Vasoreactivity in CADASIL: comparison to structural MRI and neuropsychology

Impaired cerebrovascular reactivity precedes histological and clinical evidence of CADASIL in animal models. We aimed to more fully characterise peripheral and cerebral vascular function and reactivity in a cohort of adult CADASIL patients, and explore the associations of these with conventional clinical, imaging and neuropsychological measures. 22 adults with CADASIL gave informed consent to participate in an exploratorystudy of vascular function in CADASIL. Clinical assessment, comprehensive vascular assessment, MRI and neuropsychological testing were conducted. Transcranial Doppler and arterial spin labelling MRI with hypercapnia challenge both measured cerebral vasoreactivity. Number and volume of lacunes, subcortical hyperintensity volume, microbleeds and normalised brain volume were assessed on MRI scans. Analysis was exploratory and examined associations between different markers. The results showed that cerebrovascular reactivity measured by ASL correlated with peripheral vasoreactivity measured by flow mediated dilatation. Subjects with >5 lacunes were older, with evidence of atherosclerosis and had impaired cerebral and peripheral vasoreactivity. Subjects with depressive symptoms, disability or delayed processing speed, also had impaired vasoreactivity, as well as more lacunes and brain atrophy. Impaired vasoreactivity and vascular dysfunction may play a significant role in the pathophysiology of CADASIL and vascular tests may be important to include in both longitudinal and clinical trials