From artery to memory: a comparative review of vascular cognitive impairment surgical models

Vascular cognitive impairment (VCI) encompasses a spectrum of cerebrovascular diseases ranging from mild clinical cognitive impairment to advanced vascular dementia and is recognized as a major contributor to the global dementia burden. Frequently coexisting with Alzheimer’s Disease (AD), VCI represents a complex, mixed-pathology neurodegenerative process driven by chronic cerebral hypoperfusion (CCH), white matter (WM) injury and volume loss, neurovascular dysfunction, and progressive cognitive decline. While numerous animal models have been developed to characterize the underlying mechanisms and identify therapeutic targets, the field is presently limited by the absence of a distinct framework to guide model selection based on unique pathophysiological features of recently delineated VCI subtypes. Surgical VCI models, including transient and permanent occlusion, stenosis, or gradual occlusion approaches, differ substantially in the duration of ischemic injury, severity of hypoperfusion, and mechanism of cerebral blood flow (CBF) reductions, generating diverse downstream effects on cerebral tissue damage, neuroinflammation, neurometabolic dysfunction, functional integrity, and, ultimately, memory function. No single model completely captures the heterogeneity of VCI pathology; however, each selectively captures unique aspects of disease subtypes. As such, this review aims to establish a clear, pathophysiology-driven framework to guide the selection of appropriate surgical VCI models for investigating specific VCI subtypes. To do so, we evaluate common models of carotid artery manipulation, integrating histological, neuroenergetic, and cognitive outcomes with clinically relevant imaging and patient data. This review provides practical guidance for model selection, enhancing the specificity and translational relevance of preclinical VCI investigation.