Guiding next steps for SPRINT-MIND implementation: Identifying high-benefit subgroups and comparative effects of ARB- vs. ACEI-based regimens

项目总结 阿尔茨海默病和相关痴呆(ADRD)是老年人依赖和残疾的主要原因 全球老年人口，每年给美国医疗保健系统造成超过2000亿美元的成本。因为ADRD 代表着持续的不可逆转的身体和认知能力的下降，找到了有效的方法来治疗它 预防势在必行。高血压，尤其是中年高血压，与认知风险的增加有关。 拒绝和ADRD。随机收缩压(SBP)干预试验的最新数据 (冲刺)高血压下降的记忆和认知(冲刺思维)表明强化 SBP对照组(120毫米汞柱)降低了已判定的轻度认知损害(MCI)的综合发生率。 和可能的痴呆症，以及与标准BP相比的异常脑白质病变(WML)体积 对照(&lt；140毫米汞柱)超过五年的随访。为了最大限度地影响公共卫生，关键是要确定哪些是 患者从强化SBP治疗中获得最大的认知和净收益(总体)，如果认知 好处是由于特定的抗高血压药物对认知的直接影响，独立于或在 此外，它们还具有降血压的作用。之前的动物和人类研究，以及我们的初步数据表明 血管紧张素II受体阻滞剂(ARB)对认知的影响比血管紧张素转换更大- 酶抑制剂(ACEI)。如果得到证实，这一发现将具有重要意义，因为ARB和ACEI目前 在给老年人开的最常见的药物中，被认为有同等益处 和安全。我们的目标是回答如何在老年人中安全地实现Sprint的剩余问题 患者最有可能从强化SBP治疗中获得认知方面的好处。样本量大，5 多年的随访，高质量的重复测量严格判定认知结果，大脑 成像，以及降压药物的使用，Sprint Mind提供了一种独特的、经济高效的、理想的 来回答这些问题。我们的目标是：(1)开发和验证一个量化的预测工具 患者的预期认知收益和净(总体)收益包含认知和 强化SBP治疗下SAE的心血管益处和风险，以及(2)确定比较 ARB与ACEI抗高血压药物治疗方案的剂量-反应效应 认知和大脑结构的结果与降低SBP的效果无关。尽管Sprint Mind是 在第一批证明对认知有有益预防作用的随机试验中，尚不确定 冲刺心态应该落实在哪些患者身上。这个项目的成功完成将 通过确定以下步骤来指导实施步骤：(1)哪些患者获得最大的认知和 强化SBP治疗的净收益(总体)以及(2)ARB是否对认知有更大的有益影响 结果和WML容量均高于ACEI，与其相似的降压效果无关。

PROJECT SUMMARY Alzheimer’s disease and related dementias (ADRD) are the leading cause of dependence and disability in the elderly population worldwide, costing the US healthcare system over $200 billion annually. Because ADRD represents a continuous irreversible physical and cognitive decline, identifying effective approaches for its prevention is imperative. Hypertension, particularly in midlife, is associated with an increased risk of cognitive decline and ADRD. Recent data from the randomized Systolic Blood Pressure (SBP) Intervention Trial (SPRINT) Memory and cognition IN Decreased hypertension (SPRINT MIND) demonstrated that intensive SBP control (<120 mmHg) reduced the combined incidence of adjudicated mild cognitive impairment (MCI) and probable dementia, as well as abnormal white matter lesion (WML) volume compared to standard BP control (<140 mmHg) over five years follow up. To maximize public health impact, it is critical to identify which patients derive the greatest cognitive and net (overall) benefit from intensive SBP treatment and if cognitive benefits were due to direct effects of specific antihypertensive medications on cognition independent of, or in addition to, their BP-lowering effect. Prior animal and human studies, as well as our preliminary data, suggest that angiotensin II receptor blockers (ARB) have greater effects on cognition than angiotensin-converting- enzyme inhibitors (ACEI). If verified, this finding would be significant since ARBs and ACEIs are currently among the medications most commonly prescribed to older adults and are thought to be equivalent in benefit and safety. Our objective is to answer remaining questions of how to safely implement SPRINT in older patients most likely to derive cognitive benefits from intensive SBP treatment. With its large sample size, 5 years follow-up, and high-quality repeated measures of rigorously adjudicated cognitive outcomes, brain imaging, and antihypertensive medication use, SPRINT MIND provides a unique, cost-efficient, and ideal setting to answer these questions. We aim to: (1) develop and validate a prediction tool that quantifies patients’ expected cognitive benefits and net (overall) benefit incorporating cognitive and cardiovascular benefit and risk of SAEs under intensive SBP treatment, and (2) determine comparative effects, including dose-response, of ARB- vs. ACEI-based antihypertensive medication regimens on cognitive and brain structure outcomes independent of SBP-lowering effects. Though SPRINT MIND is among the first randomized trials to demonstrate a beneficial preventive effect on cognition, it is uncertain how SPRINT-MIND should be implemented and in which patients. Successful completion of this project will guide next steps for implementation by determining: (1) which patients derive the greatest cognitive and net (overall) benefit from intensive SBP treatment and (2) if ARBs have greater beneficial effects on cognitive outcomes and WML volume than ACEIs, independent of their similar SBP lowering effects.