***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: 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 Evidence from animal experiments has suggested that the triggering and maintenance of rapid eye movement ( REM ) sleep is mainly under the control of cholinergic neurons in the brain stem . Correspondingly , studies in humans have demonstrated that the application of cholinergic agonists or cholinesterase inhibitors provokes an earlier onset of REM sleep . The present study investigated the influence of galanthamine hydrobromide , a reversible cholinesterase inhibitor , on REM sleep regulation in 18 healthy volunteers . After an adaptation night , the subjects were given two doses of galanthamine ( 10 mg and 15 mg ) or placebo at 10 p.m. in a r and omized double-blind design . Both doses of galanthamine shortened REM latency ( with statistical significance depending on the definition of REM latency used ) , increased REM density , and reduced slow wave sleep mainly in the first non-REM cycle . Higher doses of galanthamine ( 15 mg ) seem to be accompanied by unwanted side effects that warrant the application of a peripheral antidote . These results are comparable to those for other cholinomimetics and stress the usefulness of galanthamine for pharmacological challenge studies in healthy subjects and depressed patients Background Patients with Alzheimer 's disease experience a progressive loss of cognitive function , and the ability to independently perform activities of daily life . Sometimes a dependent stage is reached quite early in the disease , when caregivers decide that the patients can no longer be left alone safely . This is an important aspect of Alzheimer 's for patients , their families , and also health care providers . Underst and ing the relationship between a patient 's current cognitive status and their need for care may assist clinicians when recommending an appropriate management plan . In this study , we investigated the relationship of cognitive function to dependence on caregivers before the patients reach a severe stage of the disease . Methods Data were obtained on 1,289 patients with mild-to-moderate Alzheimer 's disease studied in two r and omised clinical trials of galantamine ( Reminyl ® ) . Cognition was assessed using the cognitive part of the Alzheimer 's Disease Assessment Scale ( ADAS-cog )  and  Mini-Mental State Examination ( MMSE ) . Patients were considered dependent if they required > 12 hours of supervision each day or had high care needs . The Disability Assessment for Dementia ( DAD ) scale was also used as a measure of dependence . Disability was predicted directly using MMSE and ADAS-cog and compared to predictions from converted scores . Results The odds ratio of dependence was significantly higher amongst the patients with worse cognitive impairment , adjusting for age , gender and antipsychotic medication use . For example , a 4-point difference in ADAS-cog score was associated with an increase of 17 % ( 95 % CI 11–23 ) in the adjusted odds for > 12 hours of supervision , and of 35 % ( 95 % CI 28–43 ) for dependence . Disability predicted directly using actual ADAS-cog and scores converted from MMSE values had close agreement using the models developed . Conclusion In patients with mild-to-moderate Alzheimer 's disease , even relatively small degrees of poorer cognitive function increased the risk of losing the ability to live independently STUDY OBJECTIVES To recognize the potential effect of acetylcholinesterase-inhibiting medications on sleep quality when used for the treatment of mild to moderate Alzheimer disease and describe sleep outcomes for patients treated with galantamine .  DESIGN This study examined sleep quality among individuals with mild to moderate Alzheimer disease using data from a 3-month , double-blind , flexible-dose trial of galantamine . The hypothesis was no difference in sleep quality between galantamine- and placebo-treated subjects . PATIENTS 136 patients treated with galantamine 24 mg per day and 125 patients treated with placebo .  MEASUREMENTS Based on caregiver reports , the sleep-related outcome measures were the Pittsburgh Sleep Quality Index and the sleep disorders item from the Neuropsychiatric Inventory . Using a P-value of 0.05 ( 2-tailed ) , analysis of covariance was used to compare treatments on mean change from baseline to month 3 ( Pittsburgh Sleep Quality Index ) or mean score at month 3 ( Neuropsychiatric Inventory ) , adjusted for baseline score and investigator . RESULTS Both patient groups had an average age of 75 years and a mean Mini-Mental Status Examination score of 20 . There were no significant differences between groups on the Pittsburgh Sleep Quality Index total ( P=0.59 ) or subscales . For galantamine and placebo , the mean adjusted changes from baseline on the total Pittsburgh Sleep Quality Index were 0.01 and -0.17 , respectively . There also was no difference on the Neuropsychiatric Inventory sleep score at month 3 ( P=0.51 ) . CONCLUSIONS Medications to treat Alzheimer disease should maintain sleep quality and have a neutral effect on sleep . These results further confirm the lack of sleep problems associated with galantamine treatment BACKGROUND Alzheimer 's disease ( AD ) is estimated to affect up to 11 % of those aged > or = 65 years in the United States , and the number of patients with AD is predicted to increase over the next few decades as the population ages . The substantial social and economic burden associated with AD is well established , with the cost of management increasing as the disease progresses . OBJECTIVE The aim of this study was to evaluate the economic impact of galantamine 16 and 24 mg/d relative to no pharmacologic treatment in the management of mild to moderate AD in the United States based on the concept of need for full-time care ( FTC ) . METHODS Calculations were made using the Assessment of Health Economics in Alzheimer 's Disease model , which applies predictive equations to estimate the need for FTC and the associated costs . The predictive equations were developed from longitudinal data on patients with AD . Inputs to the equations were derived by analyzing the data from 2 r and omized , placebo-controlled , galantamine clinical trials . Re source use ( from a payer perspective ) was estimated from US clinical trial data , and costs were estimated from several US data bases . Analyses were carried out over 10 years , and costs and benefits were discounted at 3 % . RESULTS In the base case , 3.9 to 4.6 patients need to start treatment with galantamine to avoid 1 year of FTC , depending on dose . Treated patients spent 7 % to 8 % more time pre-FTC and 12 % to 14 % less time requiring FTC , result ing in savings of 2408 to 3601 US dollars . Time horizons below 3 years , very high discontinuation rates , or increased survival with galantamine reversed the savings . Conversely , limiting treatment to responders delayed FTC by 6 to 7 months , with savings of approximately 9097 to 11,578 US dollars . CONCLUSIONS These results suggest that use of galantamine in patients with AD in the United States could reduce the use of costly re sources such as formal home care and nursing homes , leading to cost savings over time The effects of the long-acting acetylcholinesterase ( AChE ) inhibitor , galanthamine , on spatial memory were investigated in mice . Mice received ibotenic acid or sham lesions to the nucleus basalis magnocellularis ( nBM ) . Groups of nBM-lesioned and control mice were then trained on a modified Morris swim maze task . Each mouse was first placed on a platform and then into quadrants of the swim tank in a r and om order . Time required to find the hidden platform was measured . In different phases of testing , the animal had to find a platform that either remained in the same quadrant ( reference memory component ) or was moved daily ( working memory component ) . The nBM-lesioned mice took significantly longer to find the platform as compared to controls on the working , but not on the reference , memory component of the task . Galanthamine ( 5.0 mg/kg , IP ) , given 3.5 hours before testing , improved performance on the working memory task in nBM-lesioned mice by 70 % and strikingly impaired performance in controls . Galanthamine 's ability to reverse cognitive deficits induced by nBM lesions and its comparatively long half-life suggest that it may be effective in treating the central cholinergic deficits in Alzheimer 's disease patients BACKGROUND Alzheimer 's disease ( AD ) and vascular dementia ( VaD ) are the most common types of dementia worldwide . Galantamine , an acetylcholinesterase inhibitor and allosteric nicotinic modulator , has shown broad clinical benefits in patients with mild to moderate dementia due to AD , probable VaD , or AD with cerebrovascular disease (CVD)-so-called mixed dementia . OBJECTIVE The purpose of this study was to evaluate the efficacy and safety profiles of galantamine 24 mg/d in patients with VaD or AD with CVD over the longer term ( > 6 months ) . METHODS This was an open-label extension of a 6-month double-blind study of galantamine .  Patients who had been r and omized to receive galantamine 24 mg/d or placebo in the double-blind phase were eligible to continue open-label treatment with galantamine 24 mg/d for 6 months . The primary efficacy end point was change in cognition , based on scores on the 11-item Alzheimer 's Disease Assessment Scale-cognitive subscale ( ADAS-cog/11 ) . Secondary measures included changes in functional ability ( as measured on the Disability Assessment for Dementia [ DAD ] ) and behavior ( as measured on the Neuropsychiatric Inventory [ NPI ] ) . Safety and tolerability were also monitored . RESULTS Four hundred fifty-nine patients ( 240 men , 219 women ; mean [ SE ] age , 75.2 [ 0.33 ] years ) entered the open-label phase . Of these patients , 195 ( 42.5 % ) had a diagnosis of probable VaD , and 238 ( 51.9 % ) had a diagnosis of AD with CVD ; the remainder had an inconclusive diagnosis . At month 12 of the study , improvements from baseline ( the start of the double-blind phase ) in ADAS-cog/11 scores were observed in both the group that received placebo during the double-blind phase ( placebo/galantamine group : -0.3 point ; 95 % CI , -1.64 to 1.06 ) and the group that received galantamine during the double-blind phase ( galantamine/galantamine group : -0.9 point ; 95 % CI , -1.73 to 0.03 ) . Improvement in functional ability was demonstrated by statistically significant mean ( SE ) changes from baseline in DAD score in both the placebo/galantamine group ( -7.4 [ 1.68 ] ; P < or = 0.001 ) and the galantamine/galantamine group ( -3.6 [ 1.33 ] ; P < or = 0.01 ) . There was no significant change in mean ( SE ) NPI scores in either group ( 0.2 [ 0.98 ] and 0.1 [ 0.70 ] , respectively ) . Galantamine treatment was well tolerated . CONCLUSIONS In these patients with VaD and AD with CVD , galantamine treatment produced similar sustained benefits in terms of maintenance of or improvement in cognition ( ADAS-cog/11 ) , functional ability ( DAD ) , and behavior ( NPI ) after 12 months To investigate whether Galantamine significantly improves the core symptoms of Alzheimer 's disease ( AD ) OBJECTIVE To assess the efficacy and safety of galantamine in Alzheimer 's disease at 3 months using flexible dose escalation . METHODS A r and omised , double blind , placebo controlled trial in 43 cent 
    Output:
    
Galantamine consistently failed to show statistically significant treatment effects at doses of 8mg/day .
Galantamine 's adverse effects appear similar to those of other cholinesterase inhibitors , in that it tends to produce gastrointestinal effects acutely and with dosage increases .
REVIEW ER 'S CONCLUSIONS Patients in these trials were similar to those seen in earlier antidementia AD trials , and consisted primarily of mildly to moderately impaired out patients .
Galantamine 's effects on more severely impaired subjects has not yet been assessed .
In addition , although there was not a statistically significant dose-response effect , doses above 8mg/d were , for the most part , consistently statistically significant .
Thus , there is evidence demonstrating efficacy for galantamine on global ratings , cognitive tests , assessment s of ADLs and behavior .
This magnitude for the cognitive effect is similar to other cholinesterase inhibitors including donepezil , rivastigmine , and tacrine .
Galantamine 's safety profile is similar to other cholinesterase inhibitors with respect to cholinergically mediated gastrointestinal symptoms .