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

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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1657-1669
Number of pages13
Issue number2
Publication statusPublished - 16 Sept 2023


  • Aging
  • Biomarker
  • Cognitive frailty
  • Depression
  • GDF15


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