Obesity impacts brain metabolism and structure independently of amyloid and tau pathology in healthy elderly

Abstract Background: Mid-life obesity is related to increased risk for overall dementia and Alzheimer´s disease (AD) dementia. In the present work, we aimed to investigate the impact of obesity on brain structure, metabolism, and cerebrospinal fluid (CSF) biomarkers of amyloid (Aβ 1-42) and tau-pathology (total-tau and p-tau) in healthy elderly. Methods: We selected healthy controls from ADNI2 with available CSF AD biomarkers and/or fluorodeoxyglucose (FDG) PET and 3T-MRI. Participants without follow-up or with significant weight loss were excluded from the analyses. Brain cortical thickness (Cth) was evaluated with Freesurfer software and FDG uptake was measured with a surface-based method using both SPM and Freesurfer softwares. We performed regression analyses between FDG uptake, CTh, CSF AD biomarkers levels and BMI and interaction analyses with age by obesity/overweight status. Results: We included 147 individuals (mean age 73.3 years, mean BMI 27.4 Kg/m 2 ). Higher BMI was related to less cortical thickness and higher glucose metabolism in brain areas not typically involved in AD (FWE<0.05), with little overlap between them. There was no association between BMI and any of the CSF core AD biomarkers. The relationship between age and brain metabolism was modified by overweight/obesity status, but not that of age and brain structure or core CSF AD biomarkers. Conclusions: Our data support that obesity has differential effects on brain metabolism and structure independent of an underlying AD pathophysiology in cognitively unimpaired elderly.