Remote Digital Cognitive Assessment in a Trial-Ready Alzheimer’s Cohort: A Scalable Approach for Early Intervention Studies

Background: Early detection of cognitive decline in Alzheimer’s disease (AD), particularly in preclinical stages, is critical for evaluating therapeutic interventions. Traditional cognitive assessments often lack reliability and require lengthy in-person visits, limiting scalability for younger, trial-ready populations.Objectives: To evaluate the feasibility, reliability, and validity of high-frequency remote digital cognitive assessments in individuals with autosomal dominant Alzheimer’s disease (ADAD).Participants: 162 mutation carriers and non-carriers from DIAN-TU from 20 international sites (Ages 19-69 years).Measurements: Participants completed remote assessments via personal smartphones, prompted four times daily for seven days (approximately 3 minutes per session), and conventional in-clinic cognitive testing at baseline. Adherence, test–retest reliability (intraclass correlation coefficients [ICCs]), construct validity (confirmatory factor analysis), and sensitivity to clinical impairment were evaluated.Results: Average adherence was 41%. Despite this, remote measures demonstrated excellent reliability (ICCs > 0.90 after 10 sessions) and strong construct validity, with tasks loading onto memory, attention, and executive function domains. Model fit was poorer in symptomatic individuals (CDR > 0), consistent with cognitive dedifferentiation during disease progression. Both remote and traditional composites were sensitive to clinical impairment, with similar effect sizes and increasing group differences near expected symptom onset.Conclusions: High-frequency remote cognitive assessment is feasible, reliable, and valid in a relatively young international ADAD cohort. This approach offers substantial advantages for clinical trials, including reduced participant burden, improved accessibility, and enhanced reliability, supporting its integration into early-intervention studies.