NEUROBIOLOGICAL EFFECT OF LONG-TERM ESTROGEN REPLACEMENT

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DESCRIPTION (provided by applicant): This Mentored Patient-Oriented Research Career Development Award proposal contains didactic coursework, mentored instruction, and a clinical research project designed to apply the principles learned. The investigators' clinical research interest is in the integration of reproductive endocrinology with cognition, aging, and brain function and neurochemistry. The proposed clinical training and research studies in this application are designed to increase her skills in study design, biostatistics, cognitive neurosciences and neuroimaging techniques, with the ultimate goal of developing into an independent clinical investigator. The curriculum of the K30 Training Grant in Clinical Research, leading to a Master of Science in Clinical Research Design and Statistical Analysis at the UM, is included in the coursework. The goal of the research proposal is to study the neurobiological effects of long-term hormone therapy in healthy postmenopausal women. Sixty postmenopausal women, 60 years or older, will be recruited for this cross-sectional study (20 will never have used hormones, 20 will have used estrogen only for at least 10 years, and 20 will have used estrogen and progestin for at least 10 years). All women will undergo an extensive neuropsychological testing battery, a single photon emission computed tomography (SPECT) scan with a marker of cholinergic synaptic terminal density, an anatomic magnetic resonance image (MRI), and measures of estradiol and estrone. Ten women from each group will also undergo a functional MRI (fMRI) during a cognitive task designed to activate brain areas affected by estrogen and altered in Alzheimer's Disease. Comparison between groups will offer a greater understanding of the effect of hormone therapies on brain neurochemistry and cognition.