Study of the Predictive Markers and the Pathophysiological Mechanisms of Alzheimer's Disease: Transverse and Longitudinal Approach in Anatomical and Functional Multimodal Imaging

The three main objectives of this project are:

• To Identify, compare and combine the predictive markers of AD,
• To better understand the pathophysiologic mechanisms of AD,
• To study the ability of different neuroimaging techniques to monitor AD's evolution.

For these purposes, detailed neuropsychological evaluations, biological measures and brain structural & functional imaging measures are associated for a fully-comprehensive description of the different manifestations of AD through disease progression and toward identifying early markers.

Subjects are evaluated using neuropsychological tests of episodic memory (encoding vs. retrieval), executive functions (inhibition, flexibility, and updating processes), self-judgment, theory of mind, mental imagery and verbal fluency. A FDG-PET measure of resting state glucose consumption, an AV45-PET measure of amyloid deposition as well as anatomical, resting-state and activation fMRI scans are performed for each volonteer. In addition, blood and cerebro-spinal fluid samples will be performed to determine different biomarkers (Aβ1-40, Aβ1-42 and tPA as circulating blood proteins and Aβ40, Aβ42, tau and its phosphorylated form in CSF). The investigators also study the polymorphism of Apolipoprotein E as a genetic risk factor of AD.

One hundred and twenty healthy controls (40 young, 40 middle age and 40 elderly), 40 Mild Cognitive Impairment patients (MCI; i.e. isolated memory impairment and increased risk of developing AD) and 30 AD patients will be selected. Participants with increased risk of developing AD and without objective evidence will be also studied: 50 asymptomatic subjects from families carrying a genetic mutation with an autosomal dominant transmission (NORMA) and 40 Subjective Cognitive Impairment patients (SCI).