Neurovascular Coupling Mediates the Protective Effects of Cognitive Reserve in Mild Cognitive Impairment: A Multimodal MRI Study

Background: Neurovascular coupling (NVC) impairment is implicated in mild cognitive impairment (MCI). Cognitive reserve (CR) may protect against neurodegeneration, but its relationship with NVC in MCI remains unclear. Objective: This study aimed to investigate whether CR modulates NVC and its association with cognition in MCI patients. Materials and Methods: The study enrolled 113 MCI patients and 83 healthy controls (HCs). All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL) scanning to calculate the ratios of CBF to neural activity metrics (ALFF, fALFF, ReHo, DC) as measures of NVC. They also completed a battery of neuropsychological tests and the Cognitive Reserve Index Questionnaire (CRIq). Results: Compared to HCs, MCI patients showed widespread reduction in whole-brain gray matter NVC. Voxel-wise analysis revealed significantly decreased NVC ratios in cognitive-related brain regions such as the frontal and temporal lobes, while ratios were increased in visual and subcortical areas including the lingual gyrus and putamen. Correlation analysis indicated a positive correlation between the CBF/fALFF ratio in the right lingual gyrus and CRIq scores, whereas NVC ratios in the right orbital frontal gyrus and right middle frontal gyrus were negatively correlated with CRIq. Mediation analysis further demonstrated that the NVC ratios in these specific brain regions mediated the relationship between total CRIq scores and cognitive performance (as measured by MoCA, MMSE, and AVLT-Rec scores). Conclusion: CR is associated with altered NVC in MCI, suggesting a potential neuroprotective mechanism and target for early intervention.