Spatially Distributed Amyloid-β Reduces Glucose Metabolism in Mild Cognitive Impairment
Spatially Distributed Amyloid-β Reduces Glucose Metabolism in Mild Cognitive Impairment
复制标题
空间分布的淀粉样蛋白-β降低轻度认知障碍患者的糖代谢
DOI：
10.3233/jad-190560
复制
发表时间：
2020-01-01
影响因子：
4
通讯作者：
Bedell, Barry J.
中科院分区：
文献类型：
--
作者：
Carbonell, Felix;Zijdenbos, Alex P.;Bedell, Barry J.
背景资料：一些正电子发射断层扫描（PET）研究探索了淀粉样蛋白β（A β）、葡萄糖代谢和载脂蛋白E β 4基因型之间的关系。据报道，载脂蛋白E β 4，而不是聚集的A β，有助于葡萄糖低代谢在临床前阶段的阿尔茨海默氏病（AD）pathology.Objective：我们假设，典型的测量A β采取复合区域的利益与相对较高的负担，实际上涵盖了显着的模式与葡萄糖代谢的关系。相比之下，A β的空间加权测量与认知正常（CN）老化和轻度认知障碍（MCI）中的葡萄糖代谢更相关。我们已经基于葡萄糖代谢（如通过[F-18]2-氟-2-脱氧葡萄糖（FDG）PET测量的）和A β之间的交叉相关结构的联合奇异值分解（SVD）生成了淀粉样蛋白负荷评分，由阿尔茨海默病神经成像倡议研究的[F-18] florbetapir PET测量。这SVD为基础的分数揭示了皮质区域，其中减少葡萄糖代谢最大程度地与分布模式的A β。结果：从CN和MCI受试者的老年人口，我们发现，基于SVD的A β评分与葡萄糖代谢在几个皮质区域显着相关。此外，相应的A β网络的枢纽，有助于分布式葡萄糖代谢低下，这反过来，不一定是焦点的A β deposit.Conclusions：我们的方法发现隐藏的模式的葡萄糖代谢A β的关系。我们发现，基于SVD的A β评分与降低葡萄糖代谢的关系比APOE β 4基因型或A β负荷的整体测量更强。
Background: Several positron emission tomography (PET) studies have explored the relationship between amyloid-beta (A beta), glucose metabolism, and the APOE epsilon 4 genotype. It has been reported that APOE epsilon 4, and not aggregated A beta, contributes to glucose hypometabolism in pre-clinical stages of Alzheimer's disease (AD) pathology.Objective: We hypothesize that typical measurements of A beta taken either from composite regions-of-interest with relatively high burden actually cover significant patterns of the relationship with glucose metabolism. In contrast, spatially weighted measures of A beta are more related to glucose metabolism in cognitively normal (CN) aging and mild cognitive impairment (MCI).Methods: We have generated a score of amyloid burden based on a joint singular value decomposition (SVD) of the cross-correlation structure between glucose metabolism, as measured by [F-18]2-fluoro-2-deoxyglucose (FDG) PET, and A beta, as measured by [F-18] florbetapir PET, from the Alzheimer's Disease Neuroimaging Initiative study. This SVD-based score reveals cortical regions where a reduced glucose metabolism is maximally correlated with distributed patterns of A beta.Results: From an older population of CN and MCI subjects, we found that the SVD-based A beta score was significantly correlated with glucose metabolism in several cortical regions. Additionally, the corresponding A beta network has hubs that contribute to distributed glucose hypometabolism, which, in turn, are not necessarily foci of A beta deposition.Conclusions: Our approach uncovered hidden patterns of the glucose metabolism-A beta relationship. We showed that the SVD-based A beta score produces a stronger relationship with decreasing glucose metabolism than either APOE epsilon 4 genotype or global measures of A beta burden.