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

项目摘要/摘要 这项拟议的研究旨在解决对早期敏感的认知筛查工具的迫切需求 临床前阿尔茨海默病(AD)的神经认知能力下降，适用于种族/人种 不同的社区，并可在家庭、社区和初级保健环境中翻译。由于错综复杂的联系 在动眼系统和内侧颞叶之间，内侧颞叶是缠绕病理的初始部位，与记忆有关 眼球运动是评估内侧颞叶功能的一种有前途的方法，同时最小化 与传统的公开回应相关的混淆(例如，语言熟练程度、识字能力、刻板印象威胁) 认知测试。然而，记忆相关眼动对早期阿尔茨海默病的敏感性在认知上 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，申请者将利用 斯坦福大学老龄化和记忆研究中199名老年人的样本，现有的认知评估，CSF 还有血样核磁共振和Tau PET数据。在K99阶段，第一个目标是检查关联 与记忆相关的眼球运动和全球AD生物标志物之间的关系，包括(A)脑脊液AB42/40和p-tau181 和(B)认知正常的老年人的血浆p-tau181。第二个目标是检查关联 使用F18PI-2620在这些眼球跟踪分析和内侧颞叶局部tau蓄积之间的关系 Tau正电子发射体层成像。主要的假设是两种形式的记忆相关的眼动-新颖性 偏好和扫描路径恢复-在抗体阳性的脑脊液和血浆p升高的个体中将受到损害 Tau181，并与内侧颞叶灶性tau蓄积呈负相关。要完成 这些目标和R00阶段的准备，申请者将利用现有的优势在认知 记忆和衰老的神经科学，统计建模，以及磁共振成像处理和分析，以获得 3个关键领域的专业知识：(1)内侧颞叶功能的眼球跟踪测量，(2)分析和应用 体内AD生物标记物(即Tau PET成像和基于血液的生物标记物)，以及(3)种族和民族 AD研究中的差异。这些技能的发展将使申请者能够成功过渡到 在R00阶段独立，在那里他们将完成最终目标，这将使用移动眼球跟踪 一种检查记忆相关眼球运动和血液生物标记物之间关系的系统 不同种族/民族的老年人样本。在这样做的过程中，这一目标还将确立眼睛- 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 努力提高AD研究对当前社区的可用性和可访问性 代表人数不足，服务不足。对于申请者来说，这一计划将促进关键技术的快速发展 技能，并成功启动一项结合尖端流体的独立研究计划 对AD生物标记物和创新的神经认知评估进行成像，以减少AD研究中的差异。

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.