***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 To evaluate the efficacy and safety of donepezil , an acetylcholinesterase inhibitor , as a treatment for cognitive impairment and dementia in patients with Parkinson ' s disease ( PD ) . METHODS Using a r and omized , double-blind , placebo-controlled design , nine patients received placebo and seven patients received donepezil ( 2.5 - 10 mg/day ) for a mean ( SD ) duration of 15.2 ( 3.4 ) weeks . The primary efficacy outcomes were derived from a neuropsychological battery that assessed global cognitive status as well as memory , attention , psychomotor speed , and visuospatial and executive functions . Secondary efficacy outcomes were psychiatric symptom and activities of daily living ratings . Primary safety measures were motor signs and assessment s of adverse effects . RESULTS Patients on donepezil showed selective and significant ( p<0.05 ) improvement on the memory subscale of the Dementia Rating Scale . There was also a trend toward improvement on a measure of psychomotor speed and attention . There were no group differences in psychiatric status , motor function , or activities of daily living as measured at baseline or end-point . Adverse effects result ed in premature withdrawal of four patients on donepezil , two for peripheral cholinergic effects and one for increased parkinsonism . Side effects were associated with dosage increases . CONCLUSION Donepezil has a beneficial effect on memory and may improve other cognitive deficits in patients with PD and cognitive impairment . However , variable tolerability in our sample underscores the need for careful monitoring when prescribing donepezil to patients with PD , especially with dosage increases 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 BACKGROUND Evidence suggests that disease severity predicts the response of patients with Alzheimer disease ( AD ) to cholinesterase inhibitor treatment , raising the question of whether disease progression also predicts response to this treatment . OBJECTIVE To evaluate retrospectively whether rate of disease progression during placebo treatment affects response to subsequent rivastigmine tartrate therapy for patients with mild to moderately severe AD . DESIGN A 26-week , open-label extension study following a 26-week , double-blind , r and omized , placebo-controlled trial . SETTING Outpatient research centers at 22 sites in the United States . PATIENTS We studied 187 of 235 patients originally r and omized to receive placebo treatment in the double-blind phase of the trial who continued with open-label ( rivastigmine ) extension therapy .  INTERVENTION Placebo treatment for 26 weeks followed by rivastigmine treatment , 2 to 12 mg/d , for 26 weeks . MAIN OUTCOME MEASURES Alzheimer 's Disease Assessment Scale-cognitive subscale ( ADAS-Cog ) , Progressive Deterioration Scale , Mini-Mental State Examination , and Global Deterioration Scale scores . RESULTS Rivastigmine administration during open-label extension therapy benefited patients who had progressed slowly and those who had progressed rapidly during initial double-blind placebo treatment . Slowly progressive patients responded with a mean 1.03-point improvement in the week 26 ( ie , start of open-label rivastigmine treatment ) ADAS-Cog score at 12 weeks of rivastigmine treatment ( week 38 of treatment ; P = .02 vs week 26 ) . However , more rapidly progressive patients had a significantly larger mean 4.97-point improvement from the week 26 ADAS-Cog score at 12 weeks ( with respect to week 26 of treatment and slowly progressive patient scores , P<.001 for both ) . Thus , a more rapid disease progression rate while receiving placebo treatment was predictive of a significantly stronger patient response to rivastigmine therapy . This relation also was observed with the other 3 outcome measures and was still apparent when accounting for disease severity . CONCLUSIONS Rate of disease progression for patients with mild to moderate AD seems to predict response to rivastigmine treatment . Patients with more rapidly progressive disease might be particularly likely to benefit from rivastigmine therapy 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 BACKGROUND Cholinergic deficits are prominent in patients who have dementia associated with Parkinson 's disease . We investigated the effects of the dual cholinesterase inhibitor rivastigmine in such patients . METHODS Patients in whom mild-to-moderate dementia developed at least 2 years after they received a