Associations of circulating GDF15 with combined cognitive frailty and depression in older adults of the MARK-AGE study.

Nicolle Breusing, Kristina Norman, Alexander Bürkle, Tilman Grune, Eugene Jansen, Martijn E T Dollé, Mikko Hurme, Antti Hervonen, Ewa Sikora, Miriam Capri, Claudio Franceschi, Efstathios S Gonos, P Eline Slagboom, Jürgen Bernhard, Christiane Schön, Florence Debacq-Chainiaux, Olivier Toussaint, Simone Fiegl, Birgit Weinberger, Ursula Müller-Werdan, Susanne Klaus, María Moreno-Villanueva, Catrin Herpich, Bastian Kochlik

Journal: GeroScience 2024;46(2):1657-1669

PMID: 37715843

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Abstract

Growth differentiation factor-15 (GDF15) might be involved in the development of cognitive frailty and depression. Therefore, we evaluated cross-sectional associations of plasma GDF15 with combined cognitive-frailty-and-depression in older (i.e. ≥ 55 years) and younger adults of the MARK-AGE study. In the present work, samples and data of MARK-AGE ("European study to establish bioMARKers of human AGEing") participants (N = 2736) were analyzed. Cognitive frailty was determined by the global cognitive functioning score (GCF) and depression by the Self-Rating Depression Scale (SDS score). Adults were classified into three groups: (I) neither-cognitive-frailty-nor-depression, (II) either-cognitive-frailty-or-depression or (III) both-cognitive-frailty-and-depression. Cross-sectional associations were determined by unadjusted and by age, BMI, sex, comorbidities and hsCRP-adjusted linear and logistic regression analyses. Cognitive frailty, depression, age and GDF15 were significantly related within the whole study sample. High GDF15 levels were significantly associated with both-cognitive-frailty-and-depression (adjusted β = 0.177 [0.044 - 0.310], p = 0.009), and with low GCF scores and high SDS scores. High GDF15 concentrations and quartiles were significantly associated with higher odds to have both-cognitive-frailty-and-depression (adjusted odds ratio = 2.353 [1.267 - 4.372], p = 0.007; and adjusted odds ratio = 1.414 [1.025 - 1.951], p = 0.035, respectively) independent of age, BMI, sex, comorbidities and hsCRP. These associations remained significant when evaluating older adults. We conclude that plasma GDF15 concentrations are significantly associated with combined cognitive-frailty-and-depression status and, with cognitive frailty and depressive symptoms separately in old as well as young community-dwelling adults.

Address: Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.; Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.; Food4Future (F4F), c/o Leibniz Institute of Vegetable and Ornamental Crops (IGZ), Theodor-Echtermeyer-Weg 1, 14979, Grossbeeren, Germany.; Institute of Nutritional Science, University of Potsdam , Potsdam, Germany.; Department of Geriatrics and Medical Gerontology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.; Molecular Toxicology Group, Department of Biology, University of Konstanz, Constance, Germany.; Human Performance Research Centre, Department of Sport Science, University of Konstanz, Constance, Germany.; Department of Physiology of Energy Metabolism, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.; Protestant Geriatric Center Berlin (EGZB), Berlin, Germany.; Research Institute for Biomedical Aging Research, Universität Innsbruck, Rennweg 10, 6020, Innsbruck, Austria.; UMIT TIROL, Eduard-Wallnöfer-Zentrum 1, 6060, Hall in Tirol, Austria.; URBC-Narilis, University of Namur, Rue de Bruxelles 61, B-5000, Namur, Belgium.; BioTeSys GmbH, Schelztorstraße 54-56, 73728, Esslingen, Germany.; Institute of Nutritional Medicine, Department of Applied Nutritional Science/Dietetics, University of Hohenheim, Stuttgart, Germany.; Institute of Biological Research and Biotechnology, National Hellenic Research Foundation (NHRF, 48 Vas. Constantinou Ave, 11635, Athens, Greece.; Institute of Information Technology, Mathematics and Mechanics, Department of Applied Mathematics, National Research Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russia.; Department of Medical and Surgical Sciences, University of Bologna-Alma Mater Studiorum, Bologna, Italy.; Alma Mater Research Institute On Global Challenges and Climate Change (Alma Climate), University of Bologna, Bologna, Italy.; Laboratory of the Molecular Bases of Ageing, Polish Academy of Sciences, Nencki Institute of Experimental Biology, Warsaw, Poland.; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.; Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA, Bilthoven, The Netherlands.; Faculty of Chemistry, Department of Physiological Chemistry, University of Vienna, Vienna, Austria.; German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany.; Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. [email protected].; Institute of Nutritional Science, University of Potsdam , Potsdam, Germany. [email protected].; Department of Geriatrics and Medical Gerontology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany. [email protected].; German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany. [email protected].

DOI: 10.1007/s11357-023-00902-6

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MeSH Terms: Humans, Aged, Frailty, Frail Elderly, Depression, C-Reactive Protein, Cross-Sectional Studies, Cognition, Growth Differentiation Factor 15