***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 . The purpose of this study was to examine the behavioural and cognitive effects of selegiline in a group of moderately behaviourally disturbed AD patients Background : Short-term studies of L-deprenyl in Alzheimer 's disease ( AD ) suggest a beneficial effect , whereas longer-term studies are less convincing . Accordingly , we undertook a 6-month , r and omized , double-blind , placebo-controlled clinical trial to assess the potential benefit of L-deprenyl in AD . Methods : Sixty subjects were assigned to L-deprenyl ( 10 mg daily ) or placebo .  After 4 weeks of single-blind placebo , 51 subjects entered the double-blind phase . The Brief Psychiatric Rating Scale ( BPRS ) was the primary outcome measure . Secondary outcome measures were the Mini-Mental State Examination , Global Deterioration Scale , Alzheimer 's Disease Assessment Scale ( noncognitive ) , Cornell Scale for Depression in Dementia , Buschke Selective Reminding Test(BSRT ) , Relative 's Assessment of Global Symptomatology-Elderly ( RAGS-E ) , Controlled Oral Word Association Test , and Modified Continuous Performance Test . In addition , several exploratory tasks were included for future hypothesis testing . Results : We found no significant differences between the L-deprenyl and placebo groups on the primary or secondary measures . However , several measures appeared to be sensitive to change over time , including the total score on the BPRS and some of its components as well as parts of the BSRT and the RAGS-E. Conclusion : Oral L-deprenyl provides no detectable benefit on general behavior , neuropsychiatric symptoms , or cognitive function in AD after 6 months of treatment . Protocol s for future drug studies should utilize measures that are sensitive to change over time such as the BPRS Although the central cholinergic deficits are still considered to be of primary importance in Alzheimer 's disease , there is great need for an expansion of the pharmacological approach in this illness beyond the simple cholinergic replacement hypothesis . This report focuses on the concept of " combination chemotherapy " in Alzheimer 's disease as the next generation of therapeutic strategies . Based on earlier positive findings in Alzheimer patients with the monoamine oxidase B inhibitor , 1-deprenyl  , the authors speculate that a combination of physostigmine , the short-acting cholinesterase inhibitor , and 1-deprenyl might be more beneficial than either agent alone . The authors outline a sample paradigm for such combination studies , report preliminary data on the first 16 Alzheimer subjects to have received an initial combination of physostigmine and deprenyl , and point to other possible " combination chemotherapy " strategies for future study In a double blind r and omized crossover trial lasting 6 months selegiline , a selective MAO-B inhibitor , was tested against placebo for activity on verbal memory performances in Alzheimer-type dementia ( DAT ) .  Verbal memory was assessed with the Rey-Auditory-Verbal Learning Test at the start of treatment , at the time scheduled for crossover ( 90 days ) and at the end of the trial ( 180 days ) . The results suggest that selegiline possesses significant activity on some memory parameters , which seems to depend on an improvement both in information processing abilities and in learning strategies at the moment of acquisitionSommarioIn uno studio doppio cieco cross-over , r and omizzato verso placebo della durata di sei mesi , è stata analizzata l'influenza della selegilina , inibitore selettivo delle MAO-B , sulle prestazioni di memoria verbale di 22 pazienti con diagnosi clinica di demenza tipo Alzheimer ( DAT ) . L'esame della memoria verbale è stato effettuato con il Rey-Auditory Verbal Learning test all'inizio del trattamento , dopo 90 giorni , momento previsto per il cross-over , e dopo 180 giorni , al termine della sperimentazione . I risultati suggeriscono una significativa efficacia della selegilina su alcuni parametri di memoria , che sembrano riconducibili ad un miglioramento sia delle capacità di elaborazione delle informazioni , sia delle strategie di apprendimento al momento dell'acquisizione The present study evaluated the safety of and obtained preliminary data on the cognitive effects of L-deprenyl and physostigmine in patients with Alzheimer 's Disease . Seventeen out patients with Alzheimer 's Disease participated in a double-blind crossover study in which they received 4 weeks of L-deprenyl at a dose of 10 mg p.o . , q.d . , and 4 weeks of placebo in r and om order . During both the L-deprenyl and placebo periods , patients received cognitive assessment s during physostigmine ( 0.5 mg ) and placebo infusions separated by 2 days . The cognitive effects of these agents alone and in combination were measured with digit span , verbal fluency , list learning , praxis , delayed recall , and delayed recognition tasks .  