The relationship of serum macrophage inhibitory cytokine-1 levels with gray matter volumes in community-dwelling older individuals

Jiyang Jiang; Wei Wen; David A Brown; John Crawford; Anbupalam Thalamuthu; Evelyn Smith; Samuel N Breit; Tao Liu; Wanlin Zhu; Henry Brodaty; Bernhard T Baune; Julian N Trollor; Perminder S Sachdev

doi:10.1371/journal.pone.0123399

The relationship of serum macrophage inhibitory cytokine-1 levels with gray matter volumes in community-dwelling older individuals

PLoS One. 2015 Apr 13;10(4):e0123399. doi: 10.1371/journal.pone.0123399. eCollection 2015.

Authors

Affiliations

¹ Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Randwick NSW, Australia.
² 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.
³ Centre for Applied Medical Research, St. Vincent's Hospital and University of New South Wales, Darlinghurst NSW, Australia.
⁴ School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
⁵ State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China.
⁶ 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.
⁷ Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia.
⁸ 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.

Abstract

Using circulating inflammatory markers and magnetic resonance imaging (MRI), recent studies have associated inflammation with brain volumetric measures. Macrophage Inhibitory Cytokine-1 (MIC-1/GDF15) is a divergent transforming growth factor - beta (TGF-β) superfamily cytokine. To uncover the underlying mechanisms of the previous finding of a negative association between MIC-1/GDF15 serum levels and cognition, the present study aimed to examine the relationship of circulating MIC-1/GDF15 levels with human brain gray matter (GM) volumes, in a community-dwelling sample aged 70-90 years over two years (Wave 1: n = 506, Wave 2: n = 327), of which the age-related brain atrophy had been previously well defined. T1-weighted MRI scans were obtained at both waves and analyzed using the FMRIB Software Library and FreeSurfer. The results showed significantly negative associations between MIC-1/GDF15 serum levels and both subcortical and cortical GM volumes. GM volumes of the whole brain, cortex, temporal lobe, thalamus and accumbens showed significant mediating effects on the associations between MIC-1/GDF15 serum levels and global cognition scores. Increases in MIC-1/GDF15 serum levels were associated with decreases in cortical and subcortical GM volume over two years. In conclusion, MIC-1/GDF15 serum levels were inversely associated with GM volumes both cross-sectionally and longitudinally.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Cross-Sectional Studies
Female
Gray Matter / pathology*
Growth Differentiation Factor 15 / blood*
Humans
Magnetic Resonance Imaging
Male

Substances

Growth Differentiation Factor 15

Grants and funding

This research was supported by the National Health and Medical Research Council (NHMRC, https://www.nhmrc.gov.au/, NHMRC Program Grant ID 350833, NHMRC Project Grant ID 510175 and NHMRC Project Grant ID 510124), and the Australian Research Council (http://www.arc.gov.au/, DP0774213, DP0773584 and LP0669645). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.