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Journal Articles GeroScience Year : 2023

Low circulating adropin concentrations predict increased risk of cognitive decline in community-dwelling older adults

Geetika Aggarwal (1) , John E Morley (1) , Bruno Vellas , Andrew D Nguyen (1) , Andrew A Butler (2) , Sophie Guyonnet , Isabelle Carrié (3) , Lauréane Brigitte (3) , Catherine Faisant (3) , Françoise Lala (3) , Julien Delrieu (4) , Hélène Villars (5, 6) , Emeline Combrouze , Carole Badufle , Audrey Zueras , Sandrine Andrieu (7, 3, 6) , Christelle Cantet (3) , Christophe Morin (8, 9) , Gabor Abellan van Kan , Charlotte Dupuy (10) , Yves Rolland , Céline Caillaud (11) , Pierre-Jean Ousset , Françoise Lala (3) , Sherry Willis (12) , Sylvie Belleville (13) , Brigitte Gilbert (13) , Francine Fontaine , Jean-François Dartigues (14) , Isabelle Marcet , Fleur Delva (14) , Alexandra Foubert , Sandrine Cerda , Corinne Costes , Olivier Rouaud (15, 16, 17) , Patrick Manckoundia (18) , Valérie Quipourt (19) , Sophie Marilier (20) , Evelyne Franon (21) , 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 , Iléana Désormais , Noëlle Cardinaud , Marc Bonnefoy , Pierre Livet , Pascale Rebaudet , Claire Gédéon , Catherine Burdet , Flavien Terracol , Alain Pesce , Stéphanie Roth , Sylvie Chaillou , Sandrine Louchart , Kristel 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 , Sébastien Gonfrier , Yannick Gasnier , 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 , Frédéric Ricolfi , Dominique Dubois , Marie Paule Bonceour Martel , François Cotton , Alain Bonafé , Stéphane Chanalet , Françoise Hugon , Fabrice Bonneville , Christophe Cognard , François Chollet , Pierre Payoux , Thierry Voisin , Julien Delrieu (4, 22, 6) , Sophie Peiffer , Anne Hitzel , Michèle Allard , Michel Zanca , Jacques Monteil , Jacques Darcourt , Laurent Molinier , Hélène Derumeaux , Nadège Costa , Bertrand Perret , Claire Vinel , Sylvie Caspar-Bauguil , Pascale Olivier-Abbal , Sandrine Andrieu (7, 3, 6) , Christelle Cantet (3, 22, 6) , Nicola Coley
Bruno Vellas
Sophie Guyonnet
  • Function : Author
Emeline Combrouze
  • Function : Author
Carole Badufle
  • Function : Author
Audrey Zueras
  • Function : Author
Gabor Abellan van Kan
  • Function : Author
Yves Rolland
  • Function : Author
Pierre-Jean Ousset
  • Function : Author
Francine Fontaine
  • Function : Author
Isabelle Marcet
  • Function : Author
Alexandra Foubert
  • Function : Author
Sandrine Cerda
  • Function : Author
Corinne Costes
  • Function : Author
Valérie Quipourt
  • Function : Author
Lawrence Bories
  • Function : Author
Marie-Laure Pader
  • Function : Author
Marie-France Basset
  • Function : Author
Bruno Lapoujade
  • Function : Author
Valérie Faure
  • Function : Author
Michael Li Yung Tong
  • Function : Author
Christine Malick-Loiseau
  • Function : Author
Evelyne Cazaban-Campistron
  • Function : Author
Françoise Desclaux
  • Function : Author
Colette Blatge
  • Function : Author
Thierry Dantoine
  • Function : Author
Cécile Laubarie-Mouret
  • Function : Author
Isabelle Saulnier
  • Function : Author
Jean-Pierre Clément
  • Function : Author
Marie-Agnès Picat
  • Function : Author
Laurence Bernard-Bourzeix
  • Function : Author
Stéphanie Willebois
  • Function : Author
Iléana Désormais
  • Function : Author
Noëlle Cardinaud
  • Function : Author
Marc Bonnefoy
  • Function : Author
Pierre Livet
  • Function : Author
Pascale Rebaudet
  • Function : Author
Claire Gédéon
  • Function : Author
Catherine Burdet
  • Function : Author
Flavien Terracol
  • Function : Author
Alain Pesce
  • Function : Author
Stéphanie Roth
  • Function : Author
Sylvie Chaillou
  • Function : Author
Sandrine Louchart
  • Function : Author
Kristel Sudres
  • Function : Author
Nicolas Lebrun
  • Function : Author
Nadège Barro-Belaygues
  • Function : Author
Jacques Touchon
  • Function : Author
Karim Bennys
  • Function : Author
Audrey Gabelle
  • Function : Author
Aurélia Romano
  • Function : Author
Lynda Touati
  • Function : Author
Cécilia Marelli
  • Function : Author
Cécile Pays
  • Function : Author
Philippe Robert
  • Function : Author
Franck Le Duff
  • Function : Author
Claire Gervais
  • Function : Author
Sébastien Gonfrier
  • Function : Author
Yannick Gasnier
  • Function : Author
Serge Bordes
  • Function : Author
Danièle Begorre
  • Function : Author
Christian Carpuat
  • Function : Author
Khaled Khales
  • Function : Author
Jean-François Lefebvre
  • Function : Author
Samira Misbah El Idrissi
  • Function : Author
Pierre Skolil
  • Function : Author
Jean-Pierre Salles
  • Function : Author
Carole Dufouil
  • Function : Author
Stéphane Lehéricy
  • Function : Author
Marie Chupin
  • Function : Author
Jean-François Mangin
  • Function : Author
Ali Bouhayia
  • Function : Author
Michèle Allard
  • Function : Author
Frédéric Ricolfi
  • Function : Author
Dominique Dubois
  • Function : Author
Marie Paule Bonceour Martel
  • Function : Author
François Cotton
Alain Bonafé
  • Function : Author
Stéphane Chanalet
  • Function : Author
Françoise Hugon
  • Function : Author
Fabrice Bonneville
  • Function : Author
Christophe Cognard
  • Function : Author
François Chollet
  • Function : Author
Pierre Payoux
Thierry Voisin
  • Function : Author
Sophie Peiffer
  • Function : Author
Anne Hitzel
  • Function : Author
Michèle Allard
  • Function : Author
Michel Zanca
  • Function : Author
Jacques Monteil
  • Function : Author
Jacques Darcourt
  • Function : Author
Laurent Molinier
  • Function : Author
Hélène Derumeaux
  • Function : Author
Nadège Costa
  • Function : Author
Bertrand Perret
  • Function : Author
Claire Vinel
  • Function : Author
Sylvie Caspar-Bauguil
  • Function : Author
Pascale Olivier-Abbal
  • Function : Author
Nicola Coley
  • Function : Author

