Abstract

BackgroundThe present study examined the effect of massed versus spaced learning trials on 24-hour delayed recall for a visuospatial learning task. To determine the utility of measuring the incremental benefit of spaced training as a cognitive assay that may be useful in early clinical trials, we used a within-subject crossover design, with two small samples (typical sample sizes for phase I clinical trials). MethodsYoung adults and cognitively healthy older adults without significant physical, neurological, or psychiatric illness were trained on a visuospatial paired-associate learning task under a massed condition (learning trials were presented in immediate succession) and a spaced condition (learning trials were presented with 15-minute intertrial delays). ResultsStatistically significant differences between training conditions on the visuospatial task, such that young adult participants performed better on delayed recall after spaced training, were identified. Large effect sizes for young and older adults on this task suggest meaningful differences between training conditions, reflecting the expected “spacing effect.” The role of amyloid aggregation was also considered for a subset of participants; as amyloid levels increased, the benefit of spaced training decreased, suggesting that the effect of this training paradigm is modulated by disease burden. ConclusionsThe utility of this paradigm as a potential assay for phase I proof-of-concept trials, targeting molecular mechanisms that are central to the encoding and consolidation of new learning, is discussed.

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