The Computerized Cognitive Composite (C3) in an Alzheimer's Disease Secondary Prevention Trial.

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.

Déclaration de conflit d'intérêts

K Papp has served as a consultant for Biogen Idec and Digital Cognition Technologies. D Rentz has served as a consultant for Eli Lilly, Biogen Idec, Lundbeck Pharmaceuticals, and serves as a member of the Scientific Advisory Board for Neurotrack. P Maruff is a full-time employee of Cogstate Ltd. C-K. Sun has no disclosures to report. R. Raman has no disclosures to report. M. Donohue has served on scientific advisory boards for Biogen, Eli Lilly, and Neurotrack; and has consulted for Roche. His spouse is a full-time employee of Janssen. A. Schembri is a full-time employee of Cogstate Ltd. C. Stark has no disclosures to report. M Yassa has served as a consultant for Pfizer, Eli Lilly, Lundbeck and Dart Neuroscience and is chief scientific officer of Signa Therapeutics, LLC. A. Wessels is a full-time employee of Eli Lilly and Company. R. Yaari is a full-time employee of Eli Lilly and Company. K. Holdridge is a full-time employee of Eli Lilly and Company. P. Aisen has received research funding from NIA, FNIH, the Alzheimer’s Association, Janssen, Lilly and Eisai, and personal fees from Merck, Roche, Biogen, ImmunoBrain Checkpoint and Samus. R.A. Sperling has received research funding from NIH, Alzheimer’s Association and Eli Lilly for this research. She has served as a consultant for AC Immune, Biogen, Eisai, Janssen, Neurocentria and Roche. Her spouse has served as a consultant to Biogen, Janssen, and Novartis.