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October 01, 2013; 81 (14) Article

Nonmotor and diagnostic findings in subjects with de novo Parkinson disease of the DeNoPa cohort

Brit Mollenhauer, Ellen Trautmann, Friederike Sixel-Döring, Tamara Wicke, Jens Ebentheuer, Martina Schaumburg, Elisabeth Lang, Niels K. Focke, Kishore R. Kumar, Katja Lohmann, Christine Klein, Michael G. Schlossmacher, Ralf Kohnen, Tim Friede, Claudia Trenkwalder, On behalf of the DeNoPa Study Group
First published August 30, 2013, DOI: https://doi.org/10.1212/WNL.0b013e3182a6cbd5
Brit Mollenhauer
From the Center of Parkinsonism and Movement Disorders (B.M., E.T., F.S.-D., T.W., J.E., M.S., E.L., C.T.), Paracelsus-Elena-Klinik, Kassel; Department of Neurosurgery (B.M., N.K.F., C.T.), University Medical Centre, Goettingen; Department of Psychology (E.T.), University Kassel; Section of Clinical and Molecular Neurogenetics at the Department of Neurology (K.R.K., K.L., C.K.), University of Luebeck; Departments of Neuropathology (B.M.) and Medical Statistics (T.F.), University Medical Centre, Goettingen, Germany; Program in Neuroscience (M.G.S.), Ottawa Hospital Research Institute; Division of Neurology, The Ottawa Hospital, University of Ottawa, Canada; and ReSearch Pharmaceutical Services (R.K.), Nuremberg, Germany.
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Ellen Trautmann
From the Center of Parkinsonism and Movement Disorders (B.M., E.T., F.S.-D., T.W., J.E., M.S., E.L., C.T.), Paracelsus-Elena-Klinik, Kassel; Department of Neurosurgery (B.M., N.K.F., C.T.), University Medical Centre, Goettingen; Department of Psychology (E.T.), University Kassel; Section of Clinical and Molecular Neurogenetics at the Department of Neurology (K.R.K., K.L., C.K.), University of Luebeck; Departments of Neuropathology (B.M.) and Medical Statistics (T.F.), University Medical Centre, Goettingen, Germany; Program in Neuroscience (M.G.S.), Ottawa Hospital Research Institute; Division of Neurology, The Ottawa Hospital, University of Ottawa, Canada; and ReSearch Pharmaceutical Services (R.K.), Nuremberg, Germany.
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Friederike Sixel-Döring
From the Center of Parkinsonism and Movement Disorders (B.M., E.T., F.S.-D., T.W., J.E., M.S., E.L., C.T.), Paracelsus-Elena-Klinik, Kassel; Department of Neurosurgery (B.M., N.K.F., C.T.), University Medical Centre, Goettingen; Department of Psychology (E.T.), University Kassel; Section of Clinical and Molecular Neurogenetics at the Department of Neurology (K.R.K., K.L., C.K.), University of Luebeck; Departments of Neuropathology (B.M.) and Medical Statistics (T.F.), University Medical Centre, Goettingen, Germany; Program in Neuroscience (M.G.S.), Ottawa Hospital Research Institute; Division of Neurology, The Ottawa Hospital, University of Ottawa, Canada; and ReSearch Pharmaceutical Services (R.K.), Nuremberg, Germany.
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Tamara Wicke
From the Center of Parkinsonism and Movement Disorders (B.M., E.T., F.S.-D., T.W., J.E., M.S., E.L., C.T.), Paracelsus-Elena-Klinik, Kassel; Department of Neurosurgery (B.M., N.K.F., C.T.), University Medical Centre, Goettingen; Department of Psychology (E.T.), University Kassel; Section of Clinical and Molecular Neurogenetics at the Department of Neurology (K.R.K., K.L., C.K.), University of Luebeck; Departments of Neuropathology (B.M.) and Medical Statistics (T.F.), University Medical Centre, Goettingen, Germany; Program in Neuroscience (M.G.S.), Ottawa Hospital Research Institute; Division of Neurology, The Ottawa Hospital, University of Ottawa, Canada; and ReSearch Pharmaceutical Services (R.K.), Nuremberg, Germany.
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Jens Ebentheuer
From the Center of Parkinsonism and Movement Disorders (B.M., E.T., F.S.-D., T.W., J.E., M.S., E.L., C.T.), Paracelsus-Elena-Klinik, Kassel; Department of Neurosurgery (B.M., N.K.F., C.T.), University Medical Centre, Goettingen; Department of Psychology (E.T.), University Kassel; Section of Clinical and Molecular Neurogenetics at the Department of Neurology (K.R.K., K.L., C.K.), University of Luebeck; Departments of Neuropathology (B.M.) and Medical Statistics (T.F.), University Medical Centre, Goettingen, Germany; Program in Neuroscience (M.G.S.), Ottawa Hospital Research Institute; Division of Neurology, The Ottawa Hospital, University of Ottawa, Canada; and ReSearch Pharmaceutical Services (R.K.), Nuremberg, Germany.
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Martina Schaumburg
