Animal models of cognitive aging and circuit-specific vulnerability

Medial temporal lobe and prefrontal cortical structures are particularly vulnerable to dysfunction in advanced age and neurodegenerative diseases. This review focuses on cognitive aging studies in animals to illustrate the important aspects of the animal model paradigm for investigation of age-related memory and executive function loss. Particular attention is paid to the discussion of the face, construct, and predictive validity of animal models for determining the possible mechanisms of regional vulnerability in aging and for identifying novel therapeutic strategies. Aging is associated with a host of regionally specific neurobiologic alterations. Thus, targeted interventions that restore normal activity in one brain region may exacerbate aberrant activity in another, hindering the restoration of function at the behavioral level. As such, interventions that target the optimization of “cognitive networks” rather than discrete brain regions may be more effective for improving functional outcomes in the elderly.