***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Objectives : To investigate the cognitive effects of high-dose oral estrogen alone or in combination with oral methyltestosterone in postmenopausal women . Methods : Participants were tested with a r and omized , double-blind design on the Identical Pictures , Cube Comparisons , Building Memory and Shape Memory tasks before and after 4 months of hormone treatment . Results : Women receiving estrogen and methyltestosterone maintained a steady level of performance on the Building Memory task , whereas those receiving estrogen alone showed a decrease in performance . Conclusions : These results indicate that the addition of testosterone to high-dose estrogen replacement exerts a protective effect on memory performance in postmenopausal women In the last ten years , numerous mechanisms by which sex steroids modify cortical function have been described . For example , estrogen replacement improves verbal memory in women , and animal studies have shown effects of estrogen on hippocampal synaptogenesis and function . Little is known about sex steroid effects on other aspects of memory , such as frontal lobe-mediated working memory . We examined the relationships between working memory and sex steroid concentrations and whether sex steroid supplementation would modify age-related loss of working memory in older men and women . Before hormone supplementation , working memory , tested with the Subject Ordered Pointing Test ( SOP ) , was worse in older subjects than younger subjects , and there was no evidence of gender differences at either age . Testosterone supplementation  improved working memory in older men , but a similar enhancement of working memory was not found in older women supplemented with estrogen . In men , testosterone and estrogen effects were reciprocalwith better working memory related to a higher testosterone to estrogen ratio . These results suggest that sex steroids can modulate working memory in men and can act as modulators of cognition throughout life The present r and omized double blind study investigated the effects of a 2 week transdermal estradiol treatment on memory performance in 38 healthy elderly women .  Cognitive performance was tested at baseline and after 2 weeks of estradiol or placebo treatment using verbal , semantic , and spatial memory tests as well as a mental rotation task and the Stroop . Initial results showed no differences after treatment between placebo or estradiol treated subjects . However , within treatment group analysis revealed that estradiol treated subjects who reached higher estradiol levels ( larger than 29 pg/ml ) performed significantly better after treatment in the delayed recall of the paired associate test ( verbal memory ) than subjects who reached lower estradiol levels ( P < 0.05 ) . A nonsignificant trend was observed for the immediate recall condition ( P < 0.10 ) . These findings were strengthened by correlations between treatment-induced estradiol levels and changes in verbal memory performance . In addition , there was an association between estradiol levels and mood changes . However mood changes were not significantly associated with changes in verbal memory performance ( P > 0.20 ) . The present study supports the idea that estradiol replacement has specific effects on verbal memory in healthy postmenopausal women , with delayed recall being more affected . It suggests that these effects can occur relatively rapidly , and that there may be a dose response relationship of estradiol to memory enhancement . Furthermore , the fact that these results were obtained in women who had been menopausal for an average of 17 years before entering the study indicates that the brain maintains a sensitivity for estrogens even after years of low estradiol plasma concentrations Although several studies have examined the effects of estrogen replacement therapy ( ERT ) on neural activity associated with tasks of learning and memory , no study has examined such effects on a sustained attention task . This study examined the effect of low-dose estrogen replacement therapy on hemodynamic activity elicited by a visual three-stimulus oddball task recorded using event-related functional magnetic resonance imaging ( fMRI ) . Participants included 16 women between the ages of 73 and 84 who were part of a r and omized controlled double-blind study to evaluate the effect of an ultralow dose micronized estradiol on bone . No significant differences in behavioral performance were found with ERT . However , there was evidence that ERT group participants had both reductions and increases in the amplitude of hemodynamic response in a variety of subcortical and cortical brain regions . These included regions involved in perception and attention such as the occipital and parietal lobes , motor cortex , anterior cingulate and prefrontal cortex . These findings suggest that estrogen may facilitate the efficiency of brain function during the performance of sustained attention tasks in post-menopausal elderly women Estrogen has been shown to interact with the cholinergic system and influence cognition in animal models . This study investigated the