Study protocol of the DUtch PARkinson Cohort (DUPARC): a prospective, observational study of de novo Parkinson’s disease patients for the identification and validation of biomarkers for Parkinson’s disease subtypes, progression and pathophysiology
Authors: Boertien Jeffrey M. , van der Zee Sygrid , Chrysou Asterios , Gerritsen Marleen J. J. , Jansonius Nomdo M. , Spikman Jacoba M. , van Laar Teus ,   the PPNN Study Group, Verwey N. A. , Van Harten B. , Portman A. T. , Langedijk M. J. H. , Oomes P. G. , Jansen B. J. A. M. , Van Wieren T. , Van den Bogaard S. J. A. , Van Steenbergen W. , Duyff R. , Van Amerongen J. P. , Fransen P. S. S. , Polman S. K. L. , Zwartbol R. T. , Van Kesteren M. E. , Braakhekke J. P. , Trip J. , Koops L. , De Langen C. J. , De Jong G. , Hartono J. E. S. , Ybema H. , Bartels A. L. , Reesink F. E. , Postma A. G. , Vonk G. J. H. , Oen J. M. T. H. , Brinkman M. J. , Mondria T. , Holscher R. S. , Van der Meulen A. A. E. , Rutgers A. W. F. , Boekestein W. A. , Teune L. K. , Orsel P. J. L. , Hoogendijk J. E. , Van Laar T. 
Published: June 2020

Abstract
Background
Parkinson’s Disease (PD) is a heterogeneous, progressive neurodegenerative disorder which is characterized by a variety of motor and non-motor symptoms. To date, no disease modifying treatment for PD exists. Here, the study protocol of the Dutch Parkinson Cohort (DUPARC) is described. DUPARC is a longitudinal cohort study aimed at deeply phenotyping de novo PD patients who are treatment-naïve at baseline, to discover and validate biomarkers for PD progression, subtypes and pathophysiology.

Methods/design
DUPARC is a prospective cohort study in which 150 de novo PD subjects will be recruited through a collaborative network of PD treating neurologists in the northern part of the Netherlands (Parkinson Platform Northern Netherlands, PPNN). Participants will receive follow-up assessments after 1 year and 3 years, with the intention of an extended follow-up with 3 year intervals. Subjects are extensively characterized to primarily assess objectives within three major domains of PD: cognition, gastrointestinal function and vision. This includes brain magnetic resonance imaging (MRI); brain cholinergic PET-imaging with fluoroethoxybenzovesamicol (FEOBV-PET); brain dopaminergic PET-imaging with fluorodopa (FDOPA-PET); detailed neuropsychological assessments, covering all cognitive domains; gut microbiome composition; intestinal wall permeability; optical coherence tomography (OCT); genotyping; motor and non-motor symptoms; overall clinical status and lifestyle factors, including a dietary assessment; storage of blood and feces for additional analyses of inflammation and metabolic parameters. Since the start of the inclusion, at the end of 2017, over 100 PD subjects with a confirmed dopaminergic deficit on FDOPA-PET have been included.

Discussion
DUPARC is the first study to combine data within, but not limited to, the non-motor domains of cognition, gastrointestinal function and vision in PD subjects over time. As a de novo PD cohort, with treatment naïve subjects at baseline, DUPARC provides a unique opportunity for biomarker discovery and validation without the possible confounding influences of dopaminergic medication.

Trial registration
NCT04180865; registered retrospectively, November 28th 2019.