Pasha Evan P, Rutjes Elmer, Tomoto Tsubasa, Tarumi Takashi, Stowe Ann, Claassen Jurgen A H R, Munro Cullum C, Zhu David C, Zhang Rong
Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, TX, USA.
The University of Texas Southwestern Medical Center, Dallas, TX, USA.
J Alzheimers Dis. 2020;74(3):925-935. doi: 10.3233/JAD-191073.
Vascular dysfunction has been implicated in the onset and progression of Alzheimer's disease (AD), yet the relationship of arterial stiffening with brain amyloid-β (Aβ) burden in at risk patients is unclear.
We aimed to determine the relationship of aortic and carotid arterial stiffening with Aβ burden in patients with amnestic mild cognitive impairment (aMCI), a proposed transitional stage between normal aging and AD.
Thirty-two older adults with aMCI underwent 18Florbetapir PET amyloid imaging to ascertain Aβ burden via standardized uptake value ratio (SUVR). Carotid-femoral pulse wave velocity (cfPWV), which reflects aortic stiffness, and carotid β stiffness index and distensibility, which reflect local cerebral arterial stiffness, thus having direct impact on the cerebral circulation, were measured using applanation tonometry and ultrasonography.
Region-of-interest based analysis showed that precuneus and mean cortex Aβ SUVR were correlated positively with carotid β stiffness index and negatively with carotid distensibility after adjusting for age, sex, mean arterial pressure (MAP), pulse pressure (PP), and APOE4 status. Whole-brain voxel-wise analysis showed that Aβ SUVR was positively correlated with carotid β stiffness index, and negatively with carotid distensibility at the precuneus/cingulate gyrus after multiple comparison correction. cfPWV was not correlated with Aβ SUVR.
Carotid rather than aortic stiffening was independently associated with brain Aβ burden in patients with aMCI after adjusting for age, sex, MAP, PP, and APOE4 status. These findings provide evidence that arterial stiffening, particularly carotid artery stiffening, may contribute to AD pathology in patients with aMCI.
血管功能障碍与阿尔茨海默病（AD）的发生和进展有关，但在高危患者中，动脉僵硬度与脑淀粉样β蛋白（Aβ）负荷之间的关系尚不清楚。
我们旨在确定在遗忘型轻度认知障碍（aMCI）患者中，主动脉和颈动脉僵硬度与Aβ负荷之间的关系。aMCI是正常衰老和AD之间的一个过渡阶段。
32名患有aMCI的老年人接受了18氟代贝他吡PET淀粉样成像，通过标准化摄取值比率（SUVR）确定Aβ负荷。使用压平式眼压计和超声测量反映主动脉僵硬度的颈动脉-股动脉脉搏波速度（cfPWV），以及反映局部脑动脉僵硬度从而对脑循环有直接影响的颈动脉β僵硬度指数和扩张性。
基于感兴趣区域的分析显示，在调整年龄、性别、平均动脉压（MAP）、脉压（PP）和APOE4状态后，楔前叶和平均皮质Aβ SUVR与颈动脉β僵硬度指数呈正相关，与颈动脉扩张性呈负相关。全脑体素分析显示，在进行多重比较校正后，Aβ SUVR与颈动脉β僵硬度指数呈正相关，与楔前叶/扣带回的颈动脉扩张性呈负相关。cfPWV与Aβ SUVR无关。
在调整年龄、性别、MAP、PP和APOE4状态后，aMCI患者中颈动脉而非主动脉僵硬度与脑Aβ负荷独立相关。这些发现提供了证据，表明动脉僵硬度，尤其是颈动脉僵硬度，可能在aMCI患者的AD病理过程中起作用。
