NOTCH3 p.R544C variant in vascular Parkinsonism: Clinical and imaging correlates in a Taiwanese cohort. (2025)

[BACKGROUND] Vascular parkinsonism (VP) is a heterogeneous syndrome caused by cerebrovascular pathology. While generally distinguishable from Parkinson's disease (PD), overlap may occur in some cases. The genetic basis of VP remains unclear. The role of the NOTCH3 p.R544C variant-common in East Asian cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) cohorts-in VP has not been systematically evaluated.

[METHODS] We conducted a prospective study of 253 patients with parkinsonism (idiopathic PD, VP, or atypical parkinsonism), who underwent clinical evaluation, brain MRI, and testing for the NOTCH3 p.R544C variant. A comparison cohort of 48 patients with cerebral small vessel disease (CSVD) and the same variant but without parkinsonism was als