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：
10604257
负责人：
Katherine Laurel Possin
金额：
$ 96.41万
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/10604257
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 Black race Brain imaging Caregivers Caring Clinical Cognition Cognitive Dementia Diagnosis Diagnostic Differential Diagnosis Disease Enrollment Fostering Future Goals Growth Health Hispanic 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 Race Research Research Personnel Resources Surveys Symptoms Tablets Work beneficiary blood-based biomarker clinical care clinical diagnosis clinical phenotype clinical practice cognitive testing cohort dementia care diagnostic accuracy ethnic diversity health disparity populations improved innovation molecular pathology multidisciplinary novel precision medicine programs recruit social health determinants synergism 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.

项目摘要尽管生物标志物取得了进步，但每天临床实践中ADRD诊断的准确性仍然存在不足，特别是对于健康差异人群。该研究计划通过验证承诺，广泛访问和廉价的临床和基于等离子体的生物标志物在学术环境和现实世界中的临床实践中的人群。我们的整理目标是重新构想使用可伸缩精度药物工具诊断ADRD的方法。该提案协同 Co-Pis的研究计划Gil Rabinovici博士，行为神经科医生，脑成像领导者和领导者生物标志物和基于平板电脑的创新的神经心理学家兼领导者Kate Possin博士评估和痴呆症护理模型。我们将招募来自UCSF阿尔茨海默氏病的400名参与者研究中心（ADRC），包括大型，异质，深层表型临床人群（范围从认知独立的到痴呆症），有一个大的拉丁裔/西班牙裔组成部分；和750名参与者新的思想研究正在评估MCI Medicare受益人在Medicare受益人中的临床实用性或痴呆症，并强调招募黑人/非裔美国人和拉丁裔/西班牙裔患者。和合作者Peggye Dilworth-Anderson博士，采用文化细微差别的新型入学方法，提供者的工作流程和有意义的激励措施将有助于为包容性研究树立标准。所有参与者将经过一系列特定领域的认知测试，并对健康的社会决定者进行调查（SDH），认知和功能症状以及照料者因素。淀粉样蛋白，tau和神经变性将在1,000名参与者中与Sid O’Bryant博士一起测量。我们将确定脆弱性因素和护理需求将为未来的诊断护理模型提供信息。所有参与者都会经历淀粉样蛋白宠物和UCSF ADRC参与者还将接受Tau PET和MRI。我们将确定最能预测分子病理学的临床测量和血液基标志物。我们将发展考虑患者因素，SDH，认知，护理人员因素和血液生物标志物的分类器预测淀粉样蛋白和tau宠物的发现，这是宠物成像和健康结果所必需的。我们将指导和在整个项目中支持初级和早期评估者。该项目将解决ADRD研究实施里程碑9.l“改善症状性认知障碍的鉴别诊断”，而还促进了与种族/种族多样性和基于血液的生物标志物有关的其他关键里程碑。这工作将准备好该领域，以鉴定适当的疾病修饰疗法的候选者。