Project activities during the current reporting period have included bringing to closure a number of long-term investigations. In one study we evaluated, in aged surgically menopausal rhesus monkeys, the cognitive effects of four hormone therapy (HT) regimens that included progesterone and/or continuous estrogen, mimicking treatments used clinically in women. Whereas our earlier work had demonstrated that intermittent estrogen injection benefits working memory capacities mediated by the prefrontal cortex in aged ovariectormized monkeys, HT in women has often failed to influence cognitive function in clinical studies. The possibility that this discrepancy reflects differences in the formulation and timing of HT regimens, however, has not been tested systematically. Notably, none of the four hormone treatments examined in our experiments produced any beneficial effects on cognition, despite documented efficacy measured by serum hormone levels. A full-length report of these findings was recently accepted for publication pending minor revision at Neurobiology of Aging. The results have significant implications for the development of regimens aimed at promoting successful cognitive aging, and suggest that HT regimens commonly prescribed for women are unlikely to yield cognitive enhancement, at least in relation to capacities mediated by the prefrontal cortex. Consistent with this conclusion, and in stark contrast to our earlier findings for cyclic estrogen administration, quantitative morphometric analysis in the brains of the same animals failed to find any effect of HT on dendritic spine density in the prefrontal cortex (Ohm et al., 2012). Continuing project efforts, in addition to incorporating concurrent in vivo brain imaging (Shamy et al., 2012, Soc. Neurosci. Abstr.) aim to determine whether there is a temporal window of opportunity for protecting cognitive function after ovarian hormone decline, and to document the endurance characteristics of HT and withdrawal.
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