Brain Network Classification for Accurate Detection of Alzheimer’s Disease via Manifold Harmonic Discriminant Analysis

Mounting evidence shows that Alzheimer’s disease (AD) manifests the dysfunction of the brain network much earlier before the onset of clinical symptoms, making its early diagnosis possible. Current brain network analyses treat high-dimensional network data as a regular matrix or vector, which destroys the essential network topology, thereby seriously affecting diagnosis accuracy. In this context, harmonic waves provide a solid theoretical background for exploring brain network topology. However, the harmonic waves are originally intended to discover neurological disease propagation patterns in the brain, which makes it difficult to accommodate brain disease diagnosis with high heterogeneity. To address this challenge, this article proposes a network manifold harmonic discriminant analysis (MHDA) method for accurately detecting AD. Each brain network is regarded as an instance drawn on a Stiefel manifold. Every instance is represented by a set of orthonormal eigenvectors (i.e., harmonic waves) derived from its Laplacian matrix, which fully respects the topological structure of the brain network. An MHDA method within the Stiefel space is proposed to identify the group-dependent common harmonic waves, which can be used as group-specific references for downstream analyses. Extensive experiments are conducted to demonstrate the effectiveness of the proposed method in stratifying cognitively normal (CN) controls, mild cognitive impairment (MCI), and AD.