Clinical trial NCT01554202: Multi-modal Neuroimaging in Alzheimer's Disease
Official title: Study of the Predictive Markers and the Pathophysiological Mechanisms of Alzheimer's Disease: Transverse and Longitudinal Approach in Anatomical and Functional Multimodal Imaging
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Alzheimer's Disease
Keywords: Alzheimer's disease
MCI
genetic
AV45-PET
Lead sponsor: University Hospital, Caen
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2012-03-14
Enrollment: 295
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Rate of volume change of whole brain, hippocampus and other structural MRI measures
timeFrame: 3 years
measure: Rate of Decline as measured by: Cognitive Tests, Activities of Daily Living, and CDR Sum of Boxes
timeFrame: 3 years
measure: Rates of change on each specified biochemical biomarker
timeFrame: 3 years
measure: Rates of change of glucose metabolism (FDG-PET)
timeFrame: 3 years
measure: Extent of amyloid deposition as measured by 18F-AV45
timeFrame: 3 years
measure: Group differences for each imaging and biomarker measurement
timeFrame: 3 years
measure: APOE genotype
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Caen
country: France
facility: University Hospital Côte de Nacre
city: Lille
country: France
facility: University Hospital Roger Salengro
city: Rennes
country: France
facility: University Hospital Pontchaillou
city: Rouen
country: France
facility: University Hospital Rouen
city: Tours
country: France
facility: University Hospital Tours
Study officials:
affiliation: University Hospital, Caen
name: Vincent de La Sayette, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chetelat G. [Neuroimaging Alzheimer's disease: early diagnosis, monitoring, and mechanism understanding]. Med Sci (Paris). 2011 Feb;27(2):193-8. doi: 10.1051/medsci/2011272193. Epub 2011 Mar 8. French.
citation: Mevel K, Grassiot B, Chetelat G, Defer G, Desgranges B, Eustache F. [The default mode network: cognitive role and pathological disturbances]. Rev Neurol (Paris). 2010 Nov;166(11):859-72. doi: 10.1016/j.neurol.2010.01.008. Epub 2010 Mar 11. French.
citation: La Joie R, Fouquet M, Mezenge F, Landeau B, Villain N, Mevel K, Pelerin A, Eustache F, Desgranges B, Chetelat 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. doi: 10.1016/j.neuroimage.2010.06.024. Epub 2010 Jun 16.
citation: Villain N, Landeau B, Groussard M, Mevel K, Fouquet M, Dayan J, Eustache F, Desgranges B, Chetelat 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.