Age-related changes in rodent cortical acetylcholine and cognition: main effects of age versus age as an intervening variable.

Evidence from aged and demented humans has stimulated research on the effects of age on the integrity of cortical cholinergic afferents in rodents. However, a comprehensive review of the available data does not consistently support the hypothesis that normal aging in rodents robustly affects the function of basal forebrain cholinergic projections to the cortex. These data indicate the limited significance of age as an independent experimental variable in research on age-related changes in cortical acetylcholine and associated behavioral or cognitive functions. Alternatively, recent studies demonstrated that normal aging in rodents potently interacts with the consequences of experimental manipulations of this system. Thus, aging acts as an intervening variable in experiments designed to elucidate age-related changes in the vulnerability and restorative capacity of this neuronal system after injury and degenerative processes. Investigations of the interactions between the effects of age and the capacity of the cholinergic systems to respond to detrimental processes reveal robust consequences of aging on cortical acetylcholine and the cognitive functions mediated by this neuronal system.