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K.V. Papp, D.M. Rentz, P. Maruff, C.-K. Sun, R. Raman, M.C. Donohue, A. Schembri, C. Stark, M.A. Yassa, A.M. Wessels, R. Yaari, K.C. Holdridge, P.S. Aisen, R.A. Sperling, on behalf of the A4 Study Team

J Prev Alz Dis 2021;1(8):59-67

Background: Computerized cognitive assessments may improve Alzheimer’s disease (AD) secondary prevention trial efficiency and accuracy. However, they require validation against standard outcomes and relevant biomarkers. Objective: To assess the feasibility and validity of the tablet-based Computerized Cognitive Composite (C3). Design: Cross-sectional analysis of cognitive screening data from the A4 study (Anti-Amyloid in Asymptomatic AD). Setting: Multi-center international study. Participants: Clinically normal (CN) older adults (65-85; n=4486) Measurements: Participants underwent florbetapir-Positron Emission Tomography for Aβ+/- classification. They completed the C3 and standard paper and pencil measures included in the Preclinical Alzheimer’s Cognitive Composite (PACC). The C3 combines memory measures sensitive to change over time (Cogstate Brief Battery-One Card Learning) and measures shown to be declining early in AD including pattern separation (Behavioral Pattern Separation Test- Object- Lure Discrimination Index) and associative memory (Face Name Associative Memory Exam- Face-Name Matching). C3 acceptability and completion rates were assessed using qualitative and quantitative methods. C3 performance was explored in relation to Aβ+/- groups (n=1323/3163) and PACC. Results: C3 was feasible for CN older adults to complete. Rates of incomplete or invalid administrations were extremely low, even in the bottom quartile of cognitive performers (PACC). C3 was moderately correlated with PACC (r=0.39). Aβ+ performed worse on C3 compared with Aβ- [unadjusted Cohen’s d=-0.22 (95%CI: -0.31,-0.13) p<0.001] and at a magnitude comparable to the PACC [d=-0.32 (95%CI: -0.41,-0.23) p<0.001]. Better C3 performance was observed in younger, more educated, and female participants. Conclusions: These findings provide support for both the feasibility and validity of C3 and computerized cognitive outcomes more generally in AD secondary prevention trials.

K.V. Papp ; D.M. Rentz ; P. Maruff ; C.-K. Sun ; R. Raman ; M.C. Donohue ; A. Schembri ; C. Stark ; M.A. Yassa ; A.M. Wessels ; R. Yaari ; K.C. Holdridge ; P.S. Aisen ; R.A. Sperling ; on behalf of the A4 Study Team ; (2020): The Computerized Cognitive Composite (C3) in A4, an Alzheimer’s Disease Secondary Prevention Trial. The Journal of Prevention of Alzheimer’s Disease (JPAD).


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