Bowman G L, Kaye J A, Moore M, Waichunas D, Carlson N E, Quinn J F
Department of Neurology, Department of Public Health and Preventive Medicine, Oregon Health and Science University, Portland, OR, USA.
Neurology. 2007 May 22;68(21):1809-14. doi: 10.1212/01.wnl.0000262031.18018.1a.
To determine the stability and functional significance of blood-brain barrier (BBB) integrity in patients with mild to moderate Alzheimer disease (AD).
Thirty-six patients (mean age 71 +/- 7 years) with mild to moderate AD (Mini-Mental State Examination [MMSE] 19 +/- 5) participated in a biomarker study involving clinical assessments, brain imaging, and CSF and plasma collection over 1 year. BBB integrity was assessed with the CSF-albumin index (CSF-AI).
BBB disruption was present in an important subgroup of patients (n = 8/36, 22%) at all time points measured. CSF-AI was highly reproducible over 1 year with an intraclass correlation of 0.96. Age, sex, and APOE status did not correlate with CSF-AI. Vascular factors (blood pressure, Hachinski ischemia score, MR-derived white matter hyperintensity, body mass index) were not strongly associated with CSF-AI levels (p = 0.066). CSF/plasma IgG ratio correlated with CSF-AI in a manner indicating that peripheral IgG has greater access to the CNS in patients with an impaired BBB. Further evidence for the physiologic significance of the CSF-AI was noted in the form of correlations with rates of disease progression, including annual change on MMSE (r(2) = 0.11, p = 0.023), annual Clinical Dementia Rating sum-of-boxes change (r(2) = 0.29, p = 0.001), and annual ventricular volume change (r(2) = 0.17, p = 0.007).
Blood-brain barrier (BBB) impairment is a stable characteristic over 1 year and present in an important subgroup of patients with Alzheimer disease. Age, gender, APOE status, vascular risk factors, and baseline Mini-Mental State Examination score did not explain the variability in BBB integrity. A role for BBB impairment as a modifier of disease progression is suggested by correlations between CSF-albumin index and measures of disease progression over 1 year.
确定轻度至中度阿尔茨海默病（AD）患者血脑屏障（BBB）完整性的稳定性及其功能意义。
36例轻度至中度AD患者（平均年龄71±7岁，简易精神状态检查表[MMSE]评分为19±5）参与了一项生物标志物研究，该研究包括临床评估、脑成像以及为期1年的脑脊液和血浆采集。采用脑脊液白蛋白指数（CSF-AI）评估BBB完整性。
在所有测量时间点，一个重要亚组患者（n = 8/36，22%）存在BBB破坏。CSF-AI在1年内具有高度可重复性，组内相关系数为0.96。年龄、性别和APOE状态与CSF-AI无关。血管因素（血压、哈金斯基缺血评分、磁共振成像衍生的白质高信号、体重指数）与CSF-AI水平无强相关性（p = 0.066）。CSF/血浆IgG比值与CSF-AI相关，表明在BBB受损患者中，外周IgG更容易进入中枢神经系统。CSF-AI与疾病进展速率的相关性进一步证明了其生理意义，这些相关性包括MMSE的年度变化（r(2) = 0.11，p = 0.023）、年度临床痴呆评定量表总分变化（r(2) = 0.29，p = 0.001）以及年度脑室容积变化（r(2) = 0.17，p = 0.007）。
血脑屏障（BBB）损害是阿尔茨海默病患者一个重要亚组在1年内的稳定特征。年龄、性别、APOE状态、血管危险因素和基线简易精神状态检查表评分均无法解释BBB完整性的变异性。CSF-白蛋白指数与1年内疾病进展指标之间的相关性提示BBB损害在疾病进展中起修饰作用。