interaction of estrogen and cholinergic system functioning and the effects of this interaction on cognitive task performance in healthy older women . Fifteen post-menopausal women were r and omly and blindly placed on 1 mg of 17-β estradiol or placebo for 3 months after which they participated in five anticholinergic challenge sessions , where they were administered one of two doses of the antimuscarinic drug scopolamine ( SCOP ) or the antinicotinic drug mecamylamine ( MECA ) or placebo . After the first challenge phase , they were crossed over to the other hormone treatment for another 3 months and repeated the challenges . Performance in multiple domains of cognition was assessed during anticholinergic drug challenge , including attention and verbal and nonverbal learning and memory . Results showed that estrogen pretreatment attenuated the anticholinergic drug-induced impairments on tests of attention and tasks with speed components . This study is the first to demonstrate the interaction of estrogen and the cholinergic system and the effects on cognitive performance in humans . The results suggest that estrogen status may affect cholinergic system tone and may be important for cholinergic system integrity Objective : To examine how menopausal symptoms and estrogen therapy (ET)-induced symptom relief affect cognition in early menopause . Design : : There were two components . Part 1 was a cross-sectional study of 37 healthy , recently postmenopausal women with diverse menopausal symptoms . Women were categorized as having low ( n = 20 ) or high symptoms ( n = 17 ) based on a vali date d symptom question naire . Women completed mood and sleep question naires and underwent cognitive testing , which included verbal memory , visual memory , emotional memory , and verbal fluency . Thirty-two of these women went on to part 2 of the study . Fourteen were r and omly assigned to receive ET and 18 to receive placebo for 8 weeks . Before treatment and at 4 and 8 weeks , women completed the same measures as in part 1 of the study . Results : High symptom women had more negative mood ( P = 0.01 ) and lower quality sleep ( P < 0.001 ) than low symptom women . Despite suffering from more menopausal symptoms , worse mood , and poorer sleep , women in the high symptom group performed the same on cognitive testing as women in the low symptom group . Women receiving ET had greater improvements in menopausal symptoms and sleep compared with those receiving the placebo ( P ≤ 0.05 ) . ET did not improve mood  compared with placebo . Women receiving ET did not have any improvement in cognitive performance compared with those receiving the placebo . Conclusions : Menopausal symptoms do not impair cognition . ET does not improve cognition despite alleviating symptoms and improving sleep in recently naturally menopausal women with diverse menopausal symptoms Objective : To investigate the risk of AD associated with a family history of dementia , female gender , low levels of education , smoking , and head trauma . Background : These putative factors have been identified in cross-sectional studies . However , those studies are prone to bias due to systematic differences between patients and control subjects regarding survival and how risk factors are recalled . Methods : The authors performed a pooled analysis of four European population -based prospect i ve studies of individuals 65 years and older , with 528 incident dementia patients and 28,768 person-years of follow-up . Patients were detected by screening the total cohort with brief cognitive tests , followed by a diagnostic assessment of those who failed the screening tests . Dementia was diagnosed with the Diagnostic and Statistical Manual of Mental Disrders , 3rd ed . ( revised ) , and AD was diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke – Alzheimer ’s Disease and Related Disorders Association criteria . Incident rates and relative risk ( 95 % CI ) express the association of a risk factor for dementia . Results : Incident rates for dementia and AD were similar across studies . The incidence of AD increased with age . At 90 years of age and older the incidence was 63.5 ( 95 % CI , 49.7 to 81.0 ) per 1,000 person-years . Female gender , current smoking ( more strongly in men ) , and low levels of education ( more strongly in women ) increased the risk of AD significantly . A history of head trauma with unconsciousness and family history of dementia did not increase risk significantly . Conclusion : Contrary to previous reports , head trauma was not a risk factor for AD , and smoking did not protect against AD . The association of family history with the risk of AD is weaker than previously estimated on the basis of cross-sectional studies . Female gender may modify the risk of AD , whether it be via biological or behavioral factors The potential role of estrogen in protecting women from cognitive decline and reducing depressive symptoms is of great therapeutic interest . In a pilot r and omised placebo controlled cross-over study , we aim ed to determine the short-term effects of transdermal estradiol therapy on cognition and depressive symptoms in healthy cognitively normal