Short-term Hormone Therapy with Transdermal Estradiol Improves Cognition for Postmenopausal Women with Alzheimer's Disease: Results of a Randomized Controlled Trial

Article type: Research Article

Authors: Wharton, Whitney^{a; b; *} | Baker, Laura D.^{c; d} | Gleason, Carey E.^{a; b} | Dowling, Maritza^{a; b} | Barnet, Jodi H.^{a; b} | Johnson, Sterling^{a; b} | Carlsson, Cynthia^{a; b} | Craft, Suzanne^{c; d} | Asthana, Sanjay^{a; b}

Affiliations: [a] University of Wisconsin, School of Medicine and Public Health, Madison, WI, USA | [b] Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, WI, USA | [c] Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA | [d] University of Washington, School of Medicine, Seattle, WA, USA

Correspondence: [*] Correspondence to: Whitney Wharton, Ph.D. University of Wisconsin, School of Medicine and Public Health, William S. Middleton Memorial VA Hospital, 2500 Overlook Terrace, GRECC 11G Madison, WI 53705, USA. Tel.: (512) 585 2327; Fax: (608) 280 7291; E-mail: wlwharto@medicine.wisc.edu.

Abstract: We aimed to conduct a placebo-controlled, double-blind, parallel-group design intervention study to evaluate the therapeutic efficacy of hormone therapy (HT) in postmenopausal women with mild to moderate Alzheimer's disease (AD). The trial was designed to evaluate the dose-dependent effects of transdermal 17-β estradiol, unopposed and opposed with medroxyprogesterone (MPA, Provera©), for 12 months in 43 postmenopausal women with AD. Participants were assessed using cognitive measures at baseline, months 1, 3, 6, and 12 of treatment and eight weeks post treatment (month 15). The dropout rate was 49% across 12 months. As a result of the Women's Health Initiative (WHI) and anticipated increased attrition, the protocol was modified to examine data only at time points where attrition was less than 30%. The results of sensitivity analyses indicated robust and reliable data collected in the first three months of the trial. Data collected in the first three months of the trial for forty-three participants were analyzed. HT had favorable cognitive effects across multiple cognitive domains, including visual memory (p-values < 0.030) and semantic memory (p-values < 0.037) in postmenopausal women with AD. Moreover, treatment-related changes in plasma estradiol were positively correlated with improvements in visual memory. Short-term HT that includes the use of estradiol has favorable effects on cognition in women with AD.

Keywords: Alzheimer's disease, clinical trial, cognition, estradiol, estrogen, hormone therapy, medroxyprogesterone, memory

DOI: 10.3233/JAD-2011-110341

Journal: Journal of Alzheimer's Disease, vol. 26, no. 3, pp. 495-505, 2011