Taheri Saeid, Prestopnik Jill, Rosenberg Gary A
Department of Pharmaceutical Sciences, University of South Florida, Tampa, FL, United States.
Center for Functional and Molecular Imaging, University of South Florida (USF) Heart Institute, Tampa, FL, United States.
Front Aging Neurosci. 2024 Sep 25;16:1462302. doi: 10.3389/fnagi.2024.1462302. eCollection 2024.
Advances in MRI techniques enable cerebral barrier transfer rates (K ) measurement in patients with vascular cognitive impairment and dementia (VCID). However, a consensus has not been reached on the dynamic contribution and importance of cerebral barrier abnormalities to the differential diagnosis of dementia subtypes. Our goal was to investigate the dynamics of blood-brain barrier (BBB) and blood-CSF barrier (BCSFB) K in patients with VCID longitudinally and determine the effect of aging.
We studied subjects at two time points over two years; they were 65.5 years of age (SD = 15.94, M/F = 24/14) at the first visit. We studied 38 patients, 18 of whom had two visits. We calculated the BBB and BCSFB K with dynamic contrast-enhanced T1 MR, and we used H-MR spectroscopy to measure N-acetylaspartate (NAA) levels in the white matter as a marker of injury. In addition, we measured CSF levels of active-matrix metalloproteinase-3 (MMP3) as an inflammatory biomarker to aid in patient clustering.
Longitudinal BBB measurements revealed variable dynamic behavior: after two years, the BBB K increased in 55% of patients and decreased in the remaining 45% unpredictably. We did not find a significant linear model of BBB K versus age for VCID. For healthy controls, the model was K = 0.0014 + 0.0002 × age, which was significant ( = 0.046). VCID patients showed a reduction in BCSFB K compared to healthy controls ( = 0.01). Combining NAA, CSF MMP3, and K in a clustering analysis separated patients into groups.
These results suggest that BBB K in VCID is dynamic and BCSFB K reduced by age. By combining inflammatory biomarkers with BBB K data, it is possible to separate VCID patients into distinct groups with different underlying pathologies.
磁共振成像（MRI）技术的进步使得能够测量血管性认知障碍和痴呆（VCID）患者的脑屏障转运率（K）。然而，关于脑屏障异常对痴呆亚型鉴别诊断的动态作用和重要性尚未达成共识。我们的目标是纵向研究VCID患者血脑屏障（BBB）和血脑脊液屏障（BCSFB）的K值动态变化，并确定衰老的影响。
我们在两年内的两个时间点对受试者进行了研究；首次就诊时他们的年龄为65.5岁（标准差=15.94，男/女=24/14）。我们研究了38例患者，其中18例进行了两次就诊。我们使用动态对比增强T1磁共振成像计算BBB和BCSFB的K值，并使用氢磁共振波谱测量白质中N-乙酰天门冬氨酸（NAA）水平作为损伤标志物。此外，我们测量脑脊液中活性基质金属蛋白酶-3（MMP3）水平作为炎症生物标志物，以辅助患者分组。
BBB的纵向测量显示出可变的动态行为：两年后，55%的患者BBB的K值增加，其余45%的患者则不可预测地降低。我们未发现VCID患者BBB的K值与年龄之间存在显著的线性模型。对于健康对照者，模型为K = 0.0014 + 0.0002×年龄，具有显著性（P = 0.046）。与健康对照者相比，VCID患者的BCSFB的K值降低（P = 0.01）。在聚类分析中，将NAA、脑脊液MMP3和K值结合起来可将患者分为不同组。
这些结果表明，VCID患者的BBB的K值是动态变化的，且BCSFB的K值随年龄增长而降低。通过将炎症生物标志物与BBB的K值数据相结合，有可能将VCID患者分为具有不同潜在病理特征的不同组。
