P4‐385: Development and Validation of New Measures of Long‐term Memory Consolidation

Preclinical data suggest that certain classes of drugs may improve long term memory consolidation (LTMC), a domain of cognition not captured by existing clinical measures of cognition (ADAS-cog) or specific neuropsychological tests of episodic memory. Available measures of episodic memory assess performance only over short recall periods (<30 minutes). Development of validated measures to assess recall over longer periods (6–24 hours) would add to the tools available to assess memory deficits in patients, resulting in improved signal detection in proof of concept studies for Alzheimer's Disease (AD) and other cognition indications. Four LTMC tests were adapted from validated measures of short term memory to assess performance over 24 hours in small pilot studies: Word List Learning/Selective Reminding (WLLSR-24), Delayed Word Recognition (WR-24), Delayed Verbal Recall and Delayed Visual Memory. Initial validation studies in 29 AD (mean age 74) and 31 HE (mean age 76) showed: a) feasibility of test administration in AD patients, b) acceptable test-retest reliability (ICCs from 0.67 to 0.95), c) ability to discriminate between healthy elderly (HE) and AD patients, particularly for WLLSR-24 and WR-24, and d) moderate correlation with functional measures of memory assessed with the Everyday Memory Questionnaire (Pearson R from 0.4 to 0.6), a self- or caregiver-reported assessment of memory problems in everyday life. These results suggested that WLLSR-24 and WR-24 may be helpful indicators of memory consolidation and could be used to assess effects of interventions to enhance long term memory. Additional data collected from an ongoing cohort study (OPTIMA, Oxford University) supports the finding that WLLSR-24 (but not WR-24) discriminates cross-sectionally across a broader range of severity, among HE (N=30, mean age 79), mild cognitive impairment (MCI) (N=17, mean age 82), and AD (N=12, mean age 83). Six- month longitudinal data collected to date from WR-24 and WLLSR-24 do not reveal significant within-group change over time; collection and analysis of one year follow up data is pending. Adding to the reliable tools available to probe specific cognitive domains with these newly-developed tasks may enhance our ability to evaluate the efficacy of investigational drug and other targeted interventions.