Simple Blood Test Could Enable First Quantitative Assessments for Future Cerebrovascular Disease

Cerebral small vessel disease is a common cause of stroke and cognitive decline, particularly in the elderly. Presently, assessing the risk for cerebral vascular diseases involves using a mix of diagnostic imaging such as MRI scans, family medical history, demographic data, and other risk factor evaluations. Often, neurologists only discover that a patient is at risk after they have experienced a stroke or a warning cerebral event. Now, a simple blood test offers the potential for doctors to identify individuals at increased risk for stroke or cognitive decline by measuring levels of a network of inflammatory molecules, which helps calculate a risk score for susceptibility to cerebral small vessel disease.

Researchers at UCLA Health (Los Angeles, CA, USA) have developed a method to measure the concentrations of these inflammatory molecules in individuals who have not yet suffered a cerebrovascular event, thereby providing a quantitative tool to assess the risk for cerebral small vessel disease and potential future strokes. This approach centers around the interleukin-18, or IL-18, network of inflammatory molecules, which includes proteins and signaling molecules that combat various infections. Previous studies have associated certain molecules within the IL-18 network with an increased risk of cerebral small vessel disease and stroke. However, the levels of these molecules can vary in response to various conditions like the flu or autoimmune diseases, rendering them unreliable as sole predictors of stroke risk.

In 2020, this research team discovered that six molecules within the IL-18 network were linked to the presence of vascular brain injuries in MRI scans. Building on these insights, they explored whether the IL-18 network could be used to evaluate a person's likelihood of stroke or cognitive decline. They utilized health data from the long-standing Framingham Heart Study, which has been monitoring the medical histories of residents from Framingham, Massachusetts since its inception in 1948. Blood samples from study participants were analyzed for five of the six molecules identified as part of the IL-18 network.

Using these blood samples and the comprehensive medical histories from the Framingham study, the researchers devised a mathematical model that calculates a risk score based on the concentrations of IL-18 network molecules. Analysis of over 2,200 Framingham participants revealed that individuals with risk scores in the top 25% were 84% more likely to experience a stroke in their lifetime. Moreover, high-risk scores were linked with a 51% increased stroke risk, offering a predictive advantage over traditional risk assessment methods. Further research is necessary to determine whether and how an individual's risk score can be altered or mitigated.

“The same way one uses cholesterol tests to evaluate one’s future risk for heart attack, we don’t have such a thing to estimate future risk for stroke,” said Dr. Jason Hinman of the UCLA who led the study. “I believe we can do that by something as simple as a blood test which in theory can enable broader access to the best level of care and not lock it behind advanced imaging studies and specialist evaluations.”

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