***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 Alzheimer 's disease is characterized by amyloid-beta plaques , neurofibrillary tangles , gliosis , and neuronal loss . Solanezumab , a humanized monoclonal antibody , preferentially binds soluble forms of amyloid and in pre clinical studies promoted its clearance from the brain . METHODS In two phase 3 , double-blind trials ( EXPEDITION 1 and EXPEDITION 2 ) , we r and omly assigned 1012 and 1040 patients , respectively , with mild-to-moderate Alzheimer 's disease to receive placebo or solanezumab ( administered intravenously at a dose of 400 mg ) every 4 weeks for 18 months . The primary outcomes were the changes from baseline to week 80 in scores on the 11-item cognitive subscale of the Alzheimer 's Disease Assessment Scale ( ADAS-cog11 ; range , 0 to 70 , with higher scores indicating greater cognitive impairment ) and the Alzheimer 's Disease Cooperative Study -Activities of Daily Living scale ( ADCS-ADL ; range , 0 to 78 , with lower scores indicating worse functioning ) . After analysis of data from EXPEDITION 1 , the primary outcome for EXPEDITION 2 was revised to the change in scores on the 14-item cognitive subscale of the Alzheimer 's Disease Assessment Scale ( ADAS-cog14 ; range , 0 to 90 , with higher scores indicating greater impairment ) , in patients with mild Alzheimer 's disease . RESULTS Neither study showed significant improvement in the primary outcomes . The modeled difference between groups ( solanezumab group minus placebo group ) in the change from baseline was -0.8 points for the ADAS-cog11 score ( 95 % confidence interval [ CI ] , -2.1 to 0.5 ; P=0.24 ) and -0.4 points for the ADCS-ADL score ( 95 % CI , -2.3 to 1.4 ; P=0.64 ) in EXPEDITION 1 and -1.3 points ( 95 % CI , -2.5 to 0.3 ; P=0.06 ) and 1.6 points ( 95 % CI , -0.2 to 3.3 ; P=0.08 ) , respectively , in EXPEDITION 2 . Between-group differences in the changes in the ADAS-cog14 score were -1.7 points in patients with mild Alzheimer 's disease ( 95 % CI , -3.5 to 0.1 ; P=0.06 ) and -1.5 in patients with moderate Alzheimer 's disease ( 95 % CI , -4.1 to 1.1 ; P=0.26 ) . In the combined safety data set , the incidence of amyloid-related imaging abnormalities with edema or hemorrhage was 0.9 % with solanezumab and 0.4 % with placebo for edema ( P=0.27 ) and 4.9 % and 5.6 % , respectively , for hemorrhage ( P=0.49 ) . CONCLUSIONS Solanezumab , a humanized monoclonal antibody that binds amyloid , failed to improve cognition or functional ability . ( Funded by Eli Lilly ; EXPEDITION 1 and 2 Clinical Trials.gov numbers , NCT00905372 and NCT00904683 . ) There is a great interest in developing cerebrospinal fluid ( CSF ) biomarkers for diagnosis and prognosis of  Parkinson 's disease ( PD ) . CSF alpha synuclein ( α-syn ) species , namely total and oligomeric α-syn ( t-α-syn and o-α-syn ) , have shown to be of help for PD diagnosis . Preliminary evidence s show that the combination of CSF t-α-syn and classical Alzheimer 's disease ( AD ) biomarkers — β-amyloid 1–42 ( Aβ42 ) , total tau ( t-tau ) , phosphorylated tau (p-tau)—differentiate PD patients from controls , and that reduced levels of Aβ42 represent a predictive factor for development of cognitive deterioration in PD . In this prospect i ve study carried out in 44 PD patients and 25 neurological controls we wanted to verify whether the combination of CSF α-synuclein species — t-α-syn and o-α-syn— and classical AD biomarkers may help in differentiating PD from neurological controls , and if these biomarkers may predict cognitive decline . The median of follow-up duration was 3 years ( range : 2–6 years ) . Mini Mental State Examination ( MMSE ) and Montreal Cognitive Assessment ( MoCA )  were used for monitoring cognitive changes along time , being administered once a year . Oligo/total α-syn ratio ( o/t-α-syn ratio ) confirmed its diagnostic value , significantly contributing to the discrimination of PD from neurological controls . A greater diagnostic accuracy was reached when combining o/t-α-syn and Aβ42/tau ratios ( Sens = 