From the Center of Parkinsonism and Movement Disorders (B.M., E.T., F.S.-D., T.W., J.E., M.S., E.L., C.T.), Paracelsus-Elena-Klinik, Kassel; Department of Neurosurgery (B.M., N.K.F., C.T.), University Medical Centre, Goettingen; Department of Psychology (E.T.), University Kassel; Section of Clinical and Molecular Neurogenetics at the Department of Neurology (K.R.K., K.L., C.K.), University of Luebeck; Departments of Neuropathology (B.M.) and Medical Statistics (T.F.), University Medical Centre, Goettingen, Germany; Program in Neuroscience (M.G.S.), Ottawa Hospital Research Institute; Division of Neurology, The Ottawa Hospital, University of Ottawa, Canada; and ReSearch Pharmaceutical Services (R.K.), Nuremberg, Germany.
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Elisabeth Lang
From the Center of Parkinsonism and Movement Disorders (B.M., E.T., F.S.-D., T.W., J.E., M.S., E.L., C.T.), Paracelsus-Elena-Klinik, Kassel; Department of Neurosurgery (B.M., N.K.F., C.T.), University Medical Centre, Goettingen; Department of Psychology (E.T.), University Kassel; Section of Clinical and Molecular Neurogenetics at the Department of Neurology (K.R.K., K.L., C.K.), University of Luebeck; Departments of Neuropathology (B.M.) and Medical Statistics (T.F.), University Medical Centre, Goettingen, Germany; Program in Neuroscience (M.G.S.), Ottawa Hospital Research Institute; Division of Neurology, The Ottawa Hospital, University of Ottawa, Canada; and ReSearch Pharmaceutical Services (R.K.), Nuremberg, Germany.
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Niels K. Focke
From the Center of Parkinsonism and Movement Disorders (B.M., E.T., F.S.-D., T.W., J.E., M.S., E.L., C.T.), Paracelsus-Elena-Klinik, Kassel; Department of Neurosurgery (B.M., N.K.F., C.T.), University Medical Centre, Goettingen; Department of Psychology (E.T.), University Kassel; Section of Clinical and Molecular Neurogenetics at the Department of Neurology (K.R.K., K.L., C.K.), University of Luebeck; Departments of Neuropathology (B.M.) and Medical Statistics (T.F.), University Medical Centre, Goettingen, Germany; Program in Neuroscience (M.G.S.), Ottawa Hospital Research Institute; Division of Neurology, The Ottawa Hospital, University of Ottawa, Canada; and ReSearch Pharmaceutical Services (R.K.), Nuremberg, Germany.
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Kishore R. Kumar
From the Center of Parkinsonism and Movement Disorders (B.M., E.T., F.S.-D., T.W., J.E., M.S., E.L., C.T.), Paracelsus-Elena-Klinik, Kassel; Department of Neurosurgery (B.M., N.K.F., C.T.), University Medical Centre, Goettingen; Department of Psychology (E.T.), University Kassel; Section of Clinical and Molecular Neurogenetics at the Department of Neurology (K.R.K., K.L., C.K.), University of Luebeck; Departments of Neuropathology (B.M.) and Medical Statistics (T.F.), University Medical Centre, Goettingen, Germany; Program in Neuroscience (M.G.S.), Ottawa Hospital Research Institute; Division of Neurology, The Ottawa Hospital, University of Ottawa, Canada; and ReSearch Pharmaceutical Services (R.K.), Nuremberg, Germany.
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Katja Lohmann
From the Center of Parkinsonism and Movement Disorders (B.M., E.T., F.S.-D., T.W., J.E., M.S., E.L., C.T.), Paracelsus-Elena-Klinik, Kassel; Department of Neurosurgery (B.M., N.K.F., C.T.), University Medical Centre, Goettingen; Department of Psychology (E.T.), University Kassel; Section of Clinical and Molecular Neurogenetics at the Department of Neurology (K.R.K., K.L., C.K.), University of Luebeck; Departments of Neuropathology (B.M.) and Medical Statistics (T.F.), University Medical Centre, Goettingen, Germany; Program in Neuroscience (M.G.S.), Ottawa Hospital Research Institute; Division of Neurology, The Ottawa Hospital, University of Ottawa, Canada; and ReSearch Pharmaceutical Services (R.K.), Nuremberg, Germany.
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Christine Klein
From the Center of Parkinsonism and Movement Disorders (B.M., E.T., F.S.-D., T.W., J.E., M.S., E.L., C.T.), Paracelsus-Elena-Klinik, Kassel; Department of Neurosurgery (B.M., N.K.F., C.T.), University Medical Centre, Goettingen; Department of Psychology (E.T.), University Kassel; Section of Clinical and Molecular Neurogenetics at the Department of Neurology (K.R.K., K.L., C.K.), University of Luebeck; Departments of Neuropathology (B.M.) and Medical Statistics (T.F.), University Medical Centre, Goettingen, Germany; Program in Neuroscience (M.G.S.), Ottawa Hospital Research Institute; Division of Neurology, The Ottawa Hospital, University of Ottawa, Canada; and ReSearch Pharmaceutical Services (R.K.), Nuremberg, Germany.
