Network-based biOmarker Discovery of Neurodegenerative Diseases Using Multimodal Connectivity
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Multimodal connectivity graph metrics across diseases
研究概览
简要总结
The aim of the NODAL clinical trial is to demonstrate the feasibility of new, low-cost, non-invasive biomarkers of neurodegenerative pathologies as early Alzheimer and Parkinson, based on the estimation of the multimodal connectome.
详细描述
Alzheimer's (AD) and Parkinson's (PD) diseases are characterized by pre-clinical and asymptomatic phases, which can extend over decades, before progressing through different clinical stages where cognitive and/or motor symptoms appear. A major challenge for clinical neuroscience is the availability of reliable, non-invasive and inexpensive biomarkers to enable early diagnosis, be clinically relevant, and ideally contribute to prognosis and patient monitoring.
Current criteria, which are essentially clinical, have a relatively low diagnostic accuracy, which is unfortunately responsible for a delay in diagnosis, whereas it has been established that early diagnosis makes it possible to postpone the loss of autonomy, open up opportunities for clinical trials for patients, and, epidemiologically speaking, ultimately reduce the prevalence of major neurocognitive disorders.
Recent advances in neuroimaging techniques and connectome analysis have led to the identification of innovative biomarkers that reflect the disorganization of brain networks and are associated with clinical symptoms.
After participant inclusion, the experimental visit will take place over half a day, for patients with early-stage Alzheimer's or Parkinson's disease and for healthy control volunteers.
After clinical assessment, participants will undergo an MRI scan and then perform the CONFMEM experimental task.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For all participants:
- •French mother tongue
- •right-handed
- •with a level of education equal to or higher than the Certificat d'Études Primaires (Primary School Certificate)
- •Free of any medical or psychiatric condition likely to interfere with cognition (excluding diagnosis for patients)
- •Affiliated with a social security scheme
- •Having received oral and written information about the protocol and having signed a consent form to participate in this research.
- •DCS+ group:
- •- Meeting the diagnostic criteria for "subjective cognitive decline-plus" (Jessen criteria (Jessen et al., 2014).
- •Alzheimer's patients "Mild Cognitive Impairment due to Alzheimer's Disease," "MCI-MA":
- •- Meeting the diagnostic criteria for "Mild neurocognitive disorder due to Alzheimer's disease" (criteria of (Albert et al., 2011))
- •De novo" Parkinsonian patients, "MPdn":
- •- Presenting with newly diagnosed ("de novo") Parkinson's disease and free of cognitive deficits (criteria of Postuma et al., 2015 (Postuma et al., 2015))
- •Parkinsonian patients with "Mild Cognitive Impairment, "MCI-MP":
- •- Presenting Parkinson's disease associated with "mild neurocognitive impairment" (criteria of Litvan et al., 2012 (Litvan et al., 2012))
排除标准
- •All participants (healthy volunteers and patients)
- •Contraindications to MRI :
- •Abdominal circumference + upper limbs sticking to the body > 200 cm;
- •Implantable pacemaker or defibrillator;
- •Neurosurgical clips;
- •Cochlear implants ;
- •Neural or peripheral stimulator;
- •Intra-orbital or encephalic metallic foreign bodies;
- •Endoprostheses fitted less than 4 weeks ago and osteosynthesis devices fitted less than 6 weeks ago;
- •Claustrophobia.
- •Pregnant or breast-feeding women;
- •Adults under legal protection (safeguard of justice, curatorship, guardianship), persons deprived of liberty.
- •Patients only
- •Score >2 on the modified Hachinski scale (Hachinski et al., 2012)
- •Dementia according to McKhann criteria (McKhann et al., 2011)
- •Sensory deficit interfering with experimental tests
- •Healthy volunteers only
- •- Cognitive impairment (MoCA score < 26)
结局指标
主要结局
Multimodal connectivity graph metrics across diseases
时间窗: 2 hours and 30 minutes
Multi-layer graph combining the functional and structural connectivity will provide an ideal framework for identifying multimodal features. The first layer corresponds to the functional connectivity where links represent the similarity between the fMRI signal from different cerebral regions (i.e. the nodes), using the cross-correlation. The second layer represents the structural connectivity where the edges are the fiber density between the nodes. Topological metrics of graph: 1/ the nodal centrality which quantifies how important a node is within a network, 2/ the betweenness defined as the ratio of the number of the shortest paths comprising the node to the total number of shortest paths in the graph, measures the hub property of the node and 3/ local efficiency which quantify the ability of a network to transmit information at the global and local level, will be compared between patients at-risk for Alzheimer's Disease, patients with Parkinson's Disease and healthy controls.
次要结局
- Correlation between multimodal connectivity graph metrics and cognitive scores(Up to 6 months (maximum delay between the study visit and the collection of standard tasks).)
- Multimodal connectivity graph metrics across stages of disease(2 hours and 30 minutes)