To systematically review the literature on the use of both neuroimaging and neuropathologic indices of cerebrovascular disease (CVD) burden, as estimation of this burden could have multiple benefits in the diagnosis and prognosis of cognitive impairment and dementia. MEDLINE and EMBASE databases were searched (inception to June 2017) to obtain and then systematically review all pertinent neuroimaging and neuropathology studies, where an index of CVD was developed or tested. Twenty-five neuroimaging articles were obtained, which included 4 unique indices. These utilized a limited range of CVD markers from mainly structural MRI, most commonly white matter hyperintensities (WMH), cerebral microbleeds, and dilated perivascular spaces. Weighting of the constituent markers was often coarse. There were 7 unique neuropathology indices, which were heterogeneous in their regions sampled and lesions examined. There is increasing interest in indices of total CVD burden that incorporate multiple lesions, as traditional individual markers of CVD such as WMH only provide limited information. Neuropathologic indices are needed to validate neuroimaging findings. The studies clearly demonstrated proof of concept that information from multiple imaging measures of CVD provide more information, including a stronger association with cognitive impairment and dementia, than that provided by a single measure. There has been limited exploration of the psychometric properties of published indices and no comparison between indices. Further development of indices is recommended, including the use of data from diffusion tensor and perfusion imaging.