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Michael G. Schlossmacher
From the Center of Parkinsonism and Movement Disorders (B.M., E.T., F.S.-D., T.W., J.E., M.S., E.L., C.T.), Paracelsus-Elena-Klinik, Kassel; Department of Neurosurgery (B.M., N.K.F., C.T.), University Medical Centre, Goettingen; Department of Psychology (E.T.), University Kassel; Section of Clinical and Molecular Neurogenetics at the Department of Neurology (K.R.K., K.L., C.K.), University of Luebeck; Departments of Neuropathology (B.M.) and Medical Statistics (T.F.), University Medical Centre, Goettingen, Germany; Program in Neuroscience (M.G.S.), Ottawa Hospital Research Institute; Division of Neurology, The Ottawa Hospital, University of Ottawa, Canada; and ReSearch Pharmaceutical Services (R.K.), Nuremberg, Germany.
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Ralf Kohnen
From the Center of Parkinsonism and Movement Disorders (B.M., E.T., F.S.-D., T.W., J.E., M.S., E.L., C.T.), Paracelsus-Elena-Klinik, Kassel; Department of Neurosurgery (B.M., N.K.F., C.T.), University Medical Centre, Goettingen; Department of Psychology (E.T.), University Kassel; Section of Clinical and Molecular Neurogenetics at the Department of Neurology (K.R.K., K.L., C.K.), University of Luebeck; Departments of Neuropathology (B.M.) and Medical Statistics (T.F.), University Medical Centre, Goettingen, Germany; Program in Neuroscience (M.G.S.), Ottawa Hospital Research Institute; Division of Neurology, The Ottawa Hospital, University of Ottawa, Canada; and ReSearch Pharmaceutical Services (R.K.), Nuremberg, Germany.
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Tim Friede
From the Center of Parkinsonism and Movement Disorders (B.M., E.T., F.S.-D., T.W., J.E., M.S., E.L., C.T.), Paracelsus-Elena-Klinik, Kassel; Department of Neurosurgery (B.M., N.K.F., C.T.), University Medical Centre, Goettingen; Department of Psychology (E.T.), University Kassel; Section of Clinical and Molecular Neurogenetics at the Department of Neurology (K.R.K., K.L., C.K.), University of Luebeck; Departments of Neuropathology (B.M.) and Medical Statistics (T.F.), University Medical Centre, Goettingen, Germany; Program in Neuroscience (M.G.S.), Ottawa Hospital Research Institute; Division of Neurology, The Ottawa Hospital, University of Ottawa, Canada; and ReSearch Pharmaceutical Services (R.K.), Nuremberg, Germany.
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Claudia Trenkwalder
From the Center of Parkinsonism and Movement Disorders (B.M., E.T., F.S.-D., T.W., J.E., M.S., E.L., C.T.), Paracelsus-Elena-Klinik, Kassel; Department of Neurosurgery (B.M., N.K.F., C.T.), University Medical Centre, Goettingen; Department of Psychology (E.T.), University Kassel; Section of Clinical and Molecular Neurogenetics at the Department of Neurology (K.R.K., K.L., C.K.), University of Luebeck; Departments of Neuropathology (B.M.) and Medical Statistics (T.F.), University Medical Centre, Goettingen, Germany; Program in Neuroscience (M.G.S.), Ottawa Hospital Research Institute; Division of Neurology, The Ottawa Hospital, University of Ottawa, Canada; and ReSearch Pharmaceutical Services (R.K.), Nuremberg, Germany.
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From the Center of Parkinsonism and Movement Disorders (B.M., E.T., F.S.-D., T.W., J.E., M.S., E.L., C.T.), Paracelsus-Elena-Klinik, Kassel; Department of Neurosurgery (B.M., N.K.F., C.T.), University Medical Centre, Goettingen; Department of Psychology (E.T.), University Kassel; Section of Clinical and Molecular Neurogenetics at the Department of Neurology (K.R.K., K.L., C.K.), University of Luebeck; Departments of Neuropathology (B.M.) and Medical Statistics (T.F.), University Medical Centre, Goettingen, Germany; Program in Neuroscience (M.G.S.), Ottawa Hospital Research Institute; Division of Neurology, The Ottawa Hospital, University of Ottawa, Canada; and ReSearch Pharmaceutical Services (R.K.), Nuremberg, Germany.
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Citation
Nonmotor and diagnostic findings in subjects with de novo Parkinson disease of the DeNoPa cohort
Brit Mollenhauer, Ellen Trautmann, Friederike Sixel-Döring, Tamara Wicke, Jens Ebentheuer, Martina Schaumburg, Elisabeth Lang, Niels K. Focke, Kishore R. Kumar, Katja Lohmann, Christine Klein, Michael G. Schlossmacher, Ralf Kohnen, Tim Friede, Claudia Trenkwalder, On behalf of the DeNoPa Study Group
Neurology Oct 2013, 81 (14) 1226-1234; DOI: 10.1212/WNL.0b013e3182a6cbd5

