Estradiol Interacts with the Cholinergic System to Affect Verbal Memory in Postmenopausal Women: Evidence for the Critical Period Hypothesis

摘要

Estradiol has been shown to interact with the cholinergic system to affect cognition in postmenopausal women. This study further investigated the interaction of estradiol and cholinergic system functioning on verbal memory and attention in two groups of healthy younger (ages 50–62) and older (ages 70–80) postmenopausal women. Twenty-two postmenopausal women were randomly and blindly placed on 1 mg of 17-beta estradiol orally for one month then 2 mg for two months or matching placebo pills after which they participated in three anticholinergic challenge sessions when verbal memory performance was assessed. Subjects were administered either the antimuscarinic drug scopolamine (SCOP), the antinicotinic drug mecamylamine (MECA) or placebo. After the first challenge phase, they were crossed over to the other hormone treatment for another three months and repeated the challenges. Results showed that estradiol pretreatment significantly attenuated the anticholinergic drug-induced impairments on a test of episodic memory (the Buschke Selective Reminding test) for the younger group only, while estradiol treatment impaired performance of the older group. The results suggest that younger subjects may experience more cholinergic benefit from estradiol treatment than older subjects, supporting the concept of a critical period for postmenopausal estrogen use.