Biomarkers of the Locus Coeruleus Nucleus: Links With Early Tau Pathology, Cognition and Alzheimer's Disease Risk.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- diagnostic capabilities of Locus Coeruleus biomarkers for a positive PET-Tau exam
研究概览
简要总结
Alzheimer's disease (AD) is characterized by a long-lasting silent phase. Among initial events, emergence of tau pathology in locus coeruleus (LC) brainstem nucleus, well before the one observed in medial temporal cortex, is highly relevant. LC integrity and function can be assessed in vivo with MRI and pupil measures. The current research proposes to evaluate these LC markers in an aged healthy cohort (n=100, with half APOE4 positive) and to relate these markers with cerebral tau pathology, AD risk and cognitive function.
详细描述
Early tau pathology in the LC may induce dysfunction of the LC-NA system, contribute to initial cognitive decline and possibly be predictive of future AD occurrence. The present project has the following objectives: 1) to relate different biomarkers of LC function measured in vivo with AD risk and future AD occurrence, in order to evaluate their relevance for earliest AD diagnosis, 2) to investigate how LC biomarkers can account for underlying brain tau pathology in asymptomatic older individuals; a related objective will be to validate LC biomarkers as reliable proxies of tau pathology occurrence, and 3) to study the link between LC biomarkers and cognitive performance.
To complete these objectives, the project will evaluate, in healthy older volunteers from the INSPIRE-T cohort (n=100, > 60 years old), biomarkers of LC neuronal integrity, LC-forebrain connectivity, and LC tonic and phasic activity. Additionally, a positon emission tomography (PET) exam will be conducted using tau-specific tracer. Detailed cognitive assessment will also be performed, including assessment of a priori NA-dependent and NA-independent cognitive functions. In the studied cohort (n = 100), half volunteers will be recruited based on genetic AD risk (APOE4 positive) and the other half based on the absence of risk (APOE4 negative).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 60 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participant in the INSPIRE-T cohort
- •Normal cognitive assessment
- •MMSE score ≥ 27 out of 30 (Mini-Mental State Examination)
- •Normal visual abilities (in corrected or uncorrected vision)
- •Normal motor skills
排除标准
- •Subjects with a contraindication to MRI exam
- •Subjects with a known allergic reaction to the PET radiopharmaceutical ([18F] Flortaucipir) or any of its excipients
- •Subjects with an ophthalmological pathology making oculometric measurements difficult
- •Subjects with a neurodegenerative condition or a history of cerebral ischemia
- •Subjects with a psychiatric disorder and a PHQ-9 score > 10 or under treatment with NRI
研究组 & 干预措施
experimental arm
TEP exam, MRI exam, oculometry assessment and cognitive tasks
干预措施: a positon emission tomography (PET) exam (Drug)
experimental arm
TEP exam, MRI exam, oculometry assessment and cognitive tasks
干预措施: MRI Contrast (Other)
experimental arm
TEP exam, MRI exam, oculometry assessment and cognitive tasks
干预措施: oculometry assessment (Other)
experimental arm
TEP exam, MRI exam, oculometry assessment and cognitive tasks
干预措施: cognitive exams (Other)
结局指标
主要结局
diagnostic capabilities of Locus Coeruleus biomarkers for a positive PET-Tau exam
时间窗: 24 monnths
The diagnostic capabilities (sensitivity, specificity and AUC) of each of the elements of oculometry (pupillary response, number, latency and amplitude of ocular saccades), functional MRI (LC-hippocampus and LC-prefrontal cortex) and structural MRI (LC intensity) for a positive PET-Tau examination
次要结局
- The link between PET Tau uptake and PET-estimated perfusion changes(24 months)
- diagnostic capabilities of Locus Coeruleus biomarkers for a positive PET-Tau exam for the APOe4- groups(24 months)
- diagnostic capabilities of Locus Coeruleus biomarkers for a positive PET-Tau exam for the APOe4+ groups(24 months)
- The relationship between different LC biomarkers(24 months)
- The link between PET Tau uptake in oculometry(24 months)
- The link between PET Tau uptake in the structural (neuromelanin) and functional integrity of the LC by MRI(24 months)
- The link between variations in pupillometry(24 months)
- The link between variations in occulometry(24 months)
- The link between variations in the structural (neuromelanin) and functional integrity of the LC by MRI(24 months)
- The relationship between the various LC biomarkers (PET, MRI, pupillometry) and participants' cognitive performance(24 months)
- comparison between APOe4+ and APOe4-: Structural (neuromelanin) and functional integrity of the LC by MRI(24 months)
- comparison between APOe4+ and APOe4: Cognitive performance(24 months)
- comparison between APOe4+ and APOe4-: Pupillometry and oculometry(24 months)
- The reliability of the amplitude of the phasic pupil response during completion of cognitive tasks(24 months)
- The reliability of the latency of saccadic eye movements during completion of cognitive tasks(24 months)
- The reliability of the amplitude of saccadic eye movements during completion of cognitive tasks(24 months)