Animal Models of Aging and Cognition

Abstract

Human aging is associated with variable rates of cognitive decline. Aged laboratory animals, specifically rats and monkeys, show similar cognitive profiles when tested on species-appropriate behavioral tasks. Using these cognitively defined animal models, we now understand that normal aging is associated with disconnections between functionally related brain regions that support specific behaviors. We review recent work describing molecular and cellular mechanisms that lead to decreased connections between the aged hippocampus and associated cortical and basal forebrain neurons required for normal memory. We also discuss behavioral evidence that aging leads to impaired executive functions with concurrent changes to key neural substrates within the frontostriatal network. Collectively, these studies demonstrate that cognitive deficits in older individuals are related to modest, circuit-specific alterations and that data obtained from such animal models can help to better inform the design of future clinical studies and improve neuropsychiatric outcomes for older patients.