Reimagining Precision Medicine Approaches to AD Diagnosis

项目摘要 尽管生物标志物取得了进展，但在日常临床实践中ADRD诊断的准确性仍然存在 不充分，特别是对健康不平等的人口。这项研究计划通过以下方式应对这一挑战： 验证有前途的，广泛使用的和廉价的临床和血浆为基础的生物标志物在不同的 在学术环境和现实世界的临床实践中的人群。我们的终极目标是 使用可扩展的精确医学工具诊断ADRD的方法。该提案协同 行为神经学家、脑成像领域的领导者吉尔·拉宾诺维奇博士的研究项目， 生物标志物，以及神经心理学家和基于平板电脑的认知创新领导者Kate Possin博士 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研究所招募400名参与者 研究中心（ADRC），其中包括大型，异质性，深度表型临床队列（范围 从认知未受损到痴呆），其中拉丁裔/西班牙裔成分很大; 750名参与者来自 新的IDEAS研究正在评估淀粉样蛋白PET在MCI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。与 合作者Peggye Dilleh-Anderson博士，关注文化细微差别的新颖入学方法， 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制定标准。所有参与者 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，以及照顾者因素。淀粉样蛋白、tau蛋白和 神经变性将在1,000名参与者中与共同研究者Sid O 'Bryant博士进行测量。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式提供信息。所有参与者将接受 淀粉样蛋白PET和UCSF ADRC参与者将额外接受tau PET和MRI。我们将确定 临床测量和基于血液的生物标志物，最好地预测分子病理学。我们将开发 分类器考虑患者因素、SDH、认知、护理人员因素和血液生物标志物， 预测淀粉样蛋白和tau PET结果，PET成像的必要性和健康结果。我们将指导和 在整个项目中支持初级和早期阶段的调查人员。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”， 还推进了与种族/民族多样性和基于血液的生物标志物相关的其他关键里程碑。这 这项工作将使该领域准备好全面鉴定用于疾病修饰疗法的适当候选物。

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.