https://orcid.org/0000-0002-0348-3664
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Abstract
Objectives
Fatigue has been suggested as a marker of biological aging. It seems plausible that this symptom might be associated with changes in brain health. The objective of this study was to examine the associations between persistent fatigue and neuroimaging correlates in a non-disease-specific population of community-dwelling older adults.
Methods
We performed a cross-sectional analysis using data from The Multidomain Alzheimer Preventive Trial (MAPT). We included 458 subjects. Persistent fatigue was defined as meeting exhaustion criterion of Fried frailty phenotype in two consecutive clinical visits six months apart between study baseline and one year. Brain imaging correlates, assessed by magnetic resonance imaging (MRI), were the outcomes. The associations between persistent fatigue and brain correlates were explored using mixed model linear regressions with random effect at the center level.
Results
The mean age of the participants was 74.8 ± 4 years old, and 63% of the subjects were women. Forty-seven participants (10%) exhibited a persistent fatigue profile. People with persistent fatigue were older compared to subjects without persistent fatigue (76.2 years ± 4.3 vs.74.7 ± 3.9 p = 0.009). Persistent fatigue was associated with higher white matter hyperintensity volume in the fully adjusted analysis. We did not find any cross-sectional association between persistent fatigue and sub-cortical volumes and global and regional cortical thickness.
Conclusion
Persistent fatigue was cross-sectionnally associated with higher white matter hyperintensity volume in older adults. Further longitudinal studies, using an assessment tool specifically designed and validated for measuring fatigue, are needed to confirm our findings.
Acknowledgements
We would like to thank Laure Saint-Aubert for the methodological advice about neuroimaging data.
Disclosure statement
The author do not declare any conflict of interest
Authors’ contributions
DA: conceived the project, drafted the article, was responsible for data analysis and interpretation; MCe: conceived the project, modified the article with important intellectual content; JR: supervised the data analysis; KVG: drafted the article, was involved in the critical appraisal of the manuscript; MCh: management of the MRI sequences, MRI data collection and analysis; AB: Quality control of the MRI data; CF, EG: MRI data analysis and quality control; JFM, YR, SDB, BV: modified the article with important intellectual content; PSB: conceived the project, drafted the article, was involved in the critical appraisal of the manuscript
The present work was performed in the context of the Inspire Program, a research platform supported by grants from the Region Occitanie/Pyrénées-Méditerranée (Reference number: 1901175) and the European Regional Development Fund (ERDF) (Project number: MP0022856). This study received funds from Alzheimer Prevention in Occitania and Catalonia (APOC Chair of Excellence - Inspire Program).
MAPT/DSA members
MAPT study group
Principal investigator: Bruno Vellas (Toulouse); Coordination: Sophie Guyonnet; Project leader: Isabelle Carrié; CRA: Lauréane Brigitte; Investigators: Catherine Faisant, Françoise Lala, Julien Delrieu, Hélène Villars; Psychologists: Emeline Combrouze, Carole Badufle, Audrey Zueras; Methodology, statistical analysis and data management: Sandrine Andrieu, Christelle Cantet, Christophe Morin; Multidomain group: Gabor Abellan Van Kan, Charlotte Dupuy, Yves Rolland (physical and nutritional components), Céline Caillaud, Pierre-Jean Ousset (cognitive component), Françoise Lala (preventive consultation) (Toulouse). The cognitive component was designed in collaboration with Sherry Willis from the University of Seattle, and Sylvie Belleville, Brigitte Gilbert and Francine Fontaine from the University of Montreal. Co-Investigators in associated centres: Jean-François Dartigues, Isabelle Marcet, Fleur Delva, Alexandra Foubert, Sandrine Cerda (Bordeaux); Marie-Noëlle-Cuffi, Corinne Costes (Castres); Olivier Rouaud, Patrick Manckoundia, Valérie Quipourt, Sophie Marilier, Evelyne Franon (Dijon); Lawrence Bories, Marie-Laure Pader, Marie-France Basset, Bruno Lapoujade, Valérie Faure, Michael Li Yung Tong, Christine Malick-Loiseau, Evelyne Cazaban-Campistron (Foix); Françoise Desclaux, Colette Blatge (Lavaur); Thierry Dantoine, Cécile Laubarie-Mouret, Isabelle Saulnier, Jean-Pierre Clément, Marie-Agnès Picat, Laurence Bernard-Bourzeix, Stéphanie Willebois, Iléana Désormais, Noëlle Cardinaud (Limoges); Marc Bonnefoy, Pierre Livet, Pascale Rebaudet, Claire Gédéon, Catherine Burdet, Flavien Terracol (Lyon), Alain Pesce, Stéphanie Roth, Sylvie Chaillou, Sandrine Louchart (Monaco); Kristelle Sudres, Nicolas Lebrun, Nadège Barro-Belaygues (Montauban); Jacques Touchon, Karim Bennys, Audrey Gabelle, Aurélia Romano, Lynda Touati, Cécilia Marelli, Cécile Pays (Montpellier); Philippe Robert, Franck Le Duff, Claire Gervais, Sébastien Gonfrier (Nice); Yannick Gasnier and Serge Bordes, Danièle Begorre, Christian Carpuat, Khaled Khales, Jean-François Lefebvre, Samira Misbah El Idrissi, Pierre Skolil, Jean-Pierre Salles (Tarbes). MRI group: Carole Dufouil (Bordeaux), Stéphane Lehéricy, Marie Chupin, Jean-François Mangin, Ali Bouhayia (Paris); Michèle Allard (Bordeaux); Frédéric Ricolfi (Dijon); Dominique Dubois (Foix); Marie Paule Bonceour Martel (Limoges); François Cotton (Lyon); Alain Bonafé (Montpellier); Stéphane Chanalet (Nice); Françoise Hugon (Tarbes); Fabrice Bonneville, Christophe Cognard, François Chollet (Toulouse). PET scans group: Pierre Payoux, Thierry Voisin, Julien Delrieu, Sophie Peiffer, Anne Hitzel, (Toulouse); Michèle Allard (Bordeaux); Michel Zanca (Montpellier); Jacques Monteil (Limoges); Jacques Darcourt (Nice). Medico-economics group: Laurent Molinier, Hélène Derumeaux, Nadège Costa (Toulouse). Biological sample collection: Bertrand Perret, Claire Vinel, Sylvie Caspar-Bauguil (Toulouse). Safety management: Pascale Olivier-Abbas DSA Group: Sandrine Andrieu, Christelle Cantet, Nicola Coley
Funding
The MAPT study was supported by grants from the Gérontopôle of Toulouse, the French Ministry of Health (PHRC 2008, 2009), Pierre Fabre Research Institute (manufacturer of the omega 3 supplement), Exhonit erapeutics SA, Avid Radiopharmaceuticals Inc. and in part by a grant from the French National Agency for Research called “Investissements d’Avenir” no. ANR-11-LABX-0018-01. e promotion of this study was supported by the University Hospital Center of Toulouse. e data sharing activity was supported by the Association Monegasque pour la Recherche sur la maladie d’Alzheimer (AMPA) and the UMR 1027 Unit INSERM- University of Toulouse III. Sponsor’s role: None.