0.70 , Spec = 0.84 , AUC = 0.82 ; PPV = 0.89 , NPV = 0.62 , LR+ = 4.40 , DOR = 12.52 ) . Low CSF Aβ42 level was associated with a higher rate of MMSE and MoCA decline , confirming its role as independent predictive factor for cognitive decline in PD . None of the other biomarkers assessed ( t-tau , p-tau , t-α-syn and o-α-syn ) showed to have prognostic value . We conclude that combination of CSF o/t-α-syn and Aβ42/tau ratios improve the diagnostic accuracy of PD . PD patients showing low CSF Aβ42 levels at baseline are more prone to develop cognitive decline Neuropsychological ( mostly posterior-cortical ) deficits , quantitative magnetic resonance imaging ( MRI ) atrophy patterns , and low cerebrospinal fluid ( CSF ) levels of amyloid-β have been separately related to worsening cognition in Parkinson 's disease ( PD ) . However , these biomarkers have not been longitudinally assessed in combination as PD-dementia predictors . In this prospect i ve longitudinal study , 27 non-demented PD patients underwent CSF , neuropsychological and 3-T brain-MRI studies at baseline and were re-assessed 18 months later in terms of progression to dementia ( primary outcome ) and longitudinal neuropsychological and cortical thickness changes ( secondary outcomes ) . At follow-up 11 patients ( 41 % ) had progressed to dementia . Lower CSF amyloid-β , worse verbal learning , semantic fluency and visuoperceptual scores , and thinner superior-frontal/anterior cingulate and pre central regions were significant baseline dementia predictors in binary logistic regressions as quantitative and /or dichotomised traits . All participants without baseline biomarker abnormalities remained non-demented whereas all with abnormalities in each biomarker type progressed to dementia , with intermediate risk for those showing abnormalities in a single to two biomarker types ( p = 0.006 ) . Both the dementia- outcome and low baseline CSF amyloid-β were prospect ively associated with limbic and posterior-cortical neuropsychological decline and frontal , limbic and posterior-cortical thinning from baseline to follow-up . These findings suggest that the combination of CSF amyloid-β , neuropsychological and cortical thickness biomarkers might provide a basis for dementia-risk stratification and progression monitoring in PD DATA TOP ( Deprenyl and tocopherol antioxidative therapy of parkinsonism ) is a placebo-controlled clinical trial design ed to test the hypothesis that long-term treatment of patients with early Parkinson 's disease with deprenyl 10 mg/d and /or tocopherol ( vitamin E ) 2000 IU/d will extend the time until disability requires therapy with levodopa ( primary end point ) . At 28 US and Canadian sites , 800 eligible patients in the early stages of untreated Parkinson 's disease were enrolled in DATA TOP and r and omized to ( 1 ) active deprenyl , ( 2 ) active tocopherol , ( 3 ) active deprenyl and tocopherol , or ( 4 ) placebo treatments . Subjects are being evaluated systematic ally at regular intervals over 2 years to determine if and when the primary end point of disability is attained . At baseline evaluation , our cohort represented minimally disabled patients with Parkinson 's disease who did not require symptomatic anti-Parkinson 's disease medications . Despite an almost 2:1 representation of male-female subjects , no selection biases were identified that might confound the primary end-point analysis . This large DATA TOP cohort is expected to provide a high likelihood ( power ) for detecting significant treatment effects , if indeed they exist The prevalence of dementia in Parkinson 's disease ( PD ) is close to 30 % , and its incidence is 4 to 6 times higher than in age-matched general population . PD with dementia ( PDD ) is mainly characterized by a predominant and progressive frontal-subcortical impairment . The  Mattis Dementia Rating Scale ( MDRS ) is a commonly used screening test that sensitively measures the degree of frontal-subcortical defects . Although the MDRS has been vali date d as a screening test of cognitive