***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 : To examine whether the presence of domain-specific cognitive impairments would predict a response to donepezil medication in patients with mild-to-moderate Alzheimer disease ( AD ) . Methods : The protocol was an open-label study of 30 AD subjects ( mean age 74 years ; education 11 years ; Mini-Mental State Exam ( MMSE ) 23 of 30 ) beginning a 6-month course of treatment with donepezil .  Global response to treatment was determined using a combination algorithm based on changes over 6 months in the ADAS-cog , MMSE and CIBIC . In addition , a set of neuropsychological and experimental cognitive tests design ed to test five domains of cognition were administered before beginning therapy in order to determine which domain of testing would be predictive to response to treatment . The tests examined attention , short-term and working memory , learning and memory , visuo-spatial motor skills , and lexical-semantic knowledge . Results : Eighteen of the thirty subjects were rated as having responded ( stable or improved scores on the combination algorithm ) to the therapy . Responders were significantly less impaired prior to treatment on the following tests : the Clock Drawing Test , a Visual-Spatial Motor Tracking Test , and the Boston Picture Naming Test . No significant initial group differences were noted on the other neuropsychological or experimental cognitive measures . Conclusion : The tests that most reliably predicted response to donepezil in AD subjects were in the domains of visual-spatial motor abilities and lexical-semantic functioning BACKGROUND Amyloid precursor protein ( APP ) forms with apparent molecular weights of 130 , 110 , and 106 kd are present in human platelets . It has been demonstrated that Alzheimer disease ( AD ) is specifically associated with a decreased APP forms ratio in platelets . OBJECTIVE To investigate whether acetylcholinesterase ( AChE ) inhibitor treatment modifies the ratio of platelet APP forms in patients with AD . PATIENTS AND METHODS From a large sample of patients with probable AD , 30 with mild to moderate AD were selected . Each patient underwent a clinical evaluation including the  Mini-Mental State Examination ( MMSE )  and  platelet APP forms analysis  at baseline and after 30 days . During this interval , 20 of 30 patients with AD were treated with donepezil hydrochloride ( 5 mg/d ) , a piperidine phosphate-based cholinesterase inhibitor . Platelets were subjected to Western blot analysis using monoclonal antibody ( 22C11 ) . The ratio between the immunoreactivity of the higher-molecular-weight APP form ( 130 kd ) and the lower forms ( 106 and 110 kd ) was measured . RESULTS All patients taking donepezil completed the 30 days of treatment without adverse effects . The platelet APP forms ratio at baseline did not differ between the 2 AD groups ( mean + /- SD optical density ratio : untreated AD , 0.47 + /- 0.12 ; treated AD , 0.38 + /- 0.18 ) , whereas a significant difference was found at follow-up ( mean + /- SD optical density ratio : untreated AD , 0.45 + /- 0.17 ; treated AD , 0.77 + /- 0.29 ; P<.001 ) . A significant improvement in MMSE scores in treated AD patients was observed from baseline ( 16.9 + /- 3.8 ) to 30 days ( 18.9 + /- 4.42 ) ( P<.009 , 30 days vs baseline ) , but no significant correlation was found in treated AD patients between MMSE score improvement and APP forms/ratio increase ( P = .09 ) . CONCLUSIONS Administration of AChE inhibitors increases the ratio of APP forms in platelets of patients with AD , suggesting a potential effect of AChE inhibitors on APP trafficking or processing in a peripheral cell Objective : To determine the usefulness of an interactive multimedia internet-based system ( IMIS ) for the cognitive stimulation of Alzheimer ’s disease . Methods : This is a 24-week , single-blind , r and omised pilot study conducted on 46 mildly impaired patients suspected of having Alzheimer ’s disease receiving stable treatment with cholinesterase inhibitors ( ChEIs ) .  The patients were divided into three groups : ( 1 ) those who received 3 weekly , 20-min sessions of IMIS in addition to 8 h/day of an integrated psychostimulation program ( IPP ) ; ( 2 ) those who received only IPP sessions ; and ( 3 ) those who received only ChEI treatment . The primary outcome measure was the Alzheimer ’s Disease Assessment Scale-Cognitive ( ADAS-Cog ) . Secondary outcome measures were : Mini-Mental State Examination ( MMSE ) , Syndrom Kurztest , Boston Naming Test , Verbal Fluency , and the Rivermead Behavioral Memory Test story recall subtest . Results : After 12 weeks , the patients treated with both IMIS and IPP had improved outcome scores on the ADAS-Cog and MMSE , which was maintained through 24 weeks of follow-up . The patients treated with IPP alone had better outcome than those treated with ChEIs alone , but the effects were attenuated after 24 weeks . All patients had improved scores in all of the IMIS individual tasks , attaining higher levels of difficulty in all cases . Conclusion : Although both the IPP and IMIS improved cognition in patients with Alzheimer ’s disease , the IMIS program provided an improvement above and beyond that seen with IPP alone , which lasted for 24 weeks OBJECTIVES To assess the relationship between donepezil treatment and time to nursing home placement ( NHP ) for patients with Alzheimer 's disease ( AD ) . DESIGN Observational follow-up of patient NHP and vital status . SETTING Community . PARTICIPANTS Patients previously enrolled in one of three r and omized , double-blind , placebo-controlled clinical trials of donepezil and two subsequent open-label studies ( total N = 1,115 ) ; 671 patients provided complete data for analysis . MEASUREMENTS Data were obtained through follow-up interviews with caregivers and chart review s of patients with AD . Comparison groups were defined by whether patients received an effective dose of donepezil ( > /=5 mg/d ; > /=80 % compliance ) for specific numbers of weeks during the double-blind or open-label trial phase , in both phases , or in neither . Cox proportional hazards models were used to estimate