***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 post-hoc analyses reported here evaluate the specific effects of memantine treatment on ADAS-cog single-items or SIB subscales for patients with moderate to severe AD . METHODS Data from six multicentre , r and omised , placebo-controlled , parallel-group , double-blind , 6-month studies were used as the basis for these post-hoc analyses . All patients with a Mini-Mental State Examination ( MMSE ) score of less than 20 were included . Analyses of patients with moderate AD ( MMSE : 10 - 19 ) , evaluated with the Alzheimer 's disease Assessment Scale ( ADAS-cog ) and analyses of patients with moderate to severe AD ( MMSE : 3 - 14 ) , evaluated using the Severe Impairment Battery ( SIB ) , were performed separately . RESULTS The mean change from baseline showed a significant benefit of memantine treatment on both the ADAS-cog ( p < 0.01 ) and the SIB ( p < 0.001 ) total score at study end . The ADAS-cog single-item analyses showed significant benefits of memantine treatment , compared to placebo , for mean change from baseline for comm and s ( p < 0.001 ) , ideational praxis ( p < 0.05 ) , orientation ( p < 0.01 ) , comprehension ( p < 0.05 ) , and remembering test instructions ( p < 0.05 ) for observed cases ( OC ) . The SIB subscale analyses showed significant benefits of memantine , compared to placebo , for mean change from baseline for language ( p < 0.05 ) , memory ( p < 0.05 ) , orientation ( p < 0.01 ) , praxis ( p < 0.001 ) , and visuospatial ability ( p < 0.01 ) for OC . CONCLUSION Memantine shows significant benefits on overall cognitive abilities as well as on specific key cognitive domains for patients with moderate to severe AD Several clinical trials have demonstrated the efficacy and safety of the  NMDA antagonist memantine in moderately severe to severe Alzheimer ’s disease ( AD ) patients . A 28-week pharmacoeconomic study conducted in the US also showed a reduction of total healthcare costs and informal care compared to placebo . Long-term implication s of memantine treatment were modelled in the UK and Finl and and revealed reductions in dependency , institutionalization and costs . However , these conclusions were not directly applicable to the Spanish setting where patients are mainly treated within the community . The objective of this study was to estimate the long-term implication s in terms of costs and health benefits of memantine therapy compared to st and ard care using a Spanish adaptation of previous models over a 2-year time horizon . As in previous adaptations , Markov health states were defined as a combination of severity ( mild-moderate , moderately severe , severe ) and dependency plus death as the absorbing state . Spain-specific data ( costs , mortality and epidemiological data ) were obtained from local and recently published cohorts of AD patients . Data on the effectiveness of memantine were derived from a r and omized double-blind placebo-controlled clinical trial of 252 moderately severe to severe AD patients .  Effectiveness was measured as the time spent in a non-dependent health state . The evaluation was conducted over 2 years , while the efficacy of memantine was applied for 1 year only in order to ensure a conservative approach . The robustness of the model was tested by conducting stochastic analyses and various sensitivity analyses on the key assumptions . Patients receiving st and ard care were estimated to spend 6 months in a non-dependent state and to incur average total costs of € 24,700 over 2 years . The memantine strategy was associated with an additional 2.5 months in a non-dependent state and a € 700 cost reduction . Monte-Carlo simulations and sensitivity analyses supported these findings . Memantine appears to be cost-effective compared with st and ard care in moderately severe to severe AD patients in a Spanish setting . The prolonged independence provided by memantine treatment translated into cost reductions which offset drug costs and result ed in overall cost-savings BACKGROUND Vascular dementia is the second commonest form of dementia , and vascular factors contribute to the development of dementia in many patients with Alzheimer 's disease .  