Gibbs reviews the basic science, animal and neurochemical data, regarding estrogens and cognitive function. Importantly, estrogenic regulation of cognitive function is selective and does not affect all types of cognitive function but instead selectively affects specific types of behaviors. He goes on to review the impact of combination hormone therapy (HT) on cognitive performance and basic science investigations of the critical period of hormone intervention hypothesis. These findings indicate that estradiol enhancement of cognitive performance is lost over time following ovariectomy, which is consistent with Gibbs's cholinergic hypothesis and the critical window of therapeutic opportunity hypothesis (see Chapter 4). Results derived largely from rodent studies suggest that estradiol regulation of basal forebrain cholinergic neurons plays an important role in the regulation of select types of cognitive function, and may provide a mechanistic foundation for the critical period hypothesis. Gibbs proposes that identifying the specific neural circuits that account for the task-selective effects of estradiol, as well as the mechanisms by which these effects are mediated by basal forebrain cholinergic neurons, will aid in the proper use and timing of HT in postmenopausal women to sustain cognitive performance and prevent age-related cognitive decline and dementia.