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Oncotarget. 2017 Oct 31;8(62):104706-104716. doi: 10.18632/oncotarget.22218. eCollection 2017 Dec 1.

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

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Endocrinology and Diabetes Department, Obesity Unit, Hospital Clinic de Barcelona, Barcelona, Spain.
Institut d'Investigacions Biomèdiques August Pi Sunyer, Barcelona, Spain.
Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), San Sebastian, Spain.
Barcelona Down Medical Center, Fundació Catalana de Síndrome de Down, Barcelona, Spain.
General Surgery Service, Hospital de Barcelona-SCIAS, Barcelona, Spain.
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
Contributed equally


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/AΔ42 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/AΔ42 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.


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

Conflict of interest statement

CONFLICTS OF INTEREST All authors report no biomedical financial interests or potential conflicts of interest related to this work.

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