AdapDISCOM: An Adaptive Sparse Regression Method for High-Dimensional Multimodal Data With Block-Wise Missingness and Measurement Errors

Multimodal high-dimensional data are increasingly prevalent in biomedical research, yet they are often compromised by block-wise missingness and measurement errors, posing significant challenges for statistical inference and prediction. We propose AdapDISCOM, a novel adaptive direct sparse regression method that simultaneously addresses these two pervasive issues. Building on the DISCOM framework, AdapDISCOM introduces modality-specific weighting schemes to account for heterogeneity in data structures and error magnitudes across modalities. We establish the theoretical properties of AdapDISCOM, including model selection consistency and convergence rates under sub-Gaussian and heavy-tailed settings, and develop robust and computationally efficient variants (AdapDISCOM-Huber and Fast-AdapDISCOM). Extensive simulations demonstrate that AdapDISCOM consistently outperforms existing methods such as DISCOM, SCOM, and CoCoLasso, particularly under heterogeneous contamination and heavy-tailed distributions. Finally, we apply AdapDISCOM to Alzheimers Disease Neuroimaging Initiative (ADNI) data, demonstrating improved prediction of cognitive scores and reliable selection of established biomarkers, even with substantial missingness and measurement errors. AdapDISCOM provides a flexible, robust, and scalable framework for high-dimensional multimodal data analysis under realistic data imperfections.

A brain signature highly predictive of future progression to Alzheimer's dementia

Early prognosis of Alzheimer's dementia is hard. Mild cognitive impairment (MCI) typically precedes Alzheimer's dementia, yet only a fraction of MCI individuals will progress to dementia, even when screened using biomarkers. We propose here to identify a subset of individuals who share a common brain signature highly predictive of oncoming dementia. This signature was composed of brain atrophy and functional dysconnectivity and discovered using a machine learning model in patients suffering from dementia. The model recognized the same brain signature in MCI individuals, 90% of which progressed to dementia within three years. This result is a marked improvement on the state-of-the-art in prognostic precision, while the brain signature still identified 47% of all MCI progressors. We thus discovered a sizable MCI subpopulation which represents an excellent recruitment target for clinical trials at the prodromal stage of Alzheimer's disease.