Blood Pressure, Cerebral Perfusion & Cognitive Outcome In Hypertension.

描述(由申请人提供)：高血压(HTN)与脑血管调节不足、血管反应性(VR)和血流灌注受损有关。这些缺陷会导致灌流不足、脑损伤和认知障碍。HTN所致的脑白质损害(WML)是导致脑血流(CBF)和自我调节功能障碍的重要原因。缺乏自我调节使CBF更依赖于灌流压(平均动脉压：MAP)。因此，在患有HTN(HTN和WML)的受试者中，MAP和CBF之间的关系可能比健康人更强。验证这一假设具有重要的意义，因为它可能有助于为HTN受试者提供充分的血流灌注的最佳目标血压(BP)：如果建立更强的CBF对MAP的依赖，过度降低血压可能被证明是有害的。BP过高和过低都可能有害。我们计划提供最佳的证据。这项研究将包括180名认知正常的高血压老年人(90名无WML(HTN/WML-)，90名WML(HTN/WML))和50名正常血压对照(NL)，分别在基线、12个月和24个月后进行检查。我们建议检验以下四个假设：1.CBF。A.在横断面上，三组(NL、HTN/WML-、HTN/WML)的MAP-CBF关系越来越强，反映了进行性的自我调节功能障碍。B.纵向：基线BP预测随访时CBF的保存情况。2.虚拟现实。A.在横断面上，三组的VR均降低，反映了血管功能的日益受损。B.纵向：基线BP指标可预测随访时VR的保留。3.认知。在横断面上，认知与BP、CBF、VR之间的关系在三组中逐渐增强。纵向：基线BP、CBF和VR可预测随访时认知功能的变化。4.大脑测量。A.纵向上，基线BP、CBF和VR预测在随访时脑容量和脑组织代谢完整性的保存。我们建议在每组中确定：1)在随访时最有利于CBF和VR保存的基线BP值，以及2)在随访时最有利于认知和脑保存的基线BP、CBF和VR值。我们将测试BP对认知和大脑的影响是否通过CBF和VR介导。CBF和VR将使用非侵入性、抗易感性伪影的动脉旋转标记MRI进行测量，使用二氧化碳重复呼吸挑战。将对全球和局部的脑灌注和脑容量进行评估，以确定区域脆弱性。磁共振波谱将被用来评估基于全球N-乙酰天冬氨酸的大脑代谢完整性。这些数据可能会提高我们对HTN患者血压、脑血流灌注和认知之间关系的理解。证明HTN/WML-组和HTN/WML组在保存灌注、认知和脑测量方面具有不同的最佳BP将证实单独优化HTN治疗的必要性。先进的成像技术将帮助我们了解目标血压。

DESCRIPTION (provided by applicant): Hypertension (HTN) is associated with deficient cerebral vascular regulation, impaired vasoreactivity (VR) and perfusion. These deficits lead to hypoperfusion, brain damage and cognitive impairment. White matter lesions (WML), resulting from HTN, contribute to the impairment in cerebral blood flow (CBF) and autoregulation. Deficient autoregulation makes CBF more dependent on perfusion pressure (mean arterial pressure: MAP). Consequently, in subjects with HTN (and even more so with HTN and WML) the relationship between MAP and CBF may be stronger than in healthy individuals. Verifying this hypothesis has important implications, as it may help to optimally target blood pressure (BP) for adequate perfusion in subjects with HTN: Should stronger dependence of CBF on MAP be established excessive reduction of blood pressure may prove detrimental. Both too high and too low BP is likely harmful. We plan to provide evidence for an optimum. The study will include 180 cognitively normal hypertensive elderly (90 without WML (HTN/WML-), 90 with WML (HTN/WML+)) and 50 normotensive controls (NL), examined at baseline, 12 and 24 months later. We propose to test the following four hypotheses: 1. CBF. a. At cross-section the MAP-CBF relationships are increasingly stronger across 3 groups (NL, HTN/WML-, HTN/WML+), reflecting progressive dysfunction of autoregulation. b. Longitudinally: baseline BP predicts CBF preservation at follow-up. 2. VR. a. At cross-section, VR decreases across 3 groups, reflecting increasingly impaired vascular function. b. Longitudinally: baseline BP metrics predict VR preservation at follow-up. 3. Cognition. a. At cross-section, the relationship between cognition and BP, CBF, and VR is progressively stronger across 3 groups. b. Longitudinally: baseline BP, CBF and VR predict change in cognition at follow-up. 4. Brain measures. a. Longitudinally, baseline BP, CBF and VR predict preservation of brain volumes and brain tissue metabolic integrity at follow- up. We propose to determine in each group: 1) baseline BP values optimal for CBF and VR preservation at follow-up, and 2) baseline BP, CBF and VR values optimal for cognition and brain preservation at follow-up. We will test whether effects of BP on cognition and the brain are mediated through CBF and VR. CBF and VR will be measured with non- invasive, susceptibility-artifact resistant arterial spin labeling MRI using a carbon dioxide rebreathing challenge. Brain perfusion and volume will be evaluated globally and locally to determine regional vulnerability. Magnetic resonance spectroscopy will be used to assess brain metabolic integrity based on global N-acetylaspartate. These data will likely improve our understanding of the relationships between BP, brain perfusion and cognition in HTN. Documenting that HTN/WML- and HTN/WML+ groups have different optimum BP for preservation of perfusion, cognition and brain measures will confirm the need to individually optimize HTN treatment. Advanced imaging techniques will help to inform us as to the target BP values.