High-dose estradiol improves cognition for women with AD: results of a randomized study.
OBJECTIVE
To characterize the cognitive and neuroendocrine response to treatment with a high dose of estrogen for postmenopausal women with AD.


METHODS
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 weeks. Subjects were evaluated at baseline, at weeks 3, 5, and 8 during treatment, and again 8 weeks after treatment termination. During each visit, cognition was assessed with a battery of neuropsychological tests, and blood samples were collected to measure plasma estradiol as well as several other neuroendocrine 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 (Figure Copy/Memory). In addition, women treated with estrogen demonstrated improved performance on a test of semantic memory (Boston Naming Test) compared with subjects who received a placebo. Estrogen appeared to have a suppressive 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 treatment.


CONCLUSIONS
Administration of a higher dose of estrogen may enhance attention and memory for postmenopausal women with AD. Although these findings provide further clinical evidence to support a cognitive benefit of estrogen for women with AD, studies evaluating the effect of estradiol administration, in particular, using larger sample sizes and for longer treatment durations are warranted before the therapeutic potential of estrogen replacement for women with AD can be firmly established.
Asthana
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Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle/Tacoma, Tacoma, WA 98493, USA. sasthana@u.washington.edu
Baker
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Craft
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Stanczyk
F Z
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Veith
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Raskind
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Plymate
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D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D000704:Analysis of Variance; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood; D015914:Estrogen Replacement Therapy / Q000379:methods*; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008875:Middle Aged
D018972:Insulin-Like Growth Factor Binding Protein 3; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II