Neurosection, Division of MRI Research, Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA.
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
Neurobiol Aging. 2019 Apr;76:181-193. doi: 10.1016/j.neurobiolaging.2019.01.001. Epub 2019 Jan 10.
The protracted accumulation of amyloid-β (Aβ) is a major pathologic hallmark of Alzheimer's disease and may trigger secondary pathological processes that include neurovascular damage. This study was aimed at investigating long-term effects of Aβ burden on cerebral blood volume of arterioles and pial arteries (CBVa), possibly present before manifestation of dementia. Aβ burden was assessed by 11C Pittsburgh compound-B positron emission tomography in 22 controls and 18 persons with mild cognitive impairment (MCI), [ages: 75(±6) years]. After 2 years, inflow-based vascular space occupancy at ultra-high field strength of 7-Tesla was administered for measuring CBVa, and neuropsychological testing for cognitive decline. Crushing gradients were incorporated during MR-imaging to suppress signals from fast-flowing blood in large arteries, and thereby sensitize inflow-based vascular space occupancy to CBVa in pial arteries and arterioles. CBVa was significantly elevated in MCI compared to cognitively normal controls and regional CBVa related to local Aβ deposition. For both MCI and controls, Aβ burden and follow-up CBVa in several brain regions synergistically predicted cognitive decline over 2 years. Orbitofrontal CBVa was positively associated with apolipoprotein E e4 carrier status. Increased CBVa may reflect long-term effects of region-specific pathology associated with Aβ deposition. Additional studies are needed to clarify the role of the arteriolar system and the potential of CBVa as a biomarker for Aβ-related vascular downstream pathology.
淀粉样蛋白-β（Aβ）的长期积累是阿尔茨海默病的主要病理标志，可能引发包括神经血管损伤在内的继发性病理过程。本研究旨在研究 Aβ负荷对脑小动脉和软脑膜动脉（CBVa）脑血容量的长期影响，这些影响可能在痴呆出现之前就已经存在。通过 11C 匹兹堡化合物-B 正电子发射断层扫描，在 22 名对照者和 18 名轻度认知障碍（MCI）者[年龄：75（±6）岁]中评估 Aβ负荷。2 年后，在 7 特斯拉超高场强下进行基于流入的血管空间占有率测量，以测量 CBVa，并进行神经心理学测试以评估认知下降。在 MR 成像过程中纳入挤压梯度，以抑制大动脉中快速流动血液的信号，从而使流入型血管空间占有率对软脑膜动脉和小动脉中的 CBVa 敏感。与认知正常的对照组相比，MCI 患者的 CBVa 明显升高，并且局部 CBVa 与局部 Aβ沉积相关。对于 MCI 和对照组，Aβ负荷和几个脑区的随访 CBVa 协同预测了 2 年内的认知下降。眶额皮质 CBVa 与载脂蛋白 E e4 携带者状态呈正相关。增加的 CBVa 可能反映了与 Aβ 沉积相关的特定区域病理学的长期影响。需要进一步的研究来阐明小动脉系统的作用以及 CBVa 作为与 Aβ 相关血管下游病理学的生物标志物的潜力。
