***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: Introduction Progressive language impairment is among the primary components of cognitive decline in Alzheimer 's disease ( AD ) . Because expressive and receptive language help to maintain emotional connections to caregivers and support the management of AD patients ' functional needs , language plays a critical role in patients ' emotional and physical health . Using data from a large prospect i ve clinical trial comparing two doses of donepezil in patients with moderate to severe AD , we performed a post hoc analysis to determine whether a higher dose of donepezil was associated with greater benefits in language function . Methods In the original r and omized , double-blind clinical trial , 1,467 patients with moderate to severe AD ( baseline Mini-Mental State Examination ( MMSE ) score 0 to 20 ) were r and omized 2:1 to receive donepezil 23 mg/day or to continue on donepezil 10 mg/day for 24 weeks . In this post hoc analysis , the Severe Impairment Battery- Language scale ( SIB-L ) and a new 21-item SIB-derived language scale ( SIB[lang ] ) were used to explore differences in language function between the treatment groups . Correlations between SIB-L and SIB[lang ] scores and scores on the severe version of the Alzheimer 's Disease Cooperative Study -Activities of Daily Living inventory ( ADCS-ADL-sev ) , the Clinician 's Interview-Based Impression of Severity-plus caregiver input/Clinician 's Interview-Based Impression of Change-plus caregiver input ( CIBIS-plus/CIBIC-plus ) and the MMSE were also investigated . Results At week 24 , treatment with donepezil 23 mg/day was associated with an improvement in language in the full intention-to-treat population , whereas language function declined in the group treated with donepezil 10 mg/day ( SIB-L treatment difference 0.8 , P = 0.0013 ; SIB[lang ] treatment difference 0.8 , P = 0.0009 ) . Similar results were observed in a cohort of patients with more severe baseline disease ( MMSE score 0 to 16 ) . At baseline and week 24 , correlations between the SIB-derived language scales and the ADCS-ADL-sev and CIBIC-plus were moderate , but the correlations were stronger between the language scales and the MMSE scores . Conclusions Patients with moderate to severe AD receiving donepezil 23 mg/day showed greater language benefits than those receiving donepezil 10 mg/day as measured by SIB-derived language assessment s. Increasing the dose of donepezil to 23 mg/day may provide language benefits in patients with moderate to severe AD , for whom preservation of language abilities is especially critical . Clinical Trials.gov identifier : 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 Donepezil 23 mg/d , recently approved in the United States for treatment of moderate to severe Alzheimer 's disease ( AD ) , was developed to address the need for an additional treatment option for patients with advanced AD . This report , based on a pivotal phase 3 study , presents a detailed analysis of the safety and tolerability of increasing donepezil to 23 mg/d compared with continuing 10 mg/d . MethodS afety analyses comprised examination of the incidence , severity , and timing of treatment-emergent adverse events ( AEs ) and their relationship to treatment initiation ; changes in weight , electrocardiogram , vital signs , and laboratory parameters ; and the incidence of premature study discontinuation .  The analysis population ( n = 1434 ) included all r and omized patients who took at least 1 dose of study drug and had a postbaseline safety assessment . To further examine the effect of transition from a lower to a higher donepezil dose , a pooled analysis of safety data from 2 phase 3 trials of donepezil 5 mg/d and 10 mg/d was also performed . Results The safety population comprised 1434 patients : donepezil 23 mg/d ( n = 963 ) ;  donepezil  10 mg/d ( n = 471 ) ; completion rates were 71.1 % and 84.7 % , respectively . The most common AEs were nausea , vomiting , and diarrhea ( donepezil 23 mg/d : 11.8 % , 9.2 % , 8.3 % ; donepezil 10 mg/d : 3.4 % , 2.5 % , 5.3 % , respectively ) . AEs that contributed most to early discontinuations were vomiting ( 2.9 % of patients in the 23 mg/d group and 0.4 % in the 10 mg/d group ) , nausea ( 1.9 % and 0.4 % ) , diarrhea ( 1.7 % and 0.4 % ) , and dizziness ( 1.1 % and 0.0 % ) . The percentages of patients with AEs in the 23 mg/d group , as well as the timing , type , and severity of these AEs , were similar to those seen in previous donepezil trials with titration from 5 to 10 mg/d . Serious AEs were uncommon ( 23 mg/d , 8.3 % ; 10 mg/d , 9.6 % ) . Discussion The 23 mg/d dose of donepezil was associated with typical cholinergic AEs , particularly gastrointestinal-related AEs , similar to those observed in studies with a dose increase from 5 to 10 mg/d . Conclusion The good safety and predictable tolerability profile for donepezil 23 mg/d supports its favorable risk/benefit ratio in patients with moderate to