Longitudinal imaging data are routinely acquired for health studies and patient monitoring. A central goal in longitudinal studies is tracking relevant change over time. Traditional methods remove nuisance variation with custom pipelines to focus on significant changes. In this work, we present a machine learning-based method that automatically ignores irrelevant changes and extracts the time-varying signal of interest. Our method, called Learning-based Inference of Longitudinal imAge Changes (LILAC), performs a pairwise comparison of longitudinal images in order to make a temporal difference prediction. LILAC employs a convolutional Siamese architecture to extract feature pairs, followed by subtraction and a bias-free fully connected layer to learn meaningful temporal image differences. We first showcase LILAC's ability to capture key longitudinal changes by simply training it to predict the temporal ordering of images. In our experiments, temporal ordering accuracy exceeded 0.98, and predicted time differences were strongly correlated with actual changes in relevant variables (Pearson Correlation Coefficient