Effects of ovarian hormones on cognitive function in nonhuman primates

Several studies have suggested that estrogen benefits verbal memory and lowers the risk of Alzheimer's disease in women, and improves cognitive function in animal models. However, the negative outcome of the Women's Health Initiative Memory Study has challenged the rationale for using estrogen as a protective agent against age-related cognitive decline. In view of the limitations of the Women's Health Initiative Memory Study, it is clear that our understanding of estrogen effects would greatly benefit from further interactions between clinical and basic science. Animal models of menopause can provide crucial information regarding the consequences of estrogen loss and replacement on several systems, including cognition. In this paper, I review the evidence that nonhuman primates, who share numerous cognitive and physiological characteristics with humans, can substantially contribute to our understanding of estrogen influences on the brain and cognition. Studies in young adult females suggest that some aspects of cognition fluctuate with the menstrual cycle, but that ovariectomy and estrogen replacement have only modest effects on cognitive function. In contrast, data in aged, naturally or surgically menopausal monkeys indicate that estrogen modulates a broad range of cognitive domains. Neurobiological data are consistent with the cognitive findings and demonstrate an array of morphological and physiological changes in brain areas important for cognition following ovariectomy and/or estrogen replacement. It is concluded that nonhuman primates, by providing a bridge between rodent and human data, constitute invaluable models to further our understanding of hormonal actions on the brain and cognition and to develop effective hormonal interventions against brain and cognitive aging.