***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: OBJECTIVE The objective of this study was to examine the clinical utility of memantine for moderate-to-severe Alzheimer disease ( AD ) using responder analyses . METHOD Data from a previously published 24-week , r and omized , double-blind , placebo-controlled trial of 10 mg memantine twice a day in patients with moderate-to-severe AD ( N = 404 ) on stable donepezil therapy were evaluated using three sets of responder criteria . Response rates were calculated and analyzed for the intention-to-treat population using a generalized estimating equations model . The following outcomes were examined separately and in combination : the Alzheimer 's Disease Cooperative Study -Activities of Daily Living 19-Item Inventory ( ADCS-ADL19 ) , Severe Impairment Battery ( SIB ) , Clinician 's Interview-Based Impression of Change Plus Caregiver Input ( CIBIC-Plus ) , and Neuropsychiatric Inventory ( NPI ) . RESULTS When treatment response required cognitive improvement relative to baseline , memantine yielded higher response rates than placebo . When treatment response was defined as stabilization of individual outcomes , memantine result ed in significantly higher response rates than placebo for all outcomes , with number needed to treat ( NNT ) ranging from 8 - 10 . More conservative definitions of response that required simultaneous stabilization on multiple outcome measures again favored memantine treatment for six of 10 combinatorial definitions . CONCLUSIONS These responder analyses may assist clinicians in evaluating the impact of memantine in a relevant clinical scenario , i.e. , in patients with AD previously stabilized on a cholinesterase inhibitor . The current results indicate that in this setting , memantine produces both improvement and stabilization of symptoms , across multiple outcomes , and thus provides a clinical ly important treatment benefit for patients with moderate-to-severe AD Objective : To investigate the behavioral effects of memantine in moderate to severe Alzheimer disease ( AD ) . Methods : The authors conducted a hypothesis-generating , exploratory analysis of a 24-week , double-blind , placebo-controlled trial comparing memantine ( 20 mg/day ) with placebo in subjects with moderate to severe AD on stable donepezil treatment . They employed the Neuropsychiatric Inventory ( NPI ; 12-item ) , administered at baseline , week 12 , and week 24 , to assess the effects of memantine on behavior . Global , cognitive , and functional measures were collected and relationships between these assessment s and changes in behavior were determined . The intent-to-treat population was examined using last-observation-carried-forward and observed-cases approaches . Results : Patients treated with memantine had significantly lower NPI total scores than patients treated with placebo . Analyses of the 12 NPI domains revealed significant effects in favor of memantine on agitation/aggression , eating/appetite , and irritability/lability . Of patients who exhibited agitation/aggression at baseline , those treated with memantine showed significant reduction of symptoms compared with placebo-treated patients . Memantine-treated patients without agitation/aggression at baseline evidence d significantly less emergence of this symptom compared with similar patients receiving placebo .  Caregivers of patients receiving memantine  registered significantly less agitation-related distress . There were significant relationships between the NPI and the global rating scale and performance of activities of daily living , but not between changes in the NPI and cognition . Conclusion : Treatment with memantine reduced agitation/aggression , irritability , and appetite/eating disturbances .  Memantine reduced agitation/aggression in patients who were agitated at baseline and delayed its emergence in those who were free of agitation at baseline 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 Two hundred ten community-dwelling patients with Alzheimer 's disease were examined prospect ively by psychiatrists as part of a longitudinal study . Twenty-five of these patients who were institutionalized during the next 3 years were then matched to 25 patients who were not institutionalized  , and the groups were compared . The patients who had been institutionalized had higher scores on st and ardized psychiatric rating scales but not on formal neuropsychological tests of cognition . These results suggest that potentially treatable ( noncognitive ) behavioral and psychiatric symptoms are risk factors for institutionalization , and that treating these symptoms might delay or prevent institutionalization of some patients OBJECTIVE To evaluate the efficacy of donepezil in patients with early-stage Alzheimer disease . DESIGN Multicenter , r and omized , double-blind , 24-week , placebo-controlled study that enrolled patients with early-stage Alzheimer disease . Patients were r and omized in an approximately 2:1 ratio to donepezil , 5 mg/d , for the first 6 weeks , with a forced escalation to 10 mg/d thereafter ( n = 96 ) , or placebo ( n = 57 ) . The primary efficacy measure was the modified Alzheimer Disease Assessment Scale-cognitive subscale . Secondary efficacy measures included the Mini-Mental State Examination , the Computerized Memory Battery Test , the Clinical Dementia Rating Scale-Sum of the Boxes , the Patient Global Assessment Scale , and the Apathy Scale . RESULTS Improvements favoring donepezil on the Alzheimer Disease Assessment Scale-cognitive subscale were found at weeks 12 and 24 and at the end point ( last observation carried forward ) ; treatment differences were 1.9 ( P = .03 ) , 2.3 ( P = .008 ) , and 2.3 ( P = .001 ) points , respectively . Improvements favoring donepezil on the Mini-Mental State