Blood-brain barrier and cerebral small vessel disease.

Increasing evidence from neuro and retinal imaging, neuropathology, epidemiology and experimental models suggests that the primary underlying initiating cause of cerebral small vessel disease is the derangement of the blood-brain barrier. This may start some years before the first symptoms, leads to the small vessel structural changes (vessel wall thickening, disorganisation and eventual breakdown) and perivascular changes (oedema, enlarged perivascular spaces, tissue damage interpreted as "infarcts") and is fundamentally different to traditional "ischaemic" mechanisms, although small vessel occlusion due to thrombus formation on damaged vessel walls may be a late secondary phenomenon. Space limits a detailed discussion of the epidemiology and experimental evidence, so this brief review will focus on neuroimaging evidence and summarise the appearances, risk factors and associations of different components of cerebral small vessel disease as identified on imaging, discuss potential causes and, in particular, the evidence that disordered blood-brain barrier precipitates or worsens progression of cerebral small vessel disease. This mechanism may also play a role in other common disorders of ageing such as Alzheimer's disease.