There is increasing concern about the possible deleterious effects of menopause and potential beneficial effects of hormone replacement on cognitive function. Traditional hormone replacement therapy effectively reduces symptoms of menopause such as hot flashes, and has beneficial effects on the skeletal and cardiovascular systems, and probably the nervous system. However, hormone replacement therapy increases the likelihood of endometrial and perhaps breast cancer. The medical community is at a crossroads in the treatment of menopause. As alternatives to traditional hormone replacement therapy, novel estrogens and other treatments are being considered to identify a therapeutic intervention that has only neutral or beneficial effects on the target tissues. For this reason, it is important to compare the impact of these treatments on the function of all the target tissues of concern. The efficacy and safety of several of these alternative therapeutic strategies are currently being tested in the monkey model. Unfortunately, the monkey model is deficient in the area of assessment of cognitive function. This deficit is due to the fact that standard tests of nonhuman primate cognitive function have experimental requirements that severely constrain their use under many experimental conditions. These problems are currently addressed by evaluating cognitive performance in small groups of animals separate from those in which the effects of treatment on other tissues are being evaluated. This approach results in greater research expense and wastes valuable animal resources. Therefore, we propose to develop a test of cognitive function that can be administered on a large scale in a short time period and does not require special housing or extensive dietary manipulation.

In this application, we propose to develop a short and easily administered assessment of cognitive function, determine its validity against standard tests of cognitive function, determine its reliability using a test-retest paradigm, experimentally manipulate performance on this test with a pharmacological agent known to alter cognitive function, and finally, demonstrate the utility of the test in an experimental situation in which standard assessments of cognitive function are not possible. This research will further the development of the nonhuman primate model of menopause and provide a clinical evaluation of cognitive functioning that will have wide applicability in research with nonhuman primates.

R01RR014100

1993-06-01

2001-06-14