Background and purpose: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy is caused by mutations in the NOTCH3 gene and is clinically characterized by recurrent stroke and cognitive decline. Previous studies have shown an association between white matter hyperintensities on brain MRI and cognitive dysfunction in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. In the general population the presence of lacunar infarcts and microbleeds is also associated with cognitive dysfunction. The objective of this study was to determine to what extent lacunar infarcts and microbleeds on MRI contribute to cognitive decline in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.
Methods: NOTCH3 mutation analysis was performed in 62 symptomatic and asymptomatic members of 15 cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy families. Neuropsychological tests were performed on the same day as the MRI examination. MRI was semi-quantitatively scored for white matter hyperintensities, infarct lesion load, and microbleeds. Regression analysis was performed to test the association between MRI abnormalities and neuropsychological test results.
Results: Forty individuals had a NOTCH3 mutation and 22 did not. Severity of cognitive dysfunction in mutation carriers was independently associated with MRI infarct lesion load (P<0.05). In contrast, WMH lesion load and microbleeds were not associated with cognitive dysfunction after correcting for age.
Conclusions: Lacunar infarct lesion load is the most important MRI parameter associated with cognitive dysfunction in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.