Examination were found at weeks 6 , 12 , and 24 and at the end point ( last observation carried forward ) ; treatment differences were 1.4 ( P = .02 ) , 1.2 ( P = .04 ) , 1.4 ( P = .03 ) , and 1.8 ( P = .002 ) points , respectively . Donepezil-treated patients showed greater mean improvement compared with placebo-treated patients on the following Computerized Memory Battery Test subscales : facial recognition ( P = .007 in the intent-to-treat population and P = .04 in the fully evaluable population ) , first and last name total acquisition ( P = .02 ) , and name-face association delayed recall ( P = .04 ) . Donepezil was safe and well tolerated in this population ; serious adverse events occurred in similar numbers of donepezil- and placebo-treated patients . CONCLUSION These data suggest significant treatment benefits of donepezil in early-stage Alzheimer disease , supporting the initiation of therapy early in the disease course to improve daily cognitive functioning CONTEXT Memantine is a low- to moderate-affinity , uncompetitive N-methyl-D-aspartate receptor antagonist . Controlled trials have demonstrated the safety and efficacy of memantine monotherapy for patients with moderate to severe Alzheimer disease ( AD ) but no controlled trials of memantine in patients receiving a cholinesterase inhibitor have been performed . OBJECTIVE To compare the efficacy and safety of memantine vs placebo in patients with moderate to severe AD already receiving stable treatment with donepezil . DESIGN , SETTING , AND PARTICIPANTS A r and omized , double-blind , placebo-controlled clinical trial of 404 patients with moderate to severe AD and Mini-Mental State Examination scores of 5 to 14 , who received stable doses of donepezil , conducted at 37 US sites between June 11 , 2001 , and June 3 , 2002 . A total of 322 patients ( 80 % ) completed the trial . INTERVENTIONS Participants were r and omized to receive memantine ( starting dose 5 mg/d , increased to 20 mg/d , n = 203 ) or placebo ( n = 201 ) for 24 weeks . MAIN OUTCOME MEASURES Change from baseline on the Severe Impairment Battery ( SIB ) , a measure of cognition , and on a modified 19-item AD Cooperative Study -Activities of Daily Living Inventory ( ADCS-ADL19 ) . Secondary outcomes included a Clinician 's Interview-Based Impression of Change Plus Caregiver Input ( CIBIC-Plus ) , the Neuropsychiatric Inventory , and the Behavioral Rating Scale for Geriatric Patients ( BGP Care Dependency Subscale ) . RESULTS The change in total mean ( SE ) scores favored memantine vs placebo treatment for SIB ( possible score range , 0 - 100 ) , 0.9 ( 0.67 ) vs -2.5 ( 0.69 ) , respectively ( P<.001 ) ; ADCS-ADL19 ( possible score range , 0 - 54 ) , -2.0 ( 0.50 ) vs -3.4 ( 0.51 ) , respectively ( P = .03 ) ; and the CIBIC-Plus ( possible score range , 1 - 7 ) , 4.41 ( 0.074 ) vs 4.66 ( 0.075 ) , respectively ( P = .03 ) . All other secondary measures showed significant benefits of memantine treatment . Treatment discontinuations because of adverse events for memantine vs placebo were 15 ( 7.4 % ) vs 25 ( 12.4 % ) , respectively . CONCLUSIONS In patients with moderate to severe AD receiving stable doses of donepezil , memantine result ed in significantly better outcomes than placebo on measures of cognition , activities of daily living , global outcome , and behavior and was well tolerated . These results , together with previous studies , suggest that memantine represents a new approach for the treatment of patients with moderate to severe AD BACKGROUND Agitation is a common and distressing symptom in patients with Alzheimer 's disease .  Cholinesterase inhibitors improve cognitive outcomes in such patients , but the benefits of these drugs for behavioral disturbances are unclear . METHODS We r and omly assigned 272 patients with Alzheimer 's disease who had clinical ly significant agitation and no response to a brief psychosocial treatment program to receive 10 mg of donepezil per day ( 128 patients ) or placebo ( 131 patients ) for 12 weeks . The primary outcome was a change in the score on the Cohen-Mansfield Agitation Inventory ( CMAI ) ( on a scale of 29 to 203 , with higher scores indicating more agitation ) at 12 weeks . RESULTS There was no significant difference between the effects of donepezil and those of placebo on the basis of the change in CMAI scores from baseline to 12 weeks ( estimated mean difference in change [ the value for donepezil minus that for placebo ] , -0.06 ; 95 % confidence interval [ CI ] , -4.35 to 4.22 ) . Twenty-two of 108 patients ( 20.4 % ) in the placebo group and 22 of 113 ( 19.5 % ) in the donepezil group had a reduction of 30 % or greater in the CMAI score ( the value for donepezil minus that for placebo , -0.9 percentage point ; 95 % CI , -11.4 to 9.6 ) . There were also no significant differences between the placebo and donepezil groups in scores for the Neuropsychiatric Inventory , the Neuropsychiatric Inventory Caregiver Distress Scale , or the Clinician 's Global Impression of Change . CONCLUSIONS In this 12-week trial , donepezil was not more effective than placebo in treating agitation in patients with Alzheimer 's disease . ( Clinical Trials.gov number , NCT00142324 [ Clinical Trials.gov ] . ) Objective : To evaluate the efficacy and safety of donepezil for severe Alzheimer disease ( AD ) . Methods : Patients with severe AD ( Mini-Mental State Examination [ MMSE ] scores 1 to 12 and Functional Assessment Staging [ FAST ] scores ≥6 ) were enrolled in this multinational , double-blind , placebo-controlled trial at 98 sites . Patients were r and omized to donepezil 10 mg daily or placebo for 24 weeks . Primary endpoints were the Severe Impair 
    Output:
    
Conclusion : Within its licensed indication , donepezil is efficacious for the management of BPSD in AD compared with placebo