The US CADASIL Consortium recruited adults from families carrying NOTCH3 variants at 12 sites between October 2022 and January 2025, assessing them with harmonised cognitive, physical, MRI, genetic and proteomic protocols. Among 343 confirmed carriers, three quarters fell into the high genetic risk tier, and adjusted odds of a worse Clinical Dementia Rating category against 116 non-carrier relatives ranged from 2.55 to 5.08. Median age was 47.9 years and 91.4% of participants were White, in a preprint.
Why it is interesting: A single-cause cohort offers a controlled reference point for the vascular contribution to cognitive impairment, which population counts separate poorly from Alzheimer pathology.