Hypertension, Neurovascular Dysfunction, and Cognitive Impairment

Hypertension affects a significant proportion of the adult and aging population and represents an important risk factor for vascular cognitive impairment and late-life dementia. Chronic high blood pressure continuously challenges the structural and functional integrity of the cerebral vasculature, leading to microvascular rarefaction and dysfunction, and neurovascular uncoupling that typically impairs cerebral blood supply. Hypertension disrupts blood-brain barrier integrity, promotes neuroinflammation, and may contribute to amyloid deposition and Alzheimer pathology. The mechanisms underlying these harmful effects are still a focus of investigation, but studies in animal models have provided significant molecular and cellular mechanistic insights. Remaining questions relate to whether adequate treatment of hypertension may prevent deterioration of cognitive function, the threshold for blood pressure treatment, and the most effective antihypertensive drugs. Recent advances in neurovascular biology, advanced brain imaging, and detection of subtle behavioral phenotypes have begun to provide insights into these critical issues. Importantly, a parallel analysis of these parameters in animal models and humans is feasible, making it possible to foster translational advancements. In this review, we provide a critical evaluation of the evidence available in experimental models and humans to examine the progress made and identify remaining gaps in knowledge.