risk ratios for NHP and survival curves from which median times to NHP were estimated for first dementia-related placement of longer than 2 weeks and permanent placement . The models were adjusted for age , sex , baseline Mini-Mental State Examination score , whether the caregiver was a spouse , caregiver continuity , and use of other cholinesterase inhibitors after the clinical trials . RESULTS Use of donepezil of 5 mg/d or more was associated with significant delays in NHP . A cumulative dose-response relationship was observed between longer-term sustained donepezil use and delay of NHP . When donepezil was taken at an effective dose for at least 9 to 12 months , conservative estimates of the time gained before NHP were 21.4 months for first dementia-related NHP and 17.5 months for permanent NHP . CONCLUSION Use of donepezil by AD patients result ed in significant delays in NHP . Long-term use of donepezil may help AD patients live longer in community setting s , with consequent personal , social , and economic benefits A r and omized double-blind trial evaluated the efficacy and tolerability of rivastigmine , an inhibitor of acetylcholinesterase ( AChE ) and butyrylcholinesterase ( BuChE ) , and donepezil , an AChE-selective inhibitor , in patients with Alzheimer 's disease over a 2-year period . A retrospective analysis showed differential responses to cholinesterase inhibitors ( ChE-Is ) in patients younger than 75 years . This analysis investigated the effect of BuChE genotype on response to ChE-I therapy in these patients . In a retrospective analysis , patients younger than 75 who had consented to pharmacogenetic analysis were divided into groups according to BuChE genotype . Efficacy measures were the Severe Impairment Battery ( SIB ) , Neuropsychiatric Inventory ( NPI ) , Global Deterioration Scale ( GDS ) , Mini-Mental State Examination ( MMSE ) and the Alzheimer 's Disease Cooperative Study –Activities of Daily Living Scale ( ADCS-ADL ) . Changes on efficacy parameters were calculated for rivastigmine-treated and donepezil-treated patients in both groups . Of 114 ( 34.1 % ) patients younger than 75 who were successfully assessed for BuChE genotype , 76 ( 66.7 % ) were homozygous for wild-type BuChE , and 38 ( 33.3 % ) carried at least one BuChE K-variant allele . Wild-type BuChE carriers showed significantly greater responses to rivastigmine than to donepezil on the SIB , ADCS-ADL , GDS and NPI . No significant between-treatment differences in efficacy were observed in BuChE K-variant carriers , although adverse events were more frequent in rivastigmine-treated patients . In this retrospective analysis , Alzheimer 's disease patients younger than 75 with wild-type BuChE exhibited differential efficacy to rivastigmine , while BuChE K-variant carriers experienced similar long-term treatment effects with both agents . These differences may reflect rivastigmine 's ability to inhibit BuChE and OBJECTIVE The authors examined the effect of the acetylcholinesterase inhibitor donepezil on magnetic resonance markers of neurodegeneration in Alzheimer 's disease . METHOD In this r and omized , double-blind , placebo-controlled pilot study , 67 patients with mild to moderate Alzheimer 's disease received 24 weeks of treatment with  donepezil ( 5 mg/day for the first 28 days and 10 mg/day thereafter ) or placebo . Patients were reevaluated at 6-week intervals to measure change from baseline in several outcome measures , including right , left , and total hippocampal volumes , measured with magnetic resonance imaging ; brain concentrations of N-acetylaspartate , measured with proton magnetic resonance spectroscopy ; and cognition , assessed with the Alzheimer 's Disease Assessment Scale cognitive subscale . RESULTS At some interim assessment s , mean normalized measures of N-acetylaspartate concentration tended to be higher in the donepezil-treated patients than in the patients who received placebo , but these differences were not significant at endpoint . At endpoint , the donepezil-treated patients had significantly smaller mean decreases in total and right hippocampal volumes and a smaller , nearly significant mean decrease in left hippocampal volume , compared with the placebo-treated patients . Mean Alzheimer 's Disease Assessment Scale cognitive subscale scores were improved after treatment with donepezil , relative to placebo , at weeks 6 , 12 , 18 , and 24 . CONCLUSIONS These preliminary results suggest that donepezil may have a potentially protective effect in Alzheimer 's disease . Larger , longer-term confirmatory studies of the medication 's effects are warranted 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 OBJECTIVE To determine the efficacy of donepezil hydrochloride for the treatment of Alzheimer disease in patients drawn from clinical practice . DESIGN Two-center , r and omized , placebo-controlled , double-masked crossover study 
    Output:
    
Benefits of treatment were also seen on measures of activities of daily living and behaviour , but not on the quality of life score .
There were significantly more withdrawals before the end of treatment from the 10 mg/day ( but not the 5 mg/day ) donepezil group compared with placebo which may have result ed in some overestimation of beneficial changes at 10 mg/day .
Benefits on the 10 mg/day dose were marginally larger than on the 5 mg/day dose .
People with mild , moderate or severe dementia due to Alzheimer 's disease treated for periods of 12 , 24 or 52 weeks with  donepezil  experienced benefits in cognitive function , activities of daily living and behaviour .
Study clinicians rated global clinical state more positively in treated patients , and measured less decline in measures of global disease severity .
There is some evidence that use of donepezil is neither more nor less expensive compared with placebo when assessing total health care re source costs .
Benefits on the 10 mg/day dose were marginally larger than on the 5 mg/day dose .
Taking into consideration the better tolerability of the 5 mg/day donepezil compared with the 10 mg/day dose , together with the lower cost , the lower dose may be the better option .