Cerebrovascular reactivity is a main determinant of white matter hyperintensity progression in CADASIL.

BACKGROUND AND PURPOSE: Basal total cerebral blood flow (TCBF) and cerebrovascular reactivity (CVR) are assumed to play an important role in the pathophysiology of small-vessel disease. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a unique monogenetic model to study the pathophysiology of arterial small-vessel disease. The aim of this study was to investigate the role of TCBF and CVR in the progression of MR imaging abnormalities in CADASIL. MATERIALS AND METHODS: Basal TCBF was measured in 25 NOTCH3 mutation carriers and 13 control subjects at baseline. CVR after administration of acetazolamide was measured in 14 NOTCH3 mutation carriers and 9 control subjects. Increase in white matter hyperintensities (WMHs), lacunar infarcts, and microbleeds on MR imaging was measured 7 years later. RESULTS: Lower CVR at baseline was associated with larger increase of WMHs (P = .001) but not with a larger increase of lacunar infarcts or microbleeds. TCBF at baseline was not associated with an increase of MR imaging abnormalities. CONCLUSIONS: Decreased CVR is a potential predictor of disease progression as indicated by increasing WMHs in CADASIL.

MRI correlates of cognitive decline in CADASIL: a 7-year follow-up study.

BACKGROUND: Cognitive decline is one of the clinical hallmarks of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a cerebrovascular disease caused by NOTCH3 mutations. In this 7-year follow-up study, we aimed to determine whether there are associations between the different radiologic hallmarks in CADASIL and decline in specific cognitive domains. METHODS: Twenty-five NOTCH3 mutation carriers and 13 controls had standardized neuropsychological testing and MRI examinations at baseline and after a follow-up of 7 years. To identify longitudinal associations between MRI abnormalities and cognitive decline, correlation analysis was used. RESULTS: At follow-up, mutation carriers showed a decline in global cognitive function (CAMCOG, p < 0.01) and in the cognitive domains language, memory, and executive function, compared to controls. Cognitive decline, especially executive dysfunction, was associated with increase in lacunar infarcts, microbleeds, and ventricular volume. In contrast, WMHs and brain atrophy were not associated with cognitive decline. CONCLUSION: Increase in lacunar infarcts, microbleeds, and ventricular volume, but not white matter lesions or atrophy, are associated with cognitive decline in the process of CADASIL in younger-aged, mildly affected patients with CADASIL.