A Novelty Detection Approach to Effectively Predict Conversion from Mild Cognitive Impairment to Alzheimer’s Disease

Accurately recognising patients with progressive mild cognitive impairment (pMCI) who will develop Alzheimer’s disease (AD) in subsequent years is very important, as early identification of those patients will enable interventions to potentially reduce the number of those transitioning from MCI to AD. Most studies in this area have concentrated on high-dimensional neuroimaging data with supervised binary/multi-class classification algorithms. However, neuroimaging data is more costly to obtain than non-imaging, and healthcare datasets are normally imbalanced which may reduce classification performance and reliability. To address these challenges, we proposed a new strategy that employs unsupervised novelty detection (ND) techniques to predict pMCI from the AD Neuroimaging Initiative non-imaging data. ND algorithms, including the k-nearest neighbours (kNN), k-means, Gaussian mixture model (GMM), isolation forest (IF) and extreme learning machine (ELM), were employed and compared with supervised binary Support Vector Machine (SVM) and Random Forest (RF). We introduced optimisation with nested cross-validation and focused on maximising the adjusted F measure to ensure maximum generalisation of the proposed system by minimising false negative rates. Our extensive experimental results show that ND algorithms (0.727±0.029 kNN, 0.7179±0.0523 GMM, 0.7276±0.0281 ELM) obtained comparable performance to supervised binary SVM (0.7359±0.0451) with 20% stable MCI misclassification tolerance and were significantly better than RF (0.4771±0.0167). Moreover, we found that the non-invasive, readily obtainable, and cost-effective cognitive and functional assessment was the most efficient predictor for predicting the pMCI within 2 years with ND techniques. Importantly, we presented an accessible and cost-effective approach to pMCI prediction, which does not require labelled data.