The effect of hippocampal radiomic features and functional connectivity on the relationship between hippocampal volume and cognitive function in Alzheimer's disease.

Hippocampal volume is associated with cognitive function in Alzheimer's disease (AD). Hippocampal radiomic features and resting-state functional connectivity (rs-FC) are promising biomarkers and correlate with AD pathology. However, few studies have been conducted on how hippocampal biomarkers affect the cognition-structure relationship. Therefore, we aimed to investigate the effects of hippocampal radiomic features and resting-state functional connectivity (rs-FC) on this relationship in AD. We enrolled 70 AD patients and 65 healthy controls (HCs). The FreeSurfer software was used to measure hippocampal volume. We selected hippocampal radiomic features to build a model to distinguish AD patients from HCs and used a seed-based approach to calculate the hippocampal rs-FC. Furthermore, we conducted mediation and moderation analyses to investigate the effect of hippocampal radiomic features and rs-FC on the relationship between hippocampal volume and cognition in AD. The results suggested that hippocampal radiomic features mediated the association between bilateral hippocampal volume and cognition in AD. Additionally, patients with AD showed weaker rs-FC between the bilateral hippocampus and right ventral posterior cingulate cortex and stronger rs-FC between the left hippocampus and left insula than HCs. The rs-FC between the hippocampus and insula moderated the relationship between hippocampal volume and cognition in AD, suggesting that this rs-FC could exacerbate or ameliorate the effects of hippocampal volume on cognition and may be essential in improving cognitive function in AD. Our findings may not only expand existing biological knowledge of the interrelationships among hippocampal biomarkers and cognition but also provide potential targets for treatment strategies for AD.