Fifteen patients completed the study . The two drugs , used alone or in combination , were safe and well tolerated . Analyses of variance demonstrated that neither physostigmine nor L-deprenyl , whether given alone or in combination , significantly improved cognition , when compared with the double placebo condition The efficacy and tolerability of the monoamine oxidase B inhibitor selegiline and of the nootropic agent oxiracetam were compared in a single-blind , controlled , parallel study . The trial involved 22 men and 18 women with mild-to-moderate senile and presenile dementia of the Alzheimer type . The treatments were administered for 90 consecutive days as follows : one 10-mg selegiline tablet once daily and one 800-mg oxiracetam tablet twice daily . Efficacy was evaluated by means of a complex battery of neuropsychological tests , administered monthly for three months , starting from baseline . Safety was evaluated by monitoring adverse drug reactions as well as any pathological changes in hematology , blood chemistry , or liver and kidney function , measured at baseline and again at the conclusion of the study . Analysis of the results demonstrates that , at the dosage used , selegiline is more effective than oxiracetam in improving higher cognitive functions and reducing impairment in daily living . In particular , short- and long-term memory , sustained concentration , attention , verbal fluency , and visuospatial abilities were , for the most part , positively affected by selegiline .  Gastroenteric and systemic tolerability of both drugs was also very good Ten patients diagnosed as affected by primary degenerative dementia of the Alzheimer type , with a mild to moderate cognitive and behavioral impairment , were studied in a double blind design when taking for 60 days 5 mg twice a day of L-deprenyl or placebo .  Cognitive functions and cerebral blood flow were assessed at the beginning and at the end of treatment by a wide array of memory , attention , and language efficiency measures and by SPECT-99TcHMPAO procedure . Reduced CBF on the parietal lobes was demonstrated in the patients at baseline together with a reduction of memory and cognitive efficiency . At the end of the treatment patients who received L-deprenyl showed an improvement in cognitive efficiency and no changes in CBF , while patients treated with placebo showed a worsening of cognitive efficiency and further reduction of parietal lobe CBF BACKGROUND There is evidence that medications or vitamins that increase the levels of brain catecholamines and protect against oxidative damage may reduce the neuronal damage and slow the progression of Alzheimer 's disease . METHODS We conducted a double-blind , placebo-controlled , r and omized , multicenter trial in patients with Alzheimer 's disease of moderate severity . A total of 341 patients received the selective monoamine oxidase inhibitor selegiline ( 10 mg a day ) , alpha-tocopherol ( vitamin E , 2000 IU a day ) , both selegiline and alpha-tocopherol , or placebo for two years . The primary outcome was the time to the occurrence of any of the following : death , institutionalization , loss of the ability to perform basic activities of daily living , or severe dementia ( defined as a Clinical Dementia Rating of 3 ) . RESULTS Despite r and om assignment , the baseline score on the Mini-Mental State Examination was higher in the placebo group than in the other three groups , and this variable was highly predictive of the primary outcome ( P<0.001 ) . In the unadjusted analyses , there was no statistically significant difference in the outcomes among the four groups . In analyses that included the base-line score on the Mini-Mental State Examination as a covariate , there were significant delays in the time to the primary outcome for the patients treated with selegiline ( median time , 655 days ; P=0.012 ) , alpha-tocopherol ( 670 days , P=0.001 ) or combination therapy ( 585 days , P=0.049 ) , as compared with the placebo group ( 440 days ) . CONCLUSIONS In patients with moderately severe impairment from Alzheimer 's disease , treatment with selegiline or alpha-tocopherol slows the progression of disease The potential efficacy of oral l-deprenyl ( 5 mg b.i.d . ) added to the regimen of 10 patients with Alzheimer 's disease receiving either tacrine or physostigmine  was assessed in a double-blind , placebo-controlled , 4-week , two-period crossover pilot study . l-Deprenyl was associated with significant improvement in scores on the cognitive subscale of the Alzheimer 's Disease Assessment Scale , suggesting possible additive effects of l-deprenyl to the effects of cholinesterase inhibitors Controlled clinical trials of the treatment of acute myocardial