***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: 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 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 Few detailed clinico-pathological correlations of Parkinson 's disease have been published . The pathological findings in 100 patients diagnosed prospect ively by a group of consultant neurologists as having idiopathic Parkinson 's disease are reported . Seventy six had nigral Lewy bodies , and in all of these Lewy bodies were also found in the cerebral cortex . In 24 cases without Lewy bodies , diagnoses included progressive supranuclear palsy , multiple system atrophy , Alzheimer 's disease , Alzheimer-type pathology , and basal ganglia vascular disease . The retrospective application of recommended diagnostic criteria improved the diagnostic accuracy to 82 % . These observations call into question current concepts of Parkinson 's disease as a single distinct morbid entity Cerebrospinal fluid ( CSF ) biomarkers for Alzheimer ’s disease ( AD ) reflect brain biochemistry . Using combined immunoprecipitation and mass spectrometry , we have shown that amyloid beta 1 - 15 ( Aβ1 - 15 ) is produced by concerted β- and α-secretase cleavage of amyloid precursor protein ( APP ) and that the relative levels of Aβ1 - 16 in AD compared to controls are increased . Furthermore , drug-induced γ-secretase inhibition enhances the relative levels of Aβ1 - 15 and Aβ1 - 16 . Here , we investigate a novel immunoassay for Aβ1 - 15/16 in a broad range of neurodegenerative conditions . The CSF level of Aβ1 - 15/16 was measured by the bead-based amplified luminescent proximity homogeneous assay ( Alpha technology ) . Concentrations of Aβ1 - 15/16 were analyzed in subjects with Parkinson disease ( PD ; n = 90 ) , PD with dementia ( PDD ) ( n = 32 ) , dementia with Lewy bodies ( DLB ) ( n = 68 ) , AD ( n = 48 ) , progressive supranuclear palsy ( PSP ) ( n = 45 ) , multiple system atrophy ( MSA ) ( n = 46 ) , and corticobasal degeneration ( CBD ) ( n = 12 ) . The detecting antibody is specific to the C-terminal epitope of Aβ15 . We found that a carboxypeptidase ( CPB ) present in fetal bovine serum ( FBS ) , a component of the buffers used , de grade s Aβ1 - 16 to Aβ1 - 15 , which is then detected by the Aβ1 - 15/16 assay . Significantly , lower levels of Aβ1 - 15/16 were detected in PD , PDD , PSP , and MSA compared to other neurodegenerative diseases and controls . Using the specific Aβ1 - 15/16 assay , a reliable quantification of Aβ1 - 15 or Aβ1 - 15/16 in CSF sample s is obtained . We found reduced levels of Aβ1 - 15 in parkinsonian disease groups . The molecular mechanism behind this reduction is at present unknown Differential diagnosis between Parkinson 's disease ( PD ) and multiple system atrophy ( MSA ) is difficult , particularly at early disease stages , but is important for therapeutic management . The protein DJ-1 is implicated in the pathology of PD but little is known about its involvement in MSA . We aim ed to determine the diagnostic value of CSF DJ-1 and tau proteins for discriminating PD and MSA .  DJ-1 and total tau levels  were quantified in the CSF of 43 PD patients , 23 MSA patients and 30 non-neurological controls matched for age and gender . Patients were part of a study with a 3-year prospect i ve design with extended case- review follow-up of up to 9 years , ensuring maximum accuracy of the clinical diagnosis . Our results showed that CSF DJ-1 levels could distinguish MSA from PD with a 78 % sensitivity and 78 % specificity ( AUC = 0.84 ) . The combination of DJ-1 and tau proteins significantly improved this discrimination to 82 % sensitivity and 81 % specificity to identify MSA from PD ( AUC = 0.92 ) . Our results highlight the potential benefits of a combination of DJ-1 and total tau  as biomarkers for differential diagnosis of MSA and PD In order to investigate the possible role of oxidative RNA damage in the pathogenesis of Parkinson 's disease ( PD ) , the concentrations of the oxidative stress marker 8-hydroxyguanosine ( 8-OHG ) were measured in the cerebrospinal fluid ( CSF ) and the serum of patients with PD and control subjects . The concentration of 8-OHG in CSF in PD patients was approximately three-fold that in controls ( P < 0.001 ) . The concentration of 8-OHG in CSF decreased significantly with the duration of disease ( r(s ) = -0.46 , P < 0.05 ) . However , the concentration of 8-OHG in serum was not significantly altered in PD patients compared to that in controls . In addition , the concentration of 8-OHG in CSF showed no correlation with that in serum in both the controls and PD patients suggesting that the 8-OHG concentrations in the CSF do not reflect those in serum and may be probably reflect those in brain tissue . These in vivo findings suggest a possible role of 8-OHG and increased oxidative RNA damage in the early stage of the development of PD Objective : Cognitive decline associated with Parkinson disease ( PD ) is common and highly disabling . Biomarkers that help identify patients at risk for cognitive decline would be useful additions to the clinical management of the disease . Methods : A total of 45 patients with PD were enrolled in this prospect i ve cohort study and had at least 1 yearly longitudinal follow-up evaluation . CSF was collected at baseline and cognition was assessed at baseline and follow-up visits using the Mattis Dementia Rating Scale ( DRS-2 ) . CSF was tested for amyloid β 1 - 42 ( Aβ1 - 42 ) ,  p-tau181p  , and total tau levels using the Luminex xMAP platform . Mixed linear models were used to test for associations between baseline CSF biomarker levels and change in cognition over time . Results : Lower baseline CSF Aβ1 - 42 was associated with more rapid cognitive decline . Subjects with CSF Aβ1 - 42 levels ≤192 pg/mL declined an average of 5.85 ( 95 % confidence interval 2.11–9.58 , p = 0.002 ) points per year more rapidly on the DRS-2 than subjects above that cutoff , after adjustment for age , disease duration , and baseline cognitive status . CSF total tau and p-tau181p levels were not significantly associated with cognitive decline . Conclusions : Reduced CSF Aβ1 - 42 was an independent predictor of cognitive decline in patients with PD . This observation is consistent with previous research showing that Alzheimer disease pathology contributes to cognitive impairment in PD . This biomarker may provide clinical ly useful prognostic information , particularly if combined with other risk factors for cognitive impairment in PD Abstract – DATA TOP is a double‐blind , multi‐center , placebo‐controlled clinical trial aim ed at slowing the decline of patients who are in the early stages of Parkinson 's disease ( PD ) . The specific aim is to determine whether or not chronic administration of deprenyl 10 mg per day and /or tocopherol 2000 IU per day to early , otherwise untreated PD patients will prolong the time until levodopa therapy is required to treat emerging disability .  Deprenyl and tocopherol exert antioxidative effects through separate but complementary mechanisms of action . A 2 X 2 factorial design allocates eligible subjects to one of four treatment groups : 1 ) deprenyl alone , 2 ) tocopherol alone , 3 ) deprenyl plus tocopherol , or 4 ) placebo .  Eligible subjects include early PD patients ( illness duration less than 5 years and in stages I and II ) , aged 30 to 79 , who are not taking or requiring any anti‐PD medications . The major response variable is the time period from r and omization until the blinded investigator judges levodopa necessary to treat emerging parkinsonian disability . R and omization is stratified to ensure that treatment assignments are balanced for each blinded investigator . Cerebrospinal fluid is sample d just prior to r and omization and one month after washout of experimental medications in order to help distinguish between symptomatic and protective effects of interventions . Based on pilot studies it is estimated that approximately 85 % of untreated PD patients will require levodopa within two years and a total sample size of 800 subjects will provide a 95 % likelihood for detecting a 10 % “ survival'’difference between experimental medications and placebo . Between September 1987 and November 1988 , 800 eligible subjects were enrolled in DATA TOP by 34 investigators of the Parkinson Study Group , representing research centers in the United States and Canada . Primary analyses of DATA TOP should be completed in 1991 
    Output:
    
Oligomeric alpha-synuclein might be helpful in the separation of PD from controls .
Neurofilament light chain ( NfL ) has a significant role in distinguishing PD from other neurodegenerative diseases .
Several oxidative stress markers are related to disease severity , with the antioxidant urate also having a prognostic value in terms of disease severity .
Increased levels of amyloid and tau-proteins correlate with cognitive decline and may have prognostic value for cognitive deficits in PD .