Background: Given that brain pathology precedes clinical symptoms in Alzheimer’s disease (AD), identifying pre-symptomatic biomarkers is critical in order to implement symptom-delaying strategies as early as possible. Magnetic resonance imaging (MRI) is an ideal method for detecting early brain changes in Alzheimer's disease, as it is non-invasive, easily repeatable, and widely available. To date, MRI biomarker research has largely focused on neuronal loss in grey matter, but there is a lack of research on white matter and its relationship with cognitive performance. Diffusion tensor imaging (DTI) is a MRI-based technique that is particularly sensitive to microstructural white matter characteristics, making it an ideal method to study white matter changes. Methods: Longitudinal DTI and clinical data from the Alzheimer’s Disease Neuroimaging Initiative 2 database were used to examine the 1) within-group microstructural white matter changes in individuals with AD and healthy aging controls at baseline and year one; 2) the between-group microstructural differences in individuals with AD and controls at both time points; and 3) the relationship between white matter and cognitive performance at both time points. Results: 1) Within-group: Tract-based Spatial Statistics reveal that individuals with AD have reduced fractional anisotropy (FA) and increased mean diffusivity (MD) in the corpus callosum; internal and external capsule; corona radiata; posterior thalamic radiations; superior and inferior longitudinal fasciculus; fronto-occipital fasciculus; cingulate gyri; fornix; uncinate fasciculus; tapetum; medial lemniscus; cerebellar and cerebral peduncle; and hippocampal cingulum at year one compared to baseline. Controls also had reduced FA and increased MD at year one compared to baseline, but such changes were less extensive and did not include the hippocampal cingulum. 2) Between-group: Relative to controls, individuals with AD had lower FA and higher MD in the corpus callosum, internal and external capsule; corona radiata; posterior thalamic radiation; superior and inferior longitudinal fasciculus and fronto-occipital fasciculus; cingulate gyri; fornix; uncinate fasciculus; tapetum and hippocampal cingulum. 3) There was a positive relationship between FA and an ADNI- derived memory composite score in individuals with AD. Conclusion: The results revealed that DTI holds potential as an AD biomarker given its sensitivity to detect microstructural white matter characteristics. Longitudinal tracking of brain imaging and AD clinical signs in large cohorts are necessary to further evaluate potential clinical utility. / Graduate
| Identifer | oai:union.ndltd.org:uvic.ca/oai:dspace.library.uvic.ca:1828/7393 |
| Date | 05 July 2016 |
| Creators | Mayo, Chantel Dana |
| Contributors | Gawryluk, Jodie R. |
| Source Sets | University of Victoria |
| Language | English, English |
| Detected Language | English |
| Type | Thesis |
| Rights | Available to the World Wide Web, http://creativecommons.org/licenses/by-nd/2.5/ca/ |
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