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No study yet has compared the longitudinal course and prognosis between subcortical vascular cognitive impairment patients with and without genetic component. In this study, we compared the longitudinal changes in cerebral small vessel disease markers and cognitive function between subcortical vascular mild cognitive impairment (svMCI) patients with and without  NOTCH3  variant [ NOTCH3 (+) svMCI vs.  NOTCH3 (–) svMCI]. We prospectively recruited patients with svMCI and screened for  NOTCH3  variants by sequence analysis for mutational hotspots in the  NOTCH3  gene. Patients were annually followed-up for 5 years through clinical interviews, neuropsychological tests, and brain magnetic resonance imaging. Among 63 svMCI patients, 9 (14.3%) had either known mutations or possible pathogenic variants. The linear mixed effect models showed that the  NOTCH3 (+) svMCI group had much greater increases in the lacune and cerebral microbleed counts than the  NOTCH3 (–) svMCI group. However, there were no significant differences between the two groups regarding dementia conversion rate and neuropsychological score changes over 5 years.

frontiers in neurology

Comparison of Longitudinal Changes of Cerebral Small Vessel Disease Markers and Cognitive Function Between Subcortical Vascular Mild Cognitive Impairment With and Without NOTCH3 Variant: A 5-Year Follow-Up Study