Interleukin-6, interleukin-6 receptor gene variant, small-vessel disease and incident dementia
Interleukin-6, interleukin-6 receptor gene variant, small-vessel disease and incident dementia
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DOI：
10.1111/ene.12921
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发表时间：
2016-03-01
影响因子：
5.1
通讯作者：
Kitagawa, K.
中科院分区：
文献类型：
--
作者：
Miwa, K.;Okazaki, S.;Kitagawa, K.
背景和目的神经变性和血管性痴呆混合型已成为老年痴呆的主要病因。炎症与动脉粥样硬化、脑小血管病（SVD）以及认知障碍有关。然而，关于循环炎症标志物（包括基因变异和磁共振成像（MRI）结果）在痴呆事件中的预测价值的纵向数据很少。研究了循环中白细胞介素-6（IL-6）、C反应蛋白（CRP）和基因变异是否增加痴呆风险。MethodsIn一项2001年的观察性研究中，一组日本参与者的血管危险因素，基线IL-6、CRP水平、基因变异[白细胞介素-6受体（IL-6 R），rs 2228145; IL-6，rs 2097677; CRP，rs3093059]和事件全因痴呆进行了评价。基线MRI用于确定SVD（腔隙，白色高信号）和萎缩（中颞叶萎缩，双尾状核比率）。对痴呆的预测因素进行了考克斯比例风险分析，调整了年龄、性别、载脂蛋白E β 4、教育、脑血管事件、血管危险因素和MRI结果。（平均年龄67.0 ± 8.5岁，男性59%），在平均7.5 ± 3.2年的随访期间，60例痴呆患者（阿尔茨海默病31例;血管性痴呆17例;混合型6例;其他6例）被诊断出来。在校正了年龄、性别、脑血管事件、MRI结果和IL-6 R变体（rs 2228145）的多变量分析中，IL-6水平（相对风险1.68，P = 0.048）或全因痴呆的最高三分位数（相对风险2.38，P = 0.031）仍然具有显著性。尽管rs 2228145携带者的IL-6水平显著较高，但未观察到rs 2228145与痴呆之间的显著关联。相反，CRP和其余的基因变异与dementions.ConclusionsThe有害影响较高的IL-6对痴呆症仍然是一致的，无论传统的危险因素，MRI结果和IL-6 R变异。
Background and purposeMixed neurogenerative and vascular dementia has emerged as the leading cause of dementia in the elderly. Inflammation is implicated in atherosclerosis, cerebral small-vessel disease (SVD) as well as cognitive impairment. However, longitudinal data on the predictive value of circulating inflammatory markers including gene variants and magnetic resonance imaging (MRI) findings in incident dementia are scarce. It was investigated whether circulating interleukin-6 (IL-6), C-reactive protein (CRP) and gene variants increase dementia risk.MethodsIn a cohort of Japanese participants with vascular risk factors in an observational study from 2001, the association between baseline IL-6, CRP levels, gene variants [interleukin-6 receptor (IL-6R), rs2228145; IL-6, rs2097677; CRP, rs3093059] and incident all-cause dementia was evaluated. Baseline MRI was used to determine SVD (lacuna, white matter hyperintensities) and atrophy (medial-temporal lobe atrophy, bicaudate ratio). Cox proportional hazards analyses were performed for predictors of dementia, adjusting for age, sex, apolipoprotein E epsilon 4, education, cerebrovascular events, vascular risk factors and MRI findings.ResultsOf 803 subjects (mean 67.0 8.5 years, males 59%), during a mean of 7.5 +/- 3.2 years follow-up, 60 incident dementia patients (Alzheimer's disease 31; vascular dementia 17; mixed-type six; other six) were diagnosed. In multivariable analyses adjusted for age, sex, cerebrovascular events, MRI findings and IL-6R variant (rs2228145), IL-6 levels (relative risk 1.68, P = 0.048) or highest tertile (relative risk 2.38, P = 0.031) for all-cause dementia remained significant. Although subjects with rs2228145 carrier had significantly higher IL-6 levels, a significant association between rs2228145 and dementia was not observed. Conversely, CRP and remaining gene variants were not associated with dementia.ConclusionsThe deleterious effect of higher IL-6 on dementia remains consistent irrespective of conventional risk factors, MRI findings and IL-6R variant.