This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.[from CRISP website (edited)]Estrogen has multiple good neuromodulatory, neurotrophic, and neuroprotective properties. These positive effects are presumably mediated through the estrogen receptors located throughout the brain. There are many estrogen receptors in 4 sections of the brain - the neocortex, hippocampus, amygdala, and basal forebrain. These are areas of the brain are afflicted by Alzheimer's disease (AD) and have specific cognitive functions impaired in patients with AD. Moreover, these cognition-mediating regions of the brain demonstrate neurotrophic activity in response to estrogen release.Preliminary evidence from clinical studies indicates that giving estrogen improves memory in postmenopausal women with AD. In addition, results of epidemiological studies suggest that estrogen therapy might reduce the risk of developing AD. However, several issues must be evaluated before estrogen for the treatment of AD can be firmly established. These issues include the following: (1) whether the cognition- enhancing actions of estrogen are dose-dependent and persist over an extended period of administration, (2) if the good effects of estrogen on cognitive function will lead to improved skills of independent living, (3) whether the potential beneficial effects on cognition and physical function will persist when estrogen is co-administered with a progestin over both short and extended periods, and finally, (4) whether a person's genetic make up (ApoE genotype) influences the response of an individual to treatment with estrogen. The randomized, double-blind, placebo-controlled, parallel-group design clinical study, started in 2001, will evaluate the dose-dependent effects of prolonged administration of both unopposed and opposed (i.e., with a progestin) estrogen on cognitive function and skills of independent living in postmenopausal women with AD.
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