Research Papers: Gerotarget (Focus on Aging):

Weight loss in the healthy elderly might be a non-cognitive sign of preclinical Alzheimer’s disease

Amanda Jimenez, Jordi Pegueroles, María Carmona-Iragui, Eduard Vilaplana, Victor Montal, Daniel Alcolea, Laura Videla, Ignacio Illán-Gala, Adriana Pané, Anna Casajoana, Olivia Belbin, Jordi Clarimón, Violeta Moizé, Josep Vidal, Alberto Lleó, Juan Fortea _, Rafael Blesa and The Alzheimer’s Disease Neuroimaging Initiative

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Oncotarget. 2017; 8:104706-104716. https://doi.org/10.18632/oncotarget.22218

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Amanda Jimenez1,2,*, Jordi Pegueroles3,4,*, María Carmona-Iragui3,4, Eduard Vilaplana3,4, Victor Montal3,4, Daniel Alcolea3,4, Laura Videla3,5, Ignacio Illán-Gala3,4, Adriana Pané1, Anna Casajoana6, Olivia Belbin3,4, Jordi Clarimón3,4, Violeta Moizé1,2, Josep Vidal1,2,7, Alberto Lleó3,4, Juan Fortea3,4,**, Rafael Blesa3,4,** and The Alzheimer’s Disease Neuroimaging Initiative***

1 Endocrinology and Diabetes Department, Obesity Unit, Hospital Clinic de Barcelona, Barcelona, Spain

2 Institut d’Investigacions Biomèdiques August Pi Sunyer, Barcelona, Spain

3 Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain

4 Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), San Sebastian, Spain

5 Barcelona Down Medical Center, Fundació Catalana de Síndrome de Down, Barcelona, Spain

6 General Surgery Service, Hospital de Barcelona-SCIAS, Barcelona, Spain

7 Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain

* These authors have contributed equally to the manuscript

** These authors share senior authorship

*** Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (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/wp32 /content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf

Correspondence to:

Juan Fortea, email:

Amanda Jimenez, email:

Keywords: pre-clinical Alzheimer’s disease; weight loss; cerebrospinal fluid Alzheimer’s disease biomarkers; PET amyloid; magnetic resonance imaging; Gerotarget

Received: August 12, 2017 Accepted: October 05, 2017 Published: October 31, 2017


Weight loss has been proposed as a sign of pre-clinical Alzheimer Disease (AD). To test this hypothesis, we have evaluated the association between longitudinal changes in weight trajectories, cognitive performance, AD biomarker profiles and brain structure in 363 healthy controls from the Alzheimer´s Disease Neuroimaging Initiative (mean follow-up 50.5±30.5 months). Subjects were classified according to body weight trajectory into a weight loss group (WLG; relative weight loss ≥ 5%) and a non-weight loss group (non-WLG; relative weight loss < 5%). Linear mixed effects models were used to estimate the effect of body weight changes on ADAS-Cognitive score across time. Baseline CSF tau/Aß42 ratio and AV45 PET uptake were compared between WLG and non-WLG by analysis of covariance. Atrophy maps were compared between groups at baseline and longitudinally at a 2-year follow-up using Freesurfer. WLG showed increased baseline levels of cerebrospinal fluid tau/Aß42 ratio, increased PET amyloid uptake and diminished cortical thickness at baseline. WLG also showed faster cognitive decline and faster longitudinal atrophy. Our data support weight loss as a non-cognitive manifestation of pre-clinical AD.

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