One-year change in cognitive flexibility and fine motor function in middle-aged male and female marmosets (Callithrix jacchus).

The common marmoset (Callithrix jacchus) is uniquely suited for longitudinal studies of cognitive aging, due to a relatively short lifespan, sophisticated cognitive abilities, and patterns of brain aging that resemble those of humans. We examined cognitive function and fine motor skills in male and female marmosets (mean age ∼5 at study entry) followed longitudinally for 2 years. Each year, monkeys were tested on a reversal learning task with three pairs of stimuli (n = 18, 9 females) and a fine motor task requiring them to grasp small rewards from two staircases (Hill and Valley test, n = 12, 6 females). There was little evidence for a decline in cognitive flexibility between the two time points, in part because of practice effects. However, independent of year of testing, females took longer than males to reach criterion in the reversals, indicating impaired cognitive flexibility. Motivation was unlikely to contribute to this effect, as males refused a greater percentage of trials than females in the reversals. With regards to motor function, females were significantly faster than males in the Hill and Valley task. From Year 1 to Year 2, a slight slowing of motor function was observed in both sexes, but accuracy decreased significantly in males only. This study (1) demonstrates that marmosets exhibit sex differences in cognitive flexibility and fine motor function that resemble those described in humans; (2) that changes in fine motor function can already be detected at middle-age; and (3) that males may experience greater age-related changes in fine motor skills than females. Additional data points will determine whether these sex and age differences persist over time.

Baseline cortisol levels and social behavior differ as a function of handedness in marmosets (Callithrix jacchus).

Population hand preferences are rare in nonhuman primates, but individual hand preferences are consistent over a lifetime and considered to reflect an individual's preference to use a particular hemisphere when engaged in a specific task. Previous findings in marmosets have indicated that left-handed individuals tend to be more fearful than their right-handed counterparts. Based on these findings, we tested the hypotheses that left-handed marmosets are (a) more reactive to a social stressor and (b) are slower than right-handed marmosets in acquiring a reversal learning task. We examined the hand preference of 27 male and female marmosets (ages of 4-7 years old) previously tested in a social separation task and a reversal learning task. Hand preference was determined via a simple reaching task. In the social separation task, monkeys were separated from their partner and the colony for a single 7-hr session. Urinary cortisol levels and behavior were assessed at baseline, during the separation and 24 hr postseparation. Hand preferences were equally distributed between left (n = 10), right-handed (n = 10), and ambidextrous (n = 7) individuals. The separation phase was associated with an increase in cortisol levels and behavioral changes that were similar across handedness groups. However, cortisol levels at baseline were positively correlated with right-handedness, and this relationship was stronger in females than in males. In addition, the occurrence of social behaviors (pre- and postseparation) was positively correlated with right-handedness in both sexes. Baseline cortisol levels did not correlate significantly with social behavior. Acquisition of the reversals was poorer in females than males but did not differ as a function of handedness. We conclude that (a) both stress reactivity and cognitive flexibility are similar across handedness groups and (b) left-handers exhibit less social behavior and have lower basal cortisol levels than ambidextrous and right-handed subjects. The underlying causes for these differences remain to be established.

Sex differences in cognitive aging: a 4-year longitudinal study in marmosets.

Longitudinal studies are essential to understand healthy and pathological neurocognitive aging such as Alzheimer's Disease, but longitudinal designs are rare in both humans and non-human primate models of aging because of the difficulty of tracking cognitive change in long-lived primates. Common marmosets (Callithrix jacchus) are uniquely suited for aging studies due to their naturally short lifespan (10-12 years), sophisticated cognitive and social abilities and Alzheimer Disease-like neuropathology. We report the first longitudinal study of cognitive aging in marmosets (N = 28) as they transitioned from middle- (∼5 years) to old age (∼9 years). We characterized aging trajectories using reversal learning with different stimuli each year. Marmosets initially improved on cognitive performance due to practice, but worsened in the final year, suggesting the onset of age-related decline. Cognitive impairment emerged earlier in females than males and was more prominent for discrimination than for reversal learning. Sex differences in cognitive aging could not be explained by differences in motivation or motor abilities, which improved or remained stable across aging. Likewise, males and females did not differ in aging trajectories of overall behavior or reactivity to a social stressor, with the exception of a progressive decline in the initiation of social behavior in females. Patterns of cognitive aging were highly variable across marmosets of both sexes, suggesting the potential for pathological aging for some individuals. Future work will link individual cognitive trajectories to neuropathology in order to better understand the relationships between neuropathologic burden and vulnerability to age-related cognitive decline in each sex.

Robustness of sex-differences in functional connectivity over time in middle-aged marmosets.

Nonhuman primates (NHPs) are an essential research model for gaining a comprehensive understanding of the neural mechanisms of neurocognitive aging in our own species. In the present study, we used resting state functional connectivity (rsFC) to investigate the relationship between prefrontal cortical and striatal neural interactions, and cognitive flexibility, in unanaesthetized common marmosets (Callithrix jacchus) at two time points during late middle age (8 months apart, similar to a span of 5-6 years in humans). Based on our previous findings, we also determine the reproducibility of connectivity measures over the course of 8 months, particularly previously observed sex differences in rsFC. Male marmosets exhibited remarkably similar patterns of stronger functional connectivity relative to females and greater cognitive flexibility between the two imaging time points. Network analysis revealed that the consistent sex differences in connectivity and related cognitive associations were characterized by greater node strength and/or degree values in several prefrontal, premotor and temporal regions, as well as stronger intra PFC connectivity, in males compared to females. The current study supports the existence of robust sex differences in prefrontal and striatal resting state networks that may contribute to differences in cognitive function and offers insight on the neural systems that may be compromised in cognitive aging and age-related conditions such as mild cognitive impairment and Alzheimer's disease.