Validation of the Mayo Test Drive Screening Battery Composite and Stricker Learning Span for Early Detection and Monitoring of Cognitive Decline in Preclinical and Prodromal Alzheimer’s Disease

PROJECT SUMMARY/ABSTRACT The field of Alzheimer's disease (AD) is entering a new era where increasing numbers of novel treatments targeting the biological underpinnings of AD will be available within the foreseeable future. If we fail to identify cognitive impairment due to AD early, we will miss an important treatment window. There is a critical need for easily accessible, scalable, and sensitive cognitive tools that can aid early detection and monitoring of cognitive impairment and thereby allow earlier intervention to mitigate further decline. High quality, brief cognitive assessment tools that can be deployed remotely or via self-administration in clinic settings represent one key component of the future of AD research and clinical practice. These tools will help enrich clinical trials and aid triage decisions to inform specialty clinic referrals and initiation of treatment in clinics, ideally in conjunction with plasma biomarkers to address both clinical symptoms and underlying biology. Additional validation of novel remote cognitive assessment tools is needed. Mayo Test Development through Rapid Iteration, Validation and Expansion (Mayo Test Drive, MTD) is a cognitive testing platform developed for self- administered digital cognitive assessment. MTD addresses remote assessment needs and is a multi-device (smartphone, tablet, PC), flexible and easily accessible platform, with subtests that provide more in-depth assessment of targeted cognitive domains relative to typical screening tests. The MTD brief cognitive screening battery takes 15-20 minutes and includes 2 subtests: (1) the Stricker Learning Span (SLS), a novel computer adaptive word list memory test (learning and delay trials) and (2) Symbols Test, an open-source measure of visual matching and processing speed/executive function; these are combined into a screening battery composite (MTD-SBC). The overall goal of this R01 is to establish the validity of the MTD-SBC and the SLS for several specific contexts of use. Specific aims are to (1) determine cross-sectional diagnostic accuracy of MTD for clinically defined and PET biomarker-defined groups, (2) demonstrate sensitivity of MTD to amyloid- related cognitive decline over 30 months, (3) determine utility of MTD for detecting clinical progression over 45 months, and (4) determine whether MTD performance is associated with plasma biomarkers to a similar degree as in-person neuropsychological measures. Most participants will be recruited from the Mayo Clinic Study of Aging, with additional recruitment from the Alzheimer's Disease Research Center (Rochester, MN and Jacksonville, FL) and the Memory Impairment and Neurodegenerative Dementia Center - Mayo Clinic Study of Aging at the University of Mississippi Medical Center in Jackson, MS (N=2,300 across cohorts, predominantly remote administration). By increasing the representation of diverse participants and the range of social and structural determinants of health (SSDoH) with the Jackson, MS and Jacksonville, FL cohorts, we will be able to complete exploratory analyses for Aim 4 focused on whether SSDoH moderates these results. Future research will determine the combined utility of MTD and plasma biomarkers.