Early Diagnosis of Alzheimer-like Dementia: Benefit of MRI and PET Imaging

Study Overview
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Brief Summary
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The physio-pathology of Alzheimer's disease (AD) remains unknown and there is no cure. Thus, the search for objective markers of preclinical first signs of cognitive impairment, is currently a major public health issue. Early detection of the disease is a major challenge to hope to slow or even stop the neurodegenerative process before the stage of dementia. In AD the investigators observe: A reduction in the volume of brain hippocampi associated with an alteration of the diffusion of water molecules in the white matter. A structural brain degeneration coupled with a decrease in cerebral glucose metabolism. Recent publications show that cerebrospinal fluid (CSF)flow is also altered, probably due to dysfunction of the choroid plexus. Hence the potential interest to study is, in addition to conventional imaging, the imaging of CSF dynamics and choroid plexus metabolism. In that aim,the investigators use two imaging modalities: Magnetic resonance imaging (MRI) is used to assess blood and CSF flow in the brain Positron emission tomography (PET) is used to assess glucose metabolism in grey/white matter and also in choroid plexus. The investigators expect that, because of choroid plexus atrophy in AD, CSF flow would be altered as well as glucose metabolism dynamic in choroid plexus.

Official Title
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Benefit of MRI and 18F-FDG PET Imaging in the Early Diagnosis of Alzheimer-like Dementia

Conditions
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Alzheimer Disease, Mild Cognitive Impairment, Vascular Dementia

Intervention / Treatment
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* Other: Magnetic resonance imaging
* Other: Positron emission tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: over 65 Participants (or representatives) gave their written informed consent Dementia diagnosed according to Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria For Alzheimer arm: probable Alzheimer based disease according to NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association ) criteria For vascular dementia: diagnosis based on NINDS-AIREN (National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherche et l'Enseignement en Neurosciences) criteria For MCI: diagnosis based on Petersen index Exclusion Criteria: Claustrophobia Diabetes Cardiovascular disease Glycemia over 1.3 g/L Lumbar puncture within one week before MRI examination Non MR-compatible implant Suspected brain metastases No informed consent signature

Ages Eligible for Study
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Minimum Age: 65 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: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alzheimer<br>Alzheimer patients detected via conventional clinical and neuropsychological tests. They will undergo Magnetic resonance imaging and positron emission tomography examinations. | Other: Magnetic resonance imaging<br>* CSF flow measurement at Sylvius' aqueduct and cervical levels. Apparent diffusion coefficient and fractional anisotropy determination in corpus callosum, cingulum and hippocampus.<br>* Other names: Diffusion weighted imaging;Other: Positron emission tomography<br>* Tissue-time activity curves in hippocampus, cingulum, medio-temporal cortex and choroid plexus.<br>* Other names: Dynamic PET imaging;|
| Experimental: Vascular dementia<br>Vascular dementia patients detected via conventional clinical and neuropsychological tests. They will undergo magnetic resonance imaging and positron emission tomography examinations. | Other: Magnetic resonance imaging<br>* CSF flow measurement at Sylvius' aqueduct and cervical levels. Apparent diffusion coefficient and fractional anisotropy determination in corpus callosum, cingulum and hippocampus.<br>* Other names: Diffusion weighted imaging;Other: Positron emission tomography<br>* Tissue-time activity curves in hippocampus, cingulum, medio-temporal cortex and choroid plexus.<br>* Other names: Dynamic PET imaging;|
| Experimental: Mild cognitive impairment (MCI)<br>Mild cognitive impairment (MCI) patients detected via conventional clinical and neuropsychological tests. They will undergo magnetic resonance imaging and positron emission tomography examinations. | Other: Magnetic resonance imaging<br>* CSF flow measurement at Sylvius' aqueduct and cervical levels. Apparent diffusion coefficient and fractional anisotropy determination in corpus callosum, cingulum and hippocampus.<br>* Other names: Diffusion weighted imaging;Other: Positron emission tomography<br>* Tissue-time activity curves in hippocampus, cingulum, medio-temporal cortex and choroid plexus.<br>* Other names: Dynamic PET imaging;|
| Experimental: Healthy subjects (MRI)<br>Healthy subjects agreeing to undergo magnetic resonance imaging examination. | Other: Magnetic resonance imaging<br>* CSF flow measurement at Sylvius' aqueduct and cervical levels. Apparent diffusion coefficient and fractional anisotropy determination in corpus callosum, cingulum and hippocampus.<br>* Other names: Diffusion weighted imaging;|
| Experimental: Healthy subjects (PET)<br>Cognitively healthy subjects. These subjects are people addressed in the nuclear medicine department for cancer-related positron emission tomography examination. If they agree, an extended neuropsychological test will assess that they do not suffer any cognitive disorder. | Other: Positron emission tomography<br>* Tissue-time activity curves in hippocampus, cingulum, medio-temporal cortex and choroid plexus.<br>* Other names: Dynamic PET imaging;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dynamic FDG (fluoro-deoxyglucose) PET | Extraction of tissue time-activity curves ; notably in choroid plexus. | Day 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aqueductal CSF flow | Measurement of CSF flow at the Sylvius' aqueduct level. Calculation of the corresponding stroke volume. | Day 1 | 
| Follow-up MRI | MRI examination of MCI patients after one year in order to assess CSF flow differences in MCI how converted to Alzheimer. | Day 365 | 
| Follow-up PET | Dynamic FDG PET examination of MCI patients after one year in order to assess FDG dynamic evolution in MCI how converted to Alzheimer. | Day 366 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neurodegenerative disease, Elderly, Dementia, FDG-PET, MRI, Neuroimaging