HABS-HD - Project 2

HABS-HD - 项目 2

• 批准号: 10708895
• 负责人: Sid E O'Bryant
• 金额: $ 41.28万
• 依托单位: UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10708895
• 关键词: Adult; African American population; Age; Age of Onset; Alzheimer' s Disease; Alzheimer' s disease related dementia; Amyloid; Anti-Inflammatory Agents; Biological Markers; Blood Vessels; Clinical; Clinical Trials; Cognition; Collaborations; Data; Disease Outcome; Elderly; Ethnic Origin; Ethnic Population; Etiology; Genetic Markers; Genotype; Health; Hispanic Populations; Impaired cognition; Inflammation; Inflammatory; Link; Medical; Metabolic; Mexican Americans; National Institute on Aging; Nerve Degeneration; Not Hispanic or Latino; Outcome; Participant; Pathway interactions; Pattern; Pharmaceutical Preparations; Population; Population Heterogeneity; Prediction of Response to Therapy; Prevalence; Proteomics; Race; Research; Risk; TREM2 gene; Testing; Work; aging brain; apolipoprotein E-4; burden of illness; comorbidity; dementia risk; diabetic; ethnic difference; experience; health disparity; middle age; mild cognitive impairment; neuroimaging; patient subsets; racial difference; racial population; tau Proteins; vascular factor

HABS-HD PROJECT 2 ABSTRACT Milestone 1.I of the NIA Alzheimer’s Disease (AD) + Alzheimer’s Disease-Related Dementias (ADRD) Implementation Milestones explicitly calls for testing “early mechanistic pathways of multiple etiologies that may account for AD/ADRD health disparities”. Significant health disparities exist in the U.S. related to AD with African Americans (AAs) currently suffering the highest burden of AD/ADRD while Hispanics (65% of which are Mexican American [MA]) will experience the greatest increase in disease burden by 20602. MAs also develop cognitive loss at significantly younger ages. Despite these factors, AAs and MAs remain underrepresented in AD research. In fact, 83% of participants in the National Institute of Aging (NIA) Alzheimer’s Disease Centers (ADC) and 90% of the Alzheimer’s Disease Neuroimaging Initiative (ADNI)7 are non-Hispanic white (NHW). Additionally, the 2018 AT(N) framework, which represents the mechanistic pathways (amyloid [A], tau [T], neurodegeneration [N]) dominating the current clinical trial landscape, was built almost entirely on data from NHWs who are screened out for most medical comorbidities. Nevertheless, emerging data demonstrates racial/ethnic differences in AT(N) defined biomarkers and, therefore, the applicability of the framework to AAs and MAs remains unknown, which is the focus of Project 1. AAs and MAs also suffer a heavier burden of vascular, metabolic and inflammatory (VMI) factors, each of which have well-established links to AD, including AT(N) biomarkers. Therefore, VMI factors may be targetable “early mechanistic pathways” that contribute to AD health disparities that cannot be understood without inclusion of populations known to experience the highest burden from them. Project 2 will evaluate the impact of VMI factors on the prevalence, sequence and trajectories of AT(N) defined biomarkers and cognitive loss among the three largest racial/ethnic groups in the U.S. Aim 1: Examine the impact of VMI factors on the presence and progression of cognitive loss among African Americans, Mexican Americans, and non-Hispanic whites. Aim 2: Examine the impact of VMI factors on the presence, sequence and trajectories of AT(N) defined biomarkers among African Americans, Mexican Americans, and non-Hispanic whites. Aim 3: Determine if VMI factors explain the racial/ethnic specific impact of APOEε4 genotype - and other VMI-related AD genetic markers - on AT(N) defined biomarkers. Aim 4 (Project – Project Interactions): Collaborate with Projects 1 and 3 to develop a comprehensive understanding of AT(N) defined biomarkers across diverse populations. Exploratory Aim 5: Compare VMI data and VMI – AT(N) interaction data with that from other large-scale initiatives such as ADNI, LEADS, ADCs, WHICAP, SOL/INCA, ABC-DS, MarkVCID, INDEED, and others.

HABS-HD项目2摘要 NIA阿尔茨海默病(AD)+阿尔茨海默病相关痴呆(ADRD)的里程碑1.I 实施里程碑明确要求测试“多种病因的早期机械途径， 可能是AD/ADRD健康差异的原因“。在美国，与AD相关的健康差异显著 非洲裔美国人(AA)目前承受着AD/ADRD的最大负担，而西班牙裔(其中65%是 墨西哥裔美国人[MA])将经历最大的疾病负担增长20602。MA还开发了 认知能力下降的年龄要小得多。尽管有这些因素，AA和MA在以下方面的比例仍然偏低 广告研究。事实上，国家老龄研究所(NIA)阿尔茨海默氏症中心83%的参与者 阿尔茨海默病神经成像倡议(ADNI)7中90%的人是非西班牙裔白人(Nhw)。 此外，2018年AT(N)框架代表机械性途径(淀粉样蛋白[A]，tau[T]， 神经退行性变[N])主导了当前的临床试验格局，几乎完全建立在来自 对大多数医疗合并症进行筛查的卫生工作者。尽管如此，新兴数据显示 AT(N)定义的生物标志物的种族/民族差异以及该框架对AAs的适用性 而MA仍然是未知的，这是项目1的重点。AAS和MA也承受着更重的负担 血管、代谢和炎症(VMI)因子，每一种都与AD有良好的联系，包括 在(N)个生物标志物。因此，VMI因素可能是有针对性的“早期机械途径”，有助于 AD健康差异，如果不包括已知经历过 来自他们的最高负担。项目2将评估VMI因素对患病率、顺序的影响 AT(N)的轨迹定义了三个最大的种族/民族之间的生物标志物和认知损失 美国群体目标1：研究VMI因素对认知存在和发展的影响 在非裔美国人、墨西哥裔美国人和非西班牙裔白人中的损失。目标2：检查以下方面的影响 VMI因素对非洲人AT(N)定义生物标记物的存在、序列和轨迹的影响 美国人、墨西哥裔美国人和非西班牙裔白人。目标3：确定VMI因素是否可以解释 载脂蛋白Eε4基因型和其他与病毒性心肌梗塞相关的AD遗传标记对AT(N)的种族/民族特异性影响 已定义的生物标志物。目标4(项目-项目交互)：与项目1和项目3协作，制定 全面了解不同人群中AT(N)定义的生物标记物。探索性目标5： 将VMI数据和VMI-AT(N)交互数据与ADNI等其他大型计划的数据进行比较， Leads、ADC、WHICAP、SOL/INCA、ABC-DS、MarkVCID等。