The goal of this study is to examine whether the administration of estrogen to post-menopausal women and women with mild to moderate Alzheimer's disease will enhance their memory and their capacity for learning.

Estrogen (EST) may have significant benefits in preserving cognitive functioning in normal aging after menopause and in decreasing the incidence of Alzheimer's disease (AD). On a molecular level, EST has effects on a variety of cholinergic neuronal and receptor-mediated mechanisms that may be responsible for these beneficial effects. These neurons have critical relevance for the development of age-related cognitive changes and dementing disorders. However, little is known about the clinical relevance of EST-cholinergic interactions, either in normal aging or in AD.

The primary goal of this study is to test the hypothesis that three months of administration of EST to 1) normal post-menopausal women, and 2) female patients with mild-moderate AD who are concurrently treated with anticholinesterase therapy (donepezil), will positively change or blunt the negative and behavioral effects of drugs that block central cholinergic receptors (both muscarinic and nicotinic). Participants will be blindly placed on EST or placebo for three months each. After each three month period, they will be cognitively assessed after receiving single doses of the cholinergic antagonists scopolamine and mecamylamine. These results will have direct implications for the use of EST in post-menopausal women as well as interactive treatment with cholinergic drugs for AD. Researchers plan to recruit a total of 45 women (30 healthy, and 15 patients with AD).

NOTE: This study is only recruiting participants with Alzheimer's Disease at this time.

• Drug: Donepezil
• Drug: Estrogen
• Drug: Progesterone

• Newhouse PA, Potter A, Corwin J, Lenox R. Acute nicotinic blockade produces cognitive impairment in normal humans. Psychopharmacology (Berl). 1992;108(4):480-4.
• Newhouse PA, Potter A, Corwin J, Lenox R. Age-related effects of the nicotinic antagonist mecamylamine on cognition and behavior. Neuropsychopharmacology. 1994 Apr;10(2):93-107.

Inclusion Criteria:

• Normal volunteers and women with mild Alzheimer's disease:
• Non-smoker
• No use of Hormone Replacement Therapy for at least one year
• No menses for at least one year
• Normal mammogram within the last year
• minimum age is 45 for patients with Alzheimer's disease; 50 for normal volunteers
• Maximum age is 85 for patients with Alzheimer's disease; there is no maximum age for normal volunteers.

Exclusion Criteria:

• Women who are currently taking estrogen therapy.
• Women who are smokers.
• Women who have had breast cancer.

• Alzheimer's Association
• Pfizer
• Eisai Inc.