Fuchs, T.Trollor, J.Crawford, J.Brown, D.Baune, B.Samaras, K.Campbell, L.Breit, S.Brodaty, H.Sachdev, P.Smith, E.2013-11-282013-11-282013Aging Cell, 2013; 12(5):882-8891474-97181474-9726http://hdl.handle.net/2440/81371Higher levels of macrophage inhibitory cytokine-1, also known as growth differentiation factor 15 (MIC-1/GDF15), are associated with adverse health outcomes and all-cause mortality. The aim of this study was to examine the relationships between MIC-1/GDF15 serum levels and global cognition, five cognitive domains, and mild cognitive impairment (MCI), at baseline (Wave 1) and prospectively at 2 years (Wave 2), in nondemented participants aged 70-90 years. Analyses were controlled for age, sex, education, Framingham risk score, history of cerebrovascular accident, acute myocardial infarction, angina, cancer, depression, C-reactive protein, tumor necrosis factor-α, interleukins 6 and 12, and apolipoprotein ε4 genotype. Higher MIC-1/GDF15 levels were significantly associated with lower global cognition at both waves. Cross-sectional associations were found between MIC-1/GDF15 and all cognitive domains in Wave 1 (all P < 0.001) and between processing speed, memory, and executive function in Wave 2 (all P < 0.001). Only a trend was found for the prospective analyses, individuals with high MIC-1/GDF15 at baseline declined in global cognition, executive function, memory, and processing speed. However, when categorizing MIC-1/GDF15 by tertiles, prospective analyses revealed statistically significant lower memory and executive function in Wave 2 in those in the upper tertile compared with the lower tertile. Receiver operating characteristics (ROC) analysis was used to determine MIC-1/GDF15 cutoff values associated with cognitive decline and showed that a MIC-1/GDF15 level exceeding 2764 pg/ml was associated with a 20% chance of decline from normal to MCI or dementia. In summary, MIC-1/GDF15 levels are associated with cognitive performance and cognitive decline. Further research is required to determine the pathophysiology of this relationship.en© 2013 The Anatomical Society and John Wiley & Sons Ltdagingcognitive declinedementiagrowth differentiation factor-15inflammationmacrophage inhibitory cytokine-1mild cognitive impairmentJournal article002013192010.1111/acel.121160003243763000162-s2.0-8488375500217945Baune, B. [0000-0001-6548-426X]