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

血管危险因素对中风后阿尔茨海默病和相关痴呆症 (STROKE COG) 风险的影响

• 批准号: 10030919
• 负责人: Deborah Levine
• 金额: $ 310.55万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10030919
• 关键词: Address; Adult; Affect; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; American; Arteries; Automobile Driving; Biological; Biological Factors; Biology; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Cholesterol; Chronic Disease; Clinical; Clinical Research; Clinical Trials; Cognition; Cognitive; Cohort Studies; Computer Simulation; Data; Development; Diabetes Mellitus; Elderly; Epidemiology; Glucose; Glycosylated Hemoglobin; Goals; Health; Health Policy; Hemorrhage; High Prevalence; Human; Hypertension; Impaired cognition; Incidence; Individual; Intervention; Intervention Trial; Ischemic Stroke; Knowledge; LDL Cholesterol Lipoproteins; Lead; Lipids; Low-Density Lipoproteins; Measurement; Measures; Methods; Mission; Modeling; Outcome; Participant; Pharmaceutical Preparations; Policies; Population Heterogeneity; Prevention; Prevention approach; Preventive Intervention; Prospective cohort; Public Health; Race; Research; Risk; Risk Factors; Sample Size; Science; Sex Differences; Specific qualifier value; Stroke; Subgroup; Testing; Time; Translating; Treatment Factor; United States National Institutes of Health; adjudicate; brain health; cardiovascular disorder risk; clinical care; clinical practice; cohort; cost; dementia risk; design; disability; effective therapy; improved; innovation; models and simulation; novel; post stroke; post stroke cognitive impairment; public health priorities; racial difference; sex; stroke event; stroke survivor; therapy design; trial design; vascular contributions; vascular risk factor

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.

项目总结/摘要 阿尔茨海默病和阿尔茨海默病相关性痴呆（AD/ADRD）在老年人中的发病率很高 中风在了解血管危险因素（VRF）如何影响血管病变风险方面存在根本性差距。 中风后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脑健康的干预措施的关键障碍。长期 目的是开发、测试和传播VRF干预措施，以减少不同人群的卒中后AD/ADRD。本研究的目的是量化VRF如何影响卒中后AD/ADRD风险，为卒中幸存者量身定制的预防性干预措施提供信息，并为临床护理和政策提供信息。中风后AD/ADRD是一种 这是一种严重的慢性衰老疾病的极好模型，患病率高，成本高。高血压（BP）， 糖尿病和高胆固醇是理想的生物VRF，因为它们是常见的， 一系列有效的治疗方法。我们的中心假设是，中风后VRF水平有助于 中风后AD/ADRD拟议研究的基本原理是，了解VRF水平的影响 和卒中（亚）类型对卒中后AD/ADRD的影响将提高我们对血管生物学的理解， 新的和创新的方法来预防中风后AD/ADRD。以强有力的初步指导 数据，这一假设将通过3个具体目标进行检验：1）量化卒中后VRF水平的影响 中风后认知轨迹和AD/ADRD，并探讨性别和种族如何影响这些关系; 2)阐明卒中亚型和卒中后认知轨迹与AD/ADRD之间的关系， 探索VRF、性别和种族如何影响这些关系; 3）通过添加卒中后AD/ADRD和目标1和2的结果来量化现有AD/ADRD-CVD计算机模拟模型， 卒中事件的子集、样本量和试验的持续时间有足够的把握度来发现临床 VRF降低对卒中后AD/ADRD的重要和合理效应量。目标1和2的结果 将确定VRF目标，用于降低卒中后AD/ADRD风险的干预措施，以及最有可能从VRF降低中获益的卒中幸存者亚组。目标3的结果将是一个适用于中风幸存者的新模拟模型，可用于通知临床研究试验，临床护理， 施政纲要而这项研究是创新的，因为它最终将产生一个新的模拟模型，可以提供 新的指南可能会改变中风幸存者的临床实践和健康政策。拟定研究 意义重大，因为它将产生新的知识和方法，以了解最佳VRF的影响 治疗强度对卒中后AD/ADRD风险的影响，并改进卒中幸存者中VRF降低试验的设计。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，以改善卒中后AD/ADRD的预防，并减少美国老年人的AD/ADRD相关残疾。