NEUROBIOLOGICAL EFFECTS OF LONG-TERM ESTROGEN REPLACEMENT

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. With the steady increase in our aging female population, issues concerning the maintenance and improvement of the physical and mental health of postmenopausal women are extremely relevant to our society. Aging leads to the deterioration of brain function and a higher incidence of dementias such as Alzheimer's disease (AD). AD is a devastating illness and presents a tremendous economic burden to the country. Since no cures or highly effective therapies exist, preventive strategies are of particular importance in this disease. A number of studies have suggested that estrogen use can enhance cognitive performance and possibly prevent or delay the onset of debilitating dementias. The long-term protective effects of estrogen on cognitive functioning, however, are not clearly established. The goal of our research is to study the aging process in women and evaluate the effects of postmenopausal estrogen therapy on healthy brain function. Furthermore, as the health benefits and risks (i.e. breast cancer) of long-term postmenopausal hormone therapy are debated, information relevant to AD risk and quality of life will assist in appropriate recommendations for the health care of aging women. Sixty women will be recruited through bulletin board announcements, newspaper advertisements and the Women's Health Registry (a database of women interested in participating in clinical research studies). They will be selected so that they are 60 years old or older and have either received hormone therapy without interruption after menopause or no replacement. The subjects will be recruited into three groups, 20 will have never used postmenopausal hormone therapy, 20 will have used estrogen only for at least ten years, and 20 will have used estrogen and progestin for at least ten years. Magnetic Resonance Image (MRI) of anatomy and functional MRI (fMRI) of the brain will be obtained in all study participants. In addition, subjects will undergo a positron emission tomography (PET) scan for the study of a cholinergic neurotransmitter system involved in cognition. Hormone levels will be tested and cognitive tests will be performed. Acquired data will be examined to find out whether estrogen use will have the greatest positive effect on brain capabilities compared to estrogen plus progestin regimen or using no hormones at all.'