Study of the Predictive Markers and the Pathophysiological Mechanisms of Alzheimer's Disease: Transverse and Longitudinal Approach in Anatomical and Functional Multimodal Imaging
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 242
- 试验地点
- 7
- 主要终点
- Rates of change on each specified biochemical biomarker
研究概览
简要总结
Alzheimer's disease (AD) is a major public health problem due to its socio-economic weight. An early diagnosis of AD is urgently needed as it would constitute a determinant breakthrough from a social, financial and research standpoints. Therefore, the investigators need predictive markers of AD, and neuroimaging is a particularly promising tool, especially when using complementary neuroimaging techniques and a longitudinal design, allowing to assess the relationships between the different biomarkers of the disease, their dynamic and their chronology.
详细描述
The three main objectives of this project are:
- To Identify, compare and combine the predictive markers of AD,
- To better understand the pathophysiologic mechanisms of AD,
- To study the ability of different neuroimaging techniques to monitor AD's evolution.
For these purposes, detailed neuropsychological evaluations, biological measures and brain structural & functional imaging measures are associated for a fully-comprehensive description of the different manifestations of AD through disease progression and toward identifying early markers.
Subjects are evaluated using neuropsychological tests of episodic memory (encoding vs. retrieval), executive functions (inhibition, flexibility, and updating processes), self-judgment, theory of mind, mental imagery and verbal fluency. A FDG-PET measure of resting state glucose consumption, an AV45-PET measure of amyloid deposition as well as anatomical, resting-state and activation fMRI scans are performed for each volonteer. In addition, blood and cerebro-spinal fluid samples will be performed to determine different biomarkers (Aβ1-40, Aβ1-42 and tPA as circulating blood proteins and Aβ40, Aβ42, tau and its phosphorylated form in CSF). The investigators also study the polymorphism of Apolipoprotein E as a genetic risk factor of AD.
One hundred and twenty healthy controls (40 young, 40 middle age and 40 elderly), 40 Mild Cognitive Impairment patients (MCI; i.e. isolated memory impairment and increased risk of developing AD) and 30 AD patients will be selected. Participants with increased risk of developing AD and without objective evidence will be also studied: 50 asymptomatic subjects from families carrying a genetic mutation with an autosomal dominant transmission (NORMA) and 40 Subjective Cognitive Impairment patients (SCI).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Factorial
- 主要目的
- Diagnostic
- 盲法
- None
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
- •Education level > 7 years
- •Native language: French
- •Medical, neurological, neuropsychological and neuroradiological depth in accordance with the criteria for inclusion and exclusion-specific population, that is to say:
- •Healthy young volunteers: between 18 and 40 years old; normal performances compared to the age and the educational level for all tests of the diagnostic battery (± 1.65 SD).
- •Healthy Middle-aged volunteers: between 40 and 60 years old; without memory complaints, normal performances compared to the age and the educational level for all tests of the diagnostic battery (± 1.65 SD).
- •Healthy Elderly volunteers: over 60 years old, living at home, without memory complaints, normal performances compared to the age and the educational level for all tests of the diagnostic battery (± 1.65 SD).
- •SCI patients: over 60 years old ; memory complaints; memory complaint ; normal performances compared to the age and the educational level for all tests of the diagnostic battery (± 1.65 SD).
- •MCI patients: presenting the current criteria for amnestic MCI including: i) memory complaint, ii) deficits of the episodic memory (lower performance of at least 1.65 SD from the norm for age and cultural level for one or more scores of episodic memory and iii) normal performances compared to the age and the educational level of all other cognitive functions as memory, including tests to assess cognitive abilities.
- •Alzheimer's patients: presenting the standard criteria of NINCDS-ADRDA probable Alzheimer's disease, including abnormal global cognitive function and deficits in at least two cognitive domains identified by the diagnostic battery and a mild to moderate Alzheimer's disease (MMSE ≥ 15).
