Alzheimer's disease (AD) is a progressive and irreversible brain disorder that unfolds over the course of 30 years. Therefore, it is critical to capture the disease progression in an early stage such that intervention can be applied before the onset of symptoms. Machine learning (ML) models have been shown effective in predicting the onset of AD. Yet for subjects with follow-up visits, existing techniques for AD classification only aim for accurate group assignment, where the monotonically increasing risk across follow-up visits is usually ignored. Resulted fluctuating risk scores across visits violate the irreversibility of AD, hampering the trustworthiness of models and also providing little value to understanding the disease progression. To address this issue, we propose a novel regularization approach to predict AD longitudinally. Our technique aims to maintain the expected monotonicity of increasing disease risk during progression while preserving expressiveness. Specifically, we introduce a monotonicity constraint that encourages the model to predict disease risk in a consistent and ordered manner across follow-up visits. We evaluate our method using the longitudinal structural MRI and amyloid-PET imaging data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Our model outperforms existing techniques in capturing the progressiveness of disease risk, and at the same time preserves prediction accuracy.

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.