Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive impairment of memory and other cognitive functions. Regression analysis has been studied to relate neuroimaging measures to cognitive status. However, whether these measures have further predictive power to infer a trajectory of cognitive performance over time is still an under-explored but important topic in AD research. We propose a novel high-order multi-task learning model to address this issue. The proposed model explores the temporal correlations existing in imaging and cognitive data by structured sparsity-inducing norms. The sparsity of the model enables the selection of a small number of imaging measures while maintaining high prediction accuracy. The empirical studies, using the longitudinal imaging and cognitive data of the ADNI cohort, have yielded promising results.

The discovery of patient-specific imaging markers that are predictive of future disease outcomes can help us better understand individual-level heterogeneity of disease evolution. In fact, deep learning models that can provide data-driven personalized markers are much more likely to be adopted in medical practice. In this work, we demonstrate that data-driven biomarker discovery can be achieved through a counterfactual synthesis process. We show how a deep conditional generative model can be used to perturb local imaging features in baseline images that are pertinent to subject-specific future disease evolution and result in a counterfactual image that is expected to have a different future outcome. Candidate biomarkers, therefore, result from examining the set of features that are perturbed in this process. Through several experiments on a large-scale, multi-scanner, multi-center multiple sclerosis (MS) clinical trial magnetic resonance imaging (MRI) dataset of relapsing-remitting (RRMS) patients, we demonstrate that our model produces counterfactuals with changes in imaging features that reflect established clinical markers predictive of future MRI lesional activity at the population level. Additional qualitative results illustrate that our model has the potential to discover novel and subject-specific predictive markers of future activity.

Alzheimer disease (AD) is a neurodegenerative disorder characterized by progressive impairment of memory and other cognitive functions. Regression analysis has been studied to relate neuroimaging measures to cognitive status. However, whether these measures have further predictive power to infer a trajectory of cognitive performance over time is still an under-explored but important topic in AD research. We propose a novel high-order multi-task learning model to address this issue. The proposed model explores the temporal correlations existing in data features and regression tasks by the structured sparsity-inducing norms. In addition, the sparsity of the model enables the selection of a small number of MRI measures while maintaining high prediction accuracy. The empirical studies, using the baseline MRI and serial cognitive data of the ADNI cohort, have yielded promising results.