Cerebral small vessel disease: mechanistic insights, ethnic differences and prognostic value

Small vessel disease (SVD) accounts for approximately 25% of all strokes and 45% of all dementias. Although the small vessels cannot be visualised with conventional neuroimaging, the pathological changes in the cerebral white and deep grey matter secondary to SVD has been adopted as markers of SVD. These are best appreciated with magnetic resonance imaging (MRI) and includes recent small subcortical infarcts, white matter hyperintensity (WMH), lacunes, cerebral microbleeds and enlarged perivascular spaces (PVSs). There are however a number of outstanding questions regarding these surrogate neuroimaging markers of SVD and how these markers may influence clinical management. First, although a high burden of microbleeds have been associated with an increased risk of intracerebral haemorrhage (ICH) and possibly recurrent ischaemic stroke in patients with TIA or ischaemic stroke, how microbleeds should influence antithrombotic treatment use after TIA or ischaemic stroke remains uncertain. Second, the long-term prognostic implications of enlarged PVSs in patients with TIA or ischaemic stroke have not been studied. Third, although previous studies have shown possible ethnic differences in prevalence of microbleeds, whether there are any ethnic differences in prevalence of other neuroimaging markers of SVD remains unclear. Fourth, although a Total SVD Score was recently proposed to measure the global SVD burden, the prognostic value of this score in patients with TIA or ischaemic stroke has yet to be studied. Fifth, the relationships of long-term premorbid blood pressure with global SVD burden is unknown. Finally, the age and sex specific associations between renal impairment, carotid and cerebral pulsatility with burden of SVD has yet to be studied. The aim of my thesis was therefore to determine the clinical correlates, ethnic differences and long-term prognostic implications of a range of neuroimaging markers and global burden of SVD. I also aimed to determine the relationships of global SVD burden with long-term ...