Developing Univariate Neurodegeneration Biomarkers with Low-Rank and Sparse Subspace Decomposition

Abstract

Cognitive decline due to Alzheimer s disease (AD) is closely associated with brain structure alterations captured by structural magnetic resonance imaging (sMRI). It supports the validity to develop sMRI-based univariate neurodegeneration biomarkers (UNB). However, existing UNB work either fails to model large group variances or does not capture AD dementia (ADD) induced changes. We propose a novel low-rank and sparse subspace decomposition method capable of stably quantifying the morphological changes induced by ADD. Specifically, we propose a numerically efficient rank minimization mechanism to extract group common structure and impose regularization constraints to encode the original 3D morphometry connectivity. Further, we generate regions-of-interest (ROI) with group difference study between common subspaces of Aβ+AD and Aβ-cognitively unimpaired (CU) groups. A univariate morphometry index (UMI) is constructed from these ROIs by summarizing individual morphological characteristics weighted by normalized difference between Aβ+AD and Aβ-CU groups. We use hippocampal surface radial distance feature to compute the UMIs and validate our work in the Alzheimer s Disease Neuroimaging Initiative (ADNI) cohort. With hippocampal UMIs, the estimated minimum sample sizes needed to detect a 25% reduction in the mean annual change with 80% power and two-tailed P=0.05are 116, 279 and 387 for the longitudinal Aβ+AD, Aβ+mild cognitive impairment (MCI) and Aβ+CU groups, respectively. Additionally, for MCI patients, UMIs well correlate with hazard ratio of conversion to AD (4.3, 95% CI\xa0=\xa02.3-8.2) within 18 months. Our experimental results outperform traditional hippocampal volume measures and suggest the application of UMI as a potential UNB.