clinical diagnosis of Parkinson 's disease were r and omly assigned to receive placebo or 3 to 12 mg of rivastigmine per day for 24 weeks . Primary efficacy variables were the scores for the cognitive subscale of the Alzheimer 's Disease Assessment Scale ( ADAS-cog ) and Alzheimer 's Disease Cooperative Study -Clinician 's Global Impression of Change ( ADCS-CGIC ) . Secondary clinical outcomes were the scores for the Alzheimer 's Disease Cooperative Study -Activities of Daily Living , the 10-item Neuropsychiatric Inventory , the Mini-Mental State Examination , Cognitive Drug Research power of attention tests , the Verbal Fluency test , and the Ten Point Clock-Drawing test . RESULTS A total of 541 patients were enrolled , and 410 completed the study . The outcomes were better among patients treated with rivastigmine than among those who received placebo ; however , the differences between these two groups were moderate and similar to those reported in trials of rivastigmine for Alzheimer 's disease . Rivastigmine-treated patients had a mean improvement of 2.1 points in the score for the 70-point ADAS-cog , from a baseline score of 23.8 , as compared with a 0.7-point worsening in the placebo group , from a baseline score of 24.3 ( P<0.001 ) . Clinical ly meaningful improvements in the scores for the ADCS-CGIC were observed in 19.8 percent of patients in the rivastigmine group and 14.5 percent of those in the placebo group , and clinical ly meaningful worsening was observed in 13.0 percent and 23.1 percent , respectively ( mean score at 24 weeks , 3.8 and 4.3 , respectively ; P=0.007 ) . Significantly better outcomes were seen with rivastigmine with respect to all secondary efficacy variables . The most frequent adverse events were nausea ( affecting 29.0 percent of patients in the rivastigmine group and 11.2 percent of those in the placebo group , P<0.001 ) , vomiting ( 16.6 and 1.7 percent , P<0.001 ) , and tremor ( 10.2 and 3.9 percent , P=0.01 ) . CONCLUSIONS In this placebo-controlled study , rivastigmine was associated with moderate improvements in dementia associated with Parkinson 's disease but also with higher rates of nausea , vomiting , and tremor 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 Introduction The severe , cortical , cholinergic depletion accompanying Parkinson ’s disease ( PD ) is considered as a highly probable correlate of cognitive and behavioural dysfunction . Recent studies have demonstrated that cholinesterase inhibitors ( notably rivastigmine ) are beneficial in patients suffering from dementia associated with PD ( PDD ) . However , the primary efficacy variables used in such work came from scales design ed for Alzheimer ’s disease ( AD ) , even though the cognitive symptoms in PD and AD dementia do not overlap completely . The aim of the present study ( a double-blind , placebo-controlled clinical trial ) was to determine the utility of the Mattis dementia rating scale - the most commonly used scale in PD patients - to assess the efficacy of a 24-week rivastigmine treatment . Methods Twenty-eight patients with PD , who constituted a subgroup of patients enrolled to the EXPRESS study ( Emre et al , N Engl J Med 2004 ) participated in this study . They suffered from mild to moderately severe dementia ( MMSE scores above 10 and below 24 ) , with an onset of cognitive symptoms occurring at least two years after the diagnosis of PD . Patients were r and omly assigned to treatment with rivastigmine ( 3 to 12 mg per day ) or placebo . The Mattis dementia rating scale was administered to patients from six centres in France at the baseline and end-point visits . Results Compared with placebo , a 24-week rivastigmine treatment led to a significant improvement in the overall score on the Mattis dementia rating scale ( p = 0.031 ) , with a trend towards a significant improvement in the “ Attention ” subscale score ( p = 0. 
    Output:
    
A change of 4 points is considered clinical ly significant for patients with mild to moderate dementia , but the ADAS-cog is not uniformly sensitive to change over the course of the disease ( 5 ) .
The ADAS-noncog evaluates behavioral changes .
The MMSE measures orientation , attention , recall , and language , but it does not evaluate mood or disordered forms of thinking .
The SIB is a vali date d measure of cognitive function for moderate to severe dementias in the areas of orientation , attention , language , and praxis ( 7 ) .
There are no established clinical ly important differences for the MMSE or SIB .