Brit Mollenhauer1, Johannes Zimmermann2, Friederike Sixel-Döring2, Niels K Focke2, Tamara Wicke2, Jens Ebentheuer2, Martina Schaumburg2, Elisabeth Lang2, Ellen Trautmann2, Henrik Zetterberg2, Peggy Taylor2, Tim Friede2, Claudia Trenkwalder2. 1. 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. 2. 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.
Abstract
OBJECTIVE: 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). METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE: 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). METHODS: 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). RESULTS: 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 HCparticipants. CONCLUSIONS: 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: W M M Schuepbach; J Rau; K Knudsen; J Volkmann; P Krack; L Timmermann; T D Hälbig; H Hesekamp; S M Navarro; N Meier; D Falk; M Mehdorn; S Paschen; M Maarouf; M T Barbe; G R Fink; A Kupsch; D Gruber; G-H Schneider; E Seigneuret; A Kistner; P Chaynes; F Ory-Magne; C Brefel Courbon; J Vesper; A Schnitzler; L Wojtecki; J-L Houeto; B Bataille; D Maltête; P Damier; S Raoul; F Sixel-Doering; D Hellwig; A Gharabaghi; R Krüger; M O Pinsker; F Amtage; J-M Régis; T Witjas; S Thobois; P Mertens; M Kloss; A Hartmann; W H Oertel; B Post; H Speelman; Y Agid; C Schade-Brittinger; G Deuschl Journal: N Engl J Med Date: 2013-02-14 Impact factor: 91.245
Authors: Alberto Ascherio; Peter A LeWitt; Kui Xu; Shirley Eberly; Arthur Watts; Wayne R Matson; Connie Marras; Karl Kieburtz; Alice Rudolph; Mikhail B Bogdanov; Steven R Schwid; Marsha Tennis; Caroline M Tanner; M Flint Beal; Anthony E Lang; David Oakes; Stanley Fahn; Ira Shoulson; Michael A Schwarzschild Journal: Arch Neurol Date: 2009-12
Authors: Sara Hall; Annika Öhrfelt; Radu Constantinescu; Ulf Andreasson; Yulia Surova; Frederick Bostrom; Christer Nilsson; Widner Håkan; Hilde Decraemer; Katarina Någga; Lennart Minthon; Elisabet Londos; Eugeen Vanmechelen; Björn Holmberg; Henrik Zetterberg; Kaj Blennow; Oskar Hansson Journal: Arch Neurol Date: 2012-11