title: Monitoring of 30 marker candidates in early Parkinson disease as progression markers.
abstract: This was a longitudinal single-center cohort study to comprehensively explore multimodal progression markers for Parkinson disease (PD) in patients with recently diagnosed PD (n = 123) and age-matched, neurologically healthy controls (HC; n = 106).
  
  
  
  Thirty tests at baseline and after 24 months covered nonmotor symptoms (NMS), cognitive function, and REM sleep behavior disorder (RBD) by polysomnography (PSG), voxel-based morphometry (VBM) of the brain by MRI, and CSF markers. Linear mixed-effect models were used to estimate differences of rates of change and to provide standardized effect sizes (d) with 95% confidence intervals (CI).
  
  
  
  A composite panel of 10 informative markers was identified. Significant relative worsening (PD vs HC) was seen with the following markers: the Unified Parkinson's Disease Rating Scale I (d 0.39; CI 0.09-0.70), the Autonomic Scale for Outcomes in Parkinson's Disease (d 0.25; CI 0.06-0.46), the Epworth Sleepiness Scale (d 0.47; CI 0.24-0.71), the RBD Screening Questionnaire (d 0.44; CI 0.25-0.64), and RBD by PSG (d 0.37; CI 0.19-0.55) as well as VBM units of cortical gray matter (d -0.2; CI -0.3 to -0.09) and hippocampus (d -0.15; CI -0.27 to -0.03). Markers with a relative improvement included the Nonmotor Symptom (Severity) Scale (d -0.19; CI -0.36 to -0.02) and 2 depression scales (Beck Depression Inventory d -0.18; CI -0.36 to 0; Montgomery-Åsberg Depression Rating Scale d -0.26; CI -0.47 to -0.04). Unexpectedly, cognitive measures and select laboratory markers were not significantly changed in PD vs HC participants.
  
  
  
