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

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.

Postural and gait symptoms in de novo Parkinson's disease patients correlate with cholinergic white matter pathology

“…Previous studies have consistently indicated the role of the cholinergic system in axial and gait impairment in PD patients [32]. However, little data have been published so far about these cholinergic disturbances in de novo PD patients [20]. Our data show that the cholinergic system is already degenerating in de novo PD patients, especially in the PIGD subtype, who predominantly suffered from slight-to-moderate postural and gait impairment.…”

“…One-hundred fourteen de novo dopa-naïve PD patients from the DUtch PARkinson Cohort (DUPARC) with complete clinical and neuroimaging assessments by the time of study analysis were included in this study [20]. A focused interview was performed to obtain demographic information and symptom as well as medication history.…”

Gut microbiome alterations in fecal samples of treatment-naïve de novo Parkinson’s disease patients

“…For the Dutch (NL) cohort, treatment-naïve de novo PD participants were included as part of the Dutch Parkinson Cohort of de novo PD subjects (DUPARC, ClinicalTrials.gov identifier NCT04180865). 48 Inclusion criteria were PD diagnosis by a movement disorder specialist according to the Movement Disorders Society (MDS) clinical diagnostic criteria, 1 confirmed by a dopaminergic deficit quantified by FDOPA-PET or one-year follow-up if no FDOPA-PET was performed (n=8). HC did not have a neurodegenerative disorder and could not be classified as probable prodromal PD.…”

“…Shotgun metagenomic sequencing would provide complete taxonomy data at the species level and would additionally provide data on the metabolic pathways associated with the sequenced gene fragments. 48,49 Metabolomic analysis would provide actual functional readouts of the gut microbiome. Current data on the metabolome of gut microbiota suggests reduced levels of SCFAs, which would be in line with previous taxonomic studies and our current findings.…”

Diet, Microbiota and Brain Health: Unraveling the Network Intersecting Metabolism and Neurodegeneration

“…Indeed, clinical trials targeting multiple risk domains (FINGER, MAPT, preDIVA), including nutritional guidance, significantly slowed slopes of cognitive decline in the elderly population, especially on high-risk individuals [ 2 ]. At the same time, large observational studies are ongoing to comprehensively assess individuals predisposed to PD and AD and identify personalized paths for risk management [ 381 , 382 ]. Still, dietary interventions may be helpful for symptomatic relief and may assist main drug therapies by improving their pharmacokinetic and adverse effects’ profile [ 383 ].…”