Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is the most common heritable cause of vascular cognitive impairment and dementia (VCID). NOTCH3 is the name given to the gene that supports the function of vascular smooth muscle cells (muscle cells surrounding blood vessels) and that helps maintain blood vessels. When mutated or containing an error, this gene can cause CADASIL.
Although the cause of CADASIL has been linked to a single gene (NOTCH3) and can therefore be diagnosed via genetic testing, many early symptoms of the disease remain poorly understood. Notably, CADASIL first appears in different ways in different individuals. This means that there is considerable clinical and imaging variability among individuals diagnosed with CADASIL, even in families with the same NOTCH3 mutation. This variability may owe to a range of contributing causes such as vascular risk and genetic modifiers. Consequently, this study is designed to look at how a person’s body, brain, and behavior change throughout the stages of this disease and at which factors might present additional risks or protections.
Again, there is significant variability in the quality of imaging, biological, and clinical markers for VCID. Although magnetic resonance imaging (MRI) can detect changes in individuals with CADASIL fifteen years before others signs and symptoms, the pattern and the progression of these changes or imaging abnormalities require further research. Imaging markers which indicate abnormal change include total brain volume and white matter hyperintensities (or brain lesions appearing as light spots on imaging tests). Biological markers detected in plasma or cerebrospinal fluid may include neurofilament light chain (protein polymers which support nerve fibers in neurons), but no such markers are currently validated for VCID. As for clinical markers, there is no well-defined and reliable assessment of the impairments to thinking, reasoning, and remembering and of the changes in behavior which may be indicative of VCID. More sensitive assessments may also be needed to detect milder impairments and changes.