Prospective Associations of Plasma Growth Differentiation Factor 15 With Physical Performance and Cognitive Functions in Older Adults
Lingxiao He, Philipe de Souto Barreto, Juan Luis Sánchez Sánchez, Yves Rolland, Sophie Guyonnet, Angelo Parini, Alexandre Lucas, Bruno Vellas, MAPT/DSA Group, Bruno Vellas, Sophie Guyonnet, Isabelle Carrié, Lauréane Brigitte, Catherine Faisant, Françoise Lala, Julien Delrieu, Hélène Villars, Psychologists Emeline Combrouze, Carole Badufle, Audrey Zueras, Christelle Cantet, Christophe Morin, Gabor Abellán van Kan, Charlotte Dupuy, Yves Rolland, Céline Caillaud, Pierre‐Jean Ousset, Françoise Lala, Brigitte Gilbert, Francine Fontaine, Jean‐François Dartigues, Isabelle Marcet, Fleur Delva, Alexandra Foubert, Sandrine Cerda, Marie Noëlle-Cuff, Corinne Costes, Olivier Rouaud, Patrick Manckoundia, Valérie Quipourt, Sophie Marilier, Evelyne Franon, Lawrence Bories, Marie-Laure Pader, Marie-France Basset, Bruno Lapoujade, Valérie Faure, Michael Li Yung Tong, Christine Malick-Loiseau, Evelyne Cazaban-Campistron, Françoise Desclaux, Colette Blatge, Thierry Dantoine, Cécile Laubarie-Mouret, Isabelle Saulnier, Jean‐Pierre Clément, Marie-Agnès Picat, Laurence Bernard‐Bourzeix, Stéphanie Willebois, Ileana Désormais, Noëlle Cardinaud, Marc Bonnefoy, Pierre Livet, Pascale Rebaudet, Claire Gédéon, Catherine Burdet, Flavien Terracol, Alain Pesce, Stéphanie Roth, Sylvie Chaillou, Sandrine Louchart, Kristelle Sudres, Nicolas Lebrun, Nadège Barro-Belaygues, Jacques Touchon, Karim Bennys, Audrey Gabelle, Aurélia Romano, Lynda Touati, Cécilia Marelli, Cécile Pays, Philippe Robert, Franck Le Duff, Claire Gervais, S. Gonfrier, Yannick Gasnier and Serge Bordes, Danièle Begorre, Christian Carpuat, Khaled Khales, Jean‐François Lefebvre, Samira Misbah El Idrissi, Pierre Skolil, Jean-Pierre Salles, Carole Dufouil, Stéphane Lehéricy, Marie Chupin, Jean‐François Mangin, Ali Bouhayia, Michèle Allard, F. Ricolfi
Abstract
BACKGROUND: Growth differentiation factor 15 (GDF15) has been associated with several age-related disorders, but its associations with functional abilities in community-dwelling older adults are not well studied. METHODS: The study was a secondary analysis of 1 096 community-dwelling older adults (aged 69-94 years) recruited from the Multidomain Alzheimer's Preventive Trial. Plasma GDF15 was measured 1 year after participants' enrollment. Annual data of physical performance (grip strength and Short Physical Performance Battery [SPPB]) and global cognitive functions (Mini-Mental State Examination [MMSE] and a composite cognitive score) were measured for 4 years. Adjusted mixed-effects linear models were performed for cross-sectional and longitudinal association analyses. RESULTS: A higher GDF15 was cross-sectionally associated with a weaker grip strength (β = -1.1E-03, 95% CI [-2.0E-03, -1.5E-04]), a lower SPPB score (β = -3.1E-04, 95% CI [-5.4E-04, -9.0E-05]), and worse cognitive functions (β = -2.4E-04, 95% CI [-3.3E-04, -1.6E-04] for composite cognitive score; β = -4.0E-04, 95% CI [-6.4E-04, -1.6E-04] for MMSE). Participants with higher GDF15 demonstrated greater longitudinal declines in SPPB (β = -1.0E-04, 95% CI [-1.7E-04, -2.0E-05]) and composite cognitive score (β = -2.0E-05, 95% CI [-4.0E-05, -3.6E-06]). The optimal initial GDF15 cutoff values for identifying participants with minimal clinically significant decline after 1 year were 2 189 pg/mL for SPPB (AUC: 0.580) and 2 330 pg/mL for composite cognitive score (AUC: 0.587). CONCLUSIONS: Plasma GDF15 is cross-sectionally and longitudinally associated with lower-limb physical performance and global cognitive function in older adults. Circulating GDF15 alone has a limited capacity of discriminating older adults who will develop clinically significant functional declines. CLINICAL TRIAL REGISTRATION: NCT00672685.