Galantamine amplifies the acetylcholine response by inhibiting acetylcholinesterase and modulating nicotinic receptors . It has shown broad , sustained benefits in patients with Alzheimer 's disease . We investigated the effects of galantamine in patients with a diagnosis of probable vascular dementia or Alzheimer 's disease combined with cerebrovascular disease . METHODS Eligible patients were r and omly assigned galantamine 24 mg/day ( n=396 ) or placebo ( n=196 ) in a multicentre , double-blind , 6-month trial . Primary endpoints were cognition ( Alzheimer 's disease assessment scale , cognitive subscale [ ADAS-cog ] ) and global functioning ( clinician 's interview-based impression of change plus caregiver input [ CIBIC-plus ] ) . Secondary endpoints included assessment s of activities of daily living and behavioural symptoms . Patients were monitored for adverse events . Analyses were on the basis of observed case or last observation carried forward . FINDINGS Galantamine showed greater efficacy than placebo on ADAS-cog ( galantamine change -1.7 [ SE 0.4 ] vs placebo 1.0 [ 0.5 ] ; treatment effect 2.7 points ; p<0.0001 ) and CIBIC-plus ( 213 [ 74 % ] vs 95 [ 59 % ] patients remained stable or improved , p=0.0001 ) . Activities of daily living and behavioural symptoms were also significantly improved compared with placebo ( p=0.002 and p=0.016 , respectively ) . Galantamine was well tolerated . INTERPRETATION Galantamine showed a therapeutic effect on all key areas of cognitive and non-cognitive abilities in this group of dementia patients To evaluate the impact of galantamine treatment on the function , caregiver time , and re source used in the treatment of patients with mild to moderate Alzheimer 's disease ( AD ) , costs and outcomes were evaluated during a 52-week prospect i ve , r and omized , double-blind , community-controlled trial of galantamine .  Patients received either galantamine treatment ( n=72 ) or no treatment ( n=66 ) . The analysis was performed from a societal perspective . Galantamine treatment reduced time spent caring for the patients and maintained improved functional capacity , whereas , when no treatments were given , a great increase in caregiver time and progressive functional deteriorations were observed . Saved caregiver time was equivalent to 113 working days per year . After 52 weeks , mean total annual costs per patient were 14,735,000 Korea Won ( KRW ) ( USD 12,315 ) for patients with galantamine treatment and 25,325,000 KRW ( USD 21,166 ) for patients without treatment . Adjusted annual cost saving  of galantamine treatment was 6,428,000 KRW ( USD 5,372 ) when compared to no treatment ( p=0.0089 ) . Galantamine had a beneficial effect not only to slow functional decline in patients with mild to moderate AD , but also to save a substantial amount of costs , closely related to reduction in caregiver burden and decrease in caregiver time Background : Recommendations in the UK suggest restricting treatment of Alzheimer ’s disease with cholinesterase inhibitors , on cost-effectiveness grounds , to patients with moderate cognitive decline . As the economic analyses that informed these recommendations have been the subject of debate , we sought to address the potential limitations of existing models and produce estimates of donepezil treatment cost effectiveness in the UK using the most recent available data and simulation techniques . Methods : A discrete-event simulation was developed that predicts progression of Alzheimer ’s disease through correlated changes in cognition , behavioural disturbance and function . Patient-level data from seven r and omized , placebo-controlled donepezil trials and a 7-year follow-up registry provided the basis for modeling longitudinal outcomes . Individuals in the simulation were assigned unique demographic and clinical characteristics and then followed for 10 years , with severity of disease tracked on continuous scales . Patient mix and costs were developed from UK-specific literature . Analyses were run for severity subgroups to evaluate outcomes for sub- population s with disease of mild versus moderate severity from both a healthcare payer and societal perspective . All costs are reported in £ , year 2007 values , and all outcomes are discounted at 3.5 % per annum . Results : Over 10 years , treatment of all patients with mild to moderate disease  reduces overall direct medical costs by an average of over £ 2300 per patient . When unpaid caregiver time is also taken into consideration , savings increase to over £ 4700 per patient . Compared with untreated patients , patients receiving donepezil experience a discounted gain in QALYs averaging 0.11 , with their caregivers gaining , on average , 0.01 QALYs . For the subset of patients starting treatment with more severe disease , savings are more modest , averaging about £ 1600 and £ 3750 from healthcare and societal perspectives , respectively . In probabilistic sensitivity analyses , donepezil dominated no treatment between 57 % and 62 % of replications when only medical costs were considered , and between 74 % and 79 % of replications when indirect costs were included , with results more favourable for treatment initiation in the mild versus moderate severity stages of the disease . Conclusions : Although the simulation results are not definitive , they suggest that donepezil leads to health benefits and cost savings when used to treat mild to moderately severe Alzheimer ’s disease in the UK . They also indicate that both