Innovative Deep Phenotyping of African Americans at Risk for Alzheimers disease

对有阿尔茨海默病风险的非裔美国人进行创新性深层表型分析

• 批准号: 10662056
• 负责人: Rosie E Curiel Cid
• 金额: $ 141.46万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10662056
• 关键词: Acceleration; Accounting; Address; African American; African American population; Alzheimer disease detection; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-42; Amyloidosis; Apolipoprotein E; Basal Nucleus of Meynert; Biological Markers; Black race; Blood; Brain region; Cerebrospinal Fluid; Cerebrovascular Disorders; Chronic; Chronic Kidney Failure; Clinical; Clinical Research; Clinical Trials; Cognition; Cognitive; Cognitive deficits; Collection; Data; Databases; Diabetes Mellitus; Diagnostic; Diffusion Magnetic Resonance Imaging; Disease; Early Diagnosis; Elderly; Enrollment; Ensure; Equipment; European ancestry; Exhibits; Failure; Funding; Glial Fibrillary Acidic Protein; Goals; High Prevalence; Hippocampus; Hispanic; Home; Impaired cognition; Individual; Inflammation; Kidney Diseases; Knowledge; Latino; Learning; Light; Location; Magnetic Resonance Imaging; Maps; Measures; Medical; Memory; Metabolic; Modeling; Nerve Degeneration; Neuropsychology; Not Hispanic or Latino; Participant; Performance; Phenotype; Plasma; Population; Positron-Emission Tomography; Reproducibility; Research; Research Proposals; Resource Sharing; Risk; Sampling; Science; Semantics; Services; Technology; Testing; Therapeutic; Time; Transportation; Water; Work; amnestic mild cognitive impairment; blood-based biomarker; cerebrovascular; cognitive change; cognitive performance; cognitive testing; cohort; comorbidity; computerized; design; early detection biomarkers; entorhinal cortex; experience; extracellular; follow-up; genetic risk factor; imaging facilities; imaging study; inflammatory marker; innovation; learning materials; mild cognitive impairment; neurofilament; neuroimaging; neuropathology; novel; performance tests; pre-clinical; prodromal Alzheimer' s disease; prognostic; recruit; research study; single molecule; social health determinants; structural determinants; user-friendly; water diffusion

PROJECT SUMMARY A critical gap in Alzheimer’s disease (AD) and Alzheimer’s disease related disorders (ADRD) clinical research is the vast under-under-representation of Black/African American (AA) older adults. It is well-documented that AD+ADRD is more prevalent in AA individuals relative to white individuals of European ancestry. Early detection of AD+ADRD is critical for clinical trials aiming to develop optimal therapeutics. Without adequate representation of AA in cognitive and biomarker studies examining the earliest changes in AD+ADRD, the diagnostic, prognostic, and clinical utility of promising biomarkers and their effects on cognition cannot be established. Therefore, there is a pressing need to include and deeply phenotype AAs using novel cognitive and biomarker assessments that consider the multiple co-morbidities identified in this population. Study location has been identified as one of the most prevalent enrollment barriers for AA older adults. This current research proposal leverages our vast expertise in conducting home-based assessment to evaluate clinical and neuropsychological status with equipment that we place within the home. Importantly, we will provide door-to-door transportation for MRI and amyloid PET imaging studies that we have successfully employed to recruit and retain culturally diverse older adults including AA, with and without cognitive impairment into biomarker studies. This will facilitate a user-friendly and effective approach that supports the engagement of AA older adults. Other important and innovative aspects of our proposed study include: a) the use of our novel Cognitive Challenge Tests (CCTs) that employ sensitive and specific cognitive assessment paradigms that have been associated to biomarkers of AD and neurodegeneration, and have been validated for use in AA older adults with and without Mild Cognitive Impairment (MCI); b) use of state-of-the-science plasma-based markers of AD and neurodegeneration that leverage extremely sensitive SiMoA technology; c) we will uniquely relate our novel CCTs at baseline and longitudinally to changes over time in serially collected plasma biomarkers (e.g., p-tau181, p-tau217, NfL, GFAP), d) comparison of plasma markers of AD and neurodegeneration with amyloid PET imaging and extra-cellular free water diffusion as well as neurodegenerative changes on MRI; e) accounting for the comorbidity of common chronic conditions in the AA population, we will obtain sensitive measures of cerebrovascular disease, inflammation, diabetes and metabolic risk, as well as chronic kidney disease; f) structural and social determinants of health will also be assessed. The deep phenotyping of 270 non-Hispanic AA older adults in the proposed research study and our resource sharing plan will accelerate efforts to gain critically needed knowledge of AD+ADRD in a seriously underrepresented AA group. The data obtained will promote the reproducibility of this work in extant databases that include AA and can facilitate comparison of findings with non-AA samples. This important cohort will continue to be followed throughout the funding period and beyond.

项目总结 阿尔茨海默病(AD)和阿尔茨海默病相关疾病(ADRD)临床研究的关键差距 是黑人/非裔美国人(AA)老年人的代表性严重不足。有据可查的是 相对于欧洲血统的白人个体而言，AD+ADRD在AA个体中更为普遍。早些时候 AD+ADRD的检测对于旨在开发最佳治疗方法的临床试验至关重要。如果没有足够的 AA在检测AD+ADRD最早变化的认知和生物标记物研究中的代表 有希望的生物标记物的诊断、预后和临床效用及其对认知的影响不能被 已经成立了。因此，迫切需要包括和深入使用新认知的表现型AA。 以及生物标记物评估，考虑到在该人群中发现的多种并存疾病。 学习地点已被确定为AA老年人最普遍的入学障碍之一。这 目前的研究方案利用我们在进行基于家庭的评估方面的丰富专业知识来评估 临床和神经心理状态与我们放置在家里的设备。重要的是，我们会 为我们成功完成的核磁共振成像和淀粉样蛋白PET成像研究提供上门服务 受雇于招募和留住具有不同文化背景的老年人，包括有认知能力的和没有认知能力的 生物标记物研究的损害。这将促进一种用户友好和有效的方法，支持 AA老年人的订婚。我们建议的研究的其他重要和创新方面包括：a) 使用我们的新型认知挑战测试(CCT)，该测试使用敏感和特定的认知评估 与阿尔茨海默病和神经退行性变的生物标志物相关的范例，并已得到验证 适用于患有和不患有轻度认知障碍(MCI)的AA老年人；b)使用最新科学 基于血浆的AD和神经变性标记物，利用极其敏感的SiMoA技术； C)我们将独特地将我们的新型CCT在基线和纵向上与随时间顺序发生的变化联系起来 收集的血浆生物标志物(例如，p-tau181、p-tau217、NFL、GFAP)，d)AD和 淀粉样蛋白PET成像和细胞外自由水扩散的神经变性以及 MRI上的神经退行性改变；e)解释常见慢性病的共病 在AA人群中，我们将获得脑血管疾病、炎症、糖尿病和 代谢风险以及慢性肾脏疾病；f)健康的结构和社会决定因素 评估过了。在拟议的研究中，270名非西班牙裔AA老年人的深层表型 我们的资源共享计划将加快努力，以获取AD+ADRD急需的知识 在一个代表严重不足的戒酒协会团体中。获得的数据将促进这项工作在#年的可重复性。 包括AA的现有数据库，并可促进将结果与非AA样本进行比较。这 在整个供资期间及以后，将继续遵循重要的队列。