Mechanism behind clinical symptoms in cerebral small vessel disease: a neuroimaging perspective

Cerebral small vessel disease (SVD) affects the brain’s small  vessels and is a major cause of vascular cognitive impairment and dementia. Conventional MRI markers such as white matter hyper-intensities (WMH), lacunes, and micro-bleeds capture only part of the underlying pathology, failing to explain the marked heterogeneity in clinical symptoms among patients. This thesis applies advanced multi-modal neuroimaging, particularly  diffusion imaging, to uncover mechanisms linking SVD damage to clinical manifestations. Three major mechanisms are explored: (1) strategic effects, focusing on damage to the thalamus and dopaminergic and cholinergic white-matter pathways; (2) remote effects, reflecting secondary neurodegeneration related to focal lesions like WMH and cortical microinfarcts (CMIs); and (3) waste-clearance dysfunction, involving perivascular pathways, choroid plexus, and deep medullary veins. By integrating these imaging markers with cognitive and clinical data, this work elucidates multi-level pathways through which SVD disrupts brain structure, providing insights for future diagnostic and therapeutic strategies.