Multimodal MRI insights into hippocampal pathological changes across the Alzheimer's disease continuum: advances and challenges.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, with early and progressive hippocampal pathology serving as a hallmark across the AD continuum, including subjective cognitive decline, mild cognitive impairment, and AD dementia. Single-modal MRI fails to fully capture multilevel hippocampal neuropathology, hindering accurate early diagnosis and prognostic prediction of AD. This narrative review summarizes recent advances in structural MRI, diffusion tensor imaging, magnetic resonance spectroscopy, quantitative susceptibility mapping, arterial spin labeling, and functional MRI for evaluating hippocampal and medial temporal lobe abnormalities in AD. These techniques provide a multifaceted characterization of AD-associated hippocampal alterations, including macroscopic atrophy, microstructural degeneration, metabolic dysregulation, aberrant iron deposition, hemodynamic dysfunction, and abnormal neuronal activity. Hippocampal damage in AD exhibits distinct subfield specificity, hemispheric asymmetry, and stage-dependent progression, modulated by Aβ/tau pathology, neuroinflammation, and apolipoprotein E ε4 genotype. Notably, multimodal imaging fusion integrated with machine learning outperforms single-modal biomarkers, significantly improving the accuracy of AD early screening, differential diagnosis, and prognostic prediction. Nevertheless, existing studies are hampered by inadequate pathological validation, limited sample sizes, unsatisfactory reproducibility, and multicenter technical heterogeneity. Multimodal MRI offers robust non-invasive evidence for exploring AD hippocampal pathophysiology. Future large-scale multicenter longitudinal studies combining artificial intelligence will advance precision diagnosis and targeted therapy for AD by clarifying the interplay among AD pathology, genetics, and heterogeneous hippocampal injury.