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.
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.
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.
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.
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.