***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 The ADAGIO study investigated whether rasagiline has disease-modifying effects in Parkinson 's disease .  Rasagiline 1 mg per day , but not 2 mg per day , was shown to be efficacious in the primary analysis . Here , we report additional secondary and post-hoc analyses of the ADAGIO study . METHODS ADAGIO was a placebo-controlled , double-blind , multicentre , delayed-start study , in which 1176 patients with untreated early Parkinson 's disease were r and omly assigned to receive rasagiline 1 mg or 2 mg per day for 72 weeks ( early-start groups ) or placebo for 36 weeks followed by rasagiline 1 mg or 2 mg per day for 36 weeks ( delayed-start groups ) . We assessed the need for additional antiparkinsonian therapy and changes in non-motor experiences of daily living and fatigue scales ( prespecified outcomes ) and changes in unified Parkinson 's disease rating scale ( UPDRS ) scores and subscores in placebo and active groups ( post-hoc outcomes ) . The ADAGIO study is registered with Clinical Trials.gov , number NCT00256204 . FINDINGS The need for additional antiparkinsonian therapy was reduced with rasagiline 1 mg ( 25 of 288 [ 9 % ] patients ) and 2 mg ( 26 of 293 [ 9 % ] ) versus placebo ( 108 of 593 [ 18 % ] ; odds ratio for 1 mg rasagiline vs placebo 0·41 , 95 % CI 0·25 - 0·65 , p=0·0002 ; 2 mg rasagiline vs placebo 0·41 , 0·26 - 0·64 , p=0·0001 ) . At week 36 , both doses significantly improved UPDRS motor subscores  compared with placebo ( 1 mg rasagiline mean difference -1·88 [ SE 0·35 ] ; 2 mg rasagiline -2·18 [ 0·35 ] ; both p<0·0001 ) and activities of daily living subscores ( ADL ; 1 mg rasagiline -0·86 [ 0·18 ] ; 2 mg rasagiline -0·88 [ 0·18 ] ; both p<0·0001 ) , and 1 mg rasagiline significantly improved UPDRS mentation subscore ( -0·22 [ 0·08 ] ; p=0·004 ) . At week 72 , the only significant difference between early-start and delayed-start groups was for ADL subscore with the 1 mg dose ( -0·62 [ 0·29 ] ; p=0·035 ) . When assessed for the effect on non-motor symptoms at week 36 , both doses showed benefits on the Parkinson fatigue scale  versus placebo ( 1 mg rasagiline mean difference -0·14 [ SE 0·05 ] , p=0·0032 ; 2 mg rasagiline -0·19 [ 0·05 ] , p<0·0001 ) , and the 1 mg dose showed benefits on the scale for non-motor experiences of daily living compared with placebo ( mean difference -0·33 [ 0·17 ] ; p=0·049 ) . The rate of progression of total UPDRS score for patients in the placebo group was 4·3 points [ SE 0·3 ] over 36 weeks , with extrapolation to about 6 units per year . In the placebo group , patients with the lowest quartile of baseline UPDRS scores ( ≤14 ; n=160 ) progressed more slowly than did those with highest scores ( > 25·5 ; n=145 ; mean difference -3·46 [ SE 0·77 ] ; p<0·0001 ) . INTERPRETATION These findings show that rasagiline delayed the need for symptomatic antiparkinsonian drugs and emphasise the contribution of the UPDRS ADL in the response of the rasagiline 1 mg per day early-start versus delayed-start group . The rate of UPDRS deterioration was less than was anticipated from previous studies and correlated with baseline severity . Underst and ing of the pattern of UPDRS deterioration is essential to assess disease modification . FUNDING Teva Pharmaceutical Industries and H Lundbeck BACKGROUND AND PURPOSE Fatigue is a common and disabling non-motor symptom in Parkinson 's disease ( PD ) . The pathogenesis is unknown , and the treatment options are limited . The aim of the present study was to investigate the development of fatigue during the first year after diagnosis . METHODS The study design was a prospect i ve , controlled population -based longitudinal cohort study , comprising 181 de novo , drug-naïve patients with PD and 162 control participants . PD was diagnosed according to the Gelb criteria .  