***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: PURPOSE A prospect i ve , open-label phase II study was conducted to determine whether donepezil , a US Food and Drug Administration-approved reversible acetylcholinesterase inhibitor used to treat mild to moderate Alzheimer 's type dementia , improved cognitive functioning , mood , and quality of life ( QOL ) in irradiated brain tumor patients . PATIENTS AND METHODS Thirty-four patients received donepezil 5 mg/d for 6 weeks , then 10 mg/d for 18 weeks , followed by a washout period of 6 weeks off drug . Outcomes were assessed at baseline , 12 , 24 ( end of treatment ) , and 30 weeks ( end of wash-out ) . All tests were administered by a trained research nurse . RESULTS Of 35 patients who initiated the study , 24 patients ( mean age , 45 years ) remained on study for 24 weeks and completed all outcome assessment s. All 24 patients had a primary brain tumor , mostly low- grade glioma . Scores significantly improved between baseline ( pretreatment ) and week 24 on measures of attention/concentration , verbal memory , and figural memory and a trend for verbal fluency ( all P < .05 ) . Confused mood also improved from baseline to 24 weeks ( P = .004 ) , with a trend for fatigue and anger ( all P < .05 ) . Health-related QOL improved significantly from baseline to 24 weeks , particularly , for brain specific concerns with a trend for improvement in emotional and social functioning ( all P < .05 ) . CONCLUSION Cognitive functioning , mood , and health-related QOL were significantly improved following a 24-week course of the acetylcholinesterase inhibitor donepezil .  Toxicities were minimal . We are planning a double blinded , placebo-controlled , phase III trial of donepezil to confirm these favorable results BACKGROUND To determine the protective effects of memantine on cognitive function in patients receiving whole-brain radiotherapy ( WBRT ) . METHODS Adult patients with brain metastases received WBRT  and were r and omized to receive placebo or memantine ( 20 mg/d ) , within 3 days of initiating radiotherapy for 24 weeks . Serial st and ardized tests of cognitive function were performed . RESULTS Of 554 patients who were accrued , 508 were eligible . Grade 3 or 4 toxicities and study compliance were similar in the 2 arms . There was less decline in delayed recall in the memantine arm at 24 weeks ( P = .059 ) , but the difference was not statistically significant , possibly because there were only 149 analyzable patients at 24 weeks , result ing in only 35 % statistical power . The memantine arm had significantly longer time to cognitive decline ( hazard ratio 0.78 , 95 % confidence interval 0.62 - 0.99 , P = .01 ) ; the probability of cognitive function failure at 24 weeks was 53.8 % in the memantine arm and 64.9 % in the placebo arm . Superior results were seen in the memantine arm for executive function at 8 ( P = .008 ) and 16 weeks ( P = .0041 ) and for processing speed ( P = .0137 ) and delayed recognition ( P = .0149 ) at 24 weeks . CONCLUSIONS Memantine was well tolerated and had a toxicity profile very similar to placebo . Although there was less decline in the primary endpoint of delayed recall at 24 weeks , this lacked statistical significance possibly due to significant patient loss . Overall , patients treated with memantine had better cognitive function over time ; specifically , memantine delayed time to cognitive decline and reduced the rate of decline in memory , executive function , and processing speed in patients receiving WBRT . RTOG 0614 , Clinical Trials.gov number CT00566852 Limited research is available regarding the efficacy of psychostimulants in treating cognitive function in primary brain tumor patients . An open-label , r and omized , pilot trial examined both the general and differential efficacy of 4 weeks of methylpheni date ( MPH ) and modafinil ( MOD ) in 24 brain tumor patients . Participants completed cognitive tests and self-report measures of fatigue , sleep disturbance , mood and quality of life at baseline and after 4 weeks . Following stimulant treatment , there was evidence of a beneficial effect on test performance in speed of processing and executive function requiring divided attention . Patients with the greatest deficit in executive function at baseline appeared to derive the greatest benefit following stimulant therapy . Inconsistent , differential effects were found on a measure of attention in favor of MPH and on a measure of processing speed in favor of MOD . There was also evidence of a general beneficial effect on patient-reported measures of fatigue , mood , and quality of life , with no statistically significant differences between treatment arms in these measures over time . The results from this small pilot study should be interpreted with caution , but appear to warrant additional research , in larger study sample s , targeting fatigue , processing speed and executive function , and exploring different doses of stimulants . Future studies may also wish to explore the specific patient factors that may be associated with responsiveness to