Multi-modal Neuroimaging in Alzheimer's Disease

Not Applicable

• Conditions: Alzheimer's Disease
• Interventions: Behavioral: assessment of memory; Biological: circulating tPA dosage; Genetic: ApoE4; Other: Brain imaging examination MRI and PET examinations

• Registration Number: NCT01554202
• Lead Sponsor: University Hospital, Caen

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-01
• Study First Submitted: 2012-03-13
• Study First Submitted QC: 2012-03-13
• Study First Posted: 2012-03-14
• Status Verified: 2013-03
• Last Update Submitted: 2013-03-05
• Last Update Posted: 2013-03-06
• Primary Completion: 2021-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 295

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Middle age controls	circulating tPA dosage	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Middle age controls	ApoE4	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Middle age controls	Brain imaging examination MRI and PET examinations	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Young controls	ApoE4	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Young controls	Brain imaging examination MRI and PET examinations	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Middle age controls	assessment of memory	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Young controls	assessment of memory	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Young controls	circulating tPA dosage	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Autosomal dominant forms of early-onset Alzheimer disease	circulating tPA dosage	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Autosomal dominant forms of early-onset Alzheimer disease	ApoE4	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Elderly controls	assessment of memory	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Elderly controls	circulating tPA dosage	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Elderly controls	ApoE4	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Autosomal dominant forms of early-onset Alzheimer disease	Brain imaging examination MRI and PET examinations	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Subjectif Cognitive Impariment patients	assessment of memory	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Elderly controls	Brain imaging examination MRI and PET examinations	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Autosomal dominant forms of early-onset Alzheimer disease	assessment of memory	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Subjectif Cognitive Impariment patients	circulating tPA dosage	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Subjectif Cognitive Impariment patients	ApoE4	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Subjectif Cognitive Impariment patients	Brain imaging examination MRI and PET examinations	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Mild Cognitive Impairment patients	assessment of memory	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Mild Cognitive Impairment patients	circulating tPA dosage	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Mild Cognitive Impairment patients	ApoE4	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Mild Cognitive Impairment patients	Brain imaging examination MRI and PET examinations	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Alzheimer Disease patients	assessment of memory	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Alzheimer Disease patients	circulating tPA dosage	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Alzheimer Disease patients	ApoE4	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Alzheimer Disease patients	Brain imaging examination MRI and PET examinations	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Non degenerative amnsesic syndrome	assessment of memory	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Non degenerative amnsesic syndrome	circulating tPA dosage	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Non degenerative amnsesic syndrome	ApoE4	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Frontotemporal lobe dementia	circulating tPA dosage	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Frontotemporal lobe dementia	ApoE4	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Frontotemporal lobe dementia	Brain imaging examination MRI and PET examinations	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Non degenerative amnsesic syndrome	Brain imaging examination MRI and PET examinations	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
Frontotemporal lobe dementia	assessment of memory	Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (5)

University Hospital Tours; 🇫🇷 Tours, France

University Hospital Côte de Nacre; 🇫🇷 Caen, France

University Hospital Pontchaillou; 🇫🇷 Rennes, France

University Hospital Roger Salengro; 🇫🇷 Lille, France

University Hospital Rouen; 🇫🇷 Rouen, France