| dc.description.abstract | Cognitive changes in aging and Alzheimer’s disease (AD) are often accompanied by pronounced disturbances of circadian timekeeping, especially the sleep-wake cycle. Normal circadian timekeeping has an important impact on human health and performance by providing the temporal coordination of internal processes to ensure their occurrence at the “right time” relative to each other and the external environment. The aging of the rodent circadian system is characterized by changes comparable to those in human aging and AD. Common disturbances in the sleep-wake rhythms of aged rodents include alterations in circadian activity. However, not all aged rodents show these changes, demonstrating the variability characteristic of human aging in pre-dementia or mild cognitive impairment (MCI). Because the aging population also shows variability in onset and magnitude of cognitive impairment, we explored the relationship between these cognitive deficits and sleep disturbances during aging in mice. The circadian rhythm of locomotor activity was continuously analyzed for 30-40 days in young (3-5 mo), middle-aged (12-14 mo), and aged (18-24 mo) mice. We then evaluated the mice in the Barnes maze for learning and memory performance. Aged mice exhibited significant cognitive impairment in conjunction with striking changes in their circadian patterns of activity. Data from middle-aged animals (12-14 mo) showed that changes in circadian activity occur before deficits in learning and memory. Interestingly, we observed a gender-specific relationship between cognitive impairment in the Barnes maze and increased variability in daily onset times of circadian activity in aged female mice (20-24 mo). This data is the foundation of our model to further understand the relationship between circadian synchronization and cognitive impairment, and to probe possible mechanisms of underlying age-related changes. | |
