Hypertension, Neurodegeneration, and Cognitive Decline

Elevated blood pressure is a well-established risk factor for age-related cognitive decline. Long linked to cognitive impairment on vascular bases, increasing evidence suggests a potential association of hypertension with the neurodegenerative pathology underlying Alzheimer disease. Hypertension is well known to disrupt the structural and functional integrity of the cerebral vasculature. However, the mechanisms by which these alterations lead to brain damage, enhance Alzheimer pathology, and promote cognitive impairment remain to be established. Furthermore, critical questions concerning whether lowering blood pressure by antihypertensive medications prevents cognitive impairment have not been answered. Recent developments in neurovascular biology, brain imaging, and epidemiology, as well as new clinical trials, have provided insights into these critical issues. In particular, clinical and basic findings on the link between neurovascular dysfunction and the pathobiology of neurodegeneration have shed new light on the overlap between vascular and Alzheimer pathology. In this review, we will examine the progress made in the relationship between hypertension and cognitive impairment and, after a critical evaluation of the evidence, attempt to identify remaining knowledge gaps and future research directions that may advance our understanding of one of the leading health challenges of our time.