Operationally defining cognitive reserve genes.

Variability in cognitive decline is related to the environment, lifestyle factors, and individual differences in biological aging, including cognitive reserve, plastic properties of the brain, which account for better-than-expected cognition for a given level of brain aging or pathology. Cognitive reserve has not been thoroughly investigated in aged rodents. To address this gap, cognitive reserve was examined using Gene Expression Omnibus data for the CA1 region of the hippocampus of young and aged behaviorally characterized male rats. Statistical filtering identified brain aging and potential cognitive reserve genes, and multiple regression was employed to confirm cognitive reserve genes as genes that predicted better-than-expected cognition for a given level of brain aging. In general, cognitive reserve genes, in which increased expression was associated with better cognition, were not different with age or directly correlated with measures of cognition and appear to act as negative regulators of aging processes, including neuroinflammation and oxidative stress. The results suggest that, for some animals, resilience mechanisms are activated to counteract aging stressors that impair cognition. In contrast, cognitive reserve genes, in which decreased expression was associated with better cognition, were linked to nervous system development and cation transport, suggesting adaptive changes in the circuit to preserve cognition.