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Increased A and neurofibrillary tangle deposition in the brain subsequently promote further cerebrovascular dysfunction via increased ROS production and inflammation ( Systemic vascular structure and function Though it remains unclear whether reductions in CBF or cerebral metabolism occurs first in the ADRD cascade, mechanical factors such as systemic and cerebral arterial stiffening are additional early stage vascular markers implicated in cerebral hypoperfusion in older adulthood beyond the typical effects of aging (Mitchell, 2011