排除标准
- •The sudden onset of cognitive impairments (as opposed to their slow and gradual installation in Alzheimer's disease)
- •A chronic neurological, psychiatric, endocrine, hepatic or infectious complaint
- •A history of major disease (an uncontrolled diabetes, a lung, heart, metabolic, hematologic, endocrine disease or a severe cancer)
- •A medication that may interfere with memory or metabolic measures
- •A alcohol or drugs abuse
- •The cons-indications to MRI (claustrophobia, metallic object in the body)
- •A predominantly left-hand (score below 50% in Edinburgh Inventory)
- •Protected adults, and persons not affiliated with a social security system will not participate in this study
- •The inclusion of a participant in another biomedical research protocol
研究组 & 干预措施
Young controls
干预措施: Circulating biomarkers measure (Biological)
Young controls
干预措施: ApoE4 (Genetic)
Young controls
干预措施: Brain imaging examination MRI and PET examinations (Other)
Middle age controls
干预措施: Memory assessment (Behavioral)
Middle age controls
干预措施: Circulating biomarkers measure (Biological)
Middle age controls
干预措施: ApoE4 (Genetic)
Middle age controls
干预措施: Brain imaging examination MRI and PET examinations (Other)
Elderly controls
干预措施: Memory assessment (Behavioral)
Elderly controls
干预措施: Circulating biomarkers measure (Biological)
Elderly controls
干预措施: ApoE4 (Genetic)
Elderly controls
干预措施: Brain imaging examination MRI and PET examinations (Other)
Young controls
干预措施: Memory assessment (Behavioral)
Alzheimer Disease patients
干预措施: Circulating biomarkers measure (Biological)
Asymptomatic subjects
Asymptomatic subjects from families carrying a genetic mutation with an autosomal dominant transmission
干预措施: Memory assessment (Behavioral)
Asymptomatic subjects
Asymptomatic subjects from families carrying a genetic mutation with an autosomal dominant transmission
干预措施: Circulating biomarkers measure (Biological)
Asymptomatic subjects
Asymptomatic subjects from families carrying a genetic mutation with an autosomal dominant transmission
干预措施: ApoE4 (Genetic)
Alzheimer Disease patients
干预措施: ApoE4 (Genetic)
Asymptomatic subjects
Asymptomatic subjects from families carrying a genetic mutation with an autosomal dominant transmission
干预措施: Brain imaging examination MRI and PET examinations (Other)
Subjectif Cognitive Impariment patients
干预措施: Memory assessment (Behavioral)
Subjectif Cognitive Impariment patients
干预措施: Circulating biomarkers measure (Biological)
Subjectif Cognitive Impariment patients
干预措施: ApoE4 (Genetic)
Subjectif Cognitive Impariment patients
干预措施: Brain imaging examination MRI and PET examinations (Other)
Mild Cognitive Impairment patients
干预措施: Memory assessment (Behavioral)
Mild Cognitive Impairment patients
干预措施: Circulating biomarkers measure (Biological)
Mild Cognitive Impairment patients
干预措施: ApoE4 (Genetic)
Mild Cognitive Impairment patients
干预措施: Brain imaging examination MRI and PET examinations (Other)
Alzheimer Disease patients
干预措施: Memory assessment (Behavioral)
Alzheimer Disease patients
干预措施: Brain imaging examination MRI and PET examinations (Other)
Non degenerative amnsesic syndrome
干预措施: Memory assessment (Behavioral)
Non degenerative amnsesic syndrome
干预措施: Circulating biomarkers measure (Biological)
Non degenerative amnsesic syndrome
干预措施: ApoE4 (Genetic)
Non degenerative amnsesic syndrome
干预措施: Brain imaging examination MRI and PET examinations (Other)
结局指标
主要结局
Rates of change on each specified biochemical biomarker
时间窗: 3 years
Rate of volume change of whole brain, hippocampus and other structural MRI measures
时间窗: 3 years
Rates of change of glucose metabolism (FDG-PET)
时间窗: 3 years
Extent of amyloid deposition as measured by 18F-AV45
时间窗: 3 years
Rate of Decline as measured by: Cognitive Tests, Activities of Daily Living, and CDR Sum of Boxes
时间窗: 3 years
Group differences for each imaging and biomarker measurement
时间窗: 3 years
APOE genotype
时间窗: 3 years
次要结局
未报告次要终点