Mild cognitive impairment is a preclinical stage of Alzheimer's disease (AD). For effective treatment of AD, it is important to identify mild cognitive impairment (MCI) patients who are at a high risk of developing AD over the course of time. In this study, autoregressive modelling of multiple heterogeneous predictors of Alzheimer's disease is performed to capture their evolution over time. The models are trained using three different arrangements of longitudinal data. These models are then used to estimate future biomarker readings of individual test subjects. Finally, standard support vector machine classifier is employed for detecting MCI patients at risk of developing AD over the coming years. The proposed models are thoroughly evaluated for their predictive capability using both cognitive scores and MRI-derived measures. In a stratified five-fold cross validation setup, our proposed methodology delivered highest AUC of 88.93% (Accuracy = 84.29%) and 88.13% (Accuracy = 83.26%) for 1 year and 2 year ahead AD conversion prediction, respectively, on the most widely used Alzheimer's disease neuroimaging initiative data. The notable conclusions of this study are: 1) Clinical changes in MRI-derived measures can be better forecasted than cognitive scores, 2) Multiple predictor models deliver better conversion prediction than single biomarker models, 3) Cognitive score boosted by MRI-derived measures delivers better short-term ahead conversion prediction, and 4) Neuropsychological scores alone can deliver good accuracy for long-term conversion prediction.

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In Alzheimer’s disease (AD) progression, it is imperative to identify the subjects with mild cognitive impairment before clinical symptoms of AD appear. This work proposes a technique for decision support in identifying subjects who will show transition from mild cognitive impairment (MCI) to Alzheimer’s disease (AD) in the future. We used robust predictors from multivariate MRI-derived biomarkers and neuropsychological measures and tracked their longitudinal trajectories to predict signs of AD in the MCI population. Assuming piecewise linear progression of the disease, we designed a novel weighted gradient offset-based technique to forecast the future marker value using readings from at least two previous follow-up visits. Later, the complete predictor trajectories are used as features for a standard support vector machine classifier to identify MCI-to-AD progressors amongst the MCI patients enrolled in the Alzheimer’s disease neuroimaging initiative (ADNI) cohort. We explored the performance of both unimodal and multimodal models in a 5-fold cross-validation setup. The proposed technique resulted in a high classification AUC of 91.2% and 95.7% for 6-month- and 1-year-ahead AD prediction, respectively, using multimodal markers. In the end, we discuss the efficacy of MRI markers as compared to NM for MCI-to-AD conversion prediction.

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