High-dose estradiol improves cognition for women with AD - Results of a randomized study

Objective: To characterize the cognitive and neuroendocrine response to tre atment with a high dose of estrogen for postmenopausal women with AD. Metho ds: Twenty postmenopausal women with AD were randomized to receive either 0 .10 mg/day of 17 beta -estradiol by skin patch or a placebo patch for 8 wee ks. Subjects were evaluated at baseline, at weeks 3, 5, and 8 during treatm ent, and again 8 weeks after treatment termination. During each visit, cogn ition was assessed with a battery of neuropsychological tests, and blood sa mples were collected to measure plasma estradiol as well as several other n euroendocrine markers of interest. Results: Significant effects of estrogen treatment were observed on attention (Stroop Color Word Interference Test) , verbal memory (Buschke Selective Reminding Test), and visual memory (Figu re Copy/Memory). In addition, women treated with estrogen demonstrated impr oved performance on a test of semantic memory (Boston Naming Test) compared with subjects who received a placebo. Estrogen appeared to have a suppress ive effect on the insulin-like growth factor (IGF) system such that plasma concentration of IGF binding protein-3 was significantly reduced and plasma levels of estradiol and IGF-I were negatively correlated during estrogen t reatment. Conclusions: Administration of a higher dose of estrogen may enha nce attention and memory for postmenopausal women with AD. Although these f indings provide further clinical evidence to support a cognitive benefit of estrogen for women with AD, studies evaluating the effect of estradiol adm inistration, in particular, using larger sample sizes and for longer treatm ent durations are warranted before the therapeutic potential of estrogen re placement for women with AD can be firmly established.