Pathophysiological Divergence Between Vascular and Post-Stroke Dementia: Bridging Human and Experimental Perspectives

Area of Science:

• Neuroscience
• Neurology
• Pathology

Background:

• Vascular dementia (VaD) and post-stroke dementia (PSD) are major forms of vascular cognitive impairment (VCI).
• They arise from distinct cerebrovascular pathologies: VaD from chronic hypoperfusion and small vessel disease, PSD from acute ischemic events.
• VaD typically causes executive dysfunction and white matter damage, while PSD is linked to memory deficits due to hippocampal damage.

Purpose of the Study:

• To delineate the pathophysiological divergence between VaD and PSD.
• To integrate findings from human clinical studies and preclinical animal models.
• To propose a unified framework for VCI research and interventions.

Main Methods:

• Comparative analysis of human clinical studies and preclinical animal models.
• Review of rodent models of chronic hypoperfusion and transient ischemia (e.g., middle cerebral artery occlusion).
• Integration of research on neurovascular unit dysfunction, inflammation, and synaptic alterations.

Main Results:

• Chronic hypoperfusion models mimic VaD features like oligodendrocyte injury and myelin loss.
• Transient ischemia models replicate PSD characteristics, including excitotoxicity, BBB disruption, and glial activation.
• Neurovascular unit dysfunction, inflammation, and synaptic changes are implicated in both subtypes.

Conclusions:

• Recognizing mechanistic differences between VaD and PSD is crucial for improving diagnosis and treatment.
• There is a need for aged/comorbid animal models, human biomarker studies, and therapies targeting endothelial function, glial activity, and cognitive plasticity.
• A unified framework is proposed to guide future VCI research and interventions.