Memory impairment in predemential Alzheimer's disease has usually been related to medial temporal lobe dysfunction. However, atrophy of this region also induces remote cortical reorganization, resulting in both deleterious and compensatory effects with respect to memory performance. The interplay between deleterious and compensatory mechanisms remains improperly understood, partly because these effects have been shown using different neuroimaging methods (basal state (SPECT, PET), resting state (fMRI) or activation studies (PET, fMRI)). The general objective of this research project is to gain a better understanding of the mechanisms underlying cortical reorganization in relation to memory impairment in predemential AD. We identified a series of issues (section 1.2) to propose a research project based on five different studies (section 1.3). We expect our findings will provide new insights in the memory impairment of predemential AD, its functional reorganisation and ultimately, in how to monitor and modulate these reorganization mechanisms (section 1.4). The five studies described in the following project follow a broad logical order, although each is independent and is used to tackle specific scientific questions. Basically, Study 1 aims at showing positive and negative reorganisation mechanisms using PET at basal state, Study 2 aims at assessing the effect of the reorganisation of these mechanisms on memory and Study 3 will complement these findings using cerebral structural connectivity. Study 4 will be focused on bridging methodological issues between basal state PET and resting state fMRI, building mainly on study 1. We will be using CMRGlu in FDG-PET at rest for this study. Study 5 is somehow the result of all previous studies as we will incorporate in this one the methodological issues that will have been addressed in previous studies, notably Study 1 and 4. We will investigate in this study the issue of the baseline condition during plasticity imaging and during activation tasks. This project is lead by a young neurologist, Dr. Jérémie Pariente ('MCU-PH' Toulouse University Hospital and Inserm U 825). The present project involves three other young scientists, Dr. Emmanuel Barbeau (CR2, psychologist), CNRS UMR 5549, Dr. Florence Remy (MCU, physicist), CNRS UMR 5549 and Xavier Franceries (MCU, physicist), Inserm UMR 825 all in Toulouse, France. They come from two different labs that support their project, want to build a new expert group on AD and have significant and complementary expertise on the different fields required to complete this project. The synergy between the different participants to this project is good and balanced between clinical and methodological expertise. It relies on true (and demonstrated through publications) expertise on the different fields required to complete the project satisfactorily: neurology, neuropsychology, memory assessment, neuroimaging techniques, plasticity, methodological developments, research project management.