Adipokines and satiety hormones and incidence of Alzheimer’s disease and dementia in older adults: a nested case-control study

Obesity is known to have an intricate relationship with the development of Alzheimer's disease and dementia (mid-life obesity increases risk, whereas late-life adiposity may also have an effect). In this context, adipokines and satiety signals are suggested to play a role in late life, but their association with the incidence of these outcomes remains unclear. Our study aimed to assess whether five selected plasma adipokines and satiety hormones (leptin, ghrelin, resistin, adipsin, and fibroblast growth factor-21) were associated with incident Alzheimer's disease and dementia in older adults at high cardiovascular risk in a nested case-control study within the PREDIMED trial (90 dementia cases [73 of which were Alzheimer's disease], 156 controls). Participants were at high cardiovascular disease risk but free from dementia at baseline. Associations with biomarkers were assessed using multivariable conditional logistic regression. Higher resistin levels were associated with higher incidence of Alzheimer's disease in the multivariable-adjusted model (per one SD increase: OR 1.56, 95% CI 1.02 to 2.38); additional adjustment for body mass index slightly attenuated the association (OR 1.52, 95% CI 0.99 to 2.34). Our findings should be replicated in larger prospective studies but suggest that, despite the complex association between anthropometric measures and the incidence of dementia, high levels of resistin were tentatively associated with greater odds of incident Alzheimer's disease in older adults at high cardiovascular risk.

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Journal
GeroScience
Published
2026-07-02
DOI
https://doi.org/10.1007/s11357-026-02385-7
Primary Topic
Adipokines, Inflammation, and Metabolic Diseases
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article
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article

Adipokines and satiety hormones and incidence of Alzheimer’s disease and dementia in older adults: a nested case-control study

Miquel Fiol, Jordi Salas‐Salvadó, Juan Timiraos, Dolores Corella et al.
GeroScience
Adipokines, Inflammation, and Metabolic Diseases
article

Adipokines and satiety hormones and incidence of Alzheimer’s disease and dementia in older adults: a nested case-control study

Miquel Fiol, Jordi Salas‐Salvadó, Juan Timiraos, Dolores Corella, Karla Alejandra Pérez‐Vega, Raquel Cueto-Galán, José Lapetra, Miguel Ángel Martínez‐González, Álvaro Hernáez, Indira Paz‐Graniel, Javier Hernando‐Redondo, Olga Castañer, Eva M. Asensio, Juan J. Chillarón, Ramón Estruch, Marta H. Hernández, Emilio Ros, Estefania Toledo, Lluís Serra Majem, Aleix Sala-Vila, Marta Fanlo-Maresma
article en

Abstract

Obesity is known to have an intricate relationship with the development of Alzheimer's disease and dementia (mid-life obesity increases risk, whereas late-life adiposity may also have an effect). In this context, adipokines and satiety signals are suggested to play a role in late life, but their association with the incidence of these outcomes remains unclear. Our study aimed to assess whether five selected plasma adipokines and satiety hormones (leptin, ghrelin, resistin, adipsin, and fibroblast growth factor-21) were associated with incident Alzheimer's disease and dementia in older adults at high cardiovascular risk in a nested case-control study within the PREDIMED trial (90 dementia cases [73 of which were Alzheimer's disease], 156 controls). Participants were at high cardiovascular disease risk but free from dementia at baseline. Associations with biomarkers were assessed using multivariable conditional logistic regression. Higher resistin levels were associated with higher incidence of Alzheimer's disease in the multivariable-adjusted model (per one SD increase: OR 1.56, 95% CI 1.02 to 2.38); additional adjustment for body mass index slightly attenuated the association (OR 1.52, 95% CI 0.99 to 2.34). Our findings should be replicated in larger prospective studies but suggest that, despite the complex association between anthropometric measures and the incidence of dementia, high levels of resistin were tentatively associated with greater odds of incident Alzheimer's disease in older adults at high cardiovascular risk.

GeroScience
Universidad de Las Palmas de Gran Canaria (ES), Harvard University (US), Universitat de València (ES), Universitat Pompeu Fabra (ES), Hospital Universitario Insular de Gran Canaria (ES), Instituto de Salud Carlos III (ES), Institut de Recerca Biomèdica Catalunya Sud (ES), Ajuntament de L’Hospitalet (ES), Hospital Universitario Araba (ES), Navarre Institute of Health Research (ES), Centro de Investigación Biomédica en Red (ES), Hospital Clínic de Barcelona (ES), Servicio Canario de la Salud (ES), Health Research Institute of the Balearic Islands (ES), Hospital Del Mar (ES), Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (ES), Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES), Instituto de Investigación Biomédica de Málaga (ES), Agencia de Evaluación de Tecnologías Sanitarias (ES), Universitat Ramon Llull (ES), Universitat Rovira i Virgili (ES), Universidad de Navarra (ES)
Generalitat Valenciana, Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares, Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición, Agència de Gestió d'Ajuts Universitaris i de Recerca, Instituto de Salud Carlos III, HORIZON EUROPE Marie Sklodowska-Curie Actions
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Adipokines, Inflammation, and Metabolic Diseases
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