Walker Keenan A, Hoogeveen Ron C, Folsom Aaron R, Ballantyne Christie M, Knopman David S, Windham B Gwen, Jack Clifford R, Gottesman Rebecca F
From the Departments of Neurology (K.A.W., R.F.G.) and Epidemiology (R.F.G.), Johns Hopkins University School of Medicine, Baltimore, MD; Section of Cardiology (R.C.H., C.M.B.), Baylor College of Medicine; Center for Cardiovascular Disease Prevention (R.C.H., C.M.B.), Houston Methodist DeBakey Heart and Vascular Center, TX; Division of Epidemiology and Community Health (A.R.F.), School of Public Health, University of Minnesota, Minneapolis; Departments of Neurology (D.S.K.) and Radiology (C.R.J.), Mayo Clinic, Rochester, MN; and Department of Medicine (B.G.W.), University of Mississippi Medical Center, Jackson.
Neurology. 2017 Nov 28;89(22):2262-2270. doi: 10.1212/WNL.0000000000004688. Epub 2017 Nov 1.
To clarify the temporal relationship between systemic inflammation and neurodegeneration, we examined whether a higher level of circulating inflammatory markers during midlife was associated with smaller brain volumes in late life using a large biracial prospective cohort study.
Plasma levels of systemic inflammatory markers (fibrinogen, albumin, white blood cell count, von Willebrand factor, and Factor VIII) were assessed at baseline in 1,633 participants (mean age 53 [5] years, 60% female, 27% African American) enrolled in the Atherosclerosis Risk in Communities Study. Using all 5 inflammatory markers, an inflammation composite score was created for each participant. We assessed episodic memory and regional brain volumes, using 3T MRI, 24 years later.
Each SD increase in midlife inflammation composite score was associated with 1,788 mm greater ventricular ( = 0.013), 110 mm smaller hippocampal ( = 0.013), 519 mm smaller occipital ( = 0.009), and 532 mm smaller Alzheimer disease signature region ( = 0.008) volumes, and reduced episodic memory ( = 0.046) 24 years later. Compared to participants with no elevated (4th quartile) midlife inflammatory markers, participants with elevations in 3 or more markers had, on average, 5% smaller hippocampal and Alzheimer disease signature region volumes. The association between midlife inflammation and late-life brain volume was modified by age and race, whereby younger participants and white participants with higher levels of systemic inflammation during midlife were more likely to show reduced brain volumes subsequently.
Our prospective findings provide evidence for what may be an early contributory role of systemic inflammation in neurodegeneration and cognitive aging.
为阐明全身炎症与神经退行性变之间的时间关系，我们采用一项大型双种族前瞻性队列研究，检验中年时期循环炎症标志物水平较高是否与老年时期脑容量较小有关。
在社区动脉粥样硬化风险研究中纳入的1633名参与者（平均年龄53[5]岁，60%为女性，27%为非裔美国人）的基线时，评估全身炎症标志物（纤维蛋白原、白蛋白、白细胞计数、血管性血友病因子和凝血因子VIII）的血浆水平。利用所有5种炎症标志物，为每位参与者创建一个炎症综合评分。24年后，我们使用3T磁共振成像评估情景记忆和脑区体积。
中年炎症综合评分每增加1个标准差，与24年后脑室增大1788立方毫米（P = 0.013）、海马体减小110立方毫米（P = 0.013）、枕叶减小519立方毫米（P = 0.009）、阿尔茨海默病特征区域减小532立方毫米（P = 0.008）以及情景记忆减退（P = 0.046）相关。与中年炎症标志物无升高（第四四分位数）的参与者相比，3种或更多标志物升高的参与者海马体和阿尔茨海默病特征区域体积平均小5%。中年炎症与老年脑容量之间的关联因年龄和种族而有所改变，即中年时期全身炎症水平较高的年轻参与者和白人参与者随后更有可能出现脑容量减小。
我们的前瞻性研究结果为全身炎症在神经退行性变和认知衰老中可能的早期促成作用提供了证据。
