Abstract: Vascular contributions to cognitive impairment and dementia (VCID) remain a significant public health concern. Age-associated disruptions in cerebral blood flow and brain vascular permeability resulting from cerebral small vessel disease (CSVD) are the main drivers of VCID. There is a stark absence of pharmacological treatments specific to CSVD, in part due to challenges in diagnostic accuracy for CSVD pathology during the prodromal phase before clinical dementia. Magnetic resonance imaging (MRI) is the benchmark method for detecting cerebrovascular pathologies, which predominate in subcortical white matter regions. Advanced MRI techniques, including diffusion tensor imaging (DTI), which have higher diagnostic accuracy for prodromal CSVD are not routinely acquired in clinical scans. Highly sensitive and accurate blood-based biomarkers that inform the pathogenic cascades associated with CSVD and VCID offer a minimally invasive means of identifying individuals who are at risk for VCID.