***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 
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    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 Alzheimer 's disease is a progressive , neurodegenerative condition characterized by deficits in cognition , inability to perform activities of daily living , and alterations in behavior . Galantamine hydrobromide is the newest acetylcholinesterase inhibitor ( AChEI ) approved in the United States for the treatment of mild-to-moderate AD . The safety and efficacy of galantamine has been demonstrated in multiple r and omized , Phase III trials of > 2,600 patients with mild-to-moderate AD . Studies have found that galantamine  improved or maintained performance in all domains of AD ( cognition , function , behavior , and caregiver burden ) in the short term and slowed the decline in performance or maintained baseline performance through 12 months . The dual mechanism of action may make galantamine a reasonable treatment option for both newly diagnosed patients and patients who have not benefitted from or have poorly tolerated current therapy 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 The relationship between cholinergic dysfunction and cognitive and functional impairment in patients with vascular dementia ( VaD ) and Alzheimer 's disease ( AD ) with cerebrovascular disease ( CVD ) suggests a potential role for cholinomimetic therapy . Initial studies of galantamine demonstrated cognitive , behavioral , and functional benefits in these population s. 326 patients with VaD or AD with CVD who completed an initial 12-month trial were treated with galantamine 24 mg/day in a 24-month , open-label extension . This interim analysis was performed at month 12 of the open-label extension ( 248 completed the trial ) . Galantamine ( up to 24 months total ) was well tolerated in both groups . The most frequently reported adverse events , characteristic of older dementia patients , included depression , agitation , and insomnia . Gastrointestinal adverse events were less common than initially , indicating declining incidence with long-term therapy . Patients taking galantamine for the entire study demonstrated the least cognitive decline on AD Assessment Scale-cog/11 : 2.7 points vs. 3.1 points in those given placebo initially ( P < 0.001 and P = 0.003 , respectively ) . The long-term benefits of galantamine were evident in both groups ; cognitive baseline levels were maintained for approximately 21 months in VaD patients and for 12 months in patients with AD with CVD . Long-term ( up to 24 months ) galantamine therapy in patients with VaD and AD with CVD is well tolerated and associated with prolonged maintenance of cognitive function SUMMARY Background : Acetylcholinesterase inhibitors ( AChEI ) are now widely used as treatment for Alzheimer 's disease ( AD ) . Their cholinomimetic action has the potential to influence sleep quality and donepezil has been associated with sleep-related adverse events . This study examined whether galantamine , an AChEI with nicotinic modulation , is associated with nighttime sleep-related problems . Methods : Using data combined from three r and omized , double-blind trials ,  galantamine ( GAL ) and placebo-treated patients were compared on sleep-related adverse events and concomitant medications . Verbatim descriptions by patients , as recorded by physicians , were used to classify adverse events into insomnia/sleep problems and nightmares/dreams . New concomitant medications were counted when prescribed for sleep-related indications . Treatment arms were 705 subjects on GAL 24 mg ( 12 mg BID ) , 279 on GAL 16 mg ( 8 mg BID ) , and 714 on placebo .  Results : Comparing GAL 24 , GAL 16 , and placebo arms , the respective rates for insomnia/ sleep problems were 2.6 , 1.1 , and 2.2 % and for nightmares were 1.1 , 0.4 , and 0.1 % . Comparisons between GAL arms and placebo were not significant , with the exception of GAL 24 for nightmares ( p = 0.02 ) . However , due to the low frequency of nightmares in each group the clinical relevance of this difference is unknown . Rates of use for all concomitant medications indicated for sleep were 5.4 , 2.9 , and 4.6 % , respectively , with no significant differences between GAL arms and placebo . Conclusion : These results support previous findings from double-blind , placebo-controlled studies that have shown maintenance of good sleep hygiene during treatment with galantamine 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 OBJECTIVE The authors evaluated the long-term safety , efficacy , and tolerability of galantamine 24 mg/day in the treatment of Alzheimer disease by means of a 12-month , open-label extension of an earlier 5-month , double-blind , placebo-controlled trial with a 6-week withdrawal phase . METHODS Patients completing two double-blind , placebo-controlled trials ( N=699 ) were escalated to a 24-mg dose ( 12 mg bid ) of galantamine during a period of 2 weeks and treated for 12 months beyond the initial 6.5-month , double-blind period ( total treatment duration : 18.5 months ) . The primary efficacy measure was the change from baseline in the Alzheimer 's Disease Assessment Scale ( ADAS-Cog/11 ) score at 18.5 months ; secondary endpoints included total scores on the Alzheimer 's Disease Cooperative Study of Activities of Daily Living and the Neuropsychiatric Inventory . St and ard safety evaluations , including adverse-event monitoring , were performed . RESULTS Patients taking galantamine continuously throughout the double-blind and open-label studies ( N=288 ) showed sustained cognitive benefits on ADAS-Cog/11 scores at 18.5 months . Patients were maintained close to baseline cognitive ability for 12 months , and safety was as expected and documented in other large studies of galantamine . Analysis of the subgroup of patients ( N=113 ) who completed the entire 18.5 months of galantamine treatment showed that cognitive function was maintained up to 14 months . CONCLUSIONS Results of this open-label extension support the findings from previous galantamine studies and demonstrate the safety and tolerability of galantamine for up to 18.5 months 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 
    Output:
    
Galantamine 's  adverse effects appeared similar to those of other cholinesterase inhibitors and to be dose related .
Prolong release / once daily formulation of galantamine at 16 - 24mg/d was found to have similar efficacy and side-effect profile as the equivalent twice-daily regime .
AUTHORS ' CONCLUSIONS Subjects in these trials were similar to those seen in earlier anti dementia AD trials , consisting primarily of mildly to moderately impaired out patients .
Galantamine 's effect on more severely impaired subjects has not yet been assessed .
Although there was not a statistically significant dose-response effect , doses above 8 mg/d were , for the most part , consistently statistically significant .
Galantamine 's  safety profile in AD is similar to that of other cholinesterase inhibitors with respect to cholinergically mediated gastrointestinal symptoms .
It appears that doses of 16 mg/d were best tolerated in the single trial where medication was titrated over a four week period , and because this dose showed statistically indistinguishable efficacy with higher doses , it is probably most preferable initially .