The Effect of Vascular Risk Factors on Risk of Alzheimer's Disease and Related Dementias after Stroke (STROKE COG)

项目摘要/摘要 阿尔茨海默病和阿尔茨海默病相关痴呆(AD/ADRD)在老年人中的发病率很高 中风。在理解血管危险因素(VRF)如何影响心血管疾病风险方面存在着根本性的差距。 卒中后AD/ADRD。对卒中后AD/ADRD风险的生物学因素缺乏了解是设计旨在保护卒中幸存者大脑健康的干预措施的关键障碍。长期的 目标是开发、测试和传播VRF干预措施，为不同人群减少卒中后AD/ADRD。该研究的目标是量化VRF如何影响卒中后AD/ADRD风险，以便为卒中幸存者量身定做的预防性干预提供信息，并为临床护理和政策提供信息。卒中后AD/ADRD是 这是一种高患病率和高成本的严重、慢性病的绝佳模式。高血压(BP)， 糖尿病和高胆固醇是理想的生物学VRF，因为它们很常见，而且可以广泛修改 一系列有效的管理治疗方法。我们的中心假设是中风后的VRF水平有助于 至卒中后AD/ADRD。拟议研究的基本原理是，了解VRF水平的影响 而卒中(亚)型对卒中后AD/ADRD的研究将提高我们对血管生物学的理解和翻译 为预防中风后AD/ADRD采取新的创新方法。以强劲的前期工作为指导 数据，这一假设将通过3个具体目标进行检验：1)量化中风后VRF水平的影响 关于卒中后认知轨迹和AD/ADRD，并探索性别和种族如何影响这些关系； 2)明确卒中亚型与卒中后认知轨迹与AD/ADRD的关系； 探索VRF、性别和种族如何影响这些关系；以及3)通过添加卒中后AD/ADRD和AIMS 1和2的结果来量化来精炼和扩展现有的AD/ADRD-CVD计算机模拟模型 中风事件的子集、样本大小和试验持续时间，这些试验有足够的能力在临床上发现 VRF降低对卒中后AD/ADRD的重要和可信的影响大小。目标1和目标2的结果 将确定降低卒中后AD/ADRD风险的干预措施的VRF目标，以及最有可能从VRF降低中受益的卒中幸存者亚组。AIM 3的结果将是一个适用于中风幸存者的新模拟模型，可用于为临床研究试验、临床护理和 政策。这项研究具有创新性，因为它最终将产生一种新的模拟模型，可以提供 可能会改变中风幸存者的临床实践和健康政策的新指南。建议的研究是 意义重大，因为它将产生新的知识和方法来了解最佳VRF的影响 治疗强度对卒中后AD/ADRD风险的影响，并改进卒中幸存者降低VRF试验的设计。最终，这些知识有可能为制定有针对性的干预措施提供信息，以改善中风后AD/ADRD的预防，并减少美国老年人AD/ADRD相关的残疾。

PROJECT SUMMARY/ABSTRACT Alzheimer’s disease and Alzheimer’s disease-related dementia (AD/ADRD) incidence is high in older adults with stroke. There is a fundamental gap in understanding how vascular risk factors (VRFs) influence risk of post-stroke AD/ADRD. Poor understanding of the biological factors driving post-stroke AD/ADRD risk is a critical barrier to the design of interventions aimed to protect the brain health of stroke survivors. The long-term goal is to develop, test, and disseminate VRF interventions that reduce post-stroke AD/ADRD for diverse populations. The study objective is to quantify how VRFs influence post-stroke AD/ADRD risk to inform preventive interventions tailored to stroke survivors and inform clinical care and policies. Post-stroke AD/ADRD is an excellent model of a serious, chronic illness of aging with high prevalence and costs. High blood pressure (BP), diabetes, and high cholesterol are ideal biological VRFs because they are common and modifiable with a wide range of effective therapies for management. Our central hypothesis is that post-stroke VRF levels contribute to post-stroke AD/ADRD. The rationale for the proposed research is that knowing the impact of VRF levels and stroke (sub)type on post-stroke AD/ADRD will improve our understanding of vascular biology and translate into new and innovative approaches for prevention of post-stroke AD/ADRD. Guided by strong preliminary data, this hypothesis will be tested through 3 specific aims: 1) Quantify the influence of post-stroke VRF levels on post-stroke cognitive trajectories and AD/ADRD, and explore how sex and race affect these relationships; 2) Clarify the relationships between stroke subtype and post-stroke cognitive trajectories and AD/ADRD, and explore how VRFs, sex, and race affect these relationships; and 3) Refine and expand an existing AD/ADRD-CVD computer simulation model by adding post-stroke AD/ADRD and results from Aims 1 and 2 to quantify the subset of stroke events, sample size, and duration of trials that are adequately powered to find clinically important and plausible effect sizes of VRF lowering on post-stroke AD/ADRD. The results of Aims 1 and 2 will be the identification of both VRF targets for interventions to reduce post-stroke AD/ADRD risk and the sub-groups of stroke survivors most likely to benefit from VRF lowering. The results of Aim 3 will be a new simulation model applicable to stroke survivors that can be used to inform clinical research trials, clinical care, and policies. This research is innovative because it will ultimately yield a novel simulation model that could provide new guidance that may change clinical practice and health policy for stroke survivors. The proposed study is significant because it will generate new knowledge and methods to understand the impact of optimal VRF treatment intensity on post-stroke AD/ADRD risk and improve the design of VRF lowering trials in stroke survivors. Ultimately, such knowledge has the potential to inform the development of targeted interventions to improve the prevention of post-stroke AD/ADRD and to reduce AD/ADRD-related disability in older Americans.