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01.12.2012 | Research article | Ausgabe 1/2012 Open Access

BMC Medical Informatics and Decision Making 1/2012

Effective diagnosis of Alzheimer’s disease by means of large margin-based methodology

BMC Medical Informatics and Decision Making > Ausgabe 1/2012
Rosa Chaves, Javier Ramírez, Juan M Górriz, Ignacio A Illán, Manuel Gómez-Río, Cristobal Carnero, the Alzheimer’s Disease Neuroimaging Initiative
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1472-6947-12-79) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Author’s contributions

The authors contributed to the selection and discussion of the literature reviewed in this work. The authors participated in the conception and preparation of the final manuscript. All authors read and approved the final manuscript.



Functional brain images such as Single-Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) have been widely used to guide the clinicians in the Alzheimer’s Disease (AD) diagnosis. However, the subjectivity involved in their evaluation has favoured the development of Computer Aided Diagnosis (CAD) Systems.


It is proposed a novel combination of feature extraction techniques to improve the diagnosis of AD. Firstly, Regions of Interest (ROIs) are selected by means of a t-test carried out on 3D Normalised Mean Square Error (NMSE) features restricted to be located within a predefined brain activation mask. In order to address the small sample-size problem, the dimension of the feature space was further reduced by: Large Margin Nearest Neighbours using a rectangular matrix (LMNN-RECT), Principal Component Analysis (PCA) or Partial Least Squares (PLS) (the two latter also analysed with a LMNN transformation). Regarding the classifiers, kernel Support Vector Machines (SVMs) and LMNN using Euclidean, Mahalanobis and Energy-based metrics were compared.


Several experiments were conducted in order to evaluate the proposed LMNN-based feature extraction algorithms and its benefits as: i) linear transformation of the PLS or PCA reduced data, ii) feature reduction technique, and iii) classifier (with Euclidean, Mahalanobis or Energy-based methodology). The system was evaluated by means of k-fold cross-validation yielding accuracy, sensitivity and specificity values of 92.78%, 91.07% and 95.12% (for SPECT) and 90.67%, 88% and 93.33% (for PET), respectively, when a NMSE-PLS-LMNN feature extraction method was used in combination with a SVM classifier, thus outperforming recently reported baseline methods.


All the proposed methods turned out to be a valid solution for the presented problem. One of the advances is the robustness of the LMNN algorithm that not only provides higher separation rate between the classes but it also makes (in combination with NMSE and PLS) this rate variation more stable. In addition, their generalization ability is another advance since several experiments were performed on two image modalities (SPECT and PET).
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