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Abstract

Objective: To determine nonmotor signs (NMS) and evaluate the utility of several diagnostic tools in patients with de novo Parkinson disease (PD).

Methods: This is a large single-center study of the DeNoPa cohort, including frequency-matched healthy controls. This study covers motor signs, NMS, and a combination of diagnostic tests including olfactory testing, transcranial sonography of substantia nigra (TCS), and polysomnography (PSG). We report the frequency and characteristics of NMS and the outcomes of nonmotor tests at the time of diagnosis.

Results: Cross-sectional analyses of baseline investigations identified significant differences in the NMS Questionnaire (NMSQuest) and the Scopa-AUT Gastrointestinal score in 159 drug-naïve PD patients vs 110 controls. In addition, patients with PD showed reduced olfactory function, hyperechogenicity on TCS, and higher frequency of REM sleep behavior disorder (RBD). In exploring predictive markers, we found that the combination of several investigations, i.e., the NMSQuest, Scopa-AUT Gastrointestinal score, and Smell Identification Test reached an area under the receiver operating characteristic curve (AUC) of 0.913 (95% confidence interval [CI] 0.878–0.948). With the addition of serum cholesterol and mean heart rate values, the AUC value reached 0.919 (95% CI 886–0.953); when TCS and PSG were added, the AUC increased to 0.963 (95% CI 0.943–0.982).

Conclusions: We show feasibility and utility of standardized data acquisition in a large, single-center cohort of patients with de novo PD and matched healthy controls. The baseline results from our prospective investigations reached a value of >0.9 sensitivity and specificity for biological markers when we added routine laboratory investigations and quantified nonmotor features including sleep.

GLOSSARY

AUC=
area under the curve;
CI=
confidence interval;
DeNoPa=
De Novo Parkinson;
NMS=
nonmotor signs;
NPH=
normal-pressure hydrocephalus;
PD=
Parkinson disease;
PSG=
polysomnogram;
RBD=
REM sleep behavior disorder;
RBD-SQ=
REM Sleep Behavior Disorder Screening Questionnaire;
RBE=
REM behavioral events;
Scopa-AUT=
Scale for Outcomes in PD for Autonomic Symptoms;
TCS=
transcranial sonography;
UKBBC=
UK Brain Bank Criteria;
UPDRS=
Unified Parkinson's Disease Rating Scale

Footnotes

  • DeNoPa coinvestigators are listed on the Neurology® Web site at www.neurology.org.

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at www.neurology.org

  • Received March 28, 2013.
  • Accepted in final form July 1, 2013.
  • © 2013 American Academy of Neurology
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