Visceral obesity relates to deep white matter hyperintensities via inflammation
Visceral obesity relates to deep white matter hyperintensities via inflammation
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DOI：
10.1002/ana.25396
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发表时间：
2019-02-01
影响因子：
11.2
通讯作者：
Witte, A. Veronica
中科院分区：
文献类型：
--
作者：
Lampe, Leonie;Zhang, Rui;Witte, A. Veronica
目的：白色高信号（WMH）与血管危险因素有关，并增加认知能力下降、痴呆和卒中的风险。在此，我们的目的是确定肥胖是否有助于区域WMH使用全脑的方法在一个良好的特征人群为基础的队列。方法使用高分辨率3特斯拉磁共振成像评估1，825名LIFE成人研究参与者（年龄20-82岁;体重指数18.4-55.4 kg/m2）的腰臀比（WHR）、体重指数（BMI）、收缩压/舒张压、高血压、糖尿病和吸烟状况、血糖和炎症标志物以及WMH的分布。体素分析测试肥胖是否预测WMH的区域概率。此外，使用线性回归和结构方程模型，高敏C反应蛋白和白细胞介素-6（IL-6）在血液中测量的中介作用与肥胖和WMH相关。结果WHR主要与深部白色物质中较高的WMH概率相关，即使调整了年龄、性别和收缩压的影响后也是如此（平均ss = 0.0043 [0.0008 SE]，95%置信区间，[0.00427，0.0043];无阈值聚类增强，家系误差校正p < 0.05）。相反，较高的收缩压与室周白色物质区的WMH相关。中介分析表明，更高的WHR和更高的BMI通过升高IL 6而导致深部与脑室周围WMH比率增加。解释我们的研究结果表明，增加WMH负担选择性地在深白色物质的肥胖受试者与高内脏脂肪堆积，独立于常见的肥胖合并症，如高血压。中介分析表明，内脏肥胖通过促炎细胞因子的增加而导致深部白色病变，这表明了一种病理机制联系。纵向研究需要证实这一假设。神经网络2019;85：194-203。
Objective White matter hyperintensities (WMHs) are linked to vascular risk factors and increase the risk of cognitive decline, dementia, and stroke. We here aimed to determine whether obesity contributes to regional WMHs using a whole-brain approach in a well-characterized population-based cohort. Methods Waist-to-hip ratio (WHR), body mass index (BMI), systolic/diastolic blood pressure, hypertension, diabetes and smoking status, blood glucose and inflammatory markers, as well as distribution of WMH were assessed in 1,825 participants of the LIFE-adult study (age, 20-82 years; BMI, 18.4-55.4 kg/m(2)) using high-resolution 3-Tesla magnetic resonance imaging. Voxel-wise analyses tested if obesity predicts regional probability of WMH. Additionally, mediation effects of high-sensitive C-reactive protein and interleukin-6 (IL6) measured in blood were related to obesity and WMH using linear regression and structural equation models. Results WHR related to higher WMH probability predominantly in the deep white matter, even after adjusting for effects of age, sex, and systolic blood pressure (mean ss = 0.0043 [0.0008 SE], 95% confidence interval, [0.00427, 0.0043]; threshold-free cluster enhancement, family-wise error-corrected p < 0.05). Conversely, higher systolic blood pressure was associated with WMH in periventricular white matter regions. Mediation analyses indicated that both higher WHR and higher BMI contributed to increased deep-to-periventricular WMH ratio through elevated IL6. Interpretation Our results indicate an increased WMH burden selectively in the deep white matter in obese subjects with high visceral fat accumulation, independent of common obesity comorbidities such as hypertension. Mediation analyses proposed that visceral obesity contributes to deep white matter lesions through increases in proinflammatory cytokines, suggesting a pathomechanistic link. Longitudinal studies need to confirm this hypothesis. ANN NEUROL 2019;85:194-203.