derive a Statistical Agnostic (non-parametric) Mapping (SAM) for neuroimages at voxel or regional levels which is able to: (i) relieve the problem of instability with limited sample sizes when estimating the actual risk via CV; and (ii) provide an alternative way of Family-wise-error (FWE) corrected p-value maps in inferential statistics for hypothesis testing. Using several neuroimaging datasets (containing large and small effects) and random task group analyses to compute empirical familywise error rates, this novel framework resulted in a model validation method for small samples over dimension ratios, and a less-conservative procedure than FWE..-value correction to determine the significance maps from the inferences made using small upper bounds of the actual risk.MINECO/ FEDER, Spain RTI2018-098913-B100 CV20-45250 A-TIC-080-UGR18Ministerio de Universidades, Spain under the FPU Predoctoral Grant FPU 18/04902United States Department of Health & Human Services National Institutes of Health (NIH) - USA U01 AG024904DOD ADNI, Spain (Department of Defense) W81-XWH-12-2-0012United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute on Aging (NIA)United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Biomedical Imaging & Bioengineering (NIBIB)AbbVieAlzheimer's AssociationAlzheimer's Drug Discovery FoundationAraclon BiotechBioClinica, Inc.BiogenBristol-Myers SquibbCereSpir, Inc.CogstateEisai Co LtdElan Pharmaceuticals, Inc.Eli LillyEuroImmunF. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.FujirebioGE HealthcareIXICO Ltd.Janssen Alzheimer Immunotherapy Research & Development, LLC.Johnson & Johnson USALumosityLundbeck CorporationMerck & CompanyMeso Scale Diagnostics, LLC.NeuroRx ResearchNeurotrack TechnologiesNovartisPfizerPiramal ImagingServierTakeda Pharmaceutical Company LtdTransition TherapeuticsCanadian Institutes of Health Research (CIHR

C9orf72, age at onset, and ancestry help discriminate behavioral from language variants in FTLD cohorts.

OBJECTIVE: We sought to characterize C9orf72 expansions in relation to genetic ancestry and age at onset (AAO) and to use these measures to discriminate the behavioral from the language variant syndrome in a large pan-European cohort of frontotemporal lobar degeneration (FTLD) cases. METHODS: We evaluated expansions frequency in the entire cohort (n = 1,396; behavioral variant frontotemporal dementia [bvFTD] [n = 800], primary progressive aphasia [PPA] [n = 495], and FTLD-motor neuron disease [MND] [n = 101]). We then focused on the bvFTD and PPA cases and tested for association between expansion status, syndromes, genetic ancestry, and AAO applying statistical tests comprising Fisher exact tests, analysis of variance with Tukey post hoc tests, and logistic and nonlinear mixed-effects model regressions. RESULTS: We found C9orf72 pathogenic expansions in 4% of all cases (56/1,396). Expansion carriers differently distributed across syndromes: 12/101 FTLD-MND (11.9%), 40/800 bvFTD (5%), and 4/495 PPA (0.8%). While addressing population substructure through principal components analysis (PCA), we defined 2 patients groups with Central/Northern (n = 873) and Southern European (n = 523) ancestry. The proportion of expansion carriers was significantly higher in bvFTD compared to PPA (5% vs 0.8% [p = 2.17 × 10-5; odds ratio (OR) 6.4; confidence interval (CI) 2.31-24.99]), as well as in individuals with Central/Northern European compared to Southern European ancestry (4.4% vs 1.8% [p = 1.1 × 10-2; OR 2.5; CI 1.17-5.99]). Pathogenic expansions and Central/Northern European ancestry independently and inversely correlated with AAO. Our prediction model (based on expansions status, genetic ancestry, and AAO) predicted a diagnosis of bvFTD with 64% accuracy. CONCLUSIONS: Our results indicate correlation between pathogenic C9orf72 expansions, AAO, PCA-based Central/Northern European ancestry, and a diagnosis of bvFTD, implying complex genetic risk architectures differently underpinning the behavioral and language variant syndromes