Neurovascular ageing and age-related diseases

Abstract

Proper functioning of the brain is dependent on integrity of the cerebral vasculature. During ageing, a number of factors including aortic or arterial stiffness, autonomic dysregulation, neurovascular uncoupling and blood-brain barrier (BBB) damage will define the dynamics of brain blood flow and local perfusion. The nature and extent of ageing-related cerebrovascular changes, the degree of involvement of the heart and extracranial vessels and the consequent location of tissue pathology may vary considerably. Atheromatous disease retarding flow is a common vascular insult, which increases exponentially with increasing age. Arteriolosclerosis characterized as a prominent feature of small vessel disease is one of the first changes to occur during the natural history of cerebrovascular pathology. At the capillary level, the cerebral endothelium, which forms the BBB undergoes changes including reduced cytoplasm, fewer mitochondria, loss of tight junctions and thickened basement membranes with collagenosis. Astrocyte end-feet protecting the BBB retract as part of the clasmatodendrotic response whereas pericyte coverage is altered. The consequences of these microvascular changes are lacunar infarcts, cortical and subcortical microinfarcts, microbleeds and diffuse white matter disease, which involves myelin loss and axonal abnormalities. The deeper structures are particularly vulnerable because of the relatively reduced density of the microvascular network formed by perforating and penetrating end arteries. Ultimately, the integrity of both the neurovascular and gliovascular units is compromised such that there is an overall synergistic effect reflecting on ageing associated cerebral perfusion and permeability. More than one protagonist appears to be involved in ageing-related cognitive dysfunction characteristically associated with the neurocognitive disorders.