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 早发性痴呆症(EOD)是毁灭性的，因为它影响到人在一生中处于巅峰时期 承担个人和职业责任，并积极为社会做出贡献。之前的工作已经发现 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，大多数关于EOD的研究主要招募了非拉丁裔白人(NLW)。黑人和拉丁裔成年人 承担着不同和不成比例的生物和社会文化脆弱性的负担，这赋予了 老年人的ADRD风险，但这些不同人群中年轻成员的痴呆症的病因 (DPS)还没有被很好地理解。专门为研究DPS中的EOD而进行的专门和资源充足的努力， 包括确定独特的风险和复原力因素，都是迫切需要的。淀粉样蛋白的血浆生物标志物， Tau和神经变性以及远程收集的自动化临床和认知评估可以极大地 减少DPS中表征EOD的障碍，但大多数评估这些技术的研究都是 在较老的西北地区进行。不同人群青年起病痴呆患者的生物标志物评价 (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 远程实施可扩展、密集且了解文化的社区参与研究方法 招募2,000名成年人(65岁，70%DPS和30%NLW；n=1,700有认知或行为障碍[CBI] &n=300名健康对照)谁将完成基线自动化认知、临床和社会文化 社区的血浆生物标记物(Aβ42/40、P-tau217和nfl)的评估和抽血，其次是 面对面(n=1000，CBI)和300名健康对照(n=300)或远程(n=700)纵向评估。这个 年度面对面评估包括由以下机构执行的病原学诊断的“黄金标准”临床评估 专家临床医生，包括神经成像评估(核磁共振和淀粉样蛋白PET)。年度远程评价将 依靠自动化工具。这项研究的目的是：(1)比较病因、严重程度以及认知和生物标记物 (血浆生物标记物和淀粉样蛋白PET)跨民族文化群体(黑人、Latinx和NLW)的EOD概况；(2) 考察生物、心理和社会文化因素对EOD和复原力的影响(抵抗力 (3)验证血浆生物标志物和认知能力 比较血浆Aβ42/40、P-tau217和NFL诊断准确率在社区中收集的标记物 对比不同民族文化群体的“黄金标准”临床诊断和神经影像生物标志物 评价远程认知评估和临床代谢试验对血浆生物标志物的附加值 诊断准确率。符合条件的参与者将共同参加正在进行的纵向ADRD研究，重点是 EOD，其余的将通过BEYONDD返回进行纵向评估。这个项目汇集了一个 由EOD和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不同团队，以及 以社区为基础的各种伙伴组织，以创造新的资源，促进在爆炸物处理方面的包容性研究。