Estrogens produce a multitude of complex effects in the brain by means of a variety of mechanisms. Accumulating data has indicated that these actions mediate enhancing effects on cognition and mood as well as perhaps prophylaxis against age-and disease-related cognitive-cerebral decline. Phytoestrogens have demonstrated estrogenic activity. They have been studied with respect to benefits for cardiovascular function, preservation of bone, and reduction of risk for cancer, but there is little prospective research regarding effects on mental function. In addition, phytoestrogens generally are not prescribed by practitioners for mental health effects. However, many women experiencing peri-and post-menopausal symptoms consume marketed phytoestrogens, in particular soy-derived isoflavone products, under the perception of general health benefits, including presumably enhanced mental function. The goal of this exploratory research is to develop preliminary data regarding the efficacy of isoflavone phytoestrogens in producing improvement in cognitive function in late middle-aged and elderly postmenopausal women with symptoms of memory impairment and, therefore, increased risk for development of progressive dementia such as Alzheimer?s Disease. A secondary goal will be to examine changes in basal cortisol levels, as a means of assessing the effect of the intervention on an endocrine parameter that has significance for hippocampal function, particularly in the aged. We will administer a 16-week protocol of isoflavone supplementation in a randomized, double-blind, placebo-controlled study to menopausal women aged 55 to 75 years with forgetfulness and other symptoms of cognitive decline, but who do not meet criteria for probable dementia. We will assess changes in neuropsychological measures of executive function ability and episodic memory, in basal cortisol levels, and in mood. It is our expectation that the demonstration of positive responses to this intervention in this at-risk population will establish the basis for future, more comprehensive studies of dosage, mechanisms, and duration of effect. Ultimately, such research may establish the basis for the use of isoflavones as an alternative treatment that would provide mental and general health benefits without the risks associated with traditional hormone replacement therapies.
