Longitudinal Study of Brain Amyloid imaGing in MEMENTO

Study Overview
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Brief Summary
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A Multicenter national longitudinal cohort study including at least 800 individuals consecutively recruited from French Research Memory Centers and followed-up over 24 month and included in Memento.

Detailed Description
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Alzheimer's disease (AD) is the most common cause of dementia in the elderly, affecting approximately 7.3 million people in Europe. AD is a clinicopathologic entity for which the definitive diagnosis requires both the presence of the clinical signs of dementia and pathological evidence of amyloid plaque in the brain (obtained at autopsy). Currently, diagnosis of AD at early stage of the disease is hampered by the lack of noninvasive and validated biomarkers of the underlying pathology. On one hand, it is suggested that between 10% and 20% of patients currently diagnosed with AD, based on clinical evidence solely, lack AD pathology at autopsy, and on the other hand community physicians may not diagnose AD in 33% of patients with mild signs and symptoms. Thus, there is a need for validated diagnostic biomarker that could help clinicians separate patients who do not have AD from those who have pathological signs and should be referred for further evaluation and care management. Furthermore, little is known on the prognosis value for dementia conversion of current biomarkers of AD pathology at a preclinical or presymptomatic stage. Recently, 18F-labeled positron emission tomography (PET) imaging agents have been developed that bind with high affinity to the amyloid-β (Aβ) peptide fibrils that constitute amyloid plaques, and thus, have potential value as an imaging biomarkers for amyloid deposits in subjects with cognitive impairment or isolated cognitive complaints. The principal objective of this ancillary study is to investigate the prospective association between PET amyloid load, measured twice two years apart, through either Florbetapir (18F) or Flutemetamol (18F) radioligands, and dementia incidence over up to 5 years of follow-up in a sample of individuals presenting with a spectrum of cognitive profiles ranging from isolated cognitive complaints to cognitive deficits without dementia. The secondary objectives are the following: To assess the association between change in amyloid load and clinical evolution of participants (both functional and cognitive) To estimate the prevalence of new research criteria for preclinical Alzheimer's disease To investigate long-term outcome of preclinical Alzheimer's disease according to NIA-AA criteria To assess the determinants of change in amyloid load over two years To study the interrelationships between biomarkers To assess the added value of amyloid binding agent (Florbetapir (18F) and Flutemetamol (18F)) in combination with other biomarkers (neuropsychological, genetics, plasma, serum, CSF, structural neuroimaging, 18F-FDG-PET) to predict clinical dementia onset To assess the diagnostic accuracy of amyloid agent Florbetapir (18F) and Flutemetamol (18F) to differentiate AD from other types of dementia (differential diagnosis) To study the link between amyloid binding agent and survivalstudy design

Official Title
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Longitudinal Study of Brain Amyloid imaGing in MEMENTO

Conditions
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Alzheimer's Disease (AD) and Related Disorders

Intervention / Treatment
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* Drug: Flutemetamol (18F)
* Drug: Florbetapir (18F)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be included in MEMENTO To have signed a specific MEMENTO-AmyGing informed consent form, prior to any amyloid PET procedures To have had or agreed to have 18F-FDG PET scan in MEMENTO To tolerate the (18F) PET scan procedures, in the opinion of the clinical site investigator Clinical Dementia Rating scale <0.5 and not demented Exclusion Criteria: To have a current clinically significant psychiatric condition that neurologists/geriatricians feel would preclude the ability to have a research PET scan To be pregnant or breastfeading women To have Hypersensitivity to the tracer or to the excipient listed in the summary of the product carateristics (florbetapir Amyvid®) or the Investigator's Brochure (flutemetamol) To have a relevant history of severe drug allergy or hypersensitivity (relevant severe drug allergies should be determined by the clinical site investigator or co-clinical site investigator). If a subject has a history of severe drug allergies, it may be dangerous for them to participate in a study with a novel compound To have ever participated in an experimental study with an amyloid targeting agent (e.g. anti-amyloid immunotherapy, γ-secretase or γ-secretase inhibitor) unless it can be documented that the subject received only placebo during the course of the trial To receive any investigational medications, or have participated in a trial with investigational medications within the last 30 days To have participated less than 1 year ago in a biomedical research with injection of one of the amyloid radioligand or to be enrolled in an ongoing biomedical research including amyloid PET scan To have had a radiopharmaceutical imaging or treatment procedure within 7 days prior to the study imaging session

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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No

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: Florbetapir (18F)<br> | Drug: Florbetapir (18F)<br> <br> |
| Experimental: Flutemetamol (18F)<br> | Drug: Flutemetamol (18F)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression to clinical dementia stage according to standardized classifications (DSM-IV and NINCDS-ADRDA) as described in the MEMENTO protocol. |  | 24 months from baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Longitudinal evolution of amyloid load measured through either Florbetapir (18F) or Flutemetamol (18F) |  | 24 months from baseline | 
| Speed of cognitive decline based on change in cognitive performances |  | 24 months from baseline | 
| Longitudinal evolution of biomarkers measured from blood, CSF, structural neuroimaging (MRI) and glucose metabolism molecular neuroimaging (18F-FDG PET). |  | 24 months from baseline | 
| Mortality |  | 24 months from baseline | 
| Loss of autonomy based on functional activity assessment |  | 24 months from baseline | 
| Institutionalization |  | 24 months from baseline | 
| Cardiovascular event (Stroke and Coronary events) |  | 24 months from baseline | 
| Quality of life |  | 24 months from baseline | 
| Prodromal AD (Pre-symptomatic dementia) |  | 24 months from the baseline | 
| Etiology of dementia, when converted |  | 24 months from the baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's disease, Mild Cognitive Impairment