Animal models of vascular dementia: Translational potential at the present time and in 2050

Vascular dementia is a heterogeneous syndrome, and includes subcortical ischemic vascular dementia. For translational research, subcortical ischemic vascular dementia is an appropriate target since this is the most prevalent subtype and exhibits relatively uniform clinical and neuropathological changes. These changes consist of hypertensive arteriolar changes, lacunar infarctions, hypertensive hemorrhage and white matter lesions. Among various species, rodents are most frequently used, but their small volume of white matter may impede analysis of white matter lesions. Primate models have a larger volume, but the degree of white matter lesions is inconsistent. Animal models should accommodate the effect of aging and comorbidities, and in the case of primate models, low accessibility should be overcome by repeated and quantitative examinations using modern neuroimaging techniques and functional measures, especially for memory and motor function. There is no model that replicates all features of subcortical ischemic vascular dementia and, therefore, rodent and primate models should be selected appropriately for translational research.