Fatigue was assessed by the Fatigue Severity Scale ( FSS ) . Both groups were assessed for fatigue at baseline and after 1 year . RESULTS Patients reported more fatigue than the control subjects at baseline and at the 1-year follow-up evaluation . The FSS scores in the patient group improved from a mean score of 4.4 ( SD 1.6 ) to 4.0 ( SD 1.6 ) . Patients with fatigue at baseline received higher doses of dopaminergic medication during follow-up . Patients who received dopamine agonists improved slightly more than patients who received levodopa . A regression analysis did not show a correlation between an improvement in fatigue and a change in disease severity , depressive symptoms , sleep problems , apathy or cognitive impairment . CONCLUSION Fatigue is a common symptom in PD , also in early , untreated patients . During the first year of observation , an improvement in the fatigue scores was found . The improvement could not be attributed to a change in disease severity or depressive symptoms . The results indicate a better effect of dopamine agonists than of levodopa . This may have implication s for treatment in patients with PD-associated fatigue Objective : To evaluate if mental fatigue is a symptom that appears independently from other clinical features in patients with Parkinson disease ( PD ) , and to study if fatigue is persistent over time in these patients . Methods : In 1993 , 233 patients with PD were included in a community-based study of fatigue and followed prospect ively over 8 years . Fatigue was measured by a combination of a seven-point scale and parts of the Nottingham Health Profile ( NHP ) at baseline and after 4 and 8 years . In addition , the  Fatigue Severity Scale ( FSS )  was used to evaluate fatigue in 2001 . Population -averaged logistic regression models for correlated data were performed to study the relationship between fatigue and various demographic and clinical variables . Results : In patients who were followed throughout the 8-year study period , fatigue increased from 35.7 % in 1993 to 42.9 % in 1997 and 55.7 % in 2001 . Fatigue was related to disease progression , depression , and excessive daytime sleepiness ( EDS ) . However , the prevalence of fatigue in patients without depression and EDS remained high and increased from 32.1 % to 38.9 % during the study period . For about 44 % of the patients with fatigue the presence of this symptom varied during the study period , as it was persistent in 56 % of the patients with fatigue . Conclusions : The authors confirmed the high prevalence of mental fatigue in patients with Parkinson disease ( PD ) .  Fatigue is related to other non-motor features such as depression and excessive daytime sleepiness , but can not be explained by this comorbidity alone . In more than half of the patients mental fatigue is persistent and seems to be an independent symptom that develops parallel to the progressive neurodegenerative disorder of PD BACKGROUND Fatigue is one of the most disabling non-motor symptoms for people with Parkinson 's disease . Exercise may modify fatigue . This study examines prescribed exercise effects on physical activity levels , well-being , and fatigue in Parkinson 's disease . METHODS In this single-blinded trial , participants were r and omly assigned to either a 12 week community exercise program or control group . Primary outcome measures were fatigue ( Fatigue Severity Scale ) and physical activity . RESULTS Thirty-nine people with Parkinson 's disease were included : 20 in exercise and 19 in control . Sixty-five percent of the study group were fatigued ( n = 24 , mean 4.02 , SD 1.48 ) . Increased fatigue was associated with lower mobility and activity ( P < .05 ) . Individuals participated in a mean of 15 ( SD 10 ) exercise sessions with no significant change in fatigue , mobility , well-being , or physical activity after exercise ( P ≥ .05 ) . CONCLUSION Participation in weekly exercise did not improve fatigue in people with Parkinson 's Disease Objectives : Fatigue is common in Parkinson 's disease ( PD ) , causing serious negative effects on quality of life . Despite its clinical importance , the nature of fatigue in PD is poorly understood because its underlying neurobiology is unknown . Fatigue can be more complicated in advanced PD because of its chronicity . In order to find features that are innate to fatigue in PD , it would be useful to conduct a study looking at de novo PD . Assessing fatigue in de novo patients allows excluding at least one confounding factor . Methods : We prospect ively investigated 87 drug-naïve PD patients . Thirty-nine patients ( 44.8 % ) were found to have fatigue around the time of diagnosis of PD . Results : We found that depression and difficulties with