***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 examine the association between hormone therapy ( HT ) and cognitive performance or dementia , focusing on the duration and type of treatment used , as well as the timing of initiation of HT in relation to the menopause . Methods : Women 65 years and older were recruited in France as part of the Three City Study . At baseline and 2- and 4-year follow-up , women were administered a short cognitive test battery and a clinical diagnosis of dementia was made . Detailed information was also gathered relating to current and past HT use . Analysis was adjusted for a number of sociodemographic , behavioral , physical , and mental health variables , as well as APOE ε4 . Results : Among 3,130 naturally postmenopausal women , current HT users performed significantly better than never users  on verbal fluency , working memory , and psychomotor speed . These associations varied according to the type of treatment and a longer duration of HT appeared to be more beneficial . However , initiation of HT close to the menopause was not associated with better cognition . HT did not significantly reduce dementia risk over 4 years but current treatment diminished the negative effect associated with APOE ε4 . Conclusions : Current hormone therapy ( HT ) was associated with better performance in certain cognitive domains but these associations are dependent on the duration and type of treatment used . We found no evidence that HT needs to be initiated close to the menopause to have a beneficial effect on cognitive function in later life . Current HT may decrease the risk of dementia associated with the APOE ε4 allele We estimated the remaining lifetime risks of developing Alzheimer 's disease ( AD ) and dementia from all causes , based on data from longitudinal population studies . The risk of developing AD during one 's lifetime depends on both disease incidence and life expectancy . Conventional estimates of cumulative incidence overestimate the risk when there is a substantial probability of mortality due to competing causes . A total of 2,611 cognitively intact subjects ( 1,061 men , 1,550 women ; mean age , 66± 7 years ) were prospect ively evaluated for the development of AD or other dementia . A modified survival analysis was used to estimate both cumulative incidence and the sex-specific remaining lifetime risk estimates for quinquennial age groups above age 65 years . Over a 20-year follow-up period , 198 subjects developed dementia ( 120 with AD ) .  The remaining lifetime risk of AD or other dementia depended on sex , being higher in women , but varied little with age between 65 and 80 years . In a 65-year-old man , the remaining lifetime risk of AD was 6.3 % ( 95 % CI , 3.9 to 8.7 ) and the remaining lifetime risk of developing any dementing illness was 10.9 % ( 95 % CI , 8.0 to 13.8 ) ; corresponding risks for a 65-year-old woman were 12 % ( 95 % CI , 9.2 to 14.8 ) and 19 % ( 95 % CI , 17.2 to 22.5 ) . The cumulative incidence between age 65 and 100 years was much higher : for AD , 25.5 % in men and 28.1 % in women ; for dementia , 32.8 % in men and 45 % in women . The actual remaining lifetime risk of AD or dementia varies with age , sex , and life expectancy and is lower than the hypothetical risk estimated by a cumulative incidence in the same population CONTEXT Postmenopausal women have a greater risk than men of developing Alzheimer disease , but studies of the effects of estrogen therapy on Alzheimer disease have been inconsistent . On July 8 , 2002 , the study drugs , estrogen plus progestin , in the Women 's Health Initiative ( WHI ) trial were discontinued because of certain increased health risks in women receiving combined hormone therapy . OBJECTIVE To evaluate the effect of estrogen plus progestin on the incidence of dementia and mild cognitive impairment compared with placebo . DESIGN , SETTING , AND PARTICIPANTS The Women 's Health Initiative Memory Study ( WHIMS ) , a r and omized , double-blind , placebo-controlled clinical trial , began enrolling participants from the Women 's Health Initiative ( WHI ) estrogen plus progestin trial in May 1996 . Of the 4894 eligible participants of the WHI study , 4532 ( 92.6 % ) postmenopausal women free of probable dementia , aged 65 years or older , and recruited from 39 of 40 WHI clinical centers were enrolled in the WHIMS . INTERVENTION Participants received either 1 daily tablet of 0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate ( n = 2229 ) , or a matching placebo ( n = 2303 ) . MAIN OUTCOME MEASURES Incidence of probable dementia ( primary outcome ) and mild cognitive impairment ( secondary outcome ) were identified through a structured clinical assessment . RESULTS The mean ( SD ) time between the date of r and omization into WHI and the last Modified Mini-Mental State Examination ( 3MSE ) for all WHIMS participants was 4.05 ( 1.19 ) years . Overall , 61 women were diagnosed with probable dementia , 40 ( 66 % ) in the estrogen plus progestin group compared with 21 ( 34 % ) in the placebo group . The hazard ratio ( HR ) for probable dementia was 2.05 ( 95 % confidence interval [ CI ] , 1.21 - 3.48 ; 45 vs 22 per 10 000 person-years ; P = .01 ) . This increased risk would result in an additional 23 cases of dementia per 10 000 women per year . Alzheimer disease was the most common classification of dementia in both study groups . Treatment effects on mild cognitive impairment did not differ between groups ( HR , 1.07 ; 95 % CI , 0.74 - 1.55 ; 63 vs 59 cases per 10 000 person-years ; P = .72 ) . CONCLUSIONS Estrogen plus progestin therapy increased the risk for probable dementia in postmenopausal women aged 65 years or older . In addition , estrogen plus progestin therapy did not prevent mild cognitive impairment in these women . These findings , coupled with previously reported WHI data , support the conclusion that the