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Modeling disease progression through the cognitive scores has become an attractive challenge in the field of computational neuroscience due to its importance for early diagnosis of Alzheimer’s disease (AD). Several scores such as Alzheimer’s Disease Assessment Scale cognitive total score, Mini Mental State Exam score and Rey Auditory Verbal Learning Test provide a quantitative assessment of the cognitive conditions of the patients and are commonly used as objective criteria for clinical diagnosis of dementia and mild cognitive impairment (MCI). On the other hand, connectivity patterns extracted from diffusion tensor imaging (DTI) have been successfully used to classify AD and MCI subjects with machine learning algorithms proving their potential application in the clinical setting. In this work, we carried out a pilot study to investigate the strength of association between DTI structural connectivity of a mixed ADNI cohort and cognitive spectrum in AD. We developed a machine learning framework to find a generalized cognitive score that summarizes the different functional domains reflected by each cognitive clinical index and to identify the connectivity biomarkers more significantly associated with the score. The results indicate that the efficiency and the centrality of some regions can effectively track cognitive impairment in AD showing a significant correlation with the generalized cognitive score (R = 0.7).

Characterizing both neurodevelopmental and aging brain structural trajectories is important for understanding normal biological processes and atypical patterns that are related to pathological phenomena. Initiatives to share open access morphological data contributed significantly to the advance in brain structure characterization. Indeed, such initiatives allow large brain morphology multi-site datasets to be shared, which increases the statistical sensitivity of the outcomes. However, using neuroimaging data from multi-site studies requires harmonizing data across the site to avoid bias. In this work we evaluated three different harmonization techniques on the Autism Brain Imaging Data Exchange (ABIDE) dataset for age prediction analysis in two groups of subjects (i.e., controls and autism spectrum disorder). We extracted the morphological features from T1-weighted images of a mixed cohort of 654 subjects acquired from 17 sites to predict the biological age of the subjects using three machine learning regression models. A machine learning framework was developed to quantify the effects of the different harmonization strategies on the final performance of the models and on the set of morphological features that are relevant to the age prediction problem in both the presence and absence of pathology. The results show that, even if two harmonization strategies exhibit similar accuracy of predictive models, a greater mismatch occurs between the sets of most age-related predictive regions for the Autism Spectrum Disorder (ASD) subjects. Thus, we propose to use a stability index to extract meaningful features for a robust clinical validation of the outcomes of multiple harmonization strategies.