In studies leading to this application the investigators studied the modulatory role of sex hormones on the behavior of young subjects, older subjects whose sex hormones had declined, and older subjects with hormone supplementation. The investigators identified age, sex differences and hormonal effects on cognition. Mental rotation was found to be mediated by the parietal lobe and working memory by the pre-frontal lobe. Mental rotation was modulated by estrogen in women but not men, and working memory was modulated by testosterone in men, but not women. The goals of the next four years are to examine whether the cognitive effects of hormone replacement attenuate with chronic supplementation in older women, as compared to the short-term supplementation previously tested. The modulating effect of progesterone on estrogen replacement will be investigated. In the proposed series of three studies investigators will examine: 1) the effect of steroidal hormone replacement in young and older women on cognitive function in the areas of verbal skills, visual-spatial processing, and memory; 2) sex differences in cognitive function relative to hormone replacement; 3) the neural specificity of hormonal modulation effects on mental rotation and working memory tasks via functional magnetic resonance imaging (fMRI) in young and older men and women. The understanding of the cognitive effects in the proposed studies will be extended by examining directly the brain basis of sex hormones on cognition.
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