PDF(Pubmed)
Abstract：
This study investigated the earliest change of cerebral blood flow (CBF) and its relationship with β-amyloid (Aβ) burden in preclinical Alzheimer\'s disease (AD) employing dual-phase 18F-florbetaben (FBB) PET. Seventy-one cognitively normal (NC) individuals were classified as Aβ negative (Aβ-NC) or positive (Aβ+NC) based on two different cutoff values: an SUVR of > 1.08 and a Centiloid scale of > 20. The PET scans were acquired in two phases: an early phase (0-10 min, eFBB) and a delayed phase (90-110 min, dFBB), which were averaged to generate single-frame images for each phase. Furthermore, an R1 parametric map was generated from the early phase data using a simplified reference tissue model. We conducted regional and voxel-based analyses to compare the eFBB, dFBB, and R1 images between the Aβ positive and negative groups. In addition, the correlations between the CBF proxy R1 and the dFBB SUVR were analyzed. The Aβ+NC group showed significantly higher dFBB SUVR in both the global cerebral cortex and target regions compared to the Aβ-NC group, while no significant differences were observed in eFBB SUVR between the two groups. Furthermore, the Aβ+NC group exhibited significantly higher R1 values, a proxy for cerebral perfusion, in both the global cerebral cortex and target regions compared to the Aβ-NC group. Significant positive correlations were observed between R1 and dFBB SUVR in both the global cerebral cortex and target regions, which remained significant after controlling for demographics and cognitive profiles, except for the medial temporal and occipital cortices. The findings reveal increased CBF in preclinical AD and a positive correlation between CBF and amyloid pathology. The positive correlation between R1 and amyloid burden may indicate a compensatory mechanism in the preclinical stage of Alzheimer\'s disease, but to elucidate this hypothesis, further longitudinal observational studies are necessary.
摘要：
这项研究采用双相18F-氟乙苯（FBB）PET研究了临床前阿尔茨海默病（AD）中脑血流（CBF）的最早变化及其与β-淀粉样蛋白（Aβ）负荷的关系。根据两个不同的临界值：SUVR>1.08和Centiloid量表>20，将71名认知正常（NC）个体分为Aβ阴性（Aβ-NC）或阳性（AβNC）。PET扫描分为两个阶段：早期阶段（0-10分钟，eFBB)和延迟相位(90-110分钟，dFBB),对其进行平均以生成每个阶段的单帧图像。此外，使用简化的参考组织模型从早期阶段数据生成R1参数图。我们进行了区域和基于体素的分析，以比较eFBB，dFBB,Aβ阳性和阴性组之间的R1图像。此外,分析了CBF代理R1与dFBBSUVR之间的相关性。与Aβ-NC组相比，AβNC组显示出在整个大脑皮层和目标区域的dFBBSUVR明显更高，而两组之间的eFBBSUVR没有显着差异。此外，Aβ+NC组R1值明显增高,脑灌注的代表,与Aβ-NC组相比，在整个大脑皮层和目标区域。在全球大脑皮层和目标区域中，R1和dFBBSUVR之间均观察到显着正相关，在控制人口统计学和认知特征后仍然很重要，除了内侧颞骨和枕骨皮质。研究结果表明，临床前AD的CBF增加，CBF与淀粉样蛋白病理之间呈正相关。R1与淀粉样蛋白负荷之间的正相关可能表明阿尔茨海默病临床前阶段的代偿机制。但是为了阐明这个假设，进一步的纵向观察研究是必要的。
