Multi-modal Neuroimaging in Alzheimer's Disease

Study Overview
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Brief Summary
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According to estimations, Alzheimer's disease affects approximately 860,000 people aged of more than 65 years in France. This disease is characterized by disorders of cognitive functions, including memory, associated with structural and functional modifications of the brain. These changes are evolving within the pathology progression and can be evaluated with neuropsychological tests (to assess capabilities such as language, orientation, etc.) and also with brain imaging (e.g. MRI). Alzheimer's disease is still poorly understood, nevertheless currently available treatments can slow its development if the disease is diagnosed early enough. Thus, the objective is to identify markers for early diagnosis of Alzheimer's disease, to better describe the evolution of this disease. The three main objectives of this project are to identify, compare and combine predictive markers of Alzheimer's disease to make a significant contribution to the understanding of the pathophysiological mechanisms of Alzheimer's disease to study the ability of different neuroimaging techniques to follow the evolution of this pathology.

Official Title
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Study of the Predictive Markers and the Pathophysiological Mechanisms of Alzheimer's Disease: Transverse and Longitudinal Approach in Anatomical and Functional Multimodal Imaging

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Behavioral: assessment of memory
* Biological: circulating tPA dosage
* Genetic: ApoE4
* Other: Brain imaging examination MRI and PET examinations


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 controls: between 18 and 40 years old; normal performances compared to the age and the educational level for all tests of the diagnostic battery (± 1.5 SD). Healthy Middle-aged controls: 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 (± 1.5 SD). Healthy Elderly controls: 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 (± 1.5 SD). MCI patients: over 60 years old, presenting the current criteria for amnestic MCI including: i) memory complaint, ii) deficits of the episodic memory (lower performance of at least 1.5 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). Exclusion Criteria: 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 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 (during the study or within 12 months before inclusion)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Young controls<br>Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations. | Behavioral: assessment of memory<br> <br> Biological: circulating tPA dosage<br> <br> Genetic: ApoE4<br> <br> Other: Brain imaging examination MRI and PET examinations<br> <br> |
| Experimental: Middle age controls<br>Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations. | Behavioral: assessment of memory<br> <br> Biological: circulating tPA dosage<br> <br> Genetic: ApoE4<br> <br> Other: Brain imaging examination MRI and PET examinations<br> <br> |
| Experimental: Elderly controls<br>Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations. | Behavioral: assessment of memory<br> <br> Biological: circulating tPA dosage<br> <br> Genetic: ApoE4<br> <br> Other: Brain imaging examination MRI and PET examinations<br> <br> |
| Experimental: Autosomal dominant forms of early-onset Alzheimer disease<br>Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations. | Behavioral: assessment of memory<br> <br> Biological: circulating tPA dosage<br> <br> Genetic: ApoE4<br> <br> Other: Brain imaging examination MRI and PET examinations<br> <br> |
| Experimental: Subjectif Cognitive Impariment patients<br>Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations. | Behavioral: assessment of memory<br> <br> Biological: circulating tPA dosage<br> <br> Genetic: ApoE4<br> <br> Other: Brain imaging examination MRI and PET examinations<br> <br> |
| Experimental: Mild Cognitive Impairment patients<br>Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations. | Behavioral: assessment of memory<br> <br> Biological: circulating tPA dosage<br> <br> Genetic: ApoE4<br> <br> Other: Brain imaging examination MRI and PET examinations<br> <br> |
| Experimental: Alzheimer Disease patients<br>Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations. | Behavioral: assessment of memory<br> <br> Biological: circulating tPA dosage<br> <br> Genetic: ApoE4<br> <br> Other: Brain imaging examination MRI and PET examinations<br> <br> |
| Experimental: Non degenerative amnsesic syndrome<br>Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations. | Behavioral: assessment of memory<br> <br> Biological: circulating tPA dosage<br> <br> Genetic: ApoE4<br> <br> Other: Brain imaging examination MRI and PET examinations<br> <br> |
| Experimental: Frontotemporal lobe dementia<br>Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations. | Behavioral: assessment of memory<br> <br> Biological: circulating tPA dosage<br> <br> Genetic: ApoE4<br> <br> Other: Brain imaging examination MRI and PET examinations<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of volume change of whole brain, hippocampus and other structural MRI measures |  | 3 years | 
| Rate of Decline as measured by: Cognitive Tests, Activities of Daily Living, and CDR Sum of Boxes |  | 3 years | 
| Rates of change on each specified biochemical biomarker |  | 3 years | 
| Rates of change of glucose metabolism (FDG-PET) |  | 3 years | 
| Extent of amyloid deposition as measured by 18F-AV45 |  | 3 years | 
| Group differences for each imaging and biomarker measurement |  | 3 years | 
| APOE genotype |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's disease, MCI, genetic, AV45-PET