***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: The efficacy and the tolerability of memantine ( 1-amino-3,5-dimethyladamantane hydrochloride , Akatinol Memantine , CAS 41100 - 52 - 1 ) were investigated in patients with mild to moderate dementia syndrome in a r and omized two-centre placebo-controlled clinical study . The test substance was administered at a dose of 10 mg/d from day 1 to day 3 and then at a dose of 2 x 10 mg/d from day 4 to the end of treatment after 42 days . Altogether , 88 patients were recruited to the study ; their average age was 71.5 years . The efficacy of memantine was judged on the basis of the baseline/6 week differences in the total sum scores of the Clinical Assessment Geriatric Scale ( SCAG ) , the Gottfries-Bräne-Steen Scale ( GBS ) , the SCAG and GBS subscales and the global assessment of the change in the patient 's condition . The effects of memantine on performance were studied with the aid of psychomotor tests and a behaviour investigation relating to activities of daily living ( ADL ) . The tolerability of memantine was assessed on the basis of the doctor 's global assessment and of entries on structured documentation forms ( DOTES/TWIS ) . Further safety parameters -- in the form of clinicochemical tests and measurements of blood pressure and heart rate -- were also monitored during the study . On both the psychopathological measurement level ( SCAG , global assessment of the change in the patient 's condition ) and the behavioural level ( GBS ) , confirmatory statistical analysis brought to light significant differences between memantine and placebo ( p less than or equal to 0.05 ) , these differences showing a superiority of memantine . The tolerability of  memantine  was good in the main . The observed adverse reactions were not serious and , except in 3 patients , were rated as causing little or no impairment . The present clinical study demonstrates the efficacy of memantine in patients suffering from mostly moderate dementia syndrome . Clinical and statistically relevant improvements in the dementia-induced disturbances were found on the both the psychopathological level ( SCAG , CGI ) and the behavioural level ( GBS ) . On the performance level also , the ADL behaviour investigation detected a highly significant improvement in the quality of performance of instrumented activities of daily living under memantine . Also the time taken to carry out these tasks was significantly reduced in comparison with placebo Memantine was investigated in a phase II double-blind trial on 30 elderly patients by comparison with a placebo with the aid of several psychometric tests . It was found that vigilance , short-term memory , and concentration improve significantly under Memantine . It was also found that  Memantine  exerted a beneficial effect on psychiatric and neurological symptoms despite the presence of an organic psychosyndrome of many years ' duration and multiple morbidity . The tolerance of the preparation was good in virtually all cases and a gradually increasing dosage is recommended . On the basis of these findings the authors assume that the therapeutic efficiency can be confirmed in a phase III trial 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 We evaluated the responses of 16 patients to preliminarily explore the spectrum of effectiveness and tolerability of the memantine , and NMDA antagonist , in the treatment of dementia in Wernicke-Korsakoff syndrome . In this study , for the first time in dementia of Wernicke-Korsakoff syndrome , the response to memantine was assessed . 16 patients with median age of 64 years and median body weight of 77 kg were treated with memantine 10 mg twice daily for up to 28 weeks . Clinical global impressions ( CGI ) , and Mini Mental Status Examination ( MMSE ) were performed during the treatment period ( after 2 , 4 , and 28 weeks ) . Efficacy measures also included the ADCS-Activities of Daily Living scale ( ADCS-ADL ) . At 28 weeks , the ADCS-ADL showed significantly less deterioration in memantine treated patients compared with placebo ( -2.3 compared with -4.3 : p = 0.005 ) . The results of MMSE demonstrate a significant and clinical ly relevant benefit for memantine relative to placebo as shown by positive outcomes in cognitive and functional assessment s.  