Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Medical Biophysics

Supervisor

Robert Bartha

Abstract

Alzheimer disease is a progressively devastating neurodegenerative disease of the brain that impairs cognition and is ultimately fatal. Cholinesterase inhibitors are the current standard treatment for Alzheimer disease and they can alleviate some of the symptoms and thus improve quality of life. Cognitive measures aid in the diagnosis and monitoring of individuals with Alzheimer disease, but they do not directly measure disease pathophysiology. The purpose of this thesis is to investigate metabolic changes measured with proton magnetic resonance spectroscopy within the hippocampus and posterior cingulate, two brain regions known to be effected in Alzheimer disease, following cholinesterase inhibitor treatment. Such treatment is aimed at increasing the deficit of acetylcholine in Alzheimer disease. Secondly, to develop a 7 Tesla proton magnetic resonance spectroscopy data acquisition and metabolite quantification protocol to be used for future studies.

In one study, proton magnetic resonance spectroscopy at 4 Tesla was used to measure the effects of four months of galantamine treatment (a cholinesterase inhibitor). An increase in the excitatory neurotransmitter glutamate was detected in the right hippocampus, and was associated with increased cognitive performance. In a second study, proton magnetic resonance spectroscopy at 3 Tesla was used to measure the effects of rivastigmine (a second cholinesterase inhibitor). The ratio of the neuronal marker N-acetylaspartate to creatine was decreased in the bilateral posterior cingulate cortex, which was associated with cognition.

Finally, a quantitative proton magnetic resonance spectroscopy protocol at 7 Tesla was developed that incorporates subject-specific macromolecule removal. Absolute in vivo metabolite concentrations measured were in agreement with previous studies, and this protocol is ideal for applications in diseased conditions where macromolecule contributions may deviate from the norm.


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