Body mass index is associated with functional brain network efficiency in midlife world trade center responders with cognitive impairment

Background: Higher body mass index (BMI) is associated with lowered risk of dementia in aging populations, possibly because it improves cognitive reserve in old age. Little is known about mechanisms implicated in reductions in vulnerability and less is known about implications of BMI in cognitively impaired (CI) individuals at midlife. Here, we examined whether BMI relates to functional brain network efficiency and cognition in a physically active cohort of midlife World Trade Center (WTC) responders with documented 9/11-related exposures, testing how systemic inflammatory burden and body composition jointly shape brain networks. Methods: Resting-state fMRI data from 99 WTC responders and 10 matched controls were analyzed. Functional cerebral network efficiency metrics included characteristic path length (CPL), clustering coefficients (CC), global efficiency (GE), and small-worldness (SWN), and were derived across proportional sparsity thresholds to enhance robustness. Multivariate models tested the effects of BMI, CI, and their interaction on network efficiency. Results: Higher BMI and CI were independently associated with cerebral network efficiency. A significant BMI × CI interaction was identified (CPL: p=0.024; SWN: p=0.010; GE: p=0.034), indicating that the positive association between BMI and network efficiency was strongest among cognitively impaired responders. Specifically, elevated BMI correlated with more integrated and efficient networks (e.g., shorter CPL and greater CC, GE, and SWN). Functional network efficiency metrics were modestly associated with attention and processing speed, but not with memory or visuospatial performance, suggesting selective relevance to cognitive domains vulnerable to early disruption. Conclusions: Consistent with hypotheses of cognitive reserve, this study provides novel evidence that functional brain network topology is influenced by BMI among cognitively impaired WTC responders. Findings highlight a complex interplay among systemic health, brain organization, and cognitive function at midlife.