Obesity and Alzheimer's disease, does the obesity paradox really exist? A magnetic resonance imaging study

// Jordi Pegueroles 1, 2, * , Amanda Jiménez 3, 5, * , Eduard Vilaplana 1, 2 , Victor Montal 1, 2 , María Carmona-Iragui 1, 2 , Adriana Pané 3 , Daniel Alcolea 1, 2 , Laura Videla 1, 2 , Anna Casajoana 4 , Jordi Clarimón 1, 2 , Emilio Ortega 3, 5, 6 , Josep Vidal 3, 5, 7 , Rafael Blesa 1, 2 , Alberto Lleó 1, 2 and Juan Fortea 1, 2 for the Alzheimer’s Disease Neuroimaging Initiative ** 1 Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau-Biomedical Research Institute Sant Pau, Barcelona, Spain 2 Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain 3 Obesity Unit, Department of Endocrinology and Nutrition, Hospital Clinic Universitari de Barcelona, Barcelona, Spain 4 Department of Gastrointestinal and Obesity Surgery, Hospital de Barcelona-SCIAS, Barcelona, Spain 5 Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain 6 Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Barcelona, Spain 7 Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas asociadas (CIBERDEM), Barcelona, Spain * These authors have contributed equally to this work ** Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database ( http://adni.loni.usc.edu ). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf . Correspondence to: Juan Fortea, email: jfortea@santpau.cat Amanda Jiménez, email: ajimene1@clinic.ub.es Keywords: preclinical Alzheimer’s disease; obesity; weight loss; magnetic resonance imaging; body mass index Received: August 10, 2018      Accepted: September 10, 2018      Published: October 05, 2018 ABSTRACT Mid-life obesity is an established risk factor for Alzheimer’s disease (AD) dementia, whereas late-life obesity has been proposed as a protective state. Weight loss, which predates cognitive decline, might explain this obesity paradox on AD risk. We aimed to assess the impact of late life obesity on brain structure taking into account weight loss as a potential confounder. We included 162 elderly controls of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) with available 3T MRI scan. Significant weight loss was defined as relative weight loss ≥5% between the baseline and last follow-up visit. To be able to capture weight loss, only subjects with a minimum clinical and anthropometrical follow-up of 12 months were included. Individuals were categorized into three groups according to body mass index (BMI) at baseline: normal-weight (BMI<25 Kg/m 2 ), overweight (BMI 25-30 Kg/m 2 ) and obese (BMI>30 Kg/m 2 ). We performed both an interaction analysis between obesity and weight loss, and stratified group analyses in the weight-stable and weigh-loss groups. We found a significant interaction between BMI and weight loss affecting brain structure in widespread cortical areas. The stratified analyses showed atrophy in occipital, inferior temporal, precuneus and frontal regions in the weight stable group, but increased cortical thickness in the weight-loss group. In conclusion, our data support that weight loss negatively confounds the association between late-life obesity and brain atrophy. The obesity paradox on AD risk might be explained by reverse causation.