Carotid atherosclerotic markers in CADASIL

Area of Science:

• Neurology
• Vascular Biology
• Genetics

Background:

• Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a genetic small vessel disease.
• NOTCH3 gene mutations cause CADASIL, but disease severity varies significantly.
• Non-genetic factors may influence CADASIL phenotype expressivity.

Purpose of the Study:

• To investigate the association between atherosclerosis and the clinical/MRI phenotype in CADASIL patients.
• To assess atherosclerosis using carotid duplex ultrasonography.
• To determine if atherosclerosis modulates disease severity in CADASIL.

Main Methods:

• 144 patients from a prospective cohort study were analyzed.
• Clinical assessment included modified Rankin Scale and Mattis Dementia Rating Scale (MDRS).
• Cerebral MRI evaluated lesion volumes, microhemorrhages, and diffusion parameters; carotid ultrasonography measured intima-media thickness (cIMT) and plaque presence.

Main Results:

• Higher cIMT correlated with lower MDRS scores (p=0.02).
• A trend suggested cIMT association with Rankin score (p=0.06).
• Carotid markers showed no significant link to stroke or most MRI parameters, but correlated with diffusion histogram data.

Conclusions:

• Atherosclerosis severity may contribute to cognitive decline in CADASIL.
• This association might be mediated by microstructural cerebral tissue damage.
• Further longitudinal studies are required to confirm these findings.