Patients with Alzheimer's disease and with early onset of symptoms (\<65 years) (AD-Y) have a multi-domain cognitive deficit, whereas memory disorders (typical of the elderly patient's AD) are less often in the foreground. In addition, some MA-J have an atypical phenotype indicating focal brain damage, although they have the same pathological lesions: amyloid deposits and tau protein deposition (DNF). This is the case of posterior cortical atrophy (PCA) characterized by complex visual disturbances and atrophy affecting the more posterior regions of the brain. Based on the clinical profile of PCA patients, a more refined anatomo-clinical classification was proposed, distinguishing a rather "ventral" form and a rather "dorsal" form. The recent arrival of tau-specific PET tracers now makes it possible to evaluate in vivo fibrillary neurodegeneration (FND), which is well correlated with the severity of cognitive disorders. Advances in MRI have shown that each neurodegenerative syndrome targets a large-scale neural network, which in turn shows a vulnerability for a specific biological disease. In the case of AD, the reason for such a difference in cognitive and anatomical impairment between patients with diffuse involvement and others with more focal involvement is not known. One possible explanation is the existence, in focal forms, of neuronal mechanisms that oppose vulnerability. These mechanisms may correspond to the so-called "resilience" phenomenon, defined as resistance to a neuropathological process by the ability to optimize cognitive performance via the efficient recruitment of neural networks. The mechanisms underlying resilience in neurodegeneration are unknown. Their identification is very important for the management and treatment of AD.
Affiliation to a social security insurance or beneficiary
Informed consent form signed by the participant or his / her legal representative
Participants aged 40 to 80 years.
Selection of AD-Y group
None
Parallel
TEP/IRM
DeviceAll participants will have a PET / MRI examination including: i) a 30-minute PET scan, 80 minutes after intravenous injection of 240 MBq of 18F-AV1451 ± 10% ii) a ZTE sequence (for attenuation correction of PET images), a 3D T1 anatomical sequence, a diffusion MRI, a functional MRI at rest (total duration: 45 minutes). These acquisitions will be made during the same exam session on a hybrid PET / MRI camera allowing simultaneous acquisitions. This visit lasts about 3 hours.
highlight of the "resilient" neural networks
For this, we will study: 1\) The topographic distribution regions of tau lesions, thanks to PET brain imaging using the 18F-AV-1451 as a ligand.
quantify the impairment (ie brain vulnerability) in AD-Y and in PCA
For this, we will study: 2\) The correlation between the distribution of these tau lesions and: the cortical volume, the indices of integrity of the white matter bundles, the functional neural networks, as well as the reorganization of the "hubs" of these networks, thanks to the structural MRI, diffusion (MRI) and functional at rest (fMRI) imaging.2)
correlation between the concentration of tau-tauphosphorylated protein in cerebrospinal fluid (CSF) with the lesion load measured in PET
this comparison is a key element of characterization of this new ligand compared to widely validated CSF biomarkers
predictive model of functional alterations based on the structural alterations of the gray matter and the white matter.
To establish this correlation the evaluation criterion is represented by the measurement of cortical thickness, the indices of integrity of the beams of the white substance (fractional anisotropy, average, radial and perpendicular diffusivities), as well as the integration values of the functional networks and the distribution of "hubs"
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Institut National de la Santé Et de la Recherche Médicale, France
Lead sponsor
France Alzheimer
Collaborator
