The Dutch Parkinson and Cognition Study
- Conditions
- Parkinson Disease
- Registration Number
- NCT04180865
- Lead Sponsor
- University Medical Center Groningen
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 150
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method [18F]FEOBV PET Baseline Cortical and subcortical cholinergic innervation as measured by \[18F\] FEOBV PET imaging
- Secondary Outcome Measures
Name Time Method Attention and working memory performance baseline Attention performance will be calculated as an average Z-score of three cognitive tests; the Stroop color-word test, the digit span and the Vienna test system reaction time measurement. Based on established normative data, a z-score for each test outcome will be calculated, representing performance compared to an age-, gender- and educational level-matched control group. A Z-score of 0 (zero) represents a performance similar to the normative data. A positive z-score represents better performance, while a negative z-score represents worse performance. There is no minimum or maximum z-score. These z-scores from all three tests will be averages to form one outcome measurement representing attention performance.
Cognitive screening baseline General cognitive performance will be assessed using a cognitive screening; the Montreal Cognitive Assessment (MOCA). The MOCA test covers the important cognitive domains including memory, attention, executive function, language and visuospatial abilities, resulting in one total score of cognitive performance. MOCA score ranges between 0 and 30, with higher scores representing better performance.
Memory performance baseline Memory performance will be calculated as an average Z-score of two cognitive tests; the Rey auditory verbal learning test for measuring verbal memory and the location learning test for measuring visual memory. Based on established normative data, a z-score for each test outcome will be calculated, representing performance compared to an age-, gender- and educational level-matched control group. A Z-score of 0 (zero) represents a performance similar to the normative data. A positive z-score represents better performance, while a negative z-score represents worse performance. There is no minimum or maximum z-score. These z-scores from both tests will be averages to form one outcome measurement representing memory performance.
Executive function performance baseline Executive function performance will be calculated as an average Z-score of four cognitive tests; the trail making test, the Wisconsin card sorting test, the Hayling Sentence completion test and the letter fluency test. Based on established normative data, a z-score for each test outcome will be calculated, representing performance compared to an age-, gender- and educational level-matched control group. A Z-score of 0 (zero) represents a performance similar to the normative data. A positive z-score represents better performance, while a negative z-score represents worse performance. There is no minimum or maximum z-score. These z-scores from all tests will be averages to form one outcome measurement representing executive performance.
Visouspatial abilities baseline Cognitive visuospatial abilities will be calculated as an average Z-score of two cognitive tests; the Judgement of line orientation and the Map search subtest of the test of everyday attention. Based on established normative data, a z-score for each test outcome will be calculated, representing performance compared to an age-, gender- and educational level-matched control group. A Z-score of 0 (zero) represents a performance similar to the normative data. A positive z-score represents better performance, while a negative z-score represents worse performance. There is no minimum or maximum z-score. These z-scores from all tests will be averages to form one outcome measurement representing visuospatial abilities.
Language performance baseline Language performance will be calculated as an average Z-score of two cognitive tests; the Boston Naming test and the verbal fluency test. Based on established normative data, a z-score for each test outcome will be calculated, representing performance compared to an age-, gender- and educational level-matched control group. A Z-score of 0 (zero) represents a performance similar to the normative data. A positive z-score represents better performance, while a negative z-score represents worse performance. There is no minimum or maximum z-score. These z-scores from all tests will be averages to form one outcome measurement representing language performance.
Brain grey matter volume Baseline, 3 year follow-up Grey matter volume as measured by structural MRI.
resting state functional MRI Baseline, 3 year follow-up resting state functional MRI
MRI: Arterial spin labeling Baseline, 3 year follow-up cerebral blood perfusion as measured by arterial spin labeling MRI
MRI: Diffusion weighted image Baseline, 3 year follow-up White matter assessment as measured by diffusion weighted image
Optical Coherence tomography Baseline and 3 year follow-up Imaging of the retinal cell layers
Social cognition baseline Social cognition abilities will be represented as a z-score calculated from the performance on the FEEST; Facial Expression of Emotion Stimuli and tests. Based on established normative data, a z-score of the test outcome will be calculated, representing performance compared to an age-, gender- and educational level-matched control group. A Z-score of 0 (zero) represents a performance similar to the normative data. A positive z-score represents better performance, while a negative z-score represents worse performance. There is no minimum or maximum z-score. These z-scores from the FEEST test represents social cognition performance.
MRI: susceptibility weighted image Baseline, 3 year follow-up Brain hemorrhage and iron storage as measured by susceptibility weighted image
fecal zonulin baseline fecal zonulin as one of the measures of intestinal wall permeability
Microbiota composition Baseline and 1 year follow-up Taxonomic classification of gut microbiota composition based on 16s ribosomal RNA-gene sequencing.
fecal alpha1-antitrypsin baseline fecal alpha1-antitrypsin as one of the measures of intestinal wall permeability
serum zonulin baseline serum zonulin as one of the measures of intestinal wall permeability
Movement Disorders Society Unified Parkinson's Disease Rating Scale III Baseline, 1 year follow-up, 3 year follow-up Motor assessment measured by the Movement Disorders Society Unified Parkinson's Disease Rating Scale III, a scale describing motor performance specific for patients with Parkinson's disease. Score between 0 and 72, with a higher score indicating more severe motor impairment.
serum lipopolysaccharide binding protein baseline serum lipopolysaccharide binding protein as one of the measures of intestinal wall permeability
multi-sugar urinary excretion test baseline multi-sugar urinary excretion test as one of the measures of intestinal wall permeability
Change in [18F] FEOBV PET over 3 years baseline, 3 year follow up Change in cortical and subcortical cholinergic innervation over a time period of 3 years, as measured by baseline and follow-up \[18F\] FEOBV
Genetic subtyping Baseline Saliva samples will be collected for clinical-genetic subtyping based on genome wide single-nucleotide polymorphism (SNP) analysis using the Illumina Screening Array (GSA-MD)
Trial Locations
- Locations (1)
University Medical Center Groningen
🇳🇱Groningen, Netherlands