Estrogen, Cognition, and a Woman’s Risk of Alzheimer’s Disease

Alzheimer’s disease affects women more often than men, and women with this form of dementia show greater naming (semantic memory) deficits during the course of their illness. Gonadal steroids exert organizational and activational effects on central nervous system neurons and influence brain function in other important ways. Several estrogenic actions are potentially relevant to Alzheimer’s disease, and it is hypothesized that one consequence of estrogen deprivation after the menopause is a higher risk of this dementing disorder. In healthy women without dementia, estrogen may enhance cognitive performance, especially in the domain of verbal memory, although the magnitude of such effects is small. Several small treatment trials of estrogen replacement in women with Alzheimer’s disease, however, suggest that estrogen’s effects on cognition could be larger in this population and may be most apparent on tasks of semantic memory. Analyses in voluntary cohorts associate postmenopausal estrogen replacement therapy with a lower risk of subsequent Alzheimer’s disease. In 3 recent epidemiologic studies, information on postmenopausal estrogen use was collected prospectively; while inconclusive, findings raise the possibility that postmenopausal estrogen replacement reduces a woman’s risk of subsequent dementia. New information from basic research and from large randomized treatment studies, cohort studies, and case-control studies is needed to resolve important unanswered clinical issues.