Blood Pressure, Cerebral Perfusion & Cognitive Outcome In Hypertension.

血压、脑灌注

• 批准号: 8798687
• 负责人: Lidia Glodzik
• 金额: $ 67.62万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-06 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8798687
• 关键词: Aging; Biological Preservation; Blood Pressure; Blood Vessels; Brain; Brain Injuries; Brain region; Carbon Dioxide; Cerebrovascular Circulation; Cerebrum; Cognition; Cognitive; Conflict (Psychology); Data; Dependence; Elderly; Ensure; Functional disorder; Goals; Health; Homeostasis; Hour; Human; Hypertension; Hypotension; Image; Imaging Techniques; Impaired cognition; Impairment; Individual; Lead; Lesion; Longitudinal Studies; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Mediating; Metabolic; Monitor; Morphologic artifacts; N-acetylaspartate; Neurons; Outcome; Perfusion; Physicians; Predisposition; Probability; Pulse Pressure; Reading; Regulation; Research Personnel; Resistance; Sleep; Spin Labels; Techniques; Testing; Time; base; blood pressure reduction; brain tissue; brain volume; cerebrovascular; cognitive performance; follow-up; hemodynamics; hypertension treatment; hypoperfusion; improved; normotensive; novel; pressure; white matter

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.

描述（由申请人提供）：高血压（HTN）与脑血管调节缺陷、血管反应性（VR）和灌注受损有关。这些缺陷导致脑灌注不足、脑损伤和认知障碍。HTN引起的白质病变（WML）导致脑血流（CBF）和自动调节功能受损。缺乏自我调节使得脑血流更依赖于灌注压（平均动脉压：MAP）。因此，在HTN患者中（HTN和WML患者更是如此），MAP和CBF之间的关系可能比健康人强。验证这一假设具有重要意义，因为它可能有助于HTN患者的最佳目标血压（BP）以获得足够的灌注：如果建立了CBF对MAP的更强依赖性，则过度降低血压可能是有害的。血压过高和过低都可能有害。我们计划为最佳方案提供证据。该研究将包括180名认知正常的高血压老年人(90名无WML （HTN/WML-)， 90名有WML (HTN/WML+)）和50名血压正常的对照组（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，MAP-CBF关系在3组（NL, HTN/WML-, HTN/WML+）中越来越强，反映了自动调节功能的进行性功能障碍。b.纵向：基线BP预测随访时CBF保存情况。2. 虚拟现实。a.在横截面上，3组的VR均下降，反映血管功能受损程度日益加重。b.纵向：基线BP指标预测随访时的VR保存情况。3. 认知。a.在横截面上，认知与BP、CBF、VR之间的关系在3组间逐渐增强。b.纵向：基线BP、CBF和VR预测随访时认知变化。4. 大脑的措施。a.纵向上，基线血压、CBF和VR预测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)随访时CBF和VR保存的最佳基线血压值；2)随访时认知和脑保存的最佳基线血压、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将采用无创、抗敏感伪影动脉自旋标记MRI，使用二氧化碳再呼吸挑战来测量。脑灌注和容量将在全球和当地进行评估，以确定区域脆弱性。磁共振波谱将用于评估基于全局n -乙酰天冬氨酸的脑代谢完整性。这些数据可能会提高我们对HTN中血压、脑灌注和认知之间关系的理解。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血压，这将证实需要单独优化HTN治疗。先进的成像技术将帮助我们了解目标BP值。