The 3D tortuosity determined in several brain areas is proposed as a new morphological biomarker (BM) to be considered in early detection of Alzheimer’s disease (AD). It is measured using the sum of angles method and it has proven to be sensitive to anatomical changes that appear in gray and white matter and temporal and parietal lobes during mild cognitive impairment (MCI). Statistical analysis showed significant differences (p<0.05) between tortuosity indices determined for healthy controls (HC) vs. MCI and HC vs. AD in most of the analyzed structures. Other clinically used BMs have also been incorporated in the analysis: beta-amyloid and tau protein CSF and plasma concentrations, as well as other image-extracted parameters. A classification strategy using random forest (RF) algorithms was implemented to discriminate between three samples of the studied populations, selected from the ADNI database. Classification rates considering only image-extracted parameters show an increase of 9.17%, when tortuosity is incorporated. An enhancement of 1.67% is obtained when BMs measured from several modalities are combined with tortuosity.

We present a discrete compactness (DC) index, together with a classification scheme, based both on the size and shape features extracted from brain volumes, to determine different aging stages: healthy controls (HC), mild cognitive impairment (MCI), and Alzheimer's disease (AD). A set of 30 brain magnetic resonance imaging (MRI) volumes for each group was segmented and two indices were measured for several structures: three-dimensional DC and normalized volumes (NVs). The discrimination power of these indices was determined by means of the area under the curve (AUC) of the receiver operating characteristic, where the proposed compactness index showed an average AUC of 0.7 for HC versus MCI comparison, 0.9 for HC versus AD separation, and 0.75 for MCI versus AD groups. In all cases, this index outperformed the discrimination capability of the NV. Using selected features from the set of DC and NV measures, three support vector machines were optimized and validated for the pairwise separation of the three classes. Our analysis shows classification rates of up to 98.3% between HC and AD, 85% between HC and MCI, and 93.3% for MCI and AD separation. These results outperform those reported in the literature and demonstrate the viability of the proposed morphological indices to classify different aging stages.

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Alzheimer's disease is a multifactorial neurodegenerative disorder preceded by a prodromal stage called mild cognitive impairment (MCI). Early diagnosis of MCI is crucial for delaying the progression and optimizing the treatment. In this study we propose a random forest (RF) classifier to distinguish between MCI and healthy control subjects (HC), identifying the most relevant features computed from structural T1-weighted and diffusion-weighted magnetic resonance images (sMRI and DWI), combined with neuro-psychological scores. To train the RF we used a set of 60 subjects (HC = 30, MCI = 30) drawn from the Alzheimer's disease neuroimaging initiative database, while testing with unseen data was carried out on a 23-subjects Mexican cohort (HC = 12, MCI = 11). Features from hippocampus, thalamus and amygdala, for left and right hemispheres were fed to the RF, with the most relevant being previously selected by applying extra trees classifier and the mean decrease in impurity index. All the analyzed brain structures presented changes in sMRI and DWI features for MCI, but those computed from sMRI contribute the most to distinguish from HC. However, sMRI+DWI improves classification performance in training area under the receiver operating characteristic curve (AUROC = 93.5 ± 8%, accuracy = 88.8 ± 9%) and testing with unseen data (AUROC = 93.79%, accuracy = 91.3%), having a better performance when neuro-psychological scores were included. Compared to other classifiers the proposed RF provide the best performance for HC/MCI discrimination and the application of a feature selection step improves its performance. These findings imply that multimodal analysis gives better results than unimodal analysis and hence may be a useful tool to assist in early MCI diagnosis.