The protocol for an observational Australian cohort study of CADASIL: The AusCADASIL study

Area of Science:

• Neuroscience
• Genetics
• Clinical Research

Background:

• Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare genetic cerebrovascular disorder with diverse clinical manifestations.
• Understanding the Australian CADASIL population is crucial for comprehensive disease characterization.

Purpose of the Study:

• To establish the first Australian CADASIL cohort (AusCADASIL).
• To examine the clinical features, longitudinal course, and progression of CADASIL in Australia.
• To investigate neuroimaging and blood biomarkers for early diagnosis and disease monitoring.

Main Methods:

• An observational study recruiting 150 CADASIL patients and 150 controls across six Australian centers.
• Data collection includes questionnaires, neuropsychological and neurological evaluations, brain MRI, ocular exams, and blood sample donation.
• Annual follow-up for 4 years to assess progression, with primary outcomes in cognitive function and neuroimaging.

Main Results:

• The study will identify common pathogenic variants within the Australian CADASIL cohort.
• Characterization of clinical presentation patterns and longitudinal progression, including imaging, biomarkers, and cognitive profiles.
• Contribution of data to an international consortium for broader research impact.

Conclusions:

• AusCADASIL represents a significant step in understanding CADASIL within the Australian context.
• The findings will enhance diagnostic capabilities and inform future therapeutic strategies.
• Cohort participants may be eligible for future clinical trials, advancing treatment options.