Brain volume changes in CADASIL: a serial MRI study in pure subcortical ischemic vascular disease
N Peters1, M Holtmannspötter, C Opherk
1Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
Insights
Brain atrophy is a key feature of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), correlating with clinical decline. Age and blood pressure predict brain volume loss, suggesting percent brain volume change as a trial endpoint.
Area of Science:
- Neurology
- Neuroimaging
- Genetics
Background:
- Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is an inherited small vessel disease.
- Brain atrophy is a known marker in sporadic vascular disease but its role in CADASIL is unclear.
Purpose of the Study:
- To investigate brain atrophy and its clinical correlates in CADASIL.
- To assess brain volume changes over time in CADASIL patients.
Main Methods:
- Normalized brain volume (NBV) and percent brain volume change (PBVC) were measured over 2 years in 76 CADASIL subjects using SIENA software.
- Clinical assessments, including neurological scales and cognitive tests, were performed.
- Risk factors like age, sex, systolic blood pressure (SBP), and homocysteine levels were analyzed.
Main Results:
- NBV correlated significantly with all clinical scores at baseline and follow-up.
- PBVC correlated with changes in most clinical scores, excluding the Mattis dementia rating scale.
- Age, male sex, and SBP were identified as risk factors for lower NBV and brain volume loss.
Conclusions:
- Brain atrophy is integral to the CADASIL disease process, linked to clinical and cognitive status.
- Age and SBP are significant risk factors for brain volume loss in CADASIL.
- PBVC shows promise as an outcome measure for interventional trials in CADASIL.
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.
