Abstract

Early diagnosis of dementia is critical for assessing disease progression and potential treatment. State-or-the-art machine learning techniques have been increasingly employed to take on this diagnostic task. In this study, we employed Generalized Matrix Learning Vector Quantization (GMLVQ) classifiers to discriminate patients with Mild Cognitive Impairment (MCI) from healthy controls based on their cognitive skills. Further, we adopted a “Learning with privileged information” approach to combine cognitive and fMRI data for the classification task. The resulting classifier operates solely on the cognitive data while it incorporates the fMRI data as privileged information (PI) during training. This novel classifier is of practical use as the collection of brain imaging data is not always possible with patients and older participants. MCI patients and healthy age-matched controls were trained to extract structure from temporal sequences. We ask whether machine learning classifiers can be used to discriminate patients from controls and whether differences between these groups relate to individual cognitive profiles. To this end, we tested participants in four cognitive tasks: working memory, cognitive inhibition, divided attention, and selective attention. We also collected fMRI data before and after training on a probabilistic sequence learning task and extracted fMRI responses and connectivity as features for machine learning classifiers. Our results show that the PI guided GMLVQ classifiers outperform the baseline classifier that only used the cognitive data. In addition, we found that for the baseline classifier, divided attention is the only relevant cognitive feature. When PI was incorporated, divided attention remained the most relevant feature while cognitive inhibition became also relevant for the task. Interestingly, this analysis for the fMRI GMLVQ classifier suggests that (1) when overall fMRI signal is used as inputs to the classifier, the post-training session is most relevant; and (2) when the graph feature reflecting underlying spatiotemporal fMRI pattern is used, the pre-training session is most relevant. Taken together these results suggest that brain connectivity before training and overall fMRI signal after training are both diagnostic of cognitive skills in MCI.

Highlights

  • Alzheimer’s Disease (AD) is the most common neurodegenerative disease in ageing

  • We are primarily interested in classification performance of M+-CD-PD classifiers, that is, classifiers using cognitive data as their inputs and incorporating brain imaging data as privileged information. this classification performance will be put in the context of performances when no brain imaging information is available (M-CD) and when the full brain imaging is available as input (M-PD)

  • For percent signal change (PSC), which is related to brain activation level, the corresponding median Macroaveraged Mean Absolute Error (MMAE) is reduced by relatively 39.6% when compared to that of M-CD

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Summary

Introduction

Alzheimer’s Disease (AD) is the most common neurodegenerative disease in ageing. It is characterized by the progressive impairment of neurons and their connections. Mild Cognitive Impairment (MCI) is the prodromal stage of AD. Accurate diagnosis of MCI (i.e., the early stage of AD) is very important for timely treatment and delay of disease progression. As MCI results in detectable loss of cognitive function, cognitive test scores have been used diagnostically (Albert et al, 2010). FMRI has been increasingly used as a diagnostic tool of MCI patients (Challis et al, 2015; Chen et al, 2015). We present a novel classifier using cognitive test scores as inputs to the classifier and using fMRI data as privileged information

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