Biomarker Evaluation in Young Onset Dementia from Diverse Populations (BEYONDD)

不同人群年轻发病痴呆症的生物标志物评估 (BEYONDD)

• 批准号: 10670503
• 负责人: ADAM L. BOXER
• 金额: $ 606.52万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10670503
• 关键词: Address; Adult; Affect; Age; Agreement; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; American; Amyloid; Amyloid beta-42; Biological; Biological Markers; Black Populations; Black race; Blood; Blood Tests; Blood Vessels; Caring; Clinical; Clinical Trials; Clinical assessments; Cognition; Cognition Disorders; Cognitive; Communities; Community Participation; Consent; Dementia; Diagnosis; Discrimination; Disease; Early Onset Alzheimer Disease; Economics; Education; Elderly; Enrollment; Etiology; Evaluation; Frequencies; Frontotemporal Lobar Degenerations; Funding; Gold; Image; Impaired cognition; Individual; Industry; Knowledge; Latinx; Latinx population; Life; Light; Longitudinal Studies; Magnetic Resonance Imaging; Matched Group; Measures; Medical; Metabolic; Nerve Degeneration; Outcome; Participant; Patients; Persons; Plasma; Population Group; Population Heterogeneity; Positron-Emission Tomography; Privatization; Procedures; Productivity; Research; Resistance; Resources; Rest; Risk; Risk Factors; Science; Scientist; Severities; Societies; Stress; Technology; Testing; Time; United States National Institutes of Health; Ursidae Family; Validation; Vascular Cognitive Impairment; Visit; Work; base; behavioral impairment; biomarker evaluation; brain health; clinical diagnosis; cognitive testing; community engaged research; comorbidity; depressive symptoms; diagnostic accuracy; diagnostic biomarker; early onset; eligible participant; executive function; functional disability; gray matter; health disparity; imaging biomarker; improved; inclusion criteria; member; neurofilament; neuroimaging; new technology; patient advocacy group; population health; psychologic; public-private partnership; recruit; remote assessment; research clinical testing; resilience; social culture; tau Proteins; tau-1; tool; vascular cognitive impairment and dementia

ABSTRACT / PROJECT SUMMARY Early onset dementia (EOD) is devastating because it affects individuals at a time of life when they have peak personal and professional responsibilities and are actively contributing to society. Previous work has identified Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) as the most common causes of EOD. Despite this, most studies of EOD primarily have recruited non-Latinx Whites (NLW). Black and Latinx adults bear a disparate and disproportionate burden of biological and sociocultural vulnerabilities that confer increased ADRD risk in older persons, but the etiologies of dementia in younger members of these Diverse Populations (DPs) are not well understood. Dedicated and well-resourced efforts specifically tailored to study EOD in DPs, including identification of unique risk and resilience factors, are urgently needed. Plasma biomarkers of amyloid, tau and neurodegeneration and remotely collected automated clinical and cognitive assessments could greatly reduce barriers to characterization of EOD in DPs, but most studies evaluating these technologies have been conducted in older NLW. The Biomarker Evaluation in Young Onset Dementia from Diverse Populations (BEYONDD) longitudinal study will address these gaps in knowledge. This five-year longitudinal study will implement a scalable, intensive, and culturally-informed community-engaged research approach to remotely enroll 2,000 adults (<65yrs with 70% DPs and 30% NLW; n=1,700 with cognitive or behavioral impairments [CBI] & n=300 healthy controls) who will complete baseline automated cognitive, clinical, and sociocultural assessments, and blood draws for plasma biomarkers (Aβ42/40, P-tau217 and NfL) in the community, followed by either in-person (n=1,000 with CBI & n=300 healthy controls) or remote (n = 700) longitudinal evaluations. The annual in-person evaluations include “gold standard” clinical evaluations for etiologic diagnosis performed by expert clinicians including neuroimaging evaluations (MRI and amyloid PET). The annual remote evaluations will rely on automated tools. The study aims to: (1) Compare the etiology, severity, and cognitive and biomarker (plasma biomarkers and amyloid PET) profiles of EOD across ethnocultural groups (Black, Latinx and NLW); (2) Examine the effects of biological, psychological and sociocultural factors on EOD and resilience (resistance to EOD despite biological risk) outcomes across ethnocultural strata; (3) Validate plasma biomarkers and cognitive markers collected in the community by comparing the diagnostic accuracy of plasma Aβ42/40, P-tau217, and NfL versus “gold standard” clinical diagnosis and neuro-imaging biomarkers across ethnocultural groups, and evaluating the added value of remote cognitive assessments and clinical metabolic tests to plasma biomarkers’ diagnostic accuracy. Eligible participants will be co-enrolled in ongoing longitudinal ADRD studies focused on EOD while the rest will return for longitudinal assessments through BEYONDD. This project brings together a diverse team of leading scientists in EOD and brain health disparities, private and public stakeholders, and diverse community-based partner organizations, to create new resources to promote inclusive research in EOD.

