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There are reported gender differences in brain connectivity associated with obesity. In the elderlies, the neural endophenotypes of obesity are yet to be elucidated. We aim at exploring the brain metabolic and connectivity correlates to different BMI levels in elderly individuals, taking into account gender as variable of interest.We evaluated the association between BMI, brain metabolism and connectivity, in elderly females and males, by retrospectively collecting a large cohort of healthy elderly subjects (N=222; age=74.03±5.88 [61.2-85.9] years; M/F=115/107; BMI=27.00±4.02 [19.21-38.79] kg/m 2 ). Subjects underwent positron emission tomography with [18F]FDG. We found that, in females, high BMI was associated with increased brain metabolism in the orbitofrontal cortex (R=0.44; p&lt;0.001). A significant BMI-by-gender interaction was present (F=7.024, p=0.009). We also revealed an altered connectivity seeding from these orbitofrontal regions, namely expressing as a decreased connectivity in crucial control/decision making circuits, and as an abnormally elevated connectivity in reward circuits, only in females. Our findings support a link between high BMI and altered brain metabolism and neural connectivity, only in elderly females. These findings indicate a strong gender effect of high BMI and obesity that brings to considerations for medical practice and health policy.

High body mass index, brain metabolism and connectivity: an unfavorable effect in elderly females