Blood-brain barrier dysfunction predicts cognitive trajectory after ischemic stroke

Area of Science:

• Neuroscience
• Vascular Biology
• Biomarkers

Background:

• Ischemic stroke significantly increases dementia risk, but the underlying mechanisms for late-stage cognitive decline remain unclear.
• While early cognition is affected by stroke severity, late dementia risk is not associated with infarct characteristics or stroke prevention.
• Existing research lacks understanding of the chronic mechanisms linking stroke to dementia.

Purpose of the Study:

• To investigate the role of chronic blood-brain barrier (BBB) dysfunction in cognitive decline following ischemic stroke.
• To identify proteomic, imaging, and structural biomarkers associated with post-stroke dementia.
• To explore potential therapeutic targets for preventing or treating cognitive impairment after stroke.

Main Methods:

• Plasma proteomic analysis was performed on stroke survivors and healthy controls to identify stroke-specific signatures.
• Longitudinal cognitive assessments (processing speed/executive function) were conducted over two years.
• Dynamic contrast-enhanced MRI was used to quantify BBB leakage in a cohort of stroke patients.
• Autopsy brain tissue analysis compared vascular mural cell coverage in individuals with and without post-stroke dementia.

Main Results:

• A distinct plasma proteomic signature associated with chronic stroke and BBB dysfunction was identified, including decreased platelet-derived growth factor B.
• This stroke-specific proteome was more pronounced in survivors experiencing cognitive decline in processing speed and executive function.
• Stroke survivors exhibited significantly higher whole-brain BBB leakage (1.7-fold) compared to controls.
• Individuals who died with dementia post-stroke showed a marked reduction in vascular mural cell coverage compared to those without dementia.

Conclusions:

• Chronic blood-brain barrier dysfunction is implicated as a key mechanism in late cognitive decline after ischemic stroke.
• Proteomic and imaging findings suggest potential biomarkers for identifying individuals at risk of post-stroke dementia.
• The study highlights vascular mural cell integrity and BBB function as critical factors and potential therapeutic targets for intervention.