Abstract / Summary
Abstract Background Digital cognitive testing and plasma biomarkers have emerged as key players for population screening and measuring drug efficacy in clinical trials for Alzheimer’s Disease (AD). Understanding test-retest reliability of these tools is essential to estimate meaningful effects of an intervention over time. Whilst some data exist on variability of plasma and digital biomarkers at very short time frames or annually, studies conducted at intermediate time scales are lacking. Data on impact on this variability on clinical decision-making are also rare. Methods Paired testing of plasma biomarkers and digital cognition was performed at 0, 3 and 6 months in a cohort of 92 individuals (55 cognitively unimpaired healthy controls (HC) and 37 patients with early AD dementia (AD)). Plasma biomarkers examined included pTau217, pTau181, NfL, GFAP and the Aβ42/40 ratio. OCTAL (Oxford Cognitive Testing Portal) digital cognitive testing platform was used to measure cognition. Results pTau181 emerged as the plasma biomarker with worst test-retest reliability and was the only measure where repeating the sample improved accuracy in group discrimination. None of the digital measures showed further improvement in diagnostic accuracy if repeated over time, reflecting high reliability. Individual metrics showed different reliability profiles based on the index used to measure variability (Coefficient of variation or Intraclass Correlation Coefficient) and varied within groups (HC and AD). Conclusion Test-retest reliability measures are essential for interpretation of meaningful effects over time for plasma and digital outcomes.