Continuous Associations between Remote Self-Administered Cognitive Measures and Imaging Biomarkers of Alzheimer's Disease.

Background: Easily accessible and self-administered cognitive assessments that can aid early detection for Alzheimer's disease (AD) dementia risk are critical for timely intervention.
Objectives/design: This cross-sectional study investigated continuous associations between Mayo Test Drive (MTD) - a remote, self-administered, multi-device compatible, web-based cognitive assessment - and AD-related imaging biomarkers.
Participants/setting: 684 adults from the Mayo Clinic Study of Aging and Mayo Clinic Alzheimer's Disease Research Center participated (age=70.4±11.2, 49.7% female). Participants were predominantly cognitively unimpaired (CU; 94.0%).
Measurements: Participants completed (1) brain amyloid and tau PET scans and MRI scans for hippocampal volume (HV) and white matter hyperintensities (WMH); (2) MTD remotely, consisting of the Stricker Learning Span and Symbols Test which combine into an MTD composite; and (3) in-person neuropsychological assessment including measures to obtain Mayo Preclinical Alzheimer's disease Cognitive Composite (Mayo-PACC) and Global-z. Multiple regressions adjusted for age, sex, and education queried associations between imaging biomarkers and scores from remote and in-person cognitive measures.
Results: Lower performances on MTD were associated with greater amyloid, entorhinal tau, and global tau PET burden, lower HV, and higher WMH. Mayo-PACC and Global-z were associated with all imaging biomarkers except global tau PET burden. MCI/Dementia participants showed lower performance on all MTD measures compared to CU with large effect sizes (Hedge's g's=1.65-2.02), with similar findings for CU versus MCI only (Hedge's g's=1.46-1.83).
Conclusion: MTD is associated with continuous measures of AD-related imaging biomarkers, demonstrating ability to detect subtle cognitive change using a brief, remote assessment in predominantly CU individuals and criterion validity for MTD.
Competing Interests: Dr. Boots has nothing to disclose. Mr. Frank reports grants from National Institutes of Health (NIH) during the conduct of the study. Ms. Fan reports grants from NIH during the conduct of the study. Ms. Christianson reports grants from NIH during the conduct of the study. Dr. Kremers reports grants from NIH during the conduct of the study. Dr. John Stricker reports grants from NIH during the conduct of the study; and a Mayo Clinic invention disclosure has been submitted for the Stricker Learning Span and the Mayo Test Drive platform. Dr. Machulda reports grants from National Institutes of Health outside the submitted work. Dr. Fields reports grants from NIH and grants from the Mangurian Foundation outside the submitted work. Dr. Hassenstab reports grants from NIH during the conduct of the study; personal fees from Parabon Nanolabs, personal fees from Roche, personal fees from AlzPath, personal fees from Prothena, personal fees and other (serves on Data Safety Monitoring Board/Advisory Board) from Caring Bridge (National Institute on Aging sponsored), personal fees and other (serves on Data Safety Monitoring Board/Advisory Board) from Wall-E (National Institute on Aging sponsored) outside the submitted work. Dr. Graff-Radford reports grants from NIH outside the submitted work; and serves as the site-PI for a clinical trial co-sponsored by Eisai and the University of Southern California, and serves on the Data Safety and Monitoring Board for StrokeNET. Dr. Vemuri reports grants from NIH during the conduct of the study. Dr. Jack reports grants from NIH and grants from GHR Foundation during the conduct of the study; and Dr. Jack receives research support from the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic. Dr. Knopman reports grants from NIH during the conduct of the study; and Dr. Knopman serves on a Data Safety Monitoring Board for the DIAN-TU study and was an investigator in clinical trials sponsored by Lilly Pharmaceuticals, Biogen, and the University of Southern California. Dr. Petersen reports grants from NIH during the conduct of the study; personal fees from Oxford University Press, personal fees from UpToDate, personal fees from Roche, Inc., personal fees from Genentech, Inc., personal fees from Eli Lilly and Co., personal fees from Nestle, Inc., and personal fees from Eisai outside the submitted work. Dr. Nikki Stricker reports grants from NIH during the conduct of the study; and a Mayo Clinic invention disclosure has been submitted for the Stricker Learning Span and the Mayo Test Drive platform.