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UBC Theses and Dissertations

Stroke and white matter hyperintensities : investigating lesion impacts on cognition and white matter structure Ferris, Jennifer Kathleen


After stroke many individuals experience chronic cognitive and motor impairments, and it is difficult to predict the severity of these impairments. In addition to the stroke infarct, age-related vascular damage occurs in the brain, notably from white matter hyperintensities (WMHs). WMHs relate to cognitive decline in older adults and share common cardiovascular risk factors with stroke. Yet, little work has considered the combined impact of WMHs and stroke lesions on brain structure and behaviour. This thesis employed diffusion tensor imaging (DTI); a neuroimaging technique that measures the microstructure of white matter pathways. We investigated how WMHs and stroke lesions are associated with cognitive outcomes and white matter structure in older adults and individuals with chronic stroke. First, we evaluated candidate white matter markers of processing speed and executive function using the trail making test (TMT). Among a group of white matter tracts, DTI microstructure of the anterior thalamic radiation emerged as a predictor of TMT performance in older adults and individuals with chronic stroke. Next, we tested the sensitivity of DTI to the presence of lesions in white matter tracts. We found that tract microstructure related to WMH lesion load in older adults and related to both WMH and stroke lesion load in individuals with chronic stroke. Further, we observed focal impacts of WMHs and stroke lesions on tract microstructure along the length of white matter tracts. Finally, we used DTI in combination with myelin water imaging to evaluate white matter structure in WMHs and surrounding white matter. We found that white matter adjacent to WMHs exhibits characteristics of a transitionary stage between healthy white matter and WMH lesions. This was observed in imaging metrics sensitive to interstitial fluid, but not in the specific marker of myelin concentration derived from myelin water imaging. In summary, DTI microstructure is a potential biomarker of cognitive performance, and a sensitive index of structural cerebrovascular damage to white matter tracts. However, the physiological implications of lesion-related changes to DTI metrics must be interpreted with caution. This thesis contributes foundational knowledge of the application and limitations of DTI as a structural biomarker in cerebrovascular disease.

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