infa rct ion offer a unique opportunity for the study of the potential influence on outcome of bias in treatment assignment . A group of 145 papers was divided into those in which the r and omization process was blinded ( 57 papers ) , those in which it may have been unblinded ( 45 papers ) , and those in which the controls were selected by a nonr and om process ( 43 papers ) . At least one prognostic variable was maldistributed ( P less than 0.05 ) in 14.0 per cent of the blinded-r and omization studies , in 26.7 per cent of the unblinded-r and omization studies , and in 58.1 per cent of the nonr and omized studies . Differences in case-fatality rates between treatment and control groups ( P less than 0.05 ) were found in 8.8 per cent of the blinded-r and omization studies , 24.4 per cent of the unblinded-r and omization studies , and 58.1 per cent of the nonr and omized studies . These data emphasize the importance of keeping those who recruit patients for clinical trials from suspecting which treatment will be assigned to the patient under consideration BACKGROUND Currently there is no regimen for managing the inappropriate behavior seen in Alzheimer 's disease that does not cause significant patient sedation . Preliminary evidence suggests selegiline may be effective in behavioral modification without the adverse effects observed with other regimens . The purpose of this study was to document the efficacy of selegiline in Alzheimer 's patients with behavior problems . METHOD Eight Alzheimer 's patients ( 6 women and 2 men ) ranging in age from 50 to 82 years ( mean + /- SD = 74.0 + /- 10.5 ) were enrolled in this single-blind study . Patients received selegiline 10 mg each day for 8 weeks . Prior to drug administration and at the end of Weeks 1 , 2 , 4 , 6 , and 8 , patients were evaluated for behavior ( BEHAVEAD ) , cognitive function ( Mini-Mental State Examination ) , and caregiver stress ( Caregiver Burden Scale ) . RESULTS Of eight enrolled patients , five were available for analysis . No statistically significant differences were found between mean baseline and mean 8-week scores for any of the three tests . However , clinical significance was noted by improvement in cognition ( orientation and recall ) , caregiver stress , and behavior . Behavior was noted to improve in the areas of paranoid and delusional ideation , hallucinations , activity disturbances , anxiety , and phobias . CONCLUSION These data suggest that some Alzheimer 's patients with behavior problems may benefit from selegiline therapy This report describes the rationale and design of a clinical trial using selegiline ( 10 mg/day ) and alpha-tocopherol ( 2,000 IU/day ) to slow the progression of dementia in Alzheimer disease ( AD ) . This study was developed by the Alzheimer 's Disease Cooperative Study ( ADCS ) , a consortium of clinical research centers actively involved in AD research . The major goal of the consortium is to design and conduct clinical investigations leading to the development of treatments for AD . This study uses a r and omized double-blind , placebo-controlled , 2 x 2 factorial , parallel group design to test two drugs for the treatment of AD . The primary outcome of the study is the time to reach any one of the following four endpoints : death , institutionalization , loss of two of three basic activities of daily living , and progression of Clinical Dementia Rating ( CDR ) stage from 2 to 3 . Patients with moderately severe disease ( CDR = 2 ) were enrolled and evaluated 10 times over a period of 2 years to determine if these agents reduce the time to reach any endpoint . A data base from the Consortium to Establish a Registry for Alzheimer 's Disease indicated adequate power analyses to observe a treatment effect on this clinical ly meaningful outcome measure . Recruitment and baseline characteristics of the population are provided . The rationale for the choice 
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The meta-analyses of emotional state show no treatment effects .
REVIEW ER 'S CONCLUSIONS Despite its initial promise , ie the potential neuroprotective properties , and its role in the treatment of Parkinson 's disease sufferers , selegiline for Alzheimer 's disease has proved disappointing .
Although there is no evidence of a significant adverse event profile , there is also no evidence of a clinical ly meaningful benefit for Alzheimer 's disease sufferers .
This is true irrespective of the outcome measure evaluated , ie cognition , emotional state , activities of daily living , and global assessment , whether in the short , or longer term ( up to 69 weeks ) , where this has been assessed .
There would seem to be no justification , therefore , to use it in the treatment of people with Alzheimer 's disease , nor for any further studies of its efficacy in Alzheimer 's disease