CADASIL is an autosomal dominant arteriopathy characterised by diffuse white matter lesions and small subcortical infarcts on neuroimaging and a variable combination of recurrent cerebral ischaemic episodes, cognitive deficits, migraine with aura and psychiatric symptoms.
Cognitive decline is one of the clinical hallmarks of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a cerebrovascular disease caused by NOTCH3 mutations.
We recently reported a patient with parkinsonism and cognitive impairment and with evidence of diffuse white matter changes on imaging, carrying a NOTCH3 nonsense mutation in exon 3 (c.307C>T), and suggested that such a hypomorphic NOTCH3 mutation was likely to be pathogenic.
The finding suggests that a disturbed neurogenic process due to Notch3-dependent micromilieu changes might be one vascular-independent mechanism contributing to cognitive decline observed in CADASIL.
The most common symptoms of CADASIL are small ischemic strokes and/or transient ischemic attacks and cognitive impairment, appearing in middle age, that may progress to frank vascular dementia.
<b>Background:</b> It remains unclear whether the degree of white matter tract damage or cerebral hypoperfusion can better predict global cognitive impairment in CADASIL.