Dementia Risk Prediction Pooling Project

项目摘要 阿尔茨海默病和相关痴呆症（ADRD）是一个主要的公共卫生问题， 在全球范围内增加。目前，超过580万美国人患有阿尔茨海默氏症或其他痴呆症， 随着我国人口继续老龄化，到2050年，这一数字将增加到1 380万人以上。巨大的进步是 在靶向治疗中可能能够降低痴呆症的风险。然而，识别 哪些患者应该接受这些预防干预目前尚不清楚， NINDS和该领域的专家作为一个重要的研究领域。我们小组和其他人所做的研究 研究表明，早在20多岁时的风险因素水平就会影响一个人未来患痴呆症的风险。 早期干预，以防止风险的积累和有针对性的干预措施，为那些在高风险， 有助于降低痴呆风险。风险预测方法可用于准确预测谁处于高风险， 制定痴呆症和目标干预措施;然而，目前的痴呆症风险预测模型 几个关键的限制，没有考虑到纵向风险因素的轨迹，一个关键的步骤， 实施精确预防方法，以确定痴呆症高危人群。 在这项研究中，我们建议开发痴呆症风险汇集项目（DRPP）， 严格协调12个中老年人前瞻性观察队列， 评估临床、遗传和行为风险因素，随访超过10年，并裁定 痴呆的确定DRPP将完成并通过基于云的 计算平台，作为本建议书R61阶段的一部分，满足 格兰特.然后，在本项目的R33阶段，我们将使用DRPP开发和验证准确的 和个性化的，动态的痴呆风险预测模型， 测量值，并且随着新的测量值的增加而容易地更新。该工具可用于临床， 指导治疗决策，并将提供给临床医生。该项目的目标是重要的， 及时，他们将提供一个风险分层工具，有针对性地干预/预防高风险个人。

PROJECT SUMMARY Alzheimer's Disease and related dementias (ADRD) are a major public health problem which is increasing worldwide. Currently, over 5.8 million Americans are living with Alzheimer's or other dementias and as our population continues to age this number will increase to over 13.8 million by 2050. Great strides are being made in targeted therapies which may be able to reduce the risk for dementia. However, identifying which patients should receive these prevention interventions is currently unknown and has been identified by NINDS and experts in the field as a critical area of research. Research done by our group and others has demonstrated that risk factor levels as early in life as the 20's influence an individual's future risk for dementia. Early intervention to prevent the accumulation of risk and targeted interventions for those at high risk could help to reduce dementia risk. Risk prediction methods can be used to accurately predict who is at high risk for developing dementia and target interventions; however, current risk prediction models for dementia have several critical limitations and none have taken into account longitudinal risk factor trajectories, a critical step to implementing precision prevention approaches to identify individuals at high risk for dementia. In this study we propose to develop the Dementia Risk Pooling Project (DRPP) by pooling and rigorously harmonizing 12 prospective observational cohorts of middle and older age adults, multiple in-person assessments of clinical, genetic and behavioral risk factors, follow-up of greater than 10 years and adjudicated dementia ascertainment. The DRPP will be completed and made available to researchers via a cloud-based computing platform as part of the R61 phase of this proposal meeting specific Go/No-Go Criteria outlined in the grant. Then, within the R33 phase of this project we will use the DRPP to develop and validate an accurate and personalized, dynamic dementia risk prediction model which incorporates longitudinal risk factor measurements and easily updates as new measurements are accrued. This tool can be used clinically to guide treatment decisions and will be made available to clinicians. The aims of this project are important and timely, they will provide a risk stratification tool for targeted intervention/prevention for high risk individuals.