psychostimulant treatment Although their neurocognitive performance is one of the major concerns of patients with high- grade gliomas ( HGG ) and although neurocognitive deficits have been described to be associated with negative outcome , neurocognitive rehabilitation is usually not integrated into the routine care of patients with malignant gliomas . In this pilot trial , a weekly group training session for attention , verbal , and memory skills was offered to patients with HGG with pre and post-training evaluation . Eleven patients , six with glioblastoma multiforme and five with WHO grade III gliomas , median age 50 years , with a Karnofsky performance score of 80–100 participated in ten group training sessions of 90 min . For evaluation at baseline and after the training by a neuropsychologist not involved in care or training of the patients ,  Trail Making Tests A and B ( TMTA and TMTB ) , Hopkins Verbal Learning Test ( HVLT ) , and the Controlled Oral Word Association Test ( COWA )  were used . Comparison of mean group differences between baseline and at post-training evaluation after 12 weeks revealed improvement across all neurocognitive variables . The patients showed a great diversity in their performances , with worsening , improvement , and stabilization . However , a significant group difference was detected only for the HVLT ( score 19.6 ± 8.9 at baseline , 23.6 ± 8.8 after 12 weeks , P = 0.04 ) . This pilot study shows that neurocognitive training in patients with HGG is feasible as group training with weekly sessions and might be able to induce improvements in attention and memory skills BACKGROUND Fatigue , cognitive deficits , and depression are frequently reported but often undertreated symptoms that can profoundly affect daily life in patients with primary brain tumors ( PBTs ) . To evaluate the effects of the psychostimulant modafinil on fatigue , depression , health-related quality of life ( HRQOL ) , and cognitive functioning in PBT patients , we performed a multicenter , double-blind placebo-controlled crossover trial . METHODS Patients r and omly received either 6 weeks of treatment with modafinil ( up to 400 mg/day ) or 6 weeks with placebo . After a 1-week washout period , the opposite treatment was provided . Assessment s took place at baseline and immediately after the first and second condition . Patients completed self-report question naires on fatigue ( Checklist Individual Strength [ CIS ] ) , depression ( Center for Epidemiologic Studies Depression Scale [ CES-D ] ) , HRQOL ( Short-Form Health Survey [ SF-36 ] ) , and self-perceived cognitive functioning ( Medical Outcomes Study [ MOS ] ) . They also underwent comprehensive neurocognitive testing . RESULTS In total , 37 patients participated . Relative to baseline , patients reported lower fatigue severity ( CIS ) and better motivation ( CIS ) in both the modafinil ( P = .010 and P = .021 , respectively ) and the placebo condition ( P < .001 and P = .027 , respectively ) . The same held for physical health ( SF-36 Physical Component Summary score ; P = .001 and P = .008 , respectively ) , working memory ( P = .040 and P = .043 ) , and information processing capacity ( P = .036 and P = .040 ) . No improvement in depressive symptoms was found in either condition . CONCLUSIONS Modafinil did not exceed the effects of placebo with respect to symptom management . Patient accrual was slow , and relatively many patients dropped out during the trial , due mostly to side effects . Other , preferably nonpharmacologic intervention studies should be considered to improve symptom management of PBT patients Background Cerebral radiation necrosis is a serious complication of radiation treatment for brain tumors . Therapeutic options include corticosteroids , anticoagulation and hyperbaric oxygen with limited efficacy . Bevacizumab , an antibody against VEGF had been reported to reduce edema in patients with suspected radiation necrosis . We retrospectively review ed 6 patients with biopsy proven cerebral radiation necrosis treated with bevacizumab between 2006 and 2008 . Results Interval MRI follow-up demonstrated radiographic response in all patients with an average reduction of 79 % for the post gadolinium studies and 49 % for the FLAIR images . The initial partial radiographic response was noted for up to a mean follow-up time of 5.9 months ( 6 weeks to 18 months ) . Conclusion Bevacizumab appears to produce radiographic response and clinical benefits in the treatment of patients with cerebral radionecrosis PURPOSE Patients with gliomas often experience cognitive deficits , including problems with attention and memory . This r and omized , controlled trial evaluated the effects of a multifaceted cognitive rehabilitation program ( CRP ) on cognitive functioning and selected quality -of-life domains in patients with gliomas . PATIENTS AND METHODS One hundred forty adult patients with low- grade and anaplastic gliomas , favorable prognostic factors , and both subjective cognitive symptoms and objective cognitive deficits were recruited from 11 hospitals in the Netherl and s. Patients