Disease progression modeling (DPM) using longitudinal data is a challenging
task in machine learning for healthcare that can provide clinicians with better
tools for diagnosis and monitoring of disease. Existing DPM algorithms neglect
temporal dependencies among measurements and make parametric assumptions about
biomarker trajectories. In addition, they do not model multiple biomarkers
jointly and need to align subjects' trajectories. In this paper, recurrent
neural networks (RNNs) are utilized to address these issues. However, in many
cases, longitudinal cohorts contain incomplete data, which hinders the
application of standard RNNs and requires a pre-processing step such as
imputation of the missing values. We, therefore, propose a generalized training
rule for the most widely used RNN architecture, long short-term memory (LSTM)
networks, that can handle missing values in both target and predictor
variables. This algorithm is applied for modeling the progression of
Alzheimer's disease (AD) using magnetic resonance imaging (MRI) biomarkers. The
results show that the proposed LSTM algorithm achieves a lower mean absolute
error for prediction of measurements across all considered MRI biomarkers
compared to using standard LSTM networks with data imputation or using a
regression-based DPM method. Moreover, applying linear discriminant analysis to
the biomarkers' values predicted by the proposed algorithm results in a larger
area under the receiver operating characteristic curve (AUC) for clinical
diagnosis of AD compared to the same alternatives, and the AUC is comparable to
state-of-the-art AUCs from a recent cross-sectional medical image
classification challenge. This paper shows that built-in handling of missing
values in LSTM network training paves the way for application of RNNs in
disease progression modeling.Comment: 9 pages, 1 figure, MIDL conferenc