Moderating role of executive function in the relationship between specific white matter changes and long-term delayed recall in aMCI patients

Advances in connectomics and network neuroscience have opened new avenues for the in-depth study of complex brain connections and networks. The neuromodulation of connectivity-based circuits and networks is consistent with the underlying complex mechanisms of episodic memory processes involving multiple brain regions, offering significant potential for future therapeutic interventions. However, the relationships among brain changes at multiple levels (single region, fiber tract, and network), episodic memory, and other cognitive domains in patients with amnestic mild cognitive impairment (aMCI) remain unknown. The objectives of this study were (1) to elucidate the characteristics of gray matter microstructure (single region level), specific white matter (fiber tract level), and large-scale brain network (network level) changes in aMCI patients and (2) to explore the hypothesis that other cognitive domains can moderate the relationships between these brain changes at multiple levels and long-term delayed recall. A cross-sectional design was used, with neuropsychological assessments and multimodal MRI scans conducted on 30 aMCI patients and 34 healthy controls. Moderation analysis was performed to explore how other cognitive domains influence the relationships between brain changes and long-term delayed recall. aMCI patients presented significant brain changes at multiple levels (single region, fiber tract, network). Furthermore, moderation analysis based on cross-sectional data revealed that other cognitive domains, particularly executive function, moderate the relationship between specific white matter changes and long-term delayed recall in aMCI patients. This study provides important insights into the complex relationships between multilevel brain alterations and cognitive function in aMCI patients. In particular, the cross-sectional findings suggest that executive function moderates the relationship between specific white matter alterations and long-term delayed recall. These findings may inform future targeted interventions aimed at improving episodic memory and delaying the progression of aMCI.