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 早发性痴呆 (EOD) 具有毁灭性，因为它会影响处于生命高峰期的个体。 个人和职业责任，并积极为社会做出贡献。之前的工作已经确定 阿尔茨海默病 (AD) 和额颞叶变性 (FTLD) 是 EOD 的最常见原因。 尽管如此，大多数 EOD 研究主要招募非拉丁裔白人 (NLW)。黑人和拉丁裔成年人 承受着不同且不成比例的生物和社会文化脆弱性负担，这些负担增加了 老年人的 ADRD 风险，但这些不同人群中年轻成员的痴呆症病因 （DP）还没有被很好地理解。专门为研究 DP 中的 EOD 而专门开展的、资源充足的工作， 迫切需要包括确定独特的风险和复原力因素。淀粉样蛋白的血浆生物标志物， tau 蛋白和神经退行性疾病以及远程收集的自动化临床和认知评估可以极大地 减少了 DP 中 EOD 表征的障碍，但评估这些技术的大多数研究都已 在旧的 NLW 进行。不同人群年轻发病痴呆症的生物标志物评估 （BEYONDD）纵向研究将解决这些知识差距。这项为期五年的纵向研究将 实施可扩展的、密集的、文化知情的社区参与研究方法，以远程 招募 2,000 名成年人（<65 岁，70% DP 和 30% NLW；n=1,700 名有认知或行为障碍的人 [CBI] & n=300 名健康对照）将完成基线自动化认知、临床和社会文化 社区中血浆生物标志物（Aβ42/40、P-tau217 和 NfL）的评估和抽血，然后 面对面（n = 1,000 名 CBI 和 n = 300 名健康对照）或远程（n = 700）纵向评估。这 年度亲自评估包括由以下机构进行的病因诊断的“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 依赖自动化工具。该研究旨在：（1）比较病因、严重程度以及认知和生物标志物 （血浆生物标志物和淀粉样蛋白 PET）跨民族文化群体（黑人、拉丁裔和 NLW）的 EOD 概况； (2) 检查生物、心理和社会文化因素对 EOD 和复原力（抵抗力）的影响 尽管有生物风险，但爆炸物爆炸）跨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 的诊断准确性，在社区收集标记物 与跨民族文化群体的“金标准”临床诊断和神经影像生物标志物比较，以及 评估远程认知评估和临床代谢测试对血浆生物标志物的附加值 诊断准确性。符合条件的参与者将共同参加正在进行的纵向 ADRD 研究，重点关注 EOD，其余的将通过 BEYONDD 返回进行纵向评估。该项目汇集了 由 EOD 和大脑健康差异领域的领先科学家、私人和公共利益相关者组成的多元化团队，以及 多样化的社区合作伙伴组织，创造新的资源来促进爆炸物处理方面的包容性研究。