Association of Rare NOTCH3 Variants With Prevalent and Incident Stroke and Dementia in the General Population

Background It is uncertain whether rare NOTCH3 variants are associated with stroke and dementia in the general population and whether they lead to alterations in cognitive function. This study aims to determine the associations of rare NOTCH3 variants with prevalent and incident stroke and dementia, as well as cognitive function changes. Methods and Results In the prospective community‐based Shunyi Study, a total of 1007 participants were included in the baseline analysis. For the follow‐up analysis, 1007 participants were included in the stroke analysis, and 870 participants in the dementia analysis. All participants underwent baseline brain magnetic resonance imaging, carotid ultrasound, and whole exome sequencing. Rare NOTCH3 variants were defined as variants with minor allele frequency