Can estrogen play a significant role in the prevention of Alzheimer's disease?

Abstract

In women the abrupt decline estrogen levels at menopause may be associated with cognitive deficits and increased risk for Alzheimer's disease (AD); estrogen replacement therapy may reduce this risk. Animal studies indicate that estrogen modulates neurotransmitter systems, regulates synaptogenesis, and is neuroprotective. These beneficial effects occur in brain areas critical to cognitive function and involved in AD. Reduced estrogen levels can compromise neuronal function and survival. Estrogen replacement therapy can reverse cognitive deficits associated with low estrogen levels and may reduce the risk of AD. However, clinical trials for estrogen replacement in the treatment of AD have produced ambiguous results. Initial, small, open-label and double blind clinical trials indicated improved cognitive function in women with AD. Recent large trials failed to show a beneficial effect for long-term estrogen replacement for women with AD. There are several variables that could affect these results, such as genetic factors, time between estrogen loss and replacement, extent and types of AD pathology, and other environmental and health factors. Presently large prospective studies are being conducted as the National Institutes of Health in the Women's Health Initiative and the Preventing Postmenopausal Memory Loss and Alzheimer's with Replacement Estrogens studies to provide a better assessment of the role of estrogen for age related health issues, including dementia.