The structural-functional connectivity coupling in the right caudal hippocampus mediates the effects of body mass index on cognitive function.

Background: Studies have demonstrated an association between cognitive decline and body mass index (BMI). However, the neural mechanisms that underlie this association remain unclear. This study aimed to investigate the relationship between BMI, cognitive function, and brain structural-functional connectivity (SC-FC) coupling.

Methods: This study included 490 healthy subjects undergoing resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) scans and cognitive function tests. Structural connectivity (SC) was constructed using DTI, and functional connectivity (FC) was constructed using rs-fMRI. The SC-FC coupling was constructed using Spearman's correlation between the SC and FC. Linear regression analyses were conducted to investigate the associations of BMI and SC-FC with cognitive function. Finally, mediation analysis was performed to test whether SC-FC coupling mediated the relationship between BMI and cognitive function.

Results: BMI was positively correlated with Fluency, TMT-A, and WMS-III-SS, while showing negative associations with BACS-SC, BVMT-R, and NAB-Mazes (all p < 0.05). Higher BMI was linked to increased SC-FC in the right caudal hippocampus (cHipp; β = 0.19) and middle temporal gyrus (MTG; β = 0.19). Mediation analyses showed that the positive effect of BMI on the right cHipp SC-FC mediated its negative impact on Fluency (45.43 % mediated); the influence of BMI on right cHipp SC-FC mediated poorer performance on NAB-Mazes (85.25 % mediated); and the positive effect of BMI on right MTG SC-FC enhanced NAB-Mazes performance (69.12 % mediated).

Conclusions: BMI influences cognitive function through its effects on brain SC-FC coupling, with distinct regional SC-FC patterns mediating both detrimental and beneficial cognitive outcomes.