"Eye-tracking and Multimodal Biomarkers to Enhance Detection of Preclinical Alzheimer's Disease in Diverse Populations."

“眼动追踪和多模式生物标志物可增强不同人群中临床前阿尔茨海默病的检测。”

• 批准号: 10689656
• 负责人: Alexandra Nicole Trelle
• 金额: $ 13.15万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10689656
• 关键词: Address; Adult; Affect; Aging; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-42; Amyloid beta-Protein; Anxiety; Area; Atrophic; Awareness; Back; Behavior; Biological Assay; Biological Markers; Blood; Blood specimen; Cerebrospinal Fluid; Clinical; Cognition; Cognitive; Communities; Community Healthcare; Conscious; Data; Data Collection; Decision Making; Deposition; Detection; Development; Diagnostic; Early Diagnosis; Education; Elderly; English Language; Enrollment; Episodic memory; Ethnic Origin; Exhibits; Eye Movements; Functional Magnetic Resonance Imaging; Generations; Goals; Hippocampus; Image; Impaired cognition; Impairment; Individual; Individual Differences; Language; Ligands; Link; Liquid substance; Magnetic Resonance Imaging; Measurement; Measures; Medial; Mediating; Memory; Methods; Multilingualism; Neurocognitive; Neurocognitive Deficit; Neurofibrillary Tangles; Participant; Pathology; Patients; Pattern; Performance; Phase; Plasma; Population Heterogeneity; Positron-Emission Tomography; Prefrontal Cortex; Process; Race; Research; Resolution; Retrieval; Risk; Risk Assessment; Sampling; Screening procedure; Site; Socioeconomic Status; Statistical Models; Stereotyping; Stimulus; System; Taxes; Temporal Lobe; Testing; Translating; Underrepresented Populations; Work; age related; blood-based biomarker; clinical risk; cognitive neuroscience; cognitive testing; design; disparity reduction; entorhinal cortex; ethnic disparity; ethnic diversity; ethnic minority population; gray matter; health care settings; image processing; improved; in vivo; indexing; innovation; literacy; memory encoding; multi-ethnic; multimodal neuroimaging; multimodality; neuroimaging marker; novel; oculomotor; patient home care; pre-clinical; preference; primary care setting; programs; racial disparity; racial diversity; racial minority population; recruit; relational memory; response; sample fixation; screening; skill acquisition; skills; spatiotemporal; tau Proteins; tau aggregation; tau-1; tool; visual tracking

PROJECT SUMMARY/ABSTRACT The proposed research seeks to address a critical need for cognitive screening tools that are sensitive to early neurocognitive decline in preclinical Alzheimer’s disease (AD), suitable for application in racially/ethnically diverse communities, and translatable across home, community, and primary care settings. Due to intricate links between the oculomotor system and the medial temporal lobe, an initial site of tangle pathology, memory-related eye-movements represent a promising method for assessment of medial temporal lobe function while minimizing confounds (e.g., language proficiency, literacy, stereotype threat) associated with overt responding in traditional cognitive tests. However, the sensitivity of memory-related eye-movements to incipient AD in cognitively unimpaired older adults remains unclear. To address this critical gap in AD research, the applicant will leverage a sample of 199 older adults in the Stanford Aging and Memory Study with existing cognitive assessments, CSF and blood samples, MRI, and Tau PET data. During the K99 phase, the first aim is to examine associations between memory-related eye-movements and global AD biomarkers including (a) CSF Ab42/40 and p-tau181 and (b) plasma p-tau181 in cognitively unimpaired older adults. The second aim is to examine associations between these eye-tracking assays and focal tau accumulation in the medial temporal lobe using F18PI-2620 Tau PET imaging. The primary hypothesis is that two forms of memory-related eye-movements – novelty preference and scanpath reinstatement – will be impaired in Ab+ individuals with elevated CSF and plasma p- tau181, and will be negatively associated with focal tau accumulation in the medial temporal lobe. To accomplish these goals and prepare for the R00 phase, the applicant will leverage existing strengths in the cognitive neuroscience of memory and aging, statistical modelling, and MR imaging processing and analysis, to gain expertise in 3 key areas: (1) eye-tracking measures of medial temporal lobe function, (2) analysis and application of in vivo AD biomarkers (i.e., Tau PET imaging and blood-based biomarkers), and (3) racial and ethnic disparities in AD research. The development of these skills will enable the applicant to successfully transition to independence in the R00 phase, where they will complete the final aim, which will use a mobile eye-tracking system to examine associations between memory-related eye-movements and blood-based biomarkers in a racially/ethnically diverse sample of older adults. In doing so, this aim will also establish the feasibility of eye- tracking data collection in home and health care settings. This project thus leverages multiple innovations that work to increase the availability and accessibility of AD research to communities that are currently underrepresented and underserved. For the applicant, this program will facilitate the rapid development of critical skills and enable the successful launch of an independent research program that combines cutting-edge fluid and imaging AD biomarkers and innovative neurocognitive assessment to mitigate disparities in AD research.

项目总结/摘要 这项拟议中的研究旨在解决对认知筛查工具的迫切需求，这些工具对早期 临床前阿尔茨海默病（AD）的神经认知下降，适用于种族/民族 不同的社区，并在家庭，社区和初级保健设置翻译。由于错综复杂的联系 在眼神经系统和内侧颞叶之间，病理缠结的初始部位，记忆相关 眼球运动是一种很有前途的方法，用于评估内侧颞叶功能，同时最小化 混淆（例如，语言能力，识字，刻板印象威胁）与传统的 认知测试然而，与记忆相关的眼动对早期AD的敏感性在认知上是不确定的。 未受损的老年人仍不清楚。为了解决AD研究中的这一关键差距，申请人将利用 斯坦福大学衰老和记忆研究中的199名老年人样本， 血液样本核磁共振和Tau PET数据在K99阶段，第一个目标是检查协会 记忆相关的眼球运动与包括（a）CSF Ab 42/40和p-tau 181的总体AD生物标志物之间的关系 和（B）认知未受损老年人的血浆p-tau 181。第二个目的是检查协会 在这些眼跟踪测定和使用F18 PI-2620的内侧颞叶中的局灶性tau累积之间 Tau PET成像。主要的假设是，两种形式的记忆相关的眼动-新奇 偏好和扫描路径恢复-将在CSF和血浆p-升高的Ab+个体中受损- tau 181，并将与内侧颞叶中的局灶性tau积聚负相关。完成 这些目标和准备R 00阶段，申请人将利用现有的优势，在认知 神经科学的记忆和老化，统计建模，磁共振成像处理和分析，以获得 在3个关键领域的专业知识：（1）内侧颞叶功能的眼动跟踪测量，（2）分析和应用 体内AD生物标志物（即，Tau PET成像和基于血液的生物标志物），和（3）种族和民族 AD研究中的差异。这些技能的发展将使申请人能够成功地过渡到 在R 00阶段的独立性，他们将完成最终的目标，这将使用移动的眼睛跟踪 系统检查记忆相关的眼球运动和血液生物标志物之间的关联， 不同种族/民族的老年人样本。在这样做的时候，这一目标也将建立眼睛的可行性- 跟踪家庭和医疗保健环境中的数据收集。因此，该项目利用了多项创新， 努力增加AD研究的可用性和可及性，以社区目前 代表性不足和服务不足。对于申请人来说，该计划将促进关键的快速发展， 技能，并使成功推出一个独立的研究计划，结合尖端的流体 和成像AD生物标志物和创新的神经认知评估，以减轻AD研究的差异。