ABSTRACT
BACKGROUND: More sensitive and less burdensome efficacy end points are urgently needed to improve the effectiveness of clinical drug development for Alzheimer disease (AD). Although conventional end points lack sensitivity, digital technologies hold promise for amplifying the detection of treatment signals and capturing cognitive anomalies at earlier disease stages. Using digital technologies and combining several test modalities allow for the collection of richer information about cognitive and functional status, which is not ascertainable via conventional paper-and-pencil tests. OBJECTIVE: This study aimed to assess the psychometric properties, operational feasibility, and patient acceptance of 10 promising technologies that are to be used as efficacy end points to measure cognition in future clinical drug trials. METHODS: The Method for Evaluating Digital Endpoints in Alzheimer Disease study is an exploratory, cross-sectional, noninterventional study that will evaluate 10 digital technologies' ability to accurately classify participants into 4 cohorts according to the severity of cognitive impairment and dementia. Moreover, this study will assess the psychometric properties of each of the tested digital technologies, including the acceptable range to assess ceiling and floor effects, concurrent validity to correlate digital outcome measures to traditional paper-and-pencil tests in AD, reliability to compare test and retest, and responsiveness to evaluate the sensitivity to change in a mild cognitive challenge model. This study included 50 eligible male and female participants (aged between 60 and 80 years), of whom 13 (26%) were amyloid-negative, cognitively healthy participants (controls); 12 (24%) were amyloid-positive, cognitively healthy participants (presymptomatic); 13 (26%) had mild cognitive impairment (predementia); and 12 (24%) had mild AD (mild dementia). This study involved 4 in-clinic visits. During the initial visit, all participants completed all conventional paper-and-pencil assessments. During the following 3 visits, the participants underwent a series of novel digital assessments. RESULTS: Participant recruitment and data collection began in June 2020 and continued until June 2021. Hence, the data collection occurred during the COVID-19 pandemic (SARS-CoV-2 virus pandemic). Data were successfully collected from all digital technologies to evaluate statistical and operational performance and patient acceptance. This paper reports the baseline demographics and characteristics of the population studied as well as the study's progress during the pandemic. CONCLUSIONS: This study was designed to generate feasibility insights and validation data to help advance novel digital technologies in clinical drug development. The learnings from this study will help guide future methods for assessing novel digital technologies and inform clinical drug trials in early AD, aiming to enhance clinical end point strategies with digital technologies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35442.
ABSTRACT
BACKGROUND: As evidenced by the further reduction in access to testing during the COVID-19 pandemic, there is an urgent, growing need for remote cognitive assessment for individuals with cognitive impairment. The Neurotrack Cognitive Battery (NCB), our response to this need, was evaluated for its temporal reliability and stability as part of ongoing validation testing. OBJECTIVE: The aim of this study is to assess the temporal reliability of the NCB tests (5 total) across a 1-week period and to determine the temporal stability of these measures across 3 consecutive administrations in a single day. METHODS: For test-retest reliability, a range of 29-66 cognitively healthy participants (ages 18-68 years) completed each cognitive assessment twice, 1 week apart. In a separate study, temporal stability was assessed using data collected from 31 different cognitively healthy participants at 3 consecutive timepoints in a single day. RESULTS: Correlations for the assessments were between 0.72 and 0.83, exceeding the standard acceptable threshold of 0.70 for temporal reliability. Intraclass correlations ranged from 0.60 to 0.84, indicating moderate to good temporal stability. CONCLUSIONS: These results highlight the NCB as a brief, easy-to-administer, and reliable assessment for remote cognitive testing. Additional validation research is underway to determine the full magnitude of the clinical utility of the NCB.