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

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, whichpredates cognitive decline, might explain this obesity paradox on AD risk. We aimedto assess the impact of late life obesity on brain structure taking into account weightloss as a potential confounder. We included 162 elderly controls of the Alzheimer'sDisease Neuroimaging Initiative (ADNI) with available 3T MRI scan. Significant weightloss was defined as relative weight loss =5% between the baseline and last followup visit. To be able to capture weight loss, only subjects with a minimum clinical andanthropometrical follow-up of 12 months were included. Individuals were categorizedinto three groups according to body mass index (BMI) at baseline: normal-weight(BMI<25 Kg/m), overweight (BMI 25-30 Kg/m) and obese (BMI>30 Kg/m). Weperformed both an interaction analysis between obesity and weight loss, and stratifiedgroup analyses in the weight-stable and weigh-loss groups. We found a significantinteraction between BMI and weight loss affecting brain structure in widespreadcortical areas. The stratified analyses showed atrophy in occipital, inferior temporal,precuneus and frontal regions in the weight stable group, but increased corticalthickness in the weight-loss group. In conclusion, our data support that weight lossnegatively confounds the association between late-life obesity and brain atrophy. Theobesity paradox on AD risk might be explained by reverse causation.