TY - JOUR
T1 - Macrophage inhibitory cytokine-1 is associated with cognitive impairment and predicts cognitive decline - the Sydney Memory and Aging Study
AU - Fuchs, Talia
AU - Trollor, Julian N.
AU - Crawford, John
AU - Brown, David A.
AU - Baune, Bernhard T.
AU - Samaras, Katherine
AU - Campbell, Lesley
AU - Breit, Samuel N.
AU - Brodaty, Henry
AU - Sachdev, Perminder
AU - Smith, Evelyn
PY - 2013/10
Y1 - 2013/10
N2 - 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.
AB - 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.
KW - Aging
KW - Cognitive decline
KW - Dementia
KW - Growth differentiation factor-15
KW - Inflammation
KW - Macrophage inhibitory cytokine-1
KW - Mild cognitive impairment
UR - http://www.scopus.com/inward/record.url?scp=84883755002&partnerID=8YFLogxK
U2 - 10.1111/acel.12116
DO - 10.1111/acel.12116
M3 - Article
C2 - 23758647
AN - SCOPUS:84883755002
SN - 1474-9718
VL - 12
SP - 882
EP - 889
JO - Aging Cell
JF - Aging Cell
IS - 5
ER -