Clinical Manifestations.

Background: Learning over repeated exposures (LORE) is an emerging paradigm that has shown sensitivity to AD biomarkers in apparently cognitively unimpaired (CU) samples using visual stimuli. We present results of a six-month study in a CU sample that explored brief (<2 minute) assessment of verbal LORE alongside other measures of memory and sleep.

Method: The Prolific platform was used to recruit 190 participants. In a baseline session we obtained a measure of sleepiness (Karolinska Sleepiness Scale), and visual and verbal measures of memory using paired associates learning (PAL) and verbal paired associates (VPA). Five-day bursts of VPA-LORE were then carried out once-monthly for six months, with participants learning a new set of word-pairs each burst. One month after the final burst, delayed recall for all 48 associates was tested in a single session. The first session of a burst comprised presentation of the month's associates, followed by a test of immediate recall. In subsequent sessions, cued-recall was tested first, after which the set was presented again. A measure of LORE was created by integrating recall scores over the burst. We used linear mixed-effects modelling to explore relationships among 1) age and baseline memory measures, measures of immediate recall and LORE and 2) between day-by-day scores, age and sleepiness.

Result: Test-retest correlations of LORE scores from burst-to-burst over the six bursts were strong (rp = .69 - .75). At baseline, sleepiness did not affect PAL-errors or VPA-errors. PAL-errors were positively associated with age (β = 0.391, p<.001) and VPA-errors, but VPA-errors were not associated with age. LORE scores were not significantly associated with age or PAL-errors. However, day-to-day learning within a burst was impacted by daily sleepiness (β = -0.122, p<.001). In contrast to LORE, delayed-recall after the final burst was significantly impacted by age (β = -0.010, p = .043).

Conclusion: Reliability of VPA-LORE was found to be good between bursts over six months. The association of LORE with PAL but not with age suggests VPA-LORE measures a stable form of memory different from PAL. Additionally, the sensitivity the task to sleepiness may be relevant for use in AD-related research given the impact of AD pathology on sleep.