Extracerebral vascular contributions to brain aging and cognitive decline

The development of cognitive impairment including dementia is one of the major contemporary healthcare crises of the current century. While the mechanism by which cognitive impairment manifests remains incompletely understood, age-related dysfunction of the large central arteries, including the aorta and common carotid arteries, that connect the heart with the brain are a novel risk factor for the onset of cognitive dysfunction including dementia. The major focus of this dissertation is to investigate the degree to which central artery stiffness contributes to the development of cognitive impairment and brain aging. In this regard, this dissertation will study potential mechanisms linking central artery stiffness with adverse alterations in brain function (Chapter 2) that may be buffered by educational attainment (Chapter 3). Educational attainment is an early life risk factor that is cognitively protective by delaying the onset of cognitive impairment. However, the degree to which education may attenuate the detrimental effects of central artery aging is unknown. Finally, one mechanism by which aging may contribute to stiffening of the central elastic arteries is through reduced availability of nitric oxide (NO), a molecule important for blood vessel function and cerebral blood flow (CBF) regulation. Therefore, this dissertation will also investigate the acute effects of increasing NO using dietary supplementation of inorganic nitrate contained in beetroot juice to study the effects of dietary supplementation with inorganic nitrate on large central artery stiffness and CBF as a potential future therapy for intervening on cognitive decline (Chapter 4).