Neurocognition, Lifestyle Modification, and Treatment Resistant Hypertension

 描述（由申请人提供）：本申请建议通过收集神经认知性能、内皮功能和脑血管储备的测量值，扩展一项正在进行的、NHLBI资助的、在顽固性高血压患者中进行的运动和饮食的随机临床试验（顽固性高血压患者生活方式改变的设施和基于网络的方法; R 01 HL 122836）。已明确HTN与不良脑血管结局（包括卒中）的风险增加相关，并且是认知能力下降和痴呆的最重要的可改变风险因素。与血压正常者相比，高血压患者表现出神经认知障碍，以及微血管缺血性脑改变。顽固性高血压（RH）患者（定义为尽管接受了最佳药物治疗但血压（BP）控制不佳）发生不良临床事件和认知障碍的风险甚至高于HTN控制患者。运动和饮食已被证明可以降低血压和改善神经认知，为缓解认知障碍提供了干预机会。然而，生活方式的改变对神经认知的影响从未在RH患者中进行过研究。 父母随机临床试验（RCT）旨在检查与标准化教育和医生建议（SEPA）对照条件相比，接受全面生活方式干预计划（C-Life）的RH患者的BP，体重，健身和心血管生物标志物的变化。C-Life干预将包括有监督的有氧运动、遵循阻止高血压饮食方法（DASH）饮食的饮食调整和结构性减肥，而随机分配到SEPA的参与者将获得有关这些健康生活方式改变的信息，但不会参加强化的监督计划。本提案的目的是检查C-Life对神经认知性能的影响，神经认知改善的机制，以及神经认知改善的维持。为了实现这一目标，我们将通过收集神经认知表现的多个指标来加强父母研究（执行功能、处理速度和记忆）、内皮功能（肱动脉血流介导的扩张）和脑血管储备（前额叶皮层脑组织氧合指数）在基线时，4个月干预后，并再次在一年的随访评估，与母公司试验评估同时进行。该研究旨在评价（a）C-Life对改善神经认知功能的有效性，（B）C-Life对内皮功能和脑血管储备的生物标志物的影响，（c）神经认知功能治疗改善的潜在介质，包括健身、内皮功能、脑血管储备、血压降低和体重减轻的改善，以及（d）健身改善的效果，DASH饮食依从性、体重减轻和血压降低对1年时神经认知表现的影响。

 DESCRIPTION (provided by applicant): The present application proposes to extend an ongoing, NHLBI-funded, randomized clinical trial of exercise and diet among individuals with resistant hypertension (Facilities and Web-based Approaches to Lifestyle Change in Resistant Hypertension; R01HL122836) by collecting measures of neurocognitive performance, endothelial function, and cerebrovascular reserve. It is well established that HTN is associated with increased risk of adverse cerebrovascular outcomes, including stroke, and is the most important modifiable risk factor for cognitive decline and dementia. Hypertensive patients exhibit neurocognitive impairments compared with normotensives, as well as microvascular ischemic brain changes. Patients with resistant hypertension (RH), defined as inadequately controlled blood pressure (BP) despite optimal pharmacological treatment, are at even higher risk of adverse clinical events and cognitive impairment compared to patients with controlled HTN. Exercise and diet have been shown to reduce BP and improve neurocognition, providing an intervention opportunity for the mitigation of cognitive impairment. However, the impact of lifestyle change on neurocognition has never been examined among patients with RH. The parent randomized clinical trial (RCT) is designed to examine changes in BP, weight, fitness, and cardiovascular biomarkers among individuals with RH undergoing a comprehensive lifestyle intervention program (C-Life) compared with standardized education and physician advice (SEPA) control condition. The C- Life intervention will consist of supervised aerobic exercise, dietary modification following the Dietary Approaches to Stop Hypertension (DASH) diet, and structured weight loss, whereas participants randomized to SEPA will be provided with information about these healthy lifestyle changes, but will not participate in the intensive, supervised program. The objective of the present proposal is to examine the effects of C-Life on neurocognitive performance, mechanisms of neurocognitive improvement, and maintenance of neurocognitive improvements. In order to accomplish this, we will enhance the parent study by collecting multiple measures of neurocognitive performance (executive function, processing speed, and memory), endothelial function (brachial artery flow mediated dilation), and cerebrovascular reserve (prefrontal cortex cerebral tissue oxygenation index) at baseline, following the 4-month intervention, and again during a one-year follow-up assessment, in tandem with parent trial assessments. The study will aim to evaluate (a) the effectiveness of C- Life on improving neurocognitive function, (b) the impact of C-Life on biomarkers of endothelial function and cerebrovascular reserve, (c) potential mediators of treatment improvements in neurocognitive function, including improvements in fitness, endothelial function, cerebrovascular reserve, BP reduction, and weight loss, and (d) the effects of improved fitness, DASH dietary adherence, reduced body weight, and BP reductions on neurocognitive performance at one-year.