Sex-specific effects of central adiposity and inflammatory markers on limbic microstructure

• Published in: NeuroImage (Orlando, Fla.) Fla.), 2019-04, Vol.189, p.793-803
• Main Authors: Metzler-Baddeley, Claudia, Mole, Jilu P., Leonaviciute, Erika, Sims, Rebecca, Kidd, Emma J., Ertefai, Benyamin, Kelso-Mitchell, Aurora, Gidney, Florence, Fasano, Fabrizio, Evans, John, Jones, Derek K., Baddeley, Roland J.
• Format: Article
• Language: English
• Subjects: Adiponectin; Adipose tissue; Adiposity; Adult; Age Factors; Aged; Alcohol; Alzheimer's disease; Body fat; Body mass index; C-reactive protein; Cingulum; Cytokines; Dementia; Diabetes; Female; Fornix; Fornix, Brain - diagnostic imaging; Fornix, Brain - pathology; Gyrus Cinguli - diagnostic imaging; Gyrus Cinguli - pathology; Hippocampus - diagnostic imaging; Hippocampus - pathology; Humans; Hypertension; Immunization; Inflammation; Inflammation - blood; Inflammation - complications; Inflammation - etiology; Interleukin 8; Intra-Abdominal Fat; Leptin; Macromolecules; Magnetic Resonance Imaging; Male; Medical imaging; Metabolic syndrome; Middle Aged; Myelin; Neurodegenerative diseases; Neuroimaging; Obesity; Obesity, Abdominal - complications; Parahippocampal gyrus; Pyramidal tracts; Sex Characteristics; Sex Factors; Substantia alba; White Matter - diagnostic imaging; White Matter - pathology
• ISSN: 1053-8119; 1095-9572; 1095-9572
• DOI: 10.1016/j.neuroimage.2019.02.007

Midlife obesity is a risk factor of late onset Alzheimer's disease (LOAD) but why this is the case remains unknown. As systemic inflammation is involved in both conditions, obesity-related neuroinflammation may contribute to damage in limbic structures important in LOAD. Here, we investigated the hypothesis that systemic inflammation would mediate central obesity related effects on limbic tissue microstructure in 166 asymptomatic individuals (38–71 years old). We employed MRI indices sensitive to myelin and neuroinflammation [macromolecular proton fraction (MPF) and kf] from quantitative magnetization transfer (qMT) together with indices from neurite orientation dispersion and density imaging (NODDI) to investigate the effects of central adiposity on the fornix, parahippocampal cingulum, uncinate fasciculus (compared with whole brain white matter and corticospinal tract) and the hippocampus. Central obesity was assessed with the Waist Hip Ratio (WHR) and abdominal visceral and subcutaneous fat area fractions (VFF, SFF), and systemic inflammation with blood plasma concentrations of leptin, adiponectin, C-reactive protein and interleukin 8. Men were significantly more centrally obese and had higher VFF than women. Individual differences in WHR and in VFF were negatively correlated with differences in fornix MPF and kf, but not with any differences in neurite microstructure. In women, age mediated the effects of VFF on fornix MPF and kf, whilst in men differences in the leptin and adiponectin ratio fully mediated the effect of WHR on fornix MPF. These results suggest that visceral fat related systemic inflammation may damage myelin-related properties of the fornix, a key limbic structure known to be involved in LOAD. •Central adiposity is linked to apparent myelin/inflammatory damage in the fornix.•Central adiposity is not linked to differences in apparent neurite microstructure.•Men were more centrally obese and had higher visceral fat fractions than women.•In women, age mediated the correlation between visceral fat and fornix myelin.•In men, adipokines mediated the correlation between WHR and fornix myelin.