Multicultural Community Dementia Screening

多元文化社区痴呆症筛查

• 批准号: 10578575
• 负责人: James E Galvin
• 金额: $ 25.39万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10578575
• 关键词: Address; Administrative Supplement; Alzheimer disease detection; Alzheimer disease screening; Alzheimer' s disease related dementia; Amyloid; Amyloid deposition; Anatomy; Angiography; Animal Model; Atrophic; Biological Markers; Brain; Brain imaging; Clinical; Clinical Trials; Cognitive; Cohort Studies; Communities; Computer software; Cultural Diversity; Curcumin; Data; Dementia; Detection; Discrimination; Disease; Early Diagnosis; Enrollment; Eye; Funding; Fundus; Future; Genetic; Gold; Image; Impaired cognition; Impairment; Individual; Institutes; Intake; Intervention; Knowledge; Lasers; Link; Magnetic Resonance Imaging; Methodology; Methods; Nerve Degeneration; Neuronal Injury; Neurons; Ophthalmoscopy; Optical Coherence Tomography; Oral; Parents; Participant; Pathology; Patients; Pharmaceutical Preparations; Phenotype; Physiological; Plasma; Population; Positron-Emission Tomography; Prevalence; Preventive; Research; Retina; Scanning; Spinal Puncture; Study Subject; Testing; Therapeutic; Time; Validation; Work; amyloid imaging; clinical care; clinical diagnosis; cognitive performance; cohort; cost effective; diagnostic biomarker; gray matter; image processing; improved; in vivo; in vivo imaging; magnetic resonance imaging biomarker; mild cognitive impairment; novel; pre-clinical; public health relevance; resilience; retinal imaging; screening; symptomatology; tau Proteins; vascular injury

ABSTRACT Community detection of Mild cognitive impairment (MCI) and early Alzheimer’s disease and related dementias (ADRD) may be limited due to the lack of screening tests characterizing the earliest signs of impairment and correspondence to biomarkers as defined by the amyloid-tau-neuronal injury/neurodegeneration (ATN) framework. Accumulating evidence suggests that neuronal injury and neurodegeneration begins decades before clinically evident cognitive decline. Thus, by the time ADRD is clinically diagnosed, irreversible neuronal damage has already occurred. This has the potential of lessening the therapeutic benefits of disease modifying medications. In R01AG071514, we are examining novel ways to overcome major challenges to improve the detection of MCI and early AD by emphasizing deep phenotyping to enhance the research value of data and biospecimens contributed by individual participants and cross validate screening efforts linking prevalence data to brain biomarkers, leveraging the ATN research framework to anchor this work. However most current ATN biomarkers are expansive, invasive and not readily accessible for clinical care. To address this critical need, we aim to develop non-invasive, easily acquired biomarkers conducive for the early detection of ADRD. The retina and brain share similar anatomic and physiologic features, but, unlike the brain, the retina is easily accessible for imaging. The retina and brain share similar anatomic and physiologic features, but, unlike the brain, the retina is easily accessible for imaging. Recent studies showed that amyloid deposition occurs not only in the brain but also in the retina, greater in patients with AD compared to normal healthy controls. For this administrative supplement, we teamed with Drs. Jianhua Wang and Hong Jiang, experts in ophthalmic imaging of the Advanced Ophthalmic Imaging lab at the Bascom Palmer Eye Institute. Confocal scanning laser ophthalmoscopy (cSLO) will be used along with OCT/OCTA to image the retina before and after oral curcumin intake. This proposed work takes advantage of well-characterized and deeply phenotyped cohort from our funded R01 AG071514. We propose 3 SPECIFIC AIMS: (1) Develop and validate retinal amyloid imaging; (2) Determine relationship of retinal amyloid imaging to brain amyloid imaging; and (3) test whether baseline retinal amyloid imaging can predict transition. At the conclusion of our study, we will collect sufficient preliminary data for future R01 proposal and the cost-effective and noninvasive method for in vivo imaging of amyloid deposition in the retina will be fully developed to be used for screening and clinical trials.

摘要 轻度认知障碍（MCI）和早期阿尔茨海默病及相关痴呆的社区检测 （ADRD）可能是有限的，由于缺乏筛选测试的特点最早的迹象损害， 对应于由淀粉样蛋白-tau-神经元损伤/神经变性（ATN）定义的生物标志物 框架.越来越多的证据表明，神经元损伤和神经退行性变早在几十年前就开始了。 临床上明显的认知能力下降因此，到ADRD被临床诊断时，不可逆的神经元损伤 已经发生了。这有可能减少疾病修饰的治疗益处。 药物治疗在R01AG071514中，我们正在研究克服主要挑战的新方法，以改善 通过强调深度表型检测MCI和早期AD，提高数据的研究价值， 个体参与者提供的生物样本和交叉验证筛查工作与流行率数据的联系 到大脑生物标记物，利用ATN研究框架来锚这项工作。然而，目前大多数ATN 生物标志物是昂贵的、侵入性的并且不容易用于临床护理。为了满足这一关键需求，我们 目的是开发非侵入性，易于获得的生物标志物，有助于早期发现ADRD。视网膜 和大脑有相似的解剖和生理特征，但与大脑不同的是，视网膜很容易接近 用于成像。视网膜和大脑具有相似的解剖学和生理学特征，但与大脑不同的是， 视网膜易于成像。最近的研究表明，淀粉样蛋白沉积不仅发生在大脑中 而且在视网膜中，与正常健康对照组相比，AD患者的视网膜中也有更大的变化。对于本行政 作为补充，我们与先进的眼科成像专家王建华和姜红博士合作， 巴斯科姆帕尔默眼科研究所的眼科成像实验室。共聚焦扫描激光检眼镜（cSLO） 将与OCT/OCTA一起沿着用于口服姜黄素前后的视网膜成像。这一拟议 这项工作利用了来自我们资助的R01 AG071514的充分表征和深度表型化的队列。我们 提出3个具体目标：（1）开发和验证视网膜淀粉样蛋白成像;（2）确定 视网膜淀粉样蛋白成像与脑淀粉样蛋白成像;以及（3）测试基线视网膜淀粉样蛋白成像是否可以 预测转型在研究完成后，我们会为日后的R01收集足够的初步数据 用于视网膜中淀粉样蛋白沉积的体内成像的建议和成本有效的非侵入性方法 将被充分开发用于筛选和临床试验。