Continuous Associations Between Remote Self-Administered Cognitive Measures and Imaging Biomarkers of Alzheimers Disease

Background: Easily accessible and self-administered cognitive assessments that can aid early detection for Alzheimers 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 Alzheimers 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 (Hedges gs=1.65-2.02), with similar findings for CU versus MCI only (Hedges gs=1.46-1.83). Conclusions: 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 Interest Statement EAB, RDF, WZF, and TJC declare no conflict of interest. WKK reports grants from National Institutes of Health (NIH) during the conduct of the study. JLS receives no personal compensation from any commercial entity. He reports grants from NIH during the conduct of the study. A Mayo Clinic invention disclosure has been submitted for the Stricker Learning Span and the Mayo Test Drive platform. MMM receives funding from NIH. JAF receives funding from the NIH and the Mangurian Foundation. JH reports grants from NIH during the conduct of the study. JGR reports grants from NIH during the conduct of the study. He serves as Site-PI for a clinical trial co-sponsored by Eisai and USC. He serves on the DSMB for StrokeNET. PV reports grants from National Institutes of Health during the conduct of the study. CRJ receives no personal compensation from any commercial entity. He receives research support from NIH, the GHR Foundation, and the Alexander Family Alzheimers Disease Research Professorship of the Mayo Clinic. DSK reports grants from NIH. He 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. RCP reports grants from NIH during the conduct of the study. He has served as a consultant for Roche, Inc.; Genentech, Inc.; Eli Lilly and Co.; Eisai, Inc.; and Nestle, Inc. He receives royalties from Oxford University Press and UpToDate. NHS receives no personal compensation from any commercial entity. She reports grants from NIH during the conduct of the study. A Mayo Clinic invention disclosure has been submitted for the Stricker Learning Span and the Mayo Test Drive platform. ### Funding Statement This research was supported by the Kevin Merszei Career Development Award in Neurodegenerative Diseases Research IHO Janet Vittone, MD, the Rochester Epidemiology Project (R01 AG034676), the National Institute on Aging of the National Institutes of Health (R01 AG081955, R21 AG073967, P30 AG062677, P50 AG016574, U01 AG006786, RF1 AG55151, R01 AG041851, R37 AG011378, RF1AG 69052), the Robert Wood Johnson Foundation, The Elsie and Marvin Dekelboum Family Foundation, GHR Foundation, Alzheimers Association, and the Mayo Foundation for Education and Research. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Mayo Clinic and Olmsted Medical Center Institutional Review Boards gave ethical approval for this work. This study was conducted in accordance with the Declaration of Helsinki. Written consent was obtained from all participants for participation in the overall study protocols (MCSA or ADRC) and oral consent was obtained for participation in the ancillary study protocol by which MTD was obtained via remote data collection. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.