ABSTRACT Loss of cognitive function is one of the most feared and devastating manifestations of aging and vascular disease. Although decades of research have identified multiple risk factors for cognitive decline and dementia, it remains unclear when in the lifespan, and for whom, prevention and intervention programs should be implemented. It has been suggested that impaired cognition could be a clinically silent disorder starting in midlife or even earlier, and may have a root extending back into early life. This is particularly relevant to hypertension, not only because hypertension has been recognized as an important modifiable risk factor for dementia and cognitive impairment, but also the prevalence of elevated blood pressure (BP) among pediatrics has been increasing worldwide. However, currently there is not enough evidence linking early life BP to midlife brain function to warrant examining treatment effects in hypertensive children on cognition or markers of brain health. The goal of this project is to disentangle the long-term impact of elevated BP in early life on brain structure and cognitive function in midlife. This will be achieved by utilizing the Georgia Stress and Heart study of over 600 children (49% black and 50% females) who were measured up to 16 times in 23 years. We have collected comprehensive data from childhood to adulthood, including 24-hour ambulatory BP (ABP), chronic stress and behaviors, as well as measures of atherosclerosis and arterial stiffness. In this project, we will conduct an additional follow-up of these subjects using magnetic resonance imaging (MRI) (including arterial spin labeling (ASL) perfusion and brain diffusion tensor imaging (DTI)), and neurocognitive testing. The specific aims are: Aim1: To examine (a) whether elevated BP levels and/or greater BP increases over time in early life are associated with altered cerebral perfusion and brain structure, and impaired cognitive function in midlife, and (b) at what age this impact starts to occur (e.g. childhood or young adulthood). Aim2: To examine whether progression of arterial stiffness and atherosclerosis (assessed by pulse wave velocity and carotid intima-media thickness measured in multiple visits) in early life (a) contributes to brain functional and structural deviation, and cognitive impairment in midlife, and (b) at least partially mediates the impact of elevated BP in early life on impaired brain and cognitive health. Aim3: To examine whether chronic stress and/or related unfavorable behaviors interact with elevated BP, and accentuate the adverse impacts on vascular, brain and cognitive health. The secondary aim is to explore whether these relationships are moderated by ethnicity and gender.
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