Publication: Journal of Neurology, Neurosurgery and Psychiatry

Bernard P H Cho, Stefania Nannoni, Eric L Harshfield, Daniel Tozer, Stefan Gräf, Steven Bell, Hugh S Markus

12 March 2021

Researchers in Cambridge have discovered that people with a small change in a gene known as NOTCH3 could be at greater risk of having a stroke and developing vascular dementia.

Their research looked at the clinical records (medical notes) and genetic data of more than 200,000 healthy volunteers from the UK BioBank between 2006-10.

They found that around 1 in 450 carried a variant (a small difference) in the NOTCH3 gene, which provides instructions for making a protein essential for the maintenance of blood vessels, including those that supply blood to the brain.

The researchers then looked at how many people with and without changes in NOTCH3 had had a stroke, vascular dementia or other related conditions and discovered that variant carriers had more than a two-fold increase in the odds of stroke.

Vascular dementia was also more frequent in people who have the NOTCH3 variant. There was also an increased association with cerebral small vessel disease (SVD), which is a major cause of stroke and dementia.

This study shows that NOTCH3 variants are common in the general population and these variants are associated with increased risk of both stroke and vascular dementia, and with MRI markers of SVD. This demonstrates that genetic variation in the NOTCH3 gene accounts for a much greater proportion of stroke in the general population than previously thought.

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