Background and Purpose-Predictors of clinical worsening in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy remain unknown. This study aims to identify demographic, clinical, and magnetic resonance imaging predictors of incident strokes, incident dementia, clinical deterioration, and death in patients with this genetically proven disease. Methods-Two hundred ninety subjects (mean age, 50.6±11.4 years) were assessed at baseline and followed up for 36 months. Incident clinical events were recorded, and clinical scores included the Mini Mental State Examination, Mattis Dementia Rating Scale, modified Rankin Scale, and Barthel index. The number of lacunes and microbleeds, the volume of white-matter hyperintensities, and brain parenchymal fraction were assessed on baseline magnetic resonance imaging. Data were analyzed by ANCOVA, multivariable logistic regression, and Cox proportional hazard models. Results-Incident stroke occurred in 55 of 278 patients (19.8%). Moderate or severe disability developed in 19 of 210 (9%) nondisabled individuals, incident dementia in 49 of 231 (20%) nondemented subjects, and 4.8% of patients died. Active smoking, the number of lacunes, and brain parenchymal fraction independently predicted incident stroke during follow-up. Gait disturbance, dementia, and brain parenchymal fraction predicted progression toward moderate or severe disability. Active smoking, disability, and brain parenchymal fraction predicted incident dementia. Age was the only significant predictor of death. The clinical and imaging characteristics of CADASIL much resemble those of the most severe forms of sporadic SVD. We, thus, reasoned that information derived from a longitudinal study in CADASIL might offer insights relevant to SVD in general. Here, we report the final results of this study obtained in a large cohort of patients followed up for 3 years.
Conclusions-Clinical
Methods
Study CohortSubjects were prospectively recruited between September 2003 and April 2011 through 2 major referral centers for CADASIL (University Hospital Lariboisière, Paris [n=178] and Ludwig Maximilians Universität, Munich [n=112]). They were included regardless of whether they had clinical manifestations of the disease if they were at least 18 years of age, had a documented mutation in the NOTCH3 gene, and were willing to be followed up. Details of the study protocol have been reported elsewhere.11 A follow-up interval of 3 years was chosen based on previous longitudinal data showing that significant changes in clinical scores can be detected within an interval of 2 years 8 when following up patients seen at major referral centers and to obtain a sufficient number of clinical events. In brief, clinical and demographic data were collected at study entry and included age, sex, years of education, and vascular risk factors (hypertension, diabetes mellitus, hypercholesteremia, smoking, and alcohol use). Blood pressure was measured at baseline and at follow-up.A history of transient ischemic attack...
