Objective: AD modifying therapies should be deployed in patients who have AD pathology but no or minimal morbidity. Recognition of such patients is difficult without early disease-specific biomarkers, current cognitive tests are insensitive, and duration, sample sizes and cost may be prohibitive. This study describes a novel trial design using a computerized cognitive test to define the pre-trial cognitive trajectory of “healthy” volunteers with cognitive decline who can then be evaluated and recruited for clinical trials.
Methods: The test, CogState, has been validated in serial evaluations of community-based volunteers, can detect intra-individual change from baseline, define cognitive trajectories within 6 months, predict PET-amyloid status, and identify individuals for further medical evaluation, biomarker studies and study recruitment.
Results: We propose a program for testing AD therapies with: (i) recruitment of concerned community volunteers; (ii) baseline then serial online computerized testing; (ii) automated detection of decline; (iv) referral for more detailed medical evaluation; (v) if no identifiable aetiology for AD, biomarker studies (e.g. PET-PIB), and (vi) enrolment of biomarker positive individuals into trials. Pre-trial decline trajectory and biomarker change would be used as clinical outcome measures. Trial durations of 8-12 months with 50-90 individuals per treatment arm are feasible (± delayed randomized withdrawal and start additions).
Conclusions: This methodology has advantages over current AD trial designs, including shorter duration, informed consent, smaller sample sizes/duration, reduced cost and multiple simultaneous trials. In addition, it allows the rapid evaluation of putative single mechanisms treatments that may only be efficacious in very early disease.