Macrophage inhibitory cytokine-1 is associated with cognitive impairment and predicts cognitive decline - the Sydney memory and aging study
Date
2013
Authors
Fuchs, T.
Trollor, J.
Crawford, J.
Brown, D.
Baune, B.
Samaras, K.
Campbell, L.
Breit, S.
Brodaty, H.
Sachdev, P.
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Journal article
Citation
Aging Cell, 2013; 12(5):882-889
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Talia Fuchs, Julian N. Trollor, John Crawford, David A. Brown, Bernhard T. Baune, Katherine Samaras, Lesley Campbell, Samuel N. Breit, Henry Brodaty, Perminder Sachdev, and Evelyn Smith
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Abstract
Higher 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.
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© 2013 The Anatomical Society and John Wiley & Sons Ltd