Memantine ( 10 mg ) was safe and well tolerated . The preliminarily findings of this study with 16 patients suggested that memantine is effective in the treatment of  dementia in Wernicke-Korsakoff syndrome Objective To investigate the cognitive effects of the N-methyl-D-aspartate receptor antagonist , memantine , with a post-hoc exploratory re analysis of a 24-week r and omized , double-blind , placebo-controlled , parallel group clinical trial comparing memantine ( 20 mg per day ) to placebo in patients with moderate to severe Alzheimer disease ( AD ) receiving treatment with the cholinesterase inhibitor , donepezil . Methods The effects of memantine on individual items of the Severe Impairment Battery ( SIB ) , subscale performance , and 3 post-hoc – derived aggregate subscales were investigated . Analyses were based on the intention-to-treat population using last observation carried forward and observed cases approaches . The SIB components were assessed at baseline , weeks 4 , 8 , 12 , 18 , and 24 . Results The mean change from baseline by visit and at study end point on the SIB showed statistically significant differences between the memantine and placebo groups at all visits beginning at week 8 ( last observation carried forward and observed cases ) . The SIB subscale analysis showed statistically significantly greater effects of  memantine  than placebo on memory , language , and praxis . When the SIB domains were aggregated using a face valid approach to create 3 higher-order subscales , memantine treatment result ed in statistically significant differences on memory , language , and praxis compared with placebo . Conclusions These post-hoc analyses support the beneficial effects of memantine on cognition observed in a previously reported clinical trial . The results presented here suggest an effect of memantine on memory , language , and praxis in patients with moderate to severe AD and support the efficacy of memantine for the treatment of cognitive deficits in AD The SKT ( Syndrom Kurztest ) has been used in the assessment of treatment responses in numerous clinical trials for treatment of dementia in German-speaking Europe . Data from 265 patients with mild to moderate Alzheimer 's disease in a study conducted in the U.S. were analyzed to evaluate factor structure , common and specific subtest content , reliability , and concurrent validity . Results confirm the presence of two primary factors of memory and attention . Test-retest reliability of the factor scores was estimated to be .75 and .93 . Test-retest reliability of the composite SKT total score was .90 . The correlations between the  SKT memory and attention factor scores and the MMSE and ADAS measurements of dementia also support validity with regard to the broader construct of cognitive dysfunction Background and Purpose — Based on the hypothesis of glutamate-induced neurotoxicity ( excitotoxicity ) in cerebral ischemia , this study examined the efficacy and tolerability of memantine , an uncompetitive N-methyl-d-aspartate antagonist , in the treatment of mild to moderate vascular dementia . Methods — In this multicenter , 28-week trial carried out in France , 321 patients received 10 mg/d memantine or placebo twice a day ; 288 patients were valid for intent-to-treat analysis . Patients had to meet the criteria for probable vascular dementia and have a Mini-Mental State ( MMSE ) score between 12 and 20 at inclusion . The 2 primary end points were the cognitive subscale of the Alzheimers Disease Assessment Scale ( ADAS-cog ) and the global Clinician ’s Interview Based Impression of Change ( CIBIC-plus ) . Results — After 28 weeks , the mean ADAS-cog scores were significantly improved relative to placebo . In the intention-to-treat population , the memantine group mean score had gained an average of 0.4 points , whereas the placebo group mean score had declined by 1.6 points , ie , a difference of 2.0 points ( 95 % confidence interval , 0.49 to 3.60 ) . The response rate for CIBIC-plus , defined as improved or stable , was 60 % with memantine compared with 52 % with placebo ( P = 0.227 , intention to treat ) . Among the secondary efficacy parameters , which were analyzed in the per- protocol subset , MMSE was significantly improved with memantine compared with deterioration with placebo ( P = 0.003 ) . The Gottf 
    Output:
    
In two six month studies , memantine improved cognition ( 1.85 ADAS-Cog points , 95 % CI 0.88 to 2.83 , p = 0.0002 ) , and behaviour ( Weighted Mean Difference ( WMD ) 0.84 95 % CI 0.06 to 0.91 , p = 0.03 ) but this was not supported by clinical global measures .4 .
The effect on agitation which is already present is unknown.5 .
Memantine is well tolerated .
AUTHORS ' CONCLUSIONS Published data suggest a small beneficial effect of memantine at six months in moderate to severe AD .
The beneficial effect on cognition in patients with mild to moderate vascular dementia was not clinical ly discernible at six months .