Age-Related Learning and Working Memory Impairment in the Common Marmoset

Aging is the greatest risk factor for the development of neurodegenerative diseases, yet we still do not understand how the aging process leads to pathologic vulnerability. The research community has relied heavily on mouse models, but the consid-erable anatomic, physiological, and cognitive differences between mice and humans limit their translational relevance. Ultimately, these barriers necessitate the development of novel aging models. As a nonhuman primate (NHP), the common marmoset (Callithrix jacchus) shares many features in common with humans and yet has a significantly shorter lifespan (10 years) than other primates, making it ideally suited to longitudinal studies of aging. Our objective was to evaluate the marmoset as a model of age-related cognitive impairment. To do this, we used the Delayed Recognition Span Task (DRST) to characterize age-related changes in working memory capacity in a cohort of sixteen marmosets, of both sexes, varying in age from young adult to geriatric. These monkeys performed thousands of trials over periods of time ranging up to 50% of their adult lifespan. To our knowledge, this represents the most thorough cognitive profiling of any marmoset aging study con-ducted to date. By analyzing individual learning curves, we found that aged animals exhibited delayed onset of learning, slowed learning rate after onset, and decreased asymptotic working memory performance. These findings are not accounted for by age-related impairments in motor speed and motivation. This work firmly establishes the marmoset as a model of age-related cognitive impairment.