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. Dollé; Eugene Jansen; Tilman Grune; Alexander Bürkle; Kristina Norman

doi:10.1007/s11357-023-00902-6

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. Dollé

Eugene Jansen, Tilman Grune, Alexander Bürkle, Kristina Norman

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1657-1669
Number of pages	13
Journal	GeroScience
Volume	46
Issue number	2
DOIs	https://doi.org/10.1007/s11357-023-00902-6
Publication status	Published - 16 Sept 2023

Funding

Open Access funding enabled and organized by Projekt DEAL. We thank the European Commission for financial support through the FP7 large-scale integrating project ‘European Study to Establish Biomarkers of Human Ageing’ (MARK-AGE; grant agreement no. 200880). We also would like to thank the Focus Area DynAge for financially supporting GDF15 analyses as well as the German Federal Ministry of Education and Research (grant agreement no. 031B0731E) as part of the joint project “f4f—food for the future” in the BMBF initiative “Agricultural systems of the future” for partially supporting this work. Moreover, publication costs were funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – 491394008.

Keywords

Aging
Biomarker
Cognitive frailty
Depression
GDF15

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Kochlik, B., Herpich, C., Moreno-Villanueva, M., Klaus, S., Müller-Werdan, U., Weinberger, B., Fiegl, S., Toussaint, O., Debacq-Chainiaux, F., Schön, C., Bernhard, J., Breusing, N., Gonos, E. S., Franceschi, C., Capri, M., Sikora, E., Hervonen, A., Hurme, M., Slagboom, P. E., ... Norman, K. (2023). Associations of circulating GDF15 with combined cognitive frailty and depression in older adults of the MARK-AGE study. GeroScience, 46(2), 1657-1669. https://doi.org/10.1007/s11357-023-00902-6

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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.",

keywords = "Aging, Biomarker, Cognitive frailty, Depression, GDF15",

author = "Bastian Kochlik and Catrin Herpich and Mar{\'i}a Moreno-Villanueva and Susanne Klaus and Ursula M{\"u}ller-Werdan and Birgit Weinberger and Simone Fiegl and Olivier Toussaint and Florence Debacq-Chainiaux and Christiane Sch{\"o}n and J{\"u}rgen Bernhard and Nicolle Breusing and Gonos, \{Efstathios S.\} and Claudio Franceschi and Miriam Capri and Ewa Sikora and Antti Hervonen and Mikko Hurme and Slagboom, \{P. Eline\} and Doll{\'e}, \{Martijn E.T.\} and Eugene Jansen and Tilman Grune and Alexander B{\"u}rkle and Kristina Norman",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

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doi = "10.1007/s11357-023-00902-6",

language = "English",

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Kochlik, B, Herpich, C, Moreno-Villanueva, M, Klaus, S, Müller-Werdan, U, Weinberger, B, Fiegl, S, Toussaint, O , Debacq-Chainiaux, F, Schön, C, Bernhard, J, Breusing, N, Gonos, ES, Franceschi, C, Capri, M, Sikora, E, Hervonen, A, Hurme, M, Slagboom, PE, Dollé, MET, Jansen, E, Grune, T, Bürkle, A & Norman, K 2023, 'Associations of circulating GDF15 with combined cognitive frailty and depression in older adults of the MARK-AGE study', GeroScience, vol. 46, no. 2, pp. 1657-1669. https://doi.org/10.1007/s11357-023-00902-6

TY - JOUR

T1 - Associations of circulating GDF15 with combined cognitive frailty and depression in older adults of the MARK-AGE study

AU - Kochlik, Bastian

AU - Herpich, Catrin

AU - Moreno-Villanueva, María

AU - Klaus, Susanne

AU - Müller-Werdan, Ursula

AU - Weinberger, Birgit

AU - Fiegl, Simone

AU - Toussaint, Olivier

AU - Debacq-Chainiaux, Florence

AU - Schön, Christiane

AU - Bernhard, Jürgen

AU - Breusing, Nicolle

AU - Gonos, Efstathios S.

AU - Franceschi, Claudio

AU - Capri, Miriam

AU - Sikora, Ewa

AU - Hervonen, Antti

AU - Hurme, Mikko

AU - Slagboom, P. Eline

AU - Dollé, Martijn E.T.

AU - Jansen, Eugene

AU - Grune, Tilman

AU - Bürkle, Alexander

AU - Norman, Kristina

PY - 2023/9/16

Y1 - 2023/9/16

N2 - 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.

AB - 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.

KW - Aging

KW - Biomarker

KW - Cognitive frailty

KW - Depression

KW - GDF15

UR - https://www.scopus.com/pages/publications/85171256325

U2 - 10.1007/s11357-023-00902-6

DO - 10.1007/s11357-023-00902-6

M3 - Article

AN - SCOPUS:85171256325

SN - 2509-2715

VL - 46

SP - 1657

EP - 1669

JO - GeroScience

JF - GeroScience

IS - 2

ER -

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

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