Reimagining Precision Medicine Approaches to AD Diagnosis

重新构想 AD 诊断的精准医学方法

基本信息

批准号：
10211331
负责人：
Katherine Laurel Possin
金额：
$ 97.94万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-15 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10211331
关键词：
Address African American Alzheimer&apos s Disease Alzheimer&apos s disease diagnosis Alzheimer&apos s disease related dementia Amyloid Award Behavioral Biological Markers Brain imaging Caregivers Caring Clinical Cognition Cognitive Dementia Diagnosis Diagnostic Differential Diagnosis Disease Enrollment Fostering Future Goals Growth Health Hispanics Impaired cognition Incentives Latino Leadership Magnetic Resonance Imaging Measures Medicare Mentors Modeling Nerve Degeneration Neurologist Outcome Participant Patients Plasma Population Heterogeneity Positron-Emission Tomography Provider Research Research Personnel Resources Surveys Symptoms Tablets Work base beneficiary blood-based biomarker clinical Diagnosis clinical care clinical phenotype clinical practice cognitive testing cohort dementia care diagnostic accuracy ethnic diversity health disparity populations imaging biomarker improved innovation molecular pathology multidisciplinary novel precision medicine programs racial and ethnic recruit social health determinants tau Proteins tool

项目摘要

PROJECT SUMMARY Despite advances in biomarkers, the accuracy of the diagnosis of ADRD in everyday clinical practice remains inadequate, particularly for health disparities populations. This research program addresses this challenge by validating promising, widely accessible and inexpensive clinical and plasma-based biomarkers in diverse populations in an academic setting and in real-world clinical practice. Our over-arching goal is to reimagine approaches to the diagnosis of ADRD using scalable precision medicine tools. The proposal synergizes the research programs of co-PIs Dr. Gil Rabinovici, a behavioral neurologist and leader in brain imaging and biomarkers, and Dr. Kate Possin, a neuropsychologist and leader in innovation of tablet-based cognitive assessments and dementia care models. We will recruit 400 participants from the UCSF Alzheimer’s Disease Research Center (ADRC), which includes large, heterogeneous, deeply phenotyped clinical cohorts (ranging from cognitively unimpaired to dementia) with a large Latino/Hispanic component; and 750 participants from the New IDEAS study, which is evaluating the clinical utility of amyloid PET in Medicare beneficiaries with MCI or dementia and emphasizes recruitment of Black/African American and Latino/Hispanic patients. With Collaborator Dr. Peggye Dilworth-Anderson, novel enrollment approaches that attend to cultural nuances, provider workflows, and meaningful incentives will help set the standard for inclusive research. All participants will undergo a brief battery of domain-specific cognitive tests, and surveys of social determinants of health (SDH), cognitive and functional symptoms, and caregiver factors. Blood based biomarkers of amyloid, tau and neurodegeneration will be measured in 1,000 participants with co-investigator Dr. Sid O’Bryant. We will identify vulnerability factors and care needs that will inform future diagnostic care models. All participants will undergo amyloid PET, and UCSF ADRC participants will additionally undergo tau PET and MRI. We will identify the clinical measures and blood-based biomarkers that best predict molecular pathology. We will develop classifiers that consider patient factors, SDH, cognition, caregiver factors, and blood-based biomarkers to predict amyloid and tau PET findings, necessity for PET imaging and health outcomes. We will mentor and support junior and early stage-investigators throughout the project. This project will address ADRD Research Implementation Milestone 9.L “Improving differential diagnosis of symptomatic cognitive impairment,” while also advancing additional key Milestones related to racial/ethnic diversity and blood-based biomarkers. This work will ready the field for inclusive identification of appropriate candidates for disease modifying therapies.

项目概要尽管生物标志物取得了进步，但日常临床实践中 ADRD 诊断的准确性仍然存在不足，特别是对于健康差异人群而言，该研究计划通过以下方式解决了这一挑战。在不同的领域验证有前景、可广泛使用且廉价的临床和血浆生物标志物我们的首要目标是重新构想学术环境和现实临床实践中的人群。该提案整合了使用可扩展的精准医学工具来诊断 ADRD 的方法。联合 PI 吉尔·拉比诺维奇 (Gil Rabinovici) 博士的研究项目，他是一位行为神经学家、脑成像和脑成像领域的领导者生物标记物，以及神经心理学家和基于平板电脑的认知创新的领导者 Kate Possin 博士我们将从 UCSF 阿尔茨海默病中心招募 400 名参与者。研究中心 (ADRC)，包括大型、异质、深度表型的临床队列（范围从认知未受损到痴呆），其中有大量拉丁裔/西班牙裔成员；750 名参与者来自 New IDEAS 研究，该研究正在评估淀粉样蛋白 PET 在患有 MCI 的医疗保险受益人中的临床效用或痴呆症，并强调招募黑人/非裔美国人和拉丁裔/西班牙裔患者。合作者 Peggye Dilworth-Anderson 博士，关注文化差异的新颖招生方法，提供商工作流程和有意义的激励措施将有助于为所有参与者制定包容性研究的标准。将接受一系列简短的特定领域认知测试以及健康社会决定因素调查 (SDH)、认知和功能症状以及护理人员因素的淀粉样蛋白、tau 和蛋白的血液生物标志物。我们将与联合研究员 Sid O’Bryant 博士一起对 1,000 名参与者进行神经退行性疾病测量。脆弱性因素和护理需求将为未来的诊断护理模式提供信息。淀粉样蛋白 PET 和 UCSF ADRC 参与者将另外接受 tau PET 和 MRI 我们将确定。我们将开发最能预测分子病理学的临床测量和血液生物标志物。考虑患者因素、SDH、认知、护理人员因素和血液生物标志物的分类器预测 PET 成像和健康结果所必需的淀粉样蛋白和 tau PET 结果，我们将提供指导和指导。在整个项目中为初级和早期研究人员提供支持该项目将致力于 ADRD 研究。实施里程碑 9.L“改善症状性认知障碍的鉴别诊断”，同时还推进了与种族/民族多样性和血液生物标志物相关的其他关键里程碑。这项工作将为全面确定疾病修饰疗法的适当候选者做好准备。