NOTCH3 and Cognitive impairment: Some researchers have proposed a CADASIL severity grading system that encompasses five levels: grade 0 (absence of symptoms), grade 1 (migraine alone), grade 2 (stroke, TIA, or mild cognitive impairment), grade 3 (requiring walking assistance or dementia), and grade 4 (bedridden or advanced stage) for patients with known pathogenic NOTCH3 mutations, characteristic ischemic lesions on brain MRI, or characteristic intravascular deposits on skin biopsy (106).