Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Maindy Road, Cathays, Cardiff, CF24 4HQ, UK.
Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Maindy Road, Cathays, Cardiff, CF24 4HQ, UK.
Neuroimage. 2019 Apr 1;189:793-803. doi: 10.1016/j.neuroimage.2019.02.007. Epub 2019 Feb 5.
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 k] 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 k, but not with any differences in neurite microstructure. In women, age mediated the effects of VFF on fornix MPF and k, 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.
中年肥胖是晚期发病阿尔茨海默病（LOAD）的一个风险因素，但具体原因尚不清楚。由于系统性炎症与这两种情况都有关，肥胖相关的神经炎症可能导致与 LOAD 相关的边缘结构受损。在这里，我们研究了这样一个假设，即系统性炎症是否会介导 166 名无症状个体（38-71 岁）的中央肥胖与边缘组织微观结构的关系。我们采用定量磁化传递（qMT）中的磁共振成像指标（大分子质子分数（MPF）和 k）以及神经丝取向分散和密度成像（NODDI）中的指标，来研究中央肥胖对穹窿、海马旁扣带回、钩束（与全脑白质和皮质脊髓束相比）和海马的影响。中央肥胖采用腰臀比（WHR）和腹部内脏脂肪和皮下脂肪面积分数（VFF、SFF）进行评估，系统性炎症采用血浆瘦素、脂联素、C 反应蛋白和白细胞介素 8 浓度进行评估。男性的中央肥胖程度明显高于女性，且内脏脂肪含量也高于女性。WHR 和 VFF 的个体差异与穹窿 MPF 和 k 的差异呈负相关，但与神经丝微观结构的任何差异均无关。在女性中，年龄介导了 VFF 对穹窿 MPF 和 k 的影响，而在男性中，瘦素和脂联素比值的差异完全介导了 WHR 对穹窿 MPF 的影响。这些结果表明，内脏脂肪相关的系统性炎症可能会损害穹窿的髓鞘相关特性，穹窿是已知与 LOAD 相关的关键边缘结构。
