From the Departments of Radiology and Nuclear Medicine (H.J.v.d.H., J.F.A.J., P.A.M.H., W.H.B.) and Department of Neuropsychology and Psychiatry/Alzheimer Center Limburg (H.J.v.d.H., S.B., F.R.J.V.), Maastricht University Medical Center, PO Box 5800, 6202 AZ, Maastricht, the Netherlands; School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands (H.J.v.d.H., S.B., J.F.A.J., P.A.M.H., F.R.J.V., W.H.B.); and Departments of Radiology (M.J.P.v.O., M.A.v.B.) and Gerontology and Geriatrics (M.M.), Leiden University Medical Center, Leiden, the Netherlands.
Radiology. 2016 Nov;281(2):527-535. doi: 10.1148/radiol.2016152244. Epub 2016 May 31.
Purpose To investigate whether the blood-brain barrier (BBB) leaks blood-circulating substances in patients with early forms of Alzheimer disease (AD), and if so, to examine the extent and pattern of leakage. Materials and Methods This study was approved by the local medical ethical committees of the Maastricht University Medical Center and Leiden University Medical Center, and written informed consent was obtained from all subjects. For this pilot study, 16 patients with early AD and 17 healthy age-matched control subjects underwent dynamic contrast material-enhanced magnetic resonance (MR) imaging sequence with dual time resolution for 25 minutes. The Patlak graphical approach was used to quantify the BBB leakage rate and local blood plasma volume. Subsequent histogram analysis was used to determine the volume fraction of the leaking brain tissue. Differences were assessed with linear regression analysis, adjusted for confounding variables. Results The BBB leakage rate was significantly higher in patients compared with that in control subjects in the total gray matter (P < .05) and cortex (P = .03). Patients had a significantly higher volume fraction of the leaking brain tissue in the gray matter (P = .004), normal-appearing white matter (P < .04), deep gray matter (P = .01), and cortex (P = .004). When all subjects were considered, scores on the Mini-Mental State Examination decreased significantly with increasing leakage in the deep gray matter (P = .007) and cortex (P < .05). Conclusion The results of this study showed global BBB leakage in patients with early AD that is associated with cognitive decline. A compromised BBB may be part of a cascade of pathologic events that eventually lead to cognitive decline and dementia. RSNA, 2016 Online supplemental material is available for this article.
目的 探讨早期阿尔茨海默病（AD）患者血脑屏障（BBB）是否漏出血液循环物质，如果是，检查漏出的程度和模式。
材料和方法 本研究经马斯特里赫特大学医学中心和莱顿大学医学中心的当地医学伦理委员会批准，所有受试者均签署了书面知情同意书。在这项初步研究中，16 例早期 AD 患者和 17 例年龄匹配的健康对照者接受了 25 分钟双时间分辨率的动态对比增强磁共振（MR）成像序列。采用 Patlak 图形方法定量 BBB 漏出率和局部血血浆容量。随后的直方图分析用于确定漏出脑组织的体积分数。使用线性回归分析评估差异，并对混杂变量进行调整。
结果 与对照组相比，患者的总灰质（P <.05）和皮质（P =.03）的 BBB 漏出率明显更高。患者的灰质（P =.004）、正常外观的白质（P <.04）、深部灰质（P =.01）和皮质（P =.004）的漏出脑组织体积分数明显更高。当考虑所有受试者时，简易精神状态检查评分与深部灰质（P =.007）和皮质（P <.05）的漏出量呈显著负相关。
结论 这项研究的结果显示，早期 AD 患者存在全身性 BBB 漏出，与认知能力下降有关。BBB 受损可能是导致认知能力下降和痴呆的一系列病理事件的一部分。RSNA，2016 在线补充材料可从本文获得。
