ALZHEIMERS DISEASE PREVENTION TRIAL WITH ESTROGENS

Columbia University Health Sciences, New York NY

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Abstract

This is a randomized, double-blind, placebo-controlled clinical trial to determine if estrogen can delay the onset of Alzheimer's disease(AD) and reduce memory decline. 900 healthy, non-demented, women, 65 years of age or older, with a family history of AD will be recruited in 18 months from 3 different cities (New York, NY, Baltimore, MD and Jacksonville, FL) over an 18 month period using 4 distinct methods: 1) healthy non-demented female relatives of patients with AD seen at each of the 3 participating AD centers; 2) women with a family history of AD contacted through community service providers surrounding each medical center, 3) women with a family history of AD identified through advertisement using local media (newspaper, television and radio) and; 4) women with a family history of AD identified from a regional sample of female Medicare recipients provided by the Health Care Finance Administration (HCFA). At study entry, family history of AD in a first degree relative will be confirmed and each participant will have a physical, neurological, neuropsychological and functional assessment to insure the absence of dementia, any other degenerative neurological disease or potentially fatal disorder. Exclusions include a history of breast, uterine or ovarian cancer, history of arterial or deep vein thrombosis, a history of breast cancer in a first-degree relative. Randomization to estrogen, estrogen with progesterone or identical placebo among eligible women will be stratified by site and hysterectomy status (hysterectomized women will be randomized to unopposed estrogen or placebo; non-hysterectomized women to opposed estrogen or placebo); non-hysterectomized women to opposed estrogen or placebo). Analyses will combine opposed and unopposed estrogen treatments into a single group and compare them to placebo. Patients will be followed over a 3 year (36-month) period, and will be examined at 6 month intervals to assess compliance, adverse events and general health status. Annual complete medical, gynecological, neuropsychological and functional assessments will occur during follow-up. Outcome measures will include incident dementia and memory decline. We will use an intent-to-treat analysis from the primary analysis. Secondary analysis will examine potential co-variates. Safety evaluations will be based on finding from annual assessments and reported adverse events. Participants who become demented will be informed of standard-of-care treatment and will continue to be followed at annual intervals for the length of the study.