Parallel patterns of age-related working memory impairment in marmosets and macaques

Abstract

As humans age, some experience cognitive impairment while others do not. When impairment does occur, it is not expressed uniformly across cognitive domains and varies in severity across individuals. Translationally relevant model systems are critical for understanding the neurobiological drivers of this variability, which is essential to uncovering the mechanisms underlying the brain’s susceptibility to the effects of aging. As such, non-human primates (NHPs) are particularly important due to shared behavioral, neuroanatomical, and age-related neuropathological features with humans. For many decades, macaque monkeys have served as the primary NHP model for studying the neurobiology of cognitive aging. More recently, the common marmoset has emerged as an advantageous model for this work due to its short lifespan that facilitates longitudinal studies. Despite their growing popularity as a model, whether marmosets exhibit patterns of age-related cognitive impairment comparable to those observed in macaques and humans remains unexplored. To address this major limitation for the development and evaluation of the marmoset as a model of cognitive aging, we directly compared working memory ability as a function of age in macaques and marmosets on the identical task. We also implemented varying delays to further tax working memory capacity. Our findings demonstrate that marmosets and macaques exhibit remarkably similar age-related working memory deficits, with macaques performing better than marmosets on longer delays. These results highlight the similarities and differences between the two most commonly used NHP models and support the value of the marmoset as a model for cognitive aging research within the neuroscience community.