***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: 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 A hybrid method based on cognitive interviewing and consensus panels was developed to pretest a question naire for caregivers of persons with Alzheimer disease ( AD ) . The objective of the question naire was to elicit caregivers '  attitudes and opinions on the use of medications to treat the disease . Thirty-one caregivers were divided into five pretest groups , within which each participant was asked to comment on question naire wording and design . The comments from participants in the first three groups were used to revise the question naire , and the revised version was given to participants in the remaining two groups . Overall , 81 % ( 118/146 ) of the participants ' comments were implemented . The number of comments made in the last two groups decreased relative to the number of comments made in the first three groups . The hybrid method enhanced the user-friendliness of the question naire and can serve as an alternative to common ad hoc pretest approaches that have little basis in theory Alzheimer 's disease is a progressive neurodegenerative disorder that results in tremendous economic and quality -of-life burdens . This paper presents estimates of the impact of tacrine use on the costs of caring for patients with Alzheimer 's disease . This study presents a cost analysis , based on a decision-analytic model constructed around the milestones in the progression of Alzheimer 's disease . Clinical data concerning the effectiveness of tacrine came from published results of an open-label follow-up study of 663 patients originally enrolled in a placebo-controlled clinical trial of tacrine .  Data concerning longevity , nursing home time , and costs of community and nursing home care are taken from several reports based on prospect i ve cohorts of patients . The use of tacrine was associated with a cost savings of $ 9,250 ( 7.5 % ) over the patient 's lifetime from diagnosis to death , even when averaged over data from patients who discontinued tacrine treatment or took only low doses . Most of the savings were due to reduced time in nursing homes . Patients who continued higher doses of tacrine experienced a cost saving of more than $ 36,500 over 5 years . Model results persisted over a wide range of sensitivity analysis variations . The use of  tacrine for patients with mild-to-moderate Alzheimer 's disease reduces the costs of medical and social services required for care , and it increases functioning and delays nursing home placement for up to 433 days . New treatments that can both improve clinical outcomes and save costs should be given serious consideration by clinicians and administrators BACKGROUND Alzheimer 's disease ( AD ) is estimated to affect up to 11 % of those aged > or = 65 years in the United States , and the number of patients with AD is predicted to increase over the next few decades as the population ages . The substantial social and economic burden associated with AD is well established , with the cost of management increasing as the disease progresses . OBJECTIVE The aim of this study was to evaluate the economic impact of galantamine 16 and 24 mg/d relative to no pharmacologic treatment in the management of mild to moderate AD in the United States based on the concept of need for full-time care ( FTC ) . METHODS Calculations were made using the Assessment of Health Economics in Alzheimer 's Disease model , which applies predictive equations to estimate the need for FTC and the associated costs . The predictive equations were developed from longitudinal data on patients with AD . Inputs to the equations were derived by analyzing the data from 2 r and omized , placebo-controlled , galantamine clinical trials . Re source use ( from a payer perspective ) was estimated from US clinical trial data , and costs were estimated from several US data bases . Analyses were carried out over 10 years , and costs and benefits were discounted at 3 % . RESULTS In the base case , 3.9 to 4.6 patients need to start treatment with galantamine to avoid 1 year of FTC , depending on dose . Treated patients spent 7 % to 8 % more time pre-FTC and 12 % to 14 % less time requiring FTC , result ing in savings of 2408 to 3601 US dollars . Time horizons below 3 years , very high discontinuation rates , or increased survival with galantamine reversed the savings . Conversely , limiting treatment to responders delayed FTC by 6 to 7 months , with savings of approximately 9097 to 11,578 US dollars . CONCLUSIONS These results suggest that use of galantamine in patients with AD in the United States could reduce the use of costly re sources such as formal home care and nursing homes , leading to cost savings over time Background In patients with moderately severe to severe Alzheimer ’s disease , the N-methyl-D-aspartate ( NMDA ) antagonist memantine has been shown to improve outcomes and to be associated with reductions in re source utilisation and total healthcare costs relative to no pharmacological intervention after 28 weeks in phase III clinical and pharmacoeconomic studies . However , the longer term cost implication s of treatment with memantine are not known . Objective To evaluate the effect of treatment with memantine in patients with moderately severe to severe Alzheimer ’s disease on re source use and on cost and patient outcomes in Finl and over a 5-year time horizon . Methods A Markov model was constructed to simulate a patient ’s progression through a finite series of health states with a time horizon of 5 years . The states were defined in terms of physical dependency , place of residency ( community or institution ) , and cognitive function . Each 6-month Markov cycle was repeated ten times . A 5 % rate was used to discount costs . Inputs for the model were derived from epidemiological data collected during the Kuopio 75 + Study , a Finnish population -based health survey of dementia and functional capacity among individuals aged ≥75 years .  