Drug Development

The Mini Mental State Examination (MMSE) is a commonly used inclusionary screening measure of cognition in Alzheimer's disease (AD) trials. The Wechsler Memory Test-IV Logical Memory (WMS-IV LM) subtest has emerged as an additional screening measure to assess episodic memory loss and assist with appropriate enrollment for trials recruiting early AD participants. The WMS-IV LM II delayed memory score has been utilized for inclusion based on score ranges indicative of episodic memory loss by age The WMS-IV LM is more time-intensive and complex for raters to administer. This study investigated the utility of adding WMS-IV LM at screening.

Data from two multinational Phase 2 AD trials that utilized the MMSE and WMS-IV LM as screening measures were included. eCOA alerts were programmed to trigger if a participant did not meet MMSE and/or WMS-IV LM II inclusionary criteria. These alerts were used to explore the rate of exclusion for each measure. Correlation between WMS-IV LM II and MMSE total scores was also examined.

2517 screening visits where both the MMSE and WMS-IV LM were administered were included in the analysis. Of these 2517 screening visits, 43% (1089/2517) did not trigger either the WMS-IV LM II or MMSE exclusion alert. The MMSE exclusion alert alone triggered in 22.73% of the visits (572/2517) and the WMS-IV LM II exclusion alert alone triggered in 31.70% (798/2517) of the visits. MMSE total scores and WMS-IV LM II scores were weakly correlated r(2516) = .38, p< .001.

The present study found that less than half of participants did not screen fail due to MMSE or WMS-IV LM II inclusionary criteria. About 30% of participants did not screen fail on the MMSE but proceeded to screen fail on the WMS-IV LM II. This indicates that the WMS-IV LM II, which is being used as an indicator of episodic memory impairment, provided utility above and beyond a more general and brief screening tool such as the MMSE in these AD trials. Although the WMS-IV LM II may be cumbersome and lengthy to administer, it appears useful in improving classification of early AD participants.