  Current CSF biomarkers and cognitive scales do not represent useful progression markers. However, sleep and imaging measures, and to some extent NMS, assessed using adequate scales, may be more informative markers to quantify progression.
authors.affiliation: From Paracelsus-Elena-Klinik (B.M., F.S.-D., T.W., J.E., M.S., E.L., E.T., C.T.), Kassel; Departments of Neurosurgery (B.M., C.T.) and Medical Statistics (T.F.) and Institute of Neuropathology (B.M.), University Medical Centre Göttingen; Psychologische Hochschule Berlin (J.Z.); Department of Neurology/Epileptology and Hertie Institute of Clinical Brain Research (N.K.F.), University of Tübingen, Germany; Clinical Neurochemistry Laboratory (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; and BioLegend (P.T.), Dedham, MA. brit.mollenhauer@paracelsus-kliniken.de.
authors.forename: Brit
authors.initials: B
authors.lastname: Mollenhauer
authors.affiliation: From Paracelsus-Elena-Klinik (B.M., F.S.-D., T.W., J.E., M.S., E.L., E.T., C.T.), Kassel; Departments of Neurosurgery (B.M., C.T.) and Medical Statistics (T.F.) and Institute of Neuropathology (B.M.), University Medical Centre Göttingen; Psychologische Hochschule Berlin (J.Z.); Department of Neurology/Epileptology and Hertie Institute of Clinical Brain Research (N.K.F.), University of Tübingen, Germany; Clinical Neurochemistry Laboratory (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; and BioLegend (P.T.), Dedham, MA.
authors.forename: Johannes
authors.initials: J
authors.lastname: Zimmermann
authors.affiliation: From Paracelsus-Elena-Klinik (B.M., F.S.-D., T.W., J.E., M.S., E.L., E.T., C.T.), Kassel; Departments of Neurosurgery (B.M., C.T.) and Medical Statistics (T.F.) and Institute of Neuropathology (B.M.), University Medical Centre Göttingen; Psychologische Hochschule Berlin (J.Z.); Department of Neurology/Epileptology and Hertie Institute of Clinical Brain Research (N.K.F.), University of Tübingen, Germany; Clinical Neurochemistry Laboratory (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; and BioLegend (P.T.), Dedham, MA.
authors.forename: Friederike
authors.initials: F
authors.lastname: Sixel-Döring
authors.affiliation: From Paracelsus-Elena-Klinik (B.M., F.S.-D., T.W., J.E., M.S., E.L., E.T., C.T.), Kassel; Departments of Neurosurgery (B.M., C.T.) and Medical Statistics (T.F.) and Institute of Neuropathology (B.M.), University Medical Centre Göttingen; Psychologische Hochschule Berlin (J.Z.); Department of Neurology/Epileptology and Hertie Institute of Clinical Brain Research (N.K.F.), University of Tübingen, Germany; Clinical Neurochemistry Laboratory (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; and BioLegend (P.T.), Dedham, MA.
authors.forename: Niels K
authors.initials: NK
authors.lastname: Focke
authors.affiliation: From Paracelsus-Elena-Klinik (B.M., F.S.-D., T.W., J.E., M.S., E.L., E.T., C.T.), Kassel; Departments of Neurosurgery (B.M., C.T.) and Medical Statistics (T.F.) and Institute of Neuropathology (B.M.), University Medical Centre Göttingen; Psychologische Hochschule Berlin (J.Z.); Department of Neurology/Epileptology and Hertie Institute of Clinical Brain Research (N.K.F.), University of Tübingen, Germany; Clinical Neurochemistry Laboratory (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; and BioLegend (P.T.), Dedham, MA.
authors.forename: Tamara
authors.initials: T
authors.lastname: Wicke
authors.affiliation: From Paracelsus-Elena-Klinik (B.M., F.S.-D., T.W., J.E., M.S., E.L., E.T., C.T.), Kassel; Departments of Neurosurgery (B.M., C.T.) and Medical Statistics (T.F.) and Institute of Neuropathology (B.M.), University Medical Centre Göttingen; Psychologische Hochschule Berlin (J.Z.); Department of Neurology/Epileptology and Hertie Institute of Clinical Brain Research (N.K.F.), University of Tübingen, Germany; Clinical Neurochemistry Laboratory (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; and BioLegend (P.T.), Dedham, MA.
authors.forename: Jens
authors.initials: J
authors.lastname: Ebentheuer
authors.affiliation: From Paracelsus-Elena-Klinik (B.M., F.S.-D., T.W., J.E., M.S., E.L., E.T., C.T.), Kassel; Departments of Neurosurgery (B.M., C.T.) and Medical Statistics (T.F.) and Institute of Neuropathology (B.M.), University Medical Centre Göttingen; Psychologische Hochschule Berlin (J.Z.); Department of Neurology/Epileptology and Hertie Institute of Clinical Brain Research (N.K.F.), University of Tübingen, Germany; Clinical Neurochemistry Laboratory (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; and BioLegend (P.T.), Dedham, MA.
authors.forename: Martina
authors.initials: M
authors.lastname: Schaumburg
authors.affiliation: From Paracelsus-Elena-Klinik (B.M., F.S.-D., T.W., J.E., M.S., E.L., E.T., C.T.), Kassel; Departments of Neurosurgery (B.M., C.T.) and Medical Statistics (T.F.) and Institute of Neuropathology (B.M.), University Medical Centre Göttingen; Psychologische Hochschule Berlin (J.Z.); Department of Neurology/Epileptology and Hertie Institute of Clinical Brain Research (N.K.F.), University of Tübingen, Germany; Clinical Neurochemistry Laboratory (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; and BioLegend (P.T.), Dedham, MA.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lang
authors.affiliation: From Paracelsus-Elena-Klinik (B.M., F.S.-D., T.W., J.E., M.S., E.L., E.T., C.T.), Kassel; Departments of Neurosurgery (B.M., C.T.) and Medical Statistics (T.F.) and Institute of Neuropathology (B.M.), University Medical Centre Göttingen; Psychologische Hochschule Berlin (J.Z.); Department of Neurology/Epileptology and Hertie Institute of Clinical Brain Research (N.K.F.), University of Tübingen, Germany; Clinical Neurochemistry Laboratory (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; and BioLegend (P.T.), Dedham, MA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Trautmann
authors.affiliation: From Paracelsus-Elena-Klinik (B.M., F.S.-D., T.W., J.E., M.S., E.L., E.T., C.T.), Kassel; Departments of Neurosurgery (B.M., C.T.) and Medical Statistics (T.F.) and Institute of Neuropathology (B.M.), University Medical Centre Göttingen; Psychologische Hochschule Berlin (J.Z.); Department of Neurology/Epileptology and Hertie Institute of Clinical Brain Research (N.K.F.), University of Tübingen, Germany; Clinical Neurochemistry Laboratory (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; and BioLegend (P.T.), Dedham, MA.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: From Paracelsus-Elena-Klinik (B.M., F.S.-D., T.W., J.E., M.S., E.L., E.T., C.T.), Kassel; Departments of Neurosurgery (B.M., C.T.) and Medical Statistics (T.F.) and Institute of Neuropathology (B.M.), University Medical Centre Göttingen; Psychologische Hochschule Berlin (J.Z.); Department of Neurology/Epileptology and Hertie Institute of Clinical Brain Research (N.K.F.), University of Tübingen, Germany; Clinical Neurochemistry Laboratory (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; and BioLegend (P.T.), Dedham, MA.
authors.forename: Peggy
authors.initials: P
authors.lastname: Taylor
authors.affiliation: From Paracelsus-Elena-Klinik (B.M., F.S.-D., T.W., J.E., M.S., E.L., E.T., C.T.), Kassel; Departments of Neurosurgery (B.M., C.T.) and Medical Statistics (T.F.) and Institute of Neuropathology (B.M.), University Medical Centre Göttingen; Psychologische Hochschule Berlin (J.Z.); Department of Neurology/Epileptology and Hertie Institute of Clinical Brain Research (N.K.F.), University of Tübingen, Germany; Clinical Neurochemistry Laboratory (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; and BioLegend (P.T.), Dedham, MA.
authors.forename: Tim
authors.initials: T
authors.lastname: Friede
authors.affiliation: From Paracelsus-Elena-Klinik (B.M., F.S.-D., T.W., J.E., M.S., E.L., E.T., C.T.), Kassel; Departments of Neurosurgery (B.M., C.T.) and Medical Statistics (T.F.) and Institute of Neuropathology (B.M.), University Medical Centre Göttingen; Psychologische Hochschule Berlin (J.Z.); Department of Neurology/Epileptology and Hertie Institute of Clinical Brain Research (N.K.F.), University of Tübingen, Germany; Clinical Neurochemistry Laboratory (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; and BioLegend (P.T.), Dedham, MA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Trenkwalder
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000000981:diagnostic imaging; D018450:Disease Progression; D015259:Dopamine Agents / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology; D017286:Polysomnography; D011379:Prognosis; D011788:Quality of Life; D012720:Severity of Illness Index
chemical_list: D000978:Antiparkinson Agents; D015415:Biomarkers; D015259:Dopamine Agents