The relationship between cerebral hemodynamics and cognitive performance has increasingly become recognized as a major challenge in clinical practice for older adults. Both diabetes and hypertension worsen brain perfusion and are major risk factors for cerebrovascular disease, stroke and dementia. Cerebrovascular reserve has emerged as a potential biomarker for monitoring pressure-perfusion-cognition relationships. Endothelial dysfunction and inflammation, microvascular disease, and mascrovascular disease affect cerebral hemodynamics and play an important role in pathohysiology and severity of multiple medical conditions, presenting as cognitive decline in the old age. Therefore, the identification of cerebrovascular vascular reactivity as a new therapeutic target is needed for prevention of cognitive decline late in life.