Alzheimer's Disease and Vascular Aging: JACC Focus Seminar

Abstract

Alzheimer's disease, the leading cause of dementia in the elderly, is a neurodegenerative condition characterized by accumulation of amyloid plaques and neurofibrillary tangles in the brain. However, age-related vascular changes accompany or even precede the development of Alzheimer's pathology, raising the possibility that they may have a pathogenic role. This review provides an appraisal of the alterations in cerebral and systemic vasculature, the heart, and hemostasis that occur in Alzheimer's disease and their relationships to cognitive impairment. Although the molecular pathogenesis of these alterations remains to be defined, amyloid-β is a likely contributor in the brain as in the heart. Collectively, the evidence suggests that vascular pathology is a likely pathogenic contributor to age-related dementia, including Alzheimer's disease, inextricably linked to disease onset and progression. Consequently, the contribution of vascular factors should be considered in preventive, diagnostic, and therapeutic approaches to address one of the major health challenges of our time.

Keywords: atherosclerosis; blood-brain barrier; cerebral blood flow; dementia; hypertension; vascular dysfunction.

CENTRAL ILLUSTRATION. Alzheimer’s Disease-Associated Vascular Alterations Inside and Outside the Brain

Age-related vascular changes across the cerebral vasculature and outside the brain are exacerbated in Alzheimer’s disease. Intracranial and extracranial atherosclerosis, reduced cerebral microvascular density, cerebral amyloid angiopathy, and neurovascular unit dysfunction, together with large artery stiffening and hypertensive vascular remodeling, changes in heart function, and a procoagulant state, contribute to important reductions in cerebrovascular blood flow. Amyloid-β may play a contributory role in these vascular changes.