Influence of Age on Amyloid Load in Alzheimer's Disease and in Atypical Focal Cortical Alzheimer's Disease

Study Overview
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Brief Summary
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The first objective is to asses influence of age on amyloid load measured by PET imaging using Pittsburgh B compound (PiB) radio-tracer, in Alzheimer's disease(AD). This will allow the determination of brains age-specific deterioration factors by comparing Early onset AD (EOAD), Late onset AD (LOAD)and atypical focal cortical AD (PCA and LPA). The amount of brain lesions in AD patients is estimated by: measuring the rate of cortical brain atrophy, FDG imaging of glucose metabolism reflecting neuronal activity, and for patients who benefited from a lumbar puncture; Cortical-spinal fluid (CSF) amounts of amyloïd and tau proteins are measured.

Detailed Description
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Literature data suggests there are different types of AD depending on their age of onset, called EOAD and LOAD. These two categories are distinguished by the localization of brain atrophy : severe and 'posterior' in EOAD and more 'anterior' in LOAD. Neuro-pathologic data suggests some atypical focal cortical atrophy, characterized by a respect of episodic memory, may be classified within EOAD. PiB-based PET imaging allows the in-vivo visualization and quantification of amyloïd load. We want to answer the question whether the amount of amyloïd protein may be lower in LOAD than EOAD in patients showing the same level of dementia, and thus identify ageing-specific cognitive disorders and understand witch factors influence etio-pathology of typical and atypical Alzheimer's disease.

Official Title
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Influence of Age on amyloïd Load in Alzheimer's Disease and in Atypical Focal Cortical Alzheimer's Disease Like Posterior Cortical Atrophy (PCA) and Logopenic Progressive Aphasia (LPA)Using Positron Emitting Tomography (PET) Imaging

Conditions
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Alzheimer's Disease, Posterior Cortical Atrophy, Logopenic Progressive Aphasia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: AD patients: clinical dementia rating between 0.5 and 2 free and cued recall test (Grober and Buschke) cued-recall < 18/48 and total recall < 40/48 atypical AD : i visual-spatial disorder and respect of episodic memory progressive evolution, Balint syndrome ii progressive language disorder constituted of logopenic aphasia respect of episodic memory controls: age over 30 MMSE over or equal to 27 normal neuropsychiatric state for age and education level Exclusion Criteria: for every patients : psychiatric disorders age under18 absence of social security counter indication to MRI supposed or actual alcoholism or drug addiction pregnancy

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| EOAD typical AD<br>this cohort is constituted with early onset typical AD. | |
| LOAD typical<br>this group is constituted with late onset typical AD | |
| atypical AD<br>this group is constituted with atypical form of focal cortical atrophy, like posterior cortical atrophy and logopenic progressive aphasia. | |
| young controls<br>under 65 | |
| old controls<br>over 65 | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PIB-PET imaging of amyloid load | PET imaging using PIB radio-tracer will give an estimation of regional amyloid load for every patient | 0 - 2 months | 
| FDG-PET imaging of glucose metabolism | PET imaging using 18F-fluorodesoxyglucose (FDG) will give a visualization of regional neuronal metabolism | 0 - 2 months | 
| clinical phenotypic assessment | the clinical evaluation includes a neurologic consulting, a neuropsychologic assessment of cognitive performances, and evaluation of autonomy | 0 - 2 months | 
| MRI | the magnetic resonance imaging will be performed using numerous modalities like T1 weighted sequences for anatomic information, T2 weighted FLAIR and TSE sequences to avoid vascular injuries and T2 GRE to avoid microbleeds, DTI for the diffusion tensor imaging and default mode FMRI, to identify neural networks involved in default concious mode. | 0 - 2 months | 
| ApoE gene sequencing | ApoE gene sequencing, will be performed after all samples have been collected. So this may be 0 to 24 month after inclusion. | 0 - 24 months after inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| amyloid and Tau measurements in cerebro-spinal fluid (csf) | some patients have a lumbar puncture that allows a direct quantification of CSF amyloid, tau and phospho-tau amounts.This measure is performed in the 6 months following the clinical assessment (at inclusion) and when a former puncture has already been done, it can be used retro-actively up to 6 months before clinical assessment. | -6 months or +6months arround T0 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PIB imaging,, brain atrophy, cognitive impairment, Pet imaging, Alzheimer's disease, amyloid protein