Abstract

The UK Dementia Research Institute (UK DRI) is an initiative funded by the Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. Funding details for UK DRI programmes will be added in 2019. Clinical impact: Small vessel diseases (SVD) affect perforating cerebral vessels less than 500 microns in diameter resulting in diverse brain disorders. They cause most vascular dementia and worsen Alzheimer’s disease (AD), in total causing up to 45% of dementias. SVD also causes 25% of ischaemic and 90% of haemorrhagic strokes,1 worsens stroke outcome,2 and increases future risk of dementia, stroke and death.3 Patients present to different services, resulting in lack of awareness of SVD’s wide impact on the brain, mechanistic understanding or effective interventions.4 SVD and neurodegeneration: Visible SVD lesions, e.g. white matter hyperintensities (WMH), lacunes, microbleeds, perivascular spaces (PVS), recent small subcortical (lacunar) infarcts, atrophy,5 share clinical effects, epidemiology, pathology, and occur in AD6 as does microvessel dysfunction.6,7,8 SVD affects the brain diffusely: peri-lesion white matter is abnormal;9 global white matter integrity declines as SVD burden increases;10 SVD lesions cause focal/regional cortical,11 long tract and global brain atrophy.1 SVD is dynamic: acute lesions can disappear, remain a WMH or cavitate;1 WMH increase12 and regress, both in sporadic13 and monogenic SVDs.14 Although lesion dynamics are poorly understood, progression worsens cognition and physical function, while regression resulted in less cognitive decline, disability or recurrent stroke in our cohort9 (in review).