Generating novel predictive models to estimate the risk of future ASCVD & Dementia in older adults

对早期医疗/外科专家向老龄化研究过渡（GEMSSTAR）竞赛赠款的回应 生成新的预测模型来估计老年人未来ASCVD和痴呆症的风险 项目概要/摘要： 一个人的基线风险在很大程度上决定了他们从许多预防性治疗中的预期获益。老年患者希望活得更长，同时保持认知功能和免于痴呆，包括阿尔茨海默病，这是老年人发病和残疾的头号原因。老年人也优先避免动脉粥样硬化性心血管疾病（ASCVD），这是老年人的头号杀手。重要的是，阿尔茨海默病和痴呆症的许多风险因素也会增加ASCVD的风险。阿尔茨海默氏病是老年人发生轻度认知障碍和痴呆的最常见病因学基础，并且可以在70-75%的病例中被确定为病因。因此，为老年患者提供包括阿尔茨海默病在内的痴呆症和ASCVD的个性化风险评估，可以促进老年人治疗决策的全面，循证和以患者为中心的方法。不幸的是，目前的风险模型是在年轻人中得出的，无法准确预测老年人的风险。其次，目前尚不清楚现有的ASCVD风险模型是否也可以预测痴呆风险，反之亦然。最后，到目前为止，还没有人评估这些风险估计是否有助于对老年人干预的治疗益处进行分层。我将利用由世界老年病学、心脏病学和流行病学专家组成的导师团队，利用来自国家心肺血液研究所（NHLBI）合并队列的≥75岁受试者的数据，开发一个临床风险模型，以估计选定基线访视后5年时痴呆（包括阿尔茨海默病）的风险（目标1）。同时，我们将开发一个临床风险模型，以估计相同时间段内≥75岁人群中ASCVD的风险。除了传统的风险因素外，我们还将使用一组新的候选预测因子来推导这些模型，这些候选预测因子以前未包括在先前的风险模型中，包括基线认知，功能状态，抑郁和流动性。然后将使用卒中地理和种族差异的原因（REGARDS）队列的数据对两种模型进行外部验证（目标2）。最后，我们将把我们的模型应用于来自收缩压干预试验（SPRINT）的≥75岁的患者，以确定老年人中强化与保守降压治疗的治疗获益是否在预测风险水平上存在差异（目标3）。一旦开发和验证，我们将开发一个基于电子健康记录的模型版本，用于临床护理的广泛传播和使用。我将通过这项工作接受的培训将使我在模型构建和部署方面拥有专业知识，并扩大我对痴呆症（包括阿尔茨海默病）的研究兴趣。这也将为未来申请保罗B奠定基础。Beeson新兴领导者职业发展奖和其他独立资助，最终目标是成为一名专注于老年人护理的独立临床研究人员。

Response to Grants for Early Medical/Surgical Specialists' Transition to Aging Research (GEMSSTAR) Competition Title: Generating novel predictive models to estimate the risk of future ASCVD & Dementia in older adults Project Summary/Abstract: A person’s baseline risk determines to a large extent their anticipated benefit from many preventive treatments. Older patients desire to live longer while maintaining cognitive function and freedom from dementia, including Alzheimer’s disease, the #1 cause of morbidity and disability in older adults. Older adults also prioritize avoiding atherosclerotic cardiovascular disease (ASCVD), the #1 killer of older adults. Importantly, many risk factors for Alzheimer’s disease and dementia also increase risk for ASCVD. Alzheimer’s disease is the most common etiologic basis for incident mild cognitive impairment and dementia in older adults and can be identified as the cause in 70-75% of cases. Thus, providing older patients with personalized risk estimates for both dementia, including Alzheimer’s disease, and ASCVD could facilitate a comprehensive, evidence-based and patient-centered approach to therapeutic decision making in older adults. Unfortunately, current risk models were derived in younger adults, and fail to accurately predict risk in older adults. Second it remains unclear whether existing ASCVD risk models can also predict dementia risk and vice versa. Finally, to date, no one has evaluated whether these risk estimates help stratify therapeutic benefits of intervention in older adults. Leveraging a mentorship team of world experts in geriatrics, cardiology, and epidemiology, I will utilize data from subjects ≥75 years old from the National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts in order to develop a clinical risk model to estimate risk of dementia, including Alzheimer’s disease, at 5 years from the selected baseline visit (Aim 1). In parallel, we will develop a clinical risk model to estimate the risk of ASCVD over the same time period in the same population of individuals ≥75 years old. In addition to traditional risk factors, we will derive these models using a novel set of candidate predictors not previously included in prior risk models including baseline cognition, functional status, depression, and mobility. Both models will then be externally validated using data from the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort (Aim 2). Finally, we will apply our model to patients ≥75 years old from the Systolic Blood Pressure Intervention Trial (SPRINT) in order to determine whether therapeutic benefit from intensive vs. conservative anti-hypertensive therapy in older adults differs across levels of predicted risk (Aim 3). Once developed and validated, we will develop an electronic health record-based version of the model for widespread dissemination and use in clinical care. The training I will receive through this work will give me expertise in model building and deployment and broaden my research interest in dementia including Alzheimer’s disease. It will also lay the groundwork for a future application for the Paul B. Beeson Emerging Leaders Career Development Award and other independent funding, with the ultimate goal of becoming an independent clinician-researcher focused on the care of older adults.