Prospective Associations of Plasma Growth Differentiation Factor 15 With Physical Performance and Cognitive Functions in Older Adults
Authors: He Lingxiao , de Souto Barreto Philipe , Sánchez Sánchez Juan Luis , Rolland Yves , Guyonnet Sophie , Parini Angelo , Lucas Alexandre , Vellas Bruno ,   MAPT/DSA Group, Vellas Bruno , Guyonnet Sophie , Carrié Isabelle , Brigitte Lauréane , Faisant Catherine , Lala Françoise , Delrieu Julien , Villars Hélène , Emeline Combrouze Psychologists: , Badufle Carole , Zueras Audrey , Cantet Christelle , Morin Christophe , Abellan Van Kan Gabor , Dupuy Charlotte , Rolland Yves , Caillaud Céline , Ousset Pierre-Jean , Lala Françoise , Gilbert Brigitte , Fontaine Francine , Dartigues Jean-François , Marcet Isabelle , Delva Fleur , Foubert Alexandra , Cerda Sandrine , Noëlle-Cuff Marie , Costes Corinne , Rouaud Olivier , Manckoundia Patrick , Quipourt Valérie , Marilier Sophie , Franon Evelyne , Bories Lawrence , Pader Marie-Laure , Basset Marie-France , Lapoujade Bruno , Faure Valérie , Li Yung Tong Michael , Malick-Loiseau Christine , Cazaban-Campistron Evelyne , Desclaux Françoise , Blatge Colette , Dantoine Thierry , Laubarie-Mouret Cécile , Saulnier Isabelle , Clément Jean-Pierre , Picat Marie-Agnès , Bernard-Bourzeix Laurence , Willebois Stéphanie , Désormais Iléana , Cardinaud Noëlle , Bonnefoy Marc , Livet Pierre , Rebaudet Pascale , Gédéon Claire , Burdet Catherine , Terracol Flavien , Pesce Alain , Roth Stéphanie , Chaillou Sylvie , Louchart Sandrine , Sudres Kristelle , Lebrun Nicolas , Barro-Belaygues Nadège , Touchon Jacques , Bennys Karim , Gabelle Audrey , Romano Aurélia , Touati Lynda , Marelli Cécilia , Pays Cécile , Robert Philippe , Le Duff Franck , Gervais Claire , Gonfrier Sébastien , Gasnier and Serge Bordes Yannick , Begorre Danièle , Carpuat Christian , Khales Khaled , Lefebvre Jean-François , Misbah El Idrissi Samira , Skolil Pierre , Salles Jean-Pierre , Dufouil Carole , Lehéricy Stéphane , Chupin Marie , Mangin Jean-François , Bouhayia Ali , Allard Michèle , Ricolfi Frédéric , Dubois Dominique , Paule Bonceour Martel Marie , Cotton François , Bonafé Alain , Chanalet Stéphane , Hugon Françoise , Bonneville Fabrice , Cognard Christophe , Chollet François , Payoux Pierre , Voisin Thierry , Delrieu Julien , Peiffer Sophie , Hitzel Anne , Allard Michèle , Zanca Michel , Monteil Jacques , Darcourt Jacques , Molinier Laurent , Derumeaux Hélène , Costa Nadège , Perret Bertrand , Vinel Claire , Caspar-Bauguil Sylvie , Olivier-Abbal Pascale 
Published: January 2022

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