title: Associations between Cerebrospinal Fluid Biomarkers and Cognition in Early Untreated Parkinson's Disease.
abstract: BACKGROUND
  Mild cognitive impairment and dementia are common, clinically important features of Parkinson's disease (PD). The underlying disease pathology is heterogeneous and not yet well characterized. Biomarkers for cognitive impairment in PD could aid in diagnostic and prognostic evaluation and in the development of new cognitive enhancing treatments.
  
  
  OBJECTIVE
  To examine the relationship between CSF markers and cognition in a large, multicenter, cohort study of early, untreated PD, and compare marker concentrations between PD patients with and without MCI and healthy, age-matched controls.
  
  
  METHODS
  414 early, untreated PD (34% with mild cognitive impairment) and 189 healthy, cognitively intact controls with baseline neuropsychological testing and CSF abeta42, t-tau, p-tau181 and α-synuclein results were included. Multiple linear regression models were constructed with a composite cognition factor, or memory-, or visuospatial- or executive-attention domains as dependent variables, and CSF markers, demographic characteristics and MDS-UPDRS III score as predictors.
  
  
  RESULTS
  Lower α-synuclein was associated with reduced performance on the executive-attention domain and the composite cognition factor in the whole PD-group. Abeta42 was significantly decreased in PD with mild cognitive impairment compared with controls after adjusting for covariates, while values in PD without MCI were identical to healthy controls.
  
  
  CONCLUSIONS
  The association between reduced CSF α-synuclein concentrations and cognition suggests that α-synuclein pathology contributes to early cognitive impairment in PD, in particular to executive-attentional dysfunction. Longitudinal analyses are needed to determine if this and other CSF biomarkers in early Parkinson's disease are associated with the risk of future cognitive decline and dementia.
authors.affiliation: Haraldsplass Deaconess Hospital, Kavli Research Center for Geriatrics and Dementia, Bergen, Norway.|Department of Clinical Medicine, University of Bergen, Norway.
authors.forename: Ragnhild E
authors.initials: RE
authors.lastname: Skogseth
authors.affiliation: TIPS -Regional Center for Clinical Research in Psychosis, Stavanger University Hospital, Norway.|Faculty of Social Sciences, University of Stavanger, Norway.
authors.forename: Kolbjorn
authors.initials: K
authors.lastname: Bronnick
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Karolinska Institute H1, Division of Clinical Geriatrics, Sweden.
authors.forename: Joana B
authors.initials: JB
authors.lastname: Pereira
authors.affiliation: Paracelsus-Elena-Klinik and Department of Neuropathology, University Medical Center Göttingen, Germany.
authors.forename: Brit
authors.initials: B
authors.lastname: Mollenhauer
authors.affiliation: Department of Psychiatry and Neurology, Perelman School of Medicine at the University of Pennsylvania; Philadelphia VA Medical Center, Philadelphia, PA, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Weintraub
authors.affiliation: Department of Neurology, Akershus University Hospital, Lørenskog, Norway.|Institute of Clinical Medicine, Campus Ahus, University of Oslo, Norway.
authors.forename: Tormod
authors.initials: T
authors.lastname: Fladby
authors.affiliation: Center forAlzheimer's Disease Research, Department of Neurobiology, CareSciences and Society, Karolinska Institutet H1, Division of Neurogeriatrics, Sweden.|Center for Age-Related Medicine Department of Psychiatry, Stavanger University Hospital, Norway.
authors.forename: Dag
authors.initials: D
authors.lastname: Aarsland
mesh_terms: D000368:Aged; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000209:etiology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000150:complications; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C497604:SNCA protein, human; D051844:alpha-Synuclein; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Mild cognitive impairment; Parkinson disease; alpha-synuclein; amyloid beta-peptides; cerebrospinal fluid; tau Proteins