The Dutch Parkinson and Cognition Study

Parkinson Disease (PD) is a heterogeneous, progressive neurodegenerative disorder which is characterized by a variety of motor and non-motor symptoms. The DUPARC study is a single-centre longitudinal cohort study aimed at deeply phenotyping newly diagnosed PD patients. The main aim is to investigate the relationship between cognitive impairment and both cholinergic and dopaminergic neurodegeneration in the early stages of the disease. In addition, gastrointestinal and visual system dysfunction in PD and their role in the underlying pathology are further explored in a longitudinal setup. Treatment-naïve participants will undergo extensive motor- and non-motor assessment, imaging, and microbiome assessment at time of diagnosis, and will be followed for at least 3 years.

Rationale: Parkinson's disease (PD) is characterized by both motor and non-motor symptoms, including cognitive decline. Mild cognitive impairment (PD-MCI) is already present at time of diagnosis in 24-36% of PD patients. Cognitive impairment in PD is associated with both cholinergic and dopaminergic deficiencies in the brain. Although dopaminergic neuronal degeneration is quite well established in relationship to the motor impairment, the rate and extent of the cholinergic neuronal degeneration in the course of PD is unknown. It is also unclear how cholinergic and dopaminergic degeneration contributes to cognitive deficits found in early and more advanced PD and its role in the progression over time. Objectives: The primary objective is to establish the relationship between cognitive impairment and cholinergic neurodegeneration in de novo PD patients, by studying cholinergic imaging using \[ 18 F\]Fluoroethoxy-Benzovesamicol (\[18F\]FEOBV) positron emission tomography (PET) and neuropsychological performance over time. Secondary objectives include: (1) the investigation of possible predictive factors using optical coherence tomography and (2) to determine the relative contributions of PD diagnosis and dopaminergic medication use to the changes in microbiota composition observed in PD patients. Study design: At baseline patients will undergo the following investigations and questionnaires: Demographics, detailed medical history, neuropsychological assessment, imaging including MRI brain, dopaminergic Fluoro-18-L-Dihydroxyphenylalanine (18F-FDOPA) and cholinergic FEOBV PET, optical coherence tomography (OCT) and microbiota composition. At one year follow-up subjects will undergo motor-, neuropsychological, and microbiota assessment. At 3 year follow up baseline measurements will be repeated in its entirety with the exception of the genetic and gastrointestinal assessments. Study population: 150 de novo PD patients, recruited from the neurological practices in the northern area of the Netherlands and healthy control subjects. Healthy age-,sex- and constipation-matched controls will be assessed on microbiota composition Assessment and endpoints related to gastroenterological assessment have been approved under a separate research protocol (NL61123.042.17 - CCMO) and has been officially linked to the overall protocol.