INTRODUCTION: The APECS and AMARANTH trials showed that beta-secretase (BACE) 
inhibitors verubecestat and lanabecestat failed to slow cognitive and functional 
decline in individuals with prodromal or early Alzheimer's disease. Here, the 
performance on secondary and exploratory cognitive measures in both studies is 
reported.
METHODS: APECS (verubecestat) and AMARANTH (lanabecestat) were randomized, 
double-blind, placebo-controlled, parallel-group, 104-week clinical trials 
conducted by different sponsors. Measures included the 3-Domain Composite 
Cognition Score (CCS-3D), Repeatable Battery for the Assessment of 
Neuropsychological Status (RBANS), Letter/Category Fluency, and Digit Symbol 
Coding.
RESULTS: Verubecestat showed worsening on the CCS-3D Total Score, Episodic 
Memory, and Attention/Processing Speed domains. Lanabecestat showed worsening on 
the RBANS Total Score, Immediate Memory, and Visuospatial/Constructional 
Indexes. Both BACE inhibitors showed worsening on Digit Symbol Coding and 
improvements on Letter/Category Fluency.
DISCUSSION: In both studies, many measures showed treatment-associated cognitive 
worsening, whereas verbal fluency tasks showed improvement.