Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease

作者：Harm J. van de Haar, Saartje Burgmans, Jacobus F.A. Jansen, Matthias J.P. van Osch, Mark A. van Buchem, Majon Muller, Paul A.M. Hofman, Frans R.J. Verhey, Walter H. Backes · 发表于：Radiology · 年份：2016 · DOI：10.1148/radiol.2016152244 · 被引用次数：634 · 研究领域：Barrier Structure and Function Studies、Acute Ischemic Stroke Management、Neurological Disease Mechanisms and Treatments

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 < ...