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Biochemical and neurophysiologic studies suggest several mechanisms by which estrogen may affect cognition:promotion of cholinergic and serotonergic activity in specific brain regions,maintenance of neural circuitry,favorable lipoprotein alterations,and prevention of cerebral ischemia.Five observational studies and 8 trials have addressed the effect of estrogen on cognitive function in nondemented postmenopausal women. Cognition seems to improve in perimenopausal women,possibly because menopausal symptoms improve,but there is no clear benefit in asymptomatic women.Ten observational studies have measured the clear benefit in asymptomatic women.Ten observational studies have measured the effect of postmenopausal estrogen use on risk of developing dementia.Meta analysis of these studies suggests a 29%decreased risk of developing dementia among estrogen users,but the findings of the studies are heterogeneous.Four trials of estrogen therapy in women with Alzheimer disease have been conducted and have had primarily positive results,but most have been small,of short duration,nonrandomized,and uncontrolled.There are plausible biological mechanisms by which estrogen might lead to improved cognition, reduced risk for dementia,or improvement in the severity of dementia. Studies conducted in women,however,have substantial methodologic problems and have produced conflicting results.Large placebo controlled trials are required to address estrogen's role in prevention and treatment of Alzheimer disease and other dementias.Given the knows risks of estrogen therapy,we do not recommend estrogen for the prevention or treatment of Alzheimer disease or other dementias until adequate trials have been completed. |
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