Predicting Alzheimer's disease progression using deep recurrent neural networks.

Journal: NeuroImage
Published Date:

Abstract

Early identification of individuals at risk of developing Alzheimer's disease (AD) dementia is important for developing disease-modifying therapies. In this study, given multimodal AD markers and clinical diagnosis of an individual from one or more timepoints, we seek to predict the clinical diagnosis, cognition and ventricular volume of the individual for every month (indefinitely) into the future. We proposed and applied a minimal recurrent neural network (minimalRNN) model to data from The Alzheimer's Disease Prediction Of Longitudinal Evolution (TADPOLE) challenge, comprising longitudinal data of 1677 participants (Marinescu et al., 2018) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We compared the performance of the minimalRNN model and four baseline algorithms up to 6 years into the future. Most previous work on predicting AD progression ignore the issue of missing data, which is a prevalent issue in longitudinal data. Here, we explored three different strategies to handle missing data. Two of the strategies treated the missing data as a "preprocessing" issue, by imputing the missing data using the previous timepoint ("forward filling") or linear interpolation ("linear filling). The third strategy utilized the minimalRNN model itself to fill in the missing data both during training and testing ("model filling"). Our analyses suggest that the minimalRNN with "model filling" compared favorably with baseline algorithms, including support vector machine/regression, linear state space (LSS) model, and long short-term memory (LSTM) model. Importantly, although the training procedure utilized longitudinal data, we found that the trained minimalRNN model exhibited similar performance, when using only 1 input timepoint or 4 input timepoints, suggesting that our approach might work well with just cross-sectional data. An earlier version of our approach was ranked 5th (out of 53 entries) in the TADPOLE challenge in 2019. The current approach is ranked 2nd out of 63 entries as of June 3rd, 2020.

Authors

  • Minh Nguyen
    Clinical Imaging Research Centre, Centre for Sleep and Cognition, N.1 Institute for Health and Memory Networks Program, National University of Singapore, Singapore; Department of Electrical and Computer Engineering, National University of Singapore, Singapore.
  • Tong He
  • Lijun An
    Department of Electrical and Computer Engineering, National University of Singapore, Singapore; Centre for Sleep and Cognition (CSC) & Centre for Translational Magnetic Resonance Research (TMR), National University of Singapore, Singapore; N.1 Institute for Health & Institute for Digital Medicine (WisDM), National University of Singapore, Singapore.
  • Daniel C Alexander
    Centre for Medical Image Computing and Dept of Computer Science, University College London, Gower Street, London WC1E 6BT, UK.
  • Jiashi Feng
  • B T Thomas Yeo
    Clinical Imaging Research Centre, Centre for Sleep and Cognition, N.1 Institute for Health and Memory Networks Program, National University of Singapore, Singapore; Department of Electrical and Computer Engineering, National University of Singapore, Singapore; Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA; Centre for Cognitive Neuroscience, Duke-NUS Medical School, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore. Electronic address: thomas.yeo@nus.edu.sg.