Abstract

Abstract The secreted peptide adropin is highly expressed in human brain tissues and correlates with RNA and proteomic risk indicators for dementia. Here we report that plasma adropin concentrations predict risk for cognitive decline in the Multidomain Alzheimer Preventive Trial (ClinicalTrials.gov Identifier, NCT00672685; mean age 75.8y, SD = 4.5 years, 60.2% female, n = 452). Cognitive ability was evaluated using a composite cognitive score (CCS) that assessed four domains: memory, language, executive function, and orientation. Relationships between plasma adropin concentrations and changes in CCS (∆CCS) were examined using Cox Proportional Hazards Regression, or by grouping into tertiles ranked low to high by adropin values and controlling for age, time between baseline and final visits, baseline CCS, and other risk factors (e.g., education, medication, APOE4 status). Risk of cognitive decline (defined as a ∆CCS of − 0.3 or more) decreased with increasing plasma adropin concentrations (hazard ratio = 0.873, 95% CI 0.780–0.977, P = 0.018). Between adropin tertiles, ∆CCS was significantly different ( P = 0.01; estimated marginal mean ± SE for the 1st to 3rd tertile, − 0.317 ± 0.064; − 0.275 ± 0.063; − 0.042 ± 0.071; n = 133,146, and 130, respectively; P < 0.05 for 1st vs. 2nd and 3rd adropin tertiles). Normalized plasma Aß 42/40 ratio and plasma neurofilament light chain, indicators of neurodegeneration, were significantly different between adropin tertile. These differences were consistent with reduced risk of cognitive decline with higher plasma adropin levels. Overall, these results suggest cognitive decline is reduced in community-dwelling older adults with higher circulating adropin levels. Further studies are needed to determine the underlying causes of the relationship and whether increasing adropin levels can delay cognitive decline.
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hal-04492066 , version 1 (06-03-2024)

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Geetika Aggarwal, John E Morley, Bruno Vellas, Andrew D Nguyen, Andrew A Butler, et al.. Low circulating adropin concentrations predict increased risk of cognitive decline in community-dwelling older adults. GeroScience, 2023, 46 (1), pp.897-911. ⟨10.1007/s11357-023-00824-3⟩. ⟨hal-04492066⟩
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