Neuroimagerie de la maladie d'Alzheimer : synthese et apport a la comprehension des mecanismes physiopathologiques

摘要

Neuroimaging in Alzheimer's disease: a synthesis and a contribution to the understanding of physiopathological mechanisms.Alzheimer's disease has become a major public health issue for occidental societies. Since animal models of Alzheimer's disease currently fail to perfectly mimic pathophysiological mechanisms or the manifestations of the disease, in vivo neuroimaging has a key role in better understanding the pathophysiology of Alzheimer's disease. The diversity of anatomical and functional neuroimaging techniques-anatomical (Tl-MRI), functional (fMRI) and diffusion tensor imaging (DTI) via magnetic resonance imaging (MRI) as well as positon emission tomography coupled to fluorodeoxyglucose (~18FDG-PET)-offers a large possibility of investigation of brain alterations in Alzheimer's disease. These techniques have thus provided morphological and functional brain alterations mapping of Alzheimer's disease: on one hand grey matter atrophy first concerns the medial temporal lobe before extending to the temporal neocortex and then other neocortical areas; on the other hand, metabolic alterations are first located within the posterior cingulate cortex and then reach the temporo-parietal area as well as the pre-frontal cortex, especially in its medial part. Assessments of white matter alterations with DTI have highlighted a variety of tract alterations including the cingulum bundle, a white matter tract connecting the medial temporal lobe to the posterior cin-gulate cortex. Finally fMRI activation studies have evidenced compensatory mechanisms through hyperactivations in Alzheimer's disease patients. Altogether these results have led to the hypothesis of two major pathophysiological mechanisms in Alzheimer's disease: on one hand compensatory mechanisms in regions where atrophy exceeds metabolic alterations, on the other disconnection between medial temporal lobe and posterior cingulate cortex through the cingulum bundle, accounting for higher metabolic than structural alterations in the posterior cingulate cortex. Our work has extensively contributed to this disconnection hypothesis thanks to the use of cross-sectional and longitudinal multi-modal neuroimaging approaches. It has underlined the relevance of distant over local mechanisms in the pathophysiology of Alzheimer's disease and offers new perspectives to the exploration of the neural bases of cognitive impairments in this disorder.