post-menopausal women over 60 years of age . Nineteen cognitively normal women , without clinical depression whom had undergone a hysterectomy in the past were recruited . Women were r and omised to receive either transdermal estradiol 50 microg/24 h ( Femseven ) or transdermal placebo for 12 weeks before crossing over to the other medication for a further 12 weeks . Cognition was assessed every 6 weeks by the cognitive drug research ( CDR ) computerised assessment which recorded both accuracy and speed in the following cognitive tests ; simple reaction time , choice reaction time , digit vigilance , visual tracking , spatial working memory , immediate and delayed word recall and delayed face and picture recall . Depressive symptoms were measured using the brief assessment scale depression card ( BASDEC ) depression rating scale at baseline , 12 and 24 weeks . Participants had a mean age of 71 , IQ of 115 and MMSE of 29 .  Simple reaction time and the BASDEC depression rating scale improved after 12 weeks of estradiol use . All other tests were unaltered by estradiol . Twelve weeks of transdermal estradiol therapy did not consistently improve the speed or accuracy of older women in various cognitive tests . However , the results do support the concept that depressive symptoms may be reduced by estradiol , and not simply due to the relief of climacteric symptoms The effects of estrogen ( E ) on memory were assessed in 19 women who required a hysterectomy and bilateral oophorectomy for benign disease . Blood sample s were drawn and memory tests were administered before surgery and again after 2 mo of postoperative treatment consisting of either monthly E or placebo ( PL ) injections . Scores on the immediate and delayed recall of paired-associates stayed at the same level in E-treated women , whereas they decreased significantly pre- to post-operatively in the PL-treated subjects . In the immediate recall of paragraphs , the scores of those given E improved postoperatively compared to baseline ; scores remained unchanged in the PL group . No hormonal effects were apparent on the immediate or delayed recall of visual material , delayed recall of paragraphs , or digit span scores . These findings suggest that variations in specific aspects of memory function may occur in surgically menopausal women coincident with changes in plasma estrone and estradiol levels CONTEXT Some studies of hormone treatment in postmenopausal women suggest benefits on specific cognitive functions , particularly memory . OBJECTIVE The objective of this study was to determine whether hormone therapy influences changes in specific cognitive functions and affect in older women . DESIGN This study was a r and omized , double-blind , placebo-controlled clinical trial . SETTING Participants were women from 14 of 40 clinical centers of the Women 's Health Initiative ( WHI ) . PARTICIPANTS Postmenopausal women ( 1416 ) aged 65 yr and older , free of probable dementia , and enrolled in WHI and the WHI Memory Study ( WHIMS ) trial of combination estrogen and progestin for a mean of 3 yr and followed for a mean of 1.35 yr , were studied . INTERVENTION Intervention was conjugated equine estrogen ( CEE ; 0.625 mg ) with 2.5 mg medroxyprogesterone acetate ( MPA ) in one daily tablet ( CEE + MPA ) or placebo . MAIN OUTCOME MEASURES Annual rates of change in specific cognitive functions and affect , adjusted for time since r and omization , were measured . RESULTS CEE + MPA had a negative impact on verbal memory ( P < or= 0.01 ) and a trend to a positive impact on figural memory ( P = 0.012 ) over time compared with placebo , but other cognitive domains were not affected . Both effects on memory were evident only after long-term therapy . CEE + MPA did not significantly influence positive affect , negative affect , or depressive symptoms . CONCLUSIONS The effect of CEE + MPA on cognitive function varies across cognitive domains in older women , reflecting both possible beneficial and detrimental actions of ovarian steroids on the aging brain . Our results extend prior findings about dementia and global cognitive function to age-related changes in specific cognitive functions and suggest directions for future research During a double-blind comparison of menopausal replacement therapy with estrogen alone compared with estrogen plus methyltestosterone ( me 
    Output:
    
There is good evidence that both ERT and HRT do not prevent cognitive decline in older postmenopausal women when given as short term or longer term ( up to five years ) therapy .
It is not known whether either specific types of ERT or HRT have specific effects in subgroups of women , although there was evidence that combined hormone therapy in similarly aged women was associated with a decrement in a number of verbal memory tests and a small improvement in a test of figural memory .
There is insufficient evidence to determine whether subgroups of women using specific types of hormone therapy could benefit from treatment .
In the meantime , based on the available evidence , ERT or HRT can not be recommended for overall cognitive improvement or maintenance in older postmenopausal women without cognitive impairment