An inverse relationship between serum macrophage inhibitory cytokine-1 levels and brain white matter integrity in community-dwelling older individuals. (December 2015) - Jiang, Jiyang
Highlights: We examined the relationships of MIC-1/GDF15 serum levels with brain WM integrity. MIC-1/GDF15 serum levels were negatively associated with mean FA values. The associations of MIC-1/GDF15 with WM integrity were stronger in MCI than CN. The FA value was a mediator in the relationships of MIC-1/GDF15 with cognition. Abstract: Macrophage inhibitory cytokine-1 (MIC-1/GDF15) is a marker of inflammation that has been associated with atherosclerosis. We have previously demonstrated its relationships with cognitive decline and cerebral gray matter volumes, suggesting its role as a biomarker of cognitive impairment. Considering that it is widely distributed in the brain, and both inflammation and vascular pathology impact on white matter (WM) integrity, we examined the relationship between MIC-1/GDF15 and measures of WM integrity, including WM volumes, mean fractional anisotropy (FA) values and WM hyperintensity (WMH) volumes in a community-dwelling non-demented sample of older individuals ( n = 327, 70–90 years old). We found that the mean FA values were negatively associated with MIC-1/GDF15 serum levels, after Bonferroni correction. The voxel-wise analysis showed negative relationships between MIC-1/GDF15 serum levels and FA values in corticospinal tract, corpus callosum (including genu, body and splenium parts), superior longitudinal fasciculus, cingulum, as well as anterior and posterior thalamic radiation. Whole brain WMH volumes, especially deep WMH volumes, showed a non-significant trend for a positive association with MIC-1/GDF15 serum levels. The associations between MIC-1/GDF15 serum levels and WM integrity showed a non-significant trend of being stronger for the individuals classified as mild cognitive impairment, compared to the normal ageing participants. The findings suggest that high serum MIC-1/GDF15 levels indicate reduced WM integrity and possibly greater WM pathology.