A Remote Digital Memory Composite to Detect Cognitive Impairment in Memory Clinic Samples in Unsupervised Settings using Mobile Devices

Mobile app-based unsupervised monitoring of cognition holds the promise to facilitate case-finding in clinical care and the individual detection of cognitive impairment in clinical and research settings. In the context of Alzheimer’s disease, this is particularly relevant for patients who seek medical advice due to memory complaints. Here we developed a Remote Digital Memory Composite (RDMC) score from an unsupervised remote and mobile cognitive assessment battery focused on episodic memory and long-term recall and assessed its construct validity, retest reliability and diagnostic accuracy when predicting MCI-grade impairment in a memory clinic sample and healthy controls. A total of 199 study participants were recruited from three cohorts and included as healthy controls (HC; n=97), individuals with subjective cognitive decline (SCD; n= 59) or patients with mild cognitive impairment (MCI; n=43). Study participants performed cognitive assessments in a fully remote and unsupervised setting via a smartphone app for cognitive testing. The derived RDMC score was highly correlated with the PACC5 score across participants and demonstrated good retest reliability. Diagnostic accuracy for discriminating memory impairment from no impairment was high (cross-validated AUC = 0.83, 95% CI [0.66, 0.99]) with a sensitivity of 0.82 and a specificity of 0.71. Our results indicate that unsupervised mobile cognitive assessments in a memory clinic setting using the implementation in the neotiv digital platform results in a good discrimination between cognitively impaired and unimpaired individuals. Thus, it is feasible to complement neuropsychological assessment of episodic memory with unsupervised and remote assessments on mobile devices. This contributes to recent efforts for implementing remotely performed episodic memory assessment for case-finding and monitoring in large research trials and clinical care. ### Competing Interest Statement DB reports personal fees from neotiv GmbH during the conduct of the study. OVB, IH, MHN and ND are full employees of neotiv GmbH and report personal fees from neotiv GmbH during the conduct of the study. ST reports Advisory Board Membership for Biogen, Roche and Grifols. JW reports personal fees from Abbott, Biogen, Boehringer-Ingelheim, Eli Lilly, MSD SHARP Dohme, Roche, Janssen Cilag, Immungenetics, Roboscreen and Pfizer during the conduct of the study. SCJ has in the past two years served on advisory boards to Roche Diagnostics, Prothena, AlzPath, Merck and Eisai. His institution has received research funding from Cerveau Technologies. ED reports personal fees from neotiv GmbH during the conduct of the study and personal fees from Biogen, Roche, Lilly, Eisai and UCL Consultancy as well as non-financial support from Rox Health outside the submitted work. DB and ED are co-founders of neotiv GmbH and own company shares. WG, XG, JG, MHN, MB, ASp, AS, KB, MW, RP and FJ, LC, KB, have nothing to disclose. ### Funding Statement This study did not receive any funding. ### 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: Ethics committees of the University Hospital Magdeburg, the Medical Faculty at University of Bonn, the Medical Faculty at Ludwig-Maximilians University Munich, the Medical Faculty at University of Tuebingen, the Medical Faculty at Rostock University, Medical Faculty at University of Goettingen and Cologne University as well as the institutional review board of the University of Wisconsin-Madison gave ethical approval of this work. 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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data, which support this study, are not publicly available, but may be provided upon reasonable request to the authors and pending a material transfer agreement.