Radiology - Theses
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ItemLongitudinal volumetric analysis of white matter hyperintensities on magnetic resonance imaging in aging and Alzheimer’s dementia( 2014)The experience of neurocognitive aging can be highly variable between individuals, with some passing into their twilight years with intact and healthy cognition while others find their mental faculties perceptibly dimmed or even impaired to the point of debilitation, with dementias such as Alzheimer’s dementia (AD) seated at this extremity of the spectrum. The burgeoning proportion of the population that is aged makes the identification of biological factors that influence cognitive trajectory with advancing age a high priority. White matter changes, evident as T2 signal hyperintensities on magnetic resonance imaging (MRI) and reflective of small vessel damage and disease, occur with increasing frequency with age and are common in the elderly, including those with dementia. Shown to be associated with cognitive impairment and AD, their relationship to vascular risk factors (VRF), association to other structural brain changes and influence on cognition remains to be clarified. A combination of manual and automated segmentation methods were applied to brain MRI from elderly patients being followed longitudinally in the Australian Imaging, Biomarkers and Lifestyles (AIBL) flagship study, yielding quantitative values for WMH, cerebral cortex and cortical structures selectively susceptible in AD. Age is a well-established risk factor for WMH, while the vascular changes underpinning white matter lesions has lead to a number of VRFs evaluated and suggested as risk factors. In this study, of the participant demographics only age was significantly associated with WMH measured both at baseline and longitudinally, while hypertension and smoking were the only VRFs found to have a significant effect in models of WMH volume. Cognitive decline and impairment is strongly related to hippocampal volume, particularly in AD patients. Amyloid is also a hallmark of AD pathology and is believed to mediate disease by its direct neurotoxic effects. In the presence of the neuropathological changes of AD the contribution of white matter lesions on cognition is not clear. This study did not find a direct relationship between WMH and cognitive decline or impairment, which were instead associated with amyloid burden and ApoE allele status. However, there was a higher burden of WMH in subjects with a significant amyloid burden and in particular in AD patients. WMH burden and rate of increase was also related to the lower cortical, hippocampal and amygdala volumes. WMH are a surrogate of microvascular damage, which can lead to impairment of vascular drainage and consequently reduced clearance of amyloid. Overall this study found that while the strength of the relationship between VRFs and WMH were not as strong in this study population, there was a significant association with cortical change and amyloid pathology, which in turn are factors in cognitive decline and impairment. This provides further evidence to support a role for cerebrovascular pathology in the pathogenesis of AD.