Introduction: CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a genetic disorder with an important predisposition for development of cerebral microbleeds (CMB). However, the relative impact of the two most common risk factors for CMB, hypertension and cerebral amyloid angiopathy, in CADASIL is uncertain.
Hypothesis: We hypothesized that APOE (apolipoprotein E, an important predictor and correlate of cerebral amyloid angiopathy) genotype and hypertension influenced the presence and distribution of CMB in patients with CADASIL.
Methods: CMB were identified as small (up to 10 mm) areas of signal void seen on 3.0T MRI susceptibility-weighted images. The locations of CMB were characterized as lobar, deep, and infra-tentorial.
Results: In 83 patients with CADASIL (mean age 62.5 years), CMB were observed in 69.9% (58/83) of the total patient population. The most common areas of CMB were deep (57.8%, 48/83), lobar (50.6%, 42/83), and infra-tentorial location (38.4%, 33/83). Hypertension was found in 59% (49/83) of patients. APOE genotype frequencies were: ε2/ε3 9.6% (8/83); ε2/ε4 2.4% (2/83); ε3/ε3 57.8% (48/83); ε3/ε4 30.1% (25/83). Hypertension was associated with presence of CMB in lobar (p<0.001), deep (p=0.035), and infra-tentorial locations (p=0.012). However, no significant associations were found between APOE genotype and presence of CMB in any location.
Conclusions: In this cohort of CADASIL patients, hypertension but not APOE genotype predicted presence of CMB in all locations. These findings suggest that hypertension may amplify the arteriopathy of CADASIL in the development of CMB.