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

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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.