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Neuroimaging markers in clinical trials for pre-dementia stages of Alzheimer's disease

Abstract : The development of new drugs and the validation and standardization of neuroimaging and biological markers for Alzheimer’s Disease (AD) clinical treatment trials is expected to be one of the major goals of AD research in the upcoming years. The present thesis aims to adress these critical issues. The first part of the thesis is focused on the proper application of Standard Operating Procedures (SOPs) for the structural neuroimaging protocols of acquisition and the implementation of neuroimaging markers in 10 Italian Memory Clinics. The second part of the thesis deals with the application of several structural and functional neuroimaging markers in the context of clinical trials investigation in mild cognitive impairment individuals. Results revealed that the implementation of SOPs at multicentre level reduces the variance of neuroimaging markers measurement detected by different scanners. Moreover, results from the employment of neuroimaging markers in pre-dementia trials in mild cognitive impairment individuals showed a significant impact of anticholinesterase therapies in reducing the hippocampal rate of atrophy, the cortical thinning as well as in increasing the activation of brain areas related to functional Magnetic Resonance Imaging (fMRI) face and location macthing tasks. These promising results support the hypothesis that structural and functional neuroimaging markers applied in a standardized manner migh be utilized as candidate surrogate outcomes in future pre-dementia trials for AD.
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Enrica Cavedo. Neuroimaging markers in clinical trials for pre-dementia stages of Alzheimer's disease. Neurobiology. Université Pierre et Marie Curie - Paris VI; Istituto di Ricovero e Cura a Carattere Scientifico. Fondazione Casimiro Mondino, 2015. English. ⟨NNT : 2015PA066703⟩. ⟨tel-01660120⟩

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