Fig. 8

Aetiology of White Matter Hyperintensities (WMH) in the human brain. Two of the major functions of cerebral arteries, arterioles and capillaries are (a) Blood Flow and the supply of nutrients to brain tissues (Red Arrow) and (b) Elimination of Interstitial Fluid (ISF) and soluble metabolites from brain tissues along basement membranes within the walls of capillaries and arteries – IPAD (Intramural Peri-Arterial Drainage) (Blue Arrow). Age changes in arteries, such as arteriosclerosis, impair both blood flow and IPAD resulting in ischaemic/hypoxic changes and a reduced drainage of fluid, particularly from the white matter, leading to WMH. A lower density of capillaries in white matter also reduces the capacity for IPAD and may be a causal factor for WMH in the ageing brain. Reduced IPAD is associated with the deposition of Amyloid-β (Aβ) in the IPAD pathways of cortical and leptomeningeal arteries as Cerebral Amyloid Angiopathy (CAA). The capacity of IPAD is further reduced by CAA and is associated with dilated, fluid-containing perivascular spaces (PVS) around arteries in the white matter and with WMH. Diagram adapted from [37]