Identifying Associations between Vascular Risk Factors and Measures of Brain Health using Multimodal Magnetic Resonance Imaging

Recent epidemiological evidence indicates that vascular risk factors (VRFs) play a significant role in cognitive decline that can contribute to the onset of dementia among older adults. The link between VRFs and dementia is supported by common neurological findings of structural deficits, cerebrovascular dysfunction and amyloid accumulation in both conditions. Despite the growing literature on VRFs and the brain, there are still many unanswered questions about their roles in pathoetiology and best imaging methods for detecting neurological effects of VRFs. The main goal of this thesis was to characterize the effect of increasing number of VRFs on brain health. Measures of structural brain integrity and cerebrovascular health were acquired using non-invasive magnetic resonance imaging (MRI). The first study of this thesis identified regions of impaired vascular reactivity and thinning of the cortical mantle in older adults with type 2 diabetes and hypertension compared to hypertension only. The next two studies focused on the associations between VRFs and brain health in two common neurodegenerative conditions: older adults with small vessel disease and older adults with mild cognitive impairment. In adults with white matter hyperintensities, a hallmark of small vessel disease, higher VRF number was associated with lower vascular reactivity in cognitively relevant regions. In older adults with mild cognitive impairment, increasing VRF number was correlated with cortical thinning in regions implicated in Alzheimer's Disease. Together, findings of this thesis highlight an association between increasing VRF number and exacerbated brain health in otherwise healthy older adults and individuals with comorbid neurodegenerative disorders. To conclude, the implications of these findings for clinical practices are discussed with focus on proper VRF management as well as the need to properly account for VRFs in neuroimaging studies.Ph.D