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From the Departments of Neurology (N.P., C.O., A.G., J.H., M.D.) and Neuroradiology (M.H.), Klinikum Großhadern, Ludwig-Maximilians-University, Munich, Germany; and Max Planck Institute of Psychiatry (P.S.) NMR Group, Munich, Germany.
Address correspondence and reprint requests to Dr. Martin Dichgans, Department of Neurology, Klinikum Großhadern, Ludwig-Maximilians-University, Marchioninistraße 15, D 81377 Munich, Germany; e-mail: martin.dichgans{at}med.uni-muenchen.de
Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease causing stroke and subcortical vascular dementia. Recent studies in sporadic subcortical ischemic vascular disease have drawn attention to brain atrophy as a clinically important marker of disease progression. However, little is known about the role of brain atrophy and its clinical correlates in CADASIL.
Method: The authors determined the normalized brain volume (NBV) and percent brain volume change (PBVC) over 2 years in 76 CADASIL subjects (45.1 ± 9.7 years) using the SIENA (structural image evaluation using normalization of atrophy) software and its adaptation for cross-sectional measurements (SIENAX). Baseline assessments included systolic blood pressure (SBP), homocysteine levels, BMI, and APOE genotyping. T2-lesion volumes and clinical scales were assessed at both time points.
Results: The NBV significantly correlated with all clinical scores (Rankin, NIH Stroke Scale, Barthel, structured interview for the diagnosis of Alzheimer dementia and multi-infarct dementia, Mattis dementia rating scale) at both time points independently of age and sex. PBVC correlated with changes of all clinical scores (all p < 0.01) except for the Mattis dementia rating scale (p = 0.10). In a linear regression model, age (p < 0.001), male sex (p < 0.01), and SBP (p = 0.07) were the main risk factors for a lower NBV at baseline. Age (p < 0.001) and SBP (p = 0.01) were risk factors for brain volume loss during follow-up. Sample size estimates showed that the number of individuals needed to demonstrate a treatment effect in a trial can be reduced when PBVC is used as an endpoint.
Conclusions: This study identifies brain atrophy as an important aspect of the disease process in CADASIL and establishes significant correlations with multiple clinical aspects including cognition. Age and systolic blood pressure are risk factors for brain volume loss during follow-up. Percent brain volume change seems promising as an adjunct outcome measure in future interventional trials.
Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the May 23 issue to find the title link for this article.
*Both authors contributed equally to this work.
Supported by grants from the Deutsche Forschungsgemeinschaft to M.D. (Di722/3-1, KFG K1 027, KFG K1 028).
Disclosure: The authors report no conflicts of interest.
Received August 31, 2005. Accepted in final form January 27, 2006.
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