risks of estrogen plus progestin outweigh the benefits OBJECTIVES The current study investigated the neurotrophic and neuroprotective action of the complex formulation of conjugated equine estrogens ( CEEs ) , the most frequently prescribed estrogen replacement therapy in the United States and the estrogen replacement therapy of the Women 's Health Initiative . METHODS Videomicroscopic , morphologic and biochemical analyses were conducted in primary cultures of hippocampal neurons to determine the neurotrophic and neuroprotective properties of CEEs . RESULTS Results of these analyses demonstrated that CEEs significantly increased hippocampal neuronal outgrowth , a cellular marker of memory formation . Dose response analyses indicated that the lowest effective concentration of CEEs exerted the maximal neurotrophic effect . Results of neuroprotection studies demonstrated that CEES induced highly significant neuroprotection against beta amyloid(25 - 35 ) , hydrogen peroxide and glutamate-induced toxicity . CONCLUSIONS CEEs induced cellular markers of memory function in neurons critical to memory and vulnerable to negative effects of aging and Alzheimer 's disease . In addition , CEEs significantly and potently protected neurons against toxic insults associated with Alzheimer 's disease . Because CEEs are the estrogen replacement therapy of the Women 's Health Initiative , results of the current study could provide cellular mechanisms for effects of CEEs on cognitive function and risk of Alzheimer 's disease derived from this prospect i ve clinical trial A prospect i ve analysis of risk factors for Alzheimer 's disease was a major objective of the Canadian Study of Health and Aging , a nationwide , population -based study . Of 6,434 eligible subjects aged 65 years or older in 1991 , 4,615 were alive in 1996 and participated in the follow-up study . All participants were cognitively normal in 1991 when they completed a risk factor question naire . Their cognitive status was reassessed 5 years later by using a similar two-phase procedure , including a screening interview , followed by a clinical examination when indicated . The analysis included 194 Alzheimer 's disease cases and 3,894 cognitively normal controls . Increasing age , fewer years of education , and the apolipoprotein E epsilon4 allele were significantly associated with increased risk of Alzheimer 's disease . Use of nonsteroidal anti-inflammatory drugs  ,  wine consumption , coffee consumption  , and  regular physical activity  were associated with a reduced risk of Alzheimer 's disease . No statistically significant association was found for family history of dementia , sex , history of depression , estrogen replacement therapy , head trauma , antiperspirant or antacid use , smoking , high blood pressure , heart disease , or stroke . The protective associations warrant further study . In particular , regular physical activity could be an important component of a preventive strategy against Alzheimer 's disease and many other conditions Over the past two decades , there has been a significant amount of research investigating the risks and benefits of hormone replacement therapy ( HRT ) with regards to neurodegenerative disease . Here , we review basic science studies , r and omized clinical trials , and epidemiological studies , and discuss the putative neuroprotective effects of HRT in the context of Alzheimer 's disease , Parkinson 's disease , frontotemporal dementia , and HIV-associated neurocognitive disorder . Findings to date suggest a reduced risk of Alzheimer 's disease and improved cognitive functioning of postmenopausal women who use 17β-estradiol .  With regards to Parkinson 's disease , there is consistent evidence from basic science studies for a neuroprotective effect of 17β-estradiol ; however , results of clinical and epidemiological studies are inconclusive at this time , and there is a paucity of research examining the association between HRT and Parkinson's-related neurocognitive impairment . Even less understood are the effects of HRT on risk for frontotemporal dementia and HIV-associated neurocognitive disorder . Limits to the existing research are discussed , along with proposed future directions for the investigation of HRT and neurodegenerative diseases 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 Background : Cross-sectional studies suggest gender differences in cognitive function and risk of AD in older persons . However , longitudinal studies comparing change in cognitive function and risk of AD in men and women have had mixed results . The authors investigated gender differences in rate of decline for different cognitive systems and for risk of developing AD . Methods : Participants were from the Religious Orders Study , a longitudinal , clinical –pathologic study of aging and AD in older Catholic nuns , priests , and brothers . Longitudinal data were available from 577 older women and 271 older men , who completed an average of 5.8 annual evaluations with more than 95 % follow-up participation in survivors . The evaluations included 21 neuropsychological tests  , from which summary measures of global cognitive function and 5 functional domains were formed , and clinical classification of AD . Results : R and om effects models were used to analyze change in cognitive function , and proportional hazards models were used to assess risk of incident AD . On average , men and women declined in all abilities during the 8-year period but did not differ in annual rates of change in analyses that controlled for age , education , and initial level of cognitive function . Risk of incident AD did not differ between men and women . Furthermore , results were unchanged after controlling for possession of the apolipoprotein- 
    Output:
    
Our findings support current recommendations that hormone therapy should not be used for dementia prevention .