were r and omly assigned to an intervention group or to a waiting-list control group . The intervention incorporated both computer-based attention retraining and compensatory skills training of attention , memory , and executive functioning . Participants completed a battery of  neuropsychological  ( NP ) tests and self-report question naires on cognitive functioning , fatigue , mental health-related quality of life , and community integration at baseline , after completion of the CRP , and at 6-month follow-up . RESULTS At the immediate post-treatment evaluation , statistically significant intervention effects were observed for measures of subjective cognitive functioning and its perceived burden but not for the objective NP outcomes or for any of the other self-report measures . At the 6-month follow-up , the CRP group performed significantly better than the control group on NP tests of attention and verbal memory and reported less mental fatigue . Group differences in other subjective outcomes were not significant at 6 months . CONCLUSION The CRP has a salutary effect on short-term cognitive complaints and on longer-term cognitive performance and mental fatigue . Additional research is needed to identify which elements of the intervention are most effective Patients with brain tumors may suffer from cognitive deficits caused by the disease and /or its treatment . Here , we review recent efforts in the research on prevention or treatment of cognitive deficits in these patients . We conclude that interest in this area is growing , but that method ological difficulties persist . In addition , we describe the recently completed first r and omized controlled trial on the effectiveness of cognitive rehabilitation  that we conducted in patients with brain cancer . By reflecting on the method ological challenges experienced in our trial , we hope to assist others in planning and conducting future studies on both pharmacological treatments and  cognitive rehabilitation programs for cognitive deficits in this patient population . We conclude with suggestions for future research directions Purpose : Analysis of the feasibility and effect of hyperbaric oxygen treatment ( HBO ) on cognitive functioning in patients with cognitive disorders after irradiation of the brain . Patients and Method : Seven patients with cognitive impairment after brain irradiation , with an interval of at least 1.5 years after treatment , were treated with 30 sessions of HBO in a phase I – II study . A comprehensive neuropsychological test battery was performed before treatment , at 3 and 6 months thereafter . Patients were r and omized into an immediate treatment group and a delayed treatment group . The delayed group had a second neuropsychological test at 3 months without treatment in that period and started HBO thereafter . Results : All eligible patients completed the HBO treatment and the extensive neuropsychological testing . One out of seven patients had a meaningful improvement in neuropsychological functioning . At 3 months there was a small , but not significant benefit in neuropsychological performance for the group with HBO compared to the group without HBO treatment . Six out of seven patients eventually showed improvement after HBO in one to nine ( median 2.5 ) of the 31 tests , although without statistical significance . Conclusion : HBO treatment was feasible and result ed in a meaningful improvement of congitive functioning in one out of seven patients . Overall there was a small but not significant improvement . Hintergrund : Es wurden die Durchführbarkeit und Wirksamkeit der hyperbaren Oxygenierung ( HBO ) auf die Gehirnfunktion bei Patienten mit kognitiven Störungen nach Hirnbestrahlung untersucht . Patientengut und Method e : In einer Phase-I/II-Studie wurden sieben Patienten mit kognitiven Störungen nach einem minimalen Intervall von 1,5 Jahren 30 HBO-Beh and lungen unterzogen . Neuropsychologische Tests wurden vor HBO sowie 3 
    Output:
    
In the first study the primary cognitive outcome of memory at six months did not reach significance , but there was significant improvement in overall cognitive function compared to placebo , with similar adverse events across groups .
The second study found no statistically significant difference between arms , with few adverse events .
There is supportive evidence that memantine may help prevent cognitive deficits for adults with brain metastases receiving cranial irradiation .
There is supportive evidence that donepezil may have a role in treating cognitive deficits in adults with primary or metastatic brain tumours who have been treated with cranial irradiation .
Further research that tries to minimise the withdrawal of consent , and subsequently reduce the requirement for imputation procedures , may offer a higher quality of evidence .There is no strong evidence to support any non-pharmacological interventions ( medical or cognitive/behavioural ) in the prevention or amelioration of cognitive deficits .
Non-r and omised studies appear promising but are as yet to be conclusive via translation into high quality evidence .