Understanding the role of estrogen on cognition and dementia.

There is growing evidence that post menopausal use of estrogen may have a beneficial effect on cognition and may reduce the risk of dementia. In a vast majority of studies, the use of estrogen replacement in the postmenopausal period was associated with a reduced risk of dementia. Meta-analyses of both retrospective case controlled and prospective studies indicate a 30% reduction in the risk of dementia, with larger effect sizes (50% reduction) reported in the latter. Some, but not all, large epidemiological studies indicate that estrogen use is associated with better performance on both verbal and visual memory testing in later life. However, studies of the effect of estrogen on patients with Alzheimer's disease are less convincing with minimal effects reported in open trials and following brief exposure. Biological mechanisms, which could be responsible for some of these effects, include activation of the cholinergic system, anti-oxidant action, neurotrophic stimulation and anti-amyloidogenic properties. Beneficial effects of estrogen in primary prevention but not secondary prevention of heart disease indicates that the ability to observe beneficial effects may depend on the point at which intervention occurs. Ongoing double-blind randomized clinical trial to determine if estrogen is a safe and effective treatment for the prevention of memory loss and Alzheimer's disease will be described. Future work will undoubtedly include the identification of specific estrogenic receptors in the central nervous system that can be selectively activated without adverse involvement of other biologic systems.