title: Tamoxifen improves cholinergically modulated cognitive performance in postmenopausal women.
abstract: Tamoxifen (TMX) is a selective estrogen receptor modulator that is used as an estrogen receptor antagonist for the treatment and prevention of breast cancer. Whether TMX has antagonist activities in the human brain is less clear and its effects on cognitive function have not been experimentally explored. This study examined how TMX affected cognitive performance in older women using a model of anticholinergic drug-induced cognitive dysfunction. Twenty-one postmenopausal women were administered 20 mg of oral TMX or placebo for 3 months. Participants then took part in five drug challenges using the anticholinergic antinicotinic agent mecamylamine (MECA) and antimuscarinic agent scopolamine (SCOP) and were tested on a comprehensive battery including tasks of attention and psychomotor function, verbal episodic memory, and spatial navigation. After a 3-month placebo washout, participants were then crossed over to the alternate treatment and repeated the drug challenges after 3 months. Compared with placebo treatment, TMX significantly attenuated the impairment from cholinergic blockade on tasks of verbal episodic memory and spatial navigation, but effects on attentional/psychomotor tasks were more variable. Analysis by APOE genotype showed that APO ɛ4+ women showed a greater beneficial effect of TMX on reversing the cholinergic impairment than APO ɛ4- women on most tasks. This study provides evidence that TMX may act as an estrogen-like agonist to enhance cholinergic system activity and hippocampally mediated learning.
authors.affiliation: 1] Vanderbilt Center for Cognitive Medicine, Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN, USA [2] Clinical Neuroscience Research Unit, Department of Psychiatry, University of Vermont College of Medicine, Burlington, VT, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Newhouse
authors.forename: Kimberly
authors.initials: K
authors.lastname: Albert
authors.forename: Robert
authors.initials: R
authors.lastname: Astur
authors.forename: Julia
authors.initials: J
authors.lastname: Johnson
authors.forename: Magdalena
authors.initials: M
authors.lastname: Naylor
authors.forename: Julie
authors.initials: J
authors.lastname: Dumas
mesh_terms: D000368:Aged; D001288:Attention / Q000187:drug effects; D018680:Cholinergic Antagonists / Q000009:adverse effects*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008464:Mecamylamine / Q000009:adverse effects; D008568:Memory / Q000187:drug effects; D008875:Middle Aged; D009483:Neuropsychological Tests; D010147:Pain Measurement; D017698:Postmenopause / Q000187:drug effects*; D011569:Psychiatric Status Rating Scales; D012601:Scopolamine / Q000009:adverse effects; D013629:Tamoxifen / Q000627:therapeutic use*; D013997:Time Factors; D014706:Verbal Learning / Q000187:drug effects
chemical_list: D018680:Cholinergic Antagonists; D004965:Estrogen Antagonists; D013629:Tamoxifen; D008464:Mecamylamine; D012601:Scopolamine