Reimagining Precision Medicine Approaches to AD Diagnosis

项目总结 尽管生物标志物取得了进展，但日常临床实践中诊断ADRD的准确性仍然存在。 不充分，特别是对健康差距人口而言。该研究计划通过以下方式应对这一挑战 在各种不同的临床和血浆生物标记物中验证有前景的、广泛获得的和廉价的 学术环境和现实世界临床实践中的人群。我们的首要目标是重新想象 使用可扩展的精确医学工具诊断ADRD的方法。这项提议使 联合PI的研究项目吉尔·拉比诺维奇博士，行为神经学家和脑成像领域的领导者 BioMarkers和凯特·波辛博士，她是神经心理学家和平板认知创新的领导者 评估和痴呆症护理模式。我们将从加州大学旧金山分校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、表型较深的临床队列(范围 从认知功能受损到痴呆症)，其中拉丁裔/西班牙裔占很大比例；来自 一项新的研究，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应用 或痴呆症，并强调招募黑人/非裔美国人和拉丁裔/拉美裔患者。使用 合作者Peggye Dilworth-Anderson博士，关注文化细微差别的新颖招生方法， 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设定标准。所有参与者 将接受一系列简短的特定领域的认知测试，并对健康的社会决定因素进行调查 (SDH)、认知和功能症状以及照顾者因素。基于血液的淀粉样蛋白、tau和 将与合作研究员西德·奥布莱恩特博士一起测量1000名参与者的神经退行性变。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式提供信息。所有参与者都将接受 UCSF ADRC参与者还将接受tau PET和MRI检查。我们将确定 最能预测分子病理学的临床措施和基于血液的生物标志物。我们将发展 考虑患者因素、SDH、认知、照顾者因素和基于血液的生物标志物的分类器 预测淀粉样蛋白和tau的PET结果，对PET成像和健康结果是必要的。我们将指导和 在整个项目中为初级和早期调查人员提供支持。该项目将针对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 还推进了与种族/民族多样性和基于血液的生物标记物有关的其他关键里程碑。这 这项工作将为包容性地确定适当的疾病修改疗法候选者做好准备。

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.