severe AD.Trial Registration 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 BACKGROUND Donepezil has been used worldwide for the treatment of severe Alzheimer 's disease ( AD ) . Whether it is also appropriate for severe AD in Chinese patients remains unknown . OBJECTIVE To determine whether donepezil is effective and tolerable for Chinese patients with severe AD . METHODS The present study was a 24-week , multicenter , double-blind , r and omized , placebo-controlled , parallel-group study conducted at 38 investigational hospitals in China . Patients with severe AD were enrolled in this trial . Patients were r and omly assigned in a 1:1 ratio to receive either donepezil or placebo ( 5 mg for 6 weeks and 10 mg for the remaining 18 weeks ) . The efficacy for donepezil were evaluated by the SIB , the Clinician 's Interview-Based Impression of Change-Plus caregiver input ( CIBIC-plus ) and the MMSE . Safety parameters were monitored throughout . RESULTS A total of 313 patients included the donepezil ( n = 157 ) and the placebo groups ( n = 156 ) . Donepezil group improved more in SIB scores ( least squares [ LS ] mean difference : 4.8 , 95 % CI 1.56 to 8.08 , p = 0.004 ) and CIBIC-plus scores ( drug-placebo difference : -0.4 , 95 % CI -0.66 to 0.03 , p = 0.04 ) than placebo groups at Week 24 . The MMSE scores between drug and placebo groups did not differ significantly . Twenty-nine patients with serious adverse events ( SAEs ) were reported in donepezil ( n = 11 ) and placebo groups ( n = 18 ) ( p = 0.08 ) . Most SAEs were not considered drug-related . CONCLUSION Donepezil for 24 weeks was more effective than placebo and showed good safety and tolerability in Chinese patients with severe AD . This study supports utility of the drug in severe stages of AD in the Chinese population Background Donepezil ( 23 mg/day ) is approved by the US Food and Drug Administration for the treatment of patients with moderate to severe Alzheimer ’s disease ( AD ) . Approval was based on results from a 24-week , r and omized , double-blind study of patients who were stable on donepezil 10 mg/day and r and omized 2:1 to either increase their donepezil dose to 23 mg/day or continue taking 10 mg/day . The objective of this study was to assess the long-term safety and tolerability of donepezil 23 mg/day in patients with moderate to severe AD . Methods Patients who completed the double-blind study and were eligible could enroll into a 12-month extension study of open-label donepezil 23 mg/day . Clinic visits took place at open-label baseline and at months 3 , 6 , 9 , and 12 . Safety analyses comprised examination of the incidence , severity , and timing of treatment-emergent adverse events ( AEs ) ; changes in weight , electrocardiogram , vital signs , and laboratory parameters ; and discontinuation due to AEs . Results 915 double-blind study completers were enrolled in the open-label extension study and 902 comprised the safety population . Mean treatment duration in this study was 10.3 ± 3.5 months . In total , 674 patients ( 74.7 % ) reported at least one AE ; in 320 of these patients ( 47.5 % ) at least one AE was considered to be possibly or probably study drug related . The majority of patients reporting AEs ( 81.9 % ) had AEs of mild or moderate severity . There were 268 patients ( 29.7 % ) who discontinued early , of which 123 ( 13.6 % ) were due to AEs . Patients increasing donepezil dose from 10 mg/day in the double-blind study to 23 mg/day in the extension study had slightly higher rates of AEs and SAEs than patients who were already receiving 23 mg ( 78.0 % and 16.9 % vs 72.8 % and 14.0 % , respectively ) . The incidence of new AEs declined rapidly after the first 2 weeks and remained low throughout the duration of the study . Conclusion This study shows that long-term treatment with donepezil 23 mg/day is 
    Output:
    
Participants receiving donepezil were more likely to withdraw from the studies before the end of treatment ( 24 % versus 20 % , OR 1.25 , 95 % CI 1.05 to 1.50 , 2846 participants , 12 studies ) or to experience an adverse event during the studies ( 72 % vs 65 % , OR 1.59 , 95 % 1.31 to 1.95 , 2500 participants , 10 studies ) .There was no evidence of a difference between donepezil and placebo for patient total healthcare re source utilisation .
There is moderate- quality evidence that people with mild , moderate or severe dementia due to Alzheimer 's disease treated for periods of 12 or 24 weeks with donepezil experience small benefits in cognitive function , activities of daily living and clinician-rated global clinical state .
There is some evidence that use of donepezil is neither more nor less expensive compared with placebo when assessing total healthcare re source costs .
Benefits on 23 mg/day were no greater than on 10 mg/day , and benefits on the 10 mg/day dose were marginally larger than on the 5 mg/day dose , but the rates of withdrawal and of adverse events before end of treatment were higher the higher the dose