Costs were considered from a societal perspective . Probabilities used in the model , together with cost and re source use differences between treatment with memantine ( Ebixa ® , Namenda ® , Axura ® ) and no pharmacological intervention , were derived from a r and omised , double-blind , placebo-controlled clinical trial that included an economic assessment . This study enrolled 252 patients with moderately severe to severe Alzheimer ’s disease . We took a conservative approach that assumed that the effectiveness of treatment with memantine was limited to 12 months ’ duration . Monte Carlo simulations were performed to evaluate the effect of treatment with memantine on duration of independence and time to institutionalisation . Sensitivity analyses included  memantine  efficacy best- ( 5 years ) and worst- ( 6 months ) case scenarios , and an analysis in which 5 % discounting was not applied . Results Memantine therapy was associated with approximately 4 extra months of independence , 1 additional month of residence in the community , and a cost reduction  relative to placebo of approximately € 1700 per patient over 5 years , despite the limiting of persistence of efficacy to 12 months ( year of costing , 2001 ) . Monte Carlo simulations and sensitivity analyses supported the findings . Conclusion : According to the model , over 5 years the additional drug costs of treating patients with moderately severe to severe Alzheimer ’s disease  with memantine were amply offset by cost savings related chiefly to increased independence and delayed institutionalisation BACKGROUND Alzheimer 's disease ( AD ) places a significant burden on health care systems worldwide . As new treatments are developed , their cost-effectiveness is often assessed to help health care professionals make informed decisions . In addition to the more common practice of assessing direct medical costs , indirect costs , including time spent in caregiving , should be evaluated . METHODS This study examined the potential effects of the dual cholinesterase inhibitor rivastigmine ( Exelon ) on caregivers of patients with AD . Results from two 26-week , placebo-controlled trials have demonstrated the clinical ly relevant and statistically significant efficacy of rivastigmine ( 6 - 12 mg/day ) compared to placebo , on cognition , activities of daily living , and global functioning . By delaying progression of AD , significant savings in caregiver burden are anticipated , as measured by time spent caregiving and its related costs . Data collected in a prospect i ve , observational study of AD patients and their caregivers were used to establish the relationship between disease severity ( based on Mini-Mental State Examination [ MMSE ] score ) and time spent caregiving ( according to the 5-item Caregivers Activity Survey score ) . A significant correlation was observed between the two scores ( N = 43 , r = -.56 , p < .0001 ) , demonstrating that more time for supervision from caregivers is required as the disease progresses . This finding was used to estimate the reduced caregiver burden result ing from the delay in disease progression that was demonstrated with use of rivastigmine . RESULTS Over a 2-year period , the reduction in time spent in caregiving reached 691 hours for caregivers of patients with mild AD ( MMSE score 21 - 30 ) , result ing in a total savings of approximately 11,253 dollars . Treatment of patients with moderately severe AD was also evaluated . The trend was similar but the impact was less , suggesting an economic benefit to early therapy . CONCLUSION Early diagnosis and a pharmacologic intervention that allows the patients to remain at home longer by delaying disease progression would have a beneficial impact on patients , caregivers , and payers , and should therefore be encouraged through initiatives design ed to identify and treat patients early in the course of disease Objective : To investigate the costs to society of Alzheimer disease ( AD ) care in a multinational , r and omized , placebo-controlled trial of donepezil in patients with moderate to severe AD . Methods : A total of 290 patients with AD ( screening st and ardized Mini-Mental State Examination score 5 to17 ) were r and omized to receive either donepezil ( n = 144 ; 5 mg/day for 28 days , followed by 10 mg/day as per clinician ’s judgment ) or placebo ( n = 146 ) for 24 weeks . The authors collected data on patient and caregiver health re source utilization prospect ively using the Canadian Utilization of Services Tracking question naire . Costs were calculated for patients and caregivers in each group based on re source utilization multiplied by the unit prices for each re source . A cost ( the average Ontario minimum wage for 1998 [ Can $ 6.85 per hour ] ) was assigned to unpaid time that caregivers spent assisting the patient with activities of daily living ( ADL ) . Results : Patient and caregiver demographics at baseline were similar across the two groups . After adjusting for baseline total cost per patient , the mean total societal cost per patient for the 24-week period was donepezil , Can $ 9,904 ( US $ 6,686 ) and placebo , Can $ 10,236 ( US $ 6,910 ) . This net cost saving of Can $ 332 ( US $ 224 ) included the average 24-week cost of donepezil treatment . Most of the cost-saving with donepezil treatment was due to less use of residential care by patients , and caregivers spending less time assisting patients with ADL . Conclusion : This cost-consequence analysis reveals economic benefits of treatment of moderate to severe AD with donepezil Abstract Objectives : To explore whether Alzheimer ’s disease patients could rate their quality of life ( QOL ) using utility-based health indexes , and to provide new knowledge about the measurement properties of these instruments for patient and caregiver proxy ratings . Methods : A convenience sample of 60 mild-moderate AD patients and their caregivers were r and omized to complete the  Quality of Well-Being Scale  ( QWB ) , Health Utilities Index ( HUI3 ) or EQ-5D and visual analogue scale ( VAS ) on two occasions . Test – retest reliability ( intraclass correlation coefficients ) and convergent validity ( Spearman correlations ) of utility scores with global health status , activities of daily living , comorbidity , mood , cognition and other utility measures were assessed . Results : Completion time was shortest 
    Output:
    
Existing AD medications were found to dominate st and ard treatment ( i.e. , no drugs ) , or they were found to be more costly and more effective than st and ard treatment .