title: An inverse relationship between serum macrophage inhibitory cytokine-1 levels and brain white matter integrity in community-dwelling older individuals.
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.
authors.affiliation: Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Randwick, NSW, Australia.
authors.forename: Jiyang
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Randwick, NSW, Australia; Department of Development Disability Neuropsychiatry, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Julian N
authors.initials: JN
authors.lastname: Trollor
authors.affiliation: Centre for Applied Medical Research, St. Vincent's Hospital and University of New South Wales, Darlinghurst, NSW, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Brown
authors.affiliation: Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Randwick, NSW, Australia.
authors.forename: John D
authors.initials: JD
authors.lastname: Crawford
authors.affiliation: Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Randwick, NSW, Australia.
authors.forename: Anbupalam
authors.initials: A
authors.lastname: Thalamuthu
authors.affiliation: Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Randwick, NSW, Australia.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Smith
authors.affiliation: Centre for Applied Medical Research, St. Vincent's Hospital and University of New South Wales, Darlinghurst, NSW, Australia.
authors.forename: Samuel N
authors.initials: SN
authors.lastname: Breit
authors.affiliation: School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Randwick, NSW, Australia; Aged Care Psychiatry, Prince of Wales Hospital, Randwick, NSW, Australia; Dementia Collaborative Research Centre, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Henry
authors.initials: H
authors.lastname: Brodaty
authors.affiliation: Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia.
authors.forename: Bernhard T
authors.initials: BT
authors.lastname: Baune
authors.affiliation: Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Randwick, NSW, Australia; Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, NSW, Australia.
authors.forename: Perminder S
authors.initials: PS
authors.lastname: Sachdev
authors.affiliation: Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Randwick, NSW, Australia; Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, NSW, Australia. Electronic address: w.wen@unsw.edu.au.
authors.forename: Wei
authors.initials: W
authors.lastname: Wen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood* / Q000473:pathology*; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000097:blood / Q000473:pathology; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D066127:White Matter / Q000473:pathology*
chemical_list: D055436:Growth Differentiation Factor 15
keywords: Ageing; Community-dwelling; Macrophage inhibitory cytokine-1; Magnetic resonance imaging; White matter integrity