***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 : The Alzheimer 's Disease Anti-inflammatory Prevention Trial ( ADAPT ) was design ed to evaluate the conventional NSAID naproxen sodium and the selective COX-2 inhibitor celecoxib for primary prevention of Alzheimer 's dementia ( AD ) . On 17 December 2004 , after the Adenoma Prevention with Celecoxib ( APC ) trial reported increased cardiovascular risks with celecoxib , the ADAPT Steering Committee suspended treatment and enrollment . This paper reports on cardiovascular and cerebrovascular events in ADAPT . Design : ADAPT is a r and omized , placebo-controlled , parallel chemoprevention trial with 1–46 mo of follow-up . Setting : The trial was conducted at six field sites in the United States : Baltimore , Maryl and ; Boston , Massachusetts ; Rochester , New York ; Seattle , Washington ; Sun City , Arizona ; and Tampa , Florida . Participants : The 2,528 participants were aged 70 y and older with a family history of AD . Interventions : Study treatments were celecoxib ( 200 mg b.i.d . ) , naproxen sodium ( 220 mg b.i.d . ) , and placebo . Outcome measures : Outcome measures were deaths , along with nonfatal myocardial infa rct ion ( MI ) , stroke , congestive heart failure ( CHF ) , transient ischemic attack ( TIA ) , and antihypertensive treatment recorded from structured interviews at scheduled intervals . Cox proportional hazards regression was used to analyze these events individually and in several composites . Results : Counts ( with 3-y incidence ) of participants who experienced cardiovascular or cerebrovascular death , MI , stroke , CHF , or TIA in the celecoxib- , naproxen- , and placebo-treated groups were 28/717 ( 5.54 % ) , 40/713 ( 8.25 % ) , and 37/1070 ( 5.68 % ) , respectively . This yielded a hazard ratio ( 95 % confidence interval [ CI ] ) for celecoxib of 1.10 ( 0.67–1.79 ) and for naproxen of 1.63 ( 1.04–2.55 ) . Antihypertensive treatment was initiated in 160/440 ( 47.43 % ) , 147/427 ( 45.00 % ) , and 164/644 ( 34.08 % ) . This yielded hazard ratios ( CIs ) of 1.56 for celecoxib ( 1.26–1.94 ) and 1.40 for naproxen ( 1.12–1.75 ) . Conclusions : For celecoxib , ADAPT data do not show the same level of risk as those of the APC trial . The data for naproxen , although not definitive , are suggestive of increased cardiovascular and cerebrovascular risk Background Menopausal hormone therapy ( MHT ) reportedly increases the risk of cognitive decline in women over age 65 y. It is unknown whether similar risks exist for recently postmenopausal women , and whether MHT affects mood in younger women . The ancillary Cognitive and Affective Study ( KEEPS-Cog ) of the Kronos Early Estrogen Prevention Study ( KEEPS ) examined the effects of up to 4 y of MHT on cognition and mood in recently postmenopausal women . Methods and Findings KEEPS , a r and omized , double-blinded , placebo-controlled clinical trial , was conducted at nine US academic centers . Of the 727 women enrolled in KEEPS , 693 ( 95.3 % ) participated in the ancillary KEEPS-Cog , with 220 women r and omized to receive 4 y of 0.45 mg/d oral conjugated equine estrogens ( o-CEE ) plus 200 mg/d micronized progesterone ( m-P ) for the first 12 d of each month , 211 women r and omized to receive 50 μg/d transdermal estradiol ( t-E2 ) plus 200 mg/d m-P for the first 12 d of each month , and 262 women r and omized to receive placebo pills and patches . Primary outcomes included the Modified Mini-Mental State examination ; four cognitive factors : verbal learning/memory , auditory attention/working memory , visual attention/executive function , and speeded language /mental flexibility ; and a mood measure , the Profile of Mood States ( POMS )  . MHT effects were analyzed using linear mixed-effects ( LME ) models , which make full use of all available data from each participant , including those with missing data . Data from those with and without full data were compared to assess for potential biases result ing from missing observations . For statistically significant results , we calculated effect sizes ( ESs ) to evaluate the magnitude of changes . On average , participants were 52.6 y old , and 1.4 y past their last menstrual period . By month 48 , 169 ( 24.4 % ) and 158 ( 22.8 % ) of the 693 women who consented for ancillary KEEPS-Cog were lost to follow-up for cognitive assessment ( 3MS and cognitive factors ) and mood evaluations ( POMS ) , respectively . However , because LME models make full use all available data , including data from women with missing data , 95.5 % of participants were included in the final analysis ( n = 662 in cognitive analyses , and n = 661 in mood analyses ) . To be included in analyses , women must have provided baseline data , and data from at least one post-baseline visit . The mean length of follow-up was 2.85 y ( st and ard deviation [ SD ] = 0.49 ) for cognitive outcomes and 2.76 ( SD = 0.57 ) for mood outcomes . No treatment-related benefits were found on cognitive outcomes . For mood , model estimates indicated that women treated with o-CEE showed improvements in depression and anxiety symptoms over the 48 mo of treatment , compared to women on placebo . The model estimate for the depression subscale was −5.36 × 10−2 ( 95 % CI , −8.27 × 10−2 to −2.44 × 10−2 ; ES = 0.49 , p < 0.001 ) and for the anxiety subscale was −3.01 × 10−2 ( 95 % CI , −5.09 × 10−2 to −9.34 × 10−3 ; ES = 0.26 , p < 0.001 ) . Mood outcomes for women r and omized to t-E2 were similar to those for women on placebo . Importantly , the KEEPS-Cog results can not be extrapolated to treatment longer than 4 y. Conclusions The KEEPS-Cog findings suggest that for recently postmenopausal women , MHT did not alter cognition as hypothesized . However , beneficial mood effects with small to medium ESs were noted with 4 y of o-CEE , but not with 4 y of t-E2 . The generalizability of these findings is limited to recently postmenopausal women with low cardiovascular risk profiles . Trial Registration Clinical Trials.gov NCT00154180 and BACKGROUND In postmenopausal women , estrogen may have a beneficial effect on cognition or reduce the risk of decline in cognitive function . Whether raloxifene , a selective estrogen-receptor modulator , might have similar actions is not known . METHODS As part of the Multiple Outcomes of Raloxifene Evaluation trial , we studied 7478 postmenopausal women with osteoporosis ( mean age , 66 years ) , who were enrolled at 178 sites in 25 countries . The women were r and omly assigned to receive raloxifene ( 60 mg or 120 mg ) or placebo daily for three years . We compared the mean scores of the groups on six tests of cognitive function , which were administered at base line and at six months and one , two , and three years . Women were classified as having a decline in cognitive function if the change in their scores at three years was in the worst 10 percent . RESULTS The mean cognitive scores in the three groups of women were similar at base line . The scores improved slightly in all three groups during the three-year study period , with no significant differences among the groups . The risk of decline in the cognitive function , as measured by four of the six tests , did not differ significantly between the two raloxifene groups combined and the placebo group , but there was a trend toward less decline in the combined raloxifene group on the two tests of verbal memory ( relative risk , 0.77 ) and attention , ( relative risk , 0.87 ) . Newly reported or worsening hot flashes did not negatively influence test scores or the effect of treatment on test performance . CONCLUSIONS Raloxifene treatment for three years does not affect overall cognitive scores in postmenopausal women with osteoporosis AIM To assess whether an intensive multifactorial treatment can reduce cognitive decrements and cognitive decline in screen-detected type 2 diabetes . METHODS The multinational ADDITION- study , a cluster-r and omized parallel group trial in patients with screen-detected type 2 diabetes , compared the effectiveness of intensive multifactorial treatment ( IT ; lifestyle advice and strict regulation of metabolic parameters ) with routine care ( RC ) on cardiovascular outcome . In The Netherl and s r and omization was stratified according to practice organization . Allocation was concealed from patients . The present study assessed the effect of IT on cognition through two  neuropsychological assessment s ( NPA ) on two occasions . The assessment s took place three and six years after the start of the intervention . Non-diabetic controls served as reference group . The first NPA was performed in 183 patients ( IT : 97 ; RC : 86 ) and 69 controls . The second NPA was performed in 135 patients ( IT : 71 ; RC : 64 ) and 55 controls . Primary outcome was a composite score , including the domains memory , information-processing speed and attention and executive function . Comparisons between the treatment groups were performed with multi-level analyses . RESULTS The first NPA showed no differences between the treatment groups ( mean difference composite z-score : 0.00 ; 95%-CI -0.16 to 0.16 ; IT vs RC ) . Over the next three years cognitive decline in the diabetic groups was within the range of the reference group and did not differ between the treatment arms ( difference decline between diabetic groups -0.12 ; -0.24 to 0.01 ; IT vs RC ) . CONCLUSIONS Six years of IT in screen-detected type 2 diabetes had no benefit on cognitive functioning over RC Reduction in testosterone levels in men during aging is associated with cognitive decline and risk of dementia . Animal studies have shown benefits for testosterone supplementation in improving cognition and reducing Alzheimer ’s disease pathology . In a r and omized , placebo-controlled , crossover study of men with subjective memory complaint and low testosterone levels , we investigated whether testosterone treatment significantly improved performance on various measures of cognitive functioning . Forty-four men were administered a battery of neuropsychological tests to establish the baseline prior to being r and omly divided into two groups . The first group ( Group A ) received 24 weeks of testosterone treatment ( T treatment ) followed by 4 weeks washout , and then 24 weeks of placebo ( P ) ; the second group ( Group B ) received the same treatments , in reverse order ( Placebo , washout , and then T treatment ) . In group A ( TèP ) , compared to baseline , there was a modest ( 1 point ) but significant improvement in general cognitive functioning as measured by the Mini Mental State Examination ( MMSE ) following testosterone treatment . This improvement from baseline was sustained following the washout period and crossover to placebo treatment . Similar Mini Mental State Examination ( MMSE ) scores were observed when comparing testosterone treatment with placebo . In group B ( PèT ) a significant increase was observed from baseline following testosterone treatment and a trend towards an increase when compared to placebo treatment . Improvements in baseline depression scores ( assessed by Geriatric Depression Scale ) were observed following testosterone/placebo treatment in both groups , and no difference was observed when comparing testosterone with placebo treatment . Our findings indicate a modest improvement on global cognition with testosterone treatment . Larger clinical trials with a longer follow- up and with the inclusion of blood and brain imaging markers are now needed to conclusively determine the significance of testosterone treatment Aims : To examine the effects of pioglitazone or endurance exercise training on cognitive function in older adults with mild cognitive impairment ( MCI ) and insulin resistance . Methods : Seventy-eight adults ( mean age ± SD : 65 ± 7 years ) with central obesity and MCI were r and omized to 6 months of endurance exercise , pioglitazone or control . Results : Sixty-six participants completed the study .  Exercise training did not significantly increase peak oxygen uptake compared to control ( p = 0.12 ) . Compared to control , insulin resistance improved in the pioglitazone group ( p = 0.002 ) but not in the exercise group ( p = 0.25 ) . There was no measureable effect of pioglitazone or exercise on cognitive performance compared to control . Conclusion : In this pilot study , pioglitazone  improved insulin resistance but not cognitive performance in older adults with MCI and insulin resistance No adverse effect upon cognitive function has been detected during the first 9 months of treatment by a thiazide diure 
    Output:
    
Participants who received donepezil were more likely to have adverse gastrointestinal symptoms , sleep disturbances , and arthritis .