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Updated: Mar 28, 2026
A Mouse Model for Vascular Cognitive Impairment and Dementia Based on Needle-guided Asymmetric Bilateral Common Carotid Artery Stenosis
Published on: November 22, 2024
Vascular cognitive impairment: Modeling a critical neurologic disease in vitro and in vivo
Alex M Helman1, M Paul Murphy1
1Department of Molecular and Cellular Biochemistry, University of Kentucky, 800 South Limestone, Lexington, KY 40536, USA; Sanders-Brown Center on Aging, University of Kentucky, 800 South Limestone, Lexington, KY 40536, USA.
Insights
Vascular contributions to cognitive impairment and dementia (VCID) is a complex condition. Better definitions and models are needed to understand and combat this growing public health issue.
Area of Science:
- Neurology
- Neuroscience
- Vascular Biology
Background:
- Vascular contributions to cognitive impairment and dementia (VCID) is a complex dementia type, involving cerebrovascular disease and other dementias like Alzheimer's disease.
- VCID spectrum ranges from mild cognitive impairment to dementia, complicated by metabolic disorders (diabetes, hypertension) and lifestyle factors (obesity, high-fat diets).
Purpose of the Study:
- To define Vascular contributions to cognitive impairment and dementia (VCID).
- To review in vitro and in vivo models for studying VCID.
Main Methods:
- Review of in vitro neurovascular unit models.
- Analysis of in vivo models including chronic cerebral hypoperfusion, NOTCH3 mutation models for small vessel disease, canine models for cerebral amyloid angiopathy (CAA), and mixed dementia models.
Main Results:
- Synthetic microvessels show promise for neurovascular unit studies.
- Canine models are valuable for studying cerebral amyloid angiopathy (CAA).
- Current models effectively represent individual VCID aspects but not the disease's heterogeneity.
Conclusions:
- VCID requires further definition into specific disease states, including guidelines for stroke characteristics and categorization of overlapping pathologies.
- Improved definitions and models are crucial for understanding VCID's contribution to dementia.
- Addressing VCID heterogeneity is vital for managing this public health challenge in an aging population.
Background:
Vascular contributions to cognitive impairment and dementia (VCID) is a complex form of dementia, combining aspects of vascular disease and other forms of dementia, such as Alzheimer's disease. VCID encompasses a wide spectrum of cerebrovascular-driven cognitive impairment, from mild cognitive impairment to fully developed dementia. This disease state is further complicated by metabolic disorders, such as type 2 diabetes and hypertension, and lifestyle factors, like obesity and high fat diets.
Scope Of Review:
This manuscript is meant to both define VCID and review the in vitro and in vivo models of the disease state. This includes in vitro models of the neurovascular unit, models of chronic cerebral hypoperfusion, animals with NOTCH3 mutations as a model of small vessel disease, large animals with cerebral amyloid angiopathy (CAA), and animal models of mixed dementia.
Major Conclusions:
Synthetic microvessels are a promising technique to study the neurovascular unit and canines, despite the cost, are an excellent model to study CAA. While there are several good models of individual aspects of VCID, the heterogeneity of the disease states prevents them from being a model of all aspects of the disease. Therefore, VCID needs to be further defined into disease states that exist within this umbrella term. This includes specific guidelines for stroke counts and stroke locations and further categorization of overlapping cerebrovascular and AD pathologies that contribute to dementia. This will allow for better models and a more thorough understanding of how vascular disease contributes to dementia.
General Significance:
VCID is the second most common form of dementia and is expected to increase in coming years. The heterogeneity of VCID makes it difficult to study, but without better definitions and models, VCID presents a major public health problem for our aging population. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.
