Novel Blood-Based Biomarkers of Cognition, Stress, and Physical or Cognitive Training in Older Adults at Risk of Dementia: Preliminary Evidence for a Role of BDNF, Irisin, and the Kynurenine Pathway

Article type: Research Article

Authors: Küster, Olivia C.^{a; b; *} | Laptinskaya, Daria^a | Fissler, Patrick^{a; b} | Schnack, Cathrin^b | Zügel, Martina^c | Nold, Verena^{a; d} | Thurm, Franka^e | Pleiner, Sina^d | Karabatsiakis, Alexander^a | von Einem, Björn^b | Weydt, Patrick^b | Liesener, André^d | Borta, Andreas^d | Woll, Alexander^f | Hengerer, Bastian^g | Kolassa, Iris-Tatjana^a | von Arnim, Christine A.F.^b

Affiliations: [a] Institute of Psychology and Education, Clinical and Biological Psychology, Ulm University, Germany | [b] Department of Neurology, Ulm University, Germany | [c] Department of Internal Medicine, Division of Sports Medicine, University Hospital Ulm, Germany | [d] Boehringer Ingelheim Pharma GmbH & Co. KG, DMPK, Biberach an der Riss, Germany | [e] Department of Psychology, TU Dresden, Germany | [f] Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Germany | [g] Boehringer Ingelheim Pharma GmbH & Co. KG, RES CNS, Biberach an der Riss, Germany

Correspondence: [*] Correspondence to: Olivia Küster, Clinical and Biological Psychology, Institute of Psychology and Education, Ulm University, 89081 Ulm, Germany. Tel.: +49 0 731/50 26592; Fax: +49 0 731/50 26599; E-mail: olivia.kuester@uni-ulm.de.

Abstract:  Psychosocial stress and physical, cognitive, and social activity predict the risk of cognitive decline and dementia. The aim of this study was to elucidate brain-derived neurotrophic factor (BDNF), irisin, and the kynurenine pathway (KP) as potential underlying biological correlates. We evaluated associations of irisin and the KP with BDNF in serum and with cognition, stress, and activities. Furthermore, changes in serum concentrations of BDNF, irisin, and KP metabolites were investigated after physical or cognitive training. Forty-seven older adults at risk of dementia were assigned to 10 weeks of physical training, cognitive training, or a wait-list control condition. Previous physical, cognitive, and social activities and stressful life events were recorded; global cognition, episodic memory, and executive functions were assessed. Serum levels of L-kynurenine, kynurenic acid, 3-hydroxykynurenine (3-HK), and quinolinic acid (QUIN) were determined by validated assays based on liquid chromatography coupled to tandem mass spectrometry. BDNF and irisin serum levels were determined with enzyme-linked immunosorbent assays. BDNF and irisin correlated positively with global cognition and episodic memory, while the neurotoxic metabolite QUIN correlated negatively with executive functions. Stressful life events were associated with reduced BDNF and increased 3-HK. 3-HK decreased after cognitive training, while BDNF tended to increase after physical training. This suggests that psychosocial stress as well as cognitive and physical training may impact BDNF serum levels and the KP. Irisin and QUIN may constitute novel serum biomarkers of cognitive impairment, in addition to BDNF. Larger scale trials are needed to replicate and extend these novel findings.

Keywords: Brain-derived neurotrophic factor, cognitive function, dementia, exercise training, kynurenine, lifestyle∥

DOI: 10.3233/JAD-170447

Journal: Journal of Alzheimer's Disease, vol. 59, no. 3, pp. 1097-1111, 2017