title: Macrophage inhibitory cytokine-1 is associated with cognitive impairment and predicts cognitive decline - the Sydney Memory and Aging Study.
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.
authors.affiliation: Department of Developmental Disability Neuropsychiatry, School of Psychiatry, University of New South Wales, Sydney, NSW, 2010, Australia.
authors.forename: Talia
authors.initials: T
authors.lastname: Fuchs
authors.forename: Julian N
authors.initials: JN
authors.lastname: Trollor
authors.forename: John
authors.initials: J
authors.lastname: Crawford
authors.forename: David A
authors.initials: DA
authors.lastname: Brown
authors.forename: Bernhard T
authors.initials: BT
authors.lastname: Baune
authors.forename: Katherine
authors.initials: K
authors.lastname: Samaras
authors.forename: Lesley
authors.initials: L
authors.lastname: Campbell
authors.forename: Samuel N
authors.initials: SN
authors.lastname: Breit
authors.forename: Henry
authors.initials: H
authors.lastname: Brodaty
authors.forename: Perminder
authors.initials: P
authors.lastname: Sachdev
authors.forename: Evelyn
authors.initials: E
authors.lastname: Smith
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood*; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000097:blood* / Q000523:psychology; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood* / Q000235:genetics; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology*
chemical_list: C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15
keywords: aging; cognitive decline; dementia; growth differentiation factor-15; inflammation; macrophage inhibitory cytokine-1; mild cognitive impairment