摘要 /项目摘要 早期发作痴呆（EOD）是毁灭性的，因为它在生命时会影响个体 个人和专业责任，并积极为社会做出贡献。以前的工作已经确定 阿尔茨海默氏病（AD）和额颞叶变性（FTLD）是EOD的最常见原因。 尽管如此，大多数对EOD主要的研究都招募了非Latinx白人（NLW）。黑人和拉丁裔成年人 会议增加了生物学和社会文化脆弱性的不同和不成比例的伯恩。 老年人的ADRD风险，但是这些不同人群的年轻成员的痴呆症病因 （DPS）不太了解。专门针对研究DPS的EOD专门量身定制的专门资源的努力， 迫切需要包括识别独特的风险和弹性因素。淀粉样蛋白的血浆生物标志物， tau和神经退行性以及远程收集的自动化临床和认知评估可以极大 减少了DPS中EOD表征的障碍，但是大多数评估这些技术的研究已经是 在较旧的NLW中进行。来自不同人群的年轻发作痴呆症的生物标志物评估 （BeyondD）纵向研究将解决知识的这些差距。这项五年的纵向研究将 实施一种可扩展，密集和文化的社区参与研究方法，以远程 招募2,000名成年人（<65岁，DPS 70％和30％NLW； n = 1,700，具有认知或行为障碍[CBI] ＆n = 300个健康对照），他们将完成基线自动认知，临床和社会文化 在社区中评估血浆生物标志物（Aβ42/40，P-TAU217和NFL）的血液，其次是 面对面（n = 1,000，CBI＆n = 300个健康对照）或远程（n = 700）纵向评估。这 年度面对面评估包括针对病因诊断的“黄金标准”临床评估 专家临床医生包括神经影像学评估（MRI和淀粉样蛋白PET）。年度远程评估将 依靠自动化工具。该研究的目的是：（1）比较病因，严重性和认知和生物标志物 （血浆生物标志物和淀粉样宠物）在民族文化群体（黑色，拉丁裔和NLW）之间的EOD谱； （2） 检查生物学，心理和社会文化因素对EOD和弹性的影响（抵抗 EOD绝望的生物学风险）各个民族文化阶层的结果； （3）验证血浆生物标志物和认知 通过比较血浆Aβ42/40，P-TAU217和NFL的诊断精度，在社区中收集的标记物 与“黄金标准”临床诊断和跨民族文化群体的神经成像生物标志物，以及 评估远程认知评估和对等离子体生物标志物的临床代谢测试的附加值 诊断准确性。符合条件的参与者将在正在进行的纵向ADRD研究中共同入学。 EOD虽然其余部分将通过BEREFD返回进行纵向评估。这个项目汇集了一个 EOD和大脑健康分布，私人和公共利益相关者以及 潜水员社区的合作伙伴组织，创造新的资源来促进EOD的包容性研究。