Arterial stiffness, pressure and flow pulsatility and brain structure and function: the Age, Gene/Environment Susceptibility - Reykjavik Study
Arterial stiffness, pressure and flow pulsatility and brain structure and function: the Age, Gene/Environment Susceptibility - Reykjavik Study
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DOI：
10.1093/brain/awr253
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发表时间：
2011-11-01
期刊：
影响因子：
14.5
通讯作者：
Launer, Lenore J.
中科院分区：
文献类型：
--
作者：
Mitchell, Gary F.;van Buchem, Mark A.;Launer, Lenore J.
主动脉僵硬度随着年龄和血管危险因素暴露而增加，并与大脑结构和功能异常的风险增加有关。高环境流量和低阻抗被认为使脑微循环对过度压力和流量脉动的有害影响敏感。然而，在高主动脉僵硬度的情况下，导致脑结构性病变和认知障碍的血流动力学机制仍不清楚。我们假设，与颈动脉相比，近端主动脉不成比例的硬化减少了这个重要界面处的波反射，从而促进了过多脉动能量传输到脑微循环中，导致微血管损伤和功能受损。为了评估这一假设，我们评估了在社区为基础的年龄、基因/环境易感性-雷克雅未克研究中参与者的颈动脉压力和流量、颈动脉-股动脉脉搏波速度、脑磁共振图像和认知评分，这些参与者没有中风、短暂性脑缺血发作或痴呆病史（n = 668，378名女性，69-93岁）。在随机子集（n = 422）中评估主动脉特性阻抗，并计算主动脉-颈动脉界面处的反射系数。颈动脉血流脉动指数与颈动脉反射系数呈负相关（R =-0.66，P < 0.001）。颈动脉脉压、搏动指数和颈动脉-股动脉脉搏波速度均与无症状皮质下梗死的风险增加相关（风险比为1.62-1.71/标准差，P < 0.002）。颈动脉-股动脉脉搏波速度与较高的白色高信号体积相关（0.108 +/- 0.045 SD/SD，P = 0.018）。搏动指数与较低的全脑体积（-0.127 +/- 0.037 SD/SD，P < 0.001）、灰质体积（-0.079 +/- 0.038 SD/SD，P = 0.038）和白色体积（-0.128 +/- 0.039 SD/SD，P < 0.001）相关。颈动脉-股动脉脉搏波速度（-0.095 +/- 0.043 SD/SD，P = 0.028）和颈动脉脉压（-0.114 +/- 0.045 SD/SD，P = 0.013）与较低的记忆力评分相关。搏动指数与较低的记忆分数（-0.165 +/- 0.039 SD/SD，P < 0.001）、较慢的处理速度（-0.118 +/- 0.033 SD/SD，P < 0.001）和评估执行功能的测试中较差的表现（-0.155 +/- 0.041 SD/SD，P < 0.001）相关。当磁共振成像测量（灰色和白色物质体积、白色物质高信号体积和普遍的皮质下梗死）被纳入认知模型时，血液动力学相关性减弱或不再显著，这与主动脉僵硬度增加和过度血流脉动性损害微循环的假设一致，导致可量化的组织损伤和认知能力降低。主动脉明显硬化与颈动脉和主动脉之间界面处的波反射减少、过度流动脉动性传输到脑中、微血管结构性脑损伤和各种认知领域的较低评分相关。
Aortic stiffness increases with age and vascular risk factor exposure and is associated with increased risk for structural and functional abnormalities in the brain. High ambient flow and low impedance are thought to sensitize the cerebral microcirculation to harmful effects of excessive pressure and flow pulsatility. However, haemodynamic mechanisms contributing to structural brain lesions and cognitive impairment in the presence of high aortic stiffness remain unclear. We hypothesized that disproportionate stiffening of the proximal aorta as compared with the carotid arteries reduces wave reflection at this important interface and thereby facilitates transmission of excessive pulsatile energy into the cerebral microcirculation, leading to microvascular damage and impaired function. To assess this hypothesis, we evaluated carotid pressure and flow, carotid-femoral pulse wave velocity, brain magnetic resonance images and cognitive scores in participants in the community-based Age, Gene/Environment Susceptibility - Reykjavik study who had no history of stroke, transient ischaemic attack or dementia (n = 668, 378 females, 69-93 years of age). Aortic characteristic impedance was assessed in a random subset (n = 422) and the reflection coefficient at the aorta-carotid interface was computed. Carotid flow pulsatility index was negatively related to the aorta-carotid reflection coefficient (R = -0.66, P < 0.001). Carotid pulse pressure, pulsatility index and carotid-femoral pulse wave velocity were each associated with increased risk for silent subcortical infarcts (hazard ratios of 1.62-1.71 per standard deviation, P < 0.002). Carotid-femoral pulse wave velocity was associated with higher white matter hyperintensity volume (0.108 +/- 0.045 SD/SD, P = 0.018). Pulsatility index was associated with lower whole brain (-0.127 +/- 0.037 SD/SD, P < 0.001), grey matter (-0.079 +/- 0.038 SD/SD, P = 0.038) and white matter (-0.128 +/- 0.039 SD/SD, P < 0.001) volumes. Carotid-femoral pulse wave velocity (-0.095 +/- 0.043 SD/SD, P = 0.028) and carotid pulse pressure (-0.114 +/- 0.045 SD/SD, P = 0.013) were associated with lower memory scores. Pulsatility index was associated with lower memory scores (-0.165 +/- 0.039 SD/SD, P < 0.001), slower processing speed (-0.118 +/- 0.033 SD/SD, P < 0.001) and worse performance on tests assessing executive function (-0.155 +/- 0.041 SD/SD, P < 0.001). When magnetic resonance imaging measures (grey and white matter volumes, white matter hyperintensity volumes and prevalent subcortical infarcts) were included in cognitive models, haemodynamic associations were attenuated or no longer significant, consistent with the hypothesis that increased aortic stiffness and excessive flow pulsatility damage the microcirculation, leading to quantifiable tissue damage and reduced cognitive performance. Marked stiffening of the aorta is associated with reduced wave reflection at the interface between carotid and aorta, transmission of excessive flow pulsatility into the brain, microvascular structural brain damage and lower scores in various cognitive domains.