Remote and unsupervised digital memory assessments can reliably detect cognitive impairment in Alzheimer's disease

INTRODUCTION: Remote unsupervised cognitive assessments have the potential to complement and facilitate cognitive assessment in clinical and research settings. METHODS: Here we evaluate the usability, validity and reliability of unsupervised remote memory assessments via mobile devices in individuals without dementia from the Swedish BioFINDER-2 study and explore their prognostic utility regarding future cognitive decline. RESULTS: Usability was rated positively; remote memory assessments showed good construct validity with traditional neuropsychological assessments and were significantly associated with tau-PET and downstream MRI measures. Memory performance at baseline was associated with future cognitive decline and prediction of future cognitive decline was further improved by combining remote digital memory assessments with plasma p-tau217. Finally, retest reliability was moderate for a single assessment and good for an aggregate of two sessions. DISCUSSION: Our results demonstrate that unsupervised digital memory assessments might be used for diagnosis and prognosis in Alzheimer's disease, potentially in combination with plasma biomarkers. ### Competing Interest Statement OH has acquired research support (for the institution) from ADx, AVID Radiopharmaceuticals, Biogen, Eli Lilly, Eisai, Fujirebio, GE Healthcare, Pfizer, and Roche. In the past 2 years, he has received consultancy/speaker fees from AC Immune, Amylyx, Alzpath, BioArctic, Biogen, Cerveau, Eisai, Eli Lilly, Fujirebio, Merck, Novartis, Novo Nordisk, Roche, Sanofi and Siemens. SP has acquired research support (for the institution) from ki elements/ADDF and Avid. In the past 2 years, he has received consultancy/speaker fees from Bioarctic, Biogen, Eisai, Lilly, and Roche. ED reports personal fees from Biogen, Roche, Lilly, Eisai and UCL Consultancy as well as non-financial support from Rox Health. DB and ED are scientific co-founders of neotiv GmbH and own company shares. The other authors report no competing interests. ### Funding Statement Work at the authors' research center was supported by the Alzheimer's Association (SG-23-1061717), Swedish Research Council (2022-00775, 2018-02052), ERA PerMed (ERAPERMED2021-184), the Knut and Alice Wallenberg foundation (2017-0383), the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's disease) at Lund University, the Swedish Alzheimer Foundation (AF-980907, AF-981132), the Swedish Brain Foundation (FO2021-0293, FO2022-0204), The Parkinson foundation of Sweden (1412/22), the Cure Alzheimer's fund, the Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, the Skane University Hospital Foundation (2020-O000028), Regionalt Forskningsstoed (2022-1259) and the Swedish federal government under the ALF agreement (2022-Projekt0080). DB was supported by funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 843074 and the donors of Alzheimer's Disease Research, a program of the BrightFocus Foundation. The precursor of 18F-flutemetamol was sponsored by GE Healthcare. The precursor of 18F-RO948 was provided by Roche. The funding sources had no role in the design and conduct of the study; in the collection, analysis, interpretation of the data; or in the preparation, review, or approval of the manuscript. ### 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 study was approved by the Regional Ethics Committee in Lund (Sweden) and the Swedish Ethical Review Authority. 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 Anonymized data will be shared by request from a qualified academic investigator for the sole purpose of replicating procedures and results presented in the article and as long as data transfer is in agreement with EU legislation on the general data protection regulation and decisions by the Ethical Review Board of Sweden and Region Skane, which should be regulated in a material transfer agreement.