Gu Yian, Vorburger Robert, Scarmeas Nikolaos, Luchsinger José A, Manly Jennifer J, Schupf Nicole, Mayeux Richard, Brickman Adam M
The Taub Institute for Research in Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, United States; The Department of Neurology, Columbia University, New York, NY, United States.
Institute of Applied Simulation, School of Life Sciences and Facility Management, Zürich University of Applied Sciences, 8820 Wädenswil, Switzerland.
Brain Behav Immun. 2017 Oct;65:150-160. doi: 10.1016/j.bbi.2017.04.022. Epub 2017 Apr 27.
The aim of this investigation was to determine whether circulating inflammatory biomarkers c-reactive protein (CRP), interleukin-6 (IL6), and alpha 1-antichymotrypsin (ACT) were related to structural brain measures assessed by magnetic resonance imaging (MRI). High-resolution structural MRI was collected on 680 non-demented elderly (mean age 80.1years) participants of a community-based, multiethnic cohort. Approximately three quarters of these participants also had peripheral inflammatory biomarkers (CRP, IL6, and ACT) measured using ELISA. Structural measures including brain volumes and cortical thickness (with both global and regional measures) were derived from MRI scans, and repeated MRI measures were obtained after 4.5years. Mean fractional anisotropy was used as the indicator of white matter integrity assessed with diffusion tensor imaging. We examined the association of inflammatory biomarkers with brain volume, cortical thickness, and white matter integrity using regression models adjusted for age, gender, ethnicity, education, APOE genotype, and intracranial volume. A doubling in CRP (b=-2.48, p=0.002) was associated with a smaller total gray matter volume, equivalent to approximately 1.5years of aging. A doubling in IL6 was associated with smaller total brain volume (b=-14.96, p<0.0001), equivalent to approximately 9years of aging. Higher IL6 was also associated with smaller gray matter (b=-6.52, p=0.002) and white matter volumes (b=-7.47, p=0.004). The volumes of most cortical regions including frontal, occipital, parietal, temporal, as well as subcortical regions including pallidum and thalamus were associated with IL6. In a model additionally adjusted for depression, vascular factors, BMI, and smoking status, the association between IL6 and brain volumes remained, and a doubling in ACT was marginally associated with 0.054 (p=0.001) millimeter thinner mean cortical thickness, equivalent to that of approximately 2.7years of aging. None of the biomarkers was associated with mean fractional anisotropy or longitudinal change of brain volumes and thickness. Among older adults, increased circulating inflammatory biomarkers were associated with smaller brain volume and cortical thickness but not the white matter tract integrity. Our preliminary findings suggest that peripheral inflammatory processes may be involved in the brain atrophy in the elderly.
本研究的目的是确定循环炎症生物标志物C反应蛋白（CRP）、白细胞介素-6（IL6）和α1-抗糜蛋白酶（ACT）是否与通过磁共振成像（MRI）评估的脑结构指标相关。对一个基于社区的多民族队列中的680名非痴呆老年人（平均年龄80.1岁）进行了高分辨率结构MRI检查。这些参与者中约四分之三还使用酶联免疫吸附测定法测量了外周炎症生物标志物（CRP、IL6和ACT）。从MRI扫描中得出包括脑容量和皮质厚度（包括整体和区域测量）在内的结构指标，并在4.5年后获得重复的MRI测量结果。平均分数各向异性用作通过扩散张量成像评估的白质完整性指标。我们使用针对年龄、性别、种族、教育程度、APOE基因型和颅内体积进行调整的回归模型，研究了炎症生物标志物与脑容量、皮质厚度和白质完整性之间的关联。CRP翻倍（b=-2.48，p=0.002）与总灰质体积减小相关，相当于约1.5年的衰老。IL6翻倍与总脑容量减小相关（b=-14.96，p<0.0001），相当于约9年的衰老。较高的IL6还与灰质（b=-6.52，p=0.002）和白质体积减小相关（b=-7.47，p=0.004）。包括额叶、枕叶、顶叶、颞叶在内的大多数皮质区域以及包括苍白球和丘脑在内的皮质下区域的体积与IL6相关。在一个额外针对抑郁、血管因素、体重指数和吸烟状况进行调整的模型中，IL6与脑容量之间的关联仍然存在，ACT翻倍与平均皮质厚度减小0.054毫米（p=0.001）相关，相当于约2.7年的衰老。没有一种生物标志物与平均分数各向异性或脑容量和厚度的纵向变化相关。在老年人中，循环炎症生物标志物升高与脑容量和皮质厚度减小相关，但与白质束完整性无关。我们的初步研究结果表明，外周炎症过程可能与老年人的脑萎缩有关。
