Just as we need multiple ingredients to make a delicious lasagna, researchers need comprehensive models to understand cognitive performance. In this study, scientists aimed to develop a cognitive index for learning that could account for age-related changes in cognitive function and sleep-wake cycles. By using a maze-based test called the Barnes maze and monitoring the daily activity patterns (circadian rhythms) of young, middle-aged, and aged mice, the researchers found that aged mice exhibited significant deficits in learning and memory compared to their younger counterparts. Moreover, they found that impairments in cognitive function were related to disruptions in the circadian rhythms of activity onset. Specifically, mice with more cognitive impairment showed greater variability in their daily activity timing. These findings suggest that disturbances in circadian rhythms may serve as early indicators of age-related cognitive decline. It remains unclear whether changes in sleep-wake cycles directly cause cognitive impairment, but this study provides valuable insights into the complex relationship between aging, cognition, and the passage of time!

Preclinical quantitative models of cognitive performance are necessary for translation from basic research to clinical studies. In rodents, non-cognitive factors are a potential influence on testing outcome and high variability in behavior requires multiple time point testing for better assessment of performance in more sophisticated tests. Thus, these models have limited translational value as most human cognitive tests characterize cognition using single digit scales to distinguish between impaired and unimpaired function. To address these limitations, we developed a cognitive index for learning based on previously described scores for strategies used by mice to escape the Barnes maze. We compared the cognitive index and circadian patterns of light-dark entrainment in young (4–6 months), middle-aged (13–14 months), and aged (18–24 months) mice as cognitive changes during aging are often accompanied by pronounced changes in sleep-wake cycle. Following continuous analysis of circadian wheel-running activity (30–40 days), the same cohorts of mice were tested in the Barnes maze. Aged mice showed significant deficits in the learning and memory portions of the Barnes maze relative to young and middle-aged animals, and the cognitive index was positively correlated to the memory portion of the task (probe) in all groups. Significant age-related alterations in circadian entrainment of the activity rhythm were observed in the middle-aged and aged cohorts. In middle-aged mice, the delayed phase angle of entrainment and increased variability in the daily onsets of activity preceded learning and memory deficits observed in aged animals. Interestingly, learning-impaired mice were distinguished by a positive relationship between the extent of Barnes-related cognitive impairment and variability in daily onsets of circadian activity. While it is unclear whether changes in the sleep-wake cycle or other circadian rhythms play a role in cognitive impairment during aging, our results suggest that circadian rhythm perturbations or misalignment may nevertheless provide an early predictor of age-related cognitive decline.

Read Full Article (External Site)