benefits and savings may be greatest when treatment is started while patients are still in the mild stages of Alzheimer ’s disease Multi-parameter evidence synthesis is a generalization of meta- analysis in which several parameters are estimated jointly . Here this approach is applied to a common form of data structure in which mixed pairwise comparisons are made between treatments in a ' chain of evidence ' structure . The data set investigated here , which first appeared in the confidence profile method literature , features three types of data relating to thrombolytic treatment following acute myocardial infa rct ion . There is information on reperfusion ( coronary patency ) following treatment , information on survival in reperfused and non-reperfused patients ( conditional survival ) , and independent information on the effect of treatment on survival without specifying reperfusion state ( overall survival ) . The objective of this study is to explore models for combining these three types of evidence within a single model , and some of the evidence consistency issues that arise . Bayesian Markov chain Monte Carlo methods are used to fit two models . The first , proposed in the confidence profile literature , assumes there are no differences between studies in baseline effects ( equal study effects ) . The second model assumes fixed treatment effects but allows for study differences in baseline reperfusion and conditional survival rates by assuming r and om study effects . The equal study effects model fits the data poorly , and cross-validation shows that the overall survival evidence is not consistent with the reperfusion and conditional survival evidence under this model . The evidence appears to be consistent within the more loosely structured r and om study effects model , but results are sensitive to prior assumptions about the between- study variance . The inconsistency between the three evidence types relates to overall survival , rather than to the effect of treatment on survival . Multi-parameter evidence synthesis , with suitable checks for evidence consistency , can be used to help determine whether chains of evidence ' add up ' epidemiologically within an overall model , and to construct parameter distributions for an entire model simultaneously , consistent with all the available data OBJECTIVE The objective of this study was to compare the efficacy and safety of the moderate-affinity , uncompetitive N-methyl-d-aspartate receptor antagonist , memantine , versus placebo in patients with mild to moderate Alzheimer disease ( AD ) . METHOD This was a r and omized , double-blind , placebo-controlled clinical trial conducted at 42 U.S. sites . Participants were 403 out patients with mild to moderate AD and Mini-Mental State Examination scores of 10 - 22 r and omized to memantine  ( 20 mg/day ; N=201 ) or placebo ( N=202 ) for 24 weeks . Primary outcomes were change from baseline at 24 weeks on the Alzheimer 's Disease Assessment Scale-Cognitive Subscale ( ADAS-cog ) , a measure of cognition , and on the Clinician 's Interview-Based Impression of Change Plus Caregiver Input ( CIBIC-Plus ) , a global measure . Secondary outcomes included change on the Neuropsychiatric Inventory ( NPI ) and the Alzheimer 's Disease Cooperative Study Activities of Daily Living Inventory ( ADCS-ADL(23 ) ) , measures of behavior and function , respectively . RESULTS Most ( 82.4 % ) participants completed the trial . Memantine result ed in significantly better outcomes than placebo on measures of cognition , global status , and behavior when based on the protocol -specified primary last observation carried forward imputation as well as a mixed-models repeated- measures approach applied to the continuous outcomes . Treatment discontinuations because of adverse events for memantine versus placebo were 19 ( 9.5 % ) and 10 ( 5.0 % ) , respectively . CONCLUSIONS These results support the safety and efficacy of memantine for the treatment of mild to moderate AD Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate 
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RESULTS Notwithst and ing the uncertainty of our results , we found in the base case that the AChEIs are probably cost saving at a willingness-to-pay ( WTP ) of £ ’ 30,000 per quality adjusted life-year ( QALY ) for people with mild-to-moderate AD .
In the deterministic results , donepezil dominates the other drugs and BSC , which , along with rivastigmine patches , are associated with greater costs and fewer QALYs .
The additional clinical effectiveness evidence identified continues to suggest clinical benefit from the AChEIs in alleviating AD symptoms , although there is debate about the magnitude of the effect .
Although there is also new evidence on the effectiveness of memantine , it remains less supportive of this drug ’s use than the evidence for AChEIs .