activities of daily living were independent risk factors for fatigue ; however , motor dysfunction was not related . Clinical ly meaningful responses to dopaminergic medication were observed . Discussion : Our study determined that fatigue occurs in the early stages of PD . It can inform clinical decision-making to significantly benefit PD patients with fatigue BACKGROUND Fatigue affects 40 % to 50 % of all PD patients and is a leading cause of disability , with no clearly established or efficacious established treatments . METHODS In this double-blinded , placebo-controlled , pilot trial , we investigated whether rasagiline improved fatigue among PD patients . Subjects were r and omized to 1 mg daily of rasagiline or placebo for 12 weeks . The primary endpoint was a change in the Modified Fatigue Impact Scale from baseline to week 12 . RESULTS Thirty PD subjects ( 16 men ) , with Modified Fatigue Impact Scale baseline score of 67 ± 15 , were r and omized ( 16 to rasagiline vs. 14 to placebo ) . Significant improvement was noted in the mean Modified Fatigue Impact Scale score of the rasagiline group ( 12 points ) as compared to placebo ( 8.5 points ) from baseline to week 12 ( P = 0.003 ) . CONCLUSION In this pilot study , rasagiline at a dose of 1 mg per day improved fatigue . Larger r and omized studies are needed to confirm this finding OBJECTIVE To identify the motor and non-motor factors that are associated with health related quality of life ( HR-QOL ) in a subgroup of Parkinson 's disease ( PD ) patients with Levodopa therapy in early clinical stages . METHODS 391 Levodopa exposed patients were evaluated during the baseline assessment of a clinical trial in China . HR-QOL was measured by the  Short Form 36 ( SF-36 ) . Motor and non-motor variables were determined during a structured interview and by clinical examination by movement disorder specialists . Multiple regression analyses were used to determine which variables were associated with low levels of HR-QOL . RESULTS Even if excluding non-motor variables from the regression model , motor factors , particularly motor deficits ( measured by motor score of UPDRS ) , rigidity ( measured by item 22 of UPDRS ) , and disease severity ( measured by Hoehn&Yahr scale ) , explained only 18.9 % of the variance of total SF-36 score . Whereas , when non-motor variables were included in the model , especially depression ( measured by CES-D ) , sleep disturbances ( measured by PSQ-I ) , and fatigue ( measured by FSS ) , 61.7 % of the variance of SF-36 score could be explained . Two motor variables , UPDRS motor score and Hoehn&Yahr score , were also contributed to the model , however , the 95 % confidence intervals ( CIs ) of these two motor factors were wide and included the null value ( CIs -0.282 , 0.019 for UPDRS motor score , and CIs -4.043 , 0.856 for Hoehn&Yahr score ) . Neither , did higher daily levodopa dose contribute significantly to both models predicting SF-36 score . CONCLUSIONS In our sample patients with levodopa therapy , motor disability and severity of parkinsonism contributed to a lesser extent to patients ' self-report distress , within the first 5 years of disease onset . The clinical factors that showed the highest predictive value for worsen HR-QOL were non-motor symptoms , such as depression , sleep disorders , and fatigue . Great effort should be made to recognize and treat those conditions , thus improving all aspects of PD and giving these patients as a good HR-QOL as possible Objectives : Fatigue is a complaint frequently encountered among patients with Parkinson ’s disease ( PD ) . Considering the possible relationship between fatigue and dopaminergic dysfuncion , we investigated the effect of pergolide mesilate ( a D2 and D1 dopamine receptor agonist ) and bromocriptine 
    Output:
    
Our analyses suggest that fatigue is a frequent , independent nonmotor symptom in PD appearing early and persisting throughout the disease course , and that establishing uniform diagnostic criteria for PD-related fatigue is critical .
In addition , several nonmotor symptoms appear to be associated with fatigue and negatively impact quality of life .
Pharmacological and nonpharmacological interventions targeting fatigue and associated symptoms may improve quality of life in patients with PD .