dysfunction in nondemented PD patients ( PD-ND ) , its utility for screening dementia in PD is unknown . In order to vali date the MDRS for diagnosis of PDD it was prospect ively administered to 92 PD patients ( 57 PD-ND , 35 PDD ) fulfilling UK-PDSBB criteria . Dementia was diagnosed according to DSM-IV-TR and a Clinical Dementia Rating ( CDR ) scale score > or=1 . Univariate , logistic regression , and ROC curve analysis were carried out to measure the discriminative power of MDRS in PDD . Regression analysis showed MDRS total scores to independently differentiate PD-ND from PDD ( P < 0.001 ) . Age and education did not predict the presence of dementia . ROC curve analysis showed a cut-off score of < or=123 on the MDRS total scores to yield high sensitivity ( 92.65 % ) , specificity ( 91.4 % ) , positive and negative predictive values ( PPV 83.3 % , NPV 96.4 % ) . A brief version of the MDRS obtained by the addition of the memory , initiation/perseveration , and conceptualization subscores yielded similar discriminant properties . The MDRS has an excellent discriminant ability to diagnose dementia in PD and provides an objective measure to distinguish PD-ND from PDD Objective : To test in vivo the proposal from clinicopathologic studies that β-amyloid ( Aβ ) pathology shortens the time to dementia in Parkinson disease ( PD ) , and to explore the utility of CSF Aβ and related measures as early prognostic biomarkers of dementia in an incident PD cohort . Methods : We assessed a population -based incident cohort of 104 patients with PD who underwent lumbar puncture at diagnosis . We analyzed CSF concentrations of Aβ42 , Aβ40 , and Aβ38 using a multiplexed immunoassay with electrochemiluminescence ( ECL ) detection and levels of Aβ42 , total tau , and phosphorylated tau using ELISA . Patients were followed prospect ively for 5 years . Dementia was diagnosed according to published criteria . Results : CSF levels of Aβ42 were significantly decreased in patients who developed dementia ( n = 20 , 19.2 % ) compared to those who did not ( n = 84 , 80.8 % ) , as measured by ECL ( −33 % , p = 0.006 ) as well as ELISA ( −36 % , p < 0.001 ) . No differences were observed for other markers . Low Aβ42 values predicted a substantially increased risk for subsequent dementia at high sensitivity ( ≥85 % ) , with hazard ratios of 9.9 ( 95 % confidence interval 2.3–43.5 , p = 0.002 ) for Aβ42ECL < 376 pg/mL and 7.6 ( 2.2–26.4 , p = 0.001 ) for Aβ42ELISA < 443 pg/mL , after adjustment for baseline age and PD – mild cognitive impairment ( MCI ) status . Aβ42 reductions tended to precede the onset of PD-MCI that progressed to dementia . Conclusions : These in vivo data support the role of Aβ pathology in the etiology and highlight the potential utility of CSF Aβ42 as an early prognostic biomarker of dementia associated with PD Objective : To investigate whether certain CSF biomarkers at baseline can predict future progression of motor symptoms and cognitive decline in patients with Parkinson disease ( PD ) . Methods : Patients and controls were recruited from hospitals in southern Sweden as part of the prospect i ve and longitudinal Swedish BioFinder Study . In the present study , we included 42 patients with PD and 69 controls who had clinical assessment and lumbar puncture at baseline .  Baseline CSF sample s were analyzed for α-synuclein ( αSyn ) , β-amyloid 1–42 ( Aβ42 ) , tau , phosphory 
    Output:
    
Findings from the review suggest a convergence of evidence that a low baseline Aβ42 in the CSF of non-demented PD patients predicts development of cognitive impairment over time .
Conversely , there is limited evidence that CSF levels of tau , either total tau or phosphorylated tau , is a useful predictive biomarker .
There are mixed results for other CSF biomarkers such as α-synuclein , Neurofilament light chain , and Heart fatty acid-binding protein .
Overall the results of this review show that certain CSF biomarkers have better predictive ability to identify PD patients who are at risk for developing cognitive impairment  .