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The Role of Aortic Stiffness and Vascular Dysregulation in Brain Aging

dc.contributor.advisorJefferson, Angela L.
dc.creatorCambronero, Francis Elena 2023
dc.description.abstractThe Role of Aortic Stiffness and Vascular Dysregulation in Brain Aging Research efforts in age-related cognitive decline, Alzheimer’s disease, and related dementias are complicated by their multifactorial nature, including the early co-occurrence of vascular dysfunction among most older adults. Stiffening of central arteries (i.e., aortic stiffness) is a primary driver of early systemic vascular dysregulation in aging, but its impact on brain health is less well-studied. The following research investigates the role of aortic stiffness in cerebrovascular and cognitive dysfunction among older adults, including risk stratification analyses. Aortic stiffness was quantified using pulse wave velocity measured on 1.5T cardiac magnetic resonance imaging (MRI). Cerebral blood flow (CBF) and large cerebral artery characteristics (i.e., thickness, diameter, patency) were captured on 3T multimodal MRI; cognitive performance was captured using comprehensive neuropsychological testing. Cross-sectional findings indicate higher aortic stiffness relates to subtle CBF reductions among cognitively unimpaired older adults, particularly in the temporal lobe of APOE ε4 allele carriers. Furthermore, aortic stiffness is associated with cognitive impairment in lexical retrieval, executive function, and visuospatial memory encoding among APOE ε4 carriers with prodromal Alzheimer’s disease. Longitudinal results indicate aortic stiffness relates to declines in information processing speed among all participants and declines in frontal lobe CBF and visuoperceptual skills among APOE ε4 carriers during a nearly 5-year mean follow-up period. Investigations into the potential intermediate role of cerebral large arteries indicate that, while large cerebral artery remodeling likely does not mediate observed associations, patency differences do relate to compromised cerebral hemodynamics. Variant structures in large cerebral arteries may thus warrant further investigation as a novel risk factor for worse arterial aging. Findings provide evidence that aortic stiffness may have utility as a novel and accessible biomarker (or mechanism) of early-stage cerebrovascular dysregulation in aging, including subtle declines in frontal-associated cerebral perfusion and cognitive networks, particularly among older adults with preexisting risk factors for worse cerebrovascular aging. Aortic stiffness may represent an early, modifiable risk factor for worse brain aging, and integrating information regarding APOE ε4 genetic risk may help identify high-risk individuals most in need of intervention.
dc.subjectcardiovascular risk factors
dc.subjectaortic stiffness
dc.subjectvascular aging
dc.subjectalzheimer's disease
dc.subjectvascular dementia
dc.subjectcognitive impairment
dc.subjectvascular dysregulation
dc.subjectcerebral blood flow
dc.subjectgenetic risk factors
dc.subjectapolipoprotein E
dc.subjectmagnetic resonance imaging
dc.subjectarterial spin labeling
dc.subjectcardiac magnetic resonance imaging
dc.subjectvessel wall imaging
dc.subjectmild cognitive impairment
dc.subjectolder adults
dc.titleThe Role of Aortic Stiffness and Vascular Dysregulation in Brain Aging
dc.type.materialtext University Graduate School
dc.contributor.committeeChairHohman, Timothy J.

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