Effects of High BMI on Synaptic Function and Metabolic Connectivity in the Brain—Evidence of Gender Difference

Abstract

Several studies reported a significant association with obesity and cognitive deficits in aging, especially for executive, attention and memory domains. The neural effects of obesity and the correlated cognitive dysfunction have yet to be elucidated. We retrospectively collected a large cohort of healthy elderlies (N=222; age=74.03±5.88y; M/F=112/105; BMI range=19.21-38.79), from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. All subjects underwent in vivo positron emission tomography with 18F-Fluorodeoxyglucose (FDG), thus we were able to evaluate the correlation between BMI, synaptic function and metabolic connectivity in the whole brain and within the resting-state neural networks, crucially considering the effect of gender. We found a significant positive correlation between BMI levels and brain metabolism in female group only (R=.435; P<0.001), with high BMI associated with increased glucose consumption in the orbitofrontal cortex. Whole brain connectivity analysis revealed an altered pattern in frontal regions in females with high BMI, namely a decreased connectivity between orbitofrontal regions and high-order prefrontal cortex, and an abnormally elevated connectivity with nucleus accumbens. The connectivity analysis of the resting-state brain networks confirmed that in elderly females with high BMI, the core of vulnerability is within the frontal regions, with impaired connectivity in executive and salience networks. In contrast, elderly males with high BMI showed loss of long-distance connections between frontal and parietal cortices, invariantly across attentional, executive and posterior default mode networks. Our findings support a strong detrimental effect of high BMI levels on brain metabolism and neural connectivity in healthy aging, with gender differences. Notably, high BMI in females affects the executive and reward systems. This evidence brings to considerations for medical practice and health policy. Disclosure A. Sala: None. M. Malpetti: None. A. Ferrulli: None. L. Gianolli: None. L. Luzi: Speaker's Bureau; Self; A. Menarini Diagnostics, AstraZeneca, Eli Lilly and Company. Research Support; Self; Gelesis. Consultant; Self; McKinsey & Company. Speaker's Bureau; Self; Menarini Group, Merck Sharp & Dohme Corp.. Research Support; Self; Novartis AG. Speaker's Bureau; Self; Novo Nordisk A/S. Research Support; Self; Sunstar Foundation. Speaker's Bureau; Self; Smith & Nephew. D. Perani: None.