***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: Introduction There are no empiric data to support guidelines for duration of therapy with antidementia drugs . This study examined whether persistent use of antidementia drugs  slows clinical progression of Alzheimer disease ( AD ) assessed by repeated measures on serial tests of cognition and function . Methods Six hundred forty-one probable AD patients were followed prospect ively at an academic center over 20 years . Cumulative drug exposure was expressed as a persistency index ( PI ) reflecting total years of drug use divided by total years of disease symptoms . Baseline and annual testing consisted of  Mini-Mental State Examination ( MMSE ) , Alzheimer 's Disease Assessment Scale-Cognitive Subscale ( ADAS-Cog ) , Baylor Profound Mental Status Examination ( BPMSE ) , Clinical Dementia Rating-Sum of Boxes ( CDR-SB ) , Physical Self-Maintenance Scale ( PSMS ) , and Instrumental Activities of Daily Living ( IADL ) . Annual change in slope of neuropsychological and functional tests as predicted by follow-up time , PI , and the interaction of these two variables was evaluated . Results PI was associated with significantly slower rates of decline ( with , without adjustment for covariates ) on MMSE ( P < 0.0001 ) , PSMS ( P < 0.05 ) , IADL ( P < 0.0001 ) , and CDR-SB ( P < 0.001 ) . There was an insignificant trend ( P = 0.053 ) for the PI to be associated with slower rate of decline on BPMSE . The association of PI with ADAS-Cog followed a quadratic trend ( P < 0.01 ) . Analysis including both linear and quadratic terms suggests that PI slowed ADAS-Cog decline temporarily . The magnitude of the favorable effect of a rate change in PI was : MMSE 1 point per year , PSMS 0.4 points per year , IADL 1.4 points per year , and CDR-SB 0.6 points per year . The change in mean test scores is additive over the follow-up period ( 3 ± 1.94 years ) . Conclusions Persistent drug treatment had a positive impact on AD progression assessed by multiple cognitive , functional , and global outcome measures . The magnitude of the treatment effect was clinical ly significant . Positive treatment effects were even found in those with advanced disease Background : Moderate vitamin B-12 deficiency is relatively common in older people . However , there is little robust evidence on the effect of vitamin B-12 supplementation on neurologic and cognitive outcomes in later life . Objective : We investigated whether vitamin B-12 supplementation benefits neurologic and cognitive function in moderately vitamin B-12–deficient older people . Design : We conducted a double-blind , r and omized , placebo-controlled trial in 7 general practice s in South East Engl and , United Kingdom . Study participants were aged ≥75 y and had moderate vitamin B-12 deficiency ( serum vitamin B-12 concentrations : 107–210 pmol/L ) in the absence of anemia and received 1 mg crystalline vitamin B-12 or a matching placebo as a daily oral tablet for 12 mo . Peripheral motor and sensory nerve conduction , central motor conduction , a clinical neurologic examination , and cognitive function were assessed before and after treatment . Results : A total of 201 participants were enrolled in the trial , and 191 subjects provided outcome data . Compared with baseline , allocation to vitamin B-12 was associated with a 177 % increase in serum concentration of vitamin B-12 ( 641 compared with 231 pmol/L ) , a 331 % increase in serum holotranscobalamin ( 240 compared with 56 pmol/L ) , and 17 % lower serum homocysteine ( 14.2 compared with 17.1 μmol/L ) . In intention-to-treat analysis of covariance models , with adjustment for baseline neurologic function , there was no evidence of an effect of supplementation on the primary outcome of the posterior tibial compound muscle action potential amplitude at 12 mo ( mean difference : −0.2 mV ; 95 % CI : –0.8 , 0.3 mV ) . There was also no evidence of an effect on any secondary peripheral nerve or central motor function outcome , or on cognitive function or clinical examination . Conclusion : Results of the trial do not support the hypothesis that the correction of moderate vitamin B-12 deficiency , in the absence of anemia and of neurologic and cognitive signs or symptoms , has beneficial effects on neurologic or cognitive function in later life . This trial was registered at www.is rct n.com as IS RCT N54195799 Purpose To prospect ively evaluate the association of vitamin/mineral supplementation with  cancer , cardiovascular , and all-cause mortality .  