The Dutch Parkinson and Cognition Study (DUPARC): A Prospective Study on Cognitive Pathology in de Novo Parkinson'Disease
试验速览
- 阶段
- 不适用
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- [18F]FEOBV PET
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
[18F]FEOBV PET
时间窗: Baseline
Cortical and subcortical cholinergic innervation as measured by \[18F\] FEOBV PET imaging
次要结局
- Attention and working memory performance(baseline)
- Cognitive screening(baseline)
- Memory performance(baseline)
- Executive function performance(baseline)
- Visouspatial abilities(baseline)
- Language performance(baseline)
- Brain grey matter volume(Baseline, 3 year follow-up)
- resting state functional MRI(Baseline, 3 year follow-up)
- MRI: Arterial spin labeling(Baseline, 3 year follow-up)
- MRI: Diffusion weighted image(Baseline, 3 year follow-up)
- Optical Coherence tomography(Baseline and 3 year follow-up)
- Social cognition(baseline)
- MRI: susceptibility weighted image(Baseline, 3 year follow-up)
- fecal zonulin(baseline)
- Microbiota composition(Baseline and 1 year follow-up)
- fecal alpha1-antitrypsin(baseline)
- serum zonulin(baseline)
- Movement Disorders Society Unified Parkinson's Disease Rating Scale III(Baseline, 1 year follow-up, 3 year follow-up)
- serum lipopolysaccharide binding protein(baseline)
- multi-sugar urinary excretion test(baseline)
- Change in [18F] FEOBV PET over 3 years(baseline, 3 year follow up)
- Genetic subtyping(Baseline)
研究者
Teus van Laar
Professor of Neurology
University Medical Center Groningen