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.
| Wang, Sophia; Jacobs, Diane; Andrews, Howard et al. (2010) Cardiovascular risk and memory in non-demented elderly women. Neurobiol Aging 31:1250-3 |
| Mitsis, Effie M; Jacobs, Diane; Luo, Xiaodong et al. (2010) Evaluating cognition in an elderly cohort via telephone assessment. Int J Geriatr Psychiatry 25:531-9 |
| Sano, Mary; Jacobs, Diane; Andrews, Howard et al. (2008) A multi-center, randomized, double blind placebo-controlled trial of estrogens to prevent Alzheimer's disease and loss of memory in women: design and baseline characteristics. Clin Trials 5:523-33 |
| Sano, Mary; Grossman, Hillel; Van Dyk, Kathleen (2008) Preventing Alzheimer's disease : separating fact from fiction. CNS Drugs 22:887-902 |
| Aloysi, Amy; Van Dyk, Kathleen; Sano, Mary (2006) Women's cognitive and affective health and neuropsychiatry. Mt Sinai J Med 73:967-75 |
| Sano, Mary (2006) Neuropsychological testing in the diagnosis of dementia. J Geriatr Psychiatry Neurol 19:155-9 |
| Sano, Mary (2003) Current concepts in the prevention of Alzheimer's disease. CNS Spectr 8:846-53 |
| Faison, Warachal Eileen; Armstrong, Dena (2003) Cultural aspects of psychosis in the elderly. J Geriatr Psychiatry Neurol 16:225-31 |
| Sano, Mary (2002) Prevention of Alzheimer's disease: where we stand. Curr Neurol Neurosci Rep 2:392-9 |
