Extracranial Vascular Arterial Stiffness Contributes to Cerebral Small Vessel Disease, Stroke, and Late-Onset Alzheimer’s Disease

Cerebrocardiovascular disease(s) (CCVD) including coronary artery disease, ischemic heart disease, and stroke are the number one cause of mortality. Structural and functional properties of the vascular arterial wall play an important role in creating extracranial vascular arterial stiffness (VAS). VAS has emerged as a marker of risk for aging, dementia, vascular contributions to impaired cognition and dementia (VCID), stroke (ischemic and hemorrhagic), misfolded proteins (amyloid beta and tau) deposition, neurodegeneration, brain atrophy, and late-onset Alzheimer’s disease. VAS is associated with increased oxidative redox stress, inflammation, vascular remodeling and calcification, increased pulse pressure, increased pulse wave velocity, and systolic hypertension, which serves as part of the multiple injurious stimuli to vulnerable neurovascular unit capillaries with high flow and low resistance. Notably, advanceing age, hypertension, atherosclerosis, and vascular calcification are the most common causes of VAS. VAS contributes to cerebral small vessel disease and chronic cerebral hypoperfusion that is capable of instigating neurodegeneration, brain atrophy, and late onset Alzheimer’s disease. This narrative review discusses the evidence that links VAS and microvessel cerebral small vessel disease (SVD) to brain structural and functional abnormalities via a heart, vascular, brain (HVB) axis, which leads to SVD, neurodegeneration, brain atrophy, impaired cognition, and late-onset Alzheimer’s disease.