Open AccessMacrophage inhibitory cytokine‐1 is associated with cognitive impairment and predicts cognitive decline – the S ydney M emory and A ging S tudy
Author(s) -
Fuchs Talia,
Trollor Julian N.,
Crawford John,
Brown David A.,
Baune Bernhard T.,
Samaras Katherine,
Campbell Lesley,
Breit Samuel N.,
Brodaty Henry,
Sachdev Perminder,
Smith Evelyn
Publication year - 2013
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12116
Subject(s) - gdf15 , cognitive decline , medicine , cognition , prospective cohort study , dementia , gerontology , demography , oncology , immunology , psychiatry , disease , sociology
Summary Higher levels of macrophage inhibitory cytokine‐1, also known as growth differentiation factor 15 ( MIC ‐1/ GDF 15), are associated with adverse health outcomes and all‐cause mortality. The aim of this study was to examine the relationships between MIC ‐1/ GDF 15 serum levels and global cognition, five cognitive domains, and mild cognitive impairment ( MCI ), at baseline ( W ave 1) and prospectively at 2 years ( W ave 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/ GDF 15 levels were significantly associated with lower global cognition at both waves. Cross‐sectional associations were found between MIC ‐1/ GDF 15 and all cognitive domains in W ave 1 (all P < 0.001) and between processing speed, memory, and executive function in W ave 2 (all P < 0.001). Only a trend was found for the prospective analyses, individuals with high MIC ‐1/ GDF 15 at baseline declined in global cognition, executive function, memory, and processing speed. However, when categorizing MIC ‐1/ GDF 15 by tertiles, prospective analyses revealed statistically significant lower memory and executive function in W ave 2 in those in the upper tertile compared with the lower tertile. Receiver operating characteristics ( ROC ) analysis was used to determine MIC ‐1/ GDF 15 cutoff values associated with cognitive decline and showed that a MIC ‐1/ GDF 15 level exceeding 2764 pg/ml was associated with a 20% chance of decline from normal to MCI or dementia. In summary, MIC ‐1/ GDF 15 levels are associated with cognitive performance and cognitive decline. Further research is required to determine the pathophysiology of this relationship.