Why study normative cognitive aging when it is not a disease?

Distinguished Career Contributions Award (DCC)Animal models have been used to explore changes in the brain that might contribute to the underlying causes of normative age-related memory impairment.The hippocampus has been a useful neural system to study for gaining insights into what brain and cognitive changes are to be expected during the aging process.For example, healthy older humans, nonhuman primates and rodents all show poorer hippocampus-dependent spatial memory and navigation ability than do their younger counterparts.Remarkably, these age-related changes begin to occur at a point in the lifespan that the species is considered to be "old".This suggests that neurobiological changes that contribute to memory alterations across time are accelerated in shorter-lived species such as the rat, compared to humans.Central in the search for the fundamental contributors to memory changes that occur across the lifespan is synapse structure, function, and plasticity, and those mechanisms that act to support synapses.Alterations in synapse function and memory circuits are highly specific to subregions and cell types, rather than uniform across brain regions, making the search for interventions complex.Nevertheless, discovering how to support synaptic health in circuits critical for memory will be key for facilitating treatment strategies that aim to optimize cognition.At least two compelling reasons can be offered to support the idea that it is critical to understand the normative aging brain.First, most neurodegenerative diseases are superimposed on an aging brain.Thus, discovering the reasons for this age-related vulnerability may provide clues for disease prevention.Second, because epidemiological data indicate that most of us will age normatively, this also presents the possibility that resilience factors against disease can be discovered, as well as factors that optimize cognitive health in those who are aging normatively.At the very least it is important to understand the normal aging brain well enough so that these states can be distinguished from pathological conditions.