Alzheimer's Disease: Therapeutic Potential of Estrogen

This is a 15-month study to determine the effectiveness of hormone replacement therapy in improving memory and the ability to live independently in postmenopausal women with Alzheimer's disease.

Estrogen is a naturally occurring hormone produced in a woman's body. The purpose of this 15-month study is to determine the effectiveness of hormone replacement therapy in improving memory and the ability to live independently in postmenopausal women with Alzheimer's disease and without other dementias. Patients who volunteer for this study will either receive a patch containing 17-ß-estradiol or will receive an inactive placebo patch. In addition, patients will be given either medroxyprogesterone or an inactive placebo pill. Neither the volunteers nor the study staff will know which type of patch or pill a patient receives. Patients must be generally healthy and have mild-to-moderate dementia. There must be a patient caregiver who can watch for side effects and ensure that the patient takes the study medications on schedule. Patients will undergo neuropsychological tests and an evaluation of the ability to live independently at each visit as well as laboratory evaluations, such as the taking of blood. Each visit will last approximately 3 hours. A total of 160 participants are being recruited.

50 micrograms (low-dose) or 100 micrograms (high-dose) transdermal 17-ß-estradiol patch, changed every 3 days, for 12 months

Cognition: delayed recall on Buschke Selective Reminding Test; Stroop Interference condition--completion time and errors; Clinician-rated Interview Based Impression of Change

Bioassays (Estradiol, estrone, medroxyprogesterone, FSH, influence of ApoE genotype in responsivity to estrogen)

Inclusion Criteria: Postmenopausal women with Alzheimer's disease and without other dementias (diagnosed by study staff or from an outside clinic) Mini Mental State Examination score greater than 15/30 Exclusion Criteria: History of cancer of reproductive tissues History of deep vein thrombosis or blot clots Diabetes Heart disease or stroke Liver problems including hepatitis Severe vision or hearing problems Tobacco use Lack of an adequate caregiver inability to perform psychometric testing

Cholerton B, Gleason CE, Baker LD, Asthana S. Estrogen and Alzheimer's disease: the story so far. Drugs Aging. 2002;19(6):405-27. doi: 10.2165/00002512-200219060-00002.

Asthana S, Baker LD, Craft S, Stanczyk FZ, Veith RC, Raskind MA, Plymate SR. High-dose estradiol improves cognition for women with AD: results of a randomized study. Neurology. 2001 Aug 28;57(4):605-12. doi: 10.1212/wnl.57.4.605.

Asthana S, Craft S, Baker LD, Raskind MA, Birnbaum RS, Lofgreen CP, Veith RC, Plymate SR. Cognitive and neuroendocrine response to transdermal estrogen in postmenopausal women with Alzheimer's disease: results of a placebo-controlled, double-blind, pilot study. Psychoneuroendocrinology. 1999 Aug;24(6):657-77. doi: 10.1016/s0306-4530(99)00020-7.