A comprehensive characterization of hippocampal feature ensemble serves as individualized brain signature for Alzheimer's disease: deep learning analysis in 3238 participants worldwide.

Abstract

Hippocampal characterization is one of the most significant hallmarks of Alzheimer's disease (AD); rather, the single-level feature is insufficient. A comprehensive hippocampal characterization is pivotal for developing a well-performing biomarker for AD. To verify whether a comprehensive characterization of hippocampal features of gray matter volume, segmentation probability, and radiomics features could better distinguish AD from normal control (NC), and to investigate whether the classification decision score could serve as a robust and individualized brain signature. A total of 3238 participants' structural MRI from four independent databases were employed to conduct a 3D residual attention network (3DRA-Net) to classify NC, mild cognitive impairment (MCI), and AD. The generalization was validated under inter-database cross-validation. The neurobiological basis of the classification decision score as a neuroimaging biomarker was systematically investigated by association with clinical profiles, as well as longitudinal trajectory analysis to reveal AD progression. All image analyses were performed only upon the single modality of T1-weighted MRI. Our study exhibited an outstanding performance (ACC = 91.6%, AUC = 0.95) of the comprehensive characterization of hippocampal features in distinguishing AD (n = 282) from NC (n = 603) in Alzheimer's Disease Neuroimaging Initiative cohort, and ACC = 89.2% and AUC = 0.93 under external validation. More importantly, the constructed score was significantly correlated with clinical profiles (p < 0.05), and dynamically altered over the AD longitudinal progression, provided compelling evidence of a solid neurobiological basis. This systemic study highlights the potential of the comprehensive characterization of hippocampal features to provide an individualized, generalizable, and biologically plausible neuroimaging biomarker for early detection of AD. • The comprehensive characterization of hippocampal features exhibited ACC = 91.6% (AUC = 0.95) in classifying AD from NC under intra-database cross-validation, and ACC = 89.2% (AUC = 0.93) in external validation. • The constructed classification score was significantly associated with clinical profiles, and dynamically altered over the AD longitudinal progression, which highlighted its potential of being an individualized, generalizable, and biologically plausible neuroimaging biomarker for early detection of AD.