Multi-modal Neuroimaging in Alzheimer's Disease (IMAP)

• Rate of volume change of whole brain, hippocampus and other structural MRI measures [ Time Frame: 3 years ] [ Designated as safety issue: No ]
• Rate of Decline as measured by: Cognitive Tests, Activities of Daily Living, and CDR Sum of Boxes [ Time Frame: 3 years ] [ Designated as safety issue: No ]
• Rates of change on each specified biochemical biomarker [ Time Frame: 3 years ] [ Designated as safety issue: No ]
• Rates of change of glucose metabolism (FDG-PET) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
• Extent of amyloid deposition as measured by 18F-AV45 [ Time Frame: 3 years ] [ Designated as safety issue: No ]
• Group differences for each imaging and biomarker measurement [ Time Frame: 3 years ] [ Designated as safety issue: No ]
• APOE genotype [ Time Frame: 3 years ] [ Designated as safety issue: No ]

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.

• Behavioral: assessment of memory
• Biological: circulating tPA dosage
• Genetic: ApoE4
• Other: Brain imaging examination MRI and PET examinations

• Experimental: Young controls
  Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
  Interventions:

  • Behavioral: assessment of memory
  • Biological: circulating tPA dosage
  • Genetic: ApoE4
  • Other: Brain imaging examination MRI and PET examinations
• Experimental: Middle age controls
  Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
  Interventions:

  • Behavioral: assessment of memory
  • Biological: circulating tPA dosage
  • Genetic: ApoE4
  • Other: Brain imaging examination MRI and PET examinations
• Experimental: Elderly controls
  Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
  Interventions:

  • Behavioral: assessment of memory
  • Biological: circulating tPA dosage
  • Genetic: ApoE4
  • Other: Brain imaging examination MRI and PET examinations
• Experimental: Autosomal dominant forms of early-onset Alzheimer disease
  Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
  Interventions:

  • Behavioral: assessment of memory
  • Biological: circulating tPA dosage
  • Genetic: ApoE4
  • Other: Brain imaging examination MRI and PET examinations
• Experimental: Subjectif Cognitive Impariment patients
  Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
  Interventions:

  • Behavioral: assessment of memory
  • Biological: circulating tPA dosage
  • Genetic: ApoE4
  • Other: Brain imaging examination MRI and PET examinations
• Experimental: Mild Cognitive Impairment patients
  Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
  Interventions:

  • Behavioral: assessment of memory
  • Biological: circulating tPA dosage
  • Genetic: ApoE4
  • Other: Brain imaging examination MRI and PET examinations
• Experimental: Alzheimer Disease patients
  Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
  Interventions:

  • Behavioral: assessment of memory
  • Biological: circulating tPA dosage
  • Genetic: ApoE4
  • Other: Brain imaging examination MRI and PET examinations
• Experimental: Non degenerative amnsesic syndrome
  Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
  Interventions:

  • Behavioral: assessment of memory
  • Biological: circulating tPA dosage
  • Genetic: ApoE4
  • Other: Brain imaging examination MRI and PET examinations
• Experimental: Frontotemporal lobe dementia
  Assessment of memory, circulating tPA dosage, ApoE4, brain imaging examination MRI and PET examinations.
  Interventions:

  • Behavioral: assessment of memory
  • Biological: circulating tPA dosage
  • Genetic: ApoE4
  • Other: Brain imaging examination MRI and PET examinations

• La Joie R, Fouquet M, Mézenge F, Landeau B, Villain N, Mevel K, Pélerin A, Eustache F, Desgranges B, Chételat G. Differential effect of age on hippocampal subfields assessed using a new high-resolution 3T MR sequence. Neuroimage. 2010 Nov 1;53(2):506-14. Epub 2010 Jun 16.
• Villain N, Landeau B, Groussard M, Mevel K, Fouquet M, Dayan J, Eustache F, Desgranges B, Chételat G. A simple way to improve anatomical mapping of functional brain imaging. J Neuroimaging. 2010 Oct;20(4):324-33. doi: 10.1111/j.1552-6569.2010.00470.x.
• Chételat G. [Neuroimaging Alzheimer's disease: early diagnosis, monitoring, and mechanism understanding]. Med Sci (Paris). 2011 Feb;27(2):193-8. Epub 2011 Mar 8. French.

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)