Abstract

In human populations, cognitive performance in early life has been identified as a strong predictor of future dementia risk. If cognitive ability were a stable trait across the adult lifespan of mice, then this species would provide an excellent framework for understanding the biology underlying this modifiable risk factor. To address this issue, longitudinal cognitive testing was performed in female C57BL/6J mice aged between 4 and 18 months of age. By tracking individuals, we were able to demonstrate that
the cognitive performance of an animal in specific tasks at 4 months of age was a remarkably reliable indicator of performance at 18 months of age. Variability in the performance of individuals was not associated with differences in macroscopic brain structure, but single-cell recording from neurons of the prefrontal cortex did identify age-related changes in membrane excitability. Most importantly, this study demonstrated that strategies adopted early in life to explore a nine-arm radial maze were
maintained across the adult lifespan and learning effects associated with repeated exposure to a test contribute to this stability. Overall, our results demonstrate that, like humans, cognitive ability in mice is a stable trait and the cognitive reserve necessary for healthy brain ageing is established early in life.