Trajectory of stratum radiatum, lacunosum and moleculare integrity in Alzheimer’s disease continuum

The atrophy of the hippocampus and its subfields represents a critical hallmark of neurodegeneration in Alzheimer's Disease (AD). However, the trajectories of stratum radiatum, lacunosum, and moleculare (SRLM) integrity along the AD continuum are still unclear. This study encompassed 178 amyloid-negative cognitively unimpaired controls (CU A-), 91 amyloid-positive cognitively unimpaired individuals (CU A+), 90 amyloid-positive patients with mild cognitive impairment (MCI A+), and 14 amyloid-positive AD patients (AD A+), to model the AD continuum. T1-weighted images facilitated the hippocampal volume segmentation, while T2-weighted images enabled both visual hippocampal atrophy and SRLM assessments. Furthermore, the associations between hippocampal metrics and cognitive function were evaluated. Across the AD continuum, CU A+ individuals exhibited lower visual SRLM integrity score compared to their CU A- counterparts. Both MCI A+ and AD A+ groups displayed reduced SRLM integrity score, increased visual hippocampal atrophy score, and decreased hippocampal volume compared to CU A-. Correlational analyses revealed significant associations between hippocampal metrics and cognitive function. Hippocampal atrophy progresseses along the AD continuum, with visual SRLM integrity score declining in the early stages of AD. These results suggest that SRLM integrity may serve as a sensitive marker for early detection of AD.