| Summary: | Alzheimer’s disease (AD) is a progressive neurodegenerative disorder clinically characterised by memory loss and cognitive decline that severely affect activities of daily living. Neuropathologically, the disease is characterised by two major proteinopathies, extracellular amyloid-beta (Aβ) plaques and intraneuronal neurofibrillary tangle pathology. The development of neuroimaging biomarkers for AD have transformed the assessment of brain changes associated with these pathological processes for the earlier detection of AD. However, additional work is needed to validate more robust neuroimaging techniques for early diagnosis in the predementia stages of AD pathophysiology. The aim of this PhD is to investigate the utility of advanced Magnetic Resonance Imaging (MRI) techniques for the earlier detection of AD across different biomarker endophenotypes of pathogenesis. These PhD investigations consist of: 1) A comparison of an automated hippocampal subfield technique over standard hippocampal volumetry for AD classification and Mild Cognitive Impairment (MCI) to AD conversion prediction, 2) A neuroimaging-proteomic study for testing the prognostic ability of novel cerebrospinal fluid (CSF) proteins in combination with structural MRI measurements for AD classification and MCI to AD conversion prediction, 3) An extensive multi-cohort study testing the neuroanatomic relationship between Apolipoprotein E (APOE), hippocampal volume, and Aβ deposition across the AD spectrum, 4) A study of the neurodevelopmental effect of APOE polymorphisms on brain structure in adolescence and 5) A neuroimaging study testing the utility of resting-state functional MRI (rsfMRI) for characterising the functional systems-level pathology of intrinsic networks anchored in the highly metabolically active posteromedial cortex. In conclusion, in this thesis I provide evidence to show the diagnostic efficacy of structural MRI techniques across different biomarker interactions for disease classification and prediction in AD, and explain the neuroanatomic role of APOE on the hippocampus across the AD spectrum, as well as demonstrating the utility of rsfMRI methods as an emerging biomarker of AD.
|
|---|
