At least 10% of persons over 65 years old and 50% of persons over 85 years old have some form of cognitive impairment ranging from mild deficits to dementia (Evans, 1990). Alzheimer's disease (AD), the most common cause of dementia, is estimated to affect 4 million people in the United States and to cost $70 billion annually (Ernst & Hay, 1994). AD affects women disproportionately to men with women having a slightly higher increased risk of AD, even after adjusting for age (Payami et al., 1996a, b). Despite the severity and prevalence of dementia and mild cognitive impairment, there are few effective treatments or prevention strategies.
Recent studies have suggested that postmenopausal estrogen therapy might improve cognition in nondemented perimenopausal and postmenopausal women, that it might prevent the development of dementia, or that it might improve the severity of dementia. While less studied, interest is growing in the role of testosterone in cognition and dementia treatment. In this chapter, the basic science on sex hormones and cognition, the clinical studies of estrogen for the prevention and treatment of dementia, and the studies of testosterone and cognitive function are reviewed.
Possible biological mechanisms of estrogen's effect on cognition
Estrogen receptors are found in the hypothalamus, the preoptic area, the anterior pituitary, the CA1 region of the hippocampus, and several other brain regions (McEwen & Woolley, 1994). How estrogens may affect neuropsychologic function remains unknown, but several mechanisms have been suggested. One mechanism is the modulation of neurotransmitters, particularly acetylcholine.