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

Alzheimers Dement (Amst). 2020 Jul 28;12(1):e12052. doi: 10.1002/dad2.12052. eCollection 2020.

Abstract

Aims/hypothesis: Midlife obesity is a risk factor for dementia. We investigated the impact of obesity on brain structure, metabolism, and cerebrospinal fluid (CSF) core Alzheimer's disease (AD) biomarkers in healthy elderly.

Methods: We selected controls from ADNI2 with CSF AD biomarkers and/or fluorodeoxyglucose positron emission tomography (FDG-PET) and 3T-MRI. We measured cortical thickness, FDG uptake, and CSF amyloid beta (Aβ)1-42, p-tau, and t-tau levels. We performed regression analyses between these biomarkers and body mass index (BMI).

Results: We included 201 individuals (mean age 73.5 years, mean BMI 27.4 kg/m2). Higher BMI was related to less cortical thickness and higher metabolism in brain areas typically not involved in AD (family-wise error [FWE] <0.05), but not to AD CSF biomarkers. It is notable that the impact of obesity on brain metabolism and structure was also found in amyloid negative individuals.

Conclusions/interpretation: In the cognitively unimpaired elderly, obesity has differential effects on brain metabolism and structure independent of an underlying AD pathophysiology.

Keywords: body mass index; cerebrospinal fluid Alzheimer's disease biomarkers; fluorodeoxyglucose PET; magnetic resonance imaging; obesity; pre‐clinical Alzheimer's disease.