Chronic cerebral hypoperfusion. An undefined, relevant entity

Despite the large body of data available, chronic cerebral hypoperfusion lacks an operative definition. In a tautological way, the term hypoperfusion is being referred to conditions of ‘‘inadequate blood flow”, ‘‘defects of perfusion” or ‘‘dysfunction of autoregulation”. The chronicity refers to sustained conditions or wavering states characterized by repeated phases of inefficient functional hyperemia. The phenomenon may affect the whole brain or defined areas. A few defined clinical disorders, including heart failure, hypotension, atherosclerosis of large or small vessels and carotid stenosis are thought to cause progressive brain disorders due to chronic hypoperfusion. The clinical relevance manifests mostly as neurocognitive disorders associated with neuroimaging changes. The available data support a conceptual framework that considers chronic cerebral hypoperfusion a likely, relevant pathogenic mechanism for the neurodegeneration-like progression of the neurocognitive disorders. The relationship between neuropathology, cerebral perfusion, and symptoms progression is, however, elusive for several aspects. Typical microangiopathy findings, such as MRI white matter hyperintensities, may appear in individuals without any cerebrovascular risk or vascular lesions. Pathology features of the MRI changes, such as demyelination and gliosis, may result from dysfunction of the neuro-vascular unit not directly associated with vascular mechanisms. In this review, we aim to overview the most common clinical conditions thought to reflect chronic