StrokeCog-BBB to Study Cognitive Outcomes Following Stroke

Post-stroke dementia is an important and understudied component of the vascular contributions to cognitive impairment and dementia. Having a stroke approximately doubles the risk of incident dementia for at least a decade afterwards, even after accounting for other vascular risk factors of dementia and the initial effects of the stroke lesion on cognition. Also, silent strokes occur in nearly half of all aging individuals and are associated with dementia. It has been established in wildtype mice that stroke triggers chronic neuroinflammation in the stroke scar and connected brain regions, and that this causes delayed-onset cognitive decline. In humans, there is neuroinflammation in the stroke scar in about half of all chronic stroke survivors on autopsy, even decades after stroke, suggesting it may play a role in people as well. However, there are no biomarkers that can currently be used in living humans to detect who is at risk of cognitive decline and dementia after stroke. The hypothesis to be tested is that inflammation-induced angiogenesis in the stroke and connected regions results in immature leaky vessels that cause blood-brain barrier leakage even very late after stroke. The goal is to establish that there is chronic blood-brain barrier dysfunction after stroke and a dysregulated angiogenesis as a potential mechanism. This would be a fundamental change in how post-stroke dementia is conceptualized and would open avenues for novel therapy development. This will also help better understand vascular contributions to cognitive impairment and dementia.

Inclusion criteria

• Aged 45 years or over
• One or more vascular risk factors (e.g. high blood pressure, diabetes or vascular disease such as angina, a previous heart attack, a heart bypass or peripheral artery disease in the legs)
• Established vascular disease (previous MI, angina, vascular stent in the peripheral bed)
• Sufficiently fluent in written and spoken English
• Living independently in the community
• Willing/able to give consent to study participation.

Exclusion criteria

• Current treatment with IL-1 blockade or established immune-suppressant therapy (e.g. IL-1Ra or IL-1 antibodies), or treatment within the last 3 months
• Currently participating in a clinical trial of investigation medicinal product (CTIMP) or device trial.
• No history of any previous ischaemic or haemorrhagic stroke, a mini-stroke or a serious brain injury
• Do not have dementia
• Renovascular Disease
• Major neurological disease (immune mediated, previous brain tumors)