Sex-Specific Patterns of Body Mass Index Relationship with White Matter Connectivity

Background: Obesity is an increasingly recognized modifiable risk factor for Alzheimer's disease (AD). Increased body mass index (BMI) is related to distinct changes in white matter (WM) fiber density and connectivity. Objective: We investigated whether sex differentially affects the relationship between BMI and WM structural connectivity. Methods: A cross-sectional sample of 231 cognitively normal participants were enrolled from the Knight Alzheimer Disease Research Center. Connectome analyses were done with diffusion data reconstructed using q-space diffeomorphic reconstruction to obtain the spin distribution function and tracts were selected using a deterministic fiber tracking algorithm. Results: We identified an inverse relationship between higher BMI and lower connectivity in the associational fibers of the temporal lobe in overweight and obese men. Normal to overweight women showed a significant positive association between BMI and connectivity in a wide array of WM fibers, an association that reversed in obese and morbidly obese women. Interaction analyses revealed that with increasing BMI, women showed higher WM connectivity in the bilateral frontoparietal and parahippocampal parts of the cingulum, while men showed lower connectivity in right sided corticostriatal and corticopontine tracts. Subgroup analyses demonstrated comparable results in participants with and without positron emission tomography or cerebrospinal fluid evidence of brain amyloidosis, indicating that the relationship between BMI and structural connectivity in men and women is independent of AD biomarker status. Conclusion: BMI influences structural connectivity of WM differently in men and women across BMI categories and this relationship does not vary as a function of preclinical AD.

Automated summary

This study investigated the relationship between body mass index (BMI) and white matter (WM) structural connectivity in cognitively normal individuals. The results revealed different effects of BMI on WM connectivity in men and women, with higher BMI associated with lower connectivity in the temporal lobe in overweight and obese men, and higher connectivity in a wide array of WM fibers in normal to overweight women. The study also found that BMI influenced WM connectivity differently in specific brain regions in men and women.