• Eva Hogervorst, Kristine Yaffe, Marcus Richards, and Felicia A H Huppert.
• Department of Human Sciences, Loughborough University, Loughborough, Leicestershire, UK, LE11 3TU. E.Hogervorst@lboro.ac.uk
• Cochrane Db Syst Rev. 2009 Jan 21; 2009 (1): CD003799CD003799.

BackgroundAs estrogens have been shown to have several potentially beneficial effects on the central nervous system, it is biologically plausible that maintaining high levels of estrogens in postmenopausal women by means of estrogen replacement therapy (ERT) could be protective against cognitive decline in women with Alzheimer's disease (AD) or other dementia syndromes.ObjectivesTo investigate the effects of ERT (estrogens only) or HRT (estrogens combined with a progestagen) compared with placebo in randomized controlled trials (RCTs) on cognitive function of postmenopausal women with dementia.Search StrategyThe Cochrane Dementia and Cognitive Improvement Group Specialized Register, which contains records from many medical databases, The Cochrane Library, EMBASE, MEDLINE, CINAHL, PsycINFO and LILACS were searched on 7 November 2007 using the terms ORT, PORT, ERT, HRT, estrogen*, oestrogen* and progesterone*.Selection CriteriaAll double-blind randomized controlled trials (RCTs) into the effect of ERT or HRT for cognitive function with a treatment period of at least two weeks in postmenopausal women with AD or other types of dementia.Data Collection And AnalysisAbstracts of the references retrieved by the searches were read by two reviewers (EH and KY) independently in order to discard those that were clearly not eligible for inclusion. The two reviewers studied the full text of the remaining references and independently selected studies for inclusion. Any disparity in the ensuing lists was resolved by discussion with all reviewers in order to arrive at the final list of included studies. The selection criteria ensured that the blinding and randomization of the included studies was adequate. The two reviewers also assessed the quality of other aspects of the included trials. One reviewer (EH) extracted the data from the studies, but was aided and checked by JB from Cochrane.Main ResultsA total of seven trials including 351 women with AD were analysed. Because different drugs were used at different studies it was not possible to combine more than two studies in any analysis.On a clinical global rating, clinicians scored patients taking CEE as significantly worse compared with the placebo group on the Clinical Dementia Rating scale after 12 months (overall WMD = 0.35, 95% CI = 0.01 to 0.69, z = 1.99, P < 0.05).Patients taking CEE had a worse performance on the delayed recall of the Paragraph Test (overall WMD = -0.45, 95% CI = -0.79 to -0.11, z = 2.60, P < 0.01) after one month than those taking placebo. They had a worse performance on Finger Tapping after 12 months (WMD = -3.90, 95% CI = -7.85 to 0.05, z = 1.93, P < 0.05).Limited positive effects were found for the lower dosage of CEE (0.625 mg/day) which showed a significant improvement in MMSE score only when assessed at two months, and disappeared after correction for multiple testing. No significant effects for MMSE were found at longer end points (3, 6 and 12 months of treatment). With a dosage of 1.25 mg/d CEE, short-term significant effects were found for Trial-Making test B at one month and Digit Span backward at four months. After two months of transdermal diestradiol (E2) treatment, a highly significant effect was observed for the word recall test (WMD = 6.50, 95% CI = 4.04 to 8.96, z = 5.19, P < 0.0001). No other significant effects were found for other outcomes measured.Authors' ConclusionsCurrently, HRT or ERT for cognitive improvement or maintenance is not indicated for women with AD.

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