Methods In the Heidelberg cohort of the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC-Heidelberg ) , which was recruited in 1994–1998 , 23,943 participants without pre-existing cancer and myocardial infa rct ion/stroke at baseline were included in the analyses . Vitamin/mineral supplementation was assessed at baseline and during follow-up . Cox regression models were used to estimate hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) . Results After an average follow-up time of 11 years , 1,101 deaths were documented ( cancer deaths = 513 and cardiovascular deaths = 264 ) . After adjustment for potential confounders , neither any vitamin/mineral supplementation nor multivitamin supplementation at baseline was statistically significantly associated with cancer , cardiovascular , or all-cause mortality . However , baseline users of antioxidant vitamin supplements had a significantly reduced risk of cancer mortality ( HR : 0.52 ; 95 % CI : 0.28 , 0.97 ) and all-cause mortality ( HR : 0.58 ; 95 % CI : 0.38 , 0.88 ) . In comparison with never users , baseline non-users who started taking vitamin/mineral supplements during follow-up had significantly increased risks of cancer mortality ( HR : 1.74 ; 95 % CI : 1.09 , 2.77 ) and all-cause mortality ( HR : 1.58 ; 95 % CI : 1.17 , 2.14 ) . Conclusions Based on limited numbers of users and cases , this cohort study suggests that supplementation of antioxidant vitamins might possibly reduce cancer and all-cause mortality . The significantly increased risks of cancer and all-cause mortality among baseline non-users who started taking supplements during follow-up may suggest a “ sick-user effect , ” which research ers should be cautious of in future observational studies BACKGROUND Despite widespread use of multivitamin supplements , their effect on cognitive health-a critical issue with aging-remains inconclusive . To date , no long-term clinical trials have studied multivitamin use and cognitive decline in older persons . OBJECTIVE To evaluate whether long-term multivitamin supplementation affects cognitive health in later life . DESIGN R and omized , double-blind , placebo-controlled trial of a multivitamin from 1997 to 1 June 2011 . The cognitive function sub study began in 1998 . Up to 4 repeated cognitive assessment s by telephone interview were completed over 12 years . ( Clinical Trials.gov : NCT00270647 ) SETTING : The Physicians ' Health Study II . PATIENTS 5947 male physicians aged 65 years or older . INTERVENTION Daily multivitamin or placebo . MEASUREMENTS A global composite score averaging 5 tests of global cognition , verbal memory , and category fluency . The secondary end point was a verbal memory score combining 4 tests of verbal memory , which is a strong predictor of Alzheimer disease . RESULTS No difference was found in mean cognitive change over time between the multivitamin and placebo groups or in the mean level of cognition at any of the 4 assessment s. Specifically , for the global composite score , the mean difference in cognitive change over follow-up was -0.01 SU ( 95 % CI , -0.04 to 0.02 SU ) when treatment was compared with placebo . Similarly , cognitive performance did not differ between the multivitamin and placebo groups on the secondary outcome , verbal memory ( mean difference in cognitive change over follow-up , -0.005 SU [ CI , -0.04 to 0.03 SU ] ) . LIMITATION Doses of vitamins may be too low or the population may be too well-nourished to benefit from a multivitamin . CONCLUSION In male physicians aged 65 years or older , long-term use of a daily multivitamin did not provide cognitive benefits . PRIMARY FUNDING SOURCE National Institutes of Health , BASF , Pfizer , and DSM Nutritional Products Background Observational studies have frequently reported an association between cognitive function and nutrition in later life but r and omised trials of B vitamins and antioxidant supplements have mostly found no beneficial effect . We examined the effect of daily supplementation with 11 vitamins and 5 minerals on cognitive function in older adults to assess the possibility that this could help to prevent cognitive decline . Methods The study was carried out as part of a r and omised double blind placebo controlled trial of micronutrient supplementation based in six primary care health centres in North East Scotl and . 910 men and women aged 65 years and over living in the community were recruited and r and omised : 456 to active treatment and 454 to placebo . The active treatment consisted of a single tablet containing eleven vitamins and five minerals in amounts ranging from 50–210 % of the UK Reference Nutrient Intake or matching placebo tablet taken daily for 12 months . Digit span forward and verbal fluency tests , which assess immediate memory and executive functioning respectively , were conducted at the start and end of the intervention period . Risk of micronutrient deficiency at baseline was assessed by a simple risk question naire . Results For digit span forward there was no evidence of an effect of supplements in all participants or in sub-groups defined by age or risk of deficiency . For verbal fluency there was no evidence of a beneficial effect in the whole study population but there was weak evidence for a beneficial effect of supplementation in the two pre-specified subgroups : in those aged 75 years and over ( n 290 ; mean difference between supplemented and placebo groups 2.8 ( 95 % CI -0.6 , 6.2 ) units ) and in those at increased risk of micronutrient deficiency assessed by the risk question naire ( n 260 ; mean difference between supplemented and placebo groups 2.5 ( 95 % CI -1.0 , 6.1 ) units ) . Conclusion The results provide no evidence for a beneficial effect of daily multivitamin and multimineral supplements on these domains of cognitive function in community-living people over 65 years . However , the possibility of beneficial effects in older people and those at greater risk of nutritional deficiency deserves further attention Importance Cohort studies have reported increased incidence of cardiovascular disease ( CVD ) among individuals with low vitamin D status . To date , r and omized clinical trials of vitamin D supplementation have not found an effect , possibly because of using too low a dose of vitamin D. Objective To examine whether monthly high-dose vitamin D supplementation prevents CVD in the general population . Design , Setting , and Participants The Vitamin D Assessment Study is a r and omized , double-blind , placebo-controlled trial that recruited participants mostly from family practice s in Auckl and , New Zeal and , from April 5 , 2011 , through November 6 , 2012 , with follow-up until July 2015 . Participants were community-resident adults aged 50 to 84 years . Of 47 905 adults invited from family practice s and 163 from community groups , 5110 participants were r and omized to receive vitamin D3 ( n = 2558 ) or placebo ( n = 2552 ) . Two participants retracted consent , and all others ( n = 5108 ) were included in the primary analysis . Interventions Oral vitamin D3 in an initial dose of 200 000 IU , followed a month later by monthly doses of 100 000 IU , or placebo for a median of 3.3 years ( range , 2.5 - 4.2 years ) . Main Outcomes and Measures The primary outcome was the number of participants with incident CVD and death , including a prespecified subgroup analysis in participants with vitamin D deficiency ( baseline deseasonalized 25-hydroxyvitamin D [ 25(OH)D ] levels < 20 ng/mL ) . Secondary outcomes were myocardial infa rct ion , angina , heart failure , hypertension , arrhythmias , arteriosclerosis , stroke , and venous thrombosis . Results Of the 5108 participants included in the analysis , the mean ( SD ) age was 65.9 ( 8.3 ) years , 2969 ( 58.1 % ) were male , and 4253 ( 83.3 % ) were of European or other ethnicity , with the remainder being Polynesian or South Asian .  Mean ( SD ) baseline deseasonalized 25(OH)D concentration was 26.5 ( 9.0 ) ng/mL , with 1270 participants ( 24.9 % ) being vitamin D deficient . In a r and 
    Output:
    
As only five included studies revealed notable benefits , presently based on the specific compounds explored here , there is not compelling